FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hemauer, S Yan, R Patrikeeva, S Mattison, D Hankins, GDV Ahmed, M Nanovskaya, T AF Hemauer, Sarah Yan, Ru Patrikeeva, Svetlana Mattison, Donald Hankins, Gary D. V. Ahmed, Mahmoud Nanovskaya, Tatiana TI Metabolism of 17-hydroxyprogesterone caproate by the dually perfused human placental lobule SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Hemauer, Sarah; Yan, Ru; Patrikeeva, Svetlana; Hankins, Gary D. V.; Ahmed, Mahmoud; Nanovskaya, Tatiana] Univ Texas Med Branch, Galveston, TX USA. [Mattison, Donald] Natl Inst Hlth, Bethesda, MD USA. RI Mattison, Donald/C-2015-2009; Yan, Ru/G-3480-2013; Mattison, Donald/L-4661-2013 OI Yan, Ru/0000-0001-6268-360X; Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2007 VL 197 IS 6 SU S MA 113 BP S45 EP S45 DI 10.1016/j.ajog.2007.10.124 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500115 ER PT J AU Hernandez, G Goodwin, TM Dossett, EC Korst, LM Romero, R AF Hernandez, Gerson Goodwin, T. M. Dossett, Emily C. Korst, Lisa M. Romero, Roberto TI The effect of nausea and vomiting of pregnancy (NVP) on screening for depression SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Hernandez, Gerson; Goodwin, T. M.; Dossett, Emily C.; Korst, Lisa M.] Univ So Calif, Kerck Sch Med, Los Angeles, CA 90089 USA. [Romero, Roberto] NICHD, NIH, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 376 BP S114 EP S114 DI 10.1016/j.ajog.2007.10.394 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500375 ER PT J AU Hitti, J Frenkel, L Smith, L Huang, S Stek, A Nachman, S Provisor, A Cotter, A Smith, E Watts, H AF Hitti, Jane Frenkel, Lisa Smith, Laura Huang, Sharon Stek, Alice Nachman, Sharon Provisor, Arthur Cotter, Amanda Smith, Elizabeth Watts, Heather TI Comparison of venous lactate concentrations in late pregnancy and postpartum: PACTG 1022 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Hitti, Jane; Frenkel, Lisa] Univ Washington, Seattle, WA 98195 USA. [Smith, Laura] Frontier Sci Technol & Res Fdn, New York, NY USA. [Huang, Sharon] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Stek, Alice] Univ So Calif, Los Angeles, CA 90089 USA. [Nachman, Sharon] SUNY Stony Brook, Stony Brook, NY USA. [Smith, Elizabeth] NIH, Bethesda, MD 20892 USA. [Watts, Heather] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC PY 2007 VL 197 IS 6 SU S MA 218 BP S72 EP S72 DI 10.1016/j.ajog.2007.10.231 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500218 ER PT J AU Holston, A Qian, C Karumanchi, A Yu, K Levine, R AF Holston, Alexander Qian, Cong Karumanchi, Ananth Yu, Kai Levine, Richard TI Circulating angiogenic factors in gestational proteinuria without hypertension SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Holston, Alexander] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD USA. [Qian, Cong] Allied Technol Grp, Rockville, MD USA. [Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Yu, Kai; Levine, Richard] NICHHD, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 455 BP S134 EP S134 DI 10.1016/j.ajog.2007.10.474 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500448 ER PT J AU Joy, S AF Joy, Saju TI Latency and infectious complications following preterm premature rupture of the membranes: Impact of body mass index SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Joy, Saju] NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 658 BP S189 EP S189 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500650 ER PT J AU Kang, JH Lee, SE Park, CW Jun, JK Romero, R Yoon, BH AF Kang, Ji Hyun Lee, Si Eun Park, Chan-Wook Jun, Jong Kwan Romero, Roberto Yoon, Bo Hyun TI Cervical fetal fibronectin: An index of intra-amniotic inflammation, histologic chorioamnionitis and impending preterm delivery in patients with preterm labor and intact membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Kang, Ji Hyun; Lee, Si Eun; Park, Chan-Wook; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Romero, Roberto] Natl Inst Hlth, NICHD, Dept Hlth & Human Serv, Detroit, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 122 BP S47 EP S47 DI 10.1016/j.ajog.2007.10.133 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500124 ER PT J AU Kim, J Han, YM Kim, JS Kim, SK Tarca, AL Draghici, S Kusanovic, JP Gotsch, F Mittal, P Hassan, S Romero, R AF Kim, Jai Han, Yu Mi Kim, Jung-Sun Kim, Sun Kwon Tarca, Adi L. Draghici, Sorin Kusanovic, Juan Pedro Gotsch, Francesca Mittal, Pooja Hassan, Sonia Romero, Roberto TI First evidence that the human amnion is functionally heterogeneous: A study of the amnion transcriptome chong SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Kim, Jai; Kim, Jung-Sun] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48202 USA. [Han, Yu Mi; Kim, Sun Kwon; Kusanovic, Juan Pedro; Gotsch, Francesca; Romero, Roberto] NIH, NICHD, DHHS, Perinatol Res Branch, Detroit, MI USA. [Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. [Mittal, Pooja; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 299 BP S93 EP S93 DI 10.1016/j.ajog.2007.10.314 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500299 ER PT J AU Kim, JS Romer, R Lajeunesse, C Han, YM Tarca, AL Mittal, P Gotsch, F Kusanovic, JP Hassan, S Kim, CJ AF Kim, Jung-Sun Romer, Roberto Lajeunesse, Christopher Han, Yu Mi Tarca, Adi L. Mittal, Podja Gotsch, Francesca Kusanovic, Juan Pedro Hassan, Sonia Kim, Chong Jai TI The molecular basis for the differential role of the umbilical artery and vein in acute funisitis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Kim, Jung-Sun; Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48202 USA. [Kim, Jung-Sun; Kim, Chong Jai] NICHD, NIH, DHHS, Perinatol Branch, Detroit, MI USA. [Romer, Roberto; Lajeunesse, Christopher; Han, Yu Mi; Gotsch, Francesca; Kusanovic, Juan Pedro] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. [Mittal, Podja; Hassan, Sonia] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 273 BP S87 EP S87 DI 10.1016/j.ajog.2007.10.287 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500273 ER PT J AU Kusanovic, JP Romero, R Espinoza, J Mittal, P Edwin, SS Erez, O Gotsch, F Mazaki-Tovi, S Than, NG Soto, E Camacho, N Quintero, R Hassan, S AF Kusanovic, Juan Pedro Romero, Roberto Espinoza, Jimmy Mittal, Pooja Edwin, Samuel S. Erez, Offer Gotsch, Francesca Mazaki-Tovi, Shali Than, Nandor Gabor Soto, Eleazar Camacho, Natalia Quintero, Ruben Hassan, Sonia TI Twin-to-twin transfusion syndrome: An anti-angiogenic state SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Kusanovic, Juan Pedro; Romero, Roberto; Edwin, Samuel S.; Erez, Offer; Gotsch, Francesca; Than, Nandor Gabor] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Espinoza, Jimmy; Mittal, Pooja; Mazaki-Tovi, Shali; Soto, Eleazar; Camacho, Natalia; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Quintero, Ruben] Univ S Florida, Fetal Therapy Dept, Div Maternal Fetal Med, Tampa, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 60 BP S27 EP S27 DI 10.1016/j.ajog.2007.10.067 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500063 ER PT J AU Lee, J Seong, HS Kim, BJ Jun, JK Romero, R Yoon, BH AF Lee, Joonho Seong, Hyo Suk Kim, Byoung Jae Jun, Jong Kwan Romero, Roberto Yoon, Bo Hyun TI Evidence in support that spontaneous preterm labor is adaptive in nature: Neonatal RDS is more common in "Indicated" than in "Spontaneous" preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Lee, Joonho; Seong, Hyo Suk; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Seoul 151, South Korea. [Seong, Hyo Suk] Seoul Natl Univ, Borame Hosp, Seoul 151, South Korea. [Romero, Roberto] NICHHD, NIH, Dept Hlth & Human Serv, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 614 BP S176 EP S176 DI 10.1016/j.ajog.2007.10.640 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500606 ER PT J AU Lee, J Oh, KJ Lee, JY Park, JS Romero, R Yoon, BH AF Lee, Joonho Oh, Kyung Joon Lee, Joo Yeon Park, Joong Shin Romero, Roberto Yoon, Bo Hyun TI The importance of intra-amniotic inflammation, in the subsequent development of atypical chronic lung disease SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Lee, Joonho; Oh, Kyung Joon; Lee, Joo Yeon; Park, Joong Shin; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Seoul 151, South Korea. [Romero, Roberto] NICHHD, NIH, Dept Hlth & Human Serv, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 615 BP S176 EP S176 DI 10.1016/j.ajog.2007.10.641 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500607 ER PT J AU Lee, SE Park, CW Oh, KJ Lee, SM Romero, R Yoon, BH AF Lee, Si Eun Park, Chan-Wook Oh, Kyung Joon Lee, Seung Mi Romero, Roberto Yoon, Bo Hyun TI Evidence supporting that a culture-proven infection has clinical implications beyond the presence of intra-amniotic inflammation with a negative amniotic fluid culture in preterm PROM SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med (SMFM) C1 [Lee, Si Eun; Park, Chan-Wook; Oh, Kyung Joon; Lee, Seung Mi; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Seoul 151, South Korea. [Romero, Roberto] NICHHD, NIH, Dept Hlth & Human Serv, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 689 BP S197 EP S197 DI 10.1016/j.ajog.2007.10.717 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500681 ER PT J AU Levine, R Qian, C Yu, K Holston, A Zhang, C Karumanchi, A Siba, B AF Levine, Richard Qian, Cong Yu, Kai Holston, Alexander Zhang, Cuilin Karumanchi, Ananth Siba, Baha TI Circulating concentrations of angiogenic factors to predict early if delivery in preeclampsia before 34 weeks SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Levine, Richard; Yu, Kai; Zhang, Cuilin] NICHHD, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Qian, Cong] Allied Technol Grp, Bethesda, MD USA. [Holston, Alexander] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD USA. [Karumanchi, Ananth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Siba, Baha] Univ Cincinnati, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 21 BP S11 EP S11 DI 10.1016/j.ajog.2007.10.024 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500024 ER PT J AU Mazaki-Tovi, S Romero, R Kusanovic, JP Erez, O Gotsch, F Mittal, P Than, NG Nhan-Chang, CL Hamill, N Vaisbuch, E Edwin, SS Nien, JK Espinoza, J Hassan, S Bryant-Greenwood, G AF Mazaki-Tovi, Shali Romero, Roberto Kusanovic, Juan Pedro Erez, Offer Gotsch, Francesca Mittal, Pooja Than, Nandor Gabor Nhan-Chang, Chia-Ling Hamill, Neil Vaisbuch, Edi Edwin, Samuel S. Nien, Jyh Kae Espinoza, Jimmy Hassan, Sonia Bryant-Greenwood, Gillian TI The adipokine visfatin participates in the host response to intra-amniotic infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Mazaki-Tovi, Shali; Mittal, Pooja; Nhan-Chang, Chia-Ling; Hamill, Neil; Espinoza, Jimmy; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Gotsch, Francesca; Than, Nandor Gabor; Vaisbuch, Edi; Edwin, Samuel S.] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Nien, Jyh Kae] Pontificia Univ Catolica Chile, Hosp Sotero Rio, CEDIP, Puente Alto, Chile. [Bryant-Greenwood, Gillian] Univ Hawaii, Dept Cell & Mol Biol, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 195 BP S66 EP S66 DI 10.1016/j.ajog.2007.10.208 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500196 ER PT J AU Mertz, H AF Mertz, Heather TI Placental endothelial nitric oxide synthase in multiple and single dose betamethasone exposed pregnancies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Mertz, Heather] NICHD, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 528 BP S154 EP S154 DI 10.1016/j.ajog.2007.10.530 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500521 ER PT J AU Mikolajczyk, R Zhang, J Chan, L Troendle, J AF Mikolajczyk, Rafael Zhang, Jun Chan, Linda Troendle, James TI Risk factors for subtypes of laceration among primiparous women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Mikolajczyk, Rafael; Zhang, Jun; Troendle, James] NIH, Bethesda, MD 20892 USA. [Chan, Linda] Naval Med Ctr, San Diego, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 320 BP S98 EP S98 DI 10.1016/j.ajog.2007.10.335 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500319 ER PT J AU Mittal, P Romero, R Kusanovic, JP Gotsch, F Mazakitovi, S Espinoza, J Erez, O Nhan-Chang, CL Than, N Vansbuch, E Edwin, SS Hassan, S AF Mittal, Pooja Romero, Roberto Kusanovic, Juan Pedro Gotsch, Francesca Mazakitovi, Shali Espinoza, Jimmy Erez, Offer Nhan-Chang, Cha-Ling Than, Nandor Vansbuch, Edi Edwin, Samuel S. Hassan, Sonia TI Granulocyte chemotactic protein-2 (CXCL6): A novel chemokine involved in the innate immune response of the amniotic cavity SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Mittal, Pooja; Mazakitovi, Shali; Espinoza, Jimmy; Nhan-Chang, Cha-Ling; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Espinoza, Jimmy; Than, Nandor; Vansbuch, Edi; Edwin, Samuel S.] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 202 BP S68 EP S68 DI 10.1016/j.ajog.2007.10.215 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500203 ER PT J AU Mobeen, N Jehan, I Banday, N Pasha, O Bartz, J Wright, L Mcclure, E Goldenberg, R AF Mobeen, Naushara Jehan, Imtiaz Banday, Ninette Pasha, Omrana Bartz, Janet Wright, Linda Mcclure, Elizabeth Goldenberg, Robert TI Periodontal disease and adverse birth outcomes: A study from Pakistan SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Mobeen, Naushara; Jehan, Imtiaz; Banday, Ninette; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan. [Bartz, Janet; Mcclure, Elizabeth] Res Triangle Inst, Chapel Hill, NC USA. [Wright, Linda] NIH, Bethesda, MD 20892 USA. [Goldenberg, Robert] Drexel Univ, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 51 BP S23 EP S23 DI 10.1016/j.ajog.2007.10.057 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500054 ER PT J AU Nhan-Chang, CL Romero, R Kusanovic, JP Gotsch, F Edwin, SS Erez, O Mittal, P Espinoza, J Friel, L Vaisbuch, E Than, NG Mazaki-Tovi, S Hassan, S AF Nhan-Chang, Chia-Ling Romero, Roberto Kusanovic, Juan Pedro Gotsch, Francesca Edwin, Samuel S. Erez, Offer Mittal, Pooja Espinoza, Jimmy Friel, Lara Vaisbuch, Edi Than, Nandor Gabor Mazaki-Tovi, Shali Hassan, Sonia TI A role for CXCL13 in the host response to intra-amniotic infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Nhan-Chang, Chia-Ling; Mittal, Pooja; Espinoza, Jimmy; Friel, Lara; Mazaki-Tovi, Shali; Hassan, Sonia] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Edwin, Samuel S.; Erez, Offer; Vaisbuch, Edi; Than, Nandor Gabor] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 48 BP S22 EP S22 DI 10.1016/j.ajog.2007.10.054 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500051 ER PT J AU Nwankwo, O Goodwin, T Davis-O'Leary, L O'Leary, D Korst, LM Romer, R AF Nwankwo, Odinaka Goodwin, T. M. Davis-O'Leary, Linda O'Leary, Dennis Korst, Lisa M. Romer, Roberto TI The first demonstration that a subset of women with hyperemesis gravidarum (HG) have abnormalities in the viestibuilo-ocular reflex (VOR) pathway: Implications for treatment SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Nwankwo, Odinaka; Goodwin, T. M.; Davis-O'Leary, Linda; O'Leary, Dennis; Korst, Lisa M.] Univ So Calif, Keck Sch Med, Los Angeles, CA USA. [Romer, Roberto] NICHD, NIH, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 58 BP S26 EP S26 DI 10.1016/j.ajog.2007.10.065 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500061 ER PT J AU Park, CW Moon, KC Park, JS Jun, JK Romero, R Yoon, BH AF Park, Chan Wook Moon, Kyung Chul Park, Joong Shin Jun, Jong Kwan Romero, Roberto Yoon, B. Hyun TI The involvement of human ammon in histologic chorioamnionitis is an indicator that a fetal and an intra-amniotic inflammatory response is more likely and severe: Clinical implications SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Park, Chan Wook; Moon, Kyung Chul; Park, Joong Shin; Jun, Jong Kwan; Yoon, B. Hyun] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Romero, Roberto] NICHHD, NIH, Dept Hlth & Human Serv, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 197 BP S66 EP S66 DI 10.1016/j.ajog.2007.10.210 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500198 ER PT J AU Park, CW Lee, SM Park, JS Jun, JK Romero, R Yoon, BH AF Park, Chan-Wook Lee, Seung Mi Park, Joong Shin Jun, Jong Kwan Romero, Roberto Yoon, Bo Hyun TI The antenatal identification of funisitis (fetal inflammation) with a rapid MMP-8 bedside test SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Park, Chan-Wook; Lee, Seung Mi; Park, Joong Shin; Jun, Jong Kwan; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Romero, Roberto] NICHD, Natl Inst Hlth, Dept Hlth & Human Serv, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 47 BP S21 EP S21 DI 10.1016/j.ajog.2007.10.053 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500050 ER PT J AU Roberson, R Toso, L Abebe, D Spong, C AF Roberson, Robin Toso, Laura Abebe, Daniel Spong, Catherine TI Altered NR2B trafficking in a Down syndrome model mediates learning deficit SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Roberson, Robin; Toso, Laura; Abebe, Daniel; Spong, Catherine] NICHD, NIAAA, NIH, Unit Perinatal & Dev Neurobiol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 31 BP S15 EP S15 DI 10.1016/j.ajog.2007.10.035 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500034 ER PT J AU Rogers, B AF Rogers, Barton TI Placental pathology associated with factor V Leiden mutation beverly SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Rogers, Barton] NICHD, MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 274 BP S87 EP S87 DI 10.1016/j.ajog.2007.10.288 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500274 ER PT J AU Rouse, D AF Rouse, Dwight TI When should labor induction be discontinued in the latent phase? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Rouse, Dwight] NICHD, MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 339 BP S103 EP S103 DI 10.1016/j.ajog.2007.10.355 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500338 ER PT J AU Rouse, D AF Rouse, Dwight TI A randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Rouse, Dwight] NICHD, MFMU, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 1 BP S2 EP S2 DI 10.1016/j.ajog.2007.10.002 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500004 ER PT J AU Sciscione, A AF Sciscione, Anthony TI Perinatal outcomes in women with twin gestations who conceived spontaneously versus by assisted reproductive techniques (ART) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Sciscione, Anthony] NICHD, MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 260 BP S84 EP S84 DI 10.1016/j.ajog.2007.10.274 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500260 ER PT J AU Seong, HS Lee, SE Kang, JH Kim, BJ Romero, R Yoon, BH AF Seong, Hyo Suk Lee, Si Eun Kang, Ji Hyun Kim, Byoung Jae Romero, Roberto Yoon, Bo Hyln TI Spontaneous labor at term, even with intact membranes, is a risk factor for intra-amniotic inflammation/infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Seong, Hyo Suk; Lee, Si Eun; Kang, Ji Hyun; Yoon, Bo Hyln] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Kim, Byoung Jae] Seoul Natl Univ, Boramae Hosp, Seoul, South Korea. [Romero, Roberto] NICHHD, NIH, Dept Hlth & Human Serv, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 331 BP S101 EP S101 DI 10.1016/j.ajog.2007.10.347 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500330 ER PT J AU Sibaj, B Freire, S Rudge, M Martins-Costa, S Koch, M Bartz, J Santos, CD Cecatti, JG Costa, JR Ramos, G Moss, N Spinnato, J AF Sibaj, Baha Freire, Salvio Rudge, Marilza Martins-Costa, Sn Koch, Matthew Bartz, Janet Santos, Cleide de Barros Cecatti, Jose Guilherme Costa, Jose Roberto Ramos, Geraldo Moss, Nancy Spinnato, Joseph, II TI Serum inhibin-A and circulating angiogenic factors levels at 12-19 weeks and at 24-28 weeks in women with previous preeclampsia (PE) and/or chronic hypertension (CHTN): Are they useful markers for prediction of subsequent PE? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Sibaj, Baha; Spinnato, Joseph, II] Univ Cincinnati, Cincinnati, OH 45221 USA. [Freire, Salvio; Santos, Cleide de Barros] Univ Fed Pernambuco, Recife, PE, Brazil. [Martins-Costa, Sn; Ramos, Geraldo] Univ Fed Rio Grande do Sul, BR-90046900 Porto Alegre, RS, Brazil. [Koch, Matthew] RTI Int, Res Triangle Pk, NC USA. [Bartz, Janet] Res Triangle Inst, Durham, NC USA. [Cecatti, Jose Guilherme] Univ Estadual Campinas, BR-13081970 Campinas, SP, Brazil. [Moss, Nancy] NICHHD, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2007 VL 197 IS 6 SU S MA 480 BP S140 EP S140 DI 10.1016/j.ajog.2007.10.553 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500473 ER PT J AU Spinnato, J Freire, S Silva, JLPE Rudge, MVC Martins-Costa, S Koch, M Goco, N Santos, CDB Cecatti, JG Costa, R Ramos, JG Moss, N Sibai, B AF Spinnato, Joseph Freire, Salvio Silva, Joao Luiz Pinto E. Rudge, Marilza Vieira Cunha Martins-Costa, Sergio Koch, Matthew Goco, Norman Santos, Cleide De Barros Cecatti, Jose Guilherme Costa, Roberto Ramos, Jose Geraldo Moss, Nancy Sibai, Baha TI Antioxidant therapy and PROM SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Spinnato, Joseph] Univ Cincinnati, Cincinnati, OH 45221 USA. [Freire, Salvio; Santos, Cleide De Barros] Univ Fed Pernambuco, Recife, PE, Brazil. [Silva, Joao Luiz Pinto E.; Cecatti, Jose Guilherme] Univ Estadual Campinas, BR-13081970 Campinas, SP, Brazil. [Rudge, Marilza Vieira Cunha; Costa, Roberto] Univ Estadual Paulista, Sao Paulo, Brazil. [Martins-Costa, Sergio; Ramos, Jose Geraldo] Univ Fed Rio Grande do Sul, BR-90046900 Porto Alegre, RS, Brazil. [Moss, Nancy] NICHHD, Rockville, MD USA. RI Rudge, Marilza /C-8338-2012 OI Rudge, Marilza /0000-0002-9227-832X NR 0 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 685 BP S196 EP S196 DI 10.1016/j.ajog.2007.10.713 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500677 ER PT J AU Than, G Romero, R Erez, O Kusanovic, JP Tarca, AL Edwin, SS Kim, CJ Hassan, S Espinoza, J Mittal, P Mazaki-Tovi, S Friel, LA Gotsch, F Vaisbuch, E Papp, Z AF Than, Gabor Romero, Roberto Erez, Offer Kusanovic, Juan Pedro Tarca, Adi L. Edwin, Samuel S. Kim, Chong Jai Hassan, Sonia Espinoza, Jimmy Mittal, Pooja Mazaki-Tovi, Shali Friel, Lara A. Gotsch, Francesca Vaisbuch, Edi Papp, Zoltan TI A role for mannose-binding lectin, a component of the innate immune system in preeclampsia nandor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Than, Gabor; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Tarca, Adi L.; Edwin, Samuel S.; Gotsch, Francesca] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48202 USA. [Hassan, Sonia; Espinoza, Jimmy; Mittal, Pooja; Mazaki-Tovi, Shali; Friel, Lara A.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. [Papp, Zoltan] Semmelweis Univ, Dept Obstet & Gynecol 1, Budapest, Hungary. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 477 BP S139 EP S139 DI 10.1016/j.ajog.2007.10.550 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500470 ER PT J AU Tita, A AF Tita, Alan TI The MFMU cesarean registry: Impact of gestational age at elective repeat cesarean on neonatal outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Tita, Alan] NICHD MEMU Network, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 86 BP S37 EP S37 DI 10.1016/j.ajog.2007.10.096 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500089 ER PT J AU Toso, L Johnson, A Bissell, S Spong, CY AF Toso, Laua Johnson, Andrea Bissell, Stephanie Spong, Catherine Y. TI Prevention of glial deficit in a Down syndrome model SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Toso, Laua; Johnson, Andrea; Bissell, Stephanie; Spong, Catherine Y.] NIH, NICHD, NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 63 BP S29 EP S29 DI 10.1016/j.ajog.2007.10.071 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500066 ER PT J AU Toso, L Johnson, A Bissell, S Roberson, R Vink, J Abebe, D Spong, C AF Toso, Laura Johnson, Andrea Bissell, Stephanie Roberson, Robin Vink, Joy Abebe, Daniel Spong, Catherine TI Prevention of learning deficit in a Down syndrome mouse model SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Toso, Laura; Johnson, Andrea; Bissell, Stephanie; Roberson, Robin; Abebe, Daniel; Spong, Catherine] NICHD, NIAAA, NIH, Bethesda, MD USA. [Vink, Joy] Georgetown Univ, Dept ObGyn, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 6 BP S3 EP S3 DI 10.1016/j.ajog.2007.10.007 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500009 ER PT J AU Tsai, J Klebanoff, M Qian, C Yu, K Levine, R AF Tsai, Jillian Klebanoff, Mark Qian, Cong Yu, Kai Levine, Richard TI Circulating angiogenic factors in spontaneous preterm labor and delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Tsai, Jillian] Vanderbilt Univ, Sch Med, Nashville, TN USA. [Klebanoff, Mark; Yu, Kai; Levine, Richard] NICHHD, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Qian, Cong] Allied Technol Grp, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 14 BP S7 EP S7 DI 10.1016/j.ajog.2007.10.016 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500017 ER PT J AU Vaisbuch, E Romero, R Erez, O Kusanovic, JP Gotsch, F Than, NG Mazaki-Tovi, S Mittal, P Edwin, SS Hassan, S AF Vaisbuch, Edi Romero, Roberto Erez, Offer Kusanovic, Juan Pedro Gotsch, Francesca Than, Nandor Gabor Mazaki-Tovi, Shali Mittal, Pooja Edwin, Samuel S. Hassan, Sonia TI Hemoglobin in amniotic fluid is increased in intra-amniotic infection/inflammation as well as in spontaneous labor at term SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Kusanovic, Juan Pedro; Gotsch, Francesca; Than, Nandor Gabor; Edwin, Samuel S.] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Mazaki-Tovi, Shali; Mittal, Pooja; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 118 BP S46 EP S46 DI 10.1016/j.ajog.2007.10.129 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500120 ER PT J AU Varner, M AF Varner, Michael TI Can fetal oxygen saturation predict chorioamnionitis? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Varner, Michael] NICHD, MFMU, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 638 BP S184 EP S184 DI 10.1016/j.ajog.2007.10.665 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500630 ER PT J AU Vink, J Toso, L Roberson, R Abebe, D Spong, C AF Vink, Joy Toso, Laura Roberson, Robin Abebe, Daniel Spong, Catherine TI Prevention of down syndrome learning deficits mediated through neuroprotective peptides, vasoactive intestinal peptide (VIP), and activity dependent neuroprotective peptide (ADNP) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Vink, Joy] Georgetown Univ, Washington, DC USA. [Toso, Laura; Roberson, Robin; Spong, Catherine] NIH, Bethesda, MD 20892 USA. [Abebe, Daniel] NICHD, NIAAA, NIH, Unit Perinatal & Dev Neurobiol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 606 BP S174 EP S174 DI 10.1016/j.ajog.2007.10.632 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500598 ER PT J AU Vink, J Toso, L Roberson, R Abebe, D Spong, C AF Vink, Joy Toso, Laura Roberson, Robin Abebe, Daniel Spong, Catherine TI Learning deficit prevention by NAP&SAL includes NMDA receptors in a down syndrome model SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Vink, Joy] Georgetown Univ, Washington, DC 20057 USA. [Toso, Laura; Roberson, Robin; Spong, Catherine] NIH, Bethesda, MD 20892 USA. [Abebe, Daniel] NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 SU S MA 433 BP S129 EP S129 DI 10.1016/j.ajog.2007.10.452 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500427 ER PT J AU Ward, C Hassan, S Romero, V Kusanovic, JP Nikita, L Mittal, P Espinoza, J Mazaki-Tovi, S Romero, R AF Ward, Clara Hassan, Sonia Romero, Vivian Kusanovic, Juan Pedro Nikita, Lorraine Mittal, Pom Espinoza, Jimmy Mazaki-Tovi, Shali Romero, Roberto TI The risk of preterm delivery in asymptomatic patients with a dynamic cervix SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Ward, Clara; Hassan, Sonia; Romero, Vivian; Nikita, Lorraine; Mittal, Pom; Espinoza, Jimmy; Mazaki-Tovi, Shali] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI USA. [Kusanovic, Juan Pedro; Romero, Roberto] DHHS, NIH, NICHD, Perinatol Res Branch, Detroit, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 135 BP S50 EP S50 DI 10.1016/j.ajog.2007.10.147 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500136 ER PT J AU Yan, R Nanovskaya, T Mattison, D Hankins, GDV Ahmed, M AF Yan, Ru Nanovskaya, Tatiana Mattison, Donald Hankins, Gary D. V. Ahmed, Mahmoud TI Metabolism of 17-hydroxyprogesterone caproate by human hepatic and placental microsomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Yan, Ru; Nanovskaya, Tatiana; Hankins, Gary D. V.; Ahmed, Mahmoud] Univ Texas Med Branch, Galveston, TX USA. [Mattison, Donald] NICHD, Ctr Res Mother & Children, Obstet Fetal Pharmacol Res Units, Bethesda, MD USA. RI Mattison, Donald/C-2015-2009; Yan, Ru/G-3480-2013; Mattison, Donald/L-4661-2013 OI Yan, Ru/0000-0001-6268-360X; Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2007 VL 197 IS 6 SU S MA 124 BP S48 EP S48 DI 10.1016/j.ajog.2007.10.135 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500126 ER PT J AU Zhang, J Sundaram, R Sun, WY Troendle, J AF Zhang, Jun Sundaram, Rajeshwari Sun, Wenyu Troendle, James TI Fetal growth and timing of parturition in humans: A prospective study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Zhang, Jun; Sundaram, Rajeshwari; Troendle, James] Natl Inst Hlth, Bethesda, MD USA. [Sun, Wenyu] NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 114 BP S45 EP S45 DI 10.1016/j.ajog.2007.10.125 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500116 ER PT J AU Zharikova, O Fokina, V Nanovskaya, T Ravindran, S Hill, R Mattison, D Hankins, GDV Ahmed, M AF Zharikova, Olga Fokina, Valentina Nanovskaya, Tatiana Ravindran, Selvan Hill, Ronald Mattison, Donald Hankins, Gary D. V. Ahmed, Mahmoud TI Identification of the major human hepatic and placental enzymes responsible for the metabolism of glyburide SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 28-FEB 02, 2008 CL Dallas, TX SP Soc Maternal Fetal Med C1 [Zharikova, Olga; Fokina, Valentina; Nanovskaya, Tatiana; Ravindran, Selvan; Hankins, Gary D. V.; Ahmed, Mahmoud] Univ Texas Med Branch, Galveston, TX USA. [Hill, Ronald] Univ Louisiana Monroe, Coll Pharm, Monroe, LA USA. [Mattison, Donald] NICHD, Ctr Res Mother & Children, Obstet Fetal Pharmacol Res Units Network, Bethesda, MD USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 2007 VL 197 IS 6 SU S MA 363 BP S111 EP S111 DI 10.1016/j.ajog.2007.10.380 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 242EY UT WOS:000251708500362 ER PT J AU Attardi, BJ Zeleznik, A Simhan, H Chiao, JP Mattison, DR Caritis, SN AF Attardi, Barbara J. Zeleznik, Anthony Simhan, Hyagriv Chiao, Jye Ping Mattison, Donald R. Caritis, Steve N. CA OFPRUN TI Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 22-25, 2006 CL Toronto, CANADA SP Soc Gynecol Invest DE glucocorticoid receptors; 17-alpha-hydroxyprogesterone caproate; preterm birth; progesterone receptors; transactivation ID BREAST-CANCER-CELLS; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; PRETERM DELIVERY; A-FORM; PARTURITION; TRANSCRIPTION; MYOMETRIUM; INITIATION; MECHANISM; PREGNANCY AB OBJECTIVE: This study was undertaken to determine whether the reduction in premature birth attributable to 17-alpha hydroxyprogesterone caproate occurs because of a greater affinity for progesterone or glucocorticoid receptors or by enhanced stimulation of progestogen responsive genes when compared with progesterone. STUDY DESIGN: We performed competitive steroid hormone receptor binding assays using cytosols expressing either recombinant human progesterone receptor-A or -B or rabbit uterine or thymic cytosols. We used 4 different carcinoma cell lines to assess transactivation of reporter genes or induction of alkaline phosphatase. RESULTS: Relative binding affinity of 17-alpha hydroxyprogesterone caproate for recombinant human progesterone receptor-B, recombinant human progesterone receptor-A, and rabbit progesterone receptors was 26-30% that of progesterone. Binding of progesterone to rabbit thymic glucocorticoid receptors was weak. 17-alpha hydroxyprogesterone caproate was comparable to progesterone in eliciting gene expression in all cell lines studied. CONCLUSION: Binding to progesterone receptors, glucocorticoid receptors, or expression of progesterone-responsive genes is no greater with 17-alpha hydroxyprogesterone caproate than with progesterone. Other mechanisms must account for the beneficial effect of 17-alpha hydroxyprogesterone caproate on preterm birth rates. C1 Bioqual Inc, Mol Endocrinol Lab, Rockville, MD 20580 USA. [Zeleznik, Anthony] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Simhan, Hyagriv; Chiao, Jye Ping; Caritis, Steve N.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Mattison, Donald R.] NICHHD, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. [OFPRUN] NICHHD, NIH, Bethesda, MD 20892 USA. RP Attardi, BJ (reprint author), Bioqual Inc, Mol Endocrinol Lab, Rockville, MD 20580 USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; caritis, steve/0000-0002-2169-0712 NR 36 TC 0 Z9 0 U1 1 U2 6 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 DEC PY 2007 VL 197 IS 6 AR 599.e1 DI 10.1016/j.ajog.2007.05.024 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 241SI UT WOS:000251675700014 ER PT J AU Bradley, CS Nygaard, IE Brown, MB Gutman, RE Kenton, KS Whitehead, WE Goode, PS Wren, PA Ghetti, C Weber, AM AF Bradley, Catherine S. Nygaard, Ingrid E. Brown, Morton B. Gutman, Robert E. Kenton, Kimberly S. Whitehead, William E. Goode, Patricia S. Wren, Patricia A. Ghetti, Chiara Weber, Anne M. CA Pelvic Floor Disorders Network TI Bowel symptoms in women 1 year after sacrocolpopexy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 13, 2007 CL Orlando, FL SP Soc Gynecol Surg DE abdominal sacrocolpopexy; bowel symptoms; constipation; pelvic organ prolapse; questionnaires ID PELVIC ORGAN PROLAPSE; RECTOVAGINAL FASCIA REATTACHMENT; RECTOCELE REPAIR; ABDOMINAL SACROCOLPOPEXY; POSTERIOR COMPARTMENT; FLOOR DISORDERS; DYSFUNCTION; CONSTIPATION; POPULATION; COLPOPEXY AB OBJECTIVE: The objective of the study was to evaluate changes in bowel symptoms after sacrocolpopexy. STUDY DESIGN: This was a prospectively planned, ancillary analysis of the Colpopexy and Urinary Reduction Efforts study, a randomized trial of sacrocolpopexy with or without Burch colposuspension in stress continent women with stages II - IV prolapse. In addition to sacrocolpopexy (+/- Burch), subjects underwent posterior vaginal or perineal procedures ( PR) at each surgeon's discretion. The preoperative and 1 year postoperative Colorectal-anal Distress Inventory (CRADI) scores were compared within and between groups using Wilcoxon signed-rank and rank-sum tests, respectively. RESULTS: The sacrocolpopexy + PR group (n = 87) had more baseline obstructive colorectal symptoms (higher CRADI and CRADI-obstructive scores: P = .04 and < .01, respectively) than the sacrocolpopexy alone group ( n = 211). CRADI total, obstructive, and pain/irritation scores significantly improved in both groups ( all P < .01). Most bothersome symptoms resolved after surgery in both groups. CONCLUSION: Most bowel symptoms improve in women with moderate to severe pelvic organ prolapse after sacrocolpopexy. C1 [Bradley, Catherine S.] Univ Iowa, Carver Coll Med, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. [Nygaard, Ingrid E.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Brown, Morton B.] Univ Michigan, Dept Biostat, Ann Arbor, MI USA. [Gutman, Robert E.] Johns Hopkins Sch Med, Dept Obstet & Gynecol, Baltimore, MD USA. [Kenton, Kimberly S.] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Whitehead, William E.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Goode, Patricia S.] Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham Atlanta Geriat Res Educ & Clin Ctr, Dept Med, Birmingham, AL USA. [Wren, Patricia A.] Oakland Univ, Sch Hlth Sci, Dept Wellness Hlth Promot & Injury Prevent, Rochester, MI USA. [Ghetti, Chiara] Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Dept Obstet & Gynecol, Pittsburgh, PA USA. [Weber, Anne M.] NIH, NICHHD, Bethesda, MD USA. RP Bradley, CS (reprint author), Univ Iowa, Carver Coll Med, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 AR 642.e1 DI 10.1016/j.ajog.2007.08.023 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 241SI UT WOS:000251675700033 ER PT J AU Burgio, KL Nygaard, IE Richter, HE Brubaker, L Gutman, RE Leng, W Wei, J Weber, AM AF Burgio, Kathryn L. Nygaard, Ingrid E. Richter, Holly E. Brubaker, Linda Gutman, Robert E. Leng, Wendy Wei, John Weber, Anne M. CA Pelvic Fl Disorders Network TI Bladder symptoms 1 year after abdominal sacrocolpopexy with and without Burch colposuspension in women without preoperative stress incontinence symptoms SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 13, 2007 CL Orlando, FL SP Soc Gynecol Surg DE irritative urinary symptoms; obstructive urinary symptoms; pelvic organ prolapse; sacrocolpopexy; urinary incontinence ID QUALITY-OF-LIFE; URINARY-INCONTINENCE; GENITAL PROLAPSE AB OBJECTIVE: The objective of the study was to examine changes in bladder symptoms 1 year after abdominal sacrocolpopexy (ASC) with vs without Burch colposuspension. STUDY DESIGN: Women without stress urinary incontinence (SUI) symptoms undergoing ASC were randomized to receive or not receive Burch. One year later, irritative, obstructive, and SUI symptoms were assessed in 305 women using Urogenital Distress Inventory subscales. A composite "stress endpoint" combined SUI symptoms, positive stress test, and retreatment. RESULTS: In all women, the mean irritative score decreased from 19.6 +/- 16.3 ( mean +/- SD) to 9.1 +/- 10.6; for obstructive symptoms, from 34.8 +/- 21.0 to 6.3 +/- 10.4 ( both P < .001). Preoperative bothersome irritative symptoms resolved in 74.6% ( 126 of 169) and obstructive symptoms in 85.1% ( 212 of 249), independent of Burch. Fewer women with Burch had urge incontinence (14.5% vs 26.8%, P = .048) and fulfilled the stress endpoint (25.0% vs 40.1%, P = .012). CONCLUSION: ASC reduced bothersome irritative and obstructive symptoms. Prophylactic Burch reduced stress and urge incontinence. C1 [Burgio, Kathryn L.] Univ Alabama, Sch Med, Dept Med, Birmingham, AL 35233 USA. [Richter, Holly E.] Univ Alabama, Sch Med, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. [Burgio, Kathryn L.] Geriat Res Educ & Clin Ctr, Dept Vet Affairs, Birmingham, AL USA. [Nygaard, Ingrid E.] Univ Utah, Ctr Hlth Sci, Dept Obstet & Gynecol, Salt Lake City, UT 84112 USA. [Brubaker, Linda] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Chicago, IL USA. [Gutman, Robert E.] Johns Hopkins Sch Med, Dept Gynecol & Obstet, Baltimore, MD USA. [Leng, Wendy] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15260 USA. [Wei, John] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI USA. [Weber, Anne M.] NIH, NICHHD, Bethesda, MD USA. RP Burgio, KL (reprint author), Univ Alabama, Birmingham VA Med Ctr, 11G, 700 S 19th St, Birmingham, AL 35233 USA. EM kburgio@aging.uab.edu NR 15 TC 0 Z9 0 U1 1 U2 1 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 DEC PY 2007 VL 197 IS 6 AR 647. e1 DI 10.1016/j.ajog.2007.08.048 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 241SI UT WOS:000251675700035 ER PT J AU Handa, VL Zyczynski, HM Burgio, KL Fitzgerald, MP Borello-France, D Janz, NK Fine, PM Whitehead, W Brown, MB Weber, AM AF Handa, Victoria L. Zyczynski, Halina M. Burgio, Kathryn L. Fitzgerald, Mary Pat Borello-France, Diane Janz, Nancy K. Fine, Paul M. Whitehead, William Brown, Morton B. Weber, Anne M. CA Pelvic Floor Disorders Network TI The impact of fecal and urinary incontinence on quality of life 6 months after childbirth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 13, 2007 CL Orlando, FL SP Soc Gynecol Surg DE childbirth; fecal incontinence; quality of life; urinary incontinence ID ANAL-SPHINCTER DISRUPTION; VAGINAL DELIVERY; PRIMIPAROUS WOMEN; OBSTETRICS UNIT; SEVERITY INDEX; SHORT-FORM; PREVALENCE; SYMPTOMS; STRESS; RISK AB OBJECTIVE: The objective of the study was to investigate the impact of postpartum fecal incontinence (FI) and urinary incontinence (UI) on quality of life (QOL). STUDY DESIGN: Seven hundred fifty-nine primiparous women in the Childbirth and Pelvic Symptoms study were interviewed 6 months postpartum. FI and UI were assessed with validated questionnaires. We measured QOL with SF-12 summary scores, health utility index score ( a measure of self-rated overall health), and the modified Manchester Health Questionnaire. RESULTS: Women with FI had worse self-rated health utility index scores (85.1 +/- 9.8 vs 88.0 +/- 11.6, P = .02) and Medical Outcomes Study Short Form Health Survey (SF-12) mental summary scores ( 46.8 +/- 9.2 vs 51.1 +/- 8.7, P <.0001) than women without FI or flatal incontinence. Women with UI had worse SF-12 mental summary scores (48.3 +/- 9.8 vs 51.6 +/- 7.8, P <.01) and self-rated health utility index scores (84.1 +/- 12.5 vs 88.7 +/- 10.1, P <.01) than women without UI. Women with both FI and UI had the lowest SF-12 mental summary scores (44.5 +/- 9.0). CONCLUSION: Six months after delivery, women experiencing FI or UI reported negative effects on health-related QOL. FI and UI together have a greater impact than either condition alone. C1 [Handa, Victoria L.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Zyczynski, Halina M.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Burgio, Kathryn L.] Univ Alabama, Tuscaloosa, AL 35487 USA. [Burgio, Kathryn L.] Birmingham VA Med Ctr, Birmingham, AL USA. [Fitzgerald, Mary Pat] Loyola Univ, Chicago, IL USA. [Borello-France, Diane] Duquesne Univ, Pittsburgh, PA USA. [Janz, Nancy K.; Brown, Morton B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Fine, Paul M.] Baylor Coll Med, Houston, TX USA. [Whitehead, William] Univ N Carolina, Chapel Hill, NC USA. [Weber, Anne M.] NIH, NICHHD, Chapel Hill, NC USA. RP Handa, VL (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA. FU NCRR NIH HHS [M01 RR002719-225499, M01 RR002719]; NICHD NIH HHS [U10 HD041268, U10 HD041263, U10 HD41268, U10 HD041248, U10 HD41250, U10 HD041268-05, U10 HD041267, U01 HD41249, U10 HD41248, U10 HD041269, U01 HD041249, U10 HD41269, U10 HD041261, U10 HD041250, U10 HD41267, U10 HD41263, U10 HD41261] NR 28 TC 4 Z9 4 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2007 VL 197 IS 6 AR 636.e1 DI 10.1016/j.ajog.2007.08.020 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 241SI UT WOS:000251675700030 PM 18060960 ER PT J AU Handa, VL Zyczynski, HM Brubaker, L Nygaard, I Janz, NK Richter, HE Wren, PA Brown, MB Weber, AM AF Handa, Victoria L. Zyczynski, Halina M. Brubaker, Linda Nygaard, Ingrid Janz, Nancy K. Richter, Holly E. Wren, Patricia A. Brown, Morton B. Weber, Anne M. CA Pelvic Fl Disorders Network TI Sexual function before and after sacrocolpopexy for pelvic organ prolapse SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 13, 2007 CL Orlando, FL SP Soc Gynecol Surg DE genital prolapse; sacrocolpopexy; sexual function ID STRESS URINARY-INCONTINENCE; BURCH COLPOSUSPENSION; RANDOMIZED-TRIAL; WOMEN; QUESTIONNAIRE; DYSFUNCTION; PREVALENCE; COLPOPEXY; SURGERY AB OBJECTIVE: The objective of the study was to describe sexual function before and after sacrocolpopexy. STUDY DESIGN: In the Colpopexy and Urinary Reduction Efforts trial, sexual function was assessed in 224 women with sexual partners before and 1 year after surgery using validated questionnaires. RESULTS: After surgery, significantly fewer women reported sexual interference from "pelvic or vaginal symptoms" (32.5% 1 year after surgery vs 7.8% prior to surgery); fear of incontinence (10.7% vs 3.3%); vaginal bulging (47.3% vs 4.6%); or pain (39.9% vs 21.6%). The proportion of women with infrequent sexual desire (32%) did not change. More women were sexually active 1 year after surgery (171, 76.3%) than before surgery (148, 66.1%). The 11 women (7.4%) who became sexually inactive were more likely than sexually active women to report infrequent sexual desire (70.0% vs 22.1%, P < .001). The addition of Burch colposuspension did not have an impact on postoperative sexual function. CONCLUSION: After sacrocolpopexy, most women reported improvements in pelvic floor symptoms that previously interfered with sexual function. The addition of Burch colposuspension did not adversely influence sexual function. C1 [Handa, Victoria L.] Johns Hopkins Univ, Dept Obstet & Gynecol, Baltimore, MD 21218 USA. [Zyczynski, Halina M.] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. [Brubaker, Linda] Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL USA. [Nygaard, Ingrid] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84112 USA. [Janz, Nancy K.] Univ Michigan, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Tuscaloosa, AL 35487 USA. [Wren, Patricia A.] Oakland Univ, Dept Wellness Hlth Promot & Injury Prevent, Rochester, MI USA. [Brown, Morton B.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Weber, Anne M.] NIH, NICHHD, Populat Res Ctr, Contracept & Reprod Hlth Branch, Bethesda, MD USA. RP Handa, VL (reprint author), Johns Hopkins Univ, Dept Obstet & Gynecol, Baltimore, MD 21218 USA. FU NICHD NIH HHS [U10 HD041263-05, U10 HD41268, U10 HD41248, U10 HD041263, U10 HD041248-05, U10 HD41261, U10 HD041268, U10 HD041250-07, U10 HD41269, U10 HD41250, R01 HD041610-05, U10 HD041248, U10 HD041269-03, U10 HD041261, U10 HD041250, U10 HD41267, U01 HD041249-07, U10 HD41263, U10 HD041267-07, U01 HD41249, U10 HD041268-05, K12 HD001267-05, U10 HD041269, U01 HD041249, U10 HD041267, U10 HD041261-07] NR 21 TC 4 Z9 5 U1 0 U2 1 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 DEC PY 2007 VL 197 IS 6 AR 629.e1 DI 10.1016/j.ajog.2007.08.016 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 241SI UT WOS:000251675700027 PM 18060957 ER PT J AU Shah, JP Parikh, S Danoff, J Gerber, LH AF Shah, Jay P. Parikh, Sagar Danoff, Jerome Gerber, Lynn H. TI Re: The myofascial trigger point region: Correlation between the degree of irritability and the prevalence of endplate noise SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Letter C1 Natl Inst Hlth, Dept Rehabil Med, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Brunswick, NJ USA. George Washington Univ, Med Ctr, Dept Exercise Sci, Washington, DC USA. George Mason Univ, Coll Hlth & Human Serv, Fairfax, VA USA. RP Shah, JP (reprint author), Natl Inst Hlth, Dept Rehabil Med, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 2007 VL 86 IS 12 BP 1033 EP 1034 DI 10.1097/01.phm.0000297445.62886.08 PG 2 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 237DG UT WOS:000251352600017 PM 18090449 ER PT J AU McConville, P Lakatta, EG Spencer, RG AF McConville, Patrick Lakatta, Edward G. Spencer, Richard G. TI Greater glycogen utilization during beta(1)- than beta(2)-adrenergic receptor stimulation in the isolated perfused rat heart SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE receptors; adrenergic; metabolism; magnetic resonance spectroscopy ID BETA-ADRENERGIC STIMULATION; NOREPINEPHRINE INFUSION; ENERGY-METABOLISM; CELLS; PHOSPHORYLATION; ADENOSINE; TURNOVER; P-31-NMR; INCREASE; GLUCOSE AB Differences in energy metabolism during beta(1) and beta(2)-adrenergic receptor (AR) stimulation have been shown to translate to differences in the elicited functional responses. It has been suggested that differential access to glycogen during beta(1) compared with beta(2)-AR stimulation may influence the peak functional response and modulation of the response during sustained adrenergic stimulation. Interleaved C-13 and P-31-NMR spectroscopy was used during beta(1) and beta(2)-AR stimulation at matched peak workload (2.5 times baseline) in the isolated perfused rat heart to monitor glycogen levels phosphorylation potential and intracellular pH. Simultaneous measurements of left ventricular (LV) function [LV developed pressure (LVDP)] heart rate (HR) and rate-pressure product (RPP = LVDP X HR) were also performed. The heart was perfused under both substrate-free (SF) conditions and with exogenous glucose (G). The greater glycogenolysis was observed during beta(1) than beta(2)-AR stimulation with G (54% vs. 38% reduction P = 0.006) and SF (92% vs. 79% reduction P = 0.04) perfusions. The greater beta(1)-AR-mediated glycogenolysis was correlated with greater ability to sustain the initial contractile response. However with SF perfusion the duration of this ability was limited: excessive early glycogen depletion caused an earlier decline in LVDP and phosphorylation potential during beta(1) than beta(2)-AR stimulation. Therefore endogenous glycogen stores are depleted earlier and to a greater extent despite a slightly weaker overall inotropic response during beta(1) than beta(2)-AR stimulation. These findings are consistent with beta(1)-AR-specific PKA-dependent glycogen phosphorylase kinase signaling. C1 Clin Invest Lab, Magnet Resonance Imaging & Spectroscopy Sect, Bethesda, MD USA. NIA, NIH, Gerontol Res Ctr, Cardiovasc Sci Lab, Bethesda, MD 20892 USA. RP Spencer, RG (reprint author), Gerontol Res Ctr, Clin Invest Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM spencerri@grc.nia.nih.gov FU Intramural NIH HHS NR 31 TC 5 Z9 5 U1 1 U2 3 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 DEC PY 2007 VL 293 IS 6 BP E1828 EP E1835 DI 10.1152/ajpendo.00288.2007 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 239HU UT WOS:000251510200044 PM 17911346 ER PT J AU Jobsis, PD Ashikaga, H Wen, H Rothstein, EC Horvath, KA McVeigh, ER Balaban, RS AF Jobsis, Paul D. Ashikaga, Hiroshi Wen, Han Rothstein, Emily C. Horvath, Keith A. McVeigh, Elliot R. Balaban, Robert S. TI The visceral pericardium: macromolecular structure and contribution to passive mechanical properties of the left ventricle SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE collagen; diastolic function; myocardial elasticity; residual stress; water permeability; elastin; 2-photon microscopy; porcine heart; optical properties ID CANINE LEFT VENTRICLE; RAT LEFT-VENTRICLE; 2ND-HARMONIC GENERATION; DIASTOLIC FUNCTION; CONNECTIVE-TISSUE; CARDIAC-MUSCLE; HUMAN HEART; COLLAGEN; DISPLACEMENT; STRAIN AB Much attention has been focused on the passive mechanical properties of the myocardium, which determines left ventricular (LV) diastolic mechanics, but the significance of the visceral pericardium (VP) has not been extensively studied. A unique en face three-dimensional volumetric view of the porcine VP was obtained using two-photon excitation fluorescence to detect elastin and backscattered second harmonic generation to detect collagen, in addition to standard light microscopy with histological staining. Below a layer of mesothelial cells, collagen and elastin fibers, extending several millimeters, form several distinct layers. The configuration of the collagen and elastin layers as well as the location of the VP at the epicardium providing a geometric advantage led to the hypothesis that VP mechanical properties play a role in the residual stress and passive stiffness of the heart. The removal of the VP by blunt dissection from porcine LV slices changed the opening angle from 53.3 +/- 10.3 to 27.3 +/- 5.7 degrees (means +/- SD, P < 0.05, n = 4). In four porcine hearts where the VP was surgically disrupted, a significant decrease in opening angle was found (35.5 +/- 4.0 degrees) as well as a rightward shift in the ex vivo pressure-volume relationship before and after disruption and a decrease in LV passive stiffness at lower LV volumes (P < 0.05). These data demonstrate the significant and previously unreported role that the VP plays in the residual stress and passive stiffness of the heart. Alterations in this layer may occur in various disease states that effect diastolic function. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Rm B1D416,MSC 1061,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsb@nih.gov RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010; OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997; Ashikaga, Hiroshi/0000-0003-3689-6892 FU Intramural NIH HHS [Z01 HL004601-20] NR 42 TC 19 Z9 19 U1 0 U2 6 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 DEC PY 2007 VL 293 IS 6 BP H3379 EP H3387 DI 10.1152/ajpheart.00967.2007 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 237TW UT WOS:000251400300019 PM 17933976 ER PT J AU Zheng, J Wang, R Zambraski, E Wu, D Jacobson, KA Liang, BT AF Zheng, Jingang Wang, Rubio Zambraski, Edward Wu, Dan Jacobson, Kenneth A. Liang, Bruce T. TI Protective roles of adenosine A1, A(2A), and A(3) receptors in skeletal muscle ischemia and reperfusion injury SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE wild-type mice; creatine kinase; phosolipase C ID MUSCULAR-DYSTROPHY; TARGETED DELETION; MOUSE HEART; MAST-CELLS; KNOCK-OUT; IN-VIVO; MYOCARDIUM; ACTIVATION; KINASE; MICE AB Although adenosine exerts cardio-and vasculoprotective effects, the roles and signaling mechanisms of different adenosine receptors in mediating skeletal muscle protection are not well understood. We used a mouse hindlimb ischemia-reperfusion model to delineate the function of three adenosine receptor subtypes. Adenosine A(3) receptor-selective agonist 2-chloro-N-6-(3-iodobenzyl) adenosine-5'-N-methyluronamide (Cl-IBMECA; 0.07 mg/kg ip) reduced skeletal muscle injury with a significant decrease in both Evans blue dye staining (5.4 +/- 2.6%, n = 8 mice vs. vehicle-treated 28 +/- 6%, n = 7 mice, P < 0.05) and serum creatine kinase level (1,840 +/- 910 U/l, n = 13 vs. vehicle-treated 12,600 +/- 3,300 U/l, n = 14, P < 0.05), an effect that was selectively blocked by an A(3) receptor antagonist 3-ethyl-5-benzyl-2-methyl-6phenyl- 4-phenylethynyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS-1191; 0.05 mg/kg). The adenosine A(1) receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 0.05 mg/kg) also exerted a cytoprotective effect, which was selectively blocked by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.2 mg/kg). The adenosine A(2A) receptor agonist 2-p-(2-carboxyethyl) phenethylamino5' -N-ethylcarboxamidoadenosine (CGS-21680; 0.07 mg/kg)-induced decrease in skeletal muscle injury was selectively blocked by the A2A antagonist 2-(2-furanyl)-7-[ 3-(4-methoxyphenyl) propyl]-7Hpyrazolo[ 4,3-e] [1,2,4] triazolo[ 1,5-C] pyrimidin-5-amine (SCH-442416; 0.017 mg/kg). The protection induced by the A(3) receptor was abrogated in phospholipase C-beta 2/beta 3 null mice, but the protection mediated by the A(1) or A(2A) receptor remained unaffected in these animals. The adenosine A(3) receptor is a novel cytoprotective receptor that signals selectively via phospholipase C-beta and represents a new target for ameliorating skeletal muscle injury. C1 Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06030 USA. USA, Environm Med Res Inst, Natick, MA 01760 USA. Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT USA. Natl Inst Hlth, Natl Inst Diabet & Digest & Kidney Dis, Mol Recognit Sect, Bethesda, MD USA. RP Liang, BT (reprint author), Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, MC-3946,263 Farmington Ave, Farmington, CT 06030 USA. EM bliang@uchc.edu RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL080706, R01 HL080706-10, R01 HL080706-11, R01 HL080706-12, R01 HL080706-13]; NIGMS NIH HHS [R01 GM054597] NR 43 TC 29 Z9 30 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 DEC PY 2007 VL 293 IS 6 BP H3685 EP H3691 DI 10.1152/ajpheart.00819.2007 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 237TW UT WOS:000251400300054 PM 17921328 ER PT J AU Reichel, V Masereeuw, R van den Heuvel, JJMW Miller, DS Fricker, G AF Reichel, Valeska Masereeuw, Rosalinde van den Heuvel, Jeroen J. M. W. Miller, David S. Fricker, Gert TI Transport of a fluorescent cAMP analog in teleost proximal tubules SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE killifish; multidrug resistance-associated protein 4 ID ORGANIC ANION TRANSPORTER; PROTEIN-KINASE-C; MULTIDRUG-RESISTANCE; CONFOCAL MICROSCOPY; DRUG EFFLUX; SHORT-TERM; KIDNEY; SECRETION; FAMILY; GENE AB Previous studies have shown that killifish ( Fundulus heteroclitus) renal proximal tubules express a luminal membrane transporter that is functionally and immunologically analogous to the mammalian multidrug resistance-associated protein isoform 2 ( Mrp2, ABCC2). Here we used confocal microscopy to investigate in killifish tubules the transport of a fluorescent cAMP analog ( fluo-cAMP), a putative substrate for Mrp2 and Mrp4 ( ABCC4). Steady-state luminal accumulation of fluo-cAMP was concentrative, specific, and metabolism-dependent, but not reduced by high K + medium or ouabain. Transport was not affected by p-aminohippurate ( organic anion transporter inhibitor) or p-glycoprotein inhibitor ( PSC833), but cell-to-lumen transport was reduced in a concentration-dependent manner by Mrp inhibitor MK571, leukotriene C4 ( LTC4), azidothymidine ( AZT), cAMP, and adefovir; the latter two compounds are Mrp4 substrates. Although MK571 and LTC4 reduced transport of the Mrp2 substrate fluorescein-methotrexate ( FL-MTX), neither cAMP, adefovir, nor AZT affected FL-MTX transport. Fluo-cAMP transport was not reduced when tubules were exposed to endothelin-1, Na nitroprusside ( an nitric oxide generator) or phorbol ester ( PKC activator), all of which signal substantial reductions in cell-to-lumen FL-MTX transport. Fluo-cAMP transport was reduced by forskolin, and this reduction was blocked by the PKA inhibitor H-89. Finally, in membrane vesicles from Spodoptera frugiperda ( Sf9) cells containing human MRP4, ATP-dependent and specific uptake of fluo-cAMP could be demonstrated. Thus, based on inhibitor specificity and regulatory signaling, cell-to-lumen transport of fluo-cAMP in killifish renal tubules is mediated by a transporter distinct from Mrp2, presumably a teleost form of Mrp4. C1 Univ Heidelberg, Inst Pharm & Mol Biotechnol, Heidelberg, Germany. Radboud Univ Nijmegen Med Ctr, Nijmegen Ctr Mol Life Sci, Dept Pharmacol & Toxicol, Nijmegen, Netherlands. Natl Inst Environm Hlth Sci, Natl Inst Hlth, Chem Pharmacol Lab, Res Triangle Pk, NC USA. RP Fricker, G (reprint author), Inst Pharm & Mol Biotechnol, INF 366, D-69120 Heidelberg, Germany. EM gert.fricker@uni-hd.de RI Masereeuw, Roos/N-3582-2014 FU NIEHS NIH HHS [ES-03828] NR 34 TC 15 Z9 15 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 2007 VL 293 IS 6 BP R2382 EP R2389 DI 10.1152/ajpregu.00029.2007 PG 8 WC Physiology SC Physiology GA 237TT UT WOS:000251400000027 PM 17855498 ER PT J AU Backinger, CL O'Connell, ME AF Backinger, Cathy L. O'Connell, Mary E. TI Developing consensus on tobacco control and research SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID SMOKING-CESSATION; POPULATION HARM; UNITED-STATES; INTERVENTIONS; ADULTS; RISK C1 NIH, NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP O'Connell, ME (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd, Rockville, MD 20852 USA. EM oconnellm@mail.nih.gov NR 20 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD DEC PY 2007 VL 33 IS 6 SU S BP S311 EP S313 DI 10.1016/j.amepre.2007.09.012 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 235PW UT WOS:000251247800001 PM 18021904 ER PT J AU Yende, S Angus, DC Ding, JZ Newman, AB Kellum, JA Li, RL Ferrell, RE Zmuda, J Kritchevsky, SB Harris, TB Garcia, M Yaffe, K Wunderink, RG AF Yende, Sachin Angus, Derek C. Ding, Jingzhong Newman, Anne B. Kellum, John A. Li, Rongling Ferrell, Robert E. Zmuda, Joseph Kritchevsky, Stephen B. Harris, Tamara B. Garcia, Melissa Yaffe, Kristine Wunderink, Richard G. CA Hlth ABC Study TI 4G/5G plasminogen activator inhibitor-1 polymorphisms and haplotypes are associated with pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE pneumonia; inflammatory markers; PAI-1; gene; haplotype ID COMMUNITY-ACQUIRED PNEUMONIA; ACUTE LUNG INJURY; IN-VITRO; PLASMINOGEN-ACTIVATOR-INHIBITOR-1 GENE; CRYPTOCOCCUS-NEOFORMANS; PNEUMOCOCCAL PNEUMONIA; MYOCARDIAL-INFARCTION; UROKINASE-DEFICIENT; IMMUNE-RESPONSE; CANDIDATE GENES AB Rationale: Plasminogen activator inhibitor (PAI)-1 inhibits urokinase and tissue plasminogen activator, required for host response to infection. Whether variation within the PAI-1 gene is associated with increased susceptibility to infection is unknown. Objectives: To ascertain the role of the 4G/5G polymorphism and other genetic variants within the PAI-1 gene. We hypothesized that variants associated with increased PAI-1 expression would be associated with an increased occurrence of community-acquired pneumonia (CAP). Methods. Longitudinal analysis (>12 yr) of the Health, Aging, and Body Composition cohort, aged 65-74 years at start of analysis. Measurements and Main Results: We genotyped the 4G/5G PAI-1 polymorphism and six additional single nucleotide polymorphisms. Of the 3,075 subjects, 272 (8.8%) had at least one hospitalization for CAP. Among whites, variants at the PAI4G,5G, PAI2846, and PAI7343 sites had higher risk of CAP (P = 0.018, 0.021, and 0.021, respectively). At these sites, variants associated with higher PAI-1 expression were associated with increased CAP susceptibility. Compared with the 5G/5G genotypes at PAI4G,5G site, the 4G/4G and 4G/5G genotypes were associated with a 1.98-fold increased risk of CAP (95% confidence interval, 1.2-3.2; P = 0.006). In whole blood stimulation assay, subjects with a 4G allele had 3.3- and 1.9-fold increased PAI-1 expression (P = 0.043 and 0.034, respectively). In haplotype analysis, the 4G/G/C/A haplotype at the PAI4G,5G, PAI2846, PAI4588, and PAI7343 single nucleotide polymorphisms was associated with higher CAP susceptibility, whereas the 5G/G/C/A haplotype was associated with lower CAP susceptibility. No associations were seen among blacks. Conclusions: Genotypes associated with increased expression of PAI-1 were associated with increased susceptibility to CAP in elderly whites. C1 Univ Pittsburgh, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA 15261 USA. Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Psychiat Neurol & Epidemiol, San Francisco, CA 94143 USA. Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Yende, S (reprint author), Univ Pittsburgh, Dept Crit Care Med, CRISMA Lab, 642A Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM yendes@upmc.edu RI Newman, Anne/C-6408-2013; Angus, Derek/E-9671-2012; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781; Wunderink, Richard/0000-0002-8527-4195 FU NHLBI NIH HHS [R01HL74104]; NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2101, N01-AG-6-2106]; NIGMS NIH HHS [R01 GM61992] NR 48 TC 28 Z9 31 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2007 VL 176 IS 11 BP 1129 EP 1137 DI 10.1164/rccm.200605-644OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 237OG UT WOS:000251384100011 PM 17761618 ER PT J AU Deshpande, KK Summers, RM Van Uitert, RL Franaszek, M Brown, L Dwyer, AJ Fletcher, JG Choi, JR Pickhardt, PJ AF Deshpande, Keshav K. Summers, Ronald M. Van Uitert, Robert L. Franaszek, Marek Brown, Linda Dwyer, Andrew J. Fletcher, Joel G. Choi, J. Richard Pickhardt, Perry J. TI Quality assessment for CT colonography: Validation of automated measurement of colonic distention and residual fluid SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Virtual Colonoscopy CY 2006 CL Boston, MA DE colon; colonography; CT; quality; virtual colonoscopy ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL NEOPLASIA; VIRTUAL COLONOSCOPY; CARBON-DIOXIDE; INSUFFLATION AB OBJECTIVE. The purpose of this study was to validate automated quality assessment (QA) software for CT colonography (CTC) by comparing results obtained with the software with results of interpretation by radiologists in the assessment of colonic distention and surface area obscured by residual fluid. MATERIALS AND METHODS. CTC scans of 30 patients were selected retrospectively to span ranges of luminal distention (well distended to poorly distended) and surface area covered by residual fluid (high amount of coverage to low amount of coverage). We used QA software developed in our laboratory to automatically measure the mean distention of each of five colonic segments (ascending, transverse, descending, sigmoid, and rectum). Three experienced radiologists visually graded each scan for distention and fluid coverage. Distention and fluid scores for specific segments were assessed with Bland-Altman analysis (mean difference with 95% limits of agreement) and the weighted kappa test. Interobserver and intraobserver variability was determined with the weighted kappa test. RESULTS. For distention scoring, the mean difference between radiologists and the QA software was 0.1% (95% limits of agreement, -25.6% and 25.9%). For fluid scoring, the mean difference was -0.6% (95% limits of agreement, -8.2% and 7.1%). There was moderate to good agreement (weighted kappa value, 0.50 - 0.78) between the radiologists' mean scores and the scores obtained with the QA software and for interreader and intrareader assessments of distention and fluid coverage. CONCLUSION. Results with the QA software agreed with radiologists' assessment of colonic distention and residual fluid coverage but were a more objective assessment. Use of this QA software can help standardize two important factors, distention and residual fluid coverage, that affect the quality of CTC, reducing two known causes of poor CTC performance. C1 NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Mayo Clin, Dept Radiol, Rochester, MN USA. Uniformed Serv Univ Hlth Sci, Walter Reed Army Med Ctr, Dept Radiol, Washington, DC USA. Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bldg 10, Rm 1C368X, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 18 TC 9 Z9 9 U1 0 U2 3 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 DEC PY 2007 VL 189 IS 6 BP 1457 EP 1463 DI 10.2214/AJR.07.2327 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 234NY UT WOS:000251172000031 PM 18029885 ER PT J AU Breman, JG Alilio, MS White, NJ AF Breman, Joel G. Alilio, Martin S. White, Nicholas J. TI Defining and defeating the intolerable burden of malaria III. Progress and perspectives - Objectives and Acknowledgements SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material C1 [Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Acad Educ Dev, NetMark Global Hlth Populat & Nutr Grp, Washington, DC USA. Mahidol Univ, Bangkok 10700, Thailand. Univ Oxford, Oxford, England. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Bldg 16,Rm 214,16 Ctr Dr,MSC 6705, Bethesda, MD 20892 USA. EM jbreman@nih.gov RI White, Nicholas/I-4629-2012 NR 0 TC 1 Z9 2 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 DEC PY 2007 VL 77 IS 6 SU S BP I EP II PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 249FJ UT WOS:000252212600001 ER PT J AU Glass, RI Fauci, AS AF Glass, Roger I. Fauci, Anthony S. TI Defining and defeating the intolerable burden of malaria III. Progress and perspectives - Introduction SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material C1 [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIH, NIAID, Bethesda, MD 20892 USA. RP Glass, RI (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr,Room B2C02,MSC 2220, Bethesda, MD 20892 USA. EM glassr@mail.nih.gov 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 DEC PY 2007 VL 77 IS 6 SU S BP IV EP V PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 249FJ UT WOS:000252212600003 ER PT J AU Breman, JG Alilio, MS White, NJ AF Breman, Joel G. Alilio, Martin S. White, Nicholas J. TI Defining and defeating the intolerable burden of malaria III. Progress and perspectives SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID SUB-SAHARAN AFRICA; COMBINATION THERAPY; VACCINE DEVELOPMENT; ANTIMALARIAL-DRUGS; RESISTANT MALARIA; WESTERN KENYA; MORTALITY; IMPACT; INTERVENTIONS; CHALLENGES C1 [Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Acad Educ Dev, NetMark Global Hlth Populat & Nutr Grp, Washington, DC USA. Mahidol Univ, Bangkok 10700, Thailand. Univ Oxford, Oxford OX1 2JD, England. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM jbreman@nih.gov RI White, Nicholas/I-4629-2012 NR 46 TC 11 Z9 13 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 DEC PY 2007 VL 77 IS 6 SU S BP VI EP XI PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 249FJ UT WOS:000252212600004 ER PT J AU Breman, JG Holloway, CN AF Breman, Joel G. Holloway, Cherice N. TI Malaria surveillance counts SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; ANTIMALARIAL-DRUG RESISTANCE; SUB-SAHARAN AFRICA; SEVERE ANEMIA; CHILDREN; BURDEN; MORTALITY; MORBIDITY; PREGNANCY; MODERATE AB Clinical and epidemiologic surveillance of malaria cases and deaths is required to follow the progress of the reinvigorated malaria control programs nationally and internationally. Current recording, transmittal, analysis, feedback, and use of malaria surveillance information is delayed and imprecise: substantially < 10% of the malaria cases and deaths are being reported. Improvements are occurring, but more emphasis should be placed on prompt, accurate diagnosis, patient management. and recording of clinical manifestations at hospitals. Neurologic signs, severe anemia, metabolic changes. hyperparasitemia, and concurrent sepsis are medical emergencies and require proper clinical and laboratory detection: equipment, reagents, supervision, and certification of laboratorians and clinicians are necessary. Birth weight should also be a major measure of progress in malarial control and overall prenatal care. Although malaria is the most frequent diagnosis at outpatient clinics and hospitals in Africa, co-existing conditions also mandate improved diagnosis, treatment. and registration. Monthly transmittal of information from health units and collation, analysis and feedback through electronic reporting systems using modern information technologies are necessary for resource planning and staff motivation. Denominators to compute rates of illness and death require accurate censuses of communities from which patients come to health units: specialized disease and demographic household surveys designed and performed by nationals are needed to complement hospital-based numerator data. Plasmodium falciparum and P. vivax should be distinguished in the laboratory; the former causes the greatest mortality but the latter is increasingly recognized as a major peril. Because vector control is now a major component of all malaria control programs, there is an urgent need to monitor anopheline sensitivity to insecticides and entomologic inoculation rates. Where interrupting transmission is a goal, parasite rates in groups at greatest risk should be performed. Continual monitoring of plasmodial sensitivity to drugs is necessary using WHO protocols. Human, entomological, and parasitological surveillance must be performed at the came time in the same places and the information shared widely and used for improving control strategies and tactics. These surveillance priorities require training, provision of equipment, supervision, and commitment to sustainability by national authorities and international collaborators and donors. C1 [Breman, Joel G.; Holloway, Cherice N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM jbreman@nih.gov NR 52 TC 33 Z9 34 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 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2007 VL 77 IS 6 SU S BP 36 EP 47 PG 12 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 249FJ UT WOS:000252212600010 PM 18165473 ER PT J AU Sadasivaiah, S Tozan, Y Breman, JG AF Sadasivaiah, Shobha Tozan, Yesim Breman, Joel G. TI Dichlorodiphenyltrichloroethane (DDT) for indoor residual spraying in Africa: How can it be used for malaria control? SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Review ID RESISTANCE MANAGEMENT STRATEGIES; PLASMODIUM-FALCIPARUM MALARIA; INSECTICIDE-TREATED BEDNETS; ANOPHELES-FUNESTUS DIPTERA; SOUTH-AFRICA; VECTOR CONTROL; ALTERNATIVE INSECTICIDES; ENVIRONMENTAL-MANAGEMENT; PYRETHROID INSECTICIDES; KNOCKDOWN RESISTANCE AB In 2006, the World Health Organization issued a position statement promoting the use of indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) for malaria vector control in epidemic and endemic areas. Other international organizations concurred because of the great burden of malaria and the relative ineffectiveness of current treatment and control strategies. Although the Stockholm Convention of 2001 targeted DDT as 1 of 12 persistent organic pollutants for phase-out and eventual elimination, it allowed a provision for its continued indoor use for disease vector control. Although DDT is a low-cost antimalarial tool, the possible adverse human health and environmental effects of exposure through IRS must be carefully weighed against the benefits to malaria control. This article discusses the controversy surrounding the use of DDT for IRS; its effective implementation in Africa; recommendations for deployment today, and training, monitoring, and research needs for effective and sustainable implementation. We consider the costs and cost effectiveness of IRS with DDT, alternative insecticides to DDT, and the importance of integrated vector control if toxicity, resistance, and other issues restrict its use. C1 [Tozan, Yesim; Breman, Joel G.] NIH, Forgarty Int Ctr, Dis Control Priorities Project, Bethesda, MD 20892 USA. [Sadasivaiah, Shobha] Cornell Univ, Weill Cornell Med Coll, New York, NY USA. [Tozan, Yesim] Columbia Univ, Earth Inst, New York, NY 10025 USA. RP Breman, JG (reprint author), NIH, Forgarty Int Ctr, Dis Control Priorities Project, Bldg 16,Room 214,16 Ctr Dr,MSC 6705, Bethesda, MD 20892 USA. EM shs2019@med.cornell.edu; tozany@mail.nih.gov; jbreman@nih.gov NR 114 TC 57 Z9 58 U1 5 U2 21 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 DEC PY 2007 VL 77 IS 6 SU S BP 249 EP 263 PG 15 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 249FJ UT WOS:000252212600037 PM 18165500 ER PT J AU Bates, N Herrington, J AF Bates, Nicole Herrington, James TI Advocacy for malaria prevention, control, and research in the twenty-first century SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ARTEMISININ; AFRICAN AB Until recent years, public interest and political investment in malaria prevention, control, and research have been stagnant. The global malaria agenda is now experiencing an unprecedented time of public and political will and momentum. At the heart of this favorable period lies a nascent, but increasingly sophisticated, global advocacy effort that has contributed to new and expanded malaria funding, programs, and technology. This paper reviews the elements of malaria's rise to political and public prominence, tracks the increase in funding and policy commitments to malaria over the past decade, and comments on an evolving policymaking progress, increasing transparency and accountability in program governance, and the impact of philanthropic investments in malaria advocacy. In addition, the principles of sound advocacy are described along with the mechanisms that will underlie sustained pro-political momentum for malaria research, resources, and results. C1 [Bates, Nicole] Global Hlth Council, Washington, DC 20036 USA. [Herrington, James] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Herrington, J (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr,MSC 2220,Bldg 31,Rm B2C11, Bethesda, MD 20892 USA. EM nbates@globalhealth.org; herringtonj@mail.nih.gov NR 31 TC 6 Z9 6 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 DEC PY 2007 VL 77 IS 6 SU S BP 314 EP 320 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 249FJ UT WOS:000252212600045 PM 18165508 ER PT J AU Dicko, A Sagara, I Diemert, D Sogoba, M Niambele, MB Dao, A Dolo, G Yalcouye, D Diallo, DA Saul, A Miller, LH Toure, YT Klion, AD Doumbo, OK AF Dicko, Alassane Sagara, Issaka Diemert, David Sogoba, Moussa Niambele, Mohamed B. Dao, Adama Dolo, Guimogo Yalcouye, Daniel Diallo, Dapa A. Saul, Allan Miller, Louis H. Toure, Yeya T. Klion, Amy D. Doumbo, Ogobara K. TI Year-to-year variation in the age-specific incidence of clinical malaria in two potential vaccine testing sites in Mali with different levels of malaria transmission intensity SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PLASMODIUM-FALCIPARUM TRANSMISSION; MORBIDITY; AFRICA; PROGRESS; CHILDREN; KENYA AB To explore the feasibility of field sites for malaria vaccine trials, we conducted a prospective study of clinical malaria incidence during two consecutive transmission seasons in children and young adults living in two areas of Mali with different entomologic inoculation rates (EIRs). Approximately 200 subjects (3 months to 2 years of age) were enrolled per site and followed weekly. Malaria smears were performed monthly in all participants and when symptoms or signs of malaria were present. In Sotuba (annual EIR < 15 infective bites per person), the incidence of clinical malaria was comparable across all age groups but varied significantly between the 2 years. In contrast, in Doneguebougou (annual EIR > 100 infective bites per person), incidence rates decreased significantly with increasing age but remained stable between years. Our results suggest that, although the age distribution of clinical malaria depends on transmission intensity, the total burden of disease may be similar or higher in settings of low transmission. C1 Univ Bamako, Pharm & Odonto Stomatol, Fac Med, Dept Epidemiol Parasitic Dis,Malaria Res & Traini, Bamako, Mali. Natl Inst Hlth, NIAID, Parasit Dis Lab, Malaria Vaccine Dev Branch, Bethesda, MD USA. RP Doumbo, OK (reprint author), Univ Bamako, Fac Med, Pharm & Odonto Stomatol, BP 1805, Bamako, Mali. EM okd@mrtcbko.org RI Saul, Allan/I-6968-2013; OI Saul, Allan/0000-0003-0665-4091; Klion, Amy/0000-0002-4986-5326 FU Intramural NIH HHS NR 16 TC 20 Z9 20 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 DEC PY 2007 VL 77 IS 6 BP 1028 EP 1033 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 248AH UT WOS:000252123200007 PM 18165516 ER PT J AU Niederehe, G AF Niederehe, George TI Mary Starke Harper (1919-2006) SO AMERICAN PSYCHOLOGIST LA English DT Biographical-Item C1 [Niederehe, George] NIMH, Bethesda, MD 20892 USA. RP Niederehe, G (reprint author), NIMH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD DEC PY 2007 VL 62 IS 9 BP 1071 EP 1071 DI 10.1037/0003-066X.62.9.1071 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 240GU UT WOS:000251576300009 ER PT J AU O'Shaughnessy, TJ Pancrazio, JJ AF O'Shaughnessy, Thomas J. Pancrazio, Joseph J. TI Broadband detection of environmental neurotoxicants SO ANALYTICAL CHEMISTRY LA English DT Article ID CULTURED NEURONAL NETWORKS; CELL-BASED BIOSENSORS; EARLY WARNING SYSTEMS; EMBRYONIC STEM-CELLS; MICROELECTRODE ARRAY; IN-VITRO; TRIMETHYLOLPROPANE PHOSPHATE; FISH CHROMATOPHORES; ACTION-POTENTIALS; NEURAL-NETWORKS C1 Natl Inst Hlth, Bethesda, MD 20892 USA. RP O'Shaughnessy, TJ (reprint author), Naval Res Lab, Code 6900, 4555 Overlook Ave, SW, Washington, DC USA. EM Thomas.oshaughnessy@nrl.navy.mil RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 NR 88 TC 8 Z9 8 U1 0 U2 12 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 DEC 1 PY 2007 VL 79 IS 23 BP 8838 EP 8845 PG 8 WC Chemistry, Analytical SC Chemistry GA 236OH UT WOS:000251311900011 ER PT J AU Lee, J Huang, BX Yuan, Z Kim, HY AF Lee, Jeongrim Huang, Bill X. Yuan, Zhixin Kim, Hee-Yong TI Simultaneous determination of salsolinol enantiomers and dopamine in human plasma and cerebrospinal fluid by chemical derivatization coupled to chiral liquid chromatography/electrospray ionization-tandem mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID BIOLOGICAL SAMPLES; GAS-CHROMATOGRAPHY; S-SALSOLINOL; TETRAHYDROISOQUINOLINE ALKALOIDS; PENTAFLUOROBENZYL BROMIDE; ELECTROCHEMICAL DETECTION; PARKINSONIAN-PATIENTS; BETA-CYCLODEXTRIN; SH-SY5Y CELLS; R-SALSOLINOL AB A sensitive, specific, and robust method to simultaneously determine enantiomeric salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL), a potential biomarker implicated in alcohol-related neurotoxicity in a stereoselective manner, and its precursor dopamine (DA) has been developed using simple chemical derivatization and chiral separation coupled with electrospray ionization-tandem mass spectrometry (ESI-MS/MS). SAL enantiomers and DA were converted to stable pentafluorobenzyl (PFB) derivatives directly from aqueous media. Bulky PFB groups introduced into the SAL structure enabled baseline separation of SAL stereoisomers on a chiral column without cumbersome chiral derivatization to unstable SAL diastereomers. Subsequent analysis by ESI-MS/MS with multiple reaction monitoring (MRM) in the presence of deuterium-labeled internal standards allowed specific detection of both derivatives with a wide dynamic range (SAL, 0.5-5000 pg; DA, 0.02-20 ng). The limit of quantitation assayed in the plasma matrix was below 10 pg for each SAL enantiomer and 100 pg for DA. Both coefficient of variance and error for inter- and intraday measurements in the blank plasma were less than 10% for SAL and DA in the concentration range of 10-4000 pg/mL and 0.1-8 ng/mL, respectively. This strategy enabled routine and specific determination of both SAL enantiomers and DA from 0.5 mL of human plasma and cerebrospinal fluid, which has not been possible using existing methodologies. C1 Natl Inst Hlth, NIAAA, Mol Signalling Lab, Bethesda, MD 20892 USA. RP Kim, HY (reprint author), Natl Inst Hlth, NIAAA, Mol Signalling Lab, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM hykim@nih.gov FU Intramural NIH HHS NR 30 TC 19 Z9 19 U1 1 U2 19 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 DEC 1 PY 2007 VL 79 IS 23 BP 9166 EP 9173 DI 10.1021/ac0715827 PG 8 WC Chemistry, Analytical SC Chemistry GA 236OH UT WOS:000251311900050 PM 17973500 ER PT J AU Arseven, A Guralnik, JM Kaleba, EO Liu, K Chan, CL McDermott, MM AF Arseven, Adnan Guralnik, Jack M. Kaleba, Erin O'Brien Liu, Kiang Chan, Cheeling McDermott, Mary McGrae TI Does lower-extremity arterial disease predict future failing among older men and women? SO ANGIOLOGY LA English DT Article ID ANKLE BRACHIAL INDEX; RISK-FACTORS; SKELETAL-MUSCLE; FALLS; COMMUNITY; MOBILITY; PERFORMANCE; PREVALENCE; FRACTURES; HEALTH AB The purpose of this study was to determine whether lower-extremity peripheral arterial disease (PAD) is an independent risk factor for falls among older persons. Men and women 55 years old and older participated. Subjects with PAD (n = 86) were identified from a noninvasive vascular laboratory and a general medicine practice. Randomly selected controls without PAD (n = 82) were identified from the same medicine practice. Subjects were categorized into PAD (ankle brachial index, <0.90) or controls (ankle brachial index, 0.90 to 1.50). Subjects underwent a comprehensive baseline evaluation for fall risk. Prospective fall data were obtained using monthly mail-in postcards and structured telephone interviews over a mean follow-up of 9.6 +/- 2.9 months. Two independent investigators blinded to PAD status reviewed each fall incident for its eligibility. A total of 37 subjects (22%) had at least I eligible fall. In an unadjusted Cox regression model, the relative risk of falling was lower among PAD subjects than among controls (relative risk, 0.54; 95% confidence interval, 0.28 to 1.06). After adjustment for age, gender, history of frequent falls in the last year, number of comorbidities, and balance and gait abnormalities, PAD was significantly associated with a lower risk of failing (relative risk, 0.43; 95% confidence interval, 0.21 to 0.87) as compared with controls. PAD is associated with a lower risk of falling as compared with persons without PAD among older men and women. Future study is needed to determine whether reduced levels of physical activity among patients with PAD account for the lower rate of falling observed here. C1 [Arseven, Adnan; McDermott, Mary McGrae] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. [Liu, Kiang; Chan, Cheeling; McDermott, Mary McGrae] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Guralnik, Jack M.] NIA, Epidemiol Demog Biometry Program, Bethesda, MD 20892 USA. [Kaleba, Erin O'Brien] Amer Med Assoc, Chicago, IL 60610 USA. RP Arseven, A (reprint author), 676 N St Clair St,Suite 200, Chicago, IL 60611 USA. EM a-arseven@northwestern.edu FU NCRR NIH HHS [RR-00048]; NHLBI NIH HHS [R01-HL58099] NR 31 TC 5 Z9 5 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0003-3197 J9 ANGIOLOGY JI Angiology PD DEC-JAN PY 2007 VL 58 IS 6 BP 725 EP 733 DI 10.1177/0003319707303650 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 246BQ UT WOS:000251982900011 PM 18071192 ER PT J AU Arora, NK Beckjord, E Hesse, B AF Arora, Neeraj K. Beckjord, Ellen Hesse, Bradford TI SUPPORTING INFORMATION SEEKING IN CANCER: INSIGHTS FROM THE 2005 HEALTH INFORMATION NATIONAL TRENDS SURVEY (HINTS) SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Arora, Neeraj K.; Beckjord, Ellen; Hesse, Bradford] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM aroran@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S11 EP S11 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300041 ER PT J AU Beckjord, E Arora, NK McLaughlin, W Hesse, BW AF Beckjord, Ellen Arora, Neeraj K. McLaughlin, Wendy Hesse, Bradford W. TI THE INFORMATION NEEDS OF ADULT CANCER SURVIVORS: A POPULATION-BASED ASSESSMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Beckjord, Ellen] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. EM beckjore@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S11 EP S11 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300039 ER PT J AU Beckjord, E Arora, NK Ramanadhan, S Hesse, BW AF Beckjord, Ellen Arora, Neeraj K. Ramanadhan, Shoba Hesse, Bradford W. TI INFORMATION MANAGEMENT IN CANCER: INSIGHTS FROM QUANTITATIVE AND QUALITATIVE RESEARCH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Beckjord, Ellen; Arora, Neeraj K.; Hesse, Bradford W.] NCI, Bethesda, MD 20892 USA. [Ramanadhan, Shoba] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. EM beckjore@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S10 EP S10 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300038 ER PT J AU Bellizzi, K Miller, SM AF Bellizzi, Keith Miller, Suzanne M. TI PATIENT REPORTED OUTCOME (PRO) ASSESSMENT IN OLDER PERSONS WITH CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bellizzi, Keith] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. [Miller, Suzanne M.] Fox Chase Canc Ctr, Psychosocial & Behav Med Program, Philadelphia, PA 19111 USA. EM bellizzk@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S7 EP S7 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300026 ER PT J AU Berrigan, D Dill, J Adamski, R Huang, L Stinchcomb, D Pickle, L AF Berrigan, David Dill, J. Adamski, R. Huang, L. Stinchcomb, D. Pickle, L. TI THE BUILT ENVIRONMENT AND WALKING/BICYCLING FOR TRANSPORTATION: TWO APPROACHES TO IDENTIFYING ENVIRONMENTAL CORRELATES OF BEHAVIOR SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Berrigan, David; Adamski, R.; Huang, L.; Stinchcomb, D.; Pickle, L.] NCI, Bethesda, MD 20892 USA. [Dill, J.] Portland State Univ, Portland, OR 97207 USA. EM berrigad@mail.nih.gov RI Dill, Jennifer/D-5971-2011 OI Dill, Jennifer/0000-0001-5498-3928 NR 0 TC 0 Z9 0 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S143 EP S143 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300558 ER PT J AU Best, A Leischow, S Cabrera, D Trochim, WM Abrams, D AF Best, Allan Leischow, Scott Cabrera, Derek Trochim, William M. Abrams, David TI SYSTEMS THINKING TO PROMOTE RESEARCH-PRACTICE INTEGRATION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Best, Allan] Vancouver Coastal Hlth Res Inst, Ctr Clin Epidemiol & Evaluat, Vancouver, BC V5Z 1L8, Canada. [Leischow, Scott] Univ Arizona, Family & Community Med, Tucson, AZ USA. [Cabrera, Derek] Cornell Univ, Coll Human Ecol, Ithaca, NY USA. [Abrams, David] NIH, Office Behav & Social Sci Res, Bethesda, MD 20892 USA. [Cabrera, Derek] Santa Fe Inst, Santa Fe, NM 87501 USA. EM allan.best@ubc.ca 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S111 EP S111 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300433 ER PT J AU Botello-Harbaum, MT Nansel, TR Haynie, D Iannotti, RJ Simons-Morton, B AF Botello-Harbaum, Maria T. Nansel, Tonja R. Haynie, Denise Iannotti, Ronald J. Simons-Morton, Bruce TI RESPONSIVENESS PARENTING STYLE IS ASSOCIATED WITH GREATER DIABETES-RELATED QUALITY OF LIFE AMONG CHILDREN AND ADOLESCENTS WITH TYPE 1 DIABETES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Botello-Harbaum, Maria T.; Nansel, Tonja R.; Haynie, Denise; Iannotti, Ronald J.; Simons-Morton, Bruce] NICHHD, Prevent Res Branch, Rockville, MD 20892 USA. EM botelloharbaumm@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S127 EP S127 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300498 ER PT J AU Brown, JP Sollers, JJ Thayer, JF Zonderman, AB Waldstein, SR AF Brown, Jessica P. Sollers, John J. Thayer, Julian F. Zonderman, Alan B. Waldstein, Shari R. TI CARDIOVASCULAR REACTIVITY AND COGNITION IN THE BALTIMORE LONGITUDINAL STUDY OF AGING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Brown, Jessica P.] UMB, SOM, Baltimore, MD 21201 USA. [Waldstein, Shari R.] UMBC, Baltimore, MD USA. [Sollers, John J.; Thayer, Julian F.; Zonderman, Alan B.] NIA IRP, Gerontol Res Ctr, Lab Personal & Cognit, Baltimore, MD USA. EM jpbrown@epi.umaryland.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S63 EP S63 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300244 ER PT J AU Fleisher, L Vanderpool, R Bush, N Squiers, L Krebill, H Davis, SW Kornfeld, J Hodorowski, JK AF Fleisher, Linda Vanderpool, Robin Bush, Nigel Squiers, Linda Krebill, Hope Davis, Sharon Watkins Kornfeld, Julie Hodorowski, Julie Keany TI TRANSLATING RESEARCH FINDINGS INTO PRACTICE: A MODEL DEVELOPED BY THE CANCER INFORMATION SERVICE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Fleisher, Linda; Vanderpool, Robin; Bush, Nigel; Squiers, Linda; Krebill, Hope; Davis, Sharon Watkins; Kornfeld, Julie; Hodorowski, Julie Keany] NCI, Canc Informat Serv, Bethesda, MD 20892 USA. [Fleisher, Linda] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Vanderpool, Robin] Univ Kentucky, Lexington, KY USA. [Bush, Nigel] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Krebill, Hope] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Davis, Sharon Watkins] No Calif Canc Ctr, Fremont, CA USA. [Kornfeld, Julie] H Lee Moffitt Canc Ctr & Res Inst, Coral Gables, FL USA. [Hodorowski, Julie Keany] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. EM linda.fleisher@fccc.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S48 EP S48 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300184 ER PT J AU Fondow, MD Emery, CF Stoney, CM Norman, G Busque, G AF Fondow, Meghan D. Emery, Charles F. Stoney, Catherine M. Norman, Greg Busque, Ginette TI EFFECTS OF VITAMIN SUPPLEMENTATION ON COGNITIVE FUNCTIONING IN MIDDLE-AGED MEN AND WOMEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Fondow, Meghan D.; Emery, Charles F.; Norman, Greg; Busque, Ginette] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Stoney, Catherine M.] NIH, Natl Ctr Complementary & Alternat Med, Washington, DC 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S135 EP S135 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300525 ER PT J AU Fondow, MD Emery, CF Stoney, CM Norman, G Busque, G AF Fondow, Meghan D. Emery, Charles F. Stoney, Catherine M. Norman, Greg Busque, Ginette TI EFFECTS OF VITAMIN SUPPLEMENTATION ON COGNITIVE FUNCTIONING IN MIDDLE-AGED MEN AND WOMEN SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Fondow, Meghan D.; Emery, Charles F.; Norman, Greg; Busque, Ginette] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Stoney, Catherine M.] Natl Ctr Complementary & Alternat Med, NIH, Washington, DC USA. EM fondow.2@osu.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S42 EP S42 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300157 ER PT J AU Graham, AL DePue, J Pinto, B Papandonatos, G Borrelli, B Neighbors, C Niaura, R Buka, S Abrams, D AF Graham, Amanda L. DePue, Judy Pinto, Bernie Papandonatos, George Borrelli, Belinda Neighbors, Charles Niaura, Raymond Buka, Stephen Abrams, David TI REPRESENTATIVENESS IN SMOKING CESSATION STUDIES: WHO REALLY JOINS? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Graham, Amanda L.; DePue, Judy; Pinto, Bernie; Borrelli, Belinda; Neighbors, Charles; Niaura, Raymond] Brown Med Sch, Dept Psychiat & Human Behavior, Providence, RI 02912 USA. [Papandonatos, George; Buka, Stephen] Brown Univ, Dept Community Hlth, Providence, RI USA. [Abrams, David] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. EM Amanda_Graham@brown.edu RI Buka, Stephen/H-7335-2014; Papandonatos, George/J-2328-2014 OI Buka, Stephen/0000-0002-8578-9308; 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S196 EP S196 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300768 ER PT J AU Hadley, D Jenkins, JF Martin, J Calzone, KA Shiloh, S Koehly, L AF Hadley, Don Jenkins, Jean F. Martin, Jean Calzone, Kathy A. Shiloh, Shoshana Koehly, Laura TI PSYCHOLOGICAL CORRELATES OF COLON CANCER SCREENING PRIOR TO AND FOLLOWING GENETIC TESTING FOR HEREDITARY NONPOLYPOSIS COLORECTAL CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hadley, Don; Jenkins, Jean F.; Martin, Jean; Koehly, Laura] NHGRI, NIH, Bethesda, MD 20892 USA. [Calzone, Kathy A.] NCI, NIH, Bethesda, MD 20892 USA. [Shiloh, Shoshana] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S132 EP S132 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300511 ER PT J AU Han, P Dunlavy, A Moser, R Klein, W AF Han, Paul Dunlavy, Andrea Moser, Richard Klein, William TI SOCIODEMOGRAPHIC AND MASS MEDIA FACTORS ASSOCIATED WITH PERCEIVED AMBIGUITY ABOUT CANCER PREVENTION RECOMMENDATIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Han, Paul; Dunlavy, Andrea; Moser, Richard] NCI, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. [Klein, William] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. EM hanp@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S173 EP S173 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300675 ER PT J AU Hurd, AL Parascandola, M Augustson, E AF Hurd, Ami L. Parascandola, Mark Augustson, Erik TI CONSUMER AWARENESS AND ATTITUDES RELATED TO NEW POTENTIAL REDUCE-EXPOSURE TOBACCO PRODUCT BRANDS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hurd, Ami L.; Parascandola, Mark; Augustson, Erik] NCI, Bethesda, MD 20892 USA. EM hurda@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S169 EP S169 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300659 ER PT J AU Kaphingst, K AF Kaphingst, Kimberly TI THE ROLE OF BELIEFS ABOUT INHERITED RISK OF CANCER IN INFORMATION SEEKING AND ATTENTION TO HEALTH INFORMATION IN THE MEDIA SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kaphingst, Kimberly] NHGRI, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S209 EP S209 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300819 ER PT J AU Kelleher, S Graves, K DeMarco, T Hecker, S Peshkin, B Isaacs, C Jandorf, L O'Neill, S Valdimarsdottir, H Schwartz, M AF Kelleher, Sarah Graves, Kristi DeMarco, Tiffani Hecker, Sharon Peshkin, Beth Isaacs, Claudine Jandorf, Lina O'Neill, Suzanne Valdimarsdottir, Heiddis Schwartz, Marc TI DECIDING ABOUT DECISION AIDS: PREDICTORS OF USE OF A CD-ROM DECISION AID SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kelleher, Sarah; Graves, Kristi; DeMarco, Tiffani; Hecker, Sharon; Peshkin, Beth; Isaacs, Claudine; Schwartz, Marc] Georgetown Univ, Lombardi Comprehens Canc Res Ctr, Washington, DC USA. [Jandorf, Lina; Valdimarsdottir, Heiddis] Mt Sinai Sch Med, New York, NY USA. [O'Neill, Suzanne] NHGRI, Bethesda, MD 20892 USA. EM sak45@georgetown.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S122 EP S122 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300477 ER PT J AU Materese, SA Latimer, AE Katulak, NA Harris, J Mowad, LZ Salovey, P AF Materese, Stephanie A. Latimer, Amy E. Katulak, Nicole A. Harris, Jennifer Mowad, Linda Z. Salovey, Peter TI FROM EDUCATION TO ENROLLMENT: HOW DECISION AIDS PROMOTING SELF-EFFICACY CAN LEAD TO INTEREST IN CLINICAL TRIALS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Materese, Stephanie A.] Yale Univ, Sch Publ Hlth, New Haven, CT 06511 USA. [Latimer, Amy E.] Queens Univ, Kingston, ON, Canada. [Mowad, Linda Z.] NCI, Canc Informat Serv, New Haven, CT USA. EM stephanie.materese@yale.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S19 EP S19 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300070 ER PT J AU Miller, MF Hamilton, AS Arora, NK Rowland, JH AF Miller, Melissa F. Hamilton, Ann S. Arora, Neeraj K. Rowland, Julia H. TI COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM) USE BY NON-HODGKIN'S LYMPHOMA SURVIVORS (NHL) AND QUALITY OF LIFE (QOL) SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Miller, Melissa F.] NCI, Canc Prevent Fellowship Program, DCP, Bethesda, MD 20892 USA. [Miller, Melissa F.; Rowland, Julia H.] NCI, Off Canc Survivorship, DCCPS, Bethesda, MD 20892 USA. [Hamilton, Ann S.] USC, Keck Sch Med, Los Angeles, CA USA. [Arora, Neeraj K.] NCI, Appl Res Program, DCCPS, Bethesda, MD 20892 USA. EM millermeli@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S29 EP S29 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300108 ER PT J AU Mitchell, CD Waldstein, SR Kelley-Moore, J Evans, MK Zonderman, AB AF Mitchell, Cory D. Waldstein, Shari R. Kelley-Moore, Jessica Evans, Michele K. Zonderman, Alan B. TI NEIGHBORHOOD SOCIOECONOMIC STATUS IS ASSOCIATED WITH CARDIOVASCULAR DISEASE PREVALENCE AND RISK FACTORS IN AN AFRICAN AMERICAN COHORT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Mitchell, Cory D.] Univ Maryland Baltimore Cty, Interdisciplinary Studies Program, Baltimore, MD 21206 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. EM mitch4@umbc.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S31 EP S31 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300118 ER PT J AU Morrill, EF Brewer, NT O'Neill, S Rimer, BK Lillie, SE Dees, EC Carey, LA AF Morrill, E. Forrest Brewer, Noel T. O'Neill, Suzanne Rimer, Barbara K. Lillie, Sarah E. Dees, E. Claire Carey, Lisa A. TI THE BUFFERING EFFECT OF POSTTRAUMATIC GROWTH: POSTTRAUMATIC STRESS, DEPRESSION AND QUALITY OF LIFE AMONG BREAST CANCER SURVIVORS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Morrill, E. Forrest] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [O'Neill, Suzanne] NIH, NHGRI, SBRB, Bethesda, MD 20892 USA. [Dees, E. Claire; Carey, Lisa A.] Univ N Carolina, Dept Hematol Oncol, Chapel Hill, NC 27599 USA. EM morrill@email.unc.edu NR 0 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S61 EP S61 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300236 ER PT J AU Nansel, TR Iannotti, RJ Simons-Morton, BG Plotnick, LP Clark, LM Zeitzoff, L AF Nansel, Tonja R. Iannotti, Ronald J. Simons-Morton, Bruce G. Plotnick, Leslie P. Clark, Loretta M. Zeitzoff, Linda TI IMPROVED BLOOD SUGAR CONTROL AMONG MIDDLE ADOLESCENTS FOLLOWING EXPOSURE TO AN INDIVIDUALIZED PROBLEM-SOLVING INTERVENTION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nansel, Tonja R.; Iannotti, Ronald J.; Simons-Morton, Bruce G.] NICHD, DESPR, NIH, Bethesda, MD 20892 USA. [Plotnick, Leslie P.; Clark, Loretta M.] Johns Hopkins Med Ctr, Baltimore, MD USA. [Zeitzoff, Linda] Childrens Hosp, Baltimore, MD USA. EM nanselt@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S86 EP S86 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300335 ER PT J AU Nelson, W Reyna, V AF Nelson, Wendy Reyna, Valerie TI NUMERACY: A CRITICAL (AND OFTEN OVERLOOKED) COMPETENCE FOR HEALTH DECISION MAKING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Nelson, Wendy; Reyna, Valerie] NCI, BBRB, BRP, DCCPS, Bethesda, MD 20892 USA. EM nelsonw@mail.nih.gov NR 0 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S8 EP S8 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300027 ER PT J AU O'Connell, ME Fagan, P Backinger, CL Augustson, E Vollinger, R Kaufman, A AF O'Connell, Mary E. Fagan, Pebbles Backinger, Cathy L. Augustson, Erik Vollinger, Robert Kaufman, Annette TI QUITTING BEHAVIORS AMONG YOUNG ADULTS AGED 18-30 IN THE US SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [O'Connell, Mary E.; Fagan, Pebbles; Backinger, Cathy L.; Augustson, Erik; Vollinger, Robert; Kaufman, Annette] NCI, Tobacco Control Res Branch DCCPS, Bethesda, MD 20892 USA. [O'Connell, Mary E.; Augustson, Erik] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. EM oconnellm@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S171 EP S171 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300665 ER PT J AU O'Neill, S Brewer, NT Lillie, S Rimer, BK Morrill, EF Carey, LA Dees, EC AF O'Neill, Suzanne Brewer, Noel T. Lillie, Sarah Rimer, Barbara K. Morrill, Edward F. Carey, Lisa A. Dees, E. C. TI PATIENTS' INTEREST IN GENE EXPRESSION ANALYSIS FOR BREAST CANCER RECURRENCE RISK SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [O'Neill, Suzanne] NHGRI, SBRB, NIH, Bethesda, MD 20892 USA. [Brewer, Noel T.; Lillie, Sarah; Rimer, Barbara K.; Morrill, Edward F.; Carey, Lisa A.; Dees, E. C.] Univ N Carolina, Chapel Hill, NC 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S131 EP S131 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300510 ER PT J AU Oh, S Heflin, L Meyerowitz, BE Stanton, AL Rowland, JH Ganz, PA AF Oh, Sindy Heflin, Lara Meyerowitz, Beth E. Stanton, Annette L. Rowland, Julia H. Ganz, Patricia A. TI QUALITY OF LIFE IN PARTNERS OF BREAST CANCER PATIENTS FOLLOWING PRIMARY TREATMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Oh, Sindy; Heflin, Lara; Meyerowitz, Beth E.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Stanton, Annette L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Stanton, Annette L.; Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. EM sindyoh@usc.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S142 EP S142 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300553 ER PT J AU Peters, JA Koehly, L Hoskins, L Kuhn, N Letocha, A Kenen, R Loud, J Greene, MH AF Peters, June A. Koehly, Laura Hoskins, Lindsey Kuhn, Natalia Letocha, Anne Kenen, Regina Loud, Jennifer Greene, Mark H. TI SISTERS IN HEREDITARY BREAST AND OVARIAN CANCER FAMILIES: COMMUNAL COPING AND PSYCHOLOGICAL WELL-BEING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Peters, June A.; Hoskins, Lindsey; Loud, Jennifer; Greene, Mark H.] DHHS, NIH, NCI, Clin Genet Branch, Rockville, MD 20852 USA. [Kenen, Regina] Coll NJ, Ewing, NJ USA. EM petersju@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S99 EP S99 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300387 ER PT J AU Pruitt, S McQueen, A Tiro, JA Rakowski, W DiClemente, CC Vernon, SW AF Pruitt, Sandi McQueen, Amy Tiro, Jasmin A. Rakowski, William DiClemente, Carlo C. Vernon, Sally W. TI FACTORIAL VALIDITY AND INVARIANCE OF A MAMMOGRAPHY PROCESSES OF CHANGE SCALE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Pruitt, Sandi; McQueen, Amy; Vernon, Sally W.] UT Houston Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. [Tiro, Jasmin A.] NCI, Bethesda, MD 20892 USA. [Rakowski, William] Brown Univ, Providence, RI 02912 USA. [DiClemente, Carlo C.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. EM Sandi.L.Pruitt@uth.tmc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S136 EP S136 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300529 ER PT J AU Pruitt, S McQueen, A Tiro, JA Rakowski, W DiClemente, CC Vernon, SW AF Pruitt, Sandi McQueen, Amy Tiro, Jasmin A. Rakowski, William DiClemente, Carlo C. Vernon, Sally W. TI FACTORIAL VALIDITY AND INVARIANCE OF A MAMMOGRAPHY PROCESSES OF CHANGE SCALE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Pruitt, Sandi; McQueen, Amy; Vernon, Sally W.] UT Houston Hlth Sci Ctr, Sch Publ Hlth, Houston, TX 77030 USA. [Tiro, Jasmin A.] Natl Canc Inst, Bethesda, MD USA. [Rakowski, William] Brown Univ, Providence, RI 02912 USA. [DiClemente, Carlo C.] Univ Maryland, Baltimore, MD 21201 USA. EM Sandi.L.Pruitt@uth.tmc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S43 EP S43 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300161 ER PT J AU Rice, SC Zonderman, AB Najjar, SS Waldstein, SR AF Rice, Sara C. Zonderman, Alan B. Najjar, Samer S. Waldstein, Shari R. TI ABSENCE OF RELATION BETWEEN DEPRESSIVE SYMPTOMATOLOGY AND CAROTID INTIMAL MEDIAL THICKNESS IN THE BALTIMORE LONGITUDINAL STUDY OF AGING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Rice, Sara C.; Waldstein, Shari R.] Univ Maryland, Dept Psychol, Baltimore, MD 21250 USA. [Rice, Sara C.; Zonderman, Alan B.; Najjar, Samer S.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM carrington@umbc.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S101 EP S101 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300394 ER PT J AU Riley, W Allison, DB Alpert, J Blumenthal, J Dunn, A Fabricatore, A Hibbeln, J Newcomer, J Vreeland, B Wadden, T AF Riley, William Allison, David B. Alpert, Jonathan Blumenthal, James Dunn, Andrea Fabricatore, Anthony Hibbeln, Joseph Newcomer, John Vreeland, Betty Wadden, Thomas TI NIMH WORKGROUP SUMMARY ON OBESITY, NUTRITION, AND PHYSICAL ACTIVITY AMONG THOSE WITH MENTAL DISORDERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Riley, William] NIMH, Bethesda, MD 20147 USA. [Allison, David B.] UAB, Birmingham, AL USA. [Alpert, Jonathan] Harvard Univ, Boston, MA 02115 USA. [Blumenthal, James] Duke, Durham, NC USA. [Dunn, Andrea] Klein Buendel, Golden, CO USA. [Fabricatore, Anthony; Wadden, Thomas] Univ Penn, Philadelphia, PA 19104 USA. [Hibbeln, Joseph] NIAAA, Bethesda, MD USA. [Newcomer, John] Washington Univ, St Louis, MO USA. [Vreeland, Betty] UMDNJ, Piscataway, NJ USA. EM wiriley@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S124 EP S124 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300484 ER PT J AU Robinson, JM Shavers, VL AF Robinson, JaMuir M. Shavers, Vickie L. TI RACIAL/ETHNIC VARIATION IN HEALTH INSURANCE COVERAGE AND CANCER SCREENING UTILIZATION SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Robinson, JaMuir M.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH,DHHS, Rockville, MD 20852 USA. [Shavers, Vickie L.] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH,DHHS, Rockville, MD 20852 USA. EM robinjam@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S203 EP S203 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300796 ER PT J AU Rossi, JS Hall, KL AF Rossi, Joseph S. Hall, Kara L. TI USE OF META-ANALYSIS IN THE DESIGN OF SUBSEQUENT STUDIES FOR THEORY TESTING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Rossi, Joseph S.] Univ Rhode Isl, Canc Prevent Res Ctr, Kingston, RI 02881 USA. [Hall, Kara L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM jsrossi@uri.edu 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S147 EP S147 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300570 ER PT J AU Rutten, LJ Hesse, BW Moser, RP McCaul, KD Rothman, AJ AF Rutten, Lila J. Hesse, Bradford W. Moser, Richard P. McCaul, Kevin D. Rothman, Alex J. TI PUBLIC UNDERSTANDING OF CANCER PREVENTION, DETECTION, AND SURVIVAL/CURE: COMPARISON WITH STATE-OF-SCIENCE EVIDENCE FOR COLON, SKIN, AND LUNG CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Rutten, Lila J.] NCI, SAIC Inc, Bethesda, MD 20892 USA. [Rothman, Alex J.] Univ Minnesota, Minneapolis, MN USA. [McCaul, Kevin D.] N Dakota State Univ, Fargo, ND 58105 USA. EM finneyl@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S172 EP S172 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300672 ER PT J AU Shaikh, AR Vinokur, A Yaroch, A Williams, G Resnicow, K AF Shaikh, Abdul R. Vinokur, Amiram Yaroch, Amy Williams, Geoffrey Resnicow, Ken TI A STRUCTURAL EQUATION ANALYSIS OF PSYCHOSOCIAL INFLUENCES ON FRUIT AND VEGETABLE CONSUMPTION IN AFRICAN AMERICANS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Shaikh, Abdul R.; Yaroch, Amy] NCI, Behav Res Program, Bethesda, MD 20892 USA. [Vinokur, Amiram; Resnicow, Ken] Univ Michigan, Ann Arbor, MI 48109 USA. [Williams, Geoffrey] Univ Rochester, Rochester, NY USA. EM shaikhab@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S186 EP S186 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300728 ER PT J AU Spriggs, A Iannotti, R Sundaram, R Botello-Harbaum, M Haynie, D Simons-Morton, B AF Spriggs, Aubrey Iannotti, Ronald Sundaram, Raji Botello-Harbaum, Maria Haynie, Denise Simons-Morton, Bruce TI CLASSROOM CONTEXT AND ALCOHOL USE AMONG WHITE, BLACK AND HISPANIC ADOLESCENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Spriggs, Aubrey] UNC, Chapel Hill, NC USA. [Iannotti, Ronald; Sundaram, Raji; Botello-Harbaum, Maria; Haynie, Denise; Simons-Morton, Bruce] NICHD, Bethesda, MD USA. EM spriggs@email.unc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S67 EP S67 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300260 ER PT J AU Stirratt, M AF Stirratt, Michael TI ADDRESSING SOCIAL AND STRUCTURAL INFLUENCES ON HIV TREATMENT ADHERENCE IN DOMESTIC AND INTERNATIONAL SETTINGS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Stirratt, Michael] NIMH, DAHBR, Rockville, MD 20852 USA. EM stirrattm@mail.nih.gov 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 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S4 EP S4 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300014 ER PT J AU Tiro, JA Vernon, SW Diamond, PM Aday, LA AF Tiro, Jasmin A. Vernon, Sally W. Diamond, Pamela M. Aday, Lu Ann TI COMPARISON OF TWO THEORY-DERIVED CAUSAL MECHANISMS THROUGH WHICH SUBJECTIVE NORMS MAY INFLUENCE MAMMOGRAPHY INTENTION AND STAGE OF CHANGE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Tiro, Jasmin A.] NCI, Div Canc Prevent & Canc Control, Bethesda, MD 20892 USA. [Tiro, Jasmin A.] NCI, Div Populat Sci, Bethesda, MD 20892 USA. [Vernon, Sally W.; Diamond, Pamela M.] Univ Texas Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX USA. [Aday, Lu Ann] Univ Texas Houston, Sch Publ Hlth, Div Management Policy & Community Hlth, Houston, TX USA. EM tiroj@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S173 EP S173 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300674 ER PT J AU Wade, CH McBride, CM Brody, LC AF Wade, Christopher H. McBride, Colleen M. Brody, Lawrence C. TI CONSIDERATIONS FOR SELECTING MARKERS IN A PROTOTYPIC GENETIC TEST THAT IS DESIGNED TO BEGIN EVALUATING THE USE OF GENETIC RISK INFORMATION IN PREVENTATIVE MEDICINE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Wade, Christopher H.; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Wade, Christopher H.; Brody, Lawrence C.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S130 EP S130 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300506 ER PT J AU White, DB Jenkins, J Bonham, V Stevens, N McBride, CM AF White, Della B. Jenkins, Jean Bonham, Vence Stevens, Nancy McBride, Colleen M. TI TOO MANY REFERRALS FOR BRCA1 AND 2 GENETIC SERVICES BY FAMILY PHYSICIANS? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [White, Della B.; Jenkins, Jean; Bonham, Vence; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Stevens, Nancy] Univ Washington, Sch Med, Seattle, WA USA. EM whitede@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD DEC PY 2007 VL 33 BP S93 EP S93 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 376LO UT WOS:000261185300363 ER PT J AU Cheung, N Islam, FMA Jacobs, DR Sharrett, AR Klein, R Polak, JF Cotch, MF Klein, BE Ouyang, P Wong, TY AF Cheung, Nino Islam, F. M. Amirul Jacobs, David R., Jr. Sharrett, A. Richey Klein, Ronald Polak, Joseph F. Cotch, Mary F. Klein, Barbara E. Ouyang, Pamala Wong, Tien Y. TI Arterial compliance and retinal vascular caliber in cerebrovascular disease SO ANNALS OF NEUROLOGY LA English DT Article ID PULSE CONTOUR ANALYSIS; SMALL-VESSEL DISEASE; WAVE-FORM ANALYSIS; MICROVASCULAR ABNORMALITIES; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; DIABETIC-RETINOPATHY; AORTIC STIFFNESS; ISCHEMIC-STROKE; BLOOD-PRESSURE AB Objective: Arterial stiffness is a newly recognized risk factor for stroke. Whether this is mediated by small- or large-artery disease is unknown. In this study, we examined the relationship between arterial stiffness and retinal vascular caliber. Methods: A cross-sectional, population-based study of 5,731 participants (aged 45 - 84 years) who were free of clinical cardiovascular disease (the Multi-Ethnic Study of Atherosclerosis). Retinal arteriolar and venular calibers were measured from retinal photographs according to standardized protocols. Small- and large-artery compliance was determined from pulse contour anal ysis. Results: After adjusting for age, sex, blood pressure, diabetes, smoking, lipid profile, and other risk factors, reduced large-artery compliance was associated with smaller retinal arteriolar caliber; each standard deviation decrease in large-artery compliance was associated with a 0.70 mu m (p=0.002) decrease in retinal arteriolar caliber. After adjusting for the same set of risk factors, reduced small-artery compliance was associated with wider retinal venular caliber; each standard deviation decrease in small artery compliance was associated with a 1.43 mu m (p=0.001) increase in retinal venular caliber. These associations remained significant after further adjustments for large-vessel atherosclerosis (carotid intima-media thickness, coronary artery calcium, and ankle-arm index). Interpretation: Reduced arterial wall compliance in large arterial beds is associated with retinal arteriolar narrowing, whereas reduced arterial wall compliance in small arterial beds is associated with retinal venular widening. These data may provide further insights into the effects of altered arterial stiffness on the cerebral microcirculation. C1 [Cheung, Nino; Islam, F. M. Amirul; Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway. [Sharrett, A. Richey] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Klein, Ronald; Klein, Barbara E.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Polak, Joseph F.] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA USA. [Cotch, Mary F.] NEI, Div Epidemiol & Clin Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Ouyang, Pamala] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD USA. [Wong, Tien Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117548, Singapore. RP Wong, TY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM twong@unimelb.edu.au RI Cheung, Ning Danny/F-2043-2013; OI Cotch, Mary Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237 FU Intramural NIH HHS [Z01 EY000403-07, Z01 EY000403-06, ZIA EY000403-08, ZIA EY000403-09, Z99 EY999999, ZIA EY000403-10]; NHLBI NIH HHS [HL69979-03, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95169] NR 43 TC 40 Z9 40 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2007 VL 62 IS 6 BP 618 EP 624 DI 10.1002/ana.21236 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 248AM UT WOS:000252123700011 PM 17918248 ER PT J AU Suzuki, Y Ichinomiya, S Kurosawa, M Ohkubo, M Watanabe, H Iwasaki, H Matsuda, J Noguchi, Y Takimoto, K Itoh, M Tabe, M Iida, M Kubo, T Ogawa, S Nanba, E Higaki, K Ohno, K Brady, RO AF Suzuki, Yoshiyuki Ichinomiya, Satoshi Kurosawa, Miek'o Ohkubo, Masato Watanabe, Hiroshi Iwasaki, Hiroyuki Matsuda, Junichiro Noguchi, Yoko Takimoto, Kazuhiro Itoh, Masayuki Tabe, Miho Iida, Masami Kubo, Takatoshi Ogawa, Seiichiro Nanba, Eiji Higaki, Katsumi Ohno, Kousaku Brady, Roscoe O. TI Chemical chaperone therapy: Clinical effect in murine G(M1)-gangliosidosis SO ANNALS OF NEUROLOGY LA English DT Article ID OCTYL-BETA-VALIENAMINE; N-ALKYL DERIVATIVES; GAUCHER-DISEASE; PHARMACOLOGICAL ENHANCEMENT; BIOLOGICAL EVALUATION; ALPHA-GALACTOSIDASE; GLUCOSIDASE; INHIBITOR; FIBROBLASTS; MUTANTS AB Certain low-molecular-weight substrate analogs act both as in vitro competitive inhibitors of lysosomal hydrolases and as intracellular enhancers (chemical chaperones) by stabilization of mutant proteins. In this study, we performed oral administration of a chaperone compound N-octyl-4-epi-beta-valienamine to G(M1)-gangliosidosis model mice expressing R201C mutant human beta-galactosidase. A newly developed neurological scoring system was used for clinical assessment. N-Octyl-4-epi-beta-valienamine was delivered rapidly to the brain, increased P-galactosidase activity, decreased ganglioside G,,, and prevented neurological deterioration within a few months. No adverse effect was observed during this experiment. N-Octyl-4-epi-beta-valienamine will be useful for chemical chaperone therapy of human G(M1)-gangliosidosis. C1 [Suzuki, Yoshiyuki; Ichinomiya, Satoshi] Int Univ Hlth & Welfare, Grad Sch, Otawara 3248501, Japan. [Kurosawa, Miek'o; Ohkubo, Masato] Int Univ Hlth & Welfare, Ctr Med Sci, Otawara 3248501, Japan. [Watanabe, Hiroshi; Iwasaki, Hiroyuki] Int Univ Hlth & Welfare, Clin Res Ctr, Otawara 3248501, Japan. [Matsuda, Junichiro; Noguchi, Yoko] Natl Inst Biomed Innovat, Biol Resource Div, Ibaraki, Japan. [Takimoto, Kazuhiro] Natl Inst Infect Dis, Div Expt Anim Res, Shinjuku Ku, Tokyo, Japan. [Itoh, Masayuki] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Retardat & Birth Defect Res, Tokyo, Japan. [Tabe, Miho] SRL Inc, Anal Ctr Med Sci, Biochem Sect, Hachioji, Tokyo, Japan. [Iida, Masami; Kubo, Takatoshi] Seikagaku Corp, Cent Res Labs, Tokyo, Japan. [Ogawa, Seiichiro] Keio Univ, Fac Sci & Technol, Dept Biosci, Kohoku Ku, Yokohama, Kanagawa 223, Japan. [Nanba, Eiji; Higaki, Katsumi] Tottori Univ, Res Ctr Biosci & Technol, Div Funct Genom, Tottori, Japan. [Ohno, Kousaku] Tottori Univ, Fac Med, Div Child Neurol, Yonago, Tottori 683, Japan. [Brady, Roscoe O.] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, Natl Inst Hlth, Bethesda, MD USA. RP Suzuki, Y (reprint author), Int Univ Hlth & Welfare, Grad Sch, Room L-423,2600-1 Kita Kanemaru, Otawara 3248501, Japan. EM stizukiy@iuhw.ac.jp NR 20 TC 39 Z9 40 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2007 VL 62 IS 6 BP 671 EP 675 DI 10.1002/ana.21284 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 248AM UT WOS:000252123700017 PM 17994547 ER PT J AU Mamede, M El Fakhri, G Abreu-E-Lima, P Gandler, W Nose, V Gerbaudo, VH AF Mamede, Marcelo El Fakhri, Georges Abreu-e-Lima, Paula Gandler, William Nose, Vania Gerbaudo, Victor H. TI Pre-operative estimation of esophageal tumor metabolic length in FDG-PET images with surgical pathology confirmation SO ANNALS OF NUCLEAR MEDICINE LA English DT Article DE PET/CT; FDG; PET; esophageal cancer; tumor length; tumor segmentation ID POSITRON-EMISSION-TOMOGRAPHY; CARCINOMA; CANCER; VOLUME; ADENOCARCINOMA; SEGMENTATION; RADIOTHERAPY; SURVIVAL AB Objective The aim of this study was to evaluate a 3D tumor segmentation method for fluorodeoxyglucose positron emission tomography (FDG-PET) in the context of noninvasive estimation of tumor metabolic length (L-m), as it correlates with surgical pathology and phantom results. Methods Thirty-four patients (7 women, 27 men) with esophageal cancer were retrospectively evaluated. All patients underwent FDG-PET-computed tomography (CT) imaging following endoscopic ultrasound (EUS). Seventeen patients had esophagectomy after PET/CT, without prior neoadjuvant therapy. Tumor length was assessed by EUS (L-e, n = 31) and histopathology (L-p, n = 17). Images were evaluated quantitatively with a 3D threshold-based region-growing program (Medical Image Processing Analysis and Visualization). L-m, total metabolic volume (V-m), maximum standardized uptake value (SUVmax), and average SUV (SUVa) over the entire tumor were obtained for several threshold values (mean activity in the liver plus 0-, 1-, 2-, 3-, and 4-SD of the activity in the liver). Results L-m showed a good correlation with L-p for all thresholds (best correlation for Lm(2-SD), r = 0.74, P < 0.001). A positive nonsignificant correlation was observed between L-p and L-e (r = 0.30, P = 0.29). Lm(2-SD) correlated well with L-e (r = 0.71, P < 0.001). Good correlations were also observed between Lm(2-SD) and V (m(2-SD)) (r = 0.89, P < 0.001) and SUVa(2-SD) (r = 0.38, P < 0.05). Vm(2-SD) also had a significant correlation with L-p (r = 0.61, P < 0.05) and L-e (r = 0.57, P < 0.001). Conclusions FDG-PET-derived tumor metabolic length of untreated esophageal carcinomas correlates well with surgical pathology results, and provides preliminary evidence that noninvasive delineation of the superior and inferior extent of viable tumor involvement might be feasible using computer-generated metabolic length measurements. C1 [Mamede, Marcelo; El Fakhri, Georges; Gerbaudo, Victor H.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Nucl Med, Boston, MA 02115 USA. [Abreu-e-Lima, Paula; Nose, Vania] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gandler, William] NIH, Ctr Informat Technol, Biomed Imaging Res Serv Sect, Bethesda, MD 20892 USA. RP Gerbaudo, VH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Nucl Med, 75 Francis St, Boston, MA 02115 USA. EM vgerbaudo@partners.org RI Mamede, Marcelo/A-1751-2014 OI Mamede, Marcelo/0000-0001-5818-0954 NR 20 TC 30 Z9 36 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0914-7187 J9 ANN NUCL MED JI Ann. Nucl. Med. PD DEC PY 2007 VL 21 IS 10 BP 553 EP 562 DI 10.1007/s12149-007-0040-0 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 243BJ UT WOS:000251769600002 PM 18092131 ER PT J AU Kaufmann, M von Minckwitz, G Bear, HD Buzdar, A McGale, P Bonnefoi, H Colleoni, M Denkert, C Eiermann, W Jackesz, R Makris, A Miller, W Pierga, JY Semiglazov, V Schneeweiss, A Souchon, R Stearns, V Untch, M Loibl, S AF Kaufmann, M. von Minckwitz, G. Bear, H. D. Buzdar, A. McGale, P. Bonnefoi, H. Colleoni, M. Denkert, C. Eiermann, W. Jackesz, R. Makris, A. Miller, W. Pierga, J. -Y. Semiglazov, V. Schneeweiss, A. Souchon, R. Stearns, V. Untch, M. Loibl, S. TI Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006 SO ANNALS OF ONCOLOGY LA English DT Review DE breast cancer; neoadjuvant therapy; recommendations ID LYMPH-NODE BIOPSY; PATHOLOGICAL COMPLETE RESPONSE; INVASIVE LOBULAR CARCINOMA; GENE-EXPRESSION PROFILES; PRIMARY CHEMOTHERAPY; PREOPERATIVE CHEMOTHERAPY; RESIDUAL DISEASE; CYCLOPHOSPHAMIDE CHEMOTHERAPY; PHYSICAL-EXAMINATION; CLINICAL PALPATION AB Neoadjuvant (primary systemic) treatment has become a standard option for primary operable disease for patients who are candidates for adjuvant systemic chemotherapy, irrespective of the size of the tumor. Because of new treatments and new understandings of breast cancer, however, recommendations published in 2006 regarding neoadjuvant treatment for operable disease required updating. Therefore, a third international panel of representatives of a number of breast cancer clinical research groups was convened in September 2006 to update these recommendations. As part of this effort, data published to date were critically reviewed and indications for neoadjuvant treatment were newly defined. C1 [Kaufmann, M.; von Minckwitz, G.; Loibl, S.] Univ Frankfurt, Frankfurt, Germany. [von Minckwitz, G.; Loibl, S.] German Breast Grp, Frankfurt, Germany. [Bear, H. D.] Virginia Commonwealth Univ, Div Surg Oncol, Massey Canc Ctr, Richmond, VA USA. [Bear, H. D.] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Buzdar, A.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [McGale, P.] Early Breast Canc Trialists Collaborat Grp, Oxford, England. [Bonnefoi, H.] Hop Univ Geneve, EORTC Breast Canc Grp, Geneva, Switzerland. [Colleoni, M.] Ist Europeo Oncol, Milan, Italy. [Denkert, C.] Charite Univ Med Berlin, Inst Pathol, Berlin, Germany. [Eiermann, W.] Krankenhaus Roten Kreuz, Frauenklin, Munich, Germany. [Jackesz, R.] Univ Klin Chirurg, Vienna, Austria. [Makris, A.] Mt Vemon Hosp, Northwood, Middx, England. [Miller, W.] Univ Edinburgh, Western Gen Hosp, Edinburgh, Midlothian, Scotland. [Pierga, J. -Y.] Inst Curie, Dept Med Oncol, Paris, France. [Semiglazov, V.] NN Petrov Oncol Res Inst, St Petersburg, Russia. [Schneeweiss, A.] Univ Heidelberg, D-6900 Heidelberg, Germany. [Souchon, R.] Allgemeines Krankenhaus Hagen, Hagen, Germany. [Stearns, V.] Johns Hopkins Univ, Sidney Kimmal Comprehens Canc Ctr, Baltimore, MD USA. [Untch, M.] Helios Klinikum Berlin Buch, Berlin, Germany. RP Kaufmann, M (reprint author), JW Goethe Univ Hosp, Dept Obstet & Gynecol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM M.Kaufmann@em.uni-frankfurt.de OI Denkert, Carsten/0000-0002-2249-0982; Semiglazov, Vladimir/0000-0003-0077-9619 NR 72 TC 175 Z9 194 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2007 VL 18 IS 12 BP 1927 EP 1934 DI 10.1093/annonc/mdm201 PG 8 WC Oncology SC Oncology GA 257CC UT WOS:000252775800003 PM 17998286 ER PT J AU Varghese, S Burness, M Xu, H Beresnev, T Pingpank, J Alexander, HR AF Varghese, Sheelu Burness, Monika Xu, Hui Beresnev, Tatiana Pingpank, James Alexander, H. Richard TI Site-specific gene expression profiles and novel molecular prognostic factors in patients with lower gastrointestinal adenocarcinoma diffusely metastatic to liver or peritoneum SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE colorectal cancer; GI adenocarcinoma; metastases; microarray ID COLORECTAL-CANCER; INTRAPERITONEAL CHEMOTHERAPY; PSEUDOMYXOMA-PERITONEI; CYTOREDUCTIVE SURGERY; INTESTINE-CADHERIN; TISSUE INHIBITOR; CARCINOMATOSIS; SURVIVAL; STATISTICS; FEATURES AB Background: Generally, colorectal and high-grade appendiceal cancers are treated similarly; treatment approach is primarily based on tumor histology and stage of disease. Patients with adenocarcinoma of the lower gastrointestinal tract frequently experience diffuse metastases isolated to liver or peritoneum and have a poor survival. Identification of novel molecular pathways in metastases from these patients may identify novel targets and prognostic factors. Methods: Microarray analyses of 20 metastatic tumors from patients with colorectal adenocarcinoma isolated to liver or peritoneum and eight high-grade appendiceal adenocarcinoma metastatic to peritoneum were performed using oligonucleotide microarray. Results: In an unsupervised hierarchical cluster analysis of 2-fold upregulated or downregulated genes, there was a clear site-specific segregation of liver versus peritoneal metastases. Genes primarily involved in metastasis, angiogenesis, cell cycle regulation, cell proliferation, and cell adhesion were distinctly altered between these two metastatic sites. Among the metastasis genes, the average expression levels of LI-cadherin, ALCAM, CD2, and CD14 were significantly higher in both metastatic sites. TIMP1 was overexpressed in both sites where as TIMP-2, IGF-1, and HIF-1 alpha were upregulated only in peritoneal metastases demonstrating the potential benefit of metastasis site-specific treatments. Subsets of genes significantly associated with poor survival were defined, a RET proto-oncogene interacting gene, GOLGA5, was highly predictive for survival in patients with colorectal adenocarcinoma. Conclusions: These results demonstrate that liver and peritoneal metastases of lower GI adenocarcinoma have distinct gene expression patterns; these distinctions may help in the development of therapies based on site of metastases. C1 Univ Maryland, Sch Med, Dept Surg, Div Surg Oncol, Baltimore, MD 21201 USA. Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), Univ Maryland, Sch Med, Dept Surg, Div Surg Oncol, Baltimore, MD 21201 USA. EM HRAlexander@smail.umaryland.edu FU Intramural NIH HHS NR 27 TC 31 Z9 32 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2007 VL 14 IS 12 BP 3460 EP 3471 DI 10.1245/s10434-007-9557-7 PG 12 WC Oncology; Surgery SC Oncology; Surgery GA 231VE UT WOS:000250976500029 PM 17899288 ER PT J AU Ghosh, K Tiwari, RC AF Ghosh, Kaushik Tiwari, Ram C. TI Empirical process approach to some two-sample problems based on ranked set samples SO ANNALS OF THE INSTITUTE OF STATISTICAL MATHEMATICS LA English DT Article DE shift function; q-Q plot; p-P plot; bootstrap; ROC curve; wilcoxon-Mann-Whitney test ID OPERATING CHARACTERISTIC CURVES; STATISTICAL-INFERENCE; NONLINEAR MODELS; CENSORED-DATA; PLOTS AB We study the asymptotic properties of both the horizontal and vertical shift functions based on independent ranked set samples drawn from continuous distributions. Several tests derived from these shift processes are developed. We show that by using balanced ranked set samples with bigger set sizes, one can decrease the width of the confidence band and hence increase the power of these tests. These theoretical findings are validated through small-scale simulation studies. An application of the proposed techniques to a cancer mortality data set is also provided. C1 New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA. NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Ghosh, K (reprint author), New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA. EM ghosh1@verizon.net NR 25 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0020-3157 J9 ANN I STAT MATH JI Ann. Inst. Stat. Math. PD DEC PY 2007 VL 59 IS 4 BP 757 EP 787 DI 10.1007/s10463-006-0073-5 PG 31 WC Statistics & Probability SC Mathematics GA 233KW UT WOS:000251090800007 ER PT J AU Petrovas, C Mueller, YM Yang, GB Altork, SR Jacobson, JM Pitsakis, PG Mounzer, KC Altman, JD Katsikis, PD AF Petrovas, Constantinos Mueller, Yvonne M. Yang, Guibin Altork, Susan R. Jacobson, Jeffrey M. Pitsakis, Peter G. Mounzer, Karam C. Altman, John D. Katsikis, Peter D. TI Actin integrity is indispensable for CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells SO APOPTOSIS LA English DT Article DE actin; apoptosis; caspase-8; HIV-specific CD8(+) T cells ID FAS-MEDIATED APOPTOSIS; CD95-MEDIATED APOPTOSIS; EZRIN ASSOCIATION; CD95; BCL-2; LYMPHOCYTES; BCL-X(L); CYTOSKELETON; RECEPTOR; DEATH AB We have recently provided data suggesting a potential role for mitochondria and Bcl-2-family molecules in apoptosis sensitivity of HIV-specific CD8(+) T cells. Here, we report on the role of filamentous (F) actin in this process. Disruption of actin by cytochalasin D (cytD) or lantrunculin A remarkably reduced CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells while their spontaneous apoptosis was unaffected. This inhibition cannot be attributed to changes of CD95/Fas distribution or levels in these cells. Furthermore, cytD treatment reduced CD95/Fas-induced apoptosis of CD8(+) T cells from HIV+ patients independently of their differentiation status. CD95/Fas-induced apoptosis of both CD38(+) and CD38(-) HIV-specific CD8(+) T cells was inhibited by cytD treatment indicating that actin mediates this apoptotic process independently of the activation level of these cells. CytD was found to reduce the activation of caspase-8 induced by short treatment of purified CD8(+) T cells from HIV+ patients with anti-CD95/Fas. Our data reveal actin as a critical mediator of HIV-specific CD8(+) T cell apoptosis; further analysis of the molecular mechanisms governing this process may potentially contribute to design new therapies targeting the enhancement of the immune system in HIV infection. C1 Drexel Univ, Coll Med, Dept Microbiol & Immunol, Inst Mol Med & Infect Dis, Philadelphia, PA 19129 USA. NIAID, NIH, Vaccine Res Ctr, Immunol Lab, Bethesda, MD 20892 USA. Drexel Univ, Coll Med, Dept Med, Philadelphia, PA 19129 USA. Philadelphia FIGHT, Philadelphia, PA 19107 USA. Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30329 USA. RP Pitsakis, PG (reprint author), Drexel Univ, Coll Med, Dept Microbiol & Immunol, Inst Mol Med & Infect Dis, 2900 Queen Lane, Philadelphia, PA 19129 USA. EM peter.katsikis@drexelmed.edu OI Katsikis, Peter/0000-0001-7690-5218; Mueller, Yvonne/0000-0002-4654-7509 FU NIAID NIH HHS [R01 AI46719, R01 AI52005] NR 36 TC 4 Z9 4 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD DEC PY 2007 VL 12 IS 12 BP 2175 EP 2186 DI 10.1007/s10495-007-0128-y PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 229DY UT WOS:000250784400005 PM 17891455 ER PT J AU Lamb, ME Orbach, Y Hershkowitz, I Horowitz, D Abbott, CB AF Lamb, Michael E. Orbach, Yael Hershkowitz, Irit Horowitz, Dvora Abbott, Craig B. TI Does the type of prompt affect the accuracy of information provided by alleged victims of abuse in forensic interviews? SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Article ID INVESTIGATIVE UTTERANCE TYPES; ANATOMICALLY DETAILED DOLLS; YOUNG CHILDRENS RESPONSES; SEXUAL-ABUSE; PEDIATRIC EXAMINATION; EYEWITNESS TESTIMONY; AGE-DIFFERENCES; QUESTION TYPE; WITNESSES; MEMORY AB Forty-three victims of sexual abuse averaging 9.78 years of age and 52 youths who admitted abusing them were interviewed about the abusive incidents. Forensically relevant details provided by the victims were categorised as confirmed, contradicted or ignored by the perpetrators. Most (66.6%) of the details were ignored, but details were more likely to be confirmed when they were elicited using invitations (open-ended free-recall prompts) rather than focused prompts. However, similar effects were not evident with respect to contradictions. The results support predictions that information elicited using free-recall prompts is more likely to be accurate than information elicited using focused prompts. Published in 2007 by John Wiley & Sons, Ltd. C1 [Lamb, Michael E.] Univ Cambridge, Fac Social & Polit Sci, Cambridge CB2 3RQ, England. [Orbach, Yael; Abbott, Craig B.] NICHHD, Bethesda, MD 20892 USA. [Hershkowitz, Irit] Univ Haifa, Sch Social Work, IL-31999 Haifa, Israel. [Horowitz, Dvora] Minist Labour & Social Affairs, Jerusalem, Israel. RP Lamb, ME (reprint author), Univ Cambridge, Fac Social & Polit Sci, Free Sch Lane, Cambridge CB2 3RQ, England. EM mel37@cam.ac.uk NR 40 TC 25 Z9 25 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0888-4080 J9 APPL COGNITIVE PSYCH JI Appl. Cogn. Psychol. PD DEC PY 2007 VL 21 IS 9 BP 1117 EP 1130 DI 10.1002/acp.1318 PG 14 WC Psychology, Experimental SC Psychology GA 247RJ UT WOS:000252097000001 ER PT J AU Tsai, CC Kao, SC Cheng, CY Kau, HC Hsu, WM Lee, CF Wei, YH AF Tsai, Chieh-Chih Kao, Shu-Ching Cheng, Ching-Yu Kau, Hui-Chuan Hsu, Wen-Ming Lee, Cheng-Feng Wei, Yau-Huei TI Oxidative stress change by systemic corticosteroid treatment among patients having active graves ophthalmopathy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID THYROID-ASSOCIATED OPHTHALMOPATHY; HUMAN ORBITAL FIBROBLASTS; DNA-DAMAGE; PERIPHERAL PARAMETERS; LIPID-PEROXIDATION; FREE-RADICALS; DISEASE; PATHOGENESIS; 8-HYDROXY-2'-DEOXYGUANOSINE; 8-HYDROXYDEOXYGUANOSINE AB Objectives: To measure the 8-hydroxy- 2'-deoxyguanosine (8-OHdG) level in patients having active Graves ophthalmopathy (GO) and to compare this oxidative stress biomarker and the clinical evolution of patients after systemic corticosteroid treatment. Methods: In 8 euthyroid patients having active GO, we determined the 8-OHdG levels in urine before, during, and after intensive corticosteroid therapy. Clinical activity and ophthalmopathy index scores were assessed. Nine age- and sex-matched healthy volunteers served as control subjects. Results: The mean 8-OHdG level was statistically significantly increased in patients having active GO compared with that of controls (17.47 vs 5.97 ng/mg of creatinine, P <. 001). During and after maximal systemic corticosteroid treatment, patients had statistically significantly lower mean 8-OHdG levels (7.19 and 10.18 ng/mg of creatinine, respectively) compared with the mean level before treatment. These changes were accompanied by decreases in clinical activity and ophthalmopathy index scores. The urinary 8-OHdG levels were subsequently elevated in 2 patients having recurrent active GO when corticosteroid therapy was tapered or withdrawn. Conclusions: Oxidative stress may have a role in the pathogenesis of GO. Urinary 8-OHdG level can be used not only as a noninvasive biomarker of oxidative stress in patients having GO but also as an objective and quantitative parameter in the follow-up of patients during immunosuppressive treatment. C1 Natl Yang Ming Univ, Dept Biochem & Mol Biol, Taipei 112, Taiwan. Natl Yang Ming Univ, Taipei Vet Gen Hosp, Dept Ophthalmol, Taipei 112, Taiwan. Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan. Koo Fdn Sun Yat Sen Canc Ctr, Dept Ophthalmol, Taipei, Taiwan. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RP Wei, YH (reprint author), Natl Yang Ming Univ, Dept Biochem & Mol Biol, 155 Li Nong St,Sect 2, Taipei 112, Taiwan. EM joeman@ym.edu.tw RI Cheng, Ching-Yu/K-7017-2013 OI Cheng, Ching-Yu/0000-0003-0655-885X NR 41 TC 19 Z9 24 U1 0 U2 1 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 DEC PY 2007 VL 125 IS 12 BP 1652 EP 1656 DI 10.1001/archopht.125.12.1652 PG 5 WC Ophthalmology SC Ophthalmology GA 239TB UT WOS:000251539500012 PM 18071117 ER PT J AU Duggal, P Klein, AP Lee, KE Klein, R Klein, BEK Bailey-Wilson, JE AF Duggal, Priya Klein, Alison P. Lee, Kristine E. Klein, Ronald Klein, Barbara E. K. Bailey-Wilson, Joan E. TI The GLC1H glaucoma locus may reflect glaucoma with elevated intraocular pressure SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter C1 NHGRI, NIH, Baltimore, MD 21224 USA. RP Duggal, P (reprint author), NHGRI, NIH, 333 Cassel Dr,Ste 1200, Baltimore, MD 21224 USA. EM pduggal@mail.nih.gov NR 2 TC 1 Z9 1 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 DEC PY 2007 VL 125 IS 12 BP 1716 EP 1717 DI 10.1001/archopht.125.12.1716-b PG 2 WC Ophthalmology SC Ophthalmology GA 239TB UT WOS:000251539500027 PM 18071131 ER PT J AU Isenberg, JS Hyodo, F Pappan, LK Abu-Asab, M Tsokos, M Krishna, MC Frazier, WA Roberts, DD AF Isenberg, Jeff S. Hyodo, Fuminori Pappan, Loretta K. Abu-Asab, Mones Tsokos, Maria Krishna, Murali C. Frazier, William A. Roberts, David D. TI Blocking Thrombospondin-1/CD47 signaling alleviates deleterious effects of aging on tissue responses to ischemia SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE nitric oxide; thrombospondin-1; perfusion; ischemia; wound healing ID SKELETAL-MUSCLE ARTERIOLES; NITRIC-OXIDE SYNTHASE; CELL RESPONSES; SMOOTH-MUSCLE; ATHEROSCLEROSIS; DISEASE; MICE; EXPRESSION; SURVIVAL; INJURY AB Objective-Decreased blood flow secondary to peripheral vascular disease underlies a significant number of chronic diseases that account for the majority of morbidity and mortality among the elderly. Blood vessel diameter and blood flow are limited by the matricellular protein thrombospondin-1 (TSP1) through its ability to block responses to the endogenous vasodilator nitric oxide (NO). In this study we investigate the role TSP1 plays in regulating blood flow in the presence of advanced age and atherosclerotic vascular disease. Methods and Results-Mice lacking TSP1 or CD47 show minimal loss of their resistance to ischemic injury with age and increased preservation of tissue perfusion immediately after injury. Treatment of WT and apolipoprotein E - null mice using therapeutic agents that decrease CD47 or enhance NO levels reverses the deleterious effects of age- and diet-induced vasculopathy and results in significantly increased tissue survival in models of ischemia. Conclusion-With increasing age and diet- induced atherosclerotic vascular disease, TSP1 and its receptor CD47 become more limiting for blood flow and tissue survival after ischemic injury. Drugs that limit TSP1/CD47 regulation of blood flow could improve outcomes from surgical interventions in the elderly and ameliorate vascular complications attendant to aging. C1 Ctr Canc Res, Natl Canc Inst, NIH, Pathol Lab,Radiat Biol Branch, Bethesda, MD USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO USA. RP Isenberg, JS (reprint author), Natl Canc Inst, Pathol Lab, Bldg 10,2A33, Bethesda, MD 20892 USA. EM isenberj@mail.nih.gov RI Roberts, David/A-9699-2008; OI Roberts, David/0000-0002-2481-2981; Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS; NHLBI NIH HHS [HL54390]; NIGMS NIH HHS [GM57573] NR 40 TC 45 Z9 45 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 2007 VL 27 IS 12 BP 2582 EP 2588 DI 10.1161/ATVBAHA.107.155390 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 234EK UT WOS:000251143300017 PM 17916772 ER PT J AU Mavragani, CP Niewold, TB Moutsopoulos, NM Pillemer, SR Wahl, SM Crow, MK AF Mavragani, Clio P. Niewold, Timothy B. Moutsopoulos, Niki M. Pillemer, Stanley R. Wahl, Sharon M. Crow, Mary K. TI Augmented interferon-alpha pathway activation in patients with Sjogren's syndrome treated with etanercept SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PLASMACYTOID DENDRITIC CELLS; I INTERFERON; IFN-ALPHA; AUTOIMMUNE-DISEASES; SALIVARY-GLANDS; EXPRESSION; BAFF; DISTINCT; CYTOKINES AB Objective. Recent clinical trials suggest that etanercept is ineffective in controlling Sjogren's syndrome (SS). To address the hypothesis that tumor necrosis factor blockade can result in increased levels of interferon-alpha (IFN alpha) and BAFF, we quantified those mediators in plasma from etanercept- and placebotreated SS patients. Methods. We studied plasma samples from 20 patients with SS treated with etanercept (25 mg twice weekly) or placebo in a 12-week, randomized, double-blind clinical trial. In addition, we studied plasma samples from 29 healthy controls. IFNa activity was determined by reporter cell assay, and BAFF levels were determined by enzyme-linked immunosorbent assay. Results. Baseline IFNa plasma activity and BAFF levels were increased in SS patients compared with healthy controls (mean +/- SD IFN alpha plasma activity score 4.43 +/- 2.60 versus 2.08 +/- 0.91; P < 0.0001) (mean SD BAFF level 0.83 +/- 0.27 ng/ml versus 0.60 +/- 0.15 ng/ml; P = 0.008). A significant increase in IFN alpha activity was detected after 12 weeks of treatment in the etanercept group, but not in the placebo group (P = 0.04 and P = 0.58, respectively). Furthermore, a statistically significant increase in BAFF levels was noted in patients receiving etanercept, but not in those receiving placebo (P = 0.01 and P = 0.56, respectively). In vitro culture of control peripheral blood mononuclear cells with etanercept resulted in a dose-dependent increase in the expression of IFNa and the IFN alpha-inducible genes IFN-induced protein with tetratricopeptide repeats 1 and BAFF. Conclusion. IFNa activity and BAFF levels are elevated in the plasma of patients with SS compared with healthy controls. Etanercept treatment exacerbates IFNa and BAFF overexpression, providing a possible explanation for the lack of efficacy of this agent in SS. C1 [Crow, Mary K.] Hosp Special Surg, New York, NY 10021 USA. [Mavragani, Clio P.; Niewold, Timothy B.; Crow, Mary K.] Hosp Special Surg, Mary Kirkland Ctr Lupus Res, New York, NY 10021 USA. [Mavragani, Clio P.; Niewold, Timothy B.; Crow, Mary K.] Cornell Univ, Weill Med Coll, New York, NY USA. [Moutsopoulos, Niki M.; Pillemer, Stanley R.; Wahl, Sharon M.] NIH, NIDR, Bethesda, MD 20892 USA. RP Crow, MK (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. EM crowm@hss.edu FU Intramural NIH HHS; NIAID NIH HHS [AI 059893, L30 AI071651, L30 AI071651-01, R01 AI059893]; NIAMS NIH HHS [AR 050829, R01 AR050829, T32 AR 07517, T32 AR007517] NR 47 TC 84 Z9 86 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2007 VL 56 IS 12 BP 3995 EP 4004 DI 10.1002/art.23062 PG 10 WC Rheumatology SC Rheumatology GA 243FS UT WOS:000251781200016 PM 18050196 ER PT J AU Charles, JF Whittaker, G Wu, Y McVicar, DW Nakamura, MC AF Charles, Julia F. Whittaker, Gillian Wu, Yalei McVicar, Daniel W. Nakamura, Mary C. TI The role of the signaling adapter LAT in osteoclastogenesis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 71st Annual Meeting of the American-College-of-Rheumatology CY NOV 06-11, 2007 CL Boston, MA SP Amer Coll Rheumatol C1 [Charles, Julia F.; Wu, Yalei; Nakamura, Mary C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Whittaker, Gillian; McVicar, Daniel W.] Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2007 VL 56 IS 12 BP 4242 EP 4242 PG 1 WC Rheumatology SC Rheumatology GA 243FS UT WOS:000251781200063 ER PT J AU Brionez, TF Assassi, S Ward, MM Diekman, L Zhou, X Davis, JC Albuquerque, SM Weisman, MH Reveille, JD AF Brionez, Tamar F. Assassi, Shervin Ward, Michael M. Diekman, Laura Zhou, Xiadong Davis, John C. Albuquerque, Sheila M. Weisman, Michael H. Reveille, John D. TI Are there clinical or genetic differences between familial and sporadic ankylosing spondylitis? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 71st Annual Meeting of the American-College-of-Rheumatology CY NOV 06-11, 2007 CL Boston, MA SP Amer Coll Rheumatol C1 [Brionez, Tamar F.; Assassi, Shervin; Diekman, Laura; Zhou, Xiadong; Albuquerque, Sheila M.] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Ward, Michael M.] NIAMS, Bethesda, MD USA. [Davis, John C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2007 VL 56 IS 12 BP 4300 EP 4300 PG 1 WC Rheumatology SC Rheumatology GA 243FS UT WOS:000251781200169 ER PT J AU Simeonov, A Yasgar, A Klumpp, C Zheng, W Shafqat, N Oppermann, U Austin, CP Inglesel, J AF Simeonov, Anton Yasgar, Adam Klumpp, Carleen Zheng, Wei Shafqat, Naeem Oppermann, Udo Austin, Christopher P. Inglesel, James TI Evaluation of micro-parallel liquid chromatography as a method for HTS-coupled actives verification SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES LA English DT Article ID AMYLOID-BETA-PEPTIDE; GAUCHER-DISEASE; CHEMICAL CHAPERONES; ALZHEIMERS-DISEASE; DISCOVERY; LIBRARIES; STRATEGY; ASSAYS AB The identification of biologically active compounds from high-throughput screening (HTS) can involve considerable postscreening analysis to verify the nature of the sample activity. In this study we evaluated the performance of micro-parallel liquid chromatography (mu PLC) as a separation-based enzyme assay platform for follow-up of compound activities found in quantitative HTS of two different targets, a hydrolase and an oxidoreductase. In an effort to couple secondary analysis to primary screening we explored the application of mu PLC immediately after a primary screen. In mu PLC, up to 24 samples can be loaded and analyzed simultaneously via high-performance liquid chromatography within a specially designed cartridge. In a proof-of-concept experiment for screen-coupled actives verification, we identified, selected, and consolidated the contents of "active" wells from a 1,536-well format HTS experiment into a 384-well plate and subsequently analyzed these samples by a 24-channel mu PLC system. The method utilized 0.6% of the original 6-mu I 1,536-well assay for the analysis. The analysis revealed several non-biological-based "positive" samples. The main examples included "false" enzyme activators resulting from an increase in well fluorescence due to fluorescent compound or impurity. The mu PLC analysis also provided a verification of the activity of two activators of glucocerebrosidase. We discuss the benefits of mu PLC and its limitations from the standpoint of ease of use and integration into a seamless postscreen workflow. C1 [Simeonov, Anton; Yasgar, Adam; Klumpp, Carleen; Austin, Christopher P.; Inglesel, James] NHGRI, NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. [Shafqat, Naeem; Oppermann, Udo] Univ Oxford, Botnar Res Ctr, Struct Genom Consortium, Oxford, England. RP Simeonov, A (reprint author), NHGRI, NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. EM asimeono@mail.nih.gov OI Zheng, Wei/0000-0003-1034-0757 FU Intramural NIH HHS; Wellcome Trust NR 23 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-658X EI 1557-8127 J9 ASSAY DRUG DEV TECHN JI ASSAY DRUG DEV. TECHNOL. PD DEC PY 2007 VL 5 IS 6 BP 815 EP 824 DI 10.1089/adt.2007.097 PG 10 WC Biochemical Research Methods; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 252UQ UT WOS:000252472500010 PM 18078381 ER PT J AU Evers, DL Slemons, RD Taubenberger, JK AF Evers, David L. Slemons, Richard D. Taubenberger, Jeffery K. TI Effect of Preservative on Recoverable RT-PCR Amplicon Length from Influenza A Virus in Bird Feces SO AVIAN DISEASES LA English DT Article DE feces; influenza; RNA extraction; RT-PCR ID IDENTIFICATION; SURVEILLANCE; SAMPLES; DUCKS AB Surveillance for avian influenza A viruses in wild bird populations is often limited by requirements for a cold chain from time of specimen collection, by availability of ultra-low temperature specimen storage within a few hours or days, and by laborious classical virologic procedures. Successful storage of specimens in preservatives at ambient temperature and subsequent detection of RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) would assist in helping influenza surveillance efforts become more widespread in remote areas, as well as more timely and inexpensive. Here, we describe bird feces spiked with influenza A virus preserved with guanidine and commercial buffers or alcohols at ambient temperature and analyzed by RT-PCR protocols. Virus-specific RT-PCR products of, at most, 206 bp were recovered for samples preserved with alcohols and up to 521 bp for samples preserved with guanidine or commercial buffers. These results suggest that this approach is feasible in the field and that preserved specimens might be better assayed molecularly when preserved in guanidine or commercial buffers. C1 [Evers, David L.; Taubenberger, Jeffery K.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Slemons, Richard D.] Ohio State Univ, Dept Vet Prevent Med, Columbus, OH 43210 USA. RP Taubenberger, JK (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov FU Intramural Research Program of the NIH, NIAID FX We thank Matthew D. Memoli for useful advice. This research was supported by the Intramural Research Program of the NIH, NIAID. The authors declare no conflicts of interest. NR 16 TC 11 Z9 12 U1 2 U2 5 PU AMER ASSOC AVIAN PATHOLOGISTS PI ATHENS PA 953 COLLEGE STATION RD, ATHENS, GA 30602-4875 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD DEC PY 2007 VL 51 IS 4 BP 965 EP 968 DI 10.1637/7880-012207-RESNOTER1.1 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 372NF UT WOS:000260907600023 PM 18251409 ER PT J AU Pistell, PJ Daffin, LW Nelson, CM Duffy, KB Bowker, JL Spangler, EL Ingram, DK Devan, BD AF Pistell, Paul J. Daffin, Lee W., Jr. Nelson, Christopher M. Duffy, Kara B. Bowker, Jonna L. Spangler, Edward L. Ingram, Donald K. Devan, Bryan D. TI Combined administration of subthreshold doses of the nitric oxide inhibitor, nitro-L-arginine, and muscarinic receptor antagonist, scopolamine, impairs complex maze learning in rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE age-related memory impairment; cholinergic; maze learning; nitric oxide; rat ID WATER MAZE; CHOLINERGIC HYPOTHESIS; PHOSPHODIESTERASE INHIBITION; COGNITIVE ENHANCEMENT; ACETYLCHOLINE-RELEASE; SYNTHASE INHIBITION; MEMORY DYSFUNCTION; ALZHEIMERS-DISEASE; BLOCKADE; PERFORMANCE AB Traditionally, research into the neurobiological mechanisms of age-related memory impairments has focused on single neurotransmitter systems. As normal and abnormal age-related declines in memory function probably involve alterations in more than one system, a more effective approach for elucidating underlying neurobiological changes and resulting impairments may be to evaluate the roles of multiple systems simultaneously. This study evaluated the interaction of the cholinergic and nitric oxide systems in rats on acquisition in the 14-unit T-maze. This task requires learning a series of turns to avoid foot shock, and most likely reflects procedural learning. Administration of scopolamine (0.1 mg/kg) or N-omega-nitro-L-arginine methyl ester (30 mg/kg) alone did not impair acquisition, whereas administration of the same doses in combination increased both the latency to complete the maze and number of errors committed. These data suggest that manipulation of learning and memory processes with multiple compounds potentially offers a clinically relevant paradigm for investigating cognitive function in normal and abnormal aging. C1 Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. Gerontol Res Ctr, NIH, NIA, Behavioral Neurosci Sect,Lab Expt Gerontol, Baltimore, MD USA. Towson Univ, Dept Psychol, Lab Comparat Neuropsychol, Towson, MD USA. RP Pistell, PJ (reprint author), Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. FU Intramural NIH HHS NR 31 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD DEC PY 2007 VL 18 IS 8 BP 801 EP 805 DI 10.1097/FBP.0b013e3282f18d2f PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 236DM UT WOS:000251283200011 PM 17989518 ER PT J AU Chng, WJ Glebov, O Bergsagel, RL Kuehl, WM AF Chng, W. J. Glebov, O. Bergsagel, R. L. Kuehl, W. M. TI Genetic events in the pathogenesis of multiple myeloma SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Review DE genetics; gene expression profiling; molecular pathogenesis; prognosis; IgH translocations; hyperdiploid ID IN-SITU HYBRIDIZATION; STEM-CELL TRANSPLANTATION; GROWTH-FACTOR RECEPTOR-3; ADVERSE PROGNOSTIC-FACTOR; COOPERATIVE-ONCOLOGY-GROUP; HIGH-DOSE THERAPY; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; CHROMOSOME-13 ABNORMALITIES; 14Q32 TRANSLOCATIONS AB The genetics of myeloma has been increasingly elucidated in recent years. Recurrent genetic events, and also biologically distinct and clinically relevant genetic subtypes of myeloma have been defined. This has facilitated our understanding of the molecular pathogenesis of the disease. In addition, some genetic abnormalities have proved to be highly reproducible prognostic factors. With the expanding therapeutic armamentarium, it is time to include genetic assessment as part of clinical evaluation of myeloma patients to guide management. In this review we examine the role of various genetic abnormalities in the molecular pathogenesis of myeloma, and the use of such abnormalities in disease classification, prognosis and clinical management. C1 [Chng, W. J.; Bergsagel, R. L.] Mayo Clin, Scottsdale, AZ 85259 USA. [Glebov, O.] Natl Canc Inst, Bethesda, MD USA. [Kuehl, W. M.] Natl Canc Inst, Genet Branch, Mol Pathogenesis Myeloma Sect, Bethesda, MD USA. RP Bergsagel, RL (reprint author), Mayo Clin, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM bergsagel.leif@mayo.edu FU NCI NIH HHS [P50 CA100707-010004, K01 CA074265, K01 CA074265-03, K01 CA074265-04, K01 CA074265-05, P50 CA100707]; NIA NIH HHS [R01 AG020686, R01 AG020686-01A1, R01 AG020686-02, R01 AG020686-03, R01 AG020686-04, R01 AG020686-05] NR 108 TC 111 Z9 115 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2007 VL 20 IS 4 BP 571 EP 596 DI 10.1016/j.beha.2007.08.004 PG 26 WC Hematology SC Hematology GA 248HF UT WOS:000252142800002 PM 18070707 ER PT J AU Chill, JH Louis, JM Delaglio, F Bax, A AF Chill, Jordan H. Louis, John M. Delaglio, Frank Bax, Ad TI Local and global structure of the monomeric subunit of the potassium channel KcsA probed by NMR SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE membrane proteins; potassium channel; NMR; RDC; solvent exchange ID INTEGRAL MEMBRANE-PROTEINS; RESIDUAL DIPOLAR COUPLINGS; K+ CHANNEL; DETERGENT MICELLES; POLYACRYLAMIDE-GELS; SELECTIVITY FILTER; N-15 RELAXATION; WEAK ALIGNMENT; SPECTROSCOPY; ASSIGNMENTS AB KcsA is a homotetrameric 68-kDa membrane-associated potassium channel which selectively gates the flux of potassium ions across the membrane. The channel is known to undergo a pH-dependent open-to-closed transition. Here we describe an NMR study of the monomeric subunit of the channel (KcsA(M)), solubilized in SDS micelles. Chemical shift, solvent exchange, backbone N-15 relaxation and residual dipolar coupling (RDC) data show the TM1 helix to remain intact, but the TM2 helix contains a distinct kink, which is subject to concentration-independent but pH-dependent conformational exchange on a microsecond time scale. The kink region, centered at G99, was previously implicated in the gating of the tetrameric KcsA channel. An RDC-based model of KcsA(M) at acidic pH orients TM1 and the two helical segments of the kinked TM2 in a configuration reminiscent of the open conformation of the channel. Thus, the transition between states appears to be an inherent capability of the monomer, with the tetrameric assembly exerting a modulatory effect upon the transition which gives the channel its physiological gating profile. Published by Elsevier B.V. C1 [Chill, Jordan H.; Louis, John M.; Delaglio, Frank; Bax, Ad] NIDDK, Natl Inst Hlth, Chem Phys Lab, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Natl Inst Hlth, Chem Phys Lab, Bldg 5,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bax@nih.gov FU Intramural NIH HHS [Z01 DK029020-23] NR 49 TC 30 Z9 30 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD DEC PY 2007 VL 1768 IS 12 BP 3260 EP 3270 DI 10.1016/j.bbamem.2007.08.006 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 253AH UT WOS:000252488900031 PM 17945182 ER PT J AU Ahn, BH Park, MH Lee, YH Kwon, TK Min, DS AF Ahn, Bong-Hyun Park, Mi Hee Lee, Young Han Kwon, Taeg Kyu Min, Do Sik TI Up-regulation of cyclooxygenase-2 mediated by phospholipase D is by cobalt chloride-induced hypoxia is ozymes in human astroglioma cells SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE cyclooxygenase-2; prostaglandin e2; cobalt chloride; hypoxia; phospholipase D ID ENDOTHELIAL GROWTH-FACTOR; HUMAN GLIOMAS; IN-VIVO; EXPRESSION; CANCER; BRAIN; PROLIFERATION; INFLAMMATION; MACROPHAGES; ASTROCYTES AB Cyclooxygenase-2 (COX-2) is an isoform of prostaglandin H synthase induced by hypoxia and has been implicated in the growth and progression of a variety of human cancers. In the present study, we investigated the role of phospholipase D (PLD) isozymes in cobalt chloride (COCl2)-induced hypoxia-driven COX-2 expression in U87 MG human astroglioma cells. COCl2 stimulated PLD activity and synthesis of COX-2 protein in a dose and time-dependent manner. Moreover, elevated expression of PLD1 and PLD2 increased hypoxia-induced COX-2 expression and prostaglandin E2 (PGE(2)) production. Pretreatment of cells with 1-butanol, but not 3-butanol, suppressed COCl2-induced COX-2 expression and PGE(2) formation. In addition, evidence that PLD activity was involved in the stimulation of COX-2 expression was provided by the observations that overexpression of wild type PLD isozymes, but not catalytically inactive PLD isozymes, stimulated COCl2-induced COX-2 expression and PGE(2) production. PLD1 enhanced COX-2 expression by COCl2 via reactive oxygen species (ROS), p38 MAPK kinase, PKC-delta, and PKA, but not ERK, whereas PLD2 enhanced COCl2-induced COX-2 expression via ROS and p38 MAPK, but not ERK, PKC-delta, and PKA. Differential regulation of COX-2 expression mediated through PLD isozymes was comparable with that of COCl2-induced PLD activity in these two PLD isozymes. Taken together, our results demonstrate for the first time that PLD1 and PLD2 isozymes enhance COCl2-induced COX-2 expression through differential signaling pathways in astroglioma cells. (c) 2007 Elsevier B.V. All rights reserved. C1 [Park, Mi Hee; Min, Do Sik] Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, Pusan 609735, South Korea. [Ahn, Bong-Hyun] NHLBI, Cardiovasc Branch Natl Heart, Bethesda, MD 20892 USA. [Lee, Young Han] IBST, Dept Biomed Sci & Technol, Seoul, South Korea. [Kwon, Taeg Kyu] Keimyung Univ, Sch Med, Dept Immunol, Taegu 700712, South Korea. RP Min, DS (reprint author), Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, 30 Jangjeon Dong, Pusan 609735, South Korea. EM minds@pusan.ac.kr NR 41 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD DEC PY 2007 VL 1773 IS 12 BP 1721 EP 1731 DI 10.1016/j.bbamcr.2007.06.001 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 251QF UT WOS:000252387800002 PM 17640750 ER PT J AU Gonzalez, RD Pertejo, YP Redondo, CA Pommier, Y Balana-Fouce, R Reguera, RA AF Gonzalez, Rosario Diaz Pertejo, Yolanda Perez Redondo, Carmen A. Pommier, Yves Balana-Fouce, Rafael Reguera, Rosa A. TI Structural insights on the small subunit of DNA topoisomerase I from the unicellular parasite Leishmania donovani SO BIOCHIMIE LA English DT Article DE DNA topoisomerase IB; camptothecin; Leishmania donovani; trypanosomatids; tropical diseases ID CAMPTOTHECIN; MECHANISM; RELAXATION; COMPLEXES; BINDING; LINKER; ENZYME; DAMAGE; ROLES; CELLS AB Leishmania donovani, the causative organism of visceral leishmaniasis, contains a unique heterodimeric DNA topoisomerase IB (LdTop1). The catalytically active enzyme consists of a large subunit (LdTop1L), which contains the non-conserved N-terminal end and a phylogenetically conserved core domain, and of a small subunit (LdTop1S) which harbours the C-terminal region with a characteristic tyrosine residue in the active site. Heterologous co-expression of LdTop1L and LdTop1S in a topoisomerase I deficient yeast strain, reconstitutes a fully functional enzyme which can be used for structural studies. The role played by the non-conserved N-terminal extension of LdTop1S in both relaxation activity and CPT sensitivity of LdTop1 has been examined co-expressing the full-length LdTop1L with several deletions of LdTop1S lacking growing sequences of the N-terminal end. The sequential deletion study shows that the first 174 amino acids of LdTop1S are dispensable in terms of relaxation activity and DNA cleavage. It is also described that the trapping of the covalent complex between LdTop1 and DNA by CPT requires a pentapeptide between amino acid residues 175 and 179 of LdTop1S. Our results suggest the crucial role played by the N-terminal extension of the small subunit of DNA topoisomerase I. (C) 2007 Published by Elsevier Masson SAS. C1 [Gonzalez, Rosario Diaz; Pertejo, Yolanda Perez; Redondo, Carmen A.; Balana-Fouce, Rafael; Reguera, Rosa A.] Univ Leon, Dept Farmacol & Toxicol, INTOXCAL, E-24071 Leon, Spain. [Pommier, Yves] NCI, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Balana-Fouce, R (reprint author), Univ Leon, Dept Farmacol & Toxicol, INTOXCAL, Campus Vegazana S-N, E-24071 Leon, Spain. EM pommier@mail.nih.gov; dftrbf@unileon.es OI perez-pertejo, yolanda/0000-0003-2361-3785; Reguera, Rosa M/0000-0001-9148-2997; Balana-Fouce, Rafael/0000-0003-0418-6116 NR 33 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 EI 1638-6183 J9 BIOCHIMIE JI Biochimie PD DEC PY 2007 VL 89 IS 12 BP 1517 EP 1527 DI 10.1016/j.biochi.2007.07.015 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 247RG UT WOS:000252096700009 ER PT J AU Whitcomb, RF Tully, JG Gasparich, GE Regassa, LB Williamson, DL French, FE AF Whitcomb, Robert F. Tully, Joseph G. Gasparich, Gail E. Regassa, Laura B. Williamson, David L. French, Frank E. TI Spiroplasma species in the Costa Rican highlands: implications for biogeography and biodiversity SO BIODIVERSITY AND CONSERVATION LA English DT Article DE Costa Rica; diversity; Georgia; horse flies; latitude; spiroplasma; tabanidae ID AD-HOC-COMMITTEE; GENUS SPIROPLASMA; MYCOPLASMA-HOMINIS; NORTH-AMERICA; GROUP-VIII; TABANIDAE; DIPTERA; CLASSIFICATION; STRAINS; HETEROGENEITY AB More than 1,000 Spiroplasma isolates have been obtained from horse flies and deer flies (Diptera:Tabanidae) in the United States and Canada. However, the spiroplasma biota of Central America is poorly known. In August of 1995 and 1998, 13 isolates were obtained in 14 attempts from horse flies of a single species, Poeciloderas quadripunctatus, taken in the Costa Rican highlands (1,100-2,000 m). The majority of the "isolates" proved to be mixtures of two or more Spiroplasma species, but after filter cloning, single strains emerged that were designated as representatives of the 13 accessions. Six distinct spiroplasma serogroups were identified from these isolations. Three of the strains are putative new species with no serological relationship to any other Spiroplasma species. A fourth strain is a putative new species that may be distantly related to S. helicoides, a southeastern U.S. species. These four strains are accorded herein status as representatives of new serogroups: strain BARC 4886 (group XXXV); strain BARC 4900 (group XXXVI); strain BARC 4908 (group XXXVII); and GSU5450 (group XXXVIII). A fifth Spiroplasma species was very closely related to S. lineolae, known previously only from the Georgia (U.S.) coast. The sixth was most closely related to subgroup VIII-3, known from Texas and the southeastern U.S. Discovery of six spiroplasma species in only 13 attempted isolations reflects diversity seldom equaled in southeast Georgia, and never elsewhere in the U.S. These results are consistent with a hypothesis that spiroplasma diversity increases from north (Nova Scotia) to south (Georgia and Costa Rica). The discovery of significant affinity between some spiroplasmas of the southeastern U.S. and the Costa Rican highlands was unexpected, but may reflect a climatically complex Pleistocene history. C1 USDA, Vegetable Lab, Beltsville, MD 20705 USA. Natl Inst Allergy & Infect Dis, Frederick Canc Res Facil, Mol Microbiol Lab, Mycoplasma Sect, Frederick, MD 21702 USA. Towson Univ, Dept Biol, Towson, MD 21252 USA. Georgia So Univ, Inst Arthropodol & Parasitol, Dept Biol, Statesboro, GA 30460 USA. SUNY Stony Brook, Dept Anatom Sci, Stony Brook, NY 11794 USA. RP Whitcomb, RF (reprint author), PO Box 1148, Patagonia, AZ 85624 USA. EM whitcomb@dakotacom.net NR 71 TC 3 Z9 7 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0960-3115 J9 BIODIVERS CONSERV JI Biodivers. Conserv. PD DEC PY 2007 VL 16 IS 13 BP 3877 EP 3894 DI 10.1007/s10531-007-9197-z PG 18 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 222ML UT WOS:000250301400012 ER PT J AU Xu, ZL Kaplan, NL Taylor, JA AF Xu, Zongli Kaplan, Norman L. Taylor, Jack A. TI TAGster: efficient selection of LD tag SNPs in single or multiple populations SO BIOINFORMATICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; NUCLEOTIDE POLYMORPHISMS; ASSOCIATION AB Genetic association studies increasingly rely on the use of linkage disequilibrium (LD) tag SNPs to reduce genotyping costs. We developed a software package TAGster to select, evaluate and visualize LD tag SNPs both for single and multiple populations. We implement several strategies to improve the efficiency of current LD tag SNP selection algorithms: (1) we modify the tag SNP selection procedure of Carlson et al. to improve selection efficiency and further generalize it to multiple populations. (2) We propose a redundant SNP elimination step to speed up the exhaustive tag SNP search algorithm proposed by Qin et al. (3) We present an additional multiple population tag SNP selection algorithm based on the framework of Howie et al., but using our modified exhaustive search procedure. We evaluate these methods using resequenced candidate gene data from the Environmental Genome Project and show improvements in both computational and tagging efficiency. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA. RP Taylor, JA (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398 FU Intramural NIH HHS [Z01 ES049033-11, Z99 ES999999] NR 6 TC 26 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD DEC 1 PY 2007 VL 23 IS 23 BP 3254 EP 3255 DI 10.1093/bioinformatics/btm426 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 236WT UT WOS:000251334800023 PM 17827206 ER PT J AU Laje, G McMahon, FJ AF Laje, Gonzalo McMahon, Francis J. TI The pharmacogenetics of major depression: Past, present, and future SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID STAR-ASTERISK-D; SEROTONIN TRANSPORTER; ANTIDEPRESSANT TREATMENT; SUICIDAL IDEATION; HUMAN GENOME; ASSOCIATION; CITALOPRAM; POLYMORPHISMS C1 NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP McMahon, FJ (reprint author), 35 Convent Dr,Room 1A202, Bethesda, MD 20892 USA. EM mcmahonf@mail.nih.gov RI Laje, Gonzalo/L-2654-2014; OI Laje, Gonzalo/0000-0003-2763-3329; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS NR 22 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2007 VL 62 IS 11 BP 1205 EP 1207 DI 10.1016/j.biopsych.2007.09.016 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 233VY UT WOS:000251119600002 PM 17949692 ER PT J AU Hasler, G Bonwetsch, R Giovacchini, G Toczek, MT Bagic, A Luckenbaugh, DA Drevets, WC Theodore, WH AF Hasler, Gregor Bonwetsch, Robert Giovacchini, Giampiero Toczek, Maria T. Bagic, Anto Luckenbaugh, David A. Drevets, Wayne C. Theodore, William H. TI 5-HT1A receptor binding in temporal lobe epilepsy patients with and without major depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE [F-18]FCWAY-PET; 5-HT1A; receptor binding; major depressive disorder; psychiatric comorbidity; serotonin; temporal lobe epilepsy ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN-REGIONS; PRONE RATS; SEROTONIN(1A); EXPRESSION; DISORDERS; COMMUNITY; NEURONS; ABNORMALITIES; IMPAIRMENT AB Background: Major depressive disorder (MDD) is the most common comorbid psychiatric condition associated with temporal lobe epilepsy (TLE). Preclinical and clinical studies suggest that 5-HT1A receptors play a role in the pathophysiology of both TLE and MDD. There is preliminary evidence for an association between decreased 5-HT1A receptor binding in limbic brain areas and affective symptoms in TLE patients. The objective of this study was to compare 5-HT1A receptor binding between TLE patients with and without MDD. For the first time, 5-HT1A receptor binding was measured in a sample large enough to permit sensitive comparisons between TLE patients with and without comorbid MDD diagnosed by clinical and structured psychiatric interviews. Methods: Thirty-seven epilepsy patients with temporal lobe foci confirmed by ictal video-electroencephalogram (EEG) monitoring were recruited from the Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke. We performed interictal positron emission tomography scanning, with [F-18]FCWAY, a fluorinated derivative of WAY100635, on a GE Medical Systems (Waukesha, Wisconsin) Advance scanner with continuous EEG monitoring. The 5-HT1A receptor binding was estimated by partial volume-corrected [F-18]FCWAYV/f(1) values. Results: In addition to decreased 5-HT1A receptor binding in the epileptic focus itself, comorbid MDD was associated with a significantly more pronounced reduction in 5-HT1A receptor binding in TLE patients, extending into non-lesional limbic brain areas outside the epileptic focus. Focus side and the presence of mesial temporal sclerosis were not associated with the presence of comorbid depression. Conclusions: Reductions in 5-HT1A receptor binding might help elucidate the neurobiological mechanisms underlying the TLE-MDD comorbidity. C1 Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, Bethesda, MD 20892 USA. RP Hasler, G (reprint author), Univ Zurich Hosp, Dept Psychiat, Culmannstr 8, CH-8091 Zurich, Switzerland. EM gregor.hasler@usz.ch RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 FU Intramural NIH HHS [Z01 NS002236-32] NR 53 TC 79 Z9 80 U1 1 U2 11 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 DEC 1 PY 2007 VL 62 IS 11 BP 1258 EP 1264 DI 10.1016/j.biopsych.2007.02.015 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 233VY UT WOS:000251119600009 PM 17588547 ER PT J AU Xu, XM Carlson, BA Zhang, Y Mix, H Kryukov, GV Glass, RS Berry, MJ Gladyshev, VN Hatfield, DL AF Xu, Xue-Ming Carlson, Bradley A. Zhang, Yan Mix, Heiko Kryukov, Gregory V. Glass, Richard S. Berry, Marla J. Gladyshev, Vadim N. Hatfield, Dolph L. TI New developments in selenium biochemistry: Selenocysteine biosynthesis in eukaryotes and archaea SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE selenocysteine; selenocysteine biosynthesis; selenocysteine synthase; selenophosphate synthetase; selenoproteins ID SERINE TRANSFER-RNA; SYNTHETASE 2 SPS2; SELENOPHOSPHATE SYNTHETASE; ESCHERICHIA-COLI; SELENOPROTEIN SYNTHESIS; IDENTIFICATION; SEQUENCE; IDENTITY; SYNTHASE; LIVER AB We used comparative genomics and experimental analyses to show that (1) eukaryotes and archaea, which possess the selenocysteine (Sec) protein insertion machinery contain an enzyme, O-phosphoseryl-transfer RNA (tRNA)([Ser]Sec) kinase (designated PSTK), which phosphorylates seryl-tRNA([Ser]Sec) to form O-phosphoseryl-tRNA([Ser]Sec) and (2) the Sec synthase (SecS) in mammals is a pyridoxal phosphate-containing protein previously described as the soluble liver antigen (SLA). SecS uses the product of PSTK, O-phosphoseryl-tRNA([Ser]Sec), and selenophosphate as substrates to generate selenocysteyl-tRNA([Ser]Sec). Sec could be synthesized on tRNA([Ser]Sec) from selenide, adenosine triphosphate (ATP), and serine using tRNA([Ser]Sec), seryl-tRNA synthetase, PSTK, selenophosphate synthetase, and SecS. The enzyme that synthesizes monoselenophosphate is a previously identified selenoprotein, selenophosphate synthetase 2 (SPS2), whereas the previously identified mammalian selenophosphate synthetase 1 did not serve this function. Monoselenophosphate also served directly in the reaction replacing ATP, selenide, and SPS2, demonstrating that this compound was the active selenium donor. Conservation of the overall pathway of Sec biosynthesis suggests that this pathway is also active in other eukaryotes and archaea that contain selenoproteins. C1 NIH, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. Univ Hawaii Manoa, Dept Cell & Mol Biol, Honolulu, HI 96813 USA. RP Hatfield, DL (reprint author), NIH, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. EM hatfield@dc37a.nci.nih.gov RI Kryukov, Gregory/A-9592-2008; Gladyshev, Vadim/A-9894-2013; OI Kryukov, Gregory/0000-0002-6131-9483 FU Intramural NIH HHS; NCI NIH HHS [CA-41108, CA080946]; NIDDK NIH HHS [DK47320, DK52963]; NIGMS NIH HHS [GM061603, GM065204] NR 32 TC 22 Z9 24 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD DEC PY 2007 VL 119 IS 3 BP 234 EP 241 DI 10.1007/s12011-007-8003-9 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 215AG UT WOS:000249779000005 PM 17916946 ER PT J AU Eapen, M Logan, BR Confer, DL Haagenson, M Wagner, JE Weisdorf, DJ Wingard, JR Rowley, SD Stroncek, D Gee, AP Horowitz, MM Anasetti, C AF Eapen, Mary Logan, Brent R. Confer, Dennis L. Haagenson, Michael Wagner, John E. Weisdorf, Daniel J. Wingard, John R. Rowley, Scott D. Stroncek, David Gee, Adrian P. Horowitz, Mary M. Anasetti, Claudio TI Peripheral blood grafts from unrelated donors are associated with increased acute and chronic graft-versus-host disease without improved survival SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol DE peripheral blood graft; graft-versus-host disease; unrelated donor transplant ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; FOLLOW-UP; RISK; RECIPIENTS; LEUKEMIA; REGISTRY AB Few studies have tested the benefits of using peripheral blood stem cell (PBSC) grafts versus bone marrow (BM) grafts for unrelated donor transplantation. Yet there has been a substantial change in clinical practice, with increasing numbers of adults receiving unrelated donor PBSC grafts. We compared outcomes after 331 PBSC and 586 BM transplants in adults with leukemia and myelodysplastic syndrome (MDS) who were followed for a median of 3 years after transplantation. PBSC recipients were less likely to have chronic myelogenous leukemia (CML) and more likely to have MDS, to have poor performance scores, and to be transplanted more recently. Outcomes were analyzed using Cox regression models. Rates of grades 2-4 acute graft-versus-host disease (GVHD) (58% versus 45%, P < .001) and chronic GVHD (cGVHD) (56% versus 42%, P < .001) were significantly higher with PBSC than with BM transplants. Rates of grade II-IV aGVHD were similar with PBSC and BM transplants. The 3-year probabilities' of treatment-related mortality (TRM), leukemia recurrence, leukemia-free, and overall survival (OS) were similar in the 2 groups with 3-year leukemia-free survival rates of 30% and 32% after transplantation of PBSC and BM, respectively. Unlike results after B-LA-matched sibling donor PBSC transplants, we did not identify a survival advantage with PBSC grafts in patients receiving unrelated donor transplants for advanced leukemia. The higher rate of cGVHD after PBSC transplants and, consequently, more frequent late adverse events warrant extended follow up of PBSC recipients. (c) 2007 American Society for Blood and Marrow Transplantation. C1 Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. Univ Florida, Shands Hosp, Gainesville, FL USA. Hackensack Univ Med Ctr, Hackensack, NJ USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Eapen, M (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 8701 Watertown Plank Rd,POB 26509, Milwaukee, WI 53226 USA. EM meapen@mcw.edu FU NCI NIH HHS [U24 CA076518, U24 CA076518-08, U24-CA76518-08] NR 20 TC 110 Z9 114 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2007 VL 13 IS 12 BP 1461 EP 1468 DI 10.1016/j.bbmt.2007.08.006 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 239CM UT WOS:000251495900008 PM 18022576 ER PT J AU Dhungana, S Michalczyk, R Boukhalfa, H Lack, JG Koppisch, AT Fairlee, JM Johnson, MT Ruggiero, CE John, SG Cox, MM Browder, CC Forsythe, JH Vanderberg, LA Neu, MP Hersman, LE AF Dhungana, Suraj Michalczyk, Ryszard Boukhalfa, Hakim Lack, Joseph G. Koppisch, Andrew T. Fairlee, Jason M. Johnson, Mitchell T. Ruggiero, Christy E. John, Seth G. Cox, Matthew M. Browder, Cindy C. Forsythe, Jennifer H. Vanderberg, Laura A. Neu, Mary P. Hersman, Larry E. TI Purification and characterization of rhodobactin: a mixed ligand siderophore from Rhodococcus rhodochrous strain OFS SO BIOMETALS LA English DT Article DE Rhodococcus; rhodobactin; siderophore; catecholate; hydroxamate ID MEDIATED IRON TRANSPORT; EXOCHELIN MN; STRUCTURAL-CHARACTERIZATION; EXTRACELLULAR SIDEROPHORE; 2,3-DIHYDROXYBENZOIC ACID; COORDINATION CHEMISTRY; BACILLUS-ANTHRACIS; GENUS RHODOCOCCUS; DONOR GROUPS; IDENTIFICATION AB The siderophore produced by Rhodococcus rhodochrous strain OFS, rhodobactin, was isolated from iron-deficient cultures and purified by a combination of XAD-7 absorptive/ partition resin column and semi-preparative HPLC. The siderophore structure was characterized using 1D and 2D H-1, C-13 and N-15 NMR techniques (DQFCOSY, TOCSY, NOESY, HSQC and LR-HSQC) and was confirmed using ESI-MS and MS/MS experiments. The structural characterization revealed that the siderophore, rhodobactin, is a mixed ligand hexadentate siderophore with two catecholate and one hydroxamate moieties for iron chelation. We further investigated the effects of Fe concentrations on siderophore production and found that Fe limiting conditions ( Fe concentrations from 0.1 mu M to 2.0 mu M) facilitated siderophore excretion. Our interests lie in the role that siderophores may have in binding metals at mixed contamination sites ( containing metals/radionuclides and organics). Given the broad metabolic capacity of this microbe and its Fe scavenging ability, R. rhodochrous OFS may have a competitive advantage over other organisms employed in bioremediation. C1 Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Ft Lewis Coll, Dept Chem, Los Alamos, NM 87545 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Hersman, LE (reprint author), Los Alamos Natl Lab, Mail Stop M888, Los Alamos, NM 87545 USA. EM hersman@lanl.gov RI Browder, Cindy/F-4700-2017; OI Michalczyk, Ryszard/0000-0001-8839-6473 NR 43 TC 13 Z9 13 U1 3 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0966-0844 J9 BIOMETALS JI Biometals PD DEC PY 2007 VL 20 IS 6 BP 853 EP 867 DI 10.1007/s10534-006-9079-y PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 224QW UT WOS:000250462500004 PM 17273817 ER PT J AU Chen, J Rodriguez, C AF Chen, Jinbo Rodriguez, Carmen TI Conditional likelihood methods for haplotype-based association analysis using matched case-control data SO BIOMETRICS LA English DT Article DE conditional likelihood; logistic regression; matched case-control study; phase ambiguity; unphased genotype data ID UNRELATED INDIVIDUALS; GENOTYPE DATA; COHORT; INFERENCE; TRAITS; FUTURE; PHASE AB Genetic epidemiologists routinely assess disease susceptibility in relation to haplotypes, that is, combinations of alleles on a single chromosome. We study statistical methods for inferring haplotype-related disease risk using single nucleotide polymorphism (SNP) genotype data from matched case-control studies, where controls are individually matched to cases on some selected factors. Assuming a logistic regression model for haplotype-disease association, we propose two conditional likelihood approaches that address the issue that haplotypes cannot be inferred with certainty from SNP genotype data (phase ambiguity). One approach is based on the likelihood of disease status conditioned on the total number of cases, genotypes, and other covariates within each matching stratum, and the other is based on the joint likelihood of disease status and genotypes conditioned only on the total number of cases and other covariates. The joint-likelihood approach is generally more efficient, particularly for assessing haplotype-environment interactions. Simulation studies demonstrated that the first approach was more robust to model assumptions on the diplotype distribution conditioned on environmental risk variables and matching factors in the control population. We applied the two methods to analyze a matched case-control study of prostate cancer. C1 Natl Canc Inst, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. RP Chen, J (reprint author), Natl Canc Inst, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Executive Blvd, Rockville, MD 20852 USA. EM chenjin@mail.nih.gov NR 20 TC 2 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2007 VL 63 IS 4 BP 1099 EP 1107 DI 10.1111/j.1541-0420.2007.00797.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 239HB UT WOS:000251508300014 PM 18078481 ER PT J AU Hayakawa, E Tokumasu, F Nardone, GA Jin, AJ Hackley, VA Dvorak, JA AF Hayakawa, Eri Tokumasu, Fuyuki Nardone, Glenn A. Jin, Albert J. Hackley, Vince A. Dvorak, James A. TI A Mycobacterium tuberculosis-derived lipid inhibits membrane fusion by modulating lipid membrane domains SO BIOPHYSICAL JOURNAL LA English DT Article ID ATOMIC-FORCE MICROSCOPY; LIGHT-SCATTERING; INFECTED MACROPHAGES; LIPOARABINOMANNAN; DYNAMICS; RAFTS; SPHINGOMYELIN; PURIFICATION; MICRODOMAINS; TRAFFICKING AB Tuberculosis is an infectious and potentially fatal disease caused by the acid-fast bacillus Mycobacterium tuberculosis (MTB). One hallmark of a tuberculosis infection is the ability of the bacterium to subvert the normal macrophage defense mechanism of the host immune response. Lipoarabinomannan ( LAM), an integral component of the MTB cell wall, is released when MTBs are taken into phagosomes and has been reported to be involved in the inhibition of phago-lysosomal (P-L) fusion. However, the physical chemistry of the effects of LAM on lipid membrane structure relative to P-L fusion has not been studied. We produced membranes in vitro composed of dioleoylphosphatidylcholine, sphingomyelin, and cholesterol to simulate phagosomal lipid membranes and quantified the effects of the addition of LAM to these membranes, using fluorescence resonance energy transfer assays and atomic force microscopy. We found that LAM inhibits vesicle fusion and markedly alters lipid membrane domain morphology and sphingomyelin-chollesterol/dioleoylphosphatidylcholine ratios. These data demonstrate that LAM induces a dramatic reorganization of lipid membranes in vitro and clarifies the role of LAM in the inhibition of P-L fusion and the survival of the MTB within the macrophage. C1 Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan. NIAID, Lab Malaria & Vector Dis, Kawaguchi, Saitama 3220012, Japan. NIH, NIAID, ORS OD, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Mat Sci & Engn Lab, Gaithersburg, MD 20899 USA. RP Tokumasu, F (reprint author), NIH, NIAID, Lab Malaria & Vector Dis, Bethesda, MD 20892 USA. EM ftokumasu@niaid.nih.gov OI Jin, Albert/0000-0003-3826-1081; Tokumasu, Fuyuki/0000-0003-2790-1071 FU Intramural NIH HHS [Z01 EB000015-02] NR 45 TC 19 Z9 19 U1 0 U2 4 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2007 VL 93 IS 11 BP 4018 EP 4030 DI 10.1529/biophysj.107.104075 PG 13 WC Biophysics SC Biophysics GA 231MS UT WOS:000250951900031 PM 17704144 ER PT J AU Nelson, EE Vinton, DT Berghorst, L Towbin, KE Hommer, RE Dickstein, DP Rich, BA Brotman, MA Pine, DS Leibenluft, E AF Nelson, Eric E. Vinton, Deborah T. Berghorst, Lisa Towbin, Kenneth E. Hommer, Rebecca E. Dickstein, Daniel P. Rich, Brendan A. Brotman, Melissa A. Pine, Daniel S. Leibenluft, Ellen TI Brain systems underlying response flexibility in healthy and bipolar adolescents: an event-related fMRI study SO BIPOLAR DISORDERS LA English DT Article DE attention; emotion regulation; inhibition; response selection ID FUNCTIONAL NEUROANATOMY; SUSTAINED ATTENTION; INHIBITORY CONTROL; DISORDER; MANIA; DEFICITS; ABNORMALITIES; PHENOMENOLOGY; ORGANIZATION; SUPPRESSION AB Previous studies have indicated abnormalities in response flexibility in pediatric bipolar disorder (BD). Dysfunction in response flexibility may contribute to the pattern of behavioral and emotional dysregulation that is characteristic of BD, since depressed and manic patients respond inflexibly to emotional stimuli (i.e., anhedonia in the case of depression or inappropriate positive affect in the case of mania). The present study was undertaken to determine if neuronal responses differed between BD and control subjects on a simple motor response flexibility task. To elucidate the neural substrates mediating response flexibility in pediatric BD, we studied 25 youth with BD and 17 age-, gender- and IQ-matched controls (CON) as they performed the change task while undergoing event-related functional magnetic resonance imaging (fMRI). The change task is a new fMRI task that requires subjects to both inhibit and replace a prepotent motor response with another motor response after the initial response has been cued. On correctly performed change trials relative to correctly performed go trials, BD patients generated significantly more activity in the left dorsolateral prefrontal cortex (DLPFC) and in the primary motor cortex than did healthy controls, even though performance levels did not differ across groups. These results indicate that functional deficits within the left DLPFC may mediate deficits in response flexibility in pediatric BD. This deficit may extend beyond the realm of motor control and also affect emotion regulation. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Nelson, EE (reprint author), NIMH, Mood & Anxiety Disorders Program, 106-C,5413 W Cedar Lane, Bethesda, MD 20892 USA. EM nelsone@intra.nimh.nih.gov RI Nelson, Eric/B-8980-2008; Brotman, Melissa/H-7409-2013; Dickstein, Daniel/L-3210-2016 OI Nelson, Eric/0000-0002-3376-2453; Dickstein, Daniel/0000-0003-1647-5329 FU Intramural NIH HHS NR 45 TC 36 Z9 36 U1 3 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2007 VL 9 IS 8 BP 810 EP 819 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 237YZ UT WOS:000251414300003 PM 18076530 ER PT J AU Aragon-Ching, JB Gillespie, J Price, DK Chuaqui, R Rodriguez-Canales, J Steinberg, SM Dahut, WL Figg, WD AF Aragon-Ching, Jeanny B. Gillespie, John Price, Douglas K. Chuaqui, Rodrigo Rodriguez-Canales, Jaime Steinberg, Seth M. Dahut, William L. Figg, William D. TI Lack of prognostic significance of prostate biopsies in metastatic androgen independent prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate biopsy; metastatic AIPC; radiotherapy; Gleason score; prostate specific antigen ID BEAM RADIATION-THERAPY; PHASE-II TRIAL; RADICAL PROSTATECTOMY; GLEASON SCORE; ADENOCARCINOMA; THALIDOMIDE; CARCINOMA; SURVIVAL; ANTIGEN; UTILITY AB Objective To assess the significance of viable tumour in the prostate of patients with metastatic androgen-independent prostate cancer (AIPC). Patients and methods We evaluated the clinicopathological features, including follow-up, of 40 men with metastatic AIPC who had a transrectal biopsy of the prostate. Results Prostate biopsies (median three cores per biopsy) showed viable tumour in 19 of 40 patients (48%). Of the 18 patients who had received radiotherapy (RT), nine had negative on-study biopsy results. A previous history of RT was not associated with overall survival in patients with biopsy-positive tumours (P = 0.84). Also, there was no statistically significant association between positive or negative biopsy status and overall survival (OS) in these 40 patients (P = 0.39), with a similar median OS of 19.6 months for biopsy-negative and 19.8 months for biopsy-positive patients, respectively. Conclusions Taking prostate biopsies at the time of documented metastatic AIPC yielded tumour in about half the patients. A previous history of RT was not associated with a negative prostate biopsy; the latter appears to have no influence on the prognosis. C1 NCI, Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, CCR, Bethesda, MD 20892 USA. NCI, Pathol Lab, CCR, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, CCR, Bethesda, MD 20892 USA. SAIC Frederick Inc, NCI, Frederick, MD USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, CCR, NIH, 900 Rockville Pikke,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016; OI Rodriguez-Canales, Jaime/0000-0002-0885-2377; Aragon-Ching, Jeanny/0000-0002-6714-141X FU Intramural NIH HHS NR 20 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD DEC PY 2007 VL 100 IS 6 BP 1245 EP 1248 DI 10.1111/j.1464-410X.2007.07173.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 225XX UT WOS:000250552700013 PM 17850370 ER PT J AU Hillmen, P Muus, P Duhrsen, U Risitano, AM Schubert, J Luzzatto, L Schrezenmeier, H Szer, J Brodsky, RA Hill, A Socie, G Bessler, M Rollins, SA Bell, L Rother, RP Young, NS AF Hillmen, Peter Muus, Petra Duhrsen, Ulrich Risitano, Antonio M. Schubert, Jorg Luzzatto, Lucio Schrezenmeier, Hubert Szer, Jeffrey Brodsky, Robert A. Hill, Anita Socie, Gerard Bessler, Monica Rollins, Scott A. Bell, Leonard Rother, Russell P. Young, Neal S. TI Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria SO BLOOD LA English DT Article ID NITRIC-OXIDE; VASCULAR ENDOTHELIUM; NATURAL-HISTORY; THROMBOSIS; PLATELETS; AGGREGATION; MECHANISM; HEMOLYSIS; DISEASE; CELLS AB Hemolysis and hemoglobinemia contribute to serious clinical sequelae in hemolytic disorders. In paroxysmal nocturnal hemoglobinuria (PNH) patients, hemolysis can contribute to thromboembolism (TIE), the most feared complication in PNH, and the leading cause of disease-related deaths. We evaluated whether long-term treatment with the complement inhibitor eculizumab reduces the rate of TIE in patients with PNH. Clinical trial participants included all patients in the 3 eculizumab PNH clinical studies, which recruited patients between 2002 and 2005 (n = 195); patients from these studies continued treatment in the current multinational open-label extension study. Thromboembolism rate with eculizumab treatment was compared with the pretreatment rate in the same patients. The TE event rate with eculizurnab treatment was 1.07 events/100 patient-years compared with 7.37 events/100 patient-years (P <.001) prior to eculizumab treatment (relative reduction, 85%; absolute reduction, 6.3 TE events/100 patient-years). With equalization of the duration of exposure before and during treatment for each patient, TE events were reduced from 39 events before eculizumab to 3 events during eculizumab (P <.001). The TE event rate in antithrombotic-treated patients (n = 103) was reduced from 10.61 to 0.62 events/100 patient-years with eculizurnab treatment (P <.001). These results show that eculizumab treatment reduces the risk of clinical thromboembolism in patients with PNH. This study is registered at http://clinicaltrials.gov C1 Leeds Gen Infirm, Leeds, W Yorkshire, England. Radboud Univ Nijmegen, Ctr Med, Nijmegen, Netherlands. Univ Essen Gesamthsch, Essen, Germany. Univ Naples Federico 2, Naples, Italy. Univ Saarland, Sch Med, Homburg, Germany. Istituto Toscano Tumori, Florence, Italy. Univ Hosp, Inst Transfus Med, Ulm, Germany. Royal Melbourne Hosp, Melbourne, Vic, Australia. Johns Hopkins Sch Med, Baltimore, MD USA. Hop St Louis, Inst Natl Sante Recherche Med, Paris, France. Washington Univ, St Louis, MO USA. Alexion Pharmaceut, Cheshire, CT USA. NHLBI, Bethesda, MD USA. RP Hillmen, P (reprint author), Leeds Gen Infirm, Dept Haematol, Great George St, Leeds LS1 3EX, W Yorkshire, England. EM peter.hillmen@nhs.net RI Muus, P./L-4539-2015; OI Szer, Jeff/0000-0001-6783-2301 NR 35 TC 195 Z9 204 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 DEC 1 PY 2007 VL 110 IS 12 BP 4123 EP 4128 DI 10.1182/blood-2007-06-095646 PG 6 WC Hematology SC Hematology GA 235ZG UT WOS:000251272200047 PM 17702897 ER PT J AU Lupien, SJ Maheu, F Tu, M Fiocco, A Schramek, TE AF Lupien, S. J. Maheu, F. Tu, M. Fiocco, A. Schramek, T. E. TI The effects of stress and stress hormones on human cognition: Implications for the field of brain and cognition SO BRAIN AND COGNITION LA English DT Review DE stress; glucocorticoids; catecholamines; memory; aging; hippocampus ID MEDIAL TEMPORAL-LOBE; PITUITARY-ADRENAL AXIS; LONG-TERM POTENTIATION; GLUCOCORTICOID-INDUCED IMPAIRMENT; DECLARATIVE MEMORY PERFORMANCE; HIPPOCAMPAL VOLUME REDUCTION; RECURRENT MAJOR DEPRESSION; PRIMED BURST POTENTIATION; ADULT HUMAN BRAINS; HEALTHY-YOUNG MEN AB In this review, we report on studies that have assessed the effects of exogenous and endogenous increases in stress hormones on human cognitive performance. We first describe the history of the studies on the effects of using exogenous stress hormones such as glucocorticoids as anti-inflammatory medications on human cognition and mental health. Here, we summarize the cases that led to the diagnosis of glucocorticoid-induced 'steroid psychosis' in human populations and which demonstrated that these stress hormones could thus cross the blood-brain barrier and access the brain where they could influence cognition and mental health. We then summarize studies that assessed the effects of the exogenous administration of glucocorticoids on cognitive performance supported by the hippocampus, the frontal lobes and amygdala. In the second section of the paper, we summarize the effects of the endogenous release of glucocorticoids induced by exposure to a stressful situation on human cognition and we further dissociate the effects of emotion from those of stress on human learning and memory. Finally, in the last section of the paper, we discuss the potential impact that the environmental context to which we expose participants when assessing their memory could have on their reactivity to stress and subsequent cognitive performance. In order to make our point, we discuss the field of memory and aging and we suggest that some of the 'age-related memory impairments' observed in the literature could be partly due to increased stress reactivity in older adults to the environmental context of testing. We also discuss the inverse negative correlations reported between hippocampal volume and memory for young and older adults and suggest that these inverse correlations could be partly due to the effects of contextual stress in young and older adults, as a function of age-related differences in hippocampal volume. (C) 2007 Published by Elsevier Inc. C1 [Lupien, S. J.; Fiocco, A.; Schramek, T. E.] McGill Univ, Douglas Hosp, Res Ctr, Ctr Studies Human Stress, Montreal, PQ, Canada. [Maheu, F.] NIMH, Mood & Anxiety Disorders Program, Emot Dev & Affect Neurosci Branch, Bethesda, MD 20892 USA. [Tu, M.] Univ British Columbia, Ctr Community Child Hlth Res, Vancouver, BC V6H 3V4, Canada. RP Lupien, SJ (reprint author), McGill Univ, Douglas Hosp, Res Ctr, Ctr Studies Human Stress, Montreal, PQ, Canada. EM sonia.lupien@mcgill.ca NR 268 TC 440 Z9 452 U1 16 U2 136 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD DEC PY 2007 VL 65 IS 3 BP 209 EP 237 DI 10.1016/j.bandc.2007.02.007 PG 29 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 246SD UT WOS:000252026400001 PM 17466428 ER PT J AU Lee, KM Choi, JY Lee, JE Noh, DY Ahn, SH Han, W Yoo, KY Hayes, RB Kang, D AF Lee, Kyoung-Mu Choi, Ji-Yeob Lee, Jong Eun Noh, Dong-Young Ahn, Sei-Hyun Han, Wonshik Yoo, Keun-Young Hayes, Richard B. Kang, Daehee TI Genetic polymorphisms of NOS3 are associated with the risk of invasive breast cancer with lymph node involvement SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE NOS3; polymorphism; breast cancer; lymph node involvement; case-control study ID NITRIC-OXIDE SYNTHASE; TUMOR-CELL-MIGRATION; EXPRESSION; GLU298ASP; METASTASIS; CLEAVAGE; ISOFORMS; DISEASE; VARIANT; GROWTH AB Endothelial nitric oxide synthase (NOS3) produces nitric oxide which is a mediator of cytotoxic effects potentially associated with breast cancer. We evaluated the role of genetic polymorphisms of NOS3 in breast cancer etiology, in a case-control study conducted in Korea. We recruited 1,385 eligible patients with histologicaly confirmed incident breast cancer cases and 968 hospital-based controls. Two potentially functional NOS3 polymorphisms in the promoter region (-786T > C) and exon 7 (894G > T, Glu298Asp) were genotyped and individual haplotypes were estimated. Odds ratios (ORs) and 95% confidential intervals (95% CIs) were calculated by unconditional logistic regression, adjusting for age, body mass index, education, family history of breast cancer in first and second degree relatives, age at first full-term pregnancy and parity. There was no overall association between the -786T > C or 894G > T genotype and breast cancer risk. However, the -786C allele was marginally associated with decreased risk for invasive breast cancer with lymph node involvement (OR = 0.76, 95% CI = 0.56-1.04). And, compared to TG-TG carriers, all other haplotype pairs were significantly associated with invasive breast cancer with lymph node involvement (OR = 0.77, 95% CI = 0.59-0.99). Our results suggest that genetic polymorphisms in NOS3 modify individual susceptibility to invasive breast cancer with lymph node involvement in Korean women. C1 Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Prevent Med, Seoul, South Korea. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, Seoul, South Korea. RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Prevent Med, Seoul, South Korea. EM dhkang@snu.ac.kr RI Noh, Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012; Choi, Ji-Yeob/J-2796-2012; Yoo, Keun-Young/J-5548-2012; OI Hayes, Richard/0000-0002-0918-661X NR 31 TC 17 Z9 17 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 IS 3 BP 433 EP 438 DI 10.1007/s10549-007-9506-y PG 6 WC Oncology SC Oncology GA 226HJ UT WOS:000250579800016 PM 17262178 ER PT J AU Brown, LM Chen, BE Pfeiffer, RM Schairer, C Hall, P Storm, H Pukkala, E Langmark, F Kaijser, M Andersson, M Joensuu, H Fossa, SD Travis, LB AF Brown, Linda Morris Chen, Bingshu E. Pfeiffer, Ruth M. Schairer, Catherine Hall, Per Storm, Hans Pukkala, Eero Langmark, Froydis Kaijser, Magnus Andersson, Michael Joensuu, Heikki Fossa, Sophie D. Travis, Lois B. TI Risk of second non-hematological malignancies among 376,825 breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE absolute risks; breast cancer; cohort study; competing risks; risk; survivor; second cancer; second malignancies; treatment ID WOMEN LESS-THAN-35 YEARS; MULTIPLE PRIMARY TUMORS; SOFT-TISSUE SARCOMA; LUNG-CANCER; RADIATION-THERAPY; ESOPHAGEAL CANCER; HODGKINS-DISEASE; CONTRALATERAL BREAST; ENDOMETRIAL CANCER; TAMOXIFEN THERAPY AB Breast cancer survivors are at increased risk of treatment-related second cancers. This study is the first to examine risk 30 or more years after diagnosis and to present absolute risks of second cancer which accounts for competing mortality. We identified 23,158 second non-hematological malignancies excluding breast in a population-based cohort of 376,825 one-year survivors of breast cancer diagnosed from 1943 to 2002 and reported to four Scandinavian cancer registries. We calculated standardized incidence ratios (SIR) and utilized a competing-risk model to calculate absolute risk of developing second cancers. The overall SIR for second cancers was 1.15 (95% confidence interval [CI] = 1.14-1.17). The SIR for potentially radiotherapy-associated cancers 30 or more years after breast cancer diagnosis was 2.19 (95% CI = 1.87-2.55). However, the largest SIRs were observed for women aged < 40 years followed for 1-9 years. At 20 years after breast cancer diagnosis, the absolute risk of developing a second cancer ranged from 0.6 to 10.3%, depending on stage and age; the difference in the absolute risk compared to the background population was greatest for women aged < 40 years with localized disease, 2.3%. At 30 years post breast cancer diagnosis, this difference reached 3.2%. These risks were small compared to the corresponding risk of dying from breast cancer. Although the absolute risks were small, we found persistent risks of second non-hematological malignancies excluding breast 30 or more years after breast cancer diagnosis, particularly for women diagnosed at young ages with localized disease. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Karolinska Inst, Stockholm, Sweden. Danish Canc Soc, Copenhagen, Denmark. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Canc Registry Norway, Oslo, Norway. Univ Helsinki, Cent Hosp, Helsinki, Finland. Univ Oslo, Rikshosp, Radiumhosp Med Ctr, N-0027 Oslo, Norway. RP Brown, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,MSC 7244, Bethesda, MD 20892 USA. EM brownl@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; OI Chen, Bingshu/0000-0001-6139-0696; Storm, Hans/0000-0001-7223-8198; Joensuu, Heikki/0000-0003-0281-2507 FU Intramural NIH HHS NR 74 TC 53 Z9 54 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 IS 3 BP 439 EP 451 DI 10.1007/s10549-007-9509-8 PG 13 WC Oncology SC Oncology GA 226HJ UT WOS:000250579800017 PM 17277968 ER PT J AU Anderson, WF Luo, S Chatterjee, N Rosenberg, PS Goodman, MT Hernandez, BY Reichman, M Dolled-Filhart, MM O'Regan, RM Perou, CM Jatoi, I Cartun, RW Sherman, ME AF Anderson, W. F. Luo, S. Chatterjee, N. Rosenberg, P. S. Goodman, M. T. Hernandez, B. Y. Reichman, M. Dolled-Filhart, M. M. O'Regan, R. M. Perou, C. M. Jatoi, I Cartun, R. W. Sherman, M. E. TI Non-proportional breast cancer mortality patterns according to expression of the HER2 protein, using the residual tissue repository of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Natl Canc Inst, Rockville, MD USA. Univ Hawaii, Honolulu, HI 96822 USA. Hartford Hosp, Hartford, CT 06115 USA. Emory Univ, Atlanta, GA 30322 USA. Univ N Carolina, Chapel Hill, NC USA. HistoRx, New Haven, CT USA. Natl Naval Med Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S58 EP S58 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500160 ER PT J AU Brown, P Arun, B Miller, A Isaacs, C Gutierrez, C Huang, J Mohsin, S Sneige, N Kim, H Sexton, K Weiss, H Hilsenbeck, S Lamph, W Negro-Vilar, A Johnson, K Elledge, R AF Brown, P. Arun, B. Miller, A. Isaacs, C. Gutierrez, C. Huang, J. Mohsin, S. Sneige, N. Kim, H. Sexton, K. Weiss, H. Hilsenbeck, S. Lamph, W. Negro-Vilar, A. Johnson, K. Elledge, R. TI Prevention of breast cancer using rexinoids: results of a phase II biomarker modulation trial using bexarotene in women at high risk of breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 [Brown, P.; Arun, B.; Miller, A.; Isaacs, C.; Gutierrez, C.; Huang, J.; Mohsin, S.; Sneige, N.; Kim, H.; Sexton, K.; Weiss, H.; Hilsenbeck, S.; Lamph, W.; Negro-Vilar, A.; Johnson, K.; Elledge, R.] Baylor Coll Med, Houston, TX 77030 USA. [Brown, P.; Arun, B.; Miller, A.; Isaacs, C.; Gutierrez, C.; Huang, J.; Mohsin, S.; Sneige, N.; Kim, H.; Sexton, K.; Weiss, H.; Hilsenbeck, S.; Lamph, W.; Negro-Vilar, A.; Johnson, K.; Elledge, R.] MD Anderson Canc Ctr, Houston, TX USA. [Brown, P.; Arun, B.; Miller, A.; Isaacs, C.; Gutierrez, C.; Huang, J.; Mohsin, S.; Sneige, N.; Kim, H.; Sexton, K.; Weiss, H.; Hilsenbeck, S.; Lamph, W.; Negro-Vilar, A.; Johnson, K.; Elledge, R.] Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. [Brown, P.; Arun, B.; Miller, A.; Isaacs, C.; Gutierrez, C.; Huang, J.; Mohsin, S.; Sneige, N.; Kim, H.; Sexton, K.; Weiss, H.; Hilsenbeck, S.; Lamph, W.; Negro-Vilar, A.; Johnson, K.; Elledge, R.] Georgetown Univ, Washington, DC USA. [Brown, P.; Arun, B.; Miller, A.; Isaacs, C.; Gutierrez, C.; Huang, J.; Mohsin, S.; Sneige, N.; Kim, H.; Sexton, K.; Weiss, H.; Hilsenbeck, S.; Lamph, W.; Negro-Vilar, A.; Johnson, K.; Elledge, R.] Ligand Pharmaceut, San Diego, CA USA. [Brown, P.; Arun, B.; Miller, A.; Isaacs, C.; Gutierrez, C.; Huang, J.; Mohsin, S.; Sneige, N.; Kim, H.; Sexton, K.; Weiss, H.; Hilsenbeck, S.; Lamph, W.; Negro-Vilar, A.; Johnson, K.; Elledge, R.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S181 EP S182 PG 2 WC Oncology SC Oncology GA 237TE UT WOS:000251398500503 ER PT J AU Fabian, CJ Kimler, BF Mayo, MS Zalles, CH Khan, SA Dooley, WC Krontiras, H Browne, D AF Fabian, C. J. Kimler, B. F. Mayo, M. S. Zalles, C. H. Khan, S. A. Dooley, W. C. Krontiras, H. Browne, D. TI Phase II tissue-based biomarker prevention trial of celecoxib in premenopausal women at high risk for development of breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Yale Univ, New Haven, CT USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Alabama, Birmingham, AL USA. Natl Canc Inst, Bethesda, MD USA. RI Dooley, William/E-7660-2013; Mayo, Matthew/E-3774-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S179 EP S179 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500497 ER PT J AU Geller, BM Ballard-Barbash, R Buisi, DSM Carney, PA Kerlikowske, K Miglioretti, DL Rosenberg, RD Taplin, SH Yankaskas, B Weaver, DL AF Geller, B. M. Ballard-Barbash, R. Buisi, D. S. M. Carney, P. A. Kerlikowske, K. Miglioretti, D. L. Rosenberg, R. D. Taplin, S. H. Yankaskas, B. Weaver, D. L. TI The breast cancer surveillance consortium: a platform for collaborative research stemming from breast cancer risk through survivorship research. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Univ Vermont, Burlington, VT USA. NCI, Bethesda, MD 20892 USA. Grp Hlth Cooperat Ctr Hlth Studies, Seattle, WA USA. Dartmouth Coll, Lebanon, NH 03756 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S265 EP S265 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500744 ER PT J AU Gomez, R Hylton, N Madhavan, S Leung, E Broadwater, G Herman, B Esserman, L AF Gomez, R. Hylton, N. Madhavan, S. Leung, E. Broadwater, G. Herman, B. Esserman, L. CA ISPY Radiol Clin Pathol I TI Preliminary results from I-SPY trial: tumor patterns on pre-treatment MRI predict breast conservation therapy eligibility. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Univ San Francisco, San Francisco, CA 94117 USA. NCI, Bethesda, MD 20892 USA. CALGB, Durham, NC USA. ACRIN, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S92 EP S92 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500251 ER PT J AU Hylton, N Carey, L DeMichele, A Blume, J Broadwater, G Madhavan, S Rosen, M George, S Esserman, L AF Hylton, N. Carey, L. DeMichele, A. Blume, J. Broadwater, G. Madhavan, S. Rosen, M. George, S. Esserman, L. TI Characterizing the biology and response of locally advanced breast cancer in women undergoing neoadjuvant therapy: preliminary results from the I-SPY trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Penn, Philadelphia, PA 19104 USA. ACRIN, Philadelphia, PA USA. CALGB, Philadelphia, PA USA. NCI, SPORE, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S22 EP S22 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500058 ER PT J AU Kerlikowske, K Desai, A Miglioretti, DL Walker, R Ballard-Borbash, RSM AF Kerlikowske, K. Desai, A. Miglioretti, D. L. Walker, R. Ballard-Borbash, R. S. M. TI Women with elevated body mass index at increased risk of breast cancer with a poor prognosis. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Johns Hopkins Univ, Baltimore, MD USA. Grp Hlth, Seattle, WA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S174 EP S175 PG 2 WC Oncology SC Oncology GA 237TE UT WOS:000251398500484 ER PT J AU Korde, L Venzon, D Smith, AW Nehrebecky, M Calhoun, T Sebring, N Drinkard, B Smith, M Prindiville, S Zujewski, J Eng-Wong, J AF Korde, L. Venzon, D. Smith, A. W. Nehrebecky, M. Calhoun, T. Sebring, N. Drinkard, B. Smith, M. Prindiville, S. Zujewski, J. Eng-Wong, J. TI A pilot study to increase physical activity in sedentary women at risk for breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 [Korde, L.; Venzon, D.; Smith, A. W.; Nehrebecky, M.; Calhoun, T.; Sebring, N.; Drinkard, B.; Smith, M.; Prindiville, S.; Zujewski, J.; Eng-Wong, J.] NCI, NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S183 EP S183 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500507 ER PT J AU Levine, PH Ganesan, C Young, HA Portera, C Yang, S Sivoin, SM AF Levine, P. H. Ganesan, C. Young, H. A. Portera, C. Yang, S. Sivoin, S. M. TI E-cadherin levels may predeict outcome in inflammatory breast cancer (IBC) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 George Washington Univ, Med Ctr, Washington, DC 20037 USA. Natl Canc Inst, Bethesda, MD USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S59 EP S59 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500162 ER PT J AU Mayer, EL Hamel, S Savoie, J Parker, LM Lin, NU Anderson, K Heymach, JV Gelman, R Ivy, SP Winer, EP Burstein, HJ AF Mayer, E. L. Hamel, S. Savoie, J. Parker, L. M. Lin, N. U. Anderson, K. Heymach, J., V Gelman, R. Ivy, S. P. Winer, E. P. Burstein, H. J. TI AZD2171 for refractory breast cancer: a phase 2 trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX USA. NCI, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S274 EP S274 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500769 ER PT J AU McCaskill-Stevens, W Procter, M Goodbrand, J Azambuja, E Leyland-Jones, B Ruschoff, J Dowselt, M Wermuth, P Dolci, S Gelber, RD Piccart-Gebhart, M AF McCaskill-Stevens, W. Procter, M. Goodbrand, J. Azambuja, E. Leyland-Jones, B. Ruschoff, J. Dowselt, M. Wermuth, P. Dolci, S. Gelber, R. D. Piccart-Gebhart, M. TI Disease-free survival according to local immunohistochemistry for HER2 and central fluorescence in situ hydridization for patients treated with adjuvant chemotherapy with and without trastuzumab in the HERA (BIG01-01) trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Natl Canc Inst, Bethesda, MD USA. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Inst Jules Bordet, B-1000 Brussels, Belgium. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Emory Univ, Atlanta, GA 30322 USA. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] TARGOS Mol Pathol GmbH, Klinikum Kasseland, Kassel, Germany. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Hoffmann La Roche AG, Basel, Switzerland. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Royal Marsden Hosp Hlth Serv Trust, London, England. [McCaskill-Stevens, W.; Procter, M.; Goodbrand, J.; Azambuja, E.; Leyland-Jones, B.; Ruschoff, J.; Dowselt, M.; Wermuth, P.; Dolci, S.; Gelber, R. D.; Piccart-Gebhart, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S18 EP S18 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500049 ER PT J AU Nieves-Alicea, R Simeone, AM Colburn, NH Tari, AM AF Nieves-Alicea, R. Simeone, A. M. Colburn, N. H. Tari, A. M. TI Programmed cell death 4, a novel inhibitor of breast cancer invasion SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Univ Texas MD Anderson Canc Ctr, Houston, TX USA. Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S28 EP S29 PG 2 WC Oncology SC Oncology GA 237TE UT WOS:000251398500076 ER PT J AU Palmieri, D Gril, BM Herring, J Vega-Valle, E Hua, EK Leiwehr, D Steinberg, SM Gilmer, TM Rubin, SD Steeg, PS AF Palmieri, D. Gril, B. M. Herring, J. Vega-Valle, E. Hua, E. K. Leiwehr, D. Steinberg, S. M. Gilmer, T. M. Rubin, S. D. Steeg, P. S. TI Lapatinib prevents the metastatic colonization of EGFR+ and Her-2+breast cancer cells in the brain SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Natl Canc Inst, Bethesda, MD USA. NCI, SAIC, Frederick, MD USA. GlaxoSmithKline Inc, Collegeville, PA USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S30 EP S30 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500080 ER PT J AU Sparano, JA Coppola, D Kazi, A Merajver, S Vahdat, L Li, T Pellegrino, C Munster, P Hoschander, S Hopkins, U Hershman, D Wright, JJ Kleer, C Sebti, S AF Sparano, J. A. Coppola, D. Kazi, A. Merajver, S. Vahdat, L. Li, T. Pellegrino, C. Munster, P. Hoschander, S. Hopkins, U. Hershman, D. Wright, J. J. Kleer, C. Sebti, S. TI The farnesyl transferase (FT ase) inhibitor (FTI) tipifarnib inhibits FT ase in vivo and enhances the efficacy of neoadjuvant dose-dense doxorubicin-cyclophosphamide (AC) in patients with locally advanced breast cancer (LABC) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Montefiore Einstein Canc Ctr, Bronx, NY USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. Columbia Univ, New York, NY 10027 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S230 EP S230 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500643 ER PT J AU Wayne, SJ Koprowski, C Neuhouser, ML Ulrich, CM Bernstein, L Gilliland, F Wiggins, C Baumgartner, K Baumgartner, R McTiernan, A Ballard-Barbash, R AF Wayne, S. J. Koprowski, C. Neuhouser, M. L. Ulrich, C. M. Bernstein, L. Gilliland, F. Wiggins, C. Baumgartner, K. Baumgartner, R. McTiernan, A. Ballard-Barbash, R. TI Breast cancer survivors who use selected herbal supplements have lower circulating estradiol and free estradiol: the Health, Eating, Activity and Lifestyle study. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 30th Annual San Antonio Breast Cancer Symposium CY DEC 13-16, 2007 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med C1 Univ New Mexico, Albuquerque, NM 87131 USA. Univ So Calif, Los Angeles, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2007 VL 106 SU 1 BP S95 EP S95 PG 1 WC Oncology SC Oncology GA 237TE UT WOS:000251398500258 ER PT J AU Caporaso, N Goldin, L Plass, C Calin, G Marti, G Bauer, S Raveche, E McMaster, ML Ng, D Landgren, O Slager, S AF Caporaso, Neil Goldin, Lynn Plass, Christoph Calin, George Marti, Gerald Bauer, Steven Raveche, Elizabeth McMaster, Mary Lou Ng, David Landgren, Ola Slager, Susan TI Chronic lymphocytic leukaemia genetics overview SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE genetic association; linkage; susceptibility; candidate genes; chronic lymphocytic leukaemia; family studies ID B-CELL LYMPHOCYTOSIS; CLL; PREDISPOSITION; EXPRESSION; REGRESSION; EXPANSION; LYMPHOMA; FAMILIES; SURVIVAL; FEATURES AB Although the familial aspect of chronic lymphocytic leukaemia (CLL) has been appreciated for decades, it is only with the recent confluence of improved molecular and gene technologies and world-wide collaborative networks that accelerated progress has become apparent. In this summary we highlight selected themes in the genetics of CLL emphasizing the opportunities and challenges of this malignancy. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD USA. Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol, Human Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Immunol & Med Genet & Comprehens Canc Ctr, Dept Mol Virol, Columbus, OH 43210 USA. US FDA, Ctr Biol Evaluat & Res, NIH, Div Cell & Gene Therapies,Cellular & Tissue T, Bethesda, MD USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Div Biostat, Rochester, MN USA. RP Caporaso, N (reprint author), Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM caporaso@nih.gov RI Slager, Susan/B-6756-2009; Plass, Christoph/H-7192-2014; OI Bauer, Steven/0000-0003-2831-846X NR 45 TC 20 Z9 21 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 630 EP 634 DI 10.1111/j.1365-2141.2007.06846.x PG 5 WC Hematology SC Hematology GA 231YC UT WOS:000250984100002 PM 18021078 ER PT J AU Shim, YK Silver, SR Caporaso, NE Marti, GE Middleton, DC Linet, MS Vogt, RF AF Shim, Youn K. Silver, Sharon R. Caporaso, Neil E. Marti, Gerald E. Middleton, Dannie C. Linet, Martha S. Vogt, Robert F. CA Int CLL MbL Workshop TI B cells behaving badly SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE chronic lymphocytic leukaemia; monoclonal B-cell; lymphocytosis; aetiology; genetics ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CLL AB The pathogenesis of B-cell lymphoproliferative disorders in general and B-cell chronic lymphocytic leukaemia in particular appears to involve dysfunctional regulation of humoral and cellular immunity with the subsequent development of genetic aberrations in B cells. In theory, either component may arise de novo or may be influenced by environmental exposures including infectious agents, antigens, genotoxic chemicals, or radiation. As an intermediary within the exposure-disease continuum, monoclonal B-cell lymphocytosis may be a helpful biomarker for teasing out these various contributions to risk. This article introduces a series of papers that resulted from an International Workshop held in May 2007 entitled 'Monoclonal B-cell Lymphocytosis and Chronic Lymphocytic Leukemia: Environmental and Genetic Risk Factors'. Research efforts, such as those described in this issue, should lead to improved interventions, more predictive biomarkers, more effective treatments, and a greater appreciation of how the immune system functions over the entire human lifespan. C1 Agcy Toxic Substances & Dis Registry, Div Hlth Studies, Atlanta, GA 30333 USA. NIOSH, Ctr Dis Control & Prevent, Div Surveillance Hazard Evaluat & Field Studi, Cincinnati, OH 45226 USA. Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA. RP Shim, YK (reprint author), Agcy Toxic Substances & Dis Registry, Div Hlth Studies, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM YShim@cdc.gov OI Silver, Sharon/0000-0002-7679-5028 NR 12 TC 1 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 658 EP 662 DI 10.1111/j.1365-2141.2007.06842.x PG 5 WC Hematology SC Hematology GA 231YC UT WOS:000250984100005 PM 18021079 ER PT J AU McMaster, ML Caporaso, N AF McMaster, Mary L. Caporaso, Neil TI Waldenstrom macroglobulinaemia and IgM monoclonal gammopathy of undetermined significance: emerging understanding of a potential precursor condition SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE monoclonal gammopathy of undetermined significance; monoclonal B cell lymphocytosis; Waldenstrom macroglobulinemia; chronic lymphocytic leukaemia; multiple myeloma ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ATOMIC-BOMB SURVIVORS; B-CELL LYMPHOCYTOSIS; NON-HODGKIN-LYMPHOMA; MULTIPLE-MYELOMA; ADULT-POPULATION; UNITED-STATES; LONG-TERM; FAMILIAL AGGREGATION; GENOMIC ABERRATIONS AB Previously thought to be best described as a plasma cell disorder, Waldenstrom macroglobulinaemia (WM) is now understood to be a distinct clinicobiological entity. WM shares B-cell origin and certain other features with both chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). WM and CLL arise from B-cells at discrete stages in their maturation process, and MM arises from B-cells that have fully differentiated into plasma cells. While MM has a well-known precursor condition, monoclonal gammopathy of undetermined significance (MGUS), CLL and WM may also have associated precursor states, monoclonal B-cell lymphocytosis (MBL) and IgM MGUS, respectively. This review explores the features that link or distinguish these haematolymphoid malignancies, with special attention to emerging data regarding IgM MGUS and its unique relationship to WM, and identifies important gaps in our understanding of the putative precursor conditions, MBL and IgM MGUS. C1 Natl Canc Inst, NIH, Bethesda, MD USA. RP McMaster, ML (reprint author), Natl Canc Inst, Genet Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM mcmastem@mail.nih.gov NR 77 TC 14 Z9 14 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 663 EP 671 DI 10.1111/j.1365-2141.2007.06845.x PG 9 WC Hematology SC Hematology GA 231YC UT WOS:000250984100006 PM 18021080 ER PT J AU Linet, MS Schubauer-Berigan, MK Weisenburger, DD Richardson, DB Landgren, O Blair, A Silver, S Field, RW Caldwell, G Hatch, M Dores, GM AF Linet, Martha S. Schubauer-Berigan, Mary K. Weisenburger, Dennis D. Richardson, David B. Landgren, Ola Blair, Aaron Silver, Sharon Field, R. William Caldwell, Glyn Hatch, Maureen Dores, Graca M. TI Chronic lymphocytic leukaemia: an overview of aetiology in light of recent developments in classification and pathogenesis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE chronic lymphocytic leukaemia; aetiology; radiation; chemicals; review ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOCYTOSIS; HAIR DYE USE; ANIMAL BREEDING WORKERS; MAGNETIC-FIELD EXPOSURE; SPONSORED-WORKING-GROUP; POPULATION CASE-CONTROL; FAMILY-CANCER DATABASE; BODY-MASS INDEX; MULTIPLE-MYELOMA AB This overview of the epidemiology of chronic lymphocytic leukaemia (CLL) summarizes the evolution of classification and coding systems and describes the intersection of pathogenesis and aetiology. The role of the putative precursor to CLL, monoclonal B-cell lymphocytosis (MBL), is considered, and ideas for future investigations of the MBL-CLL relationship are outlined. We discuss the epidemiology of CLL, focusing on descriptive patterns and methodological considerations. Postulated risk factors are reviewed including the role of ionizing and non-ionizing radiation, occupational and environmental chemical exposures, medical conditions and treatments, and lifestyle and genetic factors. We conclude by raising key questions that need to be addressed to advance our understanding of CLL aetiology. Recommendations for future epidemiological studies are given, including the standardization of reporting of CLL across cancer registries, the clarification of the natural history of MBL, and the circumvention of the methodological shortcomings of prior epidemiological investigations in relation to radiation, chemical exposures and infectious agents. C1 NCI, DCEG, REB, Bethesda, MD 20892 USA. NIOSH, Div Surveillance Hazard Evaluat & Field Studi, Cincinnati, OH 45226 USA. Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Natl Canc Inst, DCEG, Genet Epidemiol Branch, Bethesda, MD USA. Natl Canc Inst, DCEG, Occupat & Environm Epidemiol Branch, Bethesda, MD USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. Univ Kentucky, Coll Publ Hlth, Lexington, KY USA. RP Linet, MS (reprint author), NCI, DCEG, REB, 6120 Execut Blvd EPS Rm 7048, Bethesda, MD 20892 USA. EM linetm@mail.nih.gov RI Schubauer-Berigan, Mary/B-3149-2009; OI Schubauer-Berigan, Mary/0000-0002-5175-924X; Silver, Sharon/0000-0002-7679-5028 FU Intramural NIH HHS NR 168 TC 43 Z9 47 U1 8 U2 14 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 672 EP 686 DI 10.1111/j.1365-2141.2007.06847.x PG 15 WC Hematology SC Hematology GA 231YC UT WOS:000250984100007 PM 18021081 ER PT J AU Marti, G Abbasi, F Raveche, E Rawstron, AC Ghia, P Aurran, T Caporaso, N Shim, YK Vogt, RF AF Marti, Gerald Abbasi, Fatima Raveche, Elizabeth Rawstron, Andy C. Ghia, Paolo Aurran, Therese Caporaso, Neil Shim, Youn K. Vogt, Robert F. TI Overview of monoclonal B-cell lymphocytosis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; monoclonal B-cell lymphocytosis ID LAMBDA-LIGHT CHAIN; PERIPHERAL-BLOOD; VARIABLE REGION; GENE-MUTATIONS; DELTA SWITCH; LEUKEMIA; CLL; EXPRESSION; DONORS; CLONE AB Monoclonal B-cell lymphocytosis (MBL) has been the subject of more intensive investigation for the last 10 years. The increased presence of MBL in unaffected, first-degree relatives with familial chronic lymphocytic leukaemia (CLL) suggest that it is surrogate marker for early disease. In normal population studies, MBL is found to be increased in ageing subjects. Consensus criteria for the diagnosis of MBL have been proposed. The differential diagnosis has been further clarified and the prevalence of MBL is most prominent in the elderly. The aetiology of MBL is unknown but probably involves immune mechanism of senescence or altered response. Environmental health studies suggest that exposure to certain toxins may lead to MBL but further work is needed. MBL is a precursor to CLL but may also regress, remain stable or progress to clinical CLL. C1 US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD USA. Univ Med & Dent New Jersey, Sch Med, Newark, NJ 07103 USA. Leeds Teaching Hosp NHS Trust, Gen Infirm, Haematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England. Univ Viat Salute San Raffaele, Dept Oncol, Unit Lymphoid Malignancies, Milan, Italy. Inst J Paoli I Calmettes, F-13009 Marseille, France. Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD USA. Agcy Toxic Substance & Dis Registry, Div Hlth Studies, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Marti, G (reprint author), US FDA, NIH, Ctr Biol Evaluat & Res, Div Cell & Gene Therapies Off Cellular, Bdg 29B Rm 2NN08, Bethesda, MD 20892 USA. EM gemarti@helix.nih.gov RI Ghia, Paolo/K-7138-2016; OI Ghia, Paolo/0000-0003-3750-7342; Rawstron, Andy/0000-0003-0798-9790 NR 38 TC 49 Z9 51 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 701 EP 708 DI 10.1111/j.1365-2141.2007.06865.x PG 8 WC Hematology SC Hematology GA 231YC UT WOS:000250984100010 PM 18021084 ER PT J AU Landgren, O Kyle, RA AF Landgren, Ola Kyle, Robert A. TI Multiple myeloma, chronic lymphocytic leukaemia and associated precursor diseases SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE monoclonal gammopathy of undetermined significance; monoclonal B-cell lymphocytosis; multiple myeloma; chronic lymphocytic leukaemia; precursor disease ID B-CELL LYMPHOCYTOSIS; RESPIRATORY-TRACT INFECTIONS; NON-HODGKIN-LYMPHOMA; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; ANTIGENIC-STIMULATION; FAMILIAL AGGREGATION; MEDICAL CONDITIONS; UNITED-STATES; RISK AB Multiple myeloma and chronic lymphocytic leukaemia share common biological and clinical features including the presence of defined precursor conditions (monoclonal gammopathy of undetermined significance and monoclonal B-cell lymphocytosis respectively). Here, we discuss evidence from the literature on the potential aetiological roles for genetic and chronic immune stimulatory factors on the pathway from precursor to malignancy. Also, we speculate on the relationship between precursor and malignancy and talk about future directions and gaps in the literature. C1 Natl Canc Inst, NIH, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. RP Landgren, O (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov NR 64 TC 16 Z9 16 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 717 EP 723 DI 10.1111/j.1365-2141.2007.06866.x PG 7 WC Hematology SC Hematology GA 231YC UT WOS:000250984100012 PM 18021086 ER PT J AU Blair, A Purdue, MP Weisenburger, DD Baris, D AF Blair, Aaron Purdue, Mark P. Weisenburger, Dennis D. Baris, Dalsu TI Chemical exposures and risk of chronic lymphocytic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; lymphoid malignancy; monoclonal B-cell lymphocytosis; occupation; chemicals ID NON-HODGKINS-LYMPHOMA; SYNTHETIC RUBBER INDUSTRY; MULTICENTER CASE-CONTROL; ANIMAL BREEDING WORKERS; POPULATION CASE-CONTROL; MULTIPLE-MYELOMA; CHROMOSOME-ABERRATIONS; OCCUPATIONAL RISK; CANCER-MORTALITY; BENZENE EXPOSURE AB Literature on the role of chemicals in the development of chronic lymphocytic leukaemia (CLL) and monoclonal B-cell lymphocytosis in humans is sparse. This research is complicated by the rarity of these outcomes and the different disease classifications used over time. Several studies have noted excesses of CLL among farmers and a few have pointed to specific chemicals. Reports suggesting elevated CLL rates in the rubber and petroleum industries point to a possible role for solvents and other chemicals. The few studies that focus on specific chemicals suggest that CLL should be more carefully evaluated in relation to possible exposure to chemicals and solvents, particularly for benzene and butadiene. Pooled analyses of CLL studies within consortia offer an opportunity to investigate the possible aetiological role of chemical exposures with improved statistical power. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD USA. Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. RP Blair, A (reprint author), Natl Canc Inst, Occupat & Environm Epidemiol Branch, EPS Rm 8008, Bethesda, MD 20892 USA. EM blaira@mail.nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Intramural NIH HHS NR 80 TC 16 Z9 16 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 753 EP 761 DI 10.1111/j.1365-2141.2007.06874.x PG 9 WC Hematology SC Hematology GA 231YC UT WOS:000250984100016 PM 17961189 ER PT J AU Goldin, LR Caporaso, NE AF Goldin, Lynn R. Caporaso, Neil E. TI Family studies in chronic lymphocytic leukaemia and other lymphoproliferative tumours SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; familial aggregation; susceptibility genes; familial linkage; candidate genes ID NON-HODGKIN-LYMPHOMA; POPULATION-BASED SAMPLES; SUSCEPTIBILITY LOCI; HIGH-RISK; B-CLL; GENES; AGGREGATION; POLYMORPHISMS; ANTICIPATION; ASSOCIATION AB Families with multiple individuals affected with chronic lymphocytic leukaemia (CLL) and other related B-cell tumours have been described in the literature. Familial CLL does not appear to differ from sporadic CLL in terms of prognostic markers and clinical outcome. Large, population-based case-control and cohort studies have also shown significant familial aggregation of CLL and related conditions, including non-Hodgkin and Hodgkin lymphoma. Monoclonal B-cell lymphocytosis also aggregates in CLL families. However, the clinical implication of familial aggregation is minimal given the overall rarity of CLL. Linkage studies have been conducted in high-risk CLL families to screen the whole genome for loci that contribute to susceptibility but no gene mutations have yet been identified by this method. Association studies of candidate genes have implicated immune function and other genes but more studies are needed to verify these findings. The ability to conduct large scale genomic studies will play an important role in detecting susceptibility genes for CLL over the next few years and thereby help to delineate aetiological pathways. C1 Natl Canc Inst, Div Canc Epidemiol, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Goldin, LR (reprint author), Natl Canc Inst, Div Canc Epidemiol, Genet Epidemiol Branch, 6120 Execut BlvdRm 7008, Bethesda, MD 20892 USA. EM goldinl@mail.nih.gov FU Intramural NIH HHS NR 47 TC 17 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 774 EP 779 DI 10.1111/j.1365-2141.2007.06810.x PG 6 WC Hematology SC Hematology GA 231YC UT WOS:000250984100019 PM 18021091 ER PT J AU Landgren, O Gridley, G Check, D Caporaso, NE Brown, LM AF Landgren, Ola Gridley, Gloria Check, David Caporaso, Neil E. Brown, Linda Morris TI Acquired immune-related and inflammatory conditions and subsequent chronic lymphocytic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; infectious disease; susceptibility; aetiology; pathogenesis ID MEDICAL CONDITIONS; RISK; RECEPTORS; PATTERNS; DISEASE; USAGE AB Immune-mediated pathways have been recognized to be of importance in the pathogenesis of chronic lymphocytic leukaemia (CLL). We assessed a broad variety of immune-related and inflammatory conditions and subsequent CLL development among 4 million adult male veterans admitted to VA hospitals. We identified 3,680 CLL cases with up to 27 years of follow-up. Using Poisson regression analyses restricted to immune-related or inflammatory conditions that occurred more than one year before CLL, we estimated relative risk (RR) and 95% confidence intervals for CLL risk. Elevated CLL risk was found among individuals with prior chronic sinusitis (RR = 1.27, 1.01-1.61). Pneumonia had a borderline (RR = 1.13, 1.00-1.27) association with CLL; the risk was further elevated (RR = 1.35, 1.07-1.72) for latency < 5 years. Conversely, chronic non-rheumatic valvular heart disease was associated with 0.76-fold (0.58-0.99) decreased risk. Herpes zoster and simplex were associated with increased (RR = 1.98, 1.40-2.79) and borderline increased (RR = 1.69, 0.96-2.98) CLL risk. There was no general association between autoimmunity and CLL; however, autoimmune haemolytic anaemia was associated with 3.86-fold (1.93-7.74) elevated CLL risk. Individuals with chronic osteoarthritis and prostatitis had 1.14-fold (1.03-1.25) and 1.64-fold (1.14-2.37) elevated CLL risk. These association patterns suggest primary focus on infectious agents rather than autoantigens for future aetiologic CLL studies. C1 Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD USA. Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD USA. RP Landgren, O (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Check, David/J-7184-2015 OI Check, David/0000-0003-3887-0493 FU Intramural NIH HHS NR 26 TC 36 Z9 36 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 791 EP 798 DI 10.1111/j.1365-2141.2007.06859.x PG 8 WC Hematology SC Hematology GA 231YC UT WOS:000250984100021 PM 17941950 ER PT J AU Dores, GAM Anderson, WF Curtis, RE Landgren, O Ostroumova, E Bluhm, EC Rabkin, CS Devesa, SS Linet, MS AF Dores, Graca A. M. Anderson, William F. Curtis, Rochelle E. Landgren, Ola Ostroumova, Evgenia Bluhm, Elizabeth C. Rabkin, Charles S. Devesa, Susan S. Linet, Martha S. TI Chronic lymphocytic leukaemia and small lymphocytic lymphoma: overview of the descriptive epidemiology SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; small lymphocytic lymphoma; epidemiology; cancer incidence; cancer registration ID NON-HODGKINS-LYMPHOMA; SPONSORED-WORKING-GROUP; UNITED-STATES; CANCER REGISTRY; INCIDENCE RATES; SUBTYPES; DIAGNOSIS; RISK; CLASSIFICATIONS; RECOMMENDATIONS AB The 2001 World Health Organization classification scheme considers B-cell chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in an aggregate category (CLL/SLL) because of shared clinicopathological features. We have estimated age-adjusted incidence rates (IRs) of CLL and SLL in the population-based Surveillance, Epidemiology and End Results Program in the United States to analyse patterns of CLL and SLL separately and jointly. Age-standardized to the 2000 US population, overall IRs were 3.83 per 100 000 person-years for CLL (n = 15 676) and 1.31 for SLL (n = 5382) during 1993-2004. Incidence of the combined entity, CLL/SLL, was 90% higher among males compared to females, and the male:female IR ratio was significantly higher for CLL (1.98) than for SLL (1.67). CLL/SLL IRs were 25% and 77% lower among Blacks and Asian/Pacific Islanders, respectively, compared to Whites. A significant reporting delay was evident for CLL but not for SLL, so that CLL/SLL temporal trends must be interpreted cautiously. CLL and SLL IRs increased exponentially with age among all gender/race groups, with CLL IRs increasing more steeply with advancing age than SLL. Avenues of future research include assessment of delayed- and under-reporting to cancer registries and exploration of race, gender, and age effects in epidemiological studies. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. NCI, NIH, Dept Hlth & Human Serv, Biostat Branch, Bethesda, MD USA. NCI, NIH, Dept Hlth & Human Serv, Genet Epidemiol Branch, Bethesda, MD USA. NCI, NIH, Dept Hlth & Human Serv, Viral Epidemiol Branch,Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Dores, GAM (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM doresg@mail.nih.gov FU Intramural NIH HHS NR 44 TC 102 Z9 104 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 809 EP 819 DI 10.1111/j.1365-2141.2007.06856.x PG 11 WC Hematology SC Hematology GA 231YC UT WOS:000250984100023 PM 17941952 ER PT J AU Abbasi, F Longo, NS Lipsky, PE Raveche, E Schleinitz, TA Stetler-Stevenson, M Caporaso, N Marti, G AF Abbasi, Fatima Longo, Nancy S. Lipsky, Peter E. Raveche, Elizabeth Schleinitz, Therese A. Stetler-Stevenson, Maryalice Caporaso, Neil Marti, Gerald TI B-cell repertoire and clonal analysis in unaffected first degree relatives in familial chronic lymphocytic leukaemia kindred SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; monoclonal B-cell lymphocytosis; clonality ID CLL AB Monoclonal B cell lymphocytosis (MBL) was detected in four unaffected first-degree relatives (FDR) in a familial chronic lymphocytic leukaemia (CLL) kindred. The proband remains untreated and two male siblings have died. The four unaffected siblings have been followed for a five-year period. All four FDR developed a kappa(+)CD5(+) MBL detected by flow cytometry. Poymerase chain reaction (PCR) for IGHV rearrangement showed evidence of oligoclonality in three of these individuals. Single cell PCR of flow cytometric sorted kappa(+) cells combined with Ig kappa light chain gene sequencing revealed further evidence of monoclonality in two of these individuals. Three of these individuals all showed evidence of hyper-somatic mutations. The B-cell repertoire in unaffected FDR in familial CLL offers a new area to investigate the interface between the immune system and lymphoid neoplasm. C1 US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD USA. NIAMSD, Autoimmun Branch, Repertoire Anal Grp, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Sch Med, Newark, NJ 07103 USA. Inst J Paoli I Calmettes, F-13009 Marseille, France. NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. NCI, NIH, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Marti, G (reprint author), US FDA, NIH, Div Cell & Gene Therapies Off Cellular, Flow & Image Cytometry Sec Cell & Tissue Therapy, Bdb 29B Rm 2NN08, Bethesda, MD 20892 USA. EM gemarti@helix.nih.gov NR 11 TC 3 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 820 EP 823 DI 10.1111/j.1365-2141.2007.06857.x PG 4 WC Hematology SC Hematology GA 231YC UT WOS:000250984100024 PM 17941936 ER PT J AU Hardy, NM Grady, C Pentz, R Stetler-Stevenson, M Raffeld, M Fontaine, LS Babb, R Bishop, MR Caporaso, N Marti, GE AF Hardy, Nancy M. Grady, Christine Pentz, Rebecca Stetler-Stevenson, Maryalice Raffeld, Mark Fontaine, Laura S. Babb, Rebecca Bishop, Michael R. Caporaso, Neil Marti, Gerald E. TI Bioethical considerations of monoclonal B-cell lymphocytosis: donor transfer after haematopoietic stem cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; ethics; stem cell transplantation; B cells ID LEUKEMIA; CLL; FAMILIES; BLOOD; MALIGNANCIES; POPULATION; CANCER; ADULTS AB Monoclonal B-cell lymphocytosis (MBL) is a recently described laboratory finding in otherwise healthy individuals. In MBL, a light chain-restricted, clonal B-cell population, often with a chronic lymphocytic leukaemia (CLL) phenotype, is identified by flow cytometry. Although the prognostic significance remains unclear, there is an increased incidence in ageing populations and those with a family history of CLL. During the past decade of MBL study, three families have come to our attention in which prospective sibling haematopoietic stem cell donors were found to have an MBL. These families raise complex bioethical issues with regard to disclosure of research data, eligibility for clinical trials and potential donor transfer of MBL. These issues are explored in this report. Identification of MBL among prospective sibling transplant donors will become a common occurrence in transplant practice as transplantation is increasingly offered to older individuals and those with CLL. C1 NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. Canc Res Ctr, NCI, Pathol Lab, Bethesda, MD USA. Westat Corp, Rockville, MD USA. Ctr Clin, NIH, Dept Nursing, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Marti, GE (reprint author), US FDA, Ctr Biol Evaluat & Res, NIH, Div Cell & Gene Therapies,Flow & Image Cytometry, Bethesda, MD 20892 USA. EM gemarti@helix.nih.gov FU Intramural NIH HHS NR 29 TC 26 Z9 27 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 824 EP 831 DI 10.1111/j.1365-2141.2007.06862.x PG 8 WC Hematology SC Hematology GA 231YC UT WOS:000250984100025 PM 18021093 ER PT J AU Clausen, C AF Clausen, Carol TI John Ballard Blake, 1922-2006 - In memoriam SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Biographical-Item C1 [Clausen, Carol] Natl Lib Med, Bethesda, MD 20894 USA. RP Clausen, C (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD WIN PY 2007 VL 81 IS 4 BP 844 EP 846 PG 3 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 241NV UT WOS:000251664000007 ER PT J AU Fee, E Bu, L AF Fee, Elizabeth Bu, Liping TI Models of public health education: choices for the future? SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Editorial Material C1 [Fee, Elizabeth] Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. [Bu, Liping] Alma Coll, Alma, MI USA. RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. EM elizabeth_fee@nlm.nih.go NR 9 TC 3 Z9 3 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD DEC PY 2007 VL 85 IS 12 BP 977 EP 979 DI 10.2471/BLT.07.044883 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244OB UT WOS:000251874100024 PM 18278268 ER PT J AU Emanuel, EJ Grady, C AF Emanuel, Ezekiel J. Grady, Christine TI Four paradigms of clinical research and research oversight SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article ID DEVELOPING-COUNTRIES; PROTECTING COMMUNITIES; ETHICS; TRIALS; TRANSMISSION; THERAPY; BENEFIT; WORLD; DRUGS C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Sect Human Subjects Res, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 46 TC 10 Z9 10 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD WIN PY 2007 VL 16 IS 1 BP 82 EP 96 PG 15 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA 127TL UT WOS:000243609100009 PM 17345970 ER PT J AU Huang, CY Qin, J Zou, F AF Huang, Chiung-Yu Qin, Jing Zou, Fei TI Empirical likelihood-based inference for genetic mixture models SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE empirical likelihood; interval mapping; nonparametric model; normal mixture model; profile likelihood; quantitative trait loci ID QUANTITATIVE TRAIT LOCI; CONFIDENCE-INTERVALS AB The authors show how the genetic effect of a quantitative trait locus can be estimated by a nonparametric empirical likelihood method when the phenotype distributions are completely unspecified. They use an empirical likelihood ratio statistic for testing the genetic effect and obtaining confidence intervals. In addition to studying the asymptotic properties of these procedures, the authors present simulation results and illustrate their approach with a study on breast cancer resistance genes. C1 [Huang, Chiung-Yu; Qin, Jing] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. [Zou, Fei] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. RP Huang, CY (reprint author), NIAID, NIH, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM huangchi@niaid.nih.gov; jingqin@niaid.nih.gov; fzou@bios.unc.edu NR 21 TC 2 Z9 2 U1 1 U2 1 PU CANADIAN JOURNAL STATISTICS PI OTTAWA PA 675 DENBURY AVENUE, OTTAWA, ON K2A 2P2, CANADA SN 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD DEC PY 2007 VL 35 IS 4 BP 563 EP 574 PG 12 WC Statistics & Probability SC Mathematics GA 260QJ UT WOS:000253024800007 ER PT J AU Woodward, RM Brown, ML Stewart, ST Cronin, KA Cutler, DM AF Woodward, Rebecca M. Brown, Martin L. Stewart, Susan T. Cronin, Kathleen A. Cutler, David M. TI The value of medical interventions for lung cancer in the elderly - Results from SEER-CMHSF SO CANCER LA English DT Article; Proceedings Paper CT 5th World Congress of the International-Health-Economics-Association CY JUL 13, 2005 CL Barcelona, SPAIN SP Int Hlth Econ Assoc DE lung cancer; nonsmall cell lung cancer (NSCLC); benefit; cost; value; cost effectiveness; elderly; Continuous Medicare History Sample File (CMHSF); surveillance; Epidemiology and End Results Program (SEER) ID ECONOMIC-ISSUES; CHEMOTHERAPY; COSTS; SURVIVAL; OUTCOMES; CARE; STANDARD; SMOKING; QUALITY; TRENDS AB BACKGROUND. Lung cancer is the leading source of cancer mortality and spending. However, the value of spending on the treatment of lung cancer has not been conclusively demonstrated. The authors evaluated the value of medical care between 1983 and 1997 for nonsmall cell lung cancer in the elderly US population. METHODS. The authors used Surveillance, Epidemiology, and End Results (SEER) data to calculate life expectancy after diagnosis over the period 1983 to 1997. Direct costs for nonsmall cell lung cancer detection and treatment were determined by using Part A and Part B reimbursements from the Continuous Medicare History Sample File (CMHSF) data. The CMHSF and SEER data were linked to calculate lifetime treatment costs over the time period of interest. RESULTS. Life expectancy improved minimally, with an average increase of approximately 0.60 months. Total lifetime lung cancer spending rose by approximately $20,157 per patient in real, ie, adjusted for inflation, 2000 dollars from the early 1980s to the mid-1990s, for a cost-effectiveness ratio of $403,142 per life year (LY). The cost-effectiveness ratio was $143,614 for localized cancer, $145,861 for regional cancer, and $1,190,322 for metastatic cancer. CONCLUSIONS. The cost-effectiveness ratio for nonsmall cell lung cancer was higher than traditional thresholds used to define cost-effective care. The most favorable results were for persons diagnosed with early stage cancer. These results suggested caution when encouraging more intensive care for lung cancer patients without first considering the tradeoffs with the costs of this therapy and its potential effects on mortality and/or quality of life. C1 Natl Bureua Econ Res Inc, Cambridge, MA 02145 USA. Harvard Univ, Harvard Interfac Program Hlth Syst Improv, Cambridge, MA USA. Natl Canc Inst, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD USA. Natl Canc Inst, Div Canc Control & Populat Sci, Stat Res Appl Branch, Bethesda, MD USA. Harvard Univ, Dept Econ, Cambridge, England. RP Woodward, RM (reprint author), Natl Bureua Econ Res Inc, 1050 Massachussets Ave, Cambridge, MA 02145 USA. EM rwoodwar@nber.org NR 39 TC 33 Z9 33 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 DEC 1 PY 2007 VL 110 IS 11 BP 2511 EP 2518 DI 10.1002/cncr.23058 PG 8 WC Oncology SC Oncology GA 235BS UT WOS:000251209100019 PM 17955504 ER PT J AU Fouladi, M Nicholson, HS Zhou, T Laningham, F Helton, KJ Holmes, E Cohen, K Speights, RA Wright, J Pollack, IF AF Fouladi, Maryam Nicholson, H. Stacy Zhou, Tianni Laningham, Fred Helton, Kathleen J. Holmes, Emi Cohen, Kenneth Speights, Rose Anne Wright, John Pollack, Ian F. TI A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma - A children's oncology group study SO CANCER LA English DT Article DE tipifarnib; recurrent central nervous system malignancies; phase II trial; farnesyl transferase inhibitor ID CRANIOSPINAL RADIATION-THERAPY; CELL LUNG-CANCER; FARNESYLTRANSFERASE INHIBITORS; ADJUVANT CHEMOTHERAPY; GROWTH-INHIBITION; MALIGNANT GLIOMA; R115777; TRIAL; RAS; VINCRISTINE AB BACKGROUND. An open-label Phase II study of tipifarnib was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), high-grade glioma (HGG), and diffuse intrinsic brainstem glioma (BSG). METHODS. Between January 2004 and July 2005, patients were enrolled and stratified as follows: Stratum 1, recurrent or refractory MB/PNET; Stratum 2, recurrent or refractory HGG; and Stratum 3, recurrent or refractory BSG. Patients received tipifarnib 200 mg/m(2) per dose twice daily for 21 days repeated every 28 days. Patients who received enzyme-inducing anticonvulsants and other CYP3A4/5 inducers or inhibitors were excluded. The primary objective was to estimate the sustained response rate in all strata. RESULTS. Ninety-seven patients with a median age of 11.2 years (range, 3.2-21.9 years) were enrolled on the study, and 81 patients were evaluable for response. One of 35 patients with BSG and 1 of 31 patients with HGG had a sustained partial response. No responses were observed in 15 patients with MB/PNET. Eight patients (3 HGG, 1 MB, and 4 BSG) remained stable for >= 4 courses (range, 4-25 courses). The median number of courses received was 2 (range, 1-25 courses). The most frequent grade 3 and 4 toxicities included neutropenia (18.7%), thrombocytopenia (14.3%), and leukopenia (14.3%). The 6-month progression-free survival rate (+/- standard deviation) was 14% +/- 6% for HGG, 6% +/- 6% for MB/PNET and 3% +/- 3% for BSG. CONCLUSIONS. Tipifarnib tolerated well but had little activity as a single agent in children with recurrent central nervous system malignancies. C1 St Jude Childrens Res Hosp, Dept Hematol & Oncol, Memphis, TN 38105 USA. Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. Operat Ctr, Childrens Oncol Grp, Arcadia, CA USA. Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA. Natl Canc Inst, Canc Therapy Evaluat program, Bethesda, MD USA. Childrens Hosp Pittsburgh, Brain Tumor Program, Dept Neurol, Pittsburgh, PA 15213 USA. RP Fouladi, M (reprint author), St Jude Childrens Res Hosp, Dept Hematol & Oncol, 332 N Lauderdale, Memphis, TN 38105 USA. EM maryam.fouladi@stjude.org FU NCI NIH HHS [U01 CA97452]; NCRR NIH HHS [M01 RR00188] NR 53 TC 42 Z9 43 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 2007 VL 110 IS 11 BP 2535 EP 2541 DI 10.1002/cncr.23078 PG 7 WC Oncology SC Oncology GA 235BS UT WOS:000251209100022 PM 17932894 ER PT J AU Hosgood, HD Baris, D Zahm, SH Zheng, TZ Cross, AJ AF Hosgood, H. Dean, III Baris, Dalsu Zahm, Shelia Hoar Zheng, Tongzhang Cross, Amanda J. TI Diet and risk of multiple myeloma in Connecticut women SO CANCER CAUSES & CONTROL LA English DT Article DE multiple myeloma; case-control; diet; risk factors ID VITAMIN-D-3 ANALOG EB1089; NON-HODGKINS-LYMPHOMA; CANCER-RISK; RHEUMATOID-ARTHRITIS; ALCOHOL-CONSUMPTION; FISH CONSUMPTION; UNITED-STATES; CELL-GROWTH; OCCUPATION; BLACKS AB Multiple myeloma accounts for an estimated 19,900 incident cancer cases per year in the United States. A population-based case-control study, consisting of 179 incident cases and 691 controls, was conducted to examine the impact of diet on multiple myeloma risk. Diet was assessed using a food frequency questionnaire and odds ratios, 95% confidence intervals, and P-trends were calculated across quartiles of consumption. After controlling for potential confounders, we observed inverse associations for cooked tomatoes (P-trend = 0.002), cruciferous vegetables (P-trend = 0.01), fresh fish (P-trend < 0.001), alcohol (P-trend < 0.001), and vitamin A (P-trend < 0.001) with multiple myeloma risk. In contrast, consumption of cream soups (P-trend = 0.01), jello (P-trend = 0.01), ice cream (P-trend = 0.01), and pudding (P-trend < 0.001) were positively associated with multiple myeloma. Furthermore, there was a suggestion that carbohydrate intake may be positively associated, whereas vitamin D and calcium intake may be inversely associated, with multiple myeloma risk. Despite very limited data on dietary factors in relation to multiple myeloma, the findings from this study concur with previously published studies, suggesting an inverse association for consumption of fish, cruciferous vegetables and green vegetables, and a positive association for some dairy products. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06511 USA. RP Hosgood, HD (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM hosgoodd@mail.nih.gov RI Zahm, Shelia/B-5025-2015 FU NCI NIH HHS [TU2 CA105666] NR 48 TC 23 Z9 23 U1 2 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2007 VL 18 IS 10 BP 1065 EP 1076 DI 10.1007/s10552-007-9047-z PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 215MS UT WOS:000249813500003 PM 17694422 ER PT J AU Ward, MH Rusiecki, JA Lynch, CF Cantor, KP AF Ward, Mary H. Rusiecki, Jennifer A. Lynch, Charles F. Cantor, Kenneth P. TI Nitrate in public water supplies and the risk of renal cell carcinoma SO CANCER CAUSES & CONTROL LA English DT Article DE renal cell carcinoma; drinking water; nitrate; nitrite; N-nitroso compounds; diet ID MUNICIPAL DRINKING-WATER; CURED MEAT-PRODUCTS; N-NITROSO COMPOUNDS; ENDOGENOUS NITROSATION; BLADDER-CANCER; UNITED-STATES; WELL-WATER; DIET; POPULATION; NITRITE AB Drinking water and dietary sources of nitrate and nitrite can react in vivo with amines and amides to form N-nitroso compounds (NOC), potent animal carcinogens. Nitrate is a widespread contaminant of drinking water supplies especially in agricultural areas. We conducted a population-based case-control study of renal cell carcinoma in 1986-1989 in Iowa, a state with elevated levels in many public water supplies. We collected a lifetime water source history, but due to limited monitoring data, most analyses focused on the subpopulation, who used Iowa public supplies with nitrate measurements (actual or imputed data) for >= 70% of their person-years since 1960 (201 cases, 1,244 controls). We computed the average nitrate level and years using a public supply with nitrate levels > 5 and > 10 mg/l. Dietary nitrate and nitrite were estimated from a 55-item food frequency questionnaire. There was no association of renal cell carcinoma with the average nitrate level and years using public supplies > 5 and > 10 mg/l nitrate-nitrogen (10+ years > 5 mg/l odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.66, 1.60). However, higher nitrate exposure was associated with an increased risk among subgroups with above the median red meat intake (10+ years > 5 mg/l OR = 1.91, 95% CI 1.04-3.51) or below the median vitamin C intake (10+ years > 5 mg/l OR = 1.90, 95% CI 1.01, 3.56), dietary factors that increase the endogenous formation of NOC. Exclusion of long-term Des Moines residents, a large proportion of the high exposure categories, attenuated the association. These findings deserve additional study in populations with high water nitrate intake and information on dietary intakes. C1 NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,DHHS, Bethesda, MD 20892 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Ward, MH (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,DHHS, 6120 Execut Blvd,EPS 8006, Bethesda, MD 20892 USA. EM wardm@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CP-51026, N01-CP-85614] NR 46 TC 16 Z9 19 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2007 VL 18 IS 10 BP 1141 EP 1151 DI 10.1007/s10552-007-9053-1 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 215MS UT WOS:000249813500009 PM 17717631 ER PT J AU Anderson, WF Chen, BE Brinton, LA Devesa, SS AF Anderson, William F. Chen, Bingshu E. Brinton, Louise A. Devesa, Susan S. TI Qualitative age interactions (or effect modification) suggest different cancer pathways for early-onset and late-onset breast cancers SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer incidence; risk factors; breast cancer etiology; SEER; age-at-diagnosis; temporal trends ID UNITED-STATES; RISK-FACTORS; SCREENING MAMMOGRAPHY; MORTALITY-RATES; RECENT TRENDS; PREMENOPAUSAL; DIAGNOSIS; PATTERNS; ETIOLOGY; HEALTH AB Prior to 1999-2000, breast cancer incidence rates had risen for decades, though more among older than younger women. To further explore the impact of advancing age-at-diagnosis upon breast cancer incidence, we used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (1974-2003). Over time, we observed age interactions by tumor grade, stage, and race. For example, among women ages < 40 years, high-grade lesions were more common than low-grade tumors for all time periods. Among women ages 40+ years, high-grade lesions were more common during early time periods then trend lines crossed, after which low-grade tumors were more common than high-grade lesions. Notably, the transition (crossover point) occurred earlier with advancing age-at-diagnosis. The reversal (crossing) of incidence rates from high to low-grade tumors among women 40+ years is a qualitative age interaction, probably due to changing age-related risk factor and/or screening patterns, where mammography preferentially detected tumors of low malignant potential among older women. Though once thought to be rare or artifactual, qualitative age interactions suggest breast cancer heterogeneity. Indeed, if real, qualitative age interactions (effect modifications) imply different etiologic pathways for early-onset and late-onset types of breast cancer. C1 NCI, Biostat Branch, DHHS, NIH,DCEG,EPS, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, DHHS, NIH,DCEG, Bethesda, MD 20892 USA. RP Anderson, WF (reprint author), NCI, Biostat Branch, DHHS, NIH,DCEG,EPS, Room 8036,6120 Execut Blvd, Bethesda, MD 20892 USA. EM wanderso@mail.nih.gov RI Brinton, Louise/G-7486-2015; OI Brinton, Louise/0000-0003-3853-8562; Chen, Bingshu/0000-0001-6139-0696 FU Intramural NIH HHS NR 48 TC 30 Z9 30 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2007 VL 18 IS 10 BP 1187 EP 1198 DI 10.1007/s10552-007-9057-x PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 215MS UT WOS:000249813500013 PM 17823850 ER PT J AU Li, Z Tognon, CE Godinho, FJ Yasaitis, L Hock, H Herschkowitz, JI Lannon, CL Cho, E Kim, SJ Bronson, RT Perou, CM Sorensen, PH Orkin, SH AF Li, Zhe Tognon, Cristina E. Godinho, Frank J. Yasaitis, Laura Hock, Hanno Herschkowitz, Jason I. Lannon, Chris L. Cho, Eunah Kim, Seong-Jin Bronson, Roderick T. Perou, Charles M. Sorensen, Poul H. Orkin, Stuart H. TI ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex SO CANCER CELL LA English DT Article ID PROTEIN-TYROSINE KINASE; GENE FUSION; STEM-CELLS; GLAND DEVELOPMENT; EPITHELIAL-CELLS; PROSTATE-CANCER; CONGENITAL FIBROSARCOMA; TGF-BETA-1 EXPRESSION; MESOBLASTIC NEPHROMA; TRANSGENIC MICE AB To better understand the cellular origin of breast cancer, we developed a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;1 5)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Wap-Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that, in nulliparous Wap-Cre;EN females, committed alveolar bipotent or CD61* luminal progenitors are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given the increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of preclinical models. C1 [Li, Zhe; Godinho, Frank J.; Yasaitis, Laura; Hock, Hanno; Orkin, Stuart H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Godinho, Frank J.; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Li, Zhe; Hock, Hanno; Bronson, Roderick T.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Li, Zhe; Hock, Hanno; Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Tognon, Cristina E.; Lannon, Chris L.; Sorensen, Poul H.] British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada. [Herschkowitz, Jason I.; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. [Herschkowitz, Jason I.; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol, Chapel Hill, NC 27599 USA. [Cho, Eunah; Kim, Seong-Jin] NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Perou, Charles/0000-0001-9827-2247 FU NCI NIH HHS [N01-CN43308, N01CN43308, R01 CA101227, R01-CA-101227, U01 CA105423, U01 CA105423-03, U01 CA105423-04] NR 56 TC 66 Z9 67 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2007 VL 12 IS 6 BP 542 EP 558 DI 10.1016/j.ccr.2007.11.012 PG 17 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 242VG UT WOS:000251753700007 PM 18068631 ER PT J AU Vaught, JB Lockhart, N Thiel, KS Schneider, JA AF Vaught, Jimmie B. Lockhart, Nicole Thiel, Karen S. Schneider, Julie A. TI Ethical, legal, and policy issues: Dominating the biospecimen discussion SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 [Vaught, Jimmie B.; Lockhart, Nicole; Schneider, Julie A.] NIH, Off Biorepositor & Biospecimen Res, Dept Hlth & Human Serv, Bethesda, MD 25802 USA. [Thiel, Karen S.] Paton Boggs LLP, Washington, DC USA. RP Vaught, JB (reprint author), NIH, Off Biorepositor & Biospecimen Res, Bldg 31, Beckley, WV USA. EM vaughtj@mail.nih.gov NR 19 TC 13 Z9 14 U1 2 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 DEC PY 2007 VL 16 IS 12 BP 2521 EP 2523 DI 10.1158/1055-9965.EPI-07-2758 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 244HD UT WOS:000251856100001 PM 18086753 ER PT J AU Lacey, JV AF Lacey, James V., Jr. TI Ovarian cancer and menopausal hormone therapy: More data and new questions SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID ESTROGEN PLUS PROGESTIN; REPLACEMENT THERAPY; ENDOMETRIAL CANCER; RISK; HEALTH; TRIAL; WOMEN C1 [Lacey, James V., Jr.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Lacey, JV (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, MSC 7234,6120 Executive Blvd, Rockville, MD 20852 USA. EM jimlacey@nih.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2007 VL 16 IS 12 BP 2524 EP 2525 DI 10.1158/1055-9965.EPI-07-2757 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 244HD UT WOS:000251856100002 PM 18086754 ER PT J AU Lampe, JW Nishino, Y Ray, RM Wu, C Li, W Lin, MG Gao, DL Hu, Y Shannon, J Stalsberg, H Porter, PL Frankenfeld, CL Wahala, K Thomas, DB AF Lampe, Johanna W. Nishino, Yoshikazu Ray, Roberta M. Wu, Chunyuan Li, Wenjin Lin, Ming-Gang Gao, Dao Li Hu, Yongwei Shannon, Jackilen Stalsberg, Helge Porter, Peggy L. Frankenfeld, Cara L. Waehaelae, Kristiina Thomas, David B. TI Plasma isoflavones and fibrocystic breast conditions and breast cancer among women in Shanghai, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DIETARY PHYTOESTROGEN INTAKE; RISK-FACTORS; SOY INTAKE; PHYTO-ESTROGENS; DISEASE; CONSUMPTION; ADOLESCENT; NUTRITION; GENISTEIN; TISSUE AB Background: Proliferative benign breast conditions are associated with elevated risk of breast cancer, whereas nonproliferative conditions are not strongly associated with risk. Factors acting before onset of hyperplasia might be associated with both benign conditions and breast cancer, whereas those on the proliferative disease-to-cancer pathway would be associated only with cancer. Soy isoflavone exposure may influence breast cancer risk, but little is known of its association with benign conditions. Materials and Methods: We examined possible relationships between plasma genistein and daidzein concentrations and risk of breast disease in women, in a breast self-examination trial in Shanghai, China, diagnosed with breast cancer (n = 196) or a benign breast condition (n = 304), and 1,002 age-matched controls with no known breast disease. Benign conditions were classified as nonproliferative (n = 131) or proliferative with or without atypia (n = 173). Results: lsoflavone concentrations were inversely associated with risk of nonproliferative and proliferative benign fibrocystic conditions, as well as with breast cancer, both with and without concomitant proliferative changes in ipsilateral noncancerous mammary epithelium (P-trend < 0.01 for all comparisons with controls). Women in the highest quartile of plasma genistein (>76.95 ng/mL) were less likely to have breast cancer (odds ratio, 0.26; 95% confidence interval, 0.13-0.50) or benign conditions (odds ratio, 0.40; 95% confidence interval, 0.23-0.70) compared with women in the lowest quartile (<9.42 ng/mL). Observed risks for breast cancer with and without surrounding proliferative changes were not different, respectively, from observed risks for benign proliferative and nonproliferative conditions alone. Conclusion: lsoflavone exposure was inversely associated with fibrocystic breast conditions and breast cancer, and the results suggest that effects on cancer risk occur early in carcinogenesis. C1 [Lampe, Johanna W.; Ray, Roberta M.; Wu, Chunyuan; Li, Wenjin; Lin, Ming-Gang; Porter, Peggy L.; Thomas, David B.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA. [Nishino, Yoshikazu] Miyagi Canc Ctr Res Inst, Div Epidemiol, Miyagi, Japan. [Gao, Dao Li] Zhong Shan Hosp Canc Ctr, Shanghai, Peoples R China. [Hu, Yongwei] Shi Dong Hosp, Shanghai, Peoples R China. [Shannon, Jackilen] Oregon Hlth & Sci Univ, Portland, OR USA. [Stalsberg, Helge] Univ Tromso, N-9001 Tromso, Norway. [Frankenfeld, Cara L.] NCI, Bethesda, MD USA. [Waehaelae, Kristiina] Univ Helsinki, FIN-00014 Helsinki, Finland. RP Lampe, JW (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N, M4-B402,PO Box 19024, Seattle, WA 98109 USA. EM jlampe@fhcrc.org OI Frankenfeld, Cara/0000-0002-2318-0791 FU NCI NIH HHS [R01 CA75332] NR 35 TC 38 Z9 42 U1 0 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 DEC PY 2007 VL 16 IS 12 BP 2579 EP 2586 DI 10.1158/1055-9965.EPI-07-0368 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 244HD UT WOS:000251856100009 PM 18086761 ER PT J AU Hwang, ES Miglioretti, DL Ballard-Barbash, R Weaver, DL Kerlikowske, K AF Hwang, E. Shelley Miglioretti, Diana L. Ballard-Barbash, Rachel Weaver, Donald L. Kerlikowske, Karla CA Natl Canc Inst Breast Canc Surve TI Association between breast density and subsequent breast cancer following treatment for ductal carcinoma In situ SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SURGICAL ADJUVANT BREAST; MAMMOGRAPHIC DENSITY; RADIATION-THERAPY; REPLACEMENT THERAPY; LOCAL RECURRENCE; WEIGHT CHANGE; ALLELIC LOSS; RISK; TAMOXIFEN; LUMPECTOMY AB Background: Risk of invasive cancer following treatment for ductal carcinoma in situ (DCIS) is associated with both treatment- and tumor-related factors. However, it is unknown whether stromal factors such as breast density may also influence subsequent invasive breast events. We investigated whether breast density is an independent predictor of subsequent breast events among women treated for DClS. Population: A prospective cohort study of 3,274 women ages 3 0 to 93 in the Breast Cancer Surveillance Consortium treated with lumpectomy for DClS between 1993 and 2005. All subjects had an American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density measure recorded prior to diagnosis. Methods: Ipsilateral and contralateral breast cancer following lumpectomy for DCIS were ascertained through state tumor registries, regional Surveillance Epidemiology and End Results program or pathology databases. A Cox proportional hazard model was used to compare adjusted risk of breast cancer among women with high (BI-RADS 3 or 4) versus low (BI-RADS 1 or 2) breast density. Results: During a median follow-up period of 39 months (0-132 months), 133 women developed invasive breast cancer. After adjusting for age and radiation treatment, high breast density was associated with increased hazard for contralateral (hazard ratio, 3.1; 95% confidence interval, 1.6-6.1) but not ipsilateral (hazard ratio, 1.0; 95% confidence interval, 0.6-1.6) invasive breast events. Conclusion: High breast density is associated with contralateral, but not ipsilateral, invasive breast cancer following lumpectomy for DClS. Thus, women with DCIS and high breast density may especially benefit from antiestrogenic therapy to reduce the risk of contralateral invasive disease. C1 [Hwang, E. Shelley] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94115 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94115 USA. [Miglioretti, Diana L.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Ballard-Barbash, Rachel] NCI, DCCPS, Appl Res Program, Bethesda, MD USA. [Weaver, Donald L.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. RP Hwang, ES (reprint author), Univ Calif San Francisco, San Francisco Canc Ctr, 1600 Divisadero Ave,B606 San Francisco, San Francisco, CA 94115 USA. EM shelley.hwang@ucsfmedctr.org FU NCI NIH HHS [U01CA63736, K23 CA0977181-01A10, P01 CA107584, P01 CA58207, U01 CA086076, U01 CA086076-06, U01CA63731, U01CA63740, U01CA69976, U01CA70013, U01CA70040, U01CA86076, U01CA86082] NR 45 TC 9 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2007 VL 16 IS 12 BP 2587 EP 2593 DI 10.1158/1055-9965.EPI-07-0458 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 244HD UT WOS:000251856100010 PM 18086762 ER PT J AU Ahn, JY Albanes, D Peters, U Schatzkin, A Lim, U Freedman, M Chatterjee, N Andriole, GL Leitzmann, MF Hayes, RB AF Ahn, Jiyoung Albanes, Demetrius Peters, Ulrike Schatzkin, Arthur Lim, Unhee Freedman, Michal Chatterjee, Nilanjan Andriole, Gerald L. Leitzmann, Michael F. Hayes, Richard B. CA PLCOTPT TI Dairy products, calcium intake, and risk of prostate cancer in the prostate, lung, colorectal, and ovarian cancer screening trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VITAMIN-D; UNITED-STATES; COHORT; DIET; MEN; ASSOCIATIONS; METAANALYSIS; SUPPLEMENTATION; CONSUMPTION; MORTALITY AB Higher intakes of calcium and dairy products, a major source of dietary calcium, are reported to increase the risk of prostate cancer, potentially due to reductions in circulating vitamin D with increasing calcium intake. We prospectively examined the association of dairy product and calcium intake with prostate cancer risk in 29,509 men, including 1,910 cases, in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We also evaluated the relation of calcium intake with serum 25-hydroxy-vitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D], in a Prostate, Lung, Colorectal, and Ovarian Trial substudy (n = 275). Dietary intake was assessed using a food frequency questionnaire. Baseline serum 1,25(OH)2D was determined by RIA. Greater intake of dairy products, particularly low-fat dairy products, was weakly associated with increased risk of prostate cancer [relative risk (RR), 1.12; 95% confidence intervals (CI), 0.97-1.30; P trend = 0.06 for >2.75 versus <= 0.98 servings of total dairy/day; 1.23 (1.07-1.41) for low-fat dairy]. Greater dietary calcium intake was associated with increased risk of prostate cancer (RR, 1.34; 95% CI, 0.93-1.94; P trend = 0.02 for >2,000 versus <1,000 mg/day), but greater supplementary calcium intake was not associated with the risk. Associations of dairy product and dietary calcium intake were evident for nonaggressive disease (RR, 1.20; 95% CI, 0.99-1.46; P trend = 0.01 for dairy products; 1.64, 1.04-2.57; P trend = 0.002 for dietary calcium), but not aggressive disease (RR, 1.02; 95% CI, 0.81-1.28 for dairy products; 0.94, 0.49-1.80 for dietary calcium). Calcium intake was not associated with serum 25-hydroxyvitamin D and 1,25(OH)(2)D concentration. In this large prospective study in a prostate cancer screening trial, greater dietary intake of calcium and dairy products, particularly low-fat types, may be modestly associated with increased risks for nonaggressive prostate cancer, but was unrelated to aggressive disease. Furthermore, we found no relationship between calcium intake and circulating vitamin D. C1 [Ahn, Jiyoung; Albanes, Demetrius; Schatzkin, Arthur; Lim, Unhee; Freedman, Michal; Chatterjee, Nilanjan; Leitzmann, Michael F.; Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Peters, Ulrike] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Fred Hutchinson Canc Res Ctr,Canc Prevent Program, Seattle, WA 98195 USA. [Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. RP Ahn, JY (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM Ahnj@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; OI Hayes, Richard/0000-0002-0918-661X NR 42 TC 69 Z9 69 U1 6 U2 22 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 DEC PY 2007 VL 16 IS 12 BP 2623 EP 2630 DI 10.1158/1055-9965.EPI-07-0601 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 244HD UT WOS:000251856100014 PM 18086766 ER PT J AU Stolzenberg-Solomon, RZ Cross, AJ Silverman, DT Schairer, C Thompson, FE Kipnis, V Subar, AF Hollenbeck, A Schatzkin, A Sinha, R AF Stolzenberg-Solomon, Rachael Z. Cross, Amanda J. Silverman, Debra T. Schairer, Catherine Thompson, Frances E. Kipnis, Victor Subar, Amy F. Hollenbeck, Albert Schatzkin, Arthur Sinha, Rashmi TI Meat and meat-mutagen intake and pancreatic cancer risk in the NIH-AARP cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; HETEROCYCLIC AMINE CONTENT; PAST MEDICAL HISTORY; DIETARY-INTAKE; VARYING DEGREES; DNA-ADDUCTS; RED MEAT; PHIP; CARCINOGEN; COOKING AB Meat intake, particularly red meat, has been positively associated with pancreatic cancer in some epidemiologic studies. Detailed meat-cooking methods and related mutagens formed in meat cooked at high temperatures have not been evaluated prospectively as risk factors for this malignancy. We investigated the association between meat, meat-cooking methods, meat-mutagen intake, and exocrine pancreatic cancer in the NIH-American Association of Retired Persons (NIH-AARP) Diet and Health Study cohort of 537,302 individuals, aged 50 to 71 years, with complete baseline dietary data (1995-1996) ascertained from a food frequency questionnaire. A meat-cooking module was completed by 332,913 individuals 6 months after baseline. During 5 years of follow-up, 836 incident pancreatic cancer cases (555 men, 281 women) were identified. Four hundred and fifty-nine cases had complete meat module data. We used Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (0). Total, red, and high-temperature cooked meat intake was positively associated with pancreatic cancer among men (fifth versus first quintile: HR, 1.41, 95% CI, 1.08-1.83, P trend = 0.001; HR, 1.42,95% Cl, 1.05-1.91, P trend = 0.01; and HR, 1.52, 95% CI, 1.12-2.06, P trend = 0.005, respectively), but not women. Men showed significant 50% increased risks for the highest tertile of grilled/barbecued and broiled meat and significant doubling of risk for the highest quintile of overall meat-mutagenic activity (P trends < 0.01). The fifth quintile of the heterocyclic amine, 2amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline intake showed a significant 29% (P trend = 0.006) increased risk in men and women combined. These findings support the hypothesis that meat intake, particularly meat cooked at high temperatures and associated mutagens, may play a role in pancreatic cancer development. C1 [Stolzenberg-Solomon, Rachael Z.; Cross, Amanda J.; Schatzkin, Arthur; Sinha, Rashmi] Nutr Epidemiol Branch, Rockville, MD USA. [Silverman, Debra T.] Occupat Epidemiol Branch, Rockville, MD USA. [Schairer, Catherine] Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD USA. [Thompson, Frances E.; Subar, Amy F.] Div Canc Control & Populat Sci, Appl Res Program, Rockville, MD USA. [Kipnis, Victor] NIH, Dept Hlth Human Serv, NCI, Div Canc Prevent,Biometr Res Grp, Rockville, MD USA. [Hollenbeck, Albert] Amer Associat Retired Persons, Environm Anal Dept, Washington, DC USA. RP Sinha, R (reprint author), 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA. EM rs221z@nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU Intramural NIH HHS NR 60 TC 58 Z9 60 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 DEC PY 2007 VL 16 IS 12 BP 2664 EP 2675 DI 10.1158/1055-9965.EPI-07-0378 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 244HD UT WOS:000251856100020 PM 18086772 ER PT J AU Faupel-Badger, JM Diaw, L Albanes, D Virtamo, J Woodson, K Tangrea, JA AF Faupel-Badger, Jessica M. Diaw, Lena Albanes, Demetrius Virtamo, Jarmo Woodson, Karen Tangrea, Joseph A. TI Lack of association between serum levels of 25-hydroxyvitamin D and the subsequent risk of prostate cancer in finnish men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID VITAMIN-D METABOLITES; UNITED-STATES; BETA-CAROTENE; MORTALITY; EPIDEMIOLOGY; TRENDS; CELLS C1 [Faupel-Badger, Jessica M.] NCI, NIH, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. [Faupel-Badger, Jessica M.] NCI, NIH, Div Canc Prevent, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Diaw, Lena; Woodson, Karen] NCI, NIH, Ctr Canc Res, Canc Genet Branch, Bethesda, MD 20892 USA. [Albanes, Demetrius] NCI, NIH, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. [Tangrea, Joseph A.] NCI, NIH, Prostrate & Urol Canc Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Faupel-Badger, JM (reprint author), NCI, NIH, Mammary Biol & Tumorigenesis Lab, 37 Convent Dr,Bldg 37,Room 1106, Bethesda, MD 20892 USA. EM badgerje@mail.ruh.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-45035, N01-RC-37004]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 17 TC 43 Z9 43 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 DEC PY 2007 VL 16 IS 12 BP 2784 EP 2786 DI 10.1158/1055-9965.EPI-07-0672 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 244HD UT WOS:000251856100037 PM 18086789 ER PT J AU Mueller, CM Korde, L Katki, HA Rosenberg, PS Peters, JA Greene, MH AF Mueller, Christine M. Korde, Larissa Katki, Hormuzd A. Rosenberg, Philip S. Peters, June A. Greene, Mark H. TI Constitutional cytogenetic analysis in men with hereditary testicular germ cell tumor: No evidence of disease-related abnormalities SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID CANCER-PATIENTS; RISK; DELETION; FAMILY; LOCALIZATION; POPULATION; BROTHERS; SEARCH C1 [Mueller, Christine M.; Korde, Larissa; Peters, June A.; Greene, Mark H.] Natl Canc Inst, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,Clin Genet Branch, Rockville, MD 20852 USA. [Katki, Hormuzd A.; Rosenberg, Philip S.] Natl Canc Inst, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,Biostat Branch, Rockville, MD 20852 USA. RP Mueller, CM (reprint author), Natl Canc Inst, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet,Clin Genet Branch, 6120 Execut Blvd,EPS 7101, Rockville, MD 20852 USA. EM muellerc@mail.nih.gov RI Katki, Hormuzd/B-4003-2015 FU Intramural NIH HHS [ZIA CP010144-12] NR 24 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2007 VL 16 IS 12 BP 2791 EP 2794 DI 10.1158/1055-9965.EPI-07-0521 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 244HD UT WOS:000251856100039 PM 18086791 ER PT J AU Kudo-Saito, C Garnett, CT Wansley, EK Schlom, J Hodge, JW AF Kudo-Saito, Chie Garnett, Charlie T. Wansley, Elizabeth K. Schlom, JeVrey Hodge, James W. TI Intratumoral delivery of vector mediated IL-2 in combination with vaccine results in enhanced T cell avidity and anti-tumor activity SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE TRICOM; costimulation; vaccination; intratumoral; IL-2; cancer immunotherapy; TCR avidity ID COLONY-STIMULATING FACTOR; DIVERSIFIED SUBCUTANEOUS/INTRATUMORAL VACCINATION; CARCINOEMBRYONIC ANTIGEN GENE; REGIONAL LYMPH-NODES; COSTIMULATORY MOLECULES; METASTATIC MELANOMA; ESTABLISHED TUMORS; IMMUNE-RESPONSES; PRESENTING CELLS; SELF-ANTIGEN AB Systemic IL-2 is currently employed in the therapy of several tumor types, but at the price of often severe toxicities. Local vector mediated delivery of IL-2 at the tumor site may enhance local effector cell activity while reducing toxicity. To examine this, a model using CEA-transgenic mice bearing established CEA expressing tumors was employed. The vaccine regimen was a s.c. prime vaccination with recombinant vaccinia (rV) expressing transgenes for CEA and a triad of costimulatory molecules (TRICOM) followed by i.t. boosting with rF-CEA/TRICOM. The addition of intratumoral (i.t.) delivery of IL-2 via a recombinant fowlpox (rF) IL-2 vector greatly enhanced anti-tumor activity of a recombinant vaccine, resulting in complete tumor regression in 70-80% of mice. The anti-tumor activity was shown to be dependent on CD8(+) cells and NK1.1(+). Cellular immune assays revealed that the addition of rF-IL-2 to the vaccination therapy enhanced CEA-specific tetramer(+) cell numbers, cytokine release and CTL lysis of CEA(+) targets. Moreover, tumor-bearing mice vaccinated with the CEA/TRICOM displayed an antigen cascade, i.e., CD8(+) T cell responses to two other antigens expressed on the tumor and not the vaccine: wildtype p53 and endogenous retroviral antigen gp70. Mice receiving rF-IL-2 during vaccination demonstrated higher avidity CEA-speciWc, as well as higher avidity gp70-specific, CD8(+) T cells when compared with mice vaccinated without rF-IL-2. These studies demonstrate for the first time that the level and avidity of antigen specific CTL, as well as the therapeutic outcome can be improved with the use of i.t. rF-IL-2 with vaccine regimens. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015; OI Hodge, James/0000-0001-5282-3154; Garnett-Benson, Charlie/0000-0002-0238-3303; Wansley, Elizabeth/0000-0002-0110-7550 FU Intramural NIH HHS NR 51 TC 13 Z9 14 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD DEC PY 2007 VL 56 IS 12 BP 1897 EP 1910 DI 10.1007/s00262-007-0332-1 PG 14 WC Oncology; Immunology SC Oncology; Immunology GA 216ZF UT WOS:000249916900004 PM 17503041 ER PT J AU Kang, JS Wanibuchi, H Morimura, K Gonzalez, FJ Fukushima, S AF Kang, Jin Seok Wanibuchi, Hideki Morimura, Keiichirou Gonzalez, Frank J. Fukushima, Shoji TI Role of CYP2E1 in diethyinitrosamine-induced hepatocarcinogenesis in vivo SO CANCER RESEARCH LA English DT Article ID HUMAN-LIVER-MICROSOMES; CYTOCHROME P450 2E1; N-NITROSODIETHYLAMINE; METABOLIC-ACTIVATION; OXIDATIVE STRESS; HEPATOCYTE DEATH; CELL-DEATH; MICE; NITROSODIMETHYLAMINE; NITROSODIALKYLAMINES AB CYP2E1 metabolizes many low-molecular weight toxins and carcinogens. Some in vitro experiments suggest that CYP2E1 may be involved in the metabolic activation of diethylnitrosamine. However, there has been no direct evidence demonstrating a role for CYP2E1 in diethylnitrosamine-mediated carcinogenesis in vivo. To clarify this, we carried out a diethylnitrosamine-induced hepatocarcinogenesis experiment using Cyp2e1-null mice. Male 14-day-old wild-type and Cyp2e1-null mice were treated with diethyinitrosamine (10 mg/kg of body weight) and killed at weeks 24 and 36 after diethylnitrosamine treatment for investigation of tumors and at 6, 24, and 48 It for examination of apoptosis and gene expression. Liver weights of Cyp2e1-null mice were significantly different at weeks 24 and 36 compared with wild-type mice (P < 0.01). Liver tumor incidences of Cyp2e1-null mice were significantly decreased at weeks 24 and 36 compared with wild-type mice (P < 0.01). Cyp2e1-null mice showed significant decrease in the multiplicities of hepatocellular adenoma at weeks 24 and 36 (P < 0.05 and P < 0.01, respectively), and of hepatocellular carcinoma at week 36 (P < 0.01) compared with wild-type mice. Apoptotic index and caspase-3 and/or Bax mRNA expression of Cyp2e1-null mice were significantly different at 6, 24, and 48 h after diethylnitrosamine treatment compared with wild-type mice (P < 0.05). We conclude that Cyp2e1-null mice show lower tumor incidence and multiplicity compared with wild-type mice in diethylnitrosamine-induced hepatocarcinogenesis. It is suggested that CYP2E1 completely participates in diethylnitrosamine-induced hepatocarcinogenesis, and high frequency of tumors in wild-type mice could be associated with the increased apoptosis. C1 Japan Bioassay Res Ctr, Kanagawa 2570015, Japan. Osaka City Univ, Sch Med, Dept Pathol, Osaka, Japan. NIH, Natl Canc Inst, Lab Metab, Bethesda, MD 20892 USA. RP Fukushima, S (reprint author), Japan Bioassay Res Ctr, 2445 Hirasawa Hadano, Kanagawa 2570015, Japan. EM s-fukushima@jisha.or.jp NR 37 TC 71 Z9 72 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2007 VL 67 IS 23 BP 11141 EP 11146 DI 10.1158/0008-5472.CAN-07-1369 PG 6 WC Oncology SC Oncology GA 238JQ UT WOS:000251444100010 PM 18056438 ER PT J AU Sasaki, CY Slemenda, CF Ghosh, P Barberi, TJ Longo, DL AF Sasaki, Carl Y. Slemenda, Colin F. Ghosh, Paritosh Barberi, Theresa J. Longo, Dan L. TI Traf1 induction and protection from tumor necrosis factor by nuclear factor-kappa B p65 is independent of serine 536 phosphorylation SO CANCER RESEARCH LA English DT Article ID CASEIN KINASE-II; SIGNALING PATHWAY; GENE-EXPRESSION; ACTIVATION; SUBUNIT; ALPHA; TRANSCRIPTION; MECHANISM; APOPTOSIS; PROTEINS AB Abnormal nuclear factor-kappa B (NF-kappa B) signaling has been attributed to the initiation and progression of cancer. Posttranslational modification of p65 facilitates optimal NF-kappa B signaling after activation. Here, we show that the phosphorylation of serine 536 was required for p65-mediated transcription and I kappa B alpha(x expression in fibroblasts. Furthermore, tumor necrosis factor (TNF) treatment slightly induced p65 phosphorylation, and both unphosphorylated and phosphorylated p65 translocated into the nucleus. The phosphorylation of serine 536 was not required for p65-mediated protection from TNF cytotoxicity and Traf1 induction in fibroblasts. Also, the corecruitment of p65 and RNA polymerase II to the Traf1 enhancer region did not require p65 phosphorylation. However, the corecruitment of p65 and RNA polymerase 11 to the Csf2 promoter required the phosphorylation of serine 536. These findings suggested that the requirement of serine phosphorylation at residue 536 and the distance between the NF-KB response element and the start of transcription may influence which genes will be transcribed. C1 NIA, Lab Immunol, Baltimore, MD 21224 USA. RP Sasaki, CY (reprint author), NIA, Lab Immunol, 5600 Nathan Shock Drive, Baltimore, MD 21224 USA. EM sasakic@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000426-03] NR 42 TC 8 Z9 9 U1 0 U2 0 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 DEC 1 PY 2007 VL 67 IS 23 BP 11218 EP 11225 DI 10.1158/0008-5472.CAN-07-0922 PG 8 WC Oncology SC Oncology GA 238JQ UT WOS:000251444100019 PM 18056447 ER PT J AU Hansford, LM Mckee, AE Zhang, LB George, RE Gerstle, JT Thorner, PS Smith, KM Look, AT Yeger, H Miller, FD Irwin, MS Thiele, CJ Kaplan, DR AF Hansford, Loen M. Mckee, Amy E. Zhang, Libo George, Rani E. Gerstle, J. Ted Thorner, Paul S. Smith, Kristen M. Look, A. Thomas Yeger, Herman Miller, Freda D. Irwin, Meredith S. Thiele, Carol J. Kaplan, David R. TI Neuroblastoma cells isolated from bone marrow metastases contain a naturally enriched tumor-initiating cell SO CANCER RESEARCH LA English DT Article ID MINIMAL RESIDUAL DISEASE; ACUTE MYELOID-LEUKEMIA; BREAST-CANCER CELLS; STEM-CELL; PERIPHERAL-BLOOD; FLOW-CYTOMETRY; MONOCLONAL-ANTIBODIES; EXPRESSION; DIFFERENTIATION; IDENTIFICATION AB Neuroblastoma is a heterogeneous pediatric tumor thought to arise from the embryonic neural crest. Identification of the cell responsible for propagating neuroblastomas is essential to understanding this often recurrent, rapidly progressing disease. We have isolated and characterized putative tumor-initiating cells from 16 tumors and bone marrow metastases from patients in all neuroblastoma risk groups. Dissociated cells from tumors or bone marrow grew as spheres in conditions used to culture neural crest stem cells, were capable of self-renewal, and exhibited chromosomal aberrations typical of neuroblastoma. Primary spheres from all tumor risk groups differentiated under neurogenic conditions to form neurons. Tumor spheres from low-risk tumors frequently formed large neuronal networks, whereas those from high-risk tumors rarely did. As few as 10 passaged tumor sphere cells from aggressive neuroblastoma injected orthotopically into severe combined immunodeficient/Beige mice formed large neuroblastoma tumors that metastasized to liver, spleen, contralateral adrenal and kidney, and lung. Furthermore, highly tumorigenic tumor spheres were isolated from the bone marrow of patients in clinical remission, suggesting that this population of cells may predict clinical behavior and serve as a biomarker for minimal residual disease in high-risk patients. Our data indicate that high-risk neuroblastoma contains a cell with cancer stem cell properties that is enriched in tumor-initiating capacity. These cells may serve as a model system to identify the molecular determinants of neuroblastoma and to develop new therapeutic strategies for this tumor. C1 Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1L7, Canada. Hosp Sick Children, Dept Surg, Toronto, ON, Canada. Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON, Canada. Hosp Sick Children, Div Haematol Oncol, Toronto, ON, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA USA. RP Kaplan, DR (reprint author), Hosp Sick Children, Cell Biol Program, Rm 12-314,Flr 12,Toronto Med Discovery Tower,101, Toronto, ON M5G 1L7, Canada. EM dkaplan@sickkids.ca FU Intramural NIH HHS NR 47 TC 99 Z9 103 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2007 VL 67 IS 23 BP 11234 EP 11243 DI 10.1158/0008-5472.CANT-07-0718 PG 10 WC Oncology SC Oncology GA 238JQ UT WOS:000251444100021 PM 18056449 ER PT J AU Furuya, F Lu, C Willingham, MC Cheng, SY AF Furuya, Fumihiko Lu, Changxue Willingham, Mark C. Cheng, Sheue-Yann TI Inhibition of phosphatidylinositol 3-kinase delays tumor progression and blocks metastatic spread in a mouse model of thyroid cancer SO CARCINOGENESIS LA English DT Article ID CELLS IN-VIVO; PHOSPHOINOSITIDE 3-KINASE; TRANSCRIPTIONAL ACTIVITY; LIGAND-BINDING; AKT ACTIVATION; BETA-RECEPTOR; CARCINOMA; HORMONE; GENE; RESISTANCE AB Aberrant activation of the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B-signaling pathway has been associated with multiple human cancers, including thyroid cancer. Recently, we showed that, similar to human thyroid cancer, the PI3K-AKT pathway is overactivated in both the thyroid and metastatic lesions of a mouse model of follicular thyroid carcinoma (TR beta(PV/PV) mice). This TR beta(PV/PV) mouse harbors a knockin mutant thyroid hormone receptor beta gene (TR beta PV mutant) that spontaneously develops thyroid cancer and distant metastasis similar to human follicular thyroid cancer. That the activation of the PI3K-AKT signaling contributes to thyroid carcinogenesis raised the possibility that this pathway could be a potential therapeutic target in follicular thyroid carcinoma. The present study tested this possibility by treating TR beta(PV/PV) mice with LY294002 (LY), a potent and specific PI3K inhibitor, and evaluating the effect of LY on the spontaneous development of thyroid cancer. LY treatment inhibited the AKT-mammalian target of rapamycin (mTOR)-p70(S6K) signaling, and it decreased cyclin D1 and increased p27(Kip1) expression to inhibit thyroid tumor growth and reduce tumor cell proliferation. LY treatment increased caspase 3 and decreased phosphorylated-BAD to induce apoptosis. In addition, LY treatment reduced the AKT-matrix metalloproteinase 2 signaling to decrease cell motility to block metastatic spread of thyroid tumors. Thus, these altered signaling pathways converged effectively to prolong survival of TR beta(PV/PV) mice treated with LY. No significant adverse effects were observed for wild-type mice treated similarly with LY. The present study provides the first preclinical evidence for the in vivo efficacy for LY in the treatment of follicular thyroid cancer. C1 NCI, Natl Inst Hlth, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA. Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA. RP Cheng, SY (reprint author), NCI, Natl Inst Hlth, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural NIH HHS NR 40 TC 71 Z9 74 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2007 VL 28 IS 12 BP 2451 EP 2458 DI 10.1093/carcin/bgm174 PG 8 WC Oncology SC Oncology GA 239GC UT WOS:000251505800004 PM 17660507 ER PT J AU Hsing, AW Sakoda, LC Chen, J Chokkalingam, AP Sesterhenn, I Gao, YT Xu, J Zheng, SL AF Hsing, Ann W. Sakoda, Lori C. Chen, Jinbo Chokkalingam, Anand P. Sesterhenn, Isabel Gao, Yu-Tang Xu, Jianfeng Zheng, S. Lilly TI MSR1 variants and the risks of prostate cancer and benign prostatic hyperplasia: a population-based study in China SO CARCINOGENESIS LA English DT Article ID SCAVENGER RECEPTOR-1 GENE; COMMON SEQUENCE VARIANTS; GERMLINE MUTATIONS; INSULIN-RESISTANCE; ASSOCIATION; METAANALYSIS; RNASEL/HPC1; ELAC2/HPC2; HEREDITARY; PATTERNS AB Data from epidemiologic and twin studies suggest an important role of genetic susceptibility in prostate cancer. Variants of the macrophage scavenger receptor 1 (MSR1) gene have been linked to both hereditary and sporadic prostate cancer, although the evidence is inconclusive. Most studies have been conducted on Caucasians. The role of MSR1 in prostate cancer development among Asians, for whom rates of prostate cancer are low but rising rapidly, is unclear. To evaluate further the relationship between MSR1 variants and prostate cancer risk, we sequenced all the 11 MSR1 exons, exon-intron junctions, promoter regions, as well as 5' and 3' untranslated regions (UTRs) in 86 individuals from Shanghai, China. We identified a total of 21 sequence variants, including three novel variants that have not been reported previously. To balance genotyping cost and the capacity to capture sufficient genetic variation, we genotyped four haplotype-tagging variants (P275A, INDEL7, P346P and 3' UTR 70006), which capture 85% of the genetic variation in MSR1 in this population. These four variants, plus two other variants (PRO3 and INDEL1) that have been linked to prostate cancer risk in the previous studies, were typed for all study subjects, which included 130 prostate cancer cases, 130 patients with benign prostatic hyperplasia and 150 controls randomly selected from the population. Three of the six variants were associated with prostate cancer. Men with a P346P (a novel variant) G allele (AG + GG) had a significantly reduced risk of total prostate cancer [odds ratio = 0.47, 95% confidence interval (CI) 0.23-0.96], whereas those with a P275A G allele had a 37% reduced risk of prostate cancer (95% CI 0.39-1.02), with more pronounced reduction in risk seen for localized cancer cases (odds ratio = 0.25, 95% CI 0.12-0.52; P = 0.001). In addition, men with the INDEL7 variant had a 67% reduced risk of localized cancer (95% CI 0.16-0.68). Based on the four tagging variants, we inferred four major haplotypes that accounted for > 90% of the haplotype variation in this population. The haplotype frequencies were significantly different between localized prostate cancer cases and controls, with a global P value of 0.004, and the haplotype containing the minor alleles of the P275A and INDEL7 variants was associated with a significantly reduced risk of localized prostate cancer (odds ratio = 0.28, 95% CI 0.13-0.59), relative to the most common haplotype. These results, although modest and confined mainly to localized prostate cancer, suggest that MSR1 polymorphisms may play a role in prostate cancer etiology in Chinese men. The role of MSR1 warrants further investigation in larger studies and other populations. C1 NCI, Natl Inst Hlth, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Univ Penn, Philadelphia, PA 19114 USA. Univ Calif Berkeley, Berkeley, CA 94707 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Shanghai Canc Inst, Shanghai 200032, Peoples R China. Wake Forest Univ, Sch Med, Ctr Human Genome, Winston Salem, NC 27157 USA. RP Hsing, AW (reprint author), NCI, Natl Inst Hlth, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM hsinga@mail.nih.gov FU Intramural NIH HHS NR 41 TC 6 Z9 6 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 DEC PY 2007 VL 28 IS 12 BP 2530 EP 2536 DI 10.1093/carcin/bgm196 PG 7 WC Oncology SC Oncology GA 239GC UT WOS:000251505800013 PM 17768178 ER PT J AU Brenner, AV Butler, MA Wang, SS Ruder, AM Rothman, N Schulte, PA Chanock, SJ Fine, HA Linet, MS Inskip, PD AF Brenner, A. V. Butler, M. A. Wang, S. S. Ruder, A. M. Rothman, N. Schulte, P. A. Chanock, S. J. Fine, H. A. Linet, M. S. Inskip, P. D. TI Single-nucleotide polymorphisms in selected cytokine genes and risk of adult glioma SO CARCINOGENESIS LA English DT Article ID NON-HODGKIN-LYMPHOMA; SERUM IGE LEVELS; BRAIN-TUMORS; ALLERGIC CONDITIONS; IL-6 LEVELS; ASSOCIATION; HISTORY; ASTHMA; INTERLEUKIN-6; SUSCEPTIBILITY AB A role of immunological factors in glioma etiology is suggested by reports of an inverse relationship with history of allergy or autoimmune disease. To test whether single-nucleotide polymorphisms (SNPs) in cytokine genes were related to risk of adult glioma, we genotyped 11 SNPs in seven cytokine genes within a hospital-based study conducted by the National Cancer Institute and an independent, population-based study by the National Institute for Occupational Safety and Health (overall 756 cases and 1190 controls with blood samples). The IL4 (rs2243248, -1098T > G) and IL6 (rs1800795, -174G > C) polymorphisms were significantly associated with risk of glioma in the pooled analysis (P trend = 0.006 and 0.04, respectively), although these became attenuated after controlling for the false discovery rate (P trend = 0.07 and 0.22, respectively). Our results underscore the importance of pooled analyses in genetic association studies and suggest that SNPs in cytokine genes may influence susceptibility to glioma. C1 NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NIOSH, CDC, DHHS, Div Appl Res & Technol, Cincinnati, OH 45226 USA. NIOSH, CDC, DHHS, Div Surveillance Hazard Evaluat & Field Studi, Cincinnati, OH 45226 USA. NIOSH, CDC, DHHS, Educ & Informat Div, Cincinnati, OH 45226 USA. NCI, NIH, Adv Technol Corp, Core Genotyping Facil, Bethesda, MD 20892 USA. NCI, NIH, DHHS, Ctr Canc Res, Bethesda, MD 20892 USA. RP Brenner, AV (reprint author), NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM brennera@mail.nih.gov RI Ruder, Avima/I-4155-2012 OI Ruder, Avima/0000-0003-0419-6664 FU Intramural NIH HHS NR 33 TC 36 Z9 36 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2007 VL 28 IS 12 BP 2543 EP 2547 DI 10.1093/carcin/bgm210 PG 5 WC Oncology SC Oncology GA 239GC UT WOS:000251505800015 PM 17916900 ER PT J AU Pandey, J Umphress, SM Kang, Y Angdisen, J Naumova, A Mercer, KL Jacks, T Jakowlew, SB AF Pandey, Jyotsna Umphress, Sarah M. Kang, Yang Angdisen, Jerry Naumova, Alena Mercer, Kim L. Jacks, Tyler Jakowlew, Sonia B. TI Modulation of tumor induction and progression of oncogenic K-ras-positive tumors in the presence of TGF-beta 1 haploinsufficiency SO CARCINOGENESIS LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; CELL LUNG-CANCER; FACTOR-BETA; TGF-BETA; TARGETED DISRUPTION; MOLECULAR-GENETICS; EPITHELIAL-CELLS; II RECEPTOR; C-MYC; MOUSE AB Oncogenic K-ras is one of the most common genetic alterations in human lung adenocarcinomas. In addition, inactivation of clusters of tumor suppressor genes is required to bring about classical characteristics of cancer including angiogenesis as a prelude to invasion and metastasis. Transforming growth factor-beta (TGF-beta) 1 is a tumor suppressor gene that is implicated in lung cancer progression. Although in vitro studies have shown that TGF-beta 1 and Ras pathways cooperate during tumorigenesis, the biology of interaction of TGF-beta 1 and Ras has not been studied in in vivo tumorigenesis. We hypothesized that inactivation of TGF-beta 1 in addition to oncogeneic activation of K-ras would lead to early initiation and faster progression to lung adenocarcinoma and invasion and metastasis. Heterozygous (HT) TGF-beta 1 mice were mated with latent activatable (LA) mutated K-ras mice to generate TGF-beta 1(+/+), K-ras LA (wild-type (WT)/LA) and TGF-beta 1(+/-), K-ras LA (HT/LA) mice. Both HT/LA and WT/LA mice developed spontaneous lung tumors, but HT/LA mice progressed to adenocarcinomas significantly earlier compared with WT/LA mice. In addition, WT/LA adenocarcinomas had significantly higher angiogenic activity compared with HT/LA adenocarcinomas. Thus, while oncogenic K-ras mutation and insensitivity to the growth regulatory effects of TGF-beta 1 is essential for initiation and progression of mouse lung tumors to adenocarcinoma, a full gene dosage of TGF-beta 1 is required for tumor-induced angiogenesis and invasive potential. This study identifies a number of genes not previously associated with lung cancer that are involved in tumor induction and progression. In addition, we provide evidence that progression to invasive angiogenic lesions requires TGF-beta 1 responsiveness in addition to Ras mutation. C1 Natl Canc Inst, Cell & Canc Biol Branch, Rockville, MD 20850 USA. MIT, Canc Res Ctr, Cambridge, MA 02139 USA. RP Jakowlew, SB (reprint author), Natl Canc Inst, Cell & Canc Biol Branch, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. EM jakowles@mail.nih.gov FU Intramural NIH HHS NR 50 TC 9 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2007 VL 28 IS 12 BP 2589 EP 2596 DI 10.1093/carcin/bgm136 PG 8 WC Oncology SC Oncology GA 239GC UT WOS:000251505800022 PM 17690114 ER PT J AU Hollingshead, HE Killins, RL Borland, MG Girroir, EE Billin, AN Willson, TM Sharma, AK Amin, S Gonzalez, FJ Peters, JM AF Hollingshead, Holly E. Killins, Renee L. Borland, Michael G. Girroir, Elizabeth E. Billin, Andrew N. Willson, Timothy M. Sharma, Arun K. Amin, Shantu Gonzalez, Frank J. Peters, Jeffrey M. TI Peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) ligands do not potentiate growth of human cancer cell lines SO CARCINOGENESIS LA English DT Article ID HEPATOCELLULAR-CARCINOMA CELLS; E-2 SIGNALING PATHWAYS; DELTA AGONIST; METABOLIC SYNDROME; GENE-EXPRESSION; ADENOMA GROWTH; DIFFERENTIATION; BETA; CHOLESTEROL; ALPHA AB Ligands for peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) increase skeletal muscle fatty acid catabolism, improve insulin sensitivity, increase serum high-density lipoprotein cholesterol, elicit anti-inflammatory activity and induce terminal differentiation. Contradictory findings are also reported suggesting that PPAR beta/delta ligands potentiate tumorigenesis by increasing cell proliferation, by inhibiting apoptosis through phosphorylation of Akt and by increasing cyclooxygenase-2 (COX2) and vascular endothelial growth factor (VEGF) expression. The contradictory findings could be due to differences in the model system (cancer cell line versus in vivo), differences in cell culture conditions (with and without serum) or differences in ligands. The present study examined the effect of two different PPAR beta/delta ligands (GW0742 and GW501516) in human cancer cell lines (HT29, HCT116, LS-174T, HepG2 and HuH7) cultured in the presence or absence of serum and compared in vitro analysis with in vivo analysis. Neither PPAR beta/delta ligand increased cell growth or phosphorylation of Akt and no increase in the expression of VEGF or COX2 were detected in any cancer cell line in the presence or absence of serum. Similarly, liver, colon and colon polyps from mice administered these PPAR beta/delta ligands in vivo did not exhibit changes in these markers. Results from these studies demonstrate that serum withdrawal and/or differences in ligands do not underlie the disparity in responses reported in the literature. The quantitative nature of the present findings are inconsistent with the hypothesis that cancer cell lines respond differentially as compared with normal cells, and provide further evidence that PPAR beta/delta ligands do not potentiate tumorigenesis. C1 Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet Biomed Sci, University Pk, PA 16802 USA. Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA. GlaxoSmithKline Inc, Nucl Receptor Discovery Res, Res Triangle Pk, NC 27709 USA. Penn State Univ, Milton S Hershey Med Ctr, Penn State Canc Inst, Dept Pharmacol, Hershey, PA 17033 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet Biomed Sci, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011; OI Billin, Andrew/0000-0001-7752-0934 FU NCI NIH HHS [CA97999, CA89607, CA124533] NR 54 TC 44 Z9 44 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2007 VL 28 IS 12 BP 2641 EP 2649 DI 10.1093/carcin/bgm183 PG 9 WC Oncology SC Oncology GA 239GC UT WOS:000251505800028 PM 17693664 ER PT J AU Castrop, H Oppermann, M Mizel, D Huang, Y Faulhaber-Walter, R Weiss, Y Weinstein, LS Chen, M Germain, S Lu, H Ragland, D Schimel, DM Schnermann, J AF Castrop, Hayo Oppermann, Mona Mizel, Diane Huang, Yuning Faulhaber-Walter, Robert Weiss, Yvonne Weinstein, Lee S. Chen, Min Germain, Stephane Lu, Huiyan Ragland, Dan Schimel, Daniel M. Schnermann, Jurgen TI Skeletal abnormalities and extra-skeletal ossification in mice with restricted Gs alpha deletion caused by a renin promoter-Cre transgene SO CELL AND TISSUE RESEARCH LA English DT Article DE renin; bone development; ossification; transgene; cre recombinase; mouse (transgenic, hRen-Cre) ID PROGRESSIVE OSSEOUS HETEROPLASIA; STIMULATORY G-PROTEIN; HORMONE RESISTANCE; GNAS GENE; EXPRESSION; PSEUDOHYPOPARATHYROIDISM; MURINE; TISSUE; DEFICIENCY; KNOCKOUT AB We have recently generated a transgenic mouse line (termed hRen-Cre) that expresses Cre-recombinase under the control of a 12.2-kb fragment of the human renin promoter. In the present study, we have crossed hRen-Cre mice with a mouse strain in which exon 1 of the Gnas gene is flanked by loxP sites. Gnas encodes the alpha-subunit of the stimulatory G protein (Gs alpha). Our aim has been to generate a mouse model with locally restricted inactivation of Gs alpha to extend studies of the role of Gs alpha function in vivo. Mice with local Cre-mediated inactivation of Gs alpha (rCre-Gs alpha) are viable and fertile. Their most obvious phenotype consists of marked skeletal malformations of the forelimbs in which computer-tomography scans reveal shortened and fused extremity bones. Extraskeletal ossifications occur in the subcutis and in skeletal muscles associated with the affected long bones. Plasma calcium, phosphate and parathyroid hormone are normal. Skin histology has demonstrated diffuse mineralization and ossification associated with the basal cells of hair follicles. This phenotype in part resembles syndromes in humans associated with loss-of-function of Gs alpha, such as Albright hereditary osteodystrophy and progressive osseous heteroplasia. The renal phenotype of rCre-Gs alpha mice is inconspicuous. Plasma renin concentration, ambient urine osmolarity, and the glomerular filtration rate of rCre-Gs alpha mice do not differ from controls. The absence of measurable functional changes in the renin-angiotensin system indicates insufficient Cre expression in juxtaglomerular granular cells in this strain of mice. Nevertheless, the present report reaffirms the importance of Gs alpha signaling for bone development and the suppression of ectopic ossification. C1 Univ Regensburg, Inst Physiol, D-93053 Regensburg, Germany. NIDDKD, NIH, Bethesda, MD 20892 USA. INSERM, U36, Paris, France. Cambrex, Walkersville, MD USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Castrop, H (reprint author), Univ Regensburg, Inst Physiol, D-93053 Regensburg, Germany. EM hayo@castrop.com RI Germain, Stephane/E-2301-2016 OI Germain, Stephane/0000-0001-5992-1275 FU Intramural NIH HHS NR 39 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD DEC PY 2007 VL 330 IS 3 BP 487 EP 501 DI 10.1007/s00441-007-0491-6 PG 15 WC Cell Biology SC Cell Biology GA 229VE UT WOS:000250833200009 PM 17922144 ER PT J AU Frias-Staheli, N Giannakopoulos, NV Kikkert, M Taylor, SL Bridgen, A Paragas, J Richt, JA Rowland, RR Schmaljohn, CS Lenschow, DJ Snijder, EJ Garcia-Sastre, A Virgin, HW AF Frias-Staheli, Natalia Giannakopoulos, Nadia V. Kikkert, Marjolein Taylor, Shannon L. Bridgen, Anne Paragas, Jason Richt, Juergen A. Rowland, Raymond R. Schmaljohn, Connie S. Lenschow, Deborah J. Snijder, Eric J. Garcia-Sastre, Adolfo Virgin, Herbert Whiting TI Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses SO CELL HOST & MICROBE LA English DT Article ID NF-KAPPA-B; RESPIRATORY SYNDROME CORONAVIRUS; CONGO-HEMORRHAGIC-FEVER; PAPAIN-LIKE PROTEASE; INFLUENZA-A VIRUS; DEUBIQUITINATING ENZYME; NS1 PROTEIN; ANTIVIRAL MOLECULE; STIMULATED GENE-15; CYSTEINE PROTEASES AB Ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15) reversibly conjugate to proteins and mediate important innate antiviral responses. The ovarian tumor (OTU) domain represents a superfamily of predicted proteases found in eukaryotic, bacterial, and viral proteins, some of which have Ub-deconjugating activity. We show that the OTU domain-containing proteases f rom nairoviruses and arteriviruses, two unrelated groups of RNA viruses, hydrolyze Ub and ISG15 from cellular target proteins. This broad activity contrasts with the target specificity of known mammalian OTU domain-containing proteins. Expression of a viral OTU domain-containing protein antagonizes the antiviral effects of ISG15 and enhances susceptibility to Sindbis virus infection in vivo. We also show that viral OTU domain-containing proteases inhibit NF-kappa B-dependent signaling. Thus, the deconjugating activity of viral OTU proteases represents a unique viral strategy to inhibit Ub- and ISG15dependent antiviral pathways. C1 [Frias-Staheli, Natalia; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY 10029 USA. [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Emerging Pathogens Inst, New York, NY 10029 USA. [Giannakopoulos, Nadia V.; Lenschow, Deborah J.; Virgin, Herbert Whiting] Washington Univ, Sch Med, Dept Pathol & Immunol, Dept Mol Microbiol, St Louis, MO 63110 USA. [Lenschow, Deborah J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Kikkert, Marjolein; Snijder, Eric J.] Leiden Univ, Med Ctr, Ctr Infect Dis,LUMC, Dept Med Microbiol,Mol Virol Lab, NL-2300 RC Leiden, Netherlands. [Taylor, Shannon L.; Schmaljohn, Connie S.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Bridgen, Anne] Univ Ulster, Dept Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland. [Paragas, Jason] NIH, NIAID, Emerging Viral Pathogens Sect, Bethesda, MD 20892 USA. [Richt, Juergen A.] USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. [Rowland, Raymond R.] Kansas State Univ, Manhattan, KS 66506 USA. RP Garcia-Sastre, A (reprint author), Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. EM adolfo.garcia-sastre@mssm.edu; virgin@wustl.edu OI Garcia-Sastre, Adolfo/0000-0002-6551-1827 FU NIAID NIH HHS [U54 AI057158, U19 AI062623, U19 AI062623-010003, U19 AI62623, U54 AI057158-010003, U54 AI057160] NR 53 TC 182 Z9 193 U1 2 U2 7 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 DEC PY 2007 VL 2 IS 6 BP 404 EP 416 DI 10.1016/j.chom.2007.09.014 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 244GY UT WOS:000251855600006 PM 18078692 ER PT J AU Mehlhop, E Ansarah-Sobrinho, C Johnson, S Engle, M Fremont, DH Pierson, TC Diamond, MS AF Mehlhop, Erin Ansarah-Sobrinho, Camillo Johnson, Syd Engle, Michael Fremont, Daved H. Pierson, Theodore C. Diamond, Michael S. TI Complement protein C1q inhibits antibody-dependent enhancement of flavivirus infection in an IgG subclass-specific manner SO CELL HOST & MICROBE LA English DT Article ID WEST-NILE-VIRUS; DENGUE HEMORRHAGIC-FEVER; RESPIRATORY SYNCYTIAL VIRUS; VALLEY-ENCEPHALITIS-VIRUS; YELLOW-FEVER; MONOCLONAL-ANTIBODIES; MEDIATED ENHANCEMENT; IMMUNE-RESPONSE; ENHANCING ANTIBODIES; PASSIVE-IMMUNIZATION AB Severe dengue virus infection can occur in humans with pre-existing antibodies against the virus. This observation led to the hypothesis that a subneutralizing antibody level in vivo can increase viral burden and cause more severe disease. Indeed, antibody-dependent enhancement of infection (ADE) in vitro has been described for multiple viruses, including the flaviviruses dengue virus and West Nile virus. Here, we demonstrate that the complement component C1q restricts ADE by anti-flavivirus IgG antibodies in an IgG subclass-specific manner in cell culture and in mice. IgG subclasses that avidly bind C1q induced minimal ADE in the presence of C1q. These findings add a layer of complexity for the analysis of humoral immunity and flavivirus infection. C1 [Mehlhop, Erin; Fremont, Daved H.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Engle, Michael; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Ansarah-Sobrinho, Camillo; Pierson, Theodore C.] NIH, Viral Dis Lab, Viral Pathogenesis Sect, Bethesda, MD 20892 USA. [Johnson, Syd] MacroGen Inc, Rockville, MD 20850 USA. RP Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM diamond@borcim.wustl.edu FU Intramural NIH HHS; NIAID NIH HHS [AI061373, U01 AI061373, U01 AI061373-03, U54 AI057160, U54 AI057160-010003]; PHS HHS [HHSN266200600013C] NR 82 TC 67 Z9 73 U1 0 U2 2 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 DEC PY 2007 VL 2 IS 6 BP 417 EP 426 DI 10.1016/j.chom.2007.09.015 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 244GY UT WOS:000251855600007 PM 18078693 ER PT J AU Vaught, J Cosentino, M AF Vaught, Jim Cosentino, Mark TI Approaches to improving biospecimen quality through research SO CELL PRESERVATION TECHNOLOGY LA English DT Editorial Material C1 [Vaught, Jim] NCI, NIH, Dept Hlth & Human Serv, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Cosentino, Mark] SAIC Frederick Inc, Head Bioproc & DNA Extract Labs, Frederick, MD 21702 USA. RP Vaught, J (reprint author), NCI, NIH, Dept Hlth & Human Serv, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. EM vaughtj@mail.nih.gov; mcosentino@ncifcrf.gov 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 1538-344X J9 CELL PRESERV TECHNOL JI Cell Preserv. Technol. PD WIN PY 2007 VL 5 IS 4 BP 178 EP 179 DI 10.1089/cpt.2007.9986 PG 2 WC Cell Biology; Medical Laboratory Technology SC Cell Biology; Medical Laboratory Technology GA 254QY UT WOS:000252604300002 ER PT J AU Shao, W Garcia-Closas, M Alguacil, J Rothman, N Schatzkin, A Vaught, J Sigurdson, A Cosentino, M AF Shao, Wen Garcia-Closas, Montserrat Alguacil, Juan Rothman, Nat Schatzkin, Arthur Vaught, Jim Sigurdson, Alice Cosentino, Mark TI Modifications to a standard buccal collection protocol: Effects on human DNA yield SO CELL PRESERVATION TECHNOLOGY LA English DT Article ID GENOMIC DNA; CELL-DNA; MOUTHWASH; SAMPLES; CYTOBRUSH; QUALITY; COHORT; MAIL AB A standard mouthwash protocol (a single 10-mL swish of mouthwash for 45 see) was modified in an attempt to increase the amount of human buccal cell DNA per collection and to reduce the percentage of low yielding human DNA collections (<4 mu g). A group of 22 healthy individuals donated a buccal sample each week for several weeks according to the standard protocol without or with one of the following modifications: (1) decreasing the volume of mouthwash, (2) having participants externally rub or not rub their cheeks before donating a specimen, (3) donating two consecutive specimens at each collection, (4) substituting saline for mouthwash, and (5) having individuals expectorate into mouthwash. There was no significant difference in the amount of human DNA collected when 10 mL or 5 mL of mouthwash was used. Externally rubbing cheeks before donating did not significantly alter the amount of human DNA collected, regardless of whether it was one or two donations. Addition of a second donation resulted in 24% to 50% more human DNA than from only a single donation, regardless of whether 5 mL or 10 mL of mouthwash was used, with or without cheek rubbing. With two donations, the percentage of low-yielding human DNA samples was reduced up to 31%. Substituting saline for mouthwash resulted in a significantly lower amount of human buccal DNA collected, regardless of cheek rubbing, and a higher number of low-yielding samples. Expectorating directly into mouthwash while externally rubbing cheeks performed the best (17.70 mu g human DNA), followed by swishing 2-10 mL of mouthwash before expectorating (12.26 mu g). Both protocols had 95% of their samples yielding at least 4 mu g of human DNA without increasing cost; however, when selecting a collection protocol the age and health status of the cohort needs to be considered. C1 [Shao, Wen; Cosentino, Mark] NCI Frederick, SAIC Frederick Inc, Appli & Dev Directorate, Lab Biospecimen & Biorepository Res, Frederick, MD 21702 USA. [Garcia-Closas, Montserrat; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Bethesda, MD USA. [Rothman, Nat] NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, Bethesda, MD USA. [Vaught, Jim] NCI, Div Canc Epidemiol & Genet, Off Director, Bethesda, MD USA. [Sigurdson, Alice] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD USA. [Alguacil, Juan] Univ Huelva, Dept Biol Ambiental & Salud Publ, Huelva, Spain. RP Cosentino, M (reprint author), NCI Frederick, SAIC Frederick Inc, Appli & Dev Directorate, Lab Biospecimen & Biorepository Res, 1066 Boyles St,Room 100,POB B, Frederick, MD 21702 USA. EM mcosentino@ncifcrf.gov NR 15 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 1538-344X J9 CELL PRESERV TECHNOL JI Cell Preserv. Technol. PD WIN PY 2007 VL 5 IS 4 BP 216 EP 224 DI 10.1089/cpt.2007.0512 PG 9 WC Cell Biology; Medical Laboratory Technology SC Cell Biology; Medical Laboratory Technology GA 254QY UT WOS:000252604300006 ER PT J AU Groover, K Drew, K Franke, J AF Groover, Kathleen Drew, Karon Franke, Judith TI The use of compressor cycle patterns: The ability to predict freezer failure SO CELL PRESERVATION TECHNOLOGY LA English DT Article AB Biorepositories are tasked with the care and storage of priceless collections of biological specimens. Critical to the success of biorepository operations is the safe, secure, viable storage of the specimens entrusted to its care. The primary means by which this is accomplished is to ensure proper function of ultralow freezers. For a large biorepository this involves the tracking and monitoring of hundreds of freezers. Biorepository procedures typically require recording of the temperature of each freezer on a daily basis. At the Central Repository of the National Cancer Institute in Frederick, Maryland, temperature monitoring has been taken one step further. New procedures utilize the in-house 24-h temperature monitoring system to produce daily printouts of the fluctuation of temperature with time. These graphs are reviewed, and based upon an understanding of freezer compressor cycles are used to identify potential problems with freezer function. These new procedures, which can be used to predict failure, have identified specific types of temperature traces that are indicative of a failure rate 2.9 times greater than normal. C1 [Groover, Kathleen; Drew, Karon; Franke, Judith] NCI Frederick Cent Repository Serv, Fisher Bioserv Inc, Frederick, MD 21703 USA. RP Groover, K (reprint author), NCI Frederick Cent Repository Serv, Fisher Bioserv Inc, 4600 Wedgewood Blvd,Suite H, Frederick, MD 21703 USA. EM kathleen.groover@thermofisher.com NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-344X J9 CELL PRESERV TECHNOL JI Cell Preserv. Technol. PD WIN PY 2007 VL 5 IS 4 BP 225 EP 228 DI 10.1089/cpt.2007.0510 PG 4 WC Cell Biology; Medical Laboratory Technology SC Cell Biology; Medical Laboratory Technology GA 254QY UT WOS:000252604300007 ER PT J AU Freeley, M Park, J Yang, KJ Wange, RL Volkov, Y Kelleher, D Long, A AF Freeley, Michael Park, Jongsun Yang, Keum-Jin Wange, Ronald L. Volkov, Yuri Kelleher, Dermot Long, Aideen TI Loss of PTEN expression does not contribute to PDK-1 activity and PKC activation-loop phosphorylation in Jurkat leukaemic T cells SO CELLULAR SIGNALLING LA English DT Article DE PTEN; PDK-1; PKB/Akt; PKC; PP2A; phosphorylation ID PROTEIN-KINASE-C; PHOSPHOINOSITIDE-DEPENDENT KINASE; TUMOR-SUPPRESSOR GENE; 3-PHOSPHOINOSITIDE-DEPENDENT KINASE-1; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; PLASMA-MEMBRANE; IN-VIVO AB Unopposed PI3-kinase activity and 3 '-phosphoinositide production in Jurkat T cells, due to a mutation in the PTEN tumour suppressor protein, results in deregulation of PH domain-containing proteins including the serine/threonine kinase PKB/Akt. In Jurkat cells, PKB/Akt is constitutively active and phosphorylated at the activation-loop residue (Thr308). 3 '-phosphoinositide-dependent protein kinase-1 (PDK-1), an enzyme that also contains a PH domain, is thought to catalyse Thr308 phosphorylation of PKB/Akt in addition to other kinase families such as PKC isoforms. It is unknown however if the loss of PTEN in Jurkat cells also results in unregulated PDK-1 activity and whether such loss impacts on activation-loop phosphorylation of other putative PDK-1 substrates such as PKC. In this study we have addressed if loss of PTEN in Jurkat T cells affects PDK-1 catalytic activity and intracellular localisation. We demonstrate that reducing the level of 3 '-phosphoinositides in Jurkat cells with pharmacological inhibitors of PI3-kinase or expression of PTEN does not affect PDK-1 activity, Ser241 phosphorylation or intracellular localisation. In support of this finding, we show that the levels of PKC activation-loop phosphorylation are unaffected by reductions in the levels of 3 '-phosphoinositides. Instead, the dephosphorylation that occurs on PKB/Akt at Thr308 following reductions in 3 '-phosphoinositides is dependent on PP2A-like phosphatase activity. Our finding that PDK-1 functions independently of 3 '-phosphoinositides in T cells is also confirmed by studies in HuT-78 T cells. a PTEN-expressing cell line with undetectable levels of 3 '-phosphoinositides. We conclude therefore that loss of PTEN expression in Jurkat T cells does not impact on the PDK-1/PKC pathway and that only a subset of kinases, such as PKB/Akt, are perturbed as a consequence PTEN loss. (C) 2007 Elsevier Inc. All tights reserved. C1 Trinity Coll Dublin, Inst Mol Med, Dept Clin Med, Dublin, Ireland. Chungnam Natl Univ, Coll Med, Canc Res Inst, Dept Pharmacol,Cell Signaling Lab, Taejon 301131, South Korea. NIH, NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. US FDA, Div Metab & Endocrinol Prod, Silver Spring, MD 20993 USA. RP Long, A (reprint author), Trinity Coll Dublin, Inst Mol Med, Dept Clin Med, Dublin, Ireland. EM freeleym@ted.ie; insulin@cnu.ac.kr; Ronald.Wange@FDA.HHS.GOV; yvolkov@tcd.ie; dermot.kelleher@tcd.ie; longai@tcd.ie RI Park, Jongsun/E-7465-2010; OI Park, Jongsun/0000-0002-4690-1854; Freeley, Michael/0000-0002-5763-6582; Volkov, Yuri/0000-0001-7406-518X NR 78 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD DEC PY 2007 VL 19 IS 12 BP 2444 EP 2457 DI 10.1016/j.cellsig.2007.07.020 PG 14 WC Cell Biology SC Cell Biology GA 230XT UT WOS:000250910400004 PM 17826953 ER PT J AU Chen, LJ Burka, LT AF Chen, Ling-Jen Burka, Leo T. TI Chemical and enzymatic oxidation of furosemide: Formation of pyridinium salts SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID METABOLIC-ACTIVATION; 4-IPOMEANOL; BIOACTIVATION; INTERMEDIATE; FURAN; MOUSE AB Furosemide (Lasix) is frequently used in the treatment of cardiovascular and renal disease. Only one metabolite, furosemide glucuronide, has ever been identified. Oxidation of furosemide by cytochrome P450 has been demonstrated, but the metabolite(s) has never been identified. The oxidation of furosemide by dimethyldioxirane in acetone and by liver microsomal incubations was explored in this study. The first observable product from dimethyldioxirane oxidation was a ring-expanded enone resulting from an intramolecular condensation of the aldehyde group of the enonal, the secondary amine, and the carboxylic acid in a Mannich-like reaction. Keto-enol tautomerization and opening of the lactone gave a stable pyridinium salt. The pyridinium salt was also observed in the microsomal incubations of furosemide. The presence of an internal nucleophile in furosemide may have a significant effect on the toxicology and possibly the pharmacology of this furan. C1 [Chen, Ling-Jen; Burka, Leo T.] NIEHS, Chem Pharmacol Lab, Res Triangle Pk, NC 27709 USA. RP Chen, LJ (reprint author), Lovelace Respirat Res Inst, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM ljferguson@Irri.org FU Intramural NIH HHS NR 17 TC 20 Z9 20 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2007 VL 20 IS 12 BP 1741 EP 1744 DI 10.1021/tx700262z PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 242NW UT WOS:000251733400002 PM 17914885 ER PT J AU Coulter, R Blandino, M Tomlinson, JM Pauly, GT Krajewska, M Moschel, RC Peterson, LA Pegg, AE Spratt, TE AF Coulter, Richard Blandino, Maureen Tomlinson, Jessica M. Pauly, Gary T. Krajewska, Magdalena Moschel, Robert C. Peterson, Lisa A. Pegg, Anthony E. Spratt, Thomas E. TI Differences in the rate of repair of O-6-alkylguanines in different sequence contexts by O-6-alkylguanine-DNA alkyltransferase SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HUMAN O(6)-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ESCHERICHIA-COLI; OXIDATIVE DEMETHYLATION; DNA ALKYLTRANSFERASE; PROTEIN; OLIGODEOXYNUCLEOTIDES; BASE; O-6-METHYLGUANINE; ANALOGS; BINDING AB O-6-Alkylguanine-DNA alkyltransferase (AGT) repairs O-6-alkylguanine residues at different rates depending on the identity of the alkyl group as well as the sequence context. To elucidate the mechanism(s) underlying the differences in rates, we examined the repair of five alkyl groups in three different sequence, contexts. The k(inact) and K-m values were determined by measuring the rates of repair of oligodeoxynucleotide duplexes containing the O-6-alkylguanine residues with various concentrations of AGT in excess. The time course of the reactions all followed pseudo-first-order kinetics except for one of the O-6-ethylguanine substrates, which could be analyzed in a two-phase exponential equation. The differences in rates of repair between the different alkyl groups and the different sequence contexts are dependent on rates of alkyl transfer and not substrate recognition. The relative rates of reaction are in general benzyl > methyl > ethyl > 2-hydroxyethyl > 4-(3-pyridyl)-4-oxobutyl, but the absolute rates are dependent on sequence. The k(inact) values between benzyl and 4-(3-pyridyl)-4-oxobutyl range from 2300 to 350000 depending on sequence. The sequence-dependent variation in k(inact) varied the most for O-6-[4-(3-pyridyl)-4-oxobutyl]guanine, which ranged from 0.022 to 0.000016 s(-1). The results are consistent with a mechanism in which the O-6-alkylguanine can bind to AGT in either a reactive or an unreactive orientation, the proportion of which depends on the sequence context. C1 Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. [Coulter, Richard; Tomlinson, Jessica M.; Pegg, Anthony E.; Spratt, Thomas E.] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. [Blandino, Maureen; Spratt, Thomas E.] Amer Hlth Fdn, Inst Canc Prevent, Valhalla, NY 10595 USA. [Pauly, Gary T.; Krajewska, Magdalena; Moschel, Robert C.] NCI, Frederick Canc Res & Dev Ctr, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. [Peterson, Lisa A.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. RP Spratt, TE (reprint author), Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. EM tes13@psu.edu OI Spratt, Thomas/0000-0002-6805-3729; Peterson, Lisa/0000-0001-8715-4480 FU Intramural NIH HHS; NCI NIH HHS [R01 CA-59887, R01 CA75074, R01 CA059887, R01 CA-018137] NR 38 TC 27 Z9 27 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2007 VL 20 IS 12 BP 1966 EP 1971 DI 10.1021/tx700271j PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 242NW UT WOS:000251733400028 PM 17975884 ER PT J AU Ju, C You, Q Holt, M Cheng, L Pohl, LR AF Ju, Cynthia You, Qiang Holt, Michael Cheng, Linling Pohl, Lance R. TI Role of the innate immune system in drug-induced liver injury SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 234th ACS National Meeting CY AUG 19-23, 2007 CL Boston, MA SP Amer Chem Soc, Div Chem Toxicol C1 [Ju, Cynthia; You, Qiang; Holt, Michael; Cheng, Linling] Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA. [Pohl, Lance R.] NIH, NHLBI, Mol & Cellular Toxicol Sect, Bethesda, MD 20892 USA. EM Cynthia.Ju@UCHSC.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2007 VL 20 IS 12 MA 33 BP 1995 EP 1995 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 242NW UT WOS:000251733400064 ER PT J AU Kong, L Saavedra, JE Nagashima, K Zheng, J Patri, A Keefer, LK AF Kong, Li Saavedra, Joseph E. Nagashima, Kunio Zheng, Jiwen Patri, Anil Keefer, Larry K. TI Nitric oxide-induced deamidation retards and reverses fibril formation by an oligo(glutamine/asparagine) peptide SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 234th ACS National Meeting CY AUG 19-23, 2007 CL Boston, MA SP Amer Chem Soc, Div Chem Toxicol C1 [Kong, Li; Keefer, Larry K.] Natl Canc Inst, Comparat Carcinogenesis Lab, Chem Sect, Frederick, MD 21702 USA. [Saavedra, Joseph E.] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. [Nagashima, Kunio] SAIC Frederick, Image Anal Lab, Res Technol Program, Frederick, MD 21702 USA. [Zheng, Jiwen; Patri, Anil] SAIC Frederick, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA. EM kongl@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2007 VL 20 IS 12 MA 120 BP 2013 EP 2014 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 242NW UT WOS:000251733400151 ER PT J AU DiPietro, JA Costigan, K Bornstein, MH Achy-Brou, A AF DiPietro, Janet A. Costigan, Kathleen Bornstein, Marc H. Achy-Brou, Aristide TI Fetal heart rate and variability: Stability and prediction to developmental outcomes in early childhood SO CHILD DEVELOPMENT LA English DT Article ID CARDIAC VAGAL TONE; GROWTH-RETARDED FETUSES; NERVOUS-SYSTEM; VIBROACOUSTIC STIMULATION; PRETERM INFANTS; BEHAVIOR; AGE; REACTIVITY; ORIGINS; MYELINATION AB Stability in cardiac indicators before birth and their utility in predicting variation in postnatal development were examined. Fetal heart rate and variability were measured longitudinally from 20 through 38 weeks gestation (n = 137) and again at age 2 (n = 79). Significant within-individual stability during the prenatal period and into childhood was demonstrated. Fetal heart rate variability at or after 28 weeks gestation and steeper developmental trajectories were significantly associated with mental and psychomotor development at 2 years (n = 82) and language ability at 2.5 years (n = 61). These data suggest that the foundations of individual differences in autonomic control originate during gestation and the developmental momentum of the fetal period continues after birth. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reproduct Hlth, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP DiPietro, JA (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reproduct Hlth, 615 N Wolfe St,E4531, Baltimore, MD 21205 USA. EM jdipietr@jhsph.edu FU Intramural NIH HHS; NICHD NIH HHS [R01 HD27592, R01 HD027592, R01 HD027592-15]; PHS HHS [R40 MC00181] NR 64 TC 36 Z9 37 U1 4 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-3920 J9 CHILD DEV JI Child Dev. PD DEC PY 2007 VL 78 IS 6 BP 1788 EP 1798 DI 10.1111/j.1467-8624.2007.01099.x PG 11 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 227GI UT WOS:000250644800011 PM 17988321 ER PT J AU Wallis, MC Waters, PD Delbridge, ML Kirby, PJ Pask, AJ Grutzner, F Rens, W Ferguson-Smith, MA Graves, JAM AF Wallis, M. C. Waters, P. D. Delbridge, M. L. Kirby, P. J. Pask, A. J. Grutzner, F. Rens, W. Ferguson-Smith, M. A. Graves, J. A. M. TI Sex determination in platypus and echidna: autosomal location of SOX3 confirms the absence of SRY from monotremes SO CHROMOSOME RESEARCH LA English DT Article DE Ornithorhynchus anatinus; platypus; sex determination; SOX3; SRY; Tachyglossus aculeatus ID IN-SITU HYBRIDIZATION; EARLY FEMALE EMBRYOS; HUMAN X-CHROMOSOME; MAMMALIAN SEX; Y-CHROMOSOME; DETERMINING GENE; TOKUDAIA-OSIMENSIS; DETERMINING REGION; LINKED GENES; W-CHROMOSOME AB In eutherian ('placental') mammals, sex is determined by the presence or absence of the Y chromosome-borne gene SRY, which triggers testis determination. Marsupials also have a Y-borne SRY gene, implying that this mechanism is ancestral to therians, the SRY gene having diverged from its X-borne homologue SOX3 at least 180 million years ago. The rare exceptions have clearly lost and replaced the SRY mechanism recently. Other vertebrate classes have a variety of sex-determining mechanisms, but none shares the therian SRY-driven XX female:XY male system. In monotreme mammals (platypus and echidna), which branched from the therian lineage 210 million years ago, no orthologue of SRY has been found. In this study we show that its partner SOX3 is autosomal in platypus and echidna, mapping among human X chromosome orthologues to platypus chromosome 6, and to the homologous chromosome 16 in echidna. The autosomal localization of SOX3 in monotreme mammals, as well as non-mammal vertebrates, implies that SRY is absent in Prototheria and evolved later in the therian lineage 210-180 million years ago. Sex determination in platypus and echidna must therefore depend on another male-determining gene(s) on the Y chromosomes, or on the different dosage of a gene(s) on the X chromosomes. C1 [Wallis, M. C.; Waters, P. D.; Delbridge, M. L.; Kirby, P. J.; Grutzner, F.; Graves, J. A. M.] Australian Natl Univ, Res Sch Biol Sci, Comparat Genom Grp, Canberra, ACT 2601, Australia. [Kirby, P. J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Pask, A. J.] Univ Melbourne, Dept Zool, Melbourne, Vic 3010, Australia. [Rens, W.; Ferguson-Smith, M. A.] Univ Cambridge, Dept Vet Med, Cambridge Resource Ctr Comparat Genom, Cambridge CB3 0ES, England. RP Wallis, MC (reprint author), Australian Natl Univ, Res Sch Biol Sci, Comparat Genom Grp, Canberra, ACT 2601, Australia. EM mary.wallis@anu.edu.au RI Graves, Jennifer/A-1387-2008; Waters, Paul/D-1044-2009; Waters, Paul/B-7871-2015; OI Grutzner, Frank/0000-0002-3088-7314; Pask, Andrew/0000-0002-1900-2263 FU Wellcome Trust NR 70 TC 39 Z9 40 U1 2 U2 22 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD DEC PY 2007 VL 15 IS 8 BP 949 EP 959 DI 10.1007/s10577-007-1185-3 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 249TK UT WOS:000252252500001 PM 18185981 ER PT J AU Belak, M Valeri, CR Wright, DG AF Belak, M. Valeri, C. R. Wright, D. G. TI Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE CD4; immunoadsorption cytapheresis; immunosuppression; lymphocyte depletion ID LOW-DENSITY-LIPOPROTEIN; THORACIC-DUCT FISTULA; RHEUMATOID-ARTHRITIS; AFFINITY CHROMATOGRAPHY; EXTRACORPOREAL REMOVAL; MONOCLONAL-ANTIBODIES; PERIPHERAL-BLOOD; BONE-MARROW; LIFE-SPANS; CELLS AB Normal turnover of T lymphocytes is slow relative to other blood cells. Consequently, the physical removal of circulating leucocytes by thoracic duct drainage, repeated leukapheresis or blood filtration results in T cell depletion and immunosuppression. However, clinical use of such procedures is impractical compared with immunosuppressive drugs or radiation. None the less, immunosuppression by physical depletion of T cells, avoiding the systemic toxicities of drugs and radiation, might have clinical advantages if immunophenotypically distinct T cell subsets could be depleted selectively. Recent advances in targeted plasma protein apheresis using adsorbent macrobead columns prompted us to determine whether analogous techniques might permit CD4(+) T lymphocytes to be removed selectively from whole blood. To explore this possibility, we linked murine anti-human-CD4 and isotype-identical control monoclonal antibodies (mAbs) to agarose, polyacrylamide and polystyrene macrobeads (150-350 mu m) and then evaluated the selectivity, specificity and efficiency of macrobead columns to remove CD4(+) T cells from anti-coagulated whole blood at varying mAb densities and flow rates. We also examined saturation kinetics and Fc-oriention versus random coupling of mAbs to macrobeads. Sepharose 6MB macrobead (250-350 mu m) columns proved to be most effective, selectively removing up to 98% of CD4(+) T cells from whole blood. Moreover, depletion efficiency and selectivity were retained when these columns were reused after elution of adherent CD4(+) cells. These studies indicate that selective depletion of T lymphocyte subsets by whole blood immunoadsorption apheresis using mAb-linked macrobead columns may be feasible on a clinical scale. It is possible that such apheresis techniques could achieve targeted forms of immunosuppression not possible with drugs or radiation. C1 NIDDK, NIH, Mol Med Branch, Bethesda, MD 20892 USA. Boston Univ, Med Ctr, Naval Blood Res Lab, Boston, MA 02215 USA. Boston Univ, Med Ctr, Sect Hematol & Oncol, Dept Med, Boston, MA 02215 USA. RP Belak, M (reprint author), NIDDK, NIH, Mol Med Branch, Bldg 10,Room 9N312,10 Ctr Dr, Bethesda, MD 20892 USA. EM belakm@mail.nih.gov NR 50 TC 1 Z9 1 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD DEC PY 2007 VL 150 IS 3 BP 477 EP 486 DI 10.1111/j.1365-2249.2007.03518.x PG 10 WC Immunology SC Immunology GA 229PH UT WOS:000250816000011 PM 17924969 ER PT J AU Summerton, J Riedesel, M Laeyendecker, O Gaydos, C Maldeis, NE Hardick, A Morrow, RA Quinn, TC AF Summerton, Jean Riedesel, Melissa Laeyendecker, Oliver Gaydos, Charlotte Maldeis, Nancy E. Hardick, Andrew Morrow, Rhoda Ashley Quinn, Thomas C. TI Effect of sexually transmitted disease (STD) coinfections on performance of three commercially available immunosorbent assays used for detection of herpes simplex virus type 2-specific antibody in men attending Baltimore, Maryland, STD clinics SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID REAL-TIME PCR; GENITAL HERPES; GLYCOPROTEIN-G; INFECTION; FOCUS; VERIFICATION; SEROLOGY; TESTS; SERA; BIAS AB Two hundred seventy-nine serum samples from men attending sexually transmitted disease (STD) clinics in Baltimore, Maryland, were tested for herpes simplex virus type 2 (HSV-2)-specific antibody by three immunosorbent glycoprotein G-2-based assays (the Kalon, Focus, and Biokit assays). The results for all samples with positive results were confirmed by Western blotting (91/279; 32.6% HSV-2 seroprevalence). All patients were also tested for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, human immunodeficiency virus type 1, and hepatitis C virus. The Kalon assay performed very well with samples from this population (90.8% sensitive, 99.4% specific), whereas the Focus assay had a sensitivity (82.6%) much lower than that shown previously. For 19.7% of the samples, the Biokit assay gave an indeterminate result. It was found that the odds of a sample having a Biokit assay indeterminate result compared to that of having a definitive positive or negative results were 3.88 times greater for subjects concurrently infected with N. gonorrhoeae, after the effects of other STDs were controlled for (P = 0.001; 95% confidence interval, 1.78, 8.45). Unfortunately, we were unable to control for HSV-1 infection status in the regression model, which, on the basis of chi(2) analysis, might also affect the clarity of the Biokit test. The recommended index cutoff value of 1.1 for the Focus and Kalon assays was found to be optimal for this population. C1 [Summerton, Jean; Laeyendecker, Oliver; Gaydos, Charlotte; Hardick, Andrew; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21218 USA. [Riedesel, Melissa; Laeyendecker, Oliver; Quinn, Thomas C.] NIH, NIAID, Baltimore, MD USA. [Maldeis, Nancy E.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Morrow, Rhoda Ashley] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Quinn, TC (reprint author), Johns Hopkins Univ, Div Infect Dis, 1721 E Madison St,Ross Res Bldg 1159, Baltimore, MD 21205 USA. EM tquinn@jhmi.edu RI Laeyendecker, Oliver/B-9331-2009; Gaydos, Charlotte/E-9937-2010; OI Laeyendecker, Oliver/0000-0002-6429-4760 FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [U01 AI068613, U01 AI068613-02] NR 23 TC 12 Z9 12 U1 0 U2 0 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 DEC PY 2007 VL 14 IS 12 BP 1545 EP 1549 DI 10.1128/CVI.00120-07 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 242DM UT WOS:000251704700002 PM 17913866 ER PT J AU Fine, HA Kim, L Albert, PS Duic, JP Ma, H Zhang, W Tohnya, T Figg, WD Royce, C AF Fine, Howard A. Kim, Lyndon Albert, Paul S. Duic, J. Paul Ma, Hilary Zhang, Wei Tohnya, Tanyifor Figg, William D. Royce, Cheryl TI A phase I trial of lenalidomide in patients with recurrent primary central nervous system tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HIGH-GRADE GLIOMAS; GLIOBLASTOMA-MULTIFORME; MULTIPLE-MYELOMA; BRAIN-TUMORS; THALIDOMIDE; THERAPY; CC-5013; VIVO; ASTROCYTOMAS AB Purpose: Inhibition of angiogenesis represents a promising new therapeutic strategy for treating primary malignant brain tumors. Lenalidomide, a potent analogue of the antiangiogenic agent thalidomide, has shown significant activity in several hematologic malignancies, and therefore we chose to explore its tolerability and activity in patients with primary central nervous system tumors. Experimental Design: A phase I interpatient dose escalation trial of lenalidomide in patients with recurrent primary central nervous system tumors was conducted. Results: Thirty-six patients were accrued to the study, of which 28 were evaluable for toxicity, the primary end point of the trial. We show that lenalidomide can be given safely up to doses of 2 20 mg/m(2), with the only toxicity being a probable increased risk of thromboembolic disease. Pharmacokinetic studies reveal good bioavailability, linear kinetics, and no effects of enzyme-inducing antiepileptic drugs on the metabolism of lenalidomide. No objective radiographic responses were seen in any of the treated patients. In the group of 24 patients with recurrent glioblastoma, the median time to tumor progression was < 2 months and only 12.5% of patients were progression-free at 6 months. Conclusion: Lenalidomide is well tolerated in patients with recurrent glioma in doses up to 20 mg/m(2). Treatment may be associated with an increased risk of thromboembolic disease. Preliminary data suggest that single agent activity may be limited in patients with recurrent glioblastoma at the doses evaluated although larger studies will be needed to confirm these observations. C1 NCI, Neuro Oncol Branch, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. Natl Inst Neurol Disoreder & Stroke, Biometric Res Branch, Bethesda, MD USA. RP Fine, HA (reprint author), NCI, Neuro Oncol Branch, 9030 Old Georgetown Rd, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Figg Sr, William/M-2411-2016 NR 28 TC 37 Z9 38 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2007 VL 13 IS 23 BP 7101 EP 7106 DI 10.1158/1078-0432.CCR-07-1546 PG 6 WC Oncology SC Oncology GA 239PA UT WOS:000251529000025 PM 18056189 ER PT J AU Loghin, ME Prados, MD Wen, P Junck, L Lieberman, F Fine, H Fink, KL Metha, M Kuhn, J Lamborn, K Chang, SM Cloughesy, T DeAngelis, LM Robins, IH Aldape, KD Yung, WKA AF Loghin, Monica E. Prados, Michael D. Wen, Patrick Junck, Larry Lieberman, Frank Fine, Howard Fink, Karen L. Metha, Minesh Kuhn, John Lamborn, Kathleen Chang, Susan M. Cloughesy, Timothy DeAngelis, Lisa M. Robins, Ian H. Aldape, Kenneth D. Yung, W. K. Alfred TI Phase I study of temozolomide and irinotecan for recurrent malignant gliomas in patients receiving enzyme-inducing antiepileptic drugs: A North American brain tumor consortium study SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-GRADE GLIOMA; ANTITUMOR IMIDAZOTETRAZINES; TOPOISOMERASE-I; SOLID TUMORS; CPT-11; TRIAL; PHARMACOKINETICS; CANCER; CAMPTOTHECIN; XENOGRAFTS AB Purpose:To determine the maximum tolerated dose of irinotecan when administrated with temozolomide every 28 days, in patients with recurrent malignant glioma who were also receiving CYP450 enzyme-inducing antiepileptic drugs (EIAED), and to characterize the pharmacokinetics of irinotecan and its metabolites. The study was also intended to assess whether temozolomide affects the conversion of irinotecan to SN-38. Design: Patients with recurrent malignant glioma received a fixed dose of temozolomide (150 mg/m(2)) daily for 5 days from days 1 to 5 every 28 days, and an i.v. infusion of irinotecan on 2 days 1 and 15 of each cycle. The starting dose of irinotecan was 350 mg/m(2), which was escalated to 550 mg/m(2) in 50-mg/m(2) increments. The plasma pharmacokinetics of irinotecan and its active metabolite, SN-38, were determined during the infusion of irinotecan on cycle 1, day 1. Results: Thirty-three patients were enrolled into the study and treated. Thirty-one patients were evaluable for both tumor response and toxicity and two patients were evaluable for toxicity only. Common toxicities included neutropenia and thrombocytopenia, nausea, vomiting, and diarrhea. Dose-limiting toxicities were grade 3 diarrhea and nausea/vomiting. The maximum tolerated dose for irinotecan was determined to be 500 mg/m(2). Conclusions: The recommended phase II dose of irinotecan in combination with temozolomide for patients receiving EIAEDs is 500 mg/m(2), administrated every 15 days on a 28-day schedule. This study also confirmed that concomitant administration of EIAEDs increases irinotecan clearance and influences SN-38 disposition. No pharmacokinetic interaction was observed between temozolomide and irinotecan. C1 Univ Texas Houston, MD Anderson Canc Ctr, Unit 431, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Calif San Francisco, Neurooncol Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan Hosp, Dept Neurol, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Med Ctr Canc Pavilion, Pittsburgh, PA USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. Univ Wisconsin Hosp, Madison, WI USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Yung, WKA (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, Unit 431, Dept Neurooncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM wyung@mdanderson.org FU NCI NIH HHS [U01CA62399, U01 CA062399, U01CA62426, UM1 CA137443, U01CA62412, U01 CA062426, U01 CA062412] NR 35 TC 14 Z9 14 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 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2007 VL 13 IS 23 BP 7133 EP 7138 DI 10.1158/1078-0432.CCR-07-0874 PG 6 WC Oncology SC Oncology GA 239PA UT WOS:000251529000030 PM 18056194 ER PT J AU Hassan, R Broaddus, VC Wilson, S Liewehr, DJ Zhang, J AF Hassan, Raffit Broaddus, V. Courtney Wilson, Shannon Liewehr, David J. Zhang, Jingli TI Anti-mesothelin immunotoxin SS1P in combination with gemcitabine results in increased activity against mesothelin-expressing tumor xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID OVARIAN-CANCER; ANTITUMOR-ACTIVITY; MALIGNANT MESOTHELIOMA; MONOCLONAL-ANTIBODY; CHEMOTHERAPY PLUS; PANCREAS CANCER; PHAGE DISPLAY; HIGH-AFFINITY; LUNG-CANCER; PHASE-II AB Purpose: To determine the antitumor activity of the anti-mesothelin immunotoxin SS1P in combination with gemcitabine against mesothelin-expressing tumor xenografts. Experimental Design: The in vitro activity of SS1P in combination with gemcitabine against the mesothelin-expressing cell line A431/K5 was evaluated using cytotoxicity and apoptosis assays. The antitumor activity of this combination was evaluated in nude mice bearing A431/K5 tumor xenografts. Tumor-bearing mice were treated with different doses and schedules of gemcitabine alone, SS1P alone (0.2 mg/kg i.v. every other day x three doses), or with both agents together, and tumor volumes were measured over time. Results: In vitro studies failed to show the synergy of SS1P plus gemcitabine against the mesothelin-expressing A431/K5 cells. In contrast, in the in vivo setting, there was a marked synergy when SS1P was combined with gemcitabine for the treatment of mesothelin-expressing tumor xenografts. This synergy was present using different doses and schedules of gemcitabine administration. In mice treated with fractionated doses of gemcitabine in combination with SS1P, complete tumor regression was observed in all mice and was long-lasting in 60% of the animals. Also, this antitumor activity was specific to SS1P because HA22, an immunotoxin targeting CD22 not expressed on A431/K5 cells, did not increase the efficacy of gemcitabine. Conclusions: SS1P in combination with gemcitabine results in marked antitumor activity against mesothelin-expressing tumors. This combination could be potentially useful for the treatment of human cancers that express mesothelin and are responsive to gemcitabine therapy. C1 NCI, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. San Francisco Gen Hosp, Lung Biol Ctr, San Francisco, CA 94110 USA. RP Hassan, R (reprint author), NCI, Ctr Canc Res, Mol Biol Lab, 37 Convent Dr,Room 5116, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [R01 CA95671] NR 31 TC 43 Z9 44 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 DEC 1 PY 2007 VL 13 IS 23 BP 7166 EP 7171 DI 10.1158/1078-0432.CCR-07-1592 PG 6 WC Oncology SC Oncology GA 239PA UT WOS:000251529000034 PM 18056197 ER PT J AU Goodwin, RS Wilkins, DG Averin, O Choo, RE Schroeder, JR Jasinski, DR Johnson, RE Jones, HE Huestis, MA AF Goodwin, Robert S. Wilkins, Diana G. Averin, Olga Choo, Robin E. Schroeder, Jennifer R. Jasinski, Donald R. Johnson, Rolley E. Jones, Hendree E. Huestis, Marilyn A. TI Buprenorphine and norbuprenorphine in hair of pregnant women and their infants after controlled buprenorphine administration SO CLINICAL CHEMISTRY LA English DT Article ID DEALKYLATED METABOLITE; METHADONE; EXPOSURE; MOTHERS AB Background: Buprenorphine is under investigation as a pharmacotherapeutic agent for treating opioid dependence in pregnant women. We hypothesized that there would be a relationship between the cumulative maternal dose. of buprenorphine during pregnancy and the concentration of buprenorphine and norbuprenorphine in maternal and infant hair. Methods: This study examined buprenorphine and norbuprenorphine concentrations in hair obtained from 9 buprenorphine-maintained pregnant women and 4 of their infants. Specimens were analyzed by liquid chromatography-tandem mass spectrometry with limits of quantification of 3.0 pg/mg. All maternal hair specimens Were washed with methylene chloride before analysis, and when sufficient amounts of maternal hair were available, specimens also were analyzed without washing, Infant hair specimens were not washed. Results: Buprenorphine concentrations were significantly greater in unwashed hair than washed hair (P = 0.031). Norbuprenorphine concentrations were significantly greater than buprenorphine concentrations in both maternal (P = 0.0097) and infant hair (P = 0.0033). There were statistically significant associations between the cumulative maternal dose of buprenorphine administered and the concentrations of buprenorphine (washed, P < 0.0001; unwashed, P = 0.0004), norbuprenorphine (washed, P < 0.0001; unwashed, P = 0.0005), and buprenorphine plus norbuprenorphine (washed, P < 0.0001; unwashed, P = 0.0005) for both washed and unwashed maternal hair specimens. There was a significant positive association between concentrations of buprenorphine and norbuprenorphine in maternal hair (washed, P < 0.0001; unwashed, P = 0.0003), a trend for this association in infant hair (P = 0.08), and an association between buprenorphine concentrations in maternal unwashed hair and infant hair (P = 0.0002). The buprenorphine:norbuprenorphine ratio increased in distal segments. Conclusion: Buprenorphine treatment during gestation provides an opportunity for monitoring drug disposition in maternal and fetal tissues under controlled conditions. (C) 2007 American Association for Clinical Chemistry. C1 Natl Inst Drug Abuse, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Univ Utah, Dept Pharmacol & Toxicol, Ctr Human Toxicol, Salt Lake City, UT 84112 USA. Univ Pittsburgh, Dept Biol, Titusville, PA USA. Natl Inst Drug Abuse, Off Clin Director, Intramural Res Program, NIH, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Reckitt Benckiser Pharmaceut Inc, Richmond, VA USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Chem & Drug Metab Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [M01RR-02719]; NIDA NIH HHS [DA R01 12220] NR 16 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2007 VL 53 IS 12 BP 2136 EP 2143 DI 10.1373/clinchem.2007.091413 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 236CR UT WOS:000251281100014 PM 17921260 ER PT J AU Song, EQ Wang, GP Xie, HY Zhang, ZL Hu, J Peng, J Wu, DC Shi, YB Pang, DW AF Song, Er-Qun Wang, Guo-Ping Xie, Hai-Yan Zhang, Zhi-Ling Hu, Jun Peng, Jun Wu, Dao-Cheng Shi, Yun-Bo Pang, Dai-Wen TI Visual recognition and efficient isolation of apoptotic cells with a fluorescent-magnetic-biotargeting multifunctional nanospheres SO CLINICAL CHEMISTRY LA English DT Article ID IRON-OXIDE NANOPARTICLES; QUANTUM DOTS; IMMUNOMAGNETIC SELECTION; PLASMA-CELLS; ANNEXIN-V; SEPARATION; NANOCRYSTALS; PROTEIN; PURIFICATION; QUANTITATION AB Background: Fluorescent-magnetic-biotargeting multifunctional nanospheres are likely to find important applications in bioanalysis, biomedicine, and clinical diagnosis. We have been developing such multifunctional nanospheres for biomedical applications. Methods: We covalently coupled avidin onto the surfaces of fluorescent-magnetic bifunctional nanospheres to construct fluorescent-magnetic-biotargeting trifunctional nanospheres and analyzed the functionality and specificity of these trifunctional nanospheres for their ability to recognize and isolate apoptotic cells labeled with biotinylated annexin V, which recognizes phosphatidylserine exposed on the surfaces of apoptotic cells. Results: The multifunctional nanospheres can be used in combination with propidium iodide staining of nuclear DNA to identify cells at different phases of the apoptotic process. Furthermore, we demonstrate that apoptotic cells induced by exposure to ultraviolet light can be isolated simply with a magnet from living cells at an efficiency of at least 80%; these cells can then be easily visualized with a fluorescence microscope. Conclusions: Our results show that fluorescent-magnetic-biotargeting trifunctional nanospheres can be a powerful tool for rapidly recognizing, magnetically enriching and sorting, and simultaneously identifying different kinds of cells. (C) 2007 American Association for Clinical Chemistry. C1 Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Peoples R China. Wuhan Univ, State Key Lab Virol, Wuhan 430072, Peoples R China. Beijing Inst Technol, Sch Life Sci & Technol, Beijing 100081, Peoples R China. Xian Jiaotong Univ, Sch Life Sci & Technol, Xian 710049, Peoples R China. NICHHD, Sect Mol Morphogenesis, Program Cell Regulat & Metab, NIH, Bethesda, MD 20892 USA. RP Pang, DW (reprint author), Wuhan Univ, Coll Chem & Mol Sci, Wuhan 430072, Peoples R China. EM dwpang@whu.edu.cn RI Zhang, Zhi-Ling/B-3135-2010 OI Zhang, Zhi-Ling/0000-0001-7807-2264 FU Intramural NIH HHS NR 40 TC 46 Z9 49 U1 3 U2 30 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2007 VL 53 IS 12 BP 2177 EP 2185 DI 10.1373/clinchem.2007.092023 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 236CR UT WOS:000251281100019 PM 17962366 ER PT J AU McConnell, RJ Brenner, AV Oliynyk, VA Robbins, J Terekhova, GM Fink, DJ Epshtein, OV Hatch, M Shpak, VM Brill, AB Shelkovoy, YA Zablotska, LB Masnyk, IJ Howe, GR Tronko, MD AF McConnell, Robert J. Brenner, Alina V. Oliynyk, Valery A. Robbins, Jacob Terekhova, Galyna M. Fink, Daniel J. Epshtein, Ovsiy V. Hatch, Maureen Shpak, Victor M. Brill, A. Bertrand Shelkovoy, Yevgeniy A. Zablotska, Lydia B. Masnyk, Ihor J. Howe, Geoffrey R. Tronko, Mykola D. TI Factors associated with elevated serum concentrations of anti-TPO antibodies in subjects with and without diffuse goitre. Results from the Ukrainian-American Cohort Study of thyroid cancer and other thyroid diseases following the Chornobyl accident SO CLINICAL ENDOCRINOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; SURVEY NHANES-III; IODINE DEFICIENCY; ENDEMIC GOITER; AUTOIMMUNE-THYROIDITIS; NORTHWESTERN GREECE; NATIONAL-HEALTH; WHICKHAM SURVEY; DOUBLE-BLIND; IODIZED OIL AB Objectives To examine factors associated with the prevalence of elevated anti-thyroid peroxidase antibodies (ATPO) among iodine-deficient adolescents and young adults and test whether associations vary according to the presence of diffuse goitre. Design Subjects were members of the Ukrainian-American Cohort Study exposed to the Chornobyl accident whose 131 I thyroid dose estimates were below 0 center dot 2 Gy. Measurements The odds ratios (ORs) for ATPO above 60 U/ml were estimated using logistic regression models for a number of factors in the total population (N = 5133), and separately for thyroid disease-free subjects (N = 3875), those with diffuse goitre (N = 921), and diffuse goitre without autoimmune thyroiditis (AIT; N = 883). Results Elevated ATPO was found in 9 center dot 9% of the total population and ORs were significantly higher in females, older individuals, those examined in earlier calendar years, residents of Kyiv and Chernihiv oblasts, subjects with a family history of thyroid disease, higher thyroid ultrasound volume, suppressed or elevated TSH, blood collection in March to May, very low thyroglobulin (Tg), and shorter serum storage time. When thyroid disease-free subjects and those with diffuse goitre were compared, there were few differences in antibody prevalence, and after excluding individuals with AIT, the only difference was an increased prevalence of elevated ATPO at low urinary iodine in those with goitre alone. Conclusions Although a number of factors are associated with the prevalence of elevated ATPO in our study group, with the exception of urinary iodine these factors are independent of goitre, and differences between thyroid disease-free subjects and those with diffuse goitre are largely due to AIT. C1 Columbia Univ, New York, NY USA. Natl Canc Inst, Bethesda, MD USA. Inst Endocrinol & Metab, Kiev, Ukraine. NIDDK, Bethesda, MD USA. Vanderbilt Univ, Nashville, TN USA. RP McConnell, RJ (reprint author), Thyroid Ctr, Room 210,161 Ft Washington Ave, New York, NY 10032 USA. EM rjm1@columbia.edu RI Brill, Aaron/H-3732-2014 OI Brill, Aaron/0000-0001-7538-086X FU Intramural NIH HHS NR 57 TC 2 Z9 2 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2007 VL 67 IS 6 BP 879 EP 890 DI 10.1111/j.1365-2265.2007.02979.x PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 232NC UT WOS:000251025400011 PM 18052943 ER PT J AU Kitajiri, SI McNamara, R Makishima, T Husnain, T Zafar, AU Kittles, RA Ahmed, ZM Friedman, TB Griffith, AJ AF Kitajiri, S-I McNamara, R. Makishima, T. Husnain, T. Zafar, A. U. Kittles, R. A. Ahmed, Z. M. Friedman, T. B. Griffith, Andrew J. TI Identities, frequencies and origins of TMC1 mutations causing DFNB7/B11 deafness in Pakistan SO CLINICAL GENETICS LA English DT Article DE deafness; epidemiology; founder; genetic; hearing; mutation; recessive; TMC1 ID HEARING-LOSS DFNA36; GENE FAMILY; MOUSE MODEL; DOMINANT; LOCUS; BEETHOVEN AB Non-syndromic deafness is genetically heterogeneous. We previously reported that mutations of transmembrane channel-like gene 1 (TMC1) cause non-syndromic recessive deafness at the DFNB7/B11 locus on chromosome 9q13-q21 in nine Pakistani families. The goal of this study was to define the identities, origins and frequencies of TMC1 mutations in an expanded cohort of 557 large Pakistani families segregating recessive deafness. We screened affected family members for homozygosity at short-tandem repeats flanking known autosomal recessive (DFNB) deafness loci, followed by TMC1 sequence analysis in families segregating deafness linked to DFNB7/B11. We identified 10 new families segregating DFNB7/B11 deafness and TMC1 mutations, including three novel alleles. Overall, 9 different TMC1 mutations account for deafness in 19 (3.4%) of the 557 Pakistani families. A single mutation, p.R34X, causes deafness in 10 (1.8%) of the families. Genotype analysis of p.R34X-linked markers indicates that it arose from a common founder. We also detected p.R34X among normal control samples of African-American and northern European origins, raising the possibility that p.R34X and other mutations of TMC1 are prevalent contributors to the genetic load of deafness across a variety of populations and continents. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Otolaryngol Branch, Rockville, MD 20850 USA. Univ Texas, Med Branch, Dept Otolaryngol, Galveston, TX 77550 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Genet Mol Lab, Rockville, MD USA. Univ Punjab, Natl Ctr Excellencce Mol Biol, Lahore, Pakistan. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Griffith, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Otolaryngol Branch, 5 Res Court,Rm 2A01, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov RI Husnain, Tayyab/G-3805-2015 FU Intramural NIH HHS NR 18 TC 35 Z9 37 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD DEC PY 2007 VL 72 IS 6 BP 546 EP 550 DI 10.1111/j.1399-0004.2007.00895.x PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 230ZQ UT WOS:000250915800010 PM 17877751 ER PT J AU Bai, O Lin, P Vorbach, S Li, J Furlani, S Hallett, M AF Bai, Ou Lin, Peter Vorbach, Sherry Li, Jiang Furlani, Steve Hallett, Mark TI Exploration of computational methods for classification of movement intention during human voluntary movement from single trial EEG SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE movement intention; self-paced movement; combination; computational methods; classification; movement-related cortical potentials (MRCPs); event-related desynchronization/synchronization (ERD/ERS); genetic algorithm; brain-computer interface (BCI) ID BRAIN-COMPUTER-INTERFACE; EVENT-RELATED DESYNCHRONIZATION; SUPPORT VECTOR MACHINES; INDEPENDENT COMPONENT ANALYSIS; THOUGHT TRANSLATION DEVICE; SLOW CORTICAL POTENTIALS; MOTOR IMAGERY TASKS; HIGH-RESOLUTION EEG; FEATURE-SELECTION; SOURCE LOCALIZATION AB Objective: To explore effective combinations of computational methods for the prediction of movement intention preceding the production of self-paced right and left hand movements from single trial scalp electroencephalogram (EEG). Methods: Twelve naive subjects performed self-paced movements consisting of three key strokes with either hand. EEG was recorded from 128 channels. The exploration was performed offline on single trial EEG data. We proposed that a successful computational procedure for classification would consist of spatial filtering, temporal filtering, feature selection, and pattern classification. A systematic investigation was performed with combinations of spatial filtering using principal component analysis (PCA), independent component analysis (ICA), common spatial patterns analysis (CSP), and surface Laplacian derivation (SLD); temporal filtering using power spectral density estimation (PSD) and discrete wavelet transform (DWT); pattern classification using linear Mahalanobis distance classifier (LMD), quadratic Mahalanobis distance classifier (QMD), Bayesian classifier (BSC), multi-layer perceptron neural network (MLP), probabilistic neural network (PNN), and support vector machine (SVM). A robust multivariate feature selection strategy using a genetic algorithm was employed. Results: The combinations of spatial filtering using ICA and SLD, temporal filtering using PSD and DWT, and classification methods using LMD, QMD, BSC and SVM provided higher performance than those of other combinations. Utilizing one of the better combinations of ICA, PSD and SVM, the discrimination accuracy was as high as 75%. Further feature analysis showed that beta band EEG activity of the channels over right sensorimotor cortex was most appropriate for discrimination of right and left hand movement intention. Conclusions: Effective combinations of computational methods provide possible classification of human movement intention from single trial EEG. Such a method could be the basis for a potential brain-computer interface based on human natural movement, which might reduce the requirement of long-term training. Significance: Effective combinations of computational methods can classify human movement intention from single trial EEG with reasonable accuracy. Published by Elsevier Ireland Ltd. C1 [Bai, Ou; Lin, Peter; Vorbach, Sherry; Furlani, Steve; Hallett, Mark] Natl Inst Neurol Disorders, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Li, Jiang] Old Dominion Univ, Dept Elect & Comp Engn, VMASC, Norfolk, VA 23529 USA. RP Bai, O (reprint author), Natl Inst Neurol Disorders, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. EM obai@vcu.edu FU Intramural NIH HHS [NIH0011402999, Z01 NS002669-23] NR 83 TC 59 Z9 63 U1 0 U2 23 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD DEC PY 2007 VL 118 IS 12 BP 2637 EP 2655 DI 10.1016/j.clinph.2007.08.025 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 249CQ UT WOS:000252204900009 PM 17967559 ER PT J AU Myers, RM Greiner, SM Harvey, ME Griesmann, G JKuffel, M Buhrow, SA Reid, JM Federspiel, M Ames, MM Dingli, D Schweikart, K Welch, A Dispenzieri, A Peng, KW Russell, SJ AF Myers, R. M. Greiner, S. M. Harvey, M. E. Griesmann, G. JKuffel, M. Buhrow, S. A. Reid, J. M. Federspiel, M. Ames, M. M. Dingli, D. Schweikart, K. Welch, A. Dispenzieri, A. Peng, K-W Russell, S. J. TI Preclinical pharmacology and toxicology of intravenous MV-NIS, an oncolytic measles virus administered with or without cyclophosphamide SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GENETICALLY-MODIFIED MICE; SODIUM-IODIDE SYMPORTER; OVARIAN-CANCER; CARCINOEMBRYONIC ANTIGEN; IMMUNE-RESPONSES; TRANSGENIC MICE; THERAPY; RECEPTOR; VIROTHERAPY; INFECTION AB MV-NIS is an oncolytic measles virus encoding the human thyroidal sodium iodide symporter (NIS). Here, we report the results of preclinical pharmacology and toxicology studies conducted in support of our clinical protocol "Phase I Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, with or without Cyclophosphamide, in Patients with Recurrent or Refractory Multiple Myeloma.'' Dose-response studies in the KAS-6/1 myeloma xenograft model demonstrated a minimum effective dose of 4 x 10(6) TCID50 (tissue culture infectious dose 50)/kg. Toxicity studies in measles-naive squirrel monkeys and measles-susceptible transgenic mice were negative at intravenous doses up to 10(8) and 4 x 10(8) TCID50/kg, respectively. Abundant viral mRNA, maximal on day 8, was detected in cheek swabs of squirrel monkeys, more so after pretreatment with cyclophosphamide. On the basis of these data, the safe starting dose of MV-NIS for our clinical protocol was set at 1-2 x 10(4) TCID50/kg (10(6) TCID50 per patient). C1 Mayo Clin, Dept Mol Med, Rochester, MN 55905 USA. Mayo Clin, Toxicol Core, Rochester, MN USA. Mayo Clin, Viral Vector Prod Lab, Rochester, MN USA. Mayo Clin, Dept Pharmacol & Expt Therapeut, Rochester, MN USA. Mayo Clin, Div Hematol, Rochester, MN USA. NCI, Dev Therapeut Program, Toxicol & Pharmacol Branch, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Biol Resources Branch, Frederick, MD 21701 USA. RP Russell, SJ (reprint author), Mayo Clin, Dept Mol Med, Rochester, MN 55905 USA. EM sjr@mayo.edu RI Dingli, David/B-6355-2008; OI Dispenzieri, Angela/0000-0001-8780-9512 FU NCI NIH HHS [R01 CA100634, CA100634, CA118488, R01 CA100634-04, R01 CA118488, R01 CA118488-03] NR 36 TC 62 Z9 63 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2007 VL 82 IS 6 BP 700 EP 710 DI 10.1038/sj.clpt.6100409 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 233JE UT WOS:000251086400019 PM 17971816 ER PT J AU Finlayson, TL Siefert, K Ismail, AI Sohn, W AF Finlayson, Tracy L. Siefert, Kristine Ismail, Amid I. Sohn, Woosung TI Psychosocial factors and early childhood caries among low-income African-American children in Detroit SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE African-American; Early Childhood Caries (ECC); International Caries Detection and Assessment System (ICDAS); parenting stress; preschool aged children; psychological factors ID DENTAL-HEALTH EDUCATION; BOTTLE TOOTH-DECAY; ORAL-HEALTH; PRESCHOOL-CHILDREN; DEPRESSIVE SYMPTOMS; SINGLE MOTHERS; NURSING CARIES; SELF-EFFICACY; PREVALENCE; WELFARE AB Objectives: This study sought to advance knowledge of the social determinants of oral health, by examining how several specific maternal health beliefs, behaviors, and psychosocial factors relate to young children's early childhood caries (ECC) status in a lower-income African-American population. Methods: Data were collected by the Detroit Dental Health Project (NIDCR grant), a population-based study of 1021 African-American families with at least one child under 6 years of age and living in 39 low-income Census tracts in Detroit, Michigan. Analyses were limited to 719 children aged 1-5 years and their biological mothers, and conducted in SUDAAN to account for the complex sampling design. Survey data included health belief scales on mothers' self-efficacy, feelings of fatalism, knowledge about appropriate bottle use and children's oral hygiene needs, brushing habits, psychosocial measures of depressive symptoms (CES-D), parenting stress, and availability of instrumental social support. The child's age, dental insurance status, dental visit history, and 1-week brushing frequency were also included in the model. Children's ECC status, based on a dental examination, was the main outcome. The dental team used the International Caries Detection and Assessment System (ICDAS) criteria for caries detection. Each child was classified as either caries-free or having ECC or severe ECC (S-ECC) based on the case definition of ECC proposed by an expert panel for research purposes with preschool-aged children. Results: The dental team followed a specific examination protocol and established reliable and consistent ratings of ECC based on the ICDAS criteria. The inter-rater reliability kappa was 0.83 overall, and the intra-rater reliability kappa was 0.74 overall. One-third of the children had ECC, and 20% had severe ECC. Age of the child and lower parenting stress scores were each positively associated with ECC, while higher education and income were protective. Maternal oral health fatalism and knowledge of children's hygiene needs were associated with ECC among preschool-aged children. ECC was higher among younger children who had past restorative care. Conclusions: These findings call attention to the high prevalence of ECC in this population and the need to consider psychosocial as well as traditional risk factors in developing interventions to reduce oral health disparities. C1 Univ Calif Berkeley, Sch Publ Hlth, AHRQ, Berkeley, CA 94720 USA. Univ Michigan, NIMH Res Ctr Poverty Risk & Mental Hlth, Sch Social Work, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. RP Finlayson, TL (reprint author), Univ Calif Berkeley, Sch Publ Hlth, AHRQ, 140 E Warren Hall MC 7360, Berkeley, CA 94720 USA. EM tracyf@berkeley.edu OI Sohn, Woosung/0000-0002-7486-9652 FU NIDCR NIH HHS [U-54 DE14261]; NIMH NIH HHS [5 T32MH16806] NR 74 TC 66 Z9 67 U1 2 U2 24 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD DEC PY 2007 VL 35 IS 6 BP 439 EP 448 DI 10.1111/j.1600-0528.2006.00352.x PG 10 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 234TK UT WOS:000251186700005 PM 18039285 ER PT J AU Poursharif, B Korst, LA MacGibbon, KW Fejzo, MS Romero, R Goodwin, TM AF Poursharif, Borzouyeh Korst, Lisa A. MacGibbon, Kimber W. Fejzo, Marlena S. Romero, Roberto Goodwin, T. Murphy TI Elective pregnancy termination in a large cohort of women with hyperemesis gravidarum SO CONTRACEPTION LA English DT Article; Proceedings Paper CT 55th Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY MAY 05-09, 2007 CL San Diego, CA SP Amer Coll Obstetricians & Gynecologists DE hyperemesis gravidarum; nausea; vomiting; pregnancy ID WERNICKES ENCEPHALOPATHY; NAUSEA; OUTCOMES AB Background: This study was conducted to describe characteristics of women who terminated their pregnancies secondary to hyperemesis gravidarum (HG). Study Design: Data were obtained from a survey provided on an HG Web site from 2003 to 2005. Results: Of 808 women who completed the survey, 123 (15.2%) had at least one termination due to HG, and 49 (6.1%) had multiple terminations. Prominent reasons given for the terminations were inability to care for the family and self (66.7%), fear that they or their baby could die (51.2%), or that the baby would be abnormal (22.0%). These same women were three times as likely to state that their health care providers were uncaring or did not understand how sick they were [64/123 (52.0%) vs. 168/685 (24.5%), odds ratio 3.34 (95% Cl 2.21-5.05), p<.001]. Conclusion: These data suggest that the physical and psychological burden of HG has been underestimated, and that further education within the medical community may be warranted. (c) 2007 Elsevier Inc. All rights reserved. C1 [Poursharif, Borzouyeh; Korst, Lisa A.; Fejzo, Marlena S.; Goodwin, T. Murphy] Univ So Calif, LAC USC Womens & Childrens Hosp, Keck Sch Med, Dept Obstet & GynecolDiv Maternal Fetal Med, Los Angeles, CA 90033 USA. [MacGibbon, Kimber W.] Hypermesis Educ & Res Fdn, Leesburg, VA 20176 USA. [Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. RP Korst, LA (reprint author), Univ So Calif, LAC USC Womens & Childrens Hosp, Keck Sch Med, Dept Obstet & GynecolDiv Maternal Fetal Med, 5K40, Los Angeles, CA 90033 USA. EM korst@usc.edu OI MacGibbon, Kimber/0000-0002-6534-3114 FU Intramural NIH HHS NR 18 TC 27 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD DEC PY 2007 VL 76 IS 6 BP 451 EP 455 DI 10.1016/j.contraception.2007.08.009 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 241KZ UT WOS:000251656600007 PM 18061703 ER PT J AU Eichacker, PQ Natanson, C Danner, RL AF Eichacker, Peter Q. Natanson, Charles Danner, Robert L. TI Separating practice guidelines from pharmaceutical marketing SO CRITICAL CARE MEDICINE LA English DT Letter ID SURVIVING SEPSIS CAMPAIGN; GOAL-DIRECTED THERAPY; CONFLICTS-OF-INTEREST; ACTIVATED PROTEIN-C; SEPTIC SHOCK; INDUSTRY; MANAGEMENT C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bldg 10, Bethesda, MD 20892 USA. NR 26 TC 6 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 BP 2877 EP 2878 DI 10.1097/01.CCM.0000288106.55246.A5 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 237BD UT WOS:000251346700040 PM 18043217 ER PT J AU Chalfin, DB Levy, M Danis, M Rapoport, J Lemeshow, S Phillips, G AF Chalfin, Donald B. Levy, Mitchell Danis, Marion Rapoport, John Lemeshow, Stanley Phillips, Gary TI Impact of ICU management upon resource use SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Chalfin, Donald B.] Analyt Int, New York, NY USA. [Levy, Mitchell] Brown Univ, Sch Med, Providence, RI 02912 USA. [Danis, Marion] NIH, Bethesda, MD 20892 USA. [Rapoport, John] Mt Holyoke Coll, S Hadley, MA 01075 USA. [Lemeshow, Stanley; Phillips, Gary] Ohio State Univ, Columbus, OH 43210 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 607 BP A168 EP A168 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398901088 ER PT J AU Hong, SK Jang, G Pasula, R Zhang, D Martin, WJ AF Hong, Suk-Kyung Jang, Geundoo Pasula, Raj Zhang, Donglin Martin, William J. TI Alpha1-antitrypsin protect endotoxin induced acute lung injury in mice SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Hong, Suk-Kyung; Jang, Geundoo] Asan Med Ctr, Seoul, South Korea. [Pasula, Raj; Zhang, Donglin] Univ Cincinnati, Cincinnati, OH USA. [Martin, William J.] NIEHS, Translat Res Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 236 BP A60 EP A60 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398900210 ER PT J AU Klaschik, S Klinman, DM AF Klaschik, Sven Klinman, Dennis M. TI CpG DNA mediated toll-like receptor 9 activation in vivo induces two distinct pattern of gene expression SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Klaschik, Sven; Klinman, Dennis M.] NCI, NIH, LMI, CIP, Frederick, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 198 BP A48 EP A48 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398900171 ER PT J AU Meert, K Shear, K AF Meert, Kathleen Shear, Katherine TI Complicated grief in parents whose child has died in the PICU SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Meert, Kathleen] Wayne State Univ, Detroit, MI USA. Columbia Univ, New York, NY USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 674 BP A187 EP A187 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398901155 ER PT J AU Park, PK Bartlett, RH Rosenberg, AL Dechert, RE AF Park, Pauline K. Bartlett, Robert H. Rosenberg, Andrew L. Dechert, Ronald E. TI Influence of cumulative fluid balance on outcome in ARDS: A retrospective review of the ARD-SNET ARMA trials cohort SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Park, Pauline K.; Bartlett, Robert H.; Rosenberg, Andrew L.; Dechert, Ronald E.] Univ Michigan, Ann Arbor, MI 48109 USA. NHLBI, NIH, ARDSNet, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 54 BP A14 EP A14 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398900056 ER PT J AU Wardenburg, JB Schneewind, O Bae, T Otto, M De Leo, F AF Wardenburg, Juliane Bubeck Schneewind, Olaf Bae, Ted Otto, Michael De Leo, Frank TI Vaccine protection against Staphylococcus aureus pneumonia SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 37th Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 02-08, 2008 CL Honolulu, HI SP Soc Crit Care Med C1 [Wardenburg, Juliane Bubeck; Schneewind, Olaf] Univ Chicago, Chicago, IL USA. [Bae, Ted] Indiana Univ, Sch Med NW, Gary, IN USA. [Otto, Michael; De Leo, Frank] Rocky Mt Lab, Hamilton, MT 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2007 VL 35 IS 12 SU S MA 199 BP A48 EP A48 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 237TI UT WOS:000251398900173 ER PT J AU Liu, XD Jia, L AF Liu, Xiaodong Jia, Lee TI The conduct of drug metabolism studies considered good practice (I): Analytical systems and in vivo studies SO CURRENT DRUG METABOLISM LA English DT Review DE analytical techniques; drug regulations; in vivo drug metabolism; interspecies differences; major drug metabolites; metabolite identification; radiolabeled drug; pharmacokinetics ID MASS-SPECTROMETRY; P-GLYCOPROTEIN; LABORATORY-ANIMALS; S-NITROSOCAPTOPRIL; RAT PLASMA; ESI-MS; PHARMACOKINETICS; HUMANS; MODEL; BIOAVAILABILITY AB This review serial outlines practical and scientifically-based approaches to conducting contemporary drug metabolism studies considered good practice for drug development and regulatory filing. The present part addresses analytical methods used in the drug metabolism studies and evaluates advantages and disadvantages of these methods as well as the related sample preparations. The methods described here cover from conventional radioactive labeling of drugs, which includes selection of a proper radioisotope, its labeling position, and modern radio-pharmacokinetics employed in microdosing by using a radionuclide to visualize drug distribution in vivo, to currently widely-used liquid chromatography (LC) in conjunction with mass spectrometry (MS), tandem mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) for quantitative detection of metabolites and characterization of their structures. Although the analytical tools have progressed sufficiently to allow determination of metabolites, proper in vitro models and in vivo studies have to be carefully designed in order to understand drug metabolism. Points for consideration when conducting in vivo drug metabolism studies include interspecies differences in systemic exposure and metabolism pathways, identification of the major metabolites and unique human metabolites that become the regulatory focus, local metabolism in addition to liver metabolism, time points for sampling, and synthesis of the authentic metabolites to confirm their formation. The next part of this serial article will focus on in vitro drug metabolism studies. C1 China Pharmaceut Univ, Ctr Drug Met & Pharmacokinet, Nanjing 210009, Peoples R China. Natl Canc Inst, NIH, Dev Therapeut Program, Toxicol & Pharmacol Branch, Rockville, MD 20852 USA. RP Jia, L (reprint author), Rm 8042, 6130 Executive Blvd, Rockville, MD 20852 USA. EM jiale@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 54 TC 27 Z9 28 U1 1 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2002 J9 CURR DRUG METAB JI Curr. Drug Metab. PD DEC PY 2007 VL 8 IS 8 BP 815 EP 821 DI 10.2174/138920007782798153 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 235BO UT WOS:000251208700008 PM 18220562 ER PT J AU Jia, L Liu, XD AF Jia, Lee Liu, Xiaodong TI The conduct of drug metabolism studies considered good practice (II): In vitro experiments SO CURRENT DRUG METABOLISM LA English DT Review DE cytochrome P450 enzymes; drug regulations; hepatocytes; in vitro drug metabolism; microsomes ID HUMAN LIVER-MICROSOMES; MONOXIDE-BINDING PIGMENT; CYTOCHROME-P450 ENZYMES; RAT HEPATOCYTES; INDUCTION; IDENTIFICATION; DEXAMETHASONE; P-450; PHARMACOKINETICS; DISCOVERY AB In vitro drug metabolism studies, which are inexpensive and readily carried out, serve as an adequate screening mechanism to characterize drug metabolites, elucidate their pathways, and make suggestions for further in vivo testing. This publication is a sequel to part I in a series and aims at providing a general framework to guide designs and protocols of the in vitro drug metabolism studies considered good practice in an efficient manner such that it would help researchers avoid common pitfalls and misleading results. The in vitro models include hepatic and non-hepatic microsomes, cDNA-expressed recombinant human CYPs expressed in insect cells or human B lymphoblastoid, chemical P450 inhibitors, S9 fraction, hepatocytes and liver slices. Important conditions for conducting the in vitro drug metabolism studies using these models are stated, including relevant concentrations of enzymes, co-factors, inhibitors and test drugs; time of incubation and sampling in order to establish kinetics of reactions; appropriate control settings, buffer selection and method validation. Separate in vitro data should be logically integrated to explain results from animal and human studies and to provide insights into the nature and consequences of in vivo drug metabolism. This article offers technical information and data and addresses scientific rationales and practical skills related to in vitro evaluation of drug metabolism to meet regulatory requirements for drug development. C1 Natl Canc Inst, Natl Inst Hlth, Dev Therapeut Program, Toxicol & Pharmacol Branch, Rockville, MD 20852 USA. China Pharmaceut Univ, Ctr Drug Met & Pharmacokinet, Nanjing 210009, Peoples R China. RP Jia, L (reprint author), Rm 8042, 6130 Executive Blvd, Rockville, MD 20852 USA. EM jiale@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 43 TC 78 Z9 81 U1 2 U2 24 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2002 J9 CURR DRUG METAB JI Curr. Drug Metab. PD DEC PY 2007 VL 8 IS 8 BP 822 EP 829 DI 10.2174/138920007782798207 PG 8 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 235BO UT WOS:000251208700009 PM 18220563 ER PT J AU Schaffer, AA Klein, C AF Schaeffer, Alejandro A. Klein, Christoph TI Genetic heterogeneity in severe congenital neutropenia: how many aberrant pathways can kill a neutrophil? SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE apoptosis; genetics; neutrophil; primary immune deficiency; severe congenital neutropenia ID COLONY-STIMULATING-FACTOR; SHWACHMAN-DIAMOND-SYNDROME; HERMANSKY-PUDLAK-SYNDROME; GLYCOGEN-STORAGE-DISEASE; CHEDIAK-HIGASHI-SYNDROME; CARTILAGE-HAIR HYPOPLASIA; BARTH-SYNDROME; MICE LACKING; FACTOR-RECEPTOR; WHIM-SYNDROME AB Purpose of review Severe congenital neutropenia is a primary immunodeficiency in which lack of neutrophils causes inadequate innate immune host response to bacterial infections. Severe congenital neutropenia occurs with sporadic, autosomal dominant, autosomal recessive and X-linked recessive inheritance, as well as in a variety of multisystem syndromes. A principal stimulus for this review is the identification of novel genetic defects and pathophysiological insights into the role of neutrophil apoptosis. Recent findings The recent findings include identification of mutations in HAX1 in autosomal recessive severe congenital neutropenia (Kostmann disease), a large epidemiological study estimating the risk of progression from severe congenital neutropenia to leukemia, a better understanding of how heterozygous mutations in neutrophil elastase (ELA2) cause severe congenital neutropenia, molecular characterization of a novel syndromic form of severe congenital neutropenia called p14 deficiency and new animal models for several syndromic forms of severe congenital neutropenia. Summary We consider the numerous genes mutated in severe congenital neutropenia, the many attempts to make animal models of severe congenital neutropenia, and the results from both human and mouse studies investigating the molecular mechanisms of neutrophil apoptosis. Investigations of how severe congenital neutropenia genes and apoptosis pathways are connected should lead to a better understanding of the pathogenesis of neutropenia and apoptosis pathways relevant to many cell types. C1 [Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol Oncol, D-30625 Hannover, Germany. [Schaeffer, Alejandro A.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Computat Biol Branch, Bethesda, MD USA. RP Klein, C (reprint author), Hannover Med Sch, Dept Pediat Hematol Oncol, Carl Neuberg Strasse 1, D-30625 Hannover, Germany. EM klein.christoph@mh-hannover.de RI Schaffer, Alejandro/F-2902-2012 FU Intramural NIH HHS [Z01 LM000097-06, Z99 LM999999] NR 149 TC 23 Z9 24 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD DEC PY 2007 VL 7 IS 6 BP 481 EP 494 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 241CH UT WOS:000251634000004 PM 17989524 ER PT J AU Robert-Guroff, M AF Robert-Guroff, Marjorie TI Replicating and non-replicating viral vectors for vaccine development SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; VESICULAR STOMATITIS-VIRUS; HERPES-SIMPLEX-VIRUS; DEPENDENT CELLULAR CYTOTOXICITY; VENEZUELAN EQUINE ENCEPHALITIS; ALPHAVIRUS REPLICON PARTICLES; GENE-BASED VACCINE; MEMORY T-CELLS; IMMUNE-RESPONSES; RHESUS MACAQUES AB Viral vectors provide a convenient means to deliver vaccine antigens to select target cells or tissues. A broad spectrum of replicating and non-replicating vectors is available. An appropriate choice for select applications will depend on the biology of the infectious agent targeted, as well as factors such as whether the vaccine is intended to prevent infection or boost immunity in already infected individuals, prior exposure of the target population to the vector, safety, and the number and size of gene inserts needed. Here several viral vectors under development as HIV/AIDS vaccines are reviewed. A vaccine strategy based on initial priming with a replicating vector to enlist the innate immune system, target mucosal inductive sites, and prime both cellular and humoral systemic and mucosal immune responses is proposed. Subsequently, boosting with a replicating or non-replicating vector and/or protein subunits could lead to induction of necessary levels of protective immunity. C1 Natl Inst Hlth, Natl Canc Inst, Vaccine Branch, Bethesda, MD 20892 USA. RP Robert-Guroff, M (reprint author), Natl Inst Hlth, Natl Canc Inst, Vaccine Branch, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov FU Intramural NIH HHS [Z01 BC005536-20] NR 67 TC 77 Z9 81 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD DEC PY 2007 VL 18 IS 6 BP 546 EP 556 DI 10.1016/j.copbio.2007.10.010 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 257MG UT WOS:000252802600011 PM 18063357 ER PT J AU Zaoutis, T Walsch, TJ AF Zaoutis, Theoklis Walsch, Thomas J. TI Antifungal therapy for neonatal candidiasis SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE antifungal therapy; candidiasis; fungal infections; neonatal; pediatric ID LOW-BIRTH-WEIGHT; INTENSIVE-CARE-UNIT; FLUCONAZOLE PROPHYLAXIS; INVASIVE CANDIDIASIS; FUNGAL COLONIZATION; RECTAL COLONIZATION; RANDOMIZED-TRIAL; AMPHOTERICIN-B; ORAL NYSTATIN; HIGH-RISK AB Purpose of review This review focuses on recent data regarding antifungal prophylaxis and antifungal treatment of neonatal candidiasis. Recent findings Candida species are the leading cause of invasive fungal infection in the neonatal intensive care unit, and are the third most common blood culture isolates recovered from cases of late-onset sepsis in the neonatal intensive care unit. Neonatal candidemia is associated with significant morbidity and mortality. Risk factors for neonatal candidiasis have been elucidated, and prophylaxis of high-risk infants has been found to be effective, particularly in neonatal intensive care units with a high incidence of candidemia. Amphotericin B has been the mainstay of antifungal therapy for candidemia in the neonatal intensive care unit but newer agents such as echinocandins and azoles are currently being evaluated. Summary Neonatal candidiasis is a serious infection especially in extremely low-birthweight infants and prophylaxis has been shown to be effective in preventing candidiasis in high-risk infants. Newer pharmacokinetic, safety and efficacy data for both older and newer antifungal agents are emerging in neonates, and these data may help us achieve more effective management of neonatal candidiasis. C1 Univ Penn, Sch Med, Dept Pediat & Epidemiol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Infect Dis, Antimicrobial Stewardship Program, Philadelphia, PA USA. NIH, Pediat Oncol Branch, Immunocompromised Hosp Sect, Bethesda, MD USA. RP Zaoutis, T (reprint author), Childrens Hosp Philadelphia, 34th & Civic Ctr Blvd,CHOP N,Suite 1527, Philadelphia, PA 19104 USA. EM zaoutis@email.chop.edu NR 36 TC 16 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD DEC PY 2007 VL 20 IS 6 BP 592 EP 597 PG 6 WC Infectious Diseases SC Infectious Diseases GA 237QJ UT WOS:000251390500006 PM 17975409 ER PT J AU Berna, MJ Tapia, JA Sanch, V Jensen, RT AF Berna, Marc J. Tapia, Jose A. Sanch, Veronica Jensen, Robert T. TI Progress in developing cholecystokinin (CCK)/gastrin receptor ligands that have therapeutic potential SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID GASTRIC-ACID-SECRETION; CCK RECEPTORS; B RECEPTOR; RADIONUCLIDE THERAPY; HEALTHY-VOLUNTEERS; PANIC DISORDER; ULCER DISEASE; DOUBLE-BLIND; IN-VITRO; ANTAGONISTS AB Gastrin and cholecystokinin (CCK) are two of the oldest hormones and within the past 15 years there has been an exponential increase in knowledge of their pharmacology, cell biology, receptors (CCK1R and CCK2R), and roles in physiology and pathological conditions. Despite these advances there is no approved disease indication for CCK receptor antagonists and only a minor use of agonists. In this review, the important factors determining this slow therapeutic development are reviewed. To assess this it is necessary to briefly review what is known about the roles of CCK receptors (CCK1R and CCK2R) in normal human physiology, their role in pathologic conditions, the selectivity of available potent CCKR agonists/antagonists as well as to review their use in human conditions to date and the results. Despite extensive studies in animals and in humans, recent studies suggest that monotherapy with CCK1R agonists will not be effective in obesity, nor CCK2R antagonists in panic disorders or CCK2R antagonists to inhibit growth of pancreatic cancer. Areas that require more study include the use of CCK2R agonists for imaging tumors and radiotherapy, CCK2R antagonists in hypergastrinemic states especially with long-term PPI use and for potentiation of analgesia as well as use of CCK1R antagonists for a number of gastrointestinal disorders [motility disorders (irritable bowel syndrome, dyspepsia, and constipation) and pancreatitis (acute and chronic)]. C1 [Berna, Marc J.; Tapia, Jose A.; Sanch, Veronica; Jensen, Robert T.] NIDDK, Digest Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Berna, Marc J.] Univ Hosp Hamburg Eppendorf, Dept Internal Med, Hamburg, Germany. [Tapia, Jose A.] Univ Extremadura, Dept Fisiol, Caceres 10071, Spain. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Tapia, Jose/C-5181-2008 OI Tapia, Jose/0000-0002-3614-6867 FU Intramural NIH HHS [Z01 DK053101-19, Z01 DK053100-19] NR 82 TC 41 Z9 42 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD DEC PY 2007 VL 7 IS 6 BP 583 EP 592 DI 10.1016/j.coph.2007.09.011 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 244HK UT WOS:000251856800006 PM 17997137 ER PT J AU Botos, I Wlodawer, A AF Botos, Istvan Wlodawer, Alexander TI The expanding diversity of serine hydrollases SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID FAMILY INTRAMEMBRANE PROTEASE; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; CATALYTIC DYAD; LON PROTEASES; DOMAIN; ACTIVATION; REVEALS; BINDING; SPECIFICITY AB Serine hydrolases use a hydroxyl of a serine, assisted by one or more other residues, to cleave peptide bonds. They belong to several different families whose general mechanism is well known. However, the subtle structural differences that have recently been observed across a variety of families shed light on their functional diversity, including variations in mechanism of action, differences in the modes of substrate binding, and substrate-assisted orientation of catalytic residues. Of particular interest are the Rhomboid family serine proteinases that are active within the plasma membrane, for which several new structures have been reported. Because these enzymes are involved in biological and pathological processes, many are becoming important targets of drug design. C1 [Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Botos, Istvan] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010348-07] NR 35 TC 13 Z9 13 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD DEC PY 2007 VL 17 IS 6 BP 683 EP 690 DI 10.1016/j.sbi.2007.08.003 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 245EM UT WOS:000251917800008 PM 17890078 ER PT J AU Patel, VN Knox, SM Likar, KM Lathrop, CA Hossain, R Eftekhari, S Whitelock, JM Elkin, M Vlodavsky, I Hoffman, MP AF Patel, Vaishali N. Knox, Sarah M. Likar, Karen M. Lathrop, Colin A. Hossain, Rydhwana Eftekhari, Siavash Whitelock, John M. Elkin, Michael Vlodavsky, Israel Hoffman, Matthew P. TI Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis SO DEVELOPMENT LA English DT Article DE heparanase; FGF10; heparan sulfate; perlecan; salivary gland development ID FIBROBLAST-GROWTH-FACTOR; BETA-D-XYLOSIDE; SALIVARY-GLANDS; MAMMALIAN HEPARANASE; MOLECULAR-PROPERTIES; EPITHELIAL MORPHOGENESIS; CANCER PROGRESSION; RECEPTOR BINDING; TUMOR-GROWTH; IN-VITRO AB Heparan sulfate proteoglycans are essential for biological processes regulated by fibroblast growth factors (FGFs). Heparan sulfate (HS) regulates the activity of FGFs by acting as a coreceptor at the cell surface, enhancing FGF-FGFR affinity, and being a storage reservoir for FGFs in the extracellular matrix (ECM). Here we demonstrate a critical role for heparanase during mouse submandibular gland (SMG) branching morphogenesis. Heparanase, an endoglycosidase, colocalized with perlecan in the basement membrane and in epithelial clefts of SMGs. Inhibition of heparanase activity in organ culture decreased branching morphogenesis, and this inhibition was rescued specifically by FGF10 and not by other FGFs. By contrast, exogenous heparanase increased SMG branching and MAPK signaling and, surprisingly, when isolated epithelia were cultured in a three-dimensional ECM with FGF10, it increased the number of lateral branches and end buds. In a solid-phase binding assay, an FGF10-FGFR2b complex was released from the ECM by heparanase. In addition, surface plasmon resonance (SPR) analysis showed that FGF10 and the FGF10-FGFR2b complex bound to purified perlecan HS and could be released by heparanase. We used the FGF10-FGFR2b complex as a probe for HS in SMGs, and it colocalized with perlecan in the basement membrane and partly colocalized with syndecan 1 in the epithelium, and binding was reduced by treatment with heparanase. In summary, our results show heparanase releases FGF10 from perlecan HS in the basement membrane, increasing MAPK signaling, epithelial clefting, and lateral branch formation, which results in increased branching morphogenesis. C1 Natl Inst Dental & Craniofacial Res, Matrix & Morphogenesis Unit, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20817 USA. Univ New S Wales, Sch Biomed Engn, Sydney, NSW, Australia. Hadassah Hebrew Univ Med Ctr, Dept Oncol, Jerusalem, Israel. Technion Israel Inst Technol, Bruce Rappaport Fac Med, Canc & Vasc Biol Res Ctr, IL-31096 Haifa, Israel. RP Hoffman, MP (reprint author), Natl Inst Dental & Craniofacial Res, Matrix & Morphogenesis Unit, Cellular & Dev Biol Lab, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM mhoffman@mail.nih.gov OI Knox, Sarah/0000-0002-7567-083X FU Intramural NIH HHS NR 65 TC 80 Z9 83 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC 1 PY 2007 VL 134 IS 23 BP 4177 EP 4186 DI 10.1242/dev.011171 PG 10 WC Developmental Biology SC Developmental Biology GA 229DO UT WOS:000250783400006 PM 17959718 ER PT J AU DeLotto, R DeLotto, Y Steward, R Lippincott-Schwartz, J AF DeLotto, Robert DeLotto, Yvonne Steward, Ruth Lippincott-Schwartz, Jennifer TI Nucleocytoplasmic shuttling mediates the dynamic maintenance of nuclear Dorsal levels during Drosophila embryogenesis SO DEVELOPMENT LA English DT Article DE NF-kappa B; gradient formation; transcription factor dynamics; Drosophila ID NF-KAPPA-B; REL PROTEIN DORSAL; SIGNALING PATHWAYS; DEGRADATION ESTABLISHES; MORPHOGEN GRADIENT; VENTRAL PATTERN; EMBRYO; LOCALIZATION; ACTIVATION; CACTUS AB In Drosophila, the NF-kappa B/REL family transcription factor, Dorsal, redistributes from the cytoplasm to nuclei, forming a concentration gradient across the dorsoventral axis of the embryo. Using live imaging techniques in conjunction with embryos expressing a chimeric Dorsal-GFP, we demonstrate that the redistribution of Dorsal from cytoplasm to nucleus is an extremely dynamic process. Nuclear Dorsal concentration changes continuously over time in all nuclei during interphase. While Dorsal appears to be nuclearly localized primarily in ventral nuclei, it is actively shuttling into and out of all nuclei, including nuclei on the dorsal side. Nuclear export is blocked by leptomycin B, a potent inhibitor of Exportin 1 (CRM1)-mediated nuclear export. We have developed a novel in vivo assay revealing the presence of a functional leucine-rich nuclear export signal within the carboxyterminal 44 amino acids of Dorsal. We also find that diffusion of Dorsal is partially constrained to cytoplasmic islands surrounding individual syncitial nuclei. A model is proposed in which the generation and maintenance of the Dorsal gradient is a consequence of an active process involving both restricted long-range diffusion and the balancing of nuclear import with nuclear export. C1 Univ Copenhagen, Dept Mol Biol, DK-2200 Copenhagen N, Denmark. Rutgers State Univ, Dept Mol Biol & Biochem, Waksman Inst, Piscataway, NJ 08854 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP DeLotto, R (reprint author), Univ Copenhagen, Dept Mol Biol, Ole Maaloes Vej 5, DK-2200 Copenhagen N, Denmark. EM rdelotto@my.molbio.ku.dk NR 44 TC 47 Z9 49 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC 1 PY 2007 VL 134 IS 23 BP 4233 EP 4241 DI 10.1242/dev.010934 PG 9 WC Developmental Biology SC Developmental Biology GA 229DO UT WOS:000250783400011 PM 17978003 ER PT J AU Tgarashi, H Knott, JG SchultZ, RM Williams, CJ AF Tgarashi, Hideki Knott, Jason G. SchultZ, Richard M. Williams, Carnien J. TI Alterations of PLC beta 1 in mouse eggs change calcium oscillatory behavior following fertilization SO DEVELOPMENTAL BIOLOGY LA English DT Article DE egg activation; calcium; phospholipase C; RNAi; fertilization; mouse ID PHOSPHOLIPASE-C-ZETA; CA2+ OSCILLATIONS; PHOSPHATIDIC-ACID; ADENYLATE-CYCLASE; CAMKII ACTIVITY; HAMSTER EGGS; SPERM; ACTIVATION; OOCYTES; CELL AB Inositol 1,4,5-trisphosphate generated by the action of a phospholipase C (PLC) mediates release of intracellular Ca2+ that is essential for sperm-induced activation of mammalian eggs. Much attention currently focuses on the role of sperm-derived PLC in generating changes in egg intracellular Ca2+ despite the fact that PLC zeta constitutes a very small fraction of the total amount of PLC in a fertilized egg. Eggs express several isoforms of PLC, but a role for an egg-derived PLC in sperm-induced Ca2+ oscillations has not been examined. Reducing egg PLC beta 1 I by a transgenic RNAi approach resulted in a significant decrease in Ca2+ transient amplitude, but not duration or frequency, following insemination. Furthermore, overexpressing PLC beta 1 by microinjecting a Plc beta 1 cRNA significantly perturbed the duration and frequency of Ca2+ transients and disrupted the characteristic shape of the first transient. These results provide the first evidence for a role of an egg-derived PLC acting in conjunction with a sperm-derived PLC zeta in egg activation. (C) 2007 Elsevier Inc. All rights reserved. C1 [Williams, Carnien J.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Tgarashi, Hideki; Knott, Jason G.; SchultZ, Richard M.; Williams, Carnien J.] Univ Penn, Ctr Res Reprod & Womens Hlth, Philadelphia, PA 19104 USA. [SchultZ, Richard M.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. RP Williams, CJ (reprint author), NIEHS, POB 12233,MD E4-05, Res Triangle Pk, NC 27709 USA. EM williamsc5@niehs.nih.gov RI Williams, Carmen/E-2170-2013 OI Williams, Carmen/0000-0001-6440-7086 NR 46 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2007 VL 312 IS 1 BP 321 EP 330 DI 10.1016/j.ydbio.2007.09.028 PG 10 WC Developmental Biology SC Developmental Biology GA 242WF UT WOS:000251756200025 ER PT J AU Ko, SO Chung, IH Xu, X Oka, SJ Zhao, H Cho, ES Deng, CX Chai, Y AF Ko, Seung O. Chung, Il Hyuk Xu, Xun Oka, Shoji Zhao, Hu Cho, Eui Sic Deng, Chuxia Chai, Yang TI Smad4 is required to regulate the fate of cranial neural crest cells SO DEVELOPMENTAL BIOLOGY LA English DT Article DE TGF-beta; smad4; tooth; cranial neural crest cells ID CRANIOFACIAL MORPHOGENESIS; TOOTH MORPHOGENESIS; FOREGUT ENDODERM; GOOSECOID GENE; OUTFLOW TRACT; MOUSE EMBRYOS; HEAD; EXPRESSION; INDUCTION; ARCH AB Smad4 is the central mediator for TGF-beta/BMP signals, which are involved in regulating cranial neural crest (CNC) cell fort-nation, migration, proliferation and fate determination. It is unclear whether TGF-beta/BMP signals utilize Smad-dependent or -independent pathways to control the development of CNC cells. To investigate the functional significance of Smad4 in regulating CNC cells, we generated mice with neural crest specific inactivation of the Smad4 gene. Our study shows that Smad4 is not required for the migration of CNC cells, but is required in neural crest cells for the development of the cardiac outflow tract. Smad4 is essential in mediating BMP signaling in the CNC-derived ectomesenchyme during early stages of tooth development because conditional inactivation of Smad4 in neural crest derived cells results in incisor and molar development arrested at the dental lamina stage. Furthermore, Smad-mediated TGF-beta/BMP signaling controls the homeobox gene patterning of oral/aboral and proximal/distal domains within the first branchial arch. At the cellular level, a Smad4-mediated downstream target gene(s) is required for the survival of CNC cells in the proximal domain of the first branchial arch. Smad4 mutant mice show underdevelopment of the first branchial arch and midline fusion defects. Taken together, our data show that TGF-beta/BMP signals rely on Smad-dependent pathways in the ectomesenchyme to mediate epithelial-mesenchymal interactions that control craniofacial organogenesis. (c) 2007 Elsevier Inc. All rights reserved. C1 [Ko, Seung O.; Chung, Il Hyuk; Xu, Xun; Oka, Shoji; Zhao, Hu; Chai, Yang] Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. [Ko, Seung O.] Chonbuk Natl Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Jeonju 5651756, South Korea. [Cho, Eui Sic] Chonbuk Natl Univ, Inst Oral Biosci, Lab Craniofacial Biol, Jeonju 561756, South Korea. [Deng, Chuxia] NIDDK, NIH, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. RP Chai, Y (reprint author), Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, 2250 Alcazar St,CSA 103, Los Angeles, CA 90033 USA. EM ychai@usc.edu RI zhao, hu/K-3901-2012; deng, chuxia/N-6713-2016 FU NIDCR NIH HHS [DE014078, R01 DE012711, R01 DE012711-09, R01 DE012711-09S1, R01 DE014078, R01 DE014078-05, R01 DE017007, R01 DE017007-04, DE012711, R37 DE012711] NR 55 TC 47 Z9 48 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 1 PY 2007 VL 312 IS 1 BP 435 EP 447 DI 10.1016/j.ydbio.2007.09.050 PG 13 WC Developmental Biology SC Developmental Biology GA 242WF UT WOS:000251756200035 PM 17964566 ER PT J AU Battey, JF AF Battey, James F. TI Stem cells: Current challenges and future promise SO DEVELOPMENTAL DYNAMICS LA English DT Editorial Material DE stem cells; pluripotent; self-renewing; regenerative AB Stem cells have two remarkable properties. They can either renew themselves or they can differentiate into one or more adult cell types. Stem cells derived from a human embryo appear to have an unlimited capacity to self-renew in cell culture, and they are also able to differentiate into hundreds of adult cell types. Human embryonic stem cell lines offer a platform technology that has the potential to elucidate the molecular mechanisms that determine adult cell fate, generate cellular models for discovery of new drugs, and create populations of differentiated cells for novel transplantation therapies. The National Institutes of Health (NIH) has identified some of the rate-limiting steps toward realizing this potential, and has forged funding initiatives to accelerate research progress. Given the remarkable potential, NIH support for research using stem cells is an important priority for the foreseeable future. Developmental Dynamics 236:3193-3198, 2007. Published 2007 Wiley-Liss, Inc. C1 [Battey, James F.] NIH, Bethesda, MD 20892 USA. RP Battey, JF (reprint author), NIH, Bldg 31,Rm 3C02, Bethesda, MD 20892 USA. EM batteyj@nidcd.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2007 VL 236 IS 12 BP 3193 EP 3198 DI 10.1002/dvdy.21203 PG 6 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 243FJ UT WOS:000251780300001 PM 17584855 ER PT J AU Lathia, JD Rao, MS Mattson, MP Ffrench-Constant, C AF Lathia, Justin D. Rao, Mahendra S. Mattson, Mark P. ffrench-Constant, Charles TI The microenvironment of the embryonic neural stem cell: Lessons from adult niches? SO DEVELOPMENTAL DYNAMICS LA English DT Review DE review; stem cell; stem cell niche; extracellular matrix; integrins ID FIBROBLAST-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; CEREBRAL CORTICAL SIZE; HAIR FOLLICLE MORPHOGENESIS; TUMOR-INITIATING CELLS; POSTNATAL MOUSE-BRAIN; PROGENITOR CELLS; BETA-CATENIN; IN-VIVO; SELF-RENEWAL AB A better understanding of the signals regulating embryonic neural stem cells is clearly an important goal. However, many studies on neural stem cell biology are conducted on the slowly-dividing cells found in the adult CNS, where specialized microenvironments or niches maintain the stem cells throughout life. By contrast, the embryonic VZ is a transient structure that does not fulfill the criteria conventionally used to define niches. In this review we will examine whether, despite these differences, the signals found in other adult stem cell niches are present in the VZ. Using the similarities and differences we observe, we will reconsider whether the location of embryonic stem cell populations such as the VZ can be thought of as niches. Finally, we will ask how these lessons from the niche inform our understanding of neurodevelopmental diseases and cancers of the CNS. Developmental Dynamics 236:3267-3282, 2007. (c) 2007 Wiley-Liss, Inc. C1 [Lathia, Justin D.; Mattson, Mark P.] NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD USA. [Lathia, Justin D.; ffrench-Constant, Charles] Univ Cambridge, Ctr Brain Repair, Dept Pathol, Cambridge CB2 1TN, England. [Rao, Mahendra S.] Invitron Corp, Corp Res Labs, Carlsbad, CA USA. [Rao, Mahendra S.] Johns Hopkins Sch Med, Baltimore, MD USA. RP Ffrench-Constant, C (reprint author), Dept Pathol, Tennis Court Rd, Cambridge CB2 1OQP, England. EM cfc@mole.bio.cam.ac.uk RI Mattson, Mark/F-6038-2012 FU Wellcome Trust NR 226 TC 34 Z9 40 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2007 VL 236 IS 12 BP 3267 EP 3282 DI 10.1002/dvdy.21319 PG 16 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 243FJ UT WOS:000251780300008 PM 17937403 ER PT J AU Ishizuya-Oka, A Shi, YB AF Ishizuya-Oka, Atsuko Shi, Yun-Bo TI Regulation of adult intestinal epithelial stem cell development by thyroid hormone during Xenopus laevis metamorphosis SO DEVELOPMENTAL DYNAMICS LA English DT Review DE intestine; stem cell; tissue interactions; thyroid hormone; amphibian metamorphosis ID MATRIX-METALLOPROTEINASE STROMELYSIN-3; BONE MORPHOGENETIC PROTEIN-4; MOUSE SMALL-INTESTINE; ACID-BINDING PROTEIN; SONIC HEDGEHOG; CONNECTIVE-TISSUE; AMPHIBIAN METAMORPHOSIS; FROG METAMORPHOSIS; DIGESTIVE-TRACT; GENE-EXPRESSION AB During amphibian metamorphosis, most or all of the larval intestinal epithelial cells undergo apoptosis. In contrast, stem cells of yet-unknown origin actively proliferate and, under the influence of the connective tissue, differentiate into the adult epithelium analogous to the mammalian counterpart. Thus, amphibian intestinal remodeling is useful for studying the stem cell niche, the clarification of which is urgently needed for regenerative therapies. This review highlights the molecular aspects of the niche using the Xenopus laevis intestine as a model. Because amphibian metamorphosis is completely controlled by thyroid hormone (TH), the analysis of TH response genes serves as a powerful means for clarifying its molecular mechanisms. Although functional analysis of the genes is still on the way, recent progresses in organ culture and transgenic studies have gradually uncovered important roles of cell-cell and cell-extracellular matrix interactions through stromelysin-3 and sonic hedgehog(bone morphogenetic protein-4 signaling pathway in the epithelial stem cell development. Developmental Dynamics 236:3358-3368, 2007. (c) 2007 Wiley-Liss, Inc. C1 [Ishizuya-Oka, Atsuko] Nippon Med Sch, Dept Biol, Kawasaki, Kanagawa 2110063, Japan. [Shi, Yun-Bo] Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, Bethesda, MD USA. RP Ishizuya-Oka, A (reprint author), Nippon Med Sch, Dept Biol, Kawasaki, Kanagawa 2110063, Japan. EM a-oka@nms.ac.jp; shi@helix.nih.gov FU Intramural NIH HHS NR 135 TC 25 Z9 25 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2007 VL 236 IS 12 BP 3358 EP 3368 DI 10.1002/dvdy.21291 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 243FJ UT WOS:000251780300015 PM 17705305 ER PT J AU Cheng, SM Carr, CE AF Cheng, Shih-Min Carr, Catherine E. TI Functional delay of myelination of auditory delay lines in the nucleus laminaris of the barn owl SO DEVELOPMENTAL NEUROBIOLOGY LA English DT Article DE auditory delay lines; nucleus laminaris; myelination; oligodendrocyte progenitor migration; tenascin-C ID MATRIX GLYCOPROTEIN TENASCIN; CENTRAL-NERVOUS-SYSTEM; INTERAURAL TIME DIFFERENCES; FIBROBLAST-GROWTH-FACTOR; CELL-ADHESION MOLECULES; CORD-INJURED RATS; EXTRACELLULAR-MATRIX; MESSENGER-RNA; SPINAL-CORD; BRAIN-STEM AB In the barn owl, maps of interaural time difference (ITD) are created in the nucleus laminaris (NL) by interdigitating axons that act as delay lines. Adult delay line axons are myelinated, and this myelination is timely, coinciding with the attainment of adult head size, and stable ITD cues. The proximal portions of the axons become myelinated in late embryonic life, but the delay line portions of the axon in NL remain unmyelinated until the first postnatal week. Myelination of the delay lines peaks at the third week posthatch, and myelinating oligodendrocyte density approaches adult levels by one month, when the head reaches its adult width. Migration of oligodendrocyte progenitors into NL and the subsequent onset of myelination may be restricted by a glial barrier in late embryonic stages and the first posthatch week, since the loss of tenascin-C immunoreactivity in NL is correlated with oligodendrocyte progenitor migration into NL. (c) 2007 Wiley Periodicals, Inc. C1 Univ Maryland, Dept Biol, College Pk, MD 20742 USA. NIH, NINDS, LMCN, MSC, Bethesda, MD 20892 USA. RP Cheng, SM (reprint author), Univ Maryland, Dept Biol, College Pk, MD 20742 USA. EM chengsh@mail.nih.gov FU NIDCD NIH HHS [R01 DC000436, R01 DC000436-20]; PHS HHS [DCD00436] NR 81 TC 16 Z9 16 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1932-8451 J9 DEV NEUROBIOL JI Dev. Neurobiol. PD DEC PY 2007 VL 67 IS 14 BP 1957 EP 1974 DI 10.1002/dneu.20541 PG 18 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 239TG UT WOS:000251540000011 PM 17918244 ER PT J AU Franks, PW Hanson, RL Knowler, WC Moffett, C Enos, G Infante, AM Krakoff, J Looker, HC AF Franks, Paul W. Hanson, Robert L. Knowler, William C. Moffett, Carol Enos, Gleebah Infante, Aniello M. Krakoff, Jonathan Looker, Helen C. TI Childhood predictors of young-onset type 2 diabetes SO DIABETES LA English DT Article ID INSULIN-RESISTANCE SYNDROME; IMPAIRED GLUCOSE-TOLERANCE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; SYNDROME SYNDROME-X; METABOLIC SYNDROME; PIMA-INDIANS; CARDIOVASCULAR RISK; ADOLESCENTS; PREVALENCE AB OBJECTIVE-Optimal prevention of young-onset type 2 diabetes requires identification of the early-life modifiable risk factors. We aimed to do this using longitudinal data in 1,604 5- to 19-year-old initially nondiabetic American Indians. RESEARCH DESIGN AND METHODS-For type 2 diabetes prediction, we derived an optimally weighted, continuously distributed, standardized multivariate score (zMS) comprising commonly measured metabolic, anthropometric, and vascular traits (i.e., fasting and 2-h glucose, A1C, BMI, waist circumference, fasting insulin, HDL cholesterol, triglycerides, and blood pressures) and compared the predictive power for each feature against zMS. RESULTS-In separate Cox proportional hazard models, adjusted for age, sex, and ethnicity, zMS and each of its component risk factors were associated with incident type 2 diabetes. Stepwise proportional hazards models selected fasting glucose, 2-h glucose, HDL cholesterol, and BMI as independent diabetes predictors; individually, these were weaker predictors than zMS (P < 0.01). However, a parsimonious summary score combining only these variables had predictive power similar to that of zMS (P = 0.33). Although intrauterine diabetes exposure or parental history of young-onset diabetes increased a child's absolute risk of developing diabetes, the magnitude of the diabetes-risk relationships for zMS and the parsimonious score were similar irrespective of familial risk factors. CONCLUSIONS-We have determined the relative value of the features of the metabolic syndrome in childhood for the prediction of subsequent type 2 diabetes. Our findings suggest that strategies targeting obesity, dysregulated glucose homeostasis, and low HDL cholesterol during childhood and adolescence may have the most success in preventing diabetes. C1 NIDDK, Diabet Epidemiol & Clin Res Sect, Natl Inst Hlth, Phoenix, AZ 85014 USA. Umea Univ Hosp, Div Med, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. RP Hanson, RL (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, Natl Inst Hlth, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rhanson@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Franks, Paul/0000-0002-0520-7604 FU Intramural NIH HHS NR 42 TC 87 Z9 88 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2007 VL 56 IS 12 BP 2964 EP 2972 DI 10.2337/db06-1639 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HS UT WOS:000251365400018 PM 17720898 ER PT J AU Hanson, RL Bogardus, C Duggan, D Kobes, S Knowlton, M Infante, AM Marovich, L Benitez, D Baier, LJ Knowler, WC AF Hanson, Robert L. Bogardus, Clifton Duggan, David Kobes, Sayuko Knowlton, Michele Infante, Aniello M. Marovich, Leslie Benitez, Deb Baier, Leslie J. Knowler, William C. TI A search for variants associated with young-onset type 2 diabetes in American Indians in a 100K genotyping array SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; AGE-OF-ONSET; PIMA-INDIANS; LINKAGE ANALYSIS; CANDIDATE GENES; RISK LOCI; MELLITUS; TCF7L2; TRAITS; SCAN AB OBJECTIVE-To identify genetic variants in linkage disequilibrium with those conferring diabetes susceptibility, a genome-wide association study for young-onset diabetes was conducted in an American-Indian population. RESEARCH DESIGN AND METHODS-Data come from 300 case subjects with type 2 diabetes with age of onset < 25 years and 334 nondiabetic control subjects aged >= 45 years. To provide for tests of within-family association, 121 nondiabetic siblings of case subjects were included along with 140 diabetic siblings of control subjects (172 sibships). Individuals were genotyped on the Affymetrix 100K array, resulting in 80,044 usable single nucleotide polymorphisms (SNPs). SNPs were analyzed for within-family association and for general association in case and control subjects, and these tests were combined by Fisher's method, with priority given to the within-family test. RESULTS-There were more SNPs with low P values than expected theoretically under the global null hypothesis of no association, and 128 SNPs had evidence for association at P < 0.001. The association of these SNPs with diabetes was further investigated in 1,207 diabetic and 1,627 nondiabetic individuals from the population study who were not included in the genome-wide study. SNPs from 10 genomic regions showed evidence for replication at P < 0.05. These included SNPs on chromosome 3 near ZNF659, chromosome I I near FANCF, chromosome 11 near ZBTB15, and chromosome 12 near SENP1. CONCLUSIONS-These studies suggest several regions where marker alleles are potentially in linkage disequilibrium with variants that confer susceptibility to young-onset type 2 diabetes in American Indians. C1 NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. Translat Genom Res Inst, Phoenix, AZ USA. RP Hanson, RL (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, 550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rhanson@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS NR 51 TC 64 Z9 67 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2007 VL 56 IS 12 BP 3045 EP 3052 DI 10.2337/db07-0462 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HS UT WOS:000251365400028 PM 17846125 ER PT J AU Florez, JC Manning, AK Dupuis, J McAteer, J Irenze, K Gianniny, L Mirel, DB Fox, CS Cupples, LA Meigs, JB AF Florez, Jose C. Manning, Alisa K. Dupuis, Josee McAteer, Jarred Irenze, Kathryn Gianniny, Lauren Mirel, Daniel B. Fox, Caroline S. Cupples, L. Adrienne Meigs, James B. TI A 100K genome-wide association scan for diabetes and related traits in the Framingham Heart Study SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; INSULIN-RESISTANCE; TCF7L2 POLYMORPHISMS; GENETIC ASSOCIATION; COMPLEX TRAITS; TYPE-2; GLUCOSE; POPULATION; DISEASE; RISK AB OBJECTIVE-To use genome-wide fixed marker arrays and improved analytical tools to detect genetic associations with type 2 diabetes in a carefully phenotyped human sample. RESEARCH DESIGN AND METHODS-A total of 1,087 Framingham Heart Study (FHS) family members were genotyped on the Affymetrix 100K single nucleotide polymorphism (SNP) array and examined for association with incident diabetes and six diabetes-related quantitative traits. Quality control filters yielded 66,543 SNPs for association testing. We used two complementary SNP selection strategies (a "lowest P value" strategy and a,'multiple related trait" strategy) to prioritize 763 SNPs for replication. We genotyped a subset of 150 SNPs in a nonoverlapping sample of 1,465 FHS unrelated subjects and examined all 763 SNPs for in silico replication in three other 100K and one 500K genome-wide association (GWA) datasets. RESULTS- We replicated associations of 13 SNPs with one or more traits in the FHS unrelated sample (16 expected under the null); none of them showed convincing in silico replication in 100K scans. Seventy-eight SNPs were nominally associated with diabetes in one other 100K GWA scan, and two (rs2863389 and rs7935082) in more than one. Twenty-five SNPs showed promising associations with diabetes-related traits in 500K GWA reported associations were confirmed in our initial dataset. CONCLUSIONS- The FHS 100K GWA resource is useful for follow-up of genetic associations with diabetes-related quantitative traits. Discovery of new diabetes genes will require larger samples and a denser array combined with well-powered replication strategies. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org FU NCRR NIH HHS [1S10RR163736-01A1, U54 RR020278-01]; NHLBI NIH HHS [N01-HC-25195]; NIDDK NIH HHS [K23 DK-65978-04] NR 44 TC 51 Z9 54 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2007 VL 56 IS 12 BP 3063 EP 3074 DI 10.2337/db07-0451 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HS UT WOS:000251365400030 PM 17848626 ER PT J AU Guo, TW Hanson, RL Traurig, M Muller, YL Ma, LJ Mack, J Kobes, S Knowler, WC Bogardus, C Baier, LJ AF Guo, Tingwei Hanson, Robert L. Traurig, Michael Muller, Yunhua Li Ma, Lijun Mack, Janel Kobes, Sayuko Knowler, William C. Bogardus, Clifton Baier, Leslie J. TI TCF7L2 is not a major susceptibility gene for type 2 diabetes in Pima Indians SO DIABETES LA English DT Article ID AUTOSOMAL GENOMIC SCAN; JAPANESE POPULATION; INSULIN-RESISTANCE; ASSOCIATION; POLYMORPHISMS; RISK; REPLICATION; VARIANTS; MELLITUS AB OBJECTIVE-The transcription factor 7-like 2 (TCF7L2) gene was initially reported to be associated with type 2 diabetes in Icelandic, Danish, and U.S. populations. We investigated whether TCF7L2 also has a role in type 2 diabetes susceptibility in Pima Indians. RESEARCH DESIGN AND METHODS-The six variants reported to be associated with type 2 diabetes in the Icelandic study were genotyped in a population-based sample of 3,501 Pima Indians (1,561 subjects had type 2 diabetes, and 1,940 did not have diabetes). In addition, the coding and promoter regions of TCF7L2 were sequenced in 24 Pima subjects. The one variant identified by sequencing, 35 additional database variants positioned in introns, and the six variants reported in the Icelandic study were genotyped in Pima families to determine the haplotype structure of TCF7L2 among Pima Indians. Fourteen representative variants were selected and genotyped in 3,501 Pima Indians. RESULTS-The six variants initially reported to be associated with type 2 diabetes were less common in Pima Indians compared with samples of European origin, and none were associated with type 2 diabetes. One representative variant, rs1225404, was nominally associated with type 2 diabetes in a general model (additive P = 0.03, dominant P = 0.005) but not in a within-family analysis (additive P = 0.2, dominant P = 0.07). However, several variants were associated with BMI; in particular, rs12255372 was associated in both general and within-family analyses (both P = 0.0007). Modest associations were also found with traits predictive for type 2 diabetes. CONCLUSIONS-Variation within TCF7L2 does not confer major risk for type 2 diabetes among the Pima Indian population. C1 NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85004 USA. RP Baier, LJ (reprint author), NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 445 N 5th St, Phoenix, AZ 85004 USA. EM lbaier@phx.niddk.rdh.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS NR 25 TC 46 Z9 46 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2007 VL 56 IS 12 BP 3082 EP 3088 DI 10.2337/db07-0621 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HS UT WOS:000251365400032 PM 17909099 ER PT J AU Muller, YL Hanson, RL Zimmerman, C Harper, I Sutherland, J Kobes, S Knowler, WC Bogardus, C Baier, LJ AF Muller, Yunhua Li Hanson, Robert L. Zimmerman, Collin Harper, Inge Sutherland, Jeff Kobes, Sayuko Knowler, William C. Bogardus, Clifton Baier, Leslie J. CA Int Type 2 Diabet 1q Consortium TI Variants in the Ca(v)2.3 (alpha 1E) subunit of voltage-activated Ca2+ channels are associated with insulin resistance and type 2 diabetes in Pima Indians SO DIABETES LA English DT Article ID OLD ORDER AMISH; SUSCEPTIBILITY LOCUS; CHROMOSOME 1Q; GENOME-WIDE; INDEPENDENT REPLICATION; QUANTITATIVE TRAITS; GENE; EXPRESSION; LINKAGE; SCAN AB OBJECTIVE-Linkage to type 2 diabetes has been reported on chromosome 1q21-25 in Pima Indians. Fine mapping identified single nucleotide polymorphisms (SNPs) near the CACNA1E gene associated with this disease. CACNA1E encodes the voltage-dependent calcium channel Ca,2.3 Ca2+, and mice lacking this channel exhibit impaired glucose tolerance and insulin secretion. Therefore, CACNA1E was investigated as a positional candidate gene. RESEARCH DESIGN AND METHODS-CACNA1E was sequenced, and 28 SNPs were genotyped in the same group of Pima subjects who had been analyzed in the linkage study. Allele-specific expression was used to functionally evaluate a variant in the 3' untranslated region (UTR). RESULTS-A novel G/A variant in the 3'-UTR was associated with young-onset type 2 diabetes (odds ratio 2.09 per copy of the G-allele [95% Cl 1.31-3.33], adjusted P = 0.00 1) and had an effect on the evidence for linkage at chromosome 1q21-25 (P = 0.004). Among 372 nondiabetic Pima subjects who had undergone metabolic testing, the risk allele was associated with reduced insulin action including increased fasting, 30, 60, and 120 rain plasma glucose concentrations and increased fasting plasma insulin during an oral glucose tolerance test (all P < 0.01), as well as a decreased rate of insulin-stimulated glucose disposal at both physiologically and maximally stimulated insulin concentrations (both P < 0.002). Functional analysis of this variant showed that the nonrisk allele had a 2.3-fold higher expression compared with the risk allele. CONCLUSIONS-A functional variant in CACNA1E contributes to type 2 diabetes susceptibility by affecting insulin action. This variant partially explains the linkage to type 2 diabetes on chromosome 1q21-25 in Pima Indians. C1 NIDDK, Phoenix Epidemiol & Clin Res Branch, Diabet Mol Genet Sect, NIH, Phoenix, AZ 85004 USA. RP Baier, LJ (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, Diabet Mol Genet Sect, NIH, 455 N 5th St, Phoenix, AZ 85004 USA. EM lbaier@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS; NIDDK NIH HHS [R01-DK073490] NR 25 TC 13 Z9 13 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2007 VL 56 IS 12 BP 3089 EP 3094 DI 10.2337/db07-0587 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HS UT WOS:000251365400033 PM 17720895 ER PT J AU Franks, PW Jablonski, KA Delahanty, L Hanson, RL Kahn, SE Altshuler, D Knowler, WC Florez, JC AF Franks, P. W. Jablonski, K. A. Delahanty, L. Hanson, R. L. Kahn, S. E. Altshuler, D. Knowler, W. C. Florez, J. C. CA Diabetes Prevention Program Res G TI The Pro12Ala variant at the peroxisome proliferator-activated receptor gamma gene and change in obesity-related traits in the Diabetes Prevention Program SO DIABETOLOGIA LA English DT Article DE computed tomography; gene-environment interaction; obesity; peroxisome proliferator-activated receptor gamma; PPARG; PUFA intake; randomised clinical trial; subcutaneous fat; visceral fat ID DIETARY-FAT INTAKE; LIFE-STYLE INTERVENTION; BODY-MASS INDEX; PPAR-GAMMA; INSULIN SENSITIVITY; P12A POLYMORPHISM; PHYSICAL-ACTIVITY; WEIGHT CHANGE; BASE-LINE; RISK AB Aims/hypothesis Peroxisome proliferator-activated receptor. (PPAR.), encoded by the PPARG gene, regulates insulin sensitivity and adipogenesis, and may bind polyunsaturated fatty acids (PUFA) and thiazolidinediones in a ligand-dependent manner. The PPARG proline for alanine substitution at position 12 (Pro12Ala polymorphism) has been related with obesity directly and via interaction with PUFA. Methods We tested the effect-modifying role of Pro12Ala on the 1 year change in obesity-related traits in a randomised clinical trial of treatment with metformin (n= 989), troglitazone (n= 363) or lifestyle modification (n= 1,004) vs placebo (n= 1,000) for diabetes prevention in high- risk individuals. Results At baseline, Ala12 carriers had larger waists (p< 0.001) and, in a subset, more subcutaneous adipose tissue (SAT; lumbar 2/ 3; p= 0.04) than Pro12 homozygotes. There was a genotype- by- intervention interaction on 1- year weight change (p= 0.01); in the placebo arm, Pro12 homozygotes gained weight and Ala12 carriers lost weight (p= 0.001). In the metformin and lifestyle arms, weight loss occurred across genotypes, but was greatest in Ala12 carriers (p< 0.05). Troglitazone treatment induced weight gain, which tended to be greater in Ala12 carriers (p= 0.08). In the placebo group, SAT (lumbar 2/3, lumbar 4/5) decreased in Ala12 allele carriers, but was unchanged in Pro12 homozygotes (p <= 0.005). With metformin treatment, SAT decreased independently of genotype. In the lifestyle arm, SAT (lumbar 2/ 3) reductions occurred across genotypes, but were greater in Ala12 carriers (p= 0.03). A genotype-by-PUFA intake interaction on reduction in visceral fat (lumbar 4/ 5; p= 0.04) was also observed, which was most evident with metformin treatment (p< 0.001). Conclusions/ interpretation Within the Diabetes Prevention Program, the Ala12 allele influences central obesity, an effect which may differ by treatment group and dietary PUFA intake (ClinicalTrials.gov ID no: NCT00004992). C1 George Washington Univ, Ctr Biostat, Diabetes Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. MIT, Cambridge, MA 02139 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Univ Umea Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. NIH, NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. RP Franks, PW (reprint author), George Washington Univ, Ctr Biostat, Diabetes Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu RI Altshuler, David/A-4476-2009; Hanson, Robert/O-3238-2015; OI Altshuler, David/0000-0002-7250-4107; Hanson, Robert/0000-0002-4252-7068; Franks, Paul/0000-0002-0520-7604 FU Intramural NIH HHS; NIDDK NIH HHS [U01 DK048489-06, U01 DK048489] NR 39 TC 43 Z9 45 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2007 VL 50 IS 12 BP 2451 EP 2460 DI 10.1007/s00125-007-0826-6 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228HQ UT WOS:000250721400007 PM 17898990 ER PT J AU Richardson, AM Woodson, K Wang, Y Rodriguez-Canales, J Erickson, HS Tangrea, MA Novakovic, K Gonzalez, S Velasco, A Kawasaki, ES Emmert-Buck, MR Chuaqui, RF Player, A AF Richardson, Annely M. Woodson, Karen Wang, Yonghong Rodriguez-Canales, Jaime Erickson, Heidi S. Tangrea, Michael A. Novakovic, Kristian Gonzalez, Sergio Velasco, Alfredo Kawasaki, Ernest S. Emmert-Buck, Michael R. Chuaqui, Rodrigo F. Player, Audrey TI Global expression analysis of prostate cancer-associated stroma and epithelia SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE prostate cancer; microenvironment; stroma; oligonucleotide array ID OLIGOMERIC MATRIX PROTEIN; METHYLACYL-COA RACEMASE; MALIGNANT HUMAN TISSUES; MEMBRANE ANTIGEN; TUMOR MICROENVIRONMENT; BREAST-CANCER; TGF-BETA; CELLS; METASTASIS; THERAPY AB Characterization of gene expression profiles in tumor cells and the tumor microenvironment is an important step in understanding neoplastic progression. To date, there are limited data available on expression changes that occur in the tumor-associated stroma as either a cause or consequence of cancer. In the present study, we employed a 54,000 target oligonucleotide microarray to compare expression profiles in the 4 major components of the microenvironment: tumor epithelium, tumor-associated stroma, normal epithelium, and normal stroma. Cells from 5 human, whole-mount prostatectomy specimens were microdissected and the extracted and amplified mRNA was hybridized to an Affymetrix Human Genome U133 Plus 2.0 GeneChip. Using the intersection of 2 analysis methods, we identified sets of differentially expressed genes among the 4 components. Forty-four genes were found to be consistently differentially expressed in the tumor-associated stroma; 35 were found in the tumor epithelium. Interestingly, the tumor-associated stroma showed a predominant up-regulation of transcripts compared with normal stroma, in sharp contrast to the overall down-regulation seen in the tumor epithelium relative to normal epithelium. These data provide insight into the molecular changes occurring in tumor-associated stromal cells and suggest new potential targets for future diagnostic, imaging, or therapeutic intervention. C1 Natl Inst Hlth, Pathogenet Unit, Bethesda, MD USA. Natl Inst Hlth, HHMI NIH Res Scholar, Bethesda, MD USA. Natl Inst Hlth, Methylation Lab, Bethesda, MD USA. Natl Inst Hlth, Microarray Facility, Bethesda, MD USA. Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD USA. Catholic Univ, Natl Canc Inst, Santiago, Chile. Catholic Univ, Pathol & Urol, Santiago, Chile. RP Richardson, AM (reprint author), Natl Inst Hlth, Natl Canc Inst, Pathol Lab, Pathogenet Unit,HHMI NIH,Res Scholar, Bethesda, MD 20892 USA. EM ricannel@mail.nih.gov NR 55 TC 33 Z9 35 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD DEC PY 2007 VL 16 IS 4 BP 189 EP 197 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 235ZU UT WOS:000251273600001 PM 18043281 ER PT J AU Jalah, R Rosati, M Kulkarni, V Patel, V Bergamaschi, C Valentin, A Zhang, GM Sidhu, MK Eldridge, JH Weiner, DB Pavlakis, GN Felber, BK AF Jalah, Rashmi Rosati, Margherita Kulkarni, Viraj Patel, Vainav Bergamaschi, Cristina Valentin, Antonio Zhang, Gen-Mu Sidhu, Maninder K. Eldridge, John H. Weiner, David B. Pavlakis, George N. Felber, Barbara K. TI Efficient systemic expression of bioactive IL-15 in mice upon delivery of optimized DNA expression plasmids SO DNA AND CELL BIOLOGY LA English DT Article ID CD8 T-CELLS; SIMIAN RETROVIRUS TYPE-1; RHESUS MACAQUES; INTRACELLULAR TRAFFICKING; UNTRANSLATED REGION; SECONDARY STRUCTURE; SIGNAL PEPTIDE; MESSENGER-RNA; REV; INTERLEUKIN-15 AB Efficient expression vectors for interleukin 15 (IL-15) were developed combining RNA/codon optimization and modification of the IL-15 native long signal peptide. These changes resulted in elevated cytoplasmic levels of the optimized mRNA and more than 100-fold improved production of secreted human IL-15 protein. Similar modifications have also led to greatly increased rhesus macaque and murine IL-15 production. Comparison of different heterologous secretory signals showed that the tissue plasminogen activator signal is most efficient for the production of extracellular IL-15. Upon intramuscular injection of the fully optimized expression vectors in mice, IL-15 was readily detected in the serum. Serum levels represented <1% of intramuscular IL-15 and were sufficient in causing some systemic effects, such as increasing the frequency of natural killer (NK) cells in the liver. Upon hydrodynamic DNA delivery in mice, very high levels of IL-15 were produced, which increased the frequency of NK cells in liver as well as in spleen and lung. These optimized expression vectors have potential applications in vaccine and immunotherapy approaches against AIDS and cancer. C1 [Jalah, Rashmi; Kulkarni, Viraj; Zhang, Gen-Mu; Felber, Barbara K.] NCI Frederick, Ctr Canc Res, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD 21702 USA. [Rosati, Margherita; Patel, Vainav; Bergamaschi, Cristina; Valentin, Antonio; Zhang, Gen-Mu; Pavlakis, George N.] NCI Frederick, Vaccine Branch, Human Retrovirus Sect, Frederick, MD 21702 USA. [Sidhu, Maninder K.; Eldridge, John H.] Wyeth Vaccines Res, Pearl River, NY USA. [Weiner, David B.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Felber, BK (reprint author), NCI Frederick, Ctr Canc Res, Human Retrovirus Pathogenesis Sect, Vaccine Branch, 1050 Boyles St,Bldg 535,Room 209, Frederick, MD 21702 USA. EM felber@ncifcrf.gov RI Weiner, David/H-8579-2014 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 39 TC 22 Z9 24 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD DEC PY 2007 VL 26 IS 12 BP 827 EP 840 DI 10.1089/dna.2007.0645 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 247RA UT WOS:000252095800003 PM 17979522 ER PT J AU Moon, AF Garcia-Diaz, M Batra, VK Beard, WA Bebenek, K Kunkel, TA Wilson, SH Pedersen, LC AF Moon, Andrea F. Garcia-Diaz, Miguel Batra, Vinod K. Beard, William A. Bebenek, Katarzyna Kunkel, Thomas A. Wilson, Samuel H. Pedersen, Lars C. TI The X family portrait: Structural insights into biological functions of X family polymerases SO DNA REPAIR LA English DT Review DE family X polymerase; DNA polymerase beta; DNA polymerase lambda; TdT; DNA polymerase mu; gap-filling; misinsertion misalignment; frameshift lesion bypass; template-dependence; template-independence; substrate specificity ID HUMAN DNA-POLYMERASE; BASE EXCISION-REPAIR; BETA ACTIVE-SITE; TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE; INDUCED-FIT MECHANISM; END-JOINING PATHWAY; STRAND BREAK REPAIR; MU POL-MU; V(D)J RECOMBINATION; NONHOMOLOGOUS DNA AB The mammalian family X DNA polymerases (DNA polymerases beta, lambda, mu, and TdT) contribute to base excision repair and double-strand break repair by virtue of their ability to fill short gaps in DNA. Structural information now exists for all four of these enzymes, making this the first mammalian polymerase family whose structural portrait is complete. Here we consider how distinctive structural features of these enzymes contribute to their biological functions in vivo. Published by Elsevier B.V. C1 [Moon, Andrea F.; Garcia-Diaz, Miguel; Batra, Vinod K.; Beard, William A.; Bebenek, Katarzyna; Kunkel, Thomas A.; Wilson, Samuel H.; Pedersen, Lars C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Garcia-Diaz, Miguel; Bebenek, Katarzyna; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Pedersen, LC (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM pederse2@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 90 TC 103 Z9 106 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 1 PY 2007 VL 6 IS 12 BP 1709 EP 1725 DI 10.1016/j.dnarep.2007.05.009 PG 17 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 241EU UT WOS:000251640500001 PM 17631059 ER PT J AU Sakamoto, AN Stone, JE Kissling, GE McCulloch, SD Pavlov, YI Kunkel, TA AF Sakamoto, Ayako N. Stone, Jana E. Kissling, Grace E. McCulloch, Scott D. Pavlov, Youri I. Kunkel, Thomas A. TI Mutator alleles of yeast DNA polymerase zeta SO DNA REPAIR LA English DT Article DE pol zeta; translesion synthesis; mutagenesis; yeast ID NUCLEOTIDE EXCISION-REPAIR; DOUBLE-STRAND-BREAK; DEPENDENT TRANSLESION SYNTHESIS; GUANINE OXIDATION-PRODUCTS; THYMINE DIMER BYPASS; SACCHAROMYCES-CEREVISIAE; EMBRYONIC LETHALITY; INDUCED MUTAGENESIS; REV1 PROTEIN; POL-ZETA AB The yeast REV3 gene encodes the catalytic subunit of DNA polymerase zeta (pol zeta), a B family polymerase that performs mutagenic DNA synthesis in cells. To probe pol zeta mutagenic functions, we generated six mutator alleles of REV3 with amino acid replacements for Leu979, a highly conserved residue inferred to be at the pol zeta active site. Replacing Leu979 with Gly, Val, Asn, Lys, Met or Phe resulted in yeast strains with elevated UV-induced mutant frequencies. While four of these strains had reduced survival following UV irradiation, the rev3-L979F and rev3-L979M strains had normal survival, suggesting retention of pol zeta catalytic activity. UV mutagenesis in the rev3-L979F background was increased when photoproduct bypass by pol eta was eliminated by deletion of RAD30. The rev3-L979F mutation had little to no effect on mutagenesis in an ogg1 Delta background, which cannot repair 8-oxo-guanine in DNA. UV-induced can1 mutants from rev3-L979F and rad30 Delta rev3-L979F strains primarily contained base substitutions and complex mutations, suggesting error-prone bypass of UV photoproducts by L979F pol zeta. Spontaneous mutation rates in rev3-L979F and rev3-L979M strains are elevated by about two-fold overall and by two- to eight-fold for C to G transversions and complex mutations, both of which are known to be generated by wild-type pol zeta in vitro. These results indicate that Rev3p-Leu979 replacements reduce the fidelity of DNA synthesis by yeast pol zeta in vivo. In conjunction with earlier studies, the data establish that the conserved amino acid at the active site location occupied by Leu979 is critical for the fidelity of all four yeast B family polymerases. Reduced fidelity with retention of robust polymerase activity suggests that the homologous rev3-L979F allele may be useful for analyzing pol zeta functions in mammals, where REV3 deletion is lethal. (C) 2007 Elsevier B.V. All rights reserved. C1 [Stone, Jana E.; McCulloch, Scott D.; Kunkel, Thomas A.] NIEHS, NIH, DHHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Sakamoto, Ayako N.] Japan Atom Energy Agcy, Res Grp Gene Resources, Dept Ion Beam Appl Biol, Takasaki, Gumma 3701292, Japan. [Stone, Jana E.; McCulloch, Scott D.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Pavlov, Youri I.] Univ Nebraska Med Ctr, Eppley Inst Res Canc, Omaha, NE USA. [Pavlov, Youri I.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA. RP Kunkel, TA (reprint author), NIEHS, NIH, DHHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Intramural NIH HHS [Z01 ES065070-17] NR 63 TC 25 Z9 25 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 1 PY 2007 VL 6 IS 12 BP 1829 EP 1838 DI 10.1016/j.dnarep.2007.07.002 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 241EU UT WOS:000251640500013 PM 17715002 ER PT J AU Winhusen, T Somoza, E Ciraulo, DA Harrer, JM Goldsmith, RJ Grabowski, J Coleman, FS Mindrum, G Kahn, R Osman, S Mezinskis, J Li, SH Lewis, D Horn, P Montgomery, MA Elkashef, A AF Winhusen, Theresa Somoza, Eugene Ciraulo, Domenic A. Harrer, Judy M. Goldsmith, R. Jeffrey Grabowski, John Coleman, Florence S. Mindrum, Gordon Kahn, Roberta Osman, Sabuhi Mezinskis, Juris Li, Shou-Hua Lewis, Daniel Horn, Paul Montgomery, Margaret A. Elkashef, Ahmed TI A double-blind, placebo-controlled trial of tiagabine for the treatment of cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine dependence; tiagabine; clinical trial; double-blind ID METHADONE-TREATED PATIENTS; DRUG-ADDICTION; INCREASES AB Background: The potential efficacy of tiagabine for treating cocaine dependence is suggested by both pre-clinical research and two small clinical trials. Method: One hundred and forty one participants who met DSM-IV criteria for cocaine dependence were enrolled into this 12-week, double blind, placebo controlled outpatient trial. Participants received either tiagabine (20 mg/day) or matching placebo. All participants received 1 h of manualized individual cognitive behavioral therapy on a weekly basis. Outcome measures included cocaine use as determined by self-report confirmed with urine benzoylecgonine (BE) results, and qualitative and quantitative urine toxicology measures. Safety measures included adverse events, EKGs, vital signs, and laboratory tests. Results: Seventy-nine participants (i.e., 56%) completed the 12-week trial. The safety results suggest that tiagabine was safe and generally well tolerated by the participants. Participants in both groups improved significantly on cocaine craving and global functioning, with no significant differences between the groups. There were no significant changes in cocaine use as measured by self-report confirmed by urine BE or by quantitative urine toxicology results. Qualitative urine toxicology results suggest a possible weak effect for tiagabine in reducing cocaine use. Conclusion: These results suggest that tiagabine, at a dose of 20 mg/day, did not have a robust effect in decreasing cocaine use. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Univ Cincinnati, Cincinnati Addict Res Ctr, Cincinnati, OH 45220 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Vet Affairs Med Ctr VISN 10, Cincinnati, OH 45220 USA. Boston Med Ctr, Dept Psychiat, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Texas, Hlth Sci Ctr, Subst Abuse Res Ctr, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Dayton VA Med Ctr, Mental Hlth 116, Dayton, OH 45428 USA. Natl Inst Drug Abuse, Div Treatment Res & Dev, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Math, Cincinnati, OH 45221 USA. RP Winhusen, T (reprint author), Univ Cincinnati, Cincinnati Addict Res Ctr, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. EM winhusen@mdru.uc.edu OI Winhusen, Theresa/0000-0002-3364-0739; Ciraulo, Domenic/0000-0001-7706-8765 FU NIDA NIH HHS [N01-DA-9-8095] NR 25 TC 26 Z9 26 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 2007 VL 91 IS 2-3 BP 141 EP 148 DI 10.1016/j.drugalcdep.2007.05.028 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 228RN UT WOS:000250747500006 PM 17629631 ER PT J AU Moss, HB Chen, CM Yi, HY AF Moss, Howard B. Chen, Chiung M. Yi, Hsiao-Ye TI Subtypes of alcohol dependence in a nationally representative sample SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism DE alcohol dependence; epidemiology; subtypes; survey research ID GENERAL-POPULATION SAMPLE; LATENT CLASS ANALYSIS; EPIDEMIOLOGIC SURVEY; UNITED-STATES; USE DISORDER; IV; ABUSE; COOCCURRENCE; RELIABILITY; PREVALENCE AB Objective: The authors sought to empirically derive alcohol dependence (AD) subtypes based on clinical characteristics using data from a nationally representative epidemiological survey. Method: A sample of 1484 respondents to the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) with past year AD was subjected to latent class analysis in order to identify homogeneous subtypes. Results: The best-fitting model was a five-cluster solution. The largest cluster (Cluster 1: similar to 31%) was comprised of young adults, who rarely sought help for drinking, had moderately high levels of periodic heavy drinking, relatively low rates of comorbidity, and the lowest rate of multigenerational AD (similar to 22%). In contrast, Clusters 4 and 5 (similar to 21 % and 9%, respectively) had substantial rates of multigenerational AD (53% and 77%, respectively), had the most severe AD criteria profile, were associated with both comorbid psychiatric and other drug use disorders, lower levels of psychosocial functioning, and had engaged in significant help-seeking. Clusters 2 and 3 (similar to 19% each) had the latest onset, the lowest rates of periodic heavy drinking, medium/low levels of comorbidity, moderate levels of help-seeking, and higher psychosocial functioning. Conclusion: Five distinct subtypes of AD were derived, distinguishable on the basis of family history, age of AD onset, endorsement of DSM-IV AUD criteria, and the presence of comorbid psychiatric and substance use disorders. These clinically relevant subtypes, derived from the general population, may enhance our understanding of the etiology, treatment, natural history, and prevention of AD and inform the DSM-V research agenda. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 NIAAA, Bethesda, MD 20892 USA. CSR Incorp, Arlington, VA 22201 USA. RP Moss, HB (reprint author), NIAAA, Bethesda, MD 20892 USA. EM mossh@mail.nih.gov FU Intramural NIH HHS [Z99 AA999999]; NIAAA NIH HHS [N01 AA032007] NR 29 TC 118 Z9 119 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 2007 VL 91 IS 2-3 BP 149 EP 158 DI 10.1016/j.drugalcdep.2007.05.016 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 228RN UT WOS:000250747500007 PM 17597309 ER PT J AU Ghitza, UE Epstein, DH Preston, KL AF Ghitza, Udi E. Epstein, David H. Preston, Kenzie L. TI Psychosocial functioning and cocaine use during treatment: Strength of relationship depends on type of urine-testing method SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE urinalysis; substance dependence; treatment; methadone maintenance; abstinence reinforcement; psychosocial function ID SOCIAL-ADJUSTMENT; CLINICAL-TRIALS; FOLLOW-UP; SELF-REPORT; DSM-IV; DEPRESSION; ABSTINENCE; BENZOYLECGONINE; RELIABILITY; URINALYSIS AB Although improvement in psychosocial functioning is a common goal in substance-abuse treatment, the primary outcome measure in most cocaine trials is urinalysis-verified cocaine use. However, the relationship between cocaine use and psychosocial outcomes is not well documented. To investigate this relationship and identify the optimal urine-screen method, we retrospectively analyzed data from two 25-week randomized controlled trials of abstinence reinforcement (AR) in 368 cocaine/heroin users maintained on methadone. Cocaine use was measured thrice weekly by qualitative urinalysis, benzoylecgonine concentration (BE), and an estimate of New Uses of cocaine by application of an algorithm to BE. Social adjustment (SAS-SR), current diagnosis of cocaine dependence (DSM-IV criteria), and depression symptoms (Beck Depression Inventory) were determined at study exit. Cocaine use was significantly lower in AR groups than in controls. Across groups, in-treatment cocaine use was significantly associated with worse social adjustment, current cocaine dependence, and depression at exit. Significant differences were detected more frequently with New Uses than qualitative urinalysis or BE. Nevertheless, the amount of variance accounted for by the urine screens was typically < 15%. Cocaine use during treatment, especially when measured with New Uses criteria, can predict psychosocial functioning, but cannot substitute for direct measures of psychosocial functioning. Published by Elsevier Ireland Ltd. C1 NIDA, IRP, NIH DHHS, Clin Pharmacol & Therapeut Branch,Treatment Sect, Baltimore, MD 21224 USA. RP Ghitza, UE (reprint author), NIDA, IRP, NIH DHHS, Clin Pharmacol & Therapeut Branch,Treatment Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ghitzau@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z01 DA000234-15, Z99 DA999999] NR 44 TC 11 Z9 11 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 2007 VL 91 IS 2-3 BP 169 EP 177 DI 10.1016/j.drugalcdep.2007.05.018 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 228RN UT WOS:000250747500009 PM 17624688 ER PT J AU Winhusen, T Somoza, E Sarid-Segald, O Goldsmith, RJ Harrer, JM Coleman, FS Kahn, R Osman, S Mezinskis, J Li, SH Lewis, D Afshar, M Ciraulo, DA Horn, P Montgomery, MA Elkashef, A AF Winhusen, Theresa Somoza, Eugene Sarid-Segald, Ofra Goldsmith, R. Jeffrey Harrer, Judy M. Coleman, Florence S. Kahn, Roberta Osman, Sabuhi Mezinskis, Juris Li, Shou-Hua Lewis, Daniel Afshar, Maryam Ciraulo, Domenic A. Horn, Paul Montgomery, Margaret A. Elkashef, Ahmed TI A double-blind, placebo-controlled trial of reserpine for the treatment of cocaine dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine dependence; reserpine; clinical trial; double-blind ID METHAMPHETAMINE; DRUGS; DEPRESSION; ADDICTION; DOPAMINE AB Background: Cocaine's increase of dopamine is strongly associated with its reinforcing properties and, thus, agents that reduce dopamine have received much attention as candidate cocaine-dependence treatments. The potential efficacy of reserpine, a dopamine depletor, for treating cocaine dependence is suggested by both pre-clinical research and a small clinical trial. Method: One hundred and nineteen participants who met DSM-IV criteria for cocaine dependence were enrolled into this 12-week, double-blind, placebo-controlled outpatient trial. Participants received either reserpine (0.5 mg/day) or matching placebo. All participants received 1 h of manualized individual cognitive behavioral therapy on a weekly basis. Outcome measures included cocaine use as determined by self-report confirmed with urine benzoylecgonine results, cocaine craving, addiction severity index scores, and clinical global impression scores. Safety measures included adverse events, EKGs, vital signs, laboratory tests, and the Hamilton Depression Inventory. Results: Seventy-nine participants (i.e., 66%) completed the 12-week trial. The safety results suggest that reserpine was safe and well tolerated by the participants. The efficacy measures indicated no significant differences between reserpine and placebo. Conclusion: These results do not support the efficacy of reserpine as a cocaine-dependence treatment. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. CinARC, Cincinnati, OH 45220 USA. Vet Affairs Med Ctr VISN 10, Cincinnati, OH 45220 USA. Boston Univ, Sch Med, VA Boston Hlth Care Syst, MDRU,Dept Psychiat, Boston, MA 02118 USA. Dayton VA Med Ctr, Dayton, OH USA. Natl Inst Drug Abuse, Div Treatment Res & Dev, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Math, Cincinnati, OH 45221 USA. RP Winhusen, T (reprint author), Univ Cincinnati, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. EM winhusen@mdru.uc.edu OI Ciraulo, Domenic/0000-0001-7706-8765; Winhusen, Theresa/0000-0002-3364-0739 FU NIDA NIH HHS [N01-DA-9-8095] NR 24 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 2007 VL 91 IS 2-3 BP 205 EP 212 DI 10.1016/j.drugalcdep.2007.05.021 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 228RN UT WOS:000250747500013 PM 17628352 ER PT J AU Chen, LJ Lebetkin, EH Nwakpuda, EI Burka, LT AF Chen, L. -J. Lebetkin, E. H. Nwakpuda, E. I. Burka, L. T. TI Metabolism and disposition of n-butyl glycidyl ether in F344 rats and B6C3F1 mice SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID EXCRETION AB The disposition of [C-14]-labeled n-butyl glycidyl ether (BGE, 3-butoxy-1,2-epoxypropane) was studied in rats and mice. The majority of a single p.o. dose (2-200 mg/kg) was excreted in urine (rats, 84-92%; mice, 64-73%) within 24 h. The rest of the dose was excreted in feces (rats, 2.6-7.7%; mice, 5.3-12%) and in expired air as (CO2)-C-14 (rats, 1.5%; mice, 10-18%), or remained in the tissues (rats, 2.7-4.4%; mice, 1.5-1.7%). No parent BGE was detected in rat or mouse urine. Fifteen urinary metabolites were identified, including 3-butoxy-2-hydroxy-1-propanol and its monosulfate or monoglucuronide conjugates, 3-butoxy-2-hydroxypropionic acid, O-butyl-N- acetylserine, butoxyacetic acid, 2-butoxyethanol, and 3-butoxy-1-(N-acetylcystein-S-yl)-2-propanol, the mercapturic acid metabolite derived from conjugation of glutathione (GSH) with BGE at the C-1 position. Some of these metabolites underwent further omega-1 oxidation to form a 3'-hydroxybutoxy substitution. One urinary metabolite was from omega-oxidation of 3-butoxy-1-(N-acetylcystein-S-yl)-2-propanol to yield the corresponding carboxylic acid. Oxidative deamination of 3-butoxy-1(cystein-S-yl)-2-propanol gave the corresponding alpha-keto acid and alpha-hydroxy acid metabolites that were present in mouse urine but not in rat urine. An in vitro incubation of BGE with GSH showed that the conjugation occurred only at the C-1 position with or without the addition of GSH S-transferase. C1 Natl Inst Environm Sci, Res Triangle Pk, NC USA. RP Chen, LJ (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM ljferguson@lrri.org NR 11 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD DEC PY 2007 VL 35 IS 12 BP 2218 EP 2224 DI 10.1124/dmd.107.016931 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 233HL UT WOS:000251081500012 PM 17875671 ER PT J AU Donahue, A AF Donahue, Amy TI Guest editorial: Current state of knowledge-outcomes research in children with mild to severe hearing loss SO EAR AND HEARING LA English DT Editorial Material C1 NIDCD, Vestibular Branch, NIH, Bethesda, MD 20892 USA. RP Donahue, A (reprint author), NIDCD, Vestibular Branch, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD DEC PY 2007 VL 28 IS 6 BP 713 EP 714 PG 2 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 228ZA UT WOS:000250769900001 ER PT J AU King, KA Makishima, T Zalewski, CK Bakalov, VK Griffith, AJ Bondy, CA Brewer, CC AF King, Kelly A. Makishima, Tomoko Zalewski, Christopher K. Bakalov, Vladimir K. Griffith, Andrew J. Bondy, Carolyn A. Brewer, Carmen C. TI Analysis of auditory phenotype, and karyotype in 200 females with Turner syndrome SO EAR AND HEARING LA English DT Article ID HEARING-LOSS; GROWTH-HORMONE; OTITIS-MEDIA; DISEASE; WOMEN; EAR; ESTROGEN; ADULTS AB Objectives: Turner syndrome is the most common sex chromosome disorder in females, and is caused by a total or partial deletion of one X chromosome. The purpose of this study was to describe the auditory phenotype in a large group of individuals with Turner Syndrome, with analysis focusing on hearing loss and age, as well as the phenotypic relationship to karyotype variation. Design: Our analysis of auditory function was part of a large-scale, natural history study in which clinical and genetic factors related to Turner syndrome were examined. This ascertainment avoids the bias inherent in studies of patients referred to audiology or otolaryngology specialty clinics. Analysis included data from 200 females with Turner syndrome ranging in age from 7 to 61 yr (mean 27.9 yr). Results: We observed hearing loss in approximately one-half of females with Turner syndrome, and report on a common, previously unlabeled audiometric configuration found in 24% of ears tested. Our cross-sectional design revealed an observable deterioration in hearing loss above the averaged rate of age-related hearing loss seen in an otologically screened, standardized population. Karyotype analysis revealed air conduction thresholds that were significantly poorer in the 46, XdelXp and 46, XiXq groups than in the 46, XdelXq group. Conclusions: This natural history study provides a more representative description of the auditory phenotype associated with Turner syndrome than previous studies that may have been biased by the method of ascertainment. Correlative analysis of Turner syndrome-specific hearing loss features with karyotype revealed that air conduction threshold elevations are associated with loss of the p arm of chromosome X. Our cross-sectional data indicate a loss of hearing sensitivity at an accelerated rate beyond a normal age-related decline, which warrants continued audiologic monitoring in all females with Turner syndrome regardless of a history of normal hearing. C1 Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, College Pk, MD USA. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Maryland, Dept Speech & Hearing Sci, College Pk, MD 20742 USA. RP Brewer, CC (reprint author), NIH, Otolaryngol Branch, 10 Ctr Dr,Bldg 10-5C306, Bethesda, MD 20892 USA. EM brewerc@nidcd.nih.gov FU Intramural NIH HHS NR 27 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD DEC PY 2007 VL 28 IS 6 BP 831 EP 841 PG 11 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 228ZA UT WOS:000250769900011 PM 17982369 ER PT J AU Bergmann, L Hirschfeld, S Morris, C Palmeri, S Stone, A AF Bergmann, Lothar Hirschfeld, Steven Morris, Charles Palmeri, Sergio Stone, Andrew CA Biotherapy Dev Assoc BDA TI Progression-free survival as an end-point in clinical trials of biotherapeutic agents SO EJC SUPPLEMENTS LA English DT Article DE Anticancer agents; Biologics; Drug approval; Drug registration; End-point; Progression-free survival; Surrogate; Targeted agents AB Progression-free survival (PFS), the time from registration or randomisation of a patient until objective disease progression or death, can be considered as an outcome for clinical research and also as a basis for regulatory approval. Current experience suggests that greater standardisation and consistency are needed for clinical trials utilising PFS end-points. To this end, the Biotherapy Development Association (BDA) convened a breakout session on the topic of PFS during its Third Alpine Meeting held 14-16 March 2007. Representatives of the pharmaceutical industry, regulatory agencies, academia, and patient advocacy groups identified challenges, developed recommendations, and worked to build consensus regarding the conduct of clinical trials utilising PFS as an end-point to help speed new targeted biologics to the patient bedside. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Bergmann, Lothar] Goethe Univ Frankfurt, Canc Ctr Rhein Main, Med Clin 2, D-60590 Frankfurt, FRG, Germany. [Hirschfeld, Steven] NICHHD, Bethesda, MD 20814 USA. [Morris, Charles] AstraZeneca Int, Wilmington, DE USA. [Palmeri, Sergio] Univ Palermo, Chair Med Oncol, I-90127 Palermo, Italy. [Stone, Andrew] AstraZeneca Ltd, Oncol Stat Expert, Macclesfield SK10 4TG, Cheshire, England. RP Bergmann, L (reprint author), Goethe Univ Frankfurt, Canc Ctr Rhein Main, Med Clin 2, Theodor Stern Kai 7, D-60590 Frankfurt, FRG, Germany. EM L.Bergmann@em.uni-frankfurt.de RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 15 TC 3 Z9 3 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD DEC PY 2007 VL 5 IS 9 BP 23 EP 28 DI 10.1016/j.ejcsup.2007.09.002 PG 6 WC Oncology SC Oncology GA V12XR UT WOS:000207632400022 ER PT J AU Chen, HX Tinetti, A Zwierzina, H AF Chen, H. X. Tinetti, A. Zwierzina, H. TI Clinical trial design issues: Session 2 SO EJC SUPPLEMENTS LA English DT Meeting Abstract DE Trial design; Optimal biological dose (OBD); Interleukin-6; Combination therapies; Cancer vaccines C1 [Chen, H. X.] NCI, CTEP, Bethesda, MD 20852 USA. [Tinetti, A.] Global Therapeut Head Oncol Haematol & Transplan, Quintiles Med & Sci Serv, F-67832 Tanneries, France. [Zwierzina, H.] Med Univ Klin, A-6020 Innsbruck, Austria. EM Heinz.Zwierzina@i-med.ac.at NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD DEC PY 2007 VL 5 IS 9 BP 46 EP 46 DI 10.1016/j.ejcsup.2007.09.028 PG 1 WC Oncology SC Oncology GA V12XR UT WOS:000207632400030 ER PT J AU Chen, H AF Chen, H. TI OPTIMISING STRATEGIES FOR CLINICAL DEVELOPMENT OF COMBINATIONS OF TARGETED AGENTS SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 [Chen, H.] NCI, CTEP, Bethesda, MD 20852 USA. EM Helen_Chen@nih.gov NR 6 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD DEC PY 2007 VL 5 IS 9 BP 48 EP 50 DI 10.1016/j.ejcsup.2007.09.030 PG 5 WC Oncology SC Oncology GA V12XR UT WOS:000207632400032 ER PT J AU Chang, CR Blackstone, C AF Chang, Chuang-Rung Blackstone, Craig TI Drp1 phosphorylation and mitochondrial regulation SO EMBO REPORTS LA English DT Letter ID DEPENDENT PROTEIN-KINASE; GTPASE DRP1; FISSION C1 [Chang, Chuang-Rung; Blackstone, Craig] Natl Inst Neurol Disorders & Stroke, Cellular Neurol Unit, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), Natl Inst Neurol Disorders & Stroke, Cellular Neurol Unit, Natl Inst Hlth, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov RI Chang, Chuang-Rung /C-1815-2012 NR 5 TC 36 Z9 37 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD DEC PY 2007 VL 8 IS 12 BP 1088 EP 1089 DI 10.1038/sj.embor.7401118 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 247QX UT WOS:000252095500003 PM 18059302 ER PT J AU Klein, E Smith, DL Laxminarayan, R AF Klein, Eili Smith, David L. Laxminarayan, Ramanan TI Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999-2005 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID SOFT-TISSUE INFECTIONS; BLOOD-STREAM INFECTIONS; INTENSIVE-CARE UNITS; ANTIMICROBIAL RESISTANCE; RISK-FACTORS; NOSOCOMIAL INFECTIONS; CHANGING EPIDEMIOLOGY; US HOSPITALS; SURVEILLANCE; PREVALENCE AB Hospital-acquired infections with Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA) infections, are a major cause of illness and death and impose serious economic costs on patients and hospitals. However, the recent magnitude and trend of these infections have not been reported. We used national hospitalization and resistance data to estimate the annual number of hospitalizations and deaths associated with S. aureus and MRSA from 1999 through 2005. During this period, the estimated number of S. aureus-related hospitalizations increased 62%, from 294,570 to 477,927, and the estimated number of MRSArelated hospitalizations more than doubled, from 127,036 to 278,203. Our findings suggest that S. aureus and MRSA should be considered a national priority for disease control. C1 Resources Future Inc, Washington, DC 20009 USA. Natl Inst Hlth, Bethesda, MD USA. RP Laxminarayan, R (reprint author), Resources Future Inc, 1616 P St NW, Washington, DC 20009 USA. EM ramanan@rff.org RI Klein, Eili/C-3745-2012; Smith, David/L-8850-2013; OI Smith, David/0000-0003-4367-3849; Klein, Eili/0000-0002-1304-5289 NR 40 TC 473 Z9 486 U1 12 U2 57 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2007 VL 13 IS 12 BP 1840 EP 1846 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 238KN UT WOS:000251446600007 PM 18258033 ER PT J AU Gray, GC McCarthy, T Capuano, AW Setterquist, SF Olsen, CW Alavania, MC Lynch, CF AF Gray, Gregory C. McCarthy, Troy Capuano, Ana W. Setterquist, Sharon F. Olsen, Christopher W. Alavania, Michael C. Lynch, Charles F. TI Swine workers and swine influenza virus infections SO EMERGING INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; GENETIC-CHARACTERIZATION; A VIRUSES; PANDEMIC INFLUENZA; SEROLOGIC EVIDENCE; NORTH-AMERICA; PIGS; CANADA; H1N2 AB In 2004, 803 rural Iowans from the Agricultural Health Study were enrolled in a 2-year prospective study of zoonotic influenza transmission. Demographic and occupational exposure data from enrollment, 12-month, and 24-month follow-up encounters were examined for association with evidence of previous and incident influenza virus infections. When proportional odds modeling with multivariable adjustment was used, upon enrollment, swine-exposed participants (odds ratio [OR] 54.9, 95% confidence interval [CI] 13.0-232.6) and their nonswine-exposed spouses (OR 28.2, 95% Cl 6.1-130.1) were found to have an increased odds of elevated antibody level to swine influenza (H1N1) virus compared with 79 nonexposed University of Iowa personnel. Further evidence of occupational swine influenza virus infections was observed through self-reported influenza-like illness data, comparisons of enrollment and follow-up serum samples, and the isolation of a reassortant swine influenza (H1N11) virus from an ill swine farmer. Study data suggest that swine workers and their nonswine-exposed spouses are at increased risk of zoonotic influenza virus infections. C1 Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. Univ Wisconsin, Madison Sch Vet Med, Madison, WI USA. Natl Canc Inst, Bethesda, MD USA. RP Gray, GC (reprint author), Univ Iowa, Coll Publ Hlth, Dept Epidemiol, 200 Hawkins Dr,C21K GH, Iowa City, IA 52242 USA. EM gregory-gray@uiowa.edu FU NIAID NIH HHS [R21 AI059214, R21 AI059214-01] NR 30 TC 103 Z9 118 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2007 VL 13 IS 12 BP 1871 EP 1878 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 238KN UT WOS:000251446600012 PM 18258038 ER PT J AU Luo, ZJ Li, JL Qin, YF Ma, Y Liang, XH Xian, J Lu, DC Wei, MY Yang, JY Yang, MQ He, ZH AF Luo, Zuojie Li, Jianling Qin, Yinfen Ma, Yan Liang, Xinghuan Xian, Jing Lu, Decheng Wei, Minyi Yang, Jack Y. Yang, Mary Qu He, Zhiheng TI Differential expression of human telomerase catalytic subunit mRNA by in situ hybridization in pheochromocytomas SO ENDOCRINE PATHOLOGY LA English DT Article DE pheochromocytoma; hTERT mRNA; hTERT; Ki-67; p27(kip1) ID CELL-CYCLE REGULATORS; MALIGNANT PHEOCHROMOCYTOMA; PROGNOSTIC-SIGNIFICANCE; REVERSE-TRANSCRIPTASE; P27(KIP1) EXPRESSION; INHIBITOR P27(KIP1); BREAST-CANCER; BENIGN; TUMORS; KI-67 AB In pheochromocytomas, it is very difficult to predict malignant potential by conventional histology or immunohistochemical and molecular markers. We investigated the expression of human telomerase catalytic component (hTERT) mRNA, hTERT protein, Ki-67 antigen, and p27(kip1) in pheochromocytomas (27 benign, 7 suspected malignant, and 7 malignant), and evaluated the possibility of expressions of these proteins, and hTERT mRNA serve as diagnostic markers for predicting the biological behavior of these tumors. All tumors showed the classical histology and typical immunohistochemical pattern. By in situ hybridization, hTERT mRNA was expressed in 5/7 malignant tumors (defined as the presence of metastasis and/or extensive local invasion) as compared with 3/27 benign tumors. We examined the hTERT by immunohistochemistry to confirm the mRNA. hTERT mRNA expression was correlated with hTERT protein expression. All benign tumors exhibited no immunopositivity or <1% of cells stained for Ki-67 antigen. Six out of seven malignant tumors have shown either hTERT mRNA expression or Ki-67 immunoreactivity. While no statistical difference in p27(kip1) expressions was observed among benign, malignant, and suspected malignant tumors, there was a statistical difference between the normal adrenal medulla samples and tumors (p < 0.001). Thus, hTERT mRNA detection by in situ hybridization, hTERT expression, and Ki-67 antigen expression are all useful tools for differentiating malignant from benign pheochromocytomas. C1 Guangxi Med Univ, Dept Endocrinol, Nanning 530021, Peoples R China. First Affiliated Hosp, Nanning 530021, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Natl Human Genome Res Inst, US Dept Hlth & Human Serv, Rockville, MD 20850 USA. Harvard Univ, Joslin Diabet Ctr, Div Res, Sch Med, Boston, MA 02215 USA. RP Luo, ZJ (reprint author), Guangxi Med Univ, Dept Endocrinol, 6 Shuangyong Rd, Nanning 530021, Peoples R China. EM zluo888@yahoo.com.cn NR 31 TC 1 Z9 1 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD WIN PY 2007 VL 17 IS 4 BP 387 EP 398 PG 12 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 160FN UT WOS:000245926400010 ER PT J AU Mukherjee, AB Zhang, ZJ Chilton, BS AF Mukherjee, Anil B. Zhang, Zhongjian Chilton, Beverly S. TI Uteroglobin: a steroid-inducible immunomodulatory protein that founded the Secretoglobin superfamily SO ENDOCRINE REVIEWS LA English DT Review ID CELL SECRETORY PROTEIN; AMINO-ACID-SEQUENCE; RESPIRATORY-DISTRESS-SYNDROME; 10 KDA PROTEIN; RECOMBINANT HUMAN UTEROGLOBIN; TISSUE-SPECIFIC EXPRESSION; PROMOTER-BINDING PROTEINS; ANTIINFLAMMATORY PEPTIDES ANTIFLAMMINS; HETERONUCLEAR MULTIDIMENSIONAL NMR; INTERMITTENT ALLERGIC RHINITIS AB Blastokinin or uteroglobin ( UG) is a steroid-inducible, evolutionarily conserved, secreted protein that has been extensively studied from the standpoint of its structure and molecular biology. However, the physiological function( s) of UG still remains elusive. Isolated from the uterus of rabbits during early pregnancy, UG is the founding member of a growing superfamily of proteins called Secretoglobin ( Scgb). Numerous studies demonstrated that UG is a multifunctional protein with antiinflammatory/immunomodulatory properties. It inhibits soluble phospholipase A(2) activity and binds and perhaps sequesters hydrophobic ligands such as progesterone, retinols, polychlorinated biphenyls, phospholipids, and prostaglandins. In addition to its antiinflammatory activities, UG manifests antichemotactic, antiallergic, antitumorigenic, and embryonic growth-stimulatory activities. The tissue-specific expression of the UG gene is regulated by several steroid hormones, although a nonsteroid hormone, prolactin, further augments its expression in the uterus. The mucosal epithelia of virtually all organs that communicate with the external environment express UG, and it is present in the blood, urine, and other body fluids. Although the physiological functions of this protein are still under investigation, a single nucleotide polymorphism in the UG gene appears to be associated with several inflammatory/autoimmune diseases. Investigations with UG-knockout mice revealed that the absence of this protein leads to phenotypes that suggest its critical homeostatic role( s) against oxidative damage, inflammation, autoimmunity, and cancer. Recent studies on UG-binding proteins ( receptors) provide further insight into the multifunctional nature of this protein. Based on its antiinflammatory and antiallergic properties, UG is a potential drug target. C1 NICHHD, Sect Dev Genet,Endocrinol & Genet Program, Heritable Disorders Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Anat, Lubbock, TX 79430 USA. RP Mukherjee, AB (reprint author), NICHHD, Sect Dev Genet,Endocrinol & Genet Program, Heritable Disorders Branch, Natl Inst Hlth, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [HD-29457] NR 254 TC 72 Z9 79 U1 2 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD DEC PY 2007 VL 28 IS 7 BP 707 EP 725 DI 10.1210/er.2007-0018 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 238KA UT WOS:000251445300001 PM 17916741 ER PT J AU Meng, XL Rennert, OM Chan, WY AF Meng, Xing-Li Rennert, Owen M. Chan, Wai-Yee TI Human chorionic gonadotropin induces neuronal differentiation of PC12 cells through activation of stably expressed Lutropin/Choriogonadotropin receptor SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE RECEPTOR; NERVE GROWTH-FACTOR; SIGNAL-REGULATED KINASE; MALE PRECOCIOUS PUBERTY; NEURITE OUTGROWTH; PROTEIN-KINASE; SPINAL-CORD; PHEOCHROMOCYTOMA CELLS; TYROSINE KINASE; MAP KINASE AB Human chorionic gonadotropin (hCG) and LH play an important role in reproductive physiology. Both hCG and LH bind to the same LH/choriogonadotropin receptor (LH/CG-R). Recent reports documented the temporal and spatial expression of LH/CG-R in the developing and mature mammalian brain. Administration of hCG promoted nerve regeneration in vivo and neurite outgrowth and survival of primary neurons in vitro. The function of hCG/LH and LH/CG-R in the nervous system remains unclear. In this study, we report that hCG/LH induced distinct morphological and biochemical changes, characteristic of neuronal differentiation, in PC12 cells stably expressing LH/CG- R and that the differentiation effect is ligand dose and time dependent. Western blot analysis revealed that both the ERKs and p38 MAPK are activated after hCG treatment. Inhibitor studies showed both the ERK and p38 MAPK signal transduction pathways are required for this differentiation process, which is cAMP dependent and protein kinase A independent. These findings imply a potential role for hCG/LH and LH/CG- R in the development, maintenance, and regeneration of the mammalian nervous system, and in the neuropathogenesis of genetic diseases caused by a mutated LH/CG- R. C1 NICHHD, Sect Dev Genom, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. RP Chan, WY (reprint author), NICHHD, Sect Dev Genom, Lab Clin Genom, NIH, Bldg 49,Room 2A08,49 Convent Dr,MSC 4429, Bethesda, MD 20892 USA. EM chanwy@mail.nih.gov FU Intramural NIH HHS NR 47 TC 15 Z9 17 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2007 VL 148 IS 12 BP 5865 EP 5873 DI 10.1210/en.2007-0941 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 231RP UT WOS:000250967000029 PM 17761763 ER PT J AU O'Shea, PJ Guigon, CJ Williams, GR Cheng, SY AF O'Shea, Patrick J. Guigon, Celine J. Williams, Graham R. Cheng, Sheue-Yann TI Regulation of fibroblast growth factor receptor-1 (Fgfr1) by thyroid hormone: Identification of a thyroid hormone response element in the murine fgfr1 promoter SO ENDOCRINOLOGY LA English DT Article ID OSTEOCLAST FORMATION; GENE-EXPRESSION; BETA-RECEPTOR; M-CSF; BONE; RESISTANCE; TRANSCRIPTION; CELLS; SP1; OSTEOPOROSIS AB T-3 is essential for normal skeletal development, acting mainly via the TR alpha 1 nuclear receptor. Nevertheless, the mechanisms of T-3 action in bone are poorly defined. Fibroblast growth factor receptor-1 (FGFR1) is also essential for bone formation. Fgfr1 expression and activity are positively regulated by T-3 in osteoblasts, and in mice that harbor a dominant negative PV mutation targeted to TR alpha 1 or TR beta, Fgfr1 expression is sensitive to skeletal thyroid status. To investigate mechanisms underlying T-3 regulation of FGFR1, we obtained primary calvarial osteoblasts from wild-type and TR beta(PV/PV) littermate mice. T-3 treatment increased Fgfr1 expression 2-fold in wildtype cells, but 8-fold in TR beta(PV/PV) osteoblasts. The 4-fold increased T-3 sensitivity of TR beta PV/PV osteoblasts was associated with a markedly increased ratio of TR alpha 1:TR beta 1 expression that resulted from reduced TR beta 1 expression in TR beta(PV/PV) osteoblasts compared with wild-type. Bioinformatics and gel shift studies, and mutational analysis, identified a specific TR binding site 279-264 nucleotides upstream of the murine Fgfr1 promoter transcription start site. Transient transfection analysis of a series of Fgfr1 promoter 5'-deletion constructs, of a mutant reporter construct, and a series of heterologous promoter constructs, confirmed that this region of the promoter mediates a TR-dependent transcriptional response to T-3. Thus, in addition to indirect regulation of FGFR1 expression by T-3 reported previously, T-3 also activates the Fgfr1 promoter directly via a thyroid hormone response element located at positions -279/-264. C1 NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Div Med, London W12 0NN, England. Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England. RP Cheng, SY (reprint author), NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural NIH HHS; Medical Research Council [G0501486] NR 45 TC 7 Z9 7 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2007 VL 148 IS 12 BP 5966 EP 5976 DI 10.1210/en.2007-0114 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 231RP UT WOS:000250967000039 PM 17761769 ER PT J AU Wilson, DM AF Wilson, David M., III TI Processing of nonconventional DNA strand break ends SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE oxidative DNA damage; base excision repair; XRCC1; spinocerebellar ataxia; AOA1 and SCAN1 ID BASE EXCISION-REPAIR; HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; HUMAN POLYNUCLEOTIDE KINASE; SISTER-CHROMATID EXCHANGE; PROKARYOTIC RNA-POLYMERASES; TOPOISOMERASE-I COMPLEXES; WERNER-SYNDROME PROTEIN; LIGASE-III-ALPHA; HUMAN-CELLS; PHOSPHODIESTERASE TDP1 AB Single-strand breaks (SSBs) are one of the most common forms of genetic damage, arising from attack of DNA by reactive oxygen species or as intended or inadvertent products of normal cellular DNA metabolic events. Recent evidence linking defects in the enzymatic processing of nonconventional DNA SSBs, i.e., lesions incompatible with polymerase or ligase reactions, with inherited neurodegenerative disorders, reveals the importance of SSB repair in disease manifestation. I review herein the major eukaryotic enzymes (with an emphasis on the human proteins) responsible for the "clean-up" of DNA breaks harboring 3'- or 5'-blocking termini, and the cellular and disease ramifications of unrepaired SSB damage. C1 NIA, Lab Mol Gerantol, NIH, Baltimore, MD 21224 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerantol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@gre.nia.nih.gov NR 123 TC 20 Z9 21 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD DEC PY 2007 VL 48 IS 9 BP 772 EP 782 DI 10.1002/em.20346 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 242FC UT WOS:000251708900007 PM 17948279 ER PT J AU Thigpen, JE Setchell, KDR Padilla-Banks, E Haseman, JK Saunders, HE Caviness, GF Kissling, GE Grant, MG Forsythe, DB AF Thigpen, Julius E. Setchell, Kenneth D. R. Padilla-Banks, Elizabeth Haseman, Joseph K. Saunders, Hannah E. Caviness, Gordon F. Kissling, Grace E. Grant, Mary G. Forsythe, Diane B. TI Variations in phytoestrogen content between different mill dates of the same diet produces significant differences in the time of vaginal opening in CD-1 mice and F344 rats but not in CD Sprague-Dawley rats SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE dietary phytoestrogens; endocrine disruptors; rodent species/strain sensitivities in VO; end points ID LABORATORY-ANIMAL FEED; UTEROTROPHIC BIOASSAY; RODENT DIETS; OECD PROGRAM; ESTROGENIC ACTIVITY; ENDOCRINE DISRUPTOR; MOUSE BIOASSAY; SOYBEAN SEEDS; GENISTEIN; ISOFLAVONES AB BACKGROUND: The optimum test diet and rodent species/strain for evaluating endocrine-disrupting compounds (EDCs) are critical. OBJECTIVES: We conducted studies to evaluate rodent species sensitivity and the effects of diets varying in phytoestrogen content on the time of vaginal opening (VO) in CD-1 Mice, Fischer 344 (F344) rats, and CID Sprague-Dawley (S-D) rats. METHODS: Mice were weaned on postnatal day (PND) 15 and rats on PND19 and randomly assigned to control or test diets. Body weights, food consumption, and time of VO were recorded. RESULTS: The time of VO was significantly advanced in F344 rats fed diets containing daidzein and genistein, whereas these same diets did not advance VO in S-D rats. When animals were fed the AIN-76A diet spiked with genistein, time of VO was significantly advanced at all doses in CD-1 mice, at the two highest doses in F344 rats, and at the highest dose in S-D rats. The time of VO in F344 rats was more highly correlated with the phytoestrogen content than with the total metabolizable energy (ME) of 12 diets. CONCLUSIONS: The S-D rat is less sensitive to dietary phytoestrogens compared with the F344 rat or the CD-1 mouse, suggesting that the S-D rat is not the ideal model for evaluating estrogenic activity of EDCs. The profound effects of dietary phytoestrogens on the time of VO, an estrogen-sensitive marker, indicate that a standardized open-formula phytoestrogen-free diet containing a low ME level should be used to optimize the sensitivity of estrogenic bioassays. C1 NIEHS, Qual Assurance Lab, Comparat Med Branch, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Cincinnati Childrens Hosp Med Ctr, Dept Pathol, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Thigpen, JE (reprint author), NIEHS, Qual Assurance Lab, Comparat Med Branch, NIH,Dept Hlth & Human Serv, POB 12233,Mail Drop C1-06, Res Triangle Pk, NC 27709 USA. EM thigpen@niehs.nih.gov NR 42 TC 41 Z9 41 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2007 VL 115 IS 12 BP 1717 EP 1726 DI 10.1289/ehp.10165 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 237YE UT WOS:000251411500030 PM 18087589 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Some bacteria degrade explosives, others prefer boiling methanol SO ENVIRONMENTAL MICROBIOLOGY LA English DT Editorial Material ID ACCESSORY NIDAMENTAL GLAND; SQUID LOLIGO-PEALEI; SP-NOV.; ROSEIFLEXUS-CASTENHOLZII; ENTEROBACTER-SAKAZAKII; NANOARCHAEUM-EQUITANS; IGNICOCCUS-HOSPITALIS; ARCHAEON IGNICOCCUS; BACILLUS-PUMILUS; GEN. NOV. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 43 TC 5 Z9 5 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD DEC PY 2007 VL 9 IS 12 BP 2905 EP 2910 DI 10.1111/j.1462-2920.2007.01480.x PG 6 WC Microbiology SC Microbiology GA 228VS UT WOS:000250761300001 PM 17991022 ER PT J AU Stahl, SM Hahn, AA AF Stahl, Sidney M. Hahn, Anneliese A. TI The resource centers for minority aging research (RCMAR): Community/researcher interaction and relationships SO ETHNICITY & DISEASE LA English DT Editorial Material DE community research; aging; minority AB For more than a decade, the National Institute on Aging (NIA) has led a program called the Resource Centers for Minority Aging Research (RCMAR). One of the four key components of the RCMARs is a Community Liaison Core whose objectives are to conduct research on recruiting community members for scientific studies and to facilitate working relationships with host communities. The articles in this supplement represent some of the scientific knowledge available on community-based participatory research (CBPR) at the RCMARs. The hope is that this supplement will motivate others involved in CBPR to more fully engage in the conduct of science related to relationships that mutually benefit communities and researchers. C1 NIA, Behav & Social Res Program, NIH, Bethesda, MD 20892 USA. RP Stahl, SM (reprint author), NIA, Behav Proc Branch, 7201 Wisconsin Ave,533, Bethesda, MD 20892 USA. EM StahlS@nia.nih.gov NR 1 TC 3 Z9 3 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD WIN PY 2007 VL 17 IS 1 SU 1 BP 1 EP 2 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175IM UT WOS:000247007300001 ER PT J AU Brewster, DH Horner, MJD Rowan, S Jelfs, P de Vries, E Pukkala, E AF Brewster, David H. Horner, Marie-Josephe D. Rowan, Steve Jelfs, Paul de Vries, Esther Pukkala, Eero TI Left-sided excess of invasive cutaneous melanoma in six countries SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE asymmetry; epidemiology; laterality; melanoma; skin neoplasms AB To investigate the laterality of cutaneous melanoma (ICD-10 C43), we obtained data spanning the period of diagnosis 1998-2003 from six population-based cancer registries: New South Wales, Australia; England; Finland; The Netherlands; Scotland; and the Surveillance Epidemiology and End Results (SEER) Program of the United States of America (restricted to 'White' race category only). For cases with laterality recorded, the overall ratios of left- to right-sided tumours were calculated. We found that left to right ratios were consistently greater than 1.00, ranging from 1.08 (New South Wales, Australia and US SEER 'White') to 1.18 (Scotland), with an overall ratio for all registries combined of 1.10 (95% confidence interval 1.08-1.11). There were no statistically significant differences by sex or age group for all sub-sites combined, or for upper limb or lower limb melanomas. The excess of left-sided tumours seems unlikely to be explained by chance or recording bias. The most likely explanations would appear to be either differences in sun exposure and/or asymmetry of melanocyte distribution or characteristics arising at the time of embryological development. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Brewster, David H.] NHS Natl Serv Scotland, Scottish Canc Registry, Informat Serv Div, Edinburgh EH12 9EB, Midlothian, Scotland. [Horner, Marie-Josephe D.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Rowan, Steve] Off Natl Stat, Natl Canc Intelligence Ctr, SHARD, London SW1V 2QQ, England. [Jelfs, Paul] Canc Inst NSW, Canc Informat & Registries Div, Alexandria, NSW 1435, Australia. [de Vries, Esther] Erasmus MC, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands. [Pukkala, Eero] Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FI-00170 Helsinki, Finland. RP Brewster, DH (reprint author), NHS Natl Serv Scotland, Scottish Canc Registry, Informat Serv Div, Gyle Sq,1 S Gyle Crescent, Edinburgh EH12 9EB, Midlothian, Scotland. EM David.Brewster@isd.csa.scot.nhs.uk RI de Vries, Esther/A-6603-2009; OI de Vries, Esther/0000-0002-5560-2258; Brewster, David/0000-0002-5346-5608 NR 7 TC 23 Z9 23 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 2007 VL 43 IS 18 BP 2634 EP 2637 DI 10.1016/j.ejca.2007.09.021 PG 4 WC Oncology SC Oncology GA 248HB UT WOS:000252142300003 PM 17988856 ER PT J AU Giovacchini, G Bonwetsch, R Herscovitch, P Carson, RE Theodore, WH AF Giovacchini, Giampiero Bonwetsch, Robert Herscovitch, Peter Carson, Richard E. Theodore, William H. TI Cerebral blood flow in temporal lobe epilepsy: a partial volume correction study SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE temporal lobe epilepsy; partial volume correction; cerebral blood flow; positron emission tomography; cerebral glucose metabolism ID POSITRON-EMISSION-TOMOGRAPHY; COMPLEX PARTIAL SEIZURES; C-11 FLUMAZENIL PET; GLUCOSE-METABOLISM; BRAIN-REGIONS; HIPPOCAMPAL; MRI; LOCALIZATION; SPECT; PERFUSION AB Purpose Previous studies in temporal lobe epilepsy (TLE) have shown that, owing to brain atrophy, positron emission tomography (PET) can overestimate deficits in measures of cerebral function such as glucose metabolism (CMRglu) and neuroreceptor binding. The magnitude of this effect on cerebral blood flow (CBF) is unexplored. The aim of this study was to assess CBF deficits in TLE before and after magnetic resonance imaging-based partial volume correction (PVC). Methods Absolute values of CBF for 21 TLE patients and nine controls were computed before and after PVC. In TLE patients, quantitative CMRglu measurements also were obtained. Results Before PVC, regional values of CBF were significantly (p < 0.05) lower in TLE patients than in controls in all regions, except the fusiform gyrus contralateral to the epileptic focus. After PVC, statistical significance was maintained in only four regions: ipsilateral inferior temporal cortex, bilateral insula and contralateral amygdala. There was no significant difference between patients and controls in CBF asymmetry indices (AIs) in any region before or after PVC. In TLE patients, AIs for CBF were significantly smaller than for CMRglu in middle and inferior temporal cortex, fusiform gyrus and hippocampus both before and after PVC. A significant positive relationship between disease duration and AIs for CMRglu, but not CBF, was detected in hippocampus and amygdala, before but not after PVC. Conclusion PVC should be used for PET CBF measurements in patients with TLE. Reduced blood flow, in contrast to glucose metabolism, is mainly due to structural changes. C1 Univ Milan, I-20132 Milan, Italy. NINDS, Clin Epilepsy Sect, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. Yale PET Ctr, New Haven, CT USA. RP Giovacchini, G (reprint author), Univ Milan, Via Olgettina 60, I-20132 Milan, Italy. EM giovacchini.giampiero@hsr.it RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 40 TC 6 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD DEC PY 2007 VL 34 IS 12 BP 2066 EP 2072 DI 10.1007/s00259-007-0499-x PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 237JQ UT WOS:000251370400021 PM 17768621 ER PT J AU McCrae, RR Terracciano, A Realo, A Allik, J AF McCrae, Robert R. Terracciano, Antonio Realo, Anu Allik, Jueri TI Climatic warmth and national wealth: Some culture-level determinants of national character stereotypes SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article; Proceedings Paper CT 115th Annual Convention of the American-Psychological-Association CY AUG 17-20, 2007 CL San Francisco, CA SP Amer Psychol Assoc DE personality; national character; stereotypes; cross-cultural; Five-Factor Model ID PERSONALITY-TRAITS; ETHNIC-STEREOTYPES; POLITICAL VIOLENCE; 5-FACTOR MODEL; DIMENSIONS; TEMPERATURE; COMPETENCE; PROFILES; ACCURACY; VALUES AB National character stereotypes are widely shared, but do not reflect assessed levels of personality traits. In this article we present data illustrating the divergence of stereotypes and assessed personality traits in North and South Italy, test hypotheses about the associations of temperature and national wealth with national character stereotypes in 49 cultures, and explore possible links to national values and beliefs. Results suggest that warmth and wealth are common determinants of national stereotypes, but that there are also idiosyncratic influences on the perceptions of individual nations. Published in 2007 by John Wiley & Sons, Ltd. C1 [McCrae, Robert R.; Terracciano, Antonio] NIA, Gerontol Res Ctr, NIH, DHHS, Baltimore, MD 21224 USA. [Realo, Anu; Allik, Jueri] Univ Tartu, Dept Psychol, Estonian Ctr Behav & Hlth Sci, Tartu, Estonia. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, NIH, DHHS, Box 3,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mccraej@gre.nia.nih.gov RI terracciano, antonio/B-1884-2008; Allik, Juri/D-5609-2009; Realo, Anu/M-9524-2016 OI Allik, Juri/0000-0002-8358-4747; FU Intramural NIH HHS [Z99 AG999999, ZIA AG000180-25, ZIA AG000180-26] NR 65 TC 34 Z9 35 U1 4 U2 12 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD DEC PY 2007 VL 21 IS 8 BP 953 EP 976 DI 10.1002/per.647 PG 24 WC Psychology, Social SC Psychology GA 254AO UT WOS:000252558900001 PM 20046546 ER PT J AU McCrae, RR Terracciano, A Realo, A Allik, J AF McCrae, Robert R. Terracciano, Antonio Realo, Anu Allik, Jueri TI On the validity of culture-level personality and stereotype scores SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Editorial Material DE personality assessment; stereotypes; self-report; national differences ID SELF; PROFILES; TRAITS AB In response to comments by Perugini and Richetin and by Ashton, we discuss the reference-group effect as a potential source of distortion in cross-cultural comparisons and suggest some research designs to test its nature and importance. We argue that laboratory studies of personality are of limited utility in understanding personality questionnaire responses in real life. We summarise evidence in favour of the validity of aggregate personality traits and suggest that more scepticism is needed with regard to the accuracy of national character stereotypes. Published in 2007 by John Wiley & Sons, Ltd. C1 [McCrae, Robert R.; Terracciano, Antonio] NIA, Gerontol Res Ctr, NIH, DHHS, Baltimore, MD 21224 USA. [Realo, Anu; Allik, Jueri] Univ Tartu, Estonian Ctr Behav & Hlth Sci, Tartu, Estonia. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, NIH, DHHS, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; Allik, Juri/D-5609-2009; Realo, Anu/M-9524-2016 OI Allik, Juri/0000-0002-8358-4747; NR 16 TC 9 Z9 9 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD DEC PY 2007 VL 21 IS 8 BP 987 EP 991 DI 10.1002/per.659 PG 5 WC Psychology, Social SC Psychology GA 254AO UT WOS:000252558900004 ER PT J AU Rousseva, LA Gaillard, ER Paik, DC Merriam, JC Ryzhov, V Garland, DL Dillon, JP AF Rousseva, Lilia A. Gaillard, Elizabeth R. Paik, David C. Merriam, John C. Ryzhov, Victor Garland, Donita L. Dillon, James P. TI Oxindolealanine in age-related human cataracts SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE tryptophan; oxindolealanine; lens cataracts; alpha-crystallin; photo-oxidation; oxidation; mass spectrometry; HPLC ID BOVINE ALPHA-CRYSTALLIN; HUMAN LENS CRYSTALLINS; NUCLEAR CATARACT; MASS-SPECTROMETRY; OXIDIZED TRYPTOPHAN; ANTHRANILIC ACID; PROTEINS; OXIDATION; IDENTIFICATION; RESIDUES AB The present study was performed in order to obtain structural and quantitative information regarding the modifications that take place in the human lens as a result of tryptophan oxidation. In particular, the early tryptophan oxidation product, oxindolealanine (OIA) has been detected in lyophilized and hydrolyzed cataractous lenses by mass spectrometry. OIA was confirmed in human cataract samples by observing its ion (m/z 221), fragmentation pattern and absorption spectrum. Quantitative results indicate that there are differences in the amounts of OIA in the nucleus versus the cortex in human cataractous lenses. Expressed as a ratio to the level of phenylalanine (Phe), the nucleus has more than one and a half times greater levels of OIA as compared to the cortex [nucleus = (3.7 +/- 0.7) x 10(-2) versus cortex = (2.3 +/- 0.3) x 10(-2)]. Furthermore, the average value for the OIA/Phe ratio in the calf lens (controls) was (0.8 +/- 0.2) x 10(-2) as compared to (3.7 +/- 0.7) x 10(-2) in human cataractous lens nucleus (p < 0.05). The quantitative results correspond to a 4.6-fold increase of OIA in human cataractous lenses. In a separate series of experiments using HPLC with photodiode array (PDA) detection only, the differences in OIA levels in cataract nucleus versus cortex and cataracts versus controls closely matched the LC/MS data. The results suggest that OIA levels are elevated in human cataractous lenses thus providing further evidence to implicate tryptophan oxidation in this process. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Gaillard, Elizabeth R.; Paik, David C.; Merriam, John C.; Dillon, James P.] Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. [Rousseva, Lilia A.; Gaillard, Elizabeth R.; Ryzhov, Victor; Dillon, James P.] No Illinois Univ, Dept Chem & Biochem, De Kalb, IL 60115 USA. [Garland, Donita L.] NEI, Lab Mech Ocular Dis, Bethesda, MD 20892 USA. RP Dillon, JP (reprint author), Columbia Univ, Dept Ophthalmol, 635 West 165th St,Room 804, New York, NY 10032 USA. EM jpd1@columbia.edu FU NEI NIH HHS [EY02283] NR 45 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 2007 VL 85 IS 6 BP 861 EP 868 DI 10.1016/j.exer.2007.08.022 PG 8 WC Ophthalmology SC Ophthalmology GA 246VZ UT WOS:000252037100014 PM 17935715 ER PT J AU Baerlocher, GM Sloand, EM Young, NS Lansdorp, PM AF Baerlocher, Gabriela M. Sloand, Elaine M. Young, Neal S. Lansdorp, Peter M. TI Telomere length in paroxysmal nocturnal hemoglobinuria correlates with clone size SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID NATURAL-HISTORY; FLOW-CYTOMETRY; CELLS; PNH; SUBPOPULATIONS; PATHOGENESIS; PROGENITORS; DYNAMICS; GROWTH; FISH AB Objective. To study if telomere length can be used as a surrogate marker for the mitotic history in normal and affected hematopoietic cells from patients with paroxysmal nocturnal hemoglobinuria (PNH). Methods. The telomere length was measured by automated multicolor flow fluorescence in situ hybridization in glycosyl-phosphatidyl-inositol anchored protein (GPI)-negative and GPI-positive peripheral blood leukocytes. Eleven patients were studied, two with predominantly hemolytic PNH and nine with PNH associated with marrow failure. Results. Telomere length in GPI-negative cells was significantly shorter than in GPI-positive cells of the same patient (p < 0.01, n = 11). The difference in telomere length (telomere length in GPI-positive minus telomere length in GPI-negative cells) correlated with the percentage of GPI-negative white blood cells. Conclusion. Our results support the hypothesis that telomere length is correlated to the replicative history of GPI-positive and GPI-negative cells and warrant further studies of telomere length in relation to disease progression in PNH. (C) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Baerlocher, Gabriela M.; Lansdorp, Peter M.] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Sloand, Elaine M.; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Baerlocher, Gabriela M.] Univ Bern, Dept Hematol, Bern, Switzerland. [Lansdorp, Peter M.] Univ British Columbia, Dept Med, Vancouver, BC, Canada. RP Lansdorp, PM (reprint author), British Columbia Canc Agcy, Terry Fox Lab, 675 W 10th Ave,11th Floor, Vancouver, BC V5Z 1L3, Canada. EM plansdor@bccrc.ca FU NIAID NIH HHS [AI29524] NR 18 TC 2 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 2007 VL 35 IS 12 BP 1777 EP 1781 DI 10.1016/j.exphem.2007.06.010 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 239ZU UT WOS:000251557600003 PM 17697745 ER PT J AU Robertson, SM Penzak, SR Paut, A AF Robertson, Sarah M. Penzak, Scott R. Paut, Alice TI Drug interactions in the management of HIV infection: an update SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE AIDS; antiretrovirals; cytochrome P450; drug interactions; drug metabolism; HIV; P-glycoprotein; pharmacokinetics; protease inhibitors; non-nucleoside reverse transcriptase inhibitors; nucleoside reverse transcriptase inhibitors ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; PATIENTS RECEIVING DIDANOSINE; EARLY VIROLOGICAL FAILURE; HEPATITIS-C VIRUS; PURINE NUCLEOSIDE PHOSPHORYLASE; INDUCED CARBAMAZEPINE TOXICITY; HUMAN CYTOCHROME-P450 3A4; SUBOPTIMAL CD4 GAINS; PHARMACOKINETIC INTERACTION AB Improvement in the availability of antiretroviral (ARV) therapy continues to reduce HIV morbidity and mortality. With more treatment choices and better accessibility, the extent of medication use among patients with HIV/AIDS continues to grow. ARV drugs are particularly prone to drug interactions as a consequence of their metabolic and pharmacokinetic properties. The recognition and management of drug interactions in patients on ARVs is a constant challenge to medical providers. Staying abreast of drug interaction knowledge is complicated by the rate at which new information becomes available through in vivo investigation, case reports and pharmacokinetic studies. In addition, distinguishing the clinical significance of an interaction is difficult due to the large interpatient variability in pharmacokinetics exhibited by most ARV agents. This review provides an update to a previous review article published in 2005, and is intended to improve the reader's knowledge of drug interactions in the management of HIV infection. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Robertson, SM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 170 TC 19 Z9 19 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD DEC PY 2007 VL 8 IS 17 BP 2947 EP 2963 DI 10.1517/14656566.8.17.2947 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 238XT UT WOS:000251482400005 PM 18001255 ER PT J AU Li, ZJ Thiele, CJ AF Li, Zhijie Thiele, Carol J. TI Targeting Akt to increase the sensitivity of neuroblastoma to chemotherapy: lessons learned from the brain-derived neurotrophic factor/TrkB signal transduction pathway SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE Akt; Akt inhibitors; brain-derived neurotrophic factor; neuroblastoma; phosphatidylinositol 3-kinase; TrkB ID PROTEIN-KINASE-B; ETHER LIPID ANALOGS; EPIDERMAL-GROWTH-FACTOR; IN-VIVO; PHOSPHATIDYLINOSITOL 3-KINASE; ALKYL-LYSOPHOSPHOLIPIDS; SYMPATHETIC NEURONS; ANTITUMOR-ACTIVITY; APOPTOTIC STIMULI; CELLULAR-SURVIVAL AB Neuroblastoma (NB) is a neural crest precursor cell-derived extracranial solid tumor in children. Patients with a poor prognosis are often resistant to chemotherapy and have tumors that express the neuronal growth/survival factor brain-derived neurotrophic factor and its tyrosine kinase receptor, TrkB. In this article, the authors discuss a growth/survival factor-stimulated mechanism leading to chemoresistance in NB that is mediated by the PI3K/Akt signaling pathway. Besides brain-derived neurotrophic factor/TrkB, other growth/survival factors and their receptors also activate the PI3K/Akt pathway and have the potential to mediate chemoresistance in NB. These findings raise the possibility of a new therapeutic approach in NB that would target Akt, the common downstream mediator of multiple growth/survival factor signaling pathways, to enhance the efficacy of chemotherapeutics. Several classes of Akt inhibitors, including phosphaticlylinositol ether lipid analogs, alkylphospholipid analogs, allosteric Akt kinase inhibitors, HSP90 inhibitor and HIV protease inhibitors are discussed. C1 [Li, Zhijie; Thiele, Carol J.] NCI, Head Cell & Mol Biol Sect, Paediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Thiele, CJ (reprint author), NCI, Head Cell & Mol Biol Sect, Paediat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 1-3940, Bethesda, MD 20892 USA. EM ct47a@nih.gov FU Intramural NIH HHS NR 88 TC 29 Z9 29 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD DEC PY 2007 VL 11 IS 12 BP 1611 EP 1621 DI 10.1517/14728222.11.12.1611 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 239ZE UT WOS:000251556000007 PM 18020981 ER PT J AU Greggio, E Singleton, A AF Greggio, Eliso Singleton, Andrew TI Kinase signaling pathways as potential targets in the treatment of Parkinson's disease SO EXPERT REVIEW OF PROTEOMICS LA English DT Review ID EARLY-ONSET PARKINSONISM; N-TERMINAL KINASE; ALPHA-SYNUCLEIN; DOPAMINERGIC-NEURONS; PROTEIN-KINASE; OXIDATIVE STRESS; LRRK2 G2019S; LEUCINE-RICH-REPEAT-KINASE-2 LRRK2; MITOCHONDRIAL DYSFUNCTION; REGULATING KINASE-1 AB Parkinson's disease (PD) is a severe, progressive, age-associated, neurodegenerative disorder. Current therapies are symptomatic and not effective at halting or significantly slowing the disease progress. The search for etiologic-based therapies has focused largely on genetic findings made in familial forms of this disease. Mutations of five genes have been unequivocally linked to PD; two of these, LRRK2 and PINK1, encode kinases and as such are attractive tools with which to understand the disease process; furthermore, preliminary functional data suggests that these proteins, or the pathways in which they are involved, are viable therapeutic targets. Here we explore the current data and thoughts regarding LRRK2 and PINK1 and discuss further avenues of research to understand the pathologic effects of mutations at these loci and potential points of therapeutic intervention, such as within these kinases or in associated pathways such as Jun N-terminal kinase and Akt pathways. C1 [Greggio, Eliso; Singleton, Andrew] NIH, Natl Inst Aging, Neurogenet Lab, Cell Biol & Gene Express Unit, Bethesda, MD 20982 USA. RP Greggio, E (reprint author), NIH, Natl Inst Aging, Neurogenet Lab, Cell Biol & Gene Express Unit, Bethesda, MD 20982 USA. EM greggio@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Greggio, Elisa/H-6119-2013 OI Greggio, Elisa/0000-0002-8172-3598 FU Intramural NIH HHS NR 88 TC 20 Z9 20 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD DEC PY 2007 VL 4 IS 6 BP 783 EP 792 DI 10.1586/14789450.4.6.783 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 244UQ UT WOS:000251891200011 PM 18067416 ER PT J AU Oyelaran, O Gildersleeve, JC AF Oyelaran, Oyindasola Gildersleeve, Jeffrey C. TI Application of carbohydrate array technology to antigen discovery and vaccine development SO EXPERT REVIEW OF VACCINES LA English DT Review DE antibodies; antigen arrays; cancer vaccines; carbohydrates; glycans; glycoconjugates; microarrays; polysaccharide vaccines; post-translational modifications ID BACILLUS-ANTHRACIS EXOSPORIUM; IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNOLOGICAL ADJUVANT QS-21; KEYHOLE LIMPET HEMOCYANIN; HUMAN MONOCLONAL-ANTIBODY; BREAST-CANCER PATIENTS; CONJUGATE VACCINE; OLIGOSACCHARIDE MICROARRAYS; MICROTITER PLATES; MELANOMA PATIENTS AB Carbohydrate arrays are a new technology developed for high-throughput evaluation of interactions between carbohydrates and proteins, cells or viruses. Carbohydrate arrays contain many different carbohydrate structures on a solid support. The format allows one to probe hundreds or thousands of potential receptor-ligand interactions while using only tiny amounts of material. Recently, carbohydrate arrays have been applied to vaccine development in several ways. First, carbohydrate arrays have been utilized for the discovery and characterization of carbohydrate antigens. Second, they have been used to evaluate immune responses to vaccine candidates. Third, carbohydrate arrays have been used to identify and characterize reagents necessary for vaccine development. Although still at an early stage, carbohydrate array technology has tremendous potential for accelerating vaccine development. C1 [Oyelaran, Oyindasola; Gildersleeve, Jeffrey C.] Natl Canc Inst, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Gildersleeve, JC (reprint author), Natl Canc Inst, Med Chem Lab, Ctr Canc Res, NIH, 376 Boyles St,Bldg 376,Room 109, Frederick, MD 21702 USA. EM oyelarano@ncifcrf.gov; gildersleevej@ncifcrf.gov RI Gildersleeve, Jeffrey/N-3392-2014 FU Intramural NIH HHS NR 102 TC 24 Z9 25 U1 1 U2 7 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD DEC PY 2007 VL 6 IS 6 BP 957 EP 969 DI 10.1586/14760584.6.6-957 PG 13 WC Immunology SC Immunology GA 239ZG UT WOS:000251556200016 PM 18377358 ER PT J AU Appella, E Anderson, CW AF Appella, Ettore Anderson, Carl W. TI New prospects for proteomics - electron-capture (ECD) and electron-transfer dissociation (ETD) fragmentation techniques and combined fractional diagonal chromatography (COFRADIC) SO FEBS JOURNAL LA English DT Editorial Material C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Appella, E (reprint author), NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD DEC PY 2007 VL 274 IS 24 BP 6255 EP 6255 DI 10.1111/j.1742-4658.2007.06146.x PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 237OW UT WOS:000251385800001 PM 18021241 ER PT J AU Hoe, NP Lukomska, E Musser, JM Lukomski, S AF Hoe, Nancy P. Lukomska, Ewa Musser, James M. Lukomski, Slawomir TI Characterization of the immune response to collagen-like proteins Scl1 and Scl2 of serotype M1 and M28 group A Streptococcus SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE group A Streptococcus; Scl; humoral response ID SURFACE PROTEIN; INVASIVE INFECTIONS; COMPLEMENT GENE; PYOGENES; IDENTIFICATION; INHIBITOR; DISEASE; ALPHA(2)BETA(1)-INTEGRIN; PATHOGENESIS; PHARYNGITIS AB Group A Streptococcus (GAS) infections may trigger autoimmune sequelae thought to involve streptococcal antibodies cross-reactive to human antigens. Here, the antigenicity of the streptococcal collagen-like (CL) proteins, Scl1 and Scl2, that exhibit structural similarity to human collagen, was analyzed. Antibodies to Scl1.1 protein were detected in human sera from healthy individuals previously infected with M1 GAS and from patients with various GAS infections, as well as in sera from mice infected with M1 GAS. Linear B-cell epitope mapping identified immunoreactive peptides corresponding to the CL region of Scl1.1. Humoral responses to Scl1.28 and Scl2.28 were also detected in pediatric patients and mice infected with M28 GAS. C1 W Virginia Univ, Dept Microbiol Immunol & Cell Biol, Sch Med, Morgantown, WV 26506 USA. NIH, NIAID, Lab Human Bacterial Pathogenesis, Hamilton, MT USA. W Virginia Univ, Sch Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. RP Lukomski, S (reprint author), W Virginia Univ, Dept Microbiol Immunol & Cell Biol, Sch Med, 2095 Hlth Sci N,PO Box 9177, Morgantown, WV 26506 USA. EM slukomski@hsc.wvu.edu FU Intramural NIH HHS; NIAID NIH HHS [AI50666] NR 24 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD DEC PY 2007 VL 277 IS 2 BP 142 EP 149 DI 10.1111/j.1574-6968.2007.00955.x PG 8 WC Microbiology SC Microbiology GA 234UV UT WOS:000251190400004 PM 18031333 ER PT J AU Premkumar, A Venzon, DJ Avila, N Johnson, DV Remaley, AT Forman, MR Eng-Wong, J Zujewski, J Stratton, P AF Premkumar, Ahalya Venzon, David J. Avila, Nilo Johnson, Diane V. Remaley, Alan T. Forman, Michele R. Eng-Wong, Jennifer Zujewski, JoAnne Stratton, Pamela TI Gynecologic and hormonal effects of raloxifene in premenopausal women SO FERTILITY AND STERILITY LA English DT Article DE raloxifene; premenopausal women; endometrium; ovary; hormones; breast cancer ID BREAST-CANCER PATIENTS; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; UTERINE LEIOMYOMAS; TRANSVAGINAL ULTRASONOGRAPHY; OVARIAN OVERSTIMULATION; REPLACEMENT THERAPY; TAMOXIFEN THERAPY; HIGH-RISK; PREVENTION AB Objective: To assess the effects of raloxifene on the ovaries, uterus, and serum hormone levels in premenopausal women. Design: Prospective study comparing pretreatment findings with findings for those on treatment. Setting: Government research hospital. Patient(s): Thirty women 35 to 47 years of age who were at high risk of breast cancer and had regular, ovulatory menstrual cycles. Intervention(s): Raloxifene (60 mg) and calcium (1,200 mg) daily for 2 years. Main Outcome Measure(s): Sonographic evidence of ovarian stimulation (<= 2 corpora lutea, or follicular cysts of >2 cm, or single follicular cyst of >3 cm). Changes in endometrial thickness, fibroid size, hormone levels, and menstrual-cycle length. Result(s): Fifteen subjects developed some cycles with asymptomatic ovarian stimulation, and 9 developed benign endometrial polyps, compared with 2 subjects and I subject pretreatment, respectively. Uterine fibroid size was unchanged during raloxifene use in 16 subjects with fibroids. On treatment, E-2 levels increased significantly only during the follicular phase, with peak E-2 levels significantly higher in cycles showing ovarian stimulation compared with those without. Sex hormone-binding globulin increased, but levels of LH, FSH, P, DHEAS, and T did not. Endometrial thickness and cycle length were unchanged. Conclusion(s): Premenopausal subjects receiving raloxifene showed sonographic and hormonal evidence of ovarian stimulation. Endometrial thickness, cycle length, and fibroid size were unchanged. Benign asymptomatic endometrial polyps developed in some. (Fertil Steril((R)) 2007;88:1637-44. (c) 2007 by American Society for Reproductive Medicine.) C1 [Premkumar, Ahalya; Avila, Nilo] NCI, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Remaley, Alan T.] NCI, Warren G Magnuson Clin Ctr, Div Lab Med, Bethesda, MD 20892 USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Forman, Michele R.] NIH, Ctr Canc Res, Lab Biosyst & Canc, Bethesda, MD 20892 USA. [Eng-Wong, Jennifer; Zujewski, JoAnne] NIH, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. [Stratton, Pamela] NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), NIH, NICHD, Reprod Biol & Med Branch, Gynecol Consult Serv, Bldg 10,CRC,Room 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU Intramural NIH HHS NR 43 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2007 VL 88 IS 6 BP 1637 EP 1644 DI 10.1016/j.fertnstert.2007.01.095 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 244XE UT WOS:000251897800022 PM 17662283 ER PT J AU Berg, CL Gillespie, BW Merion, RM Brown, RS Abecassis, MM Trotter, JF Fisher, RA Freise, CE Ghobrial, RM Shaked, A Fair, JH Everhart, JE AF Berg, Carl L. Gillespie, Brenda W. Merion, Robert M. Brown, Robert S., Jr. Abecassis, Michael M. Trotter, James F. Fisher, Robert A. Freise, Chris E. Ghobrial, R. Mark Shaked, Abraham Fair, Jeffrey H. Everhart, James E. TI Improvement in survival associated with adult-to-adult living donor liver transplantation SO GASTROENTEROLOGY LA English DT Article ID SINGLE-CENTER EXPERIENCE/; RIGHT HEPATIC LOBE; HEPATOCELLULAR-CARCINOMA; OUTCOMES AB Background & Aims: More than 2000 adult-to-adult living donor liver transplantations (LDLT) have been performed in the United States, yet the potential benefit to liver transplant candidates of undergoing LDLT compared with waiting for deceased donor liver transplantation (DDLT) is unknown. The aim of this study was to determine whether there is a survival benefit of adult LDLT. Methods: Adults with chronic liver disease who had a potential living donor evaluated from January 1998 to February 2003 at 9 university-based hospitals were analyzed. Starting at the time of a potential donor's evaluation, we compared mortality after LDLT to mortality among those who remained on the waiting list or received DDLT. Median follow-up was 4.4 years. Comparisons were made by hazard ratios (HR) adjusted for LDLT candidate characteristics at the time of donor evaluation. Results: Among 807 potential living donor recipients, 389 underwent LDLT, 249 underwent DDLT, 99 died without transplantation, and 70 were awaiting transplantation at last follow-up. Receipt of LDLT was associated with an adjusted mortality HR of 0.56 (95% confidence interval [CI]: 0.42-0.74; P < .001) relative to candidates who did not undergo LDLT. As centers gained greater experience (>20 LDLT), LDLT benefit was magnified, with a mortality HR of 0.35 (95% CI: 0.23-0.53; P < .001). Conclusions: Adult LDLT was associated with lower mortality than the alternative of waiting for DDLT. This reduction in mortality was magnified as centers gained experience with LDLT. This reduction in transplant candidate mortality must be balanced against the risks undertaken by the living donors themselves. C1 Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Columbia Presbyterian Med Ctr, Dept Med, New York, NY 10032 USA. Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. Univ Colorado, Dept Surg, Denver, CO 80202 USA. Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Surg, Richmond, VA USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. Univ N Carolina, Dept Surg, Chapel Hill, NC USA. NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. Univ Virginia Hlth Syst, Dept Med, Charlottesville, VA 22908 USA. RP Berg, CL (reprint author), Univ Virginia Hlth Syst, Dept Med, POB 800708, Charlottesville, VA 22908 USA. EM CLB7D@hscmail.mcc.virginia.edu RI Abecassis, Michael/F-7977-2011 FU NIDDK NIH HHS [U01-DK62467, DK62444, DK62467, DK62483, DK62484, DK62494, DK62496, DK62498, DK62505, DK62531, DK62536, U01 DK062444, U01 DK062467, U01 DK062483, U01 DK062484, U01 DK062484-06, U01 DK062494, U01 DK062496, U01 DK062498, U01 DK062505, U01 DK062531, U01 DK062536, U01-DK62444, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531, U01-DK62536] NR 24 TC 105 Z9 106 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2007 VL 133 IS 6 BP 1806 EP 1813 DI 10.1053/j.gastro.2007.09.004 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239RM UT WOS:000251535400012 PM 18054553 ER PT J AU Fraser, A Longnecker, MP Lawlor, DA AF Fraser, Abigail Longnecker, Matthew P. Lawlor, Debbie A. TI Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999-2004 SO GASTROENTEROLOGY LA English DT Article ID FATTY LIVER-DISEASE; CORONARY HEART-DISEASE; GAMMA-GLUTAMYL-TRANSFERASE; INSULIN-RESISTANCE; OBESE CHILDREN; UNITED-STATES; METABOLIC SYNDROME; CHILDHOOD OBESITY; RISK; STEATOHEPATITIS AB Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver disease in children and adolescents. The majority of studies of NAFLD in children have been in select populations of the clinically obese. Study aims were to estimate the prevalence of elevated alanine aminotransferase (ALT, as a marker of NAFLD) in a general contemporary adolescent population and to identify leading risk factors for ALT elevation (>30 U/L). Metho : We analyzed data of adolescent participants (aged 12-19 years; N = 5586) in the National Health and Nutrition Examination Survey 1999-2004, a representative sample of the civilian noninstitutionalized US population. Results: The prevalence of elevated ALT levels (>30 U/L) was 7.4% among white adolescents, 11.5% among Mexican American adolescents, and 6.0% among black adolescents. Elevated ALT levels were prevalent in 12.4% of male subjects compared with 3.5% of female subjects. Multivariable associations with elevated ALT levels were found for sex (odds ratio [OR] male vs female, 7.7; 95% confidence interval [CI], 3.9-15.1), ethnicity (OR black vs white, 0.6; 95% CI, 0.3-1.3; OR Mexican American vs white, 1.6; 95% CI, 1.0-2.6), waist circumference (OR per 1 SD, 1.4; 95% CI, 1.0-2.0), and fasting insulin level (OR per I SD, 1.6; 95% CI, 1.2-2.1). Age, C-reactive protein levels, and triglyceride levels were also positively and socioeconomic position inversely associated with elevated ALT levels. The magnitude of associations were similar across ethnic groups. Conclusions: ALT level is associated with waist circumference and insulin resistance even in a young population. These characteristics could be utilized to identify adolescents who may benefit from screening for NAFLD, offering an opportunity to prevent disease progression at an early age. C1 Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England. NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Fraser, A (reprint author), Univ Bristol, Dept Social Med, Canynge Hall,Whiteladies Rd, Bristol BS8 2PR, Avon, England. EM abigail.fraser@bristol.ac.uk OI Longnecker, Matthew/0000-0001-6073-5322; Fraser, Abigail/0000-0002-7741-9470; Lawlor, Debbie A/0000-0002-6793-2262 FU Intramural NIH HHS [Z01 ES049021-11]; Medical Research Council [G0600705] NR 38 TC 166 Z9 173 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2007 VL 133 IS 6 BP 1814 EP 1820 DI 10.1053/j.gastro.2007.08.077 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 239RM UT WOS:000251535400013 PM 18054554 ER PT J AU Armbruster, S Dorrance, C Voorhees, P Pingpank, JF Kurland, JE AF Armbruster, Steven Dorrance, Colleen Voorhees, Patrick Pingpank, James F. Kurland, Jayde E. TI Malignant insulinoma: a rare presentation of a rare tumor SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 [Armbruster, Steven; Dorrance, Colleen; Kurland, Jayde E.] Natl Naval Med Ctr, Dept Gastroenterol, Dept Internal Med & Oncol, Bethesda, MD 20889 USA. [Voorhees, Patrick] Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA. [Pingpank, James F.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Armbruster, S (reprint author), Natl Naval Med Ctr, Dept Gastroenterol, Dept Internal Med & Oncol, Bethesda, MD 20889 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2007 VL 66 IS 6 BP 1228 EP 1229 DI 10.1016/j.gie.2007.06.026 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 241PZ UT WOS:000251669600030 PM 17719587 ER PT J AU Kimm, LR Deleeuw, RJ Savage, KJ Rosenwald, A Campo, E Delabie, J Ott, G Muller-Hermelink, HK Jaffe, ES Rimsza, LM Weisenburger, DD Chan, WC Staudt, LM Connors, JM Gascoyne, RD Lam, WL AF Kimm, Lindsey R. deleeuw, Ronald J. Savage, Kerry J. Rosenwald, Andreas Campo, Elias Delabie, Jan Ott, German Muller-Hermelink, Hans-Konrad Jaffe, Elaine S. Rimsza, Lisa M. Weisenburger, Dennis D. Chan, Wing C. Staudt, Louis M. Connors, Joseph M. Gascoyne, Randy D. Lam, Wan L. TI Frequent occurrence of deletions in primary mediastinal B-Cell lymphoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-NECROSIS-FACTOR; ACTIVATION; DNA; PROTEIN; LINE; DEGRADATION; PATTERNS; SOCS-1; GENES AB Primary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of diffuse large B-cell lymphoma. PMBCL has been previously studied with a variety of genomic techniques resulting in frequent detection of chromosomal gains; however, chromosomal losses have been rarely reported. This finding contrasts many other types of lymphoma, in which deletions are common. We hypothesize that segmental losses do exist but may have escaped detection by methods used in the previous studies. Using array comparative genomic hybridization to a tiling-resolution microarray encompassing the entire human genome, PMBCL samples were analyzed for genomic copy number alterations. An almost equal number of gains and losses of chromosomal material were detected throughout the genome (216 vs. 193, respectively). A selection of these DNA copy number alterations were confirmed by quantitative real-time PCR. Recurrent gains were detected at all previously reported regions of gain, including 9p seen in similar to 70% of cases. Recurrent chromosomal losses were observed at I p, 3p, 4q, 6q, 7p, and 17p, with a novel event at I p 13.1-p 13.2 representing the most frequent at 42% of cases analyzed. We conclude that consistent losses are present in the PMBCL genome. Given the similar frequency of losses to that of segmental gains of DNA, they are likely to play an important role in the pathogenesis of PMBCL. C1 British Columbia Canc Res Ctr, Dept Canc Genet & Dev Biol, Vancouver, BC V5Z 1L3, Canada. British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. Univ Wurzburg, Inst Pathol, D-97070 Wurzburg, Germany. Univ Barcelona, Sch Med, Dept Pathol, E-08007 Barcelona, Spain. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Arizona, Arizona Canc Ctr, Dept Med, Tucson, AZ USA. Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Ctr Canc Res, Natl Inst Hlth, Bethesda, MD USA. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada. RP Deleeuw, RJ (reprint author), British Columbia Canc Res Ctr, Dept Canc Genet & Dev Biol, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM rdclccuw@bccrc.ca OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 NR 29 TC 16 Z9 16 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 2007 VL 46 IS 12 BP 1090 EP 1097 DI 10.1002/gcc.20495 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 222JX UT WOS:000250293500005 PM 17823928 ER PT J AU Ohshika, Y Uhida, K Furukohri, A Shinozaki, Y Ishikawa, S Ogasawara, N Nohmi, T Maki, H Akiyama, M AF Ohshika, Yasuna Uhida, Kaori Furukohri, Asako Shinozaki, Yutaka Ishikawa, Shu Ogasawara, Naotake Nohmi, Takehik Maki, Hisaji Akiyama, Masahiro TI Inhibition of DNA replication by DNA polymerase DinB SO GENES & GENETIC SYSTEMS LA English DT Meeting Abstract C1 [Ohshika, Yasuna; Uhida, Kaori; Furukohri, Asako; Shinozaki, Yutaka; Maki, Hisaji; Akiyama, Masahiro] Nara Inst Sci & Tech, Dept Biol Sci, Nara, Japan. [Nohmi, Takehik] Natl Inst Hlth, Div Genet & Mutagenesis, Bethesda, MD USA. [Ishikawa, Shu; Ogasawara, Naotake] Nara Inst Sci & Tech, Dept Inform Sci, Nara, Japan. RI Ogasawara, Naotake/B-7971-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU GENETICS SOC JAPAN PI SHIZUOKA-KEN PA NATIONAL INST GENETICS YATA 1111, MISHIMA, SHIZUOKA-KEN, 411-8540, JAPAN SN 1341-7568 EI 1880-5779 J9 GENES GENET SYST JI Genes Genet. Syst. PD DEC PY 2007 VL 82 IS 6 BP 545 EP 545 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 277TS UT WOS:000254238200192 ER PT J AU Kumar, A Yamaguchi, TH Sharma, P Kuehn, MR AF Kumar, Amit Yamaguchi, Taihei Sharma, Prashant Kuehn, Michael R. TI Transgenic mouse lines expressing Cre recombinase specifically in posterior notochord and notochord SO GENESIS LA English DT Article DE Cre/LoxP; conditional mutagenesis; Foxa2; nodal; notochord; PNC ID LEFT-RIGHT ASYMMETRY; FLOOR PLATE; INDUCIBLE EXPRESSION; REGULATORY ELEMENTS; GENE-EXPRESSION; LATERAL PLATE; NODE; HNF-3-BETA; EMBRYO; GASTRULATION AB During development, the organizer provides instructive signals to surrounding cells as well as contributing cells to axial structures. To dissect organizer function at different developmental stages, conditional approaches such as the Cre/loxP system for conditional mutagenesis are particularly useful. Here we describe two new Cre transgenic mouse lines, Foxa2 NFP-Cre and Nodal PNC-Cre, with activity in two organizer domains, the posterior notochord (PNC) and notochord. These lines were made using defined regulatory elements from the Foxa2 and Nodal genes that direct Cre expression in overlapping domains of the IPNC and notochord. Our detailed analysis of the timing and location of Foxa2 NFP-Cre and Nodal PNC-Cre activity indicates that these lines are appropriate for conditional mutagenesis of genes expressed from early somite stages onward. C1 [Kumar, Amit; Yamaguchi, Taihei; Sharma, Prashant; Kuehn, Michael R.] Natl Canc Inst, Natl Inst Hlth, LPDS, Frederick, MD 21702 USA. RP Kuehn, MR (reprint author), Natl Canc Inst, Natl Inst Hlth, LPDS, Bldg 560-Rm 12-90, Frederick, MD 21702 USA. EM mkuehn@mail.nih.gov RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 FU Intramural NIH HHS NR 25 TC 10 Z9 10 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD DEC PY 2007 VL 45 IS 12 BP 729 EP 736 DI 10.1002/dvg.20346 PG 8 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 250NO UT WOS:000252307200001 PM 18064671 ER PT J AU Zheng, G Joo, J Zhang, C Geller, NL AF Zheng, Gang Joo, Jungnam Zhang, Chun Geller, Nancy L. TI Testing association for markers on the X chromosome SO GENETIC EPIDEMIOLOGY LA English DT Article DE age-related macular degeneration; genome-wide association; Hardy-Weinberg equilibrium; trend test; X-linked markers ID HARDY-WEINBERG EQUILIBRIUM; PREMATURE OVARIAN FAILURE; SAMPLE-SIZE; LINKAGE DISEQUILIBRIUM; GENETIC-MARKERS; POWER; DEVIATIONS; DISEASE AB Test statistics for association between markers on autosomal chromosomes and a disease have been extensively studied. No research has been reported on performance of such test statistics for association on the X chromosome. With 100,000 or more single-nucleoticle polymorphisms (SNPs) available for genome-wide association studies, thousands of them come from the X chromosome. The X chromosome contains rich information about population history and linkage disequilibrium. To identify X-linked marker susceptibility to a disease, it is important to study properties of various statistics that can be used to test for association on the X chromosome. In this article, we compare performance of several approaches for testing association on the X chromosome, and examine how departure from Hardy-Weinberg equilibrium would affect type I error and power of these association tests using X-linked SNPs. The results are applied to the X chromosome of Klein et al. [2005], a genome-wide association study with 100K SNPs for age-related macular degeneration. We found that a SNP (rs10521496) covered by DIAPH2, known to cause premature ovarian failure (POF) in females, is associated with age-related macular degeneration. C1 [Zheng, Gang; Joo, Jungnam; Geller, Nancy L.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Zhang, Chun] Roche Palo Alto LLC, Palo Alto, CA USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 24 TC 37 Z9 38 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD DEC PY 2007 VL 31 IS 8 BP 834 EP 843 DI 10.1002/gepi.20244 PG 10 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 240GF UT WOS:000251574600003 PM 17549761 ER PT J AU Riegert-Johnson, DL Macaya, D Hefferon, TW Boardman, LA AF Riegert-Johnson, Douglas L. Macaya, Daniela Hefferon, Timothy W. Boardman, Lisa A. TI Medical errors related to inappropriate genetic testing in liver transplant patients SO GENETIC TESTING LA English DT Article AB Genetic testing of genes that encode proteins expressed by liver hepatocytes (clotting factors, alpha(1)-antitrypsin, cytochrome P450 enzymes) is common in clinical practice. These tests use DNA extracted from peripheral blood lymphocytes (PBL) and are based on the assumption that PBL DNA can be used as a surrogate for hepatocyte DNA. However, in individuals who have undergone liver transplantation, hepatocyte DNA is that of the donor while PBL DNA remains that of the recipient. It follows that in liver transplant patients, genetic testing of the recipient's PBL DNA does not provide accurate results for proteins expressed by donor hepatocytes. Therefore, genetic testing of clotting factors, alpha(1)-1-antitrypsin, cytochrome P450 enzymes, and other proteins expressed by hepatocytes is unreliable and inappropriate in liver transplant patients (inappropriate genetic testing). A review of the records of 215 consecutive liver transplant patients at our institution identified: one medical error and one near-miss medical error related to inappropriate genetic testing, 14 cases of inappropriate genetic testing, and 21 unnecessary duplicate genetic testing requests. We recommend laboratories performing genetic testing create systems to prevent inappropriate and duplicate genetic testing and that physicians be cognizant of the appropriate indications for genetic testing in liver transplant patients. C1 [Riegert-Johnson, Douglas L.; Boardman, Lisa A.] Mayo Clin, Div Gastroenterol, Coll Med, Rochester, MN 55905 USA. [Macaya, Daniela] Univ Costa Rica, Dept Med Genet, San Jose, Costa Rica. [Hefferon, Timothy W.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Riegert-Johnson, DL (reprint author), Mayo Clin, Div Gastroenterol, Coll Med, 200 1st St, Rochester, MN 55905 USA. EM riegertjohnson.douglas@mayo.edu NR 2 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD DEC PY 2007 VL 11 IS 4 BP 451 EP 453 DI 10.1089/gte.2007.0052 PG 3 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 254AR UT WOS:000252559200016 PM 18294063 ER PT J AU Evertts, AG Plymire, C Craig, NL Levin, HL AF Evertts, Adam G. Plymire, Christopher Craig, Nancy L. Levin, Henry L. TI The hermes transposon of Musca domestica is an efficient tool for the mutagenesis of Schizosaccharomyces pombe SO GENETICS LA English DT Article ID GENE DISRUPTION; FISSION YEAST; RETROTRANSPOSON; EXPRESSION; GENOME AB Currently, no transposon-based method for the mutagenesis of Schizosaccharomyces pombe exists. We have developed such a system based on teh introduction of the hermes transposon from the housefly into S. pombe. This system efficiently disrupts openreading frames and allows the insertion sites to be readily identified. C1 [Evertts, Adam G.; Plymire, Christopher; Levin, Henry L.] NICHHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Craig, Nancy L.] Howard Hughes Med Inst, Dept Mol Biol, Baltimore, MD 21205 USA. [Craig, Nancy L.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Levin, HL (reprint author), NICHHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, 18T,Room 106, Bethesda, MD 20892 USA. EM henry_levin@nih.gov FU Intramural NIH HHS NR 18 TC 14 Z9 14 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 2007 VL 177 IS 4 BP 2519 EP 2523 DI 10.1534/genetics.107.081075 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 245QF UT WOS:000251949800045 PM 17947404 ER PT J AU Siepel, A Diekhans, M Brejova, B Langton, L Stevens, M Comstock, CLG Davis, C Ewing, B Oommen, S Lau, C Yu, HC Li, JF Roe, BA Green, P Gerhard, DS Temple, G Haussler, D Brent, MR AF Siepel, Adam Diekhans, Mark Brejova, Brona Langton, Laura Stevens, Michael Comstock, Charles L. G. Davis, Colleen Ewing, Brent Oommen, Shelly Lau, Christopher Yu, Hung-Chun Li, Jianfeng Roe, Bruce A. Green, Phil Gerhard, Daniela S. Temple, Gary Haussler, David Brent, Michael R. TI Targeted discovery of novel human exons by comparative genomics SO GENOME RESEARCH LA English DT Article ID EXPRESSED SEQUENCE TAGS; MAMMALIAN GENE COLLECTION; ENCODE REGIONS; CDNA-CLONES; INNER-EAR; PREDICTION; MOUSE; RNA; IDENTIFICATION; ANNOTATION AB A complete and accurate set of human protein-coding gene annotations is perhaps the single most important resource for genomic research after the human-genome sequence itself, yet the major gene catalogs remain incomplete and imperfect. Here we describe a genome-wide effort, carried out as part of the Mammalian Gene Collection ( MGC) project, to identify human genes not yet in the gene catalogs. Our approach was to produce gene predictions by algorithms that rely on comparative sequence data but do not require direct cDNA evidence, then to test predicted novel genes by RT-PCR. We have identified 734 novel gene fragments ( NGFs) containing 2188 exons with, at most, weak prior cDNA support. These NGFs correspond to an estimated 563 distinct genes, of which > 160 are completely absent from the major gene catalogs, while hundreds of others represent significant extensions of known genes. The NGFs appear to be predominantly protein-coding genes rather than noncoding RNAs, unlike novel transcribed sequences identified by technologies such as tiling arrays and CAGE. They tend to be expressed at low levels and in a tissue-specific manner, and they are enriched for roles in motor activity, cell adhesion, connective tissue, and central nervous system development. Our results demonstrate that many important genes and gene fragments have been missed by traditional approaches to gene discovery but can be identified by their evolutionary signatures using comparative sequence data. However, they suggest that hundreds - not thousands - of protein-coding genes are completely missing from the current gene catalogs. C1 Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. Washington Univ, Lab Computat Genom, St Louis, MO 63130 USA. Univ Washington, Howard Hughes Med Inst, Dept Genom Sci, Seattle, WA 98195 USA. Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73109 USA. NCI, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. RP Siepel, A (reprint author), Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. EM acs4@cornell.edu RI Brejova, Brona/I-3718-2014; OI Brejova, Brona/0000-0002-9483-1766; Siepel, Adam/0000-0002-3557-7219; Yu, Hung-Chun/0000-0002-4980-8508 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 63 TC 33 Z9 33 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD DEC PY 2007 VL 17 IS 12 BP 1763 EP 1773 DI 10.1101/gr.7128207 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 237FP UT WOS:000251359900007 PM 17989246 ER PT J AU Dhungana, S Anthony, CR Hersman, LE AF Dhungana, Suraj Anthony, Charles R., III Hersman, Larry E. TI Ferrihydrite dissolution by pyridine-2,6-bis(monothiocarboxylic acid) and hydrolysis products SO GEOCHIMICA ET COSMOCHIMICA ACTA LA English DT Article; Proceedings Paper CT Symposium on Physical Chemistry of Soil and Aquifer Systems held in Honor of Garrison Sposito CY 2006 CL San Francisco, CA SP ACS, Geochem, Environm Chem Div, ACS, Colloid & Surface Chem Div ID MEDIATED IRON TRANSPORT; PYRIDINE-2,6-BIS(THIOCARBOXYLIC ACID); REDUCTIVE DISSOLUTION; COORDINATION CHEMISTRY; PSEUDOMONAS-MENDOCINA; PROMOTED DISSOLUTION; ELECTRON-TRANSFER; IRON(III) OXIDES; REDOX PROCESSES; WATER EXCHANGE AB Pyridine-2,6-bis(monothiocarboxylate) (pdtc), a metabolic product of microorganisms, including Pseudomonas putida and Pseudomonas stutzeri was investigated for its ability of dissolve Fe(III)(hydr) oxides at pH 7.5. Concentration dependent dissolution of ferrihydrite under anaerobic environment showed saturation of the dissolution rate at the higher concentration of pdtc. The surface controlled ferrihydrite dissolution rate was determined to be 1.2 x 10(-6) mol m(-2) h(-1). Anaerobic dissolution of ferrihydrite by pyridine-2,6-dicarboxylic acid or dipicolinic acid (dpa), a hydrolysis product of pdtc, was investigated to study the mechanism(s) involved in the pdtc facilitated ferrihydrite dissolution. These studies suggest that pdtc dissolved ferrihydrite using a reduction step, where dpa chelates the Fe reduced by a second hydrolysis product, H2S. Dpa facilitated dissolution of ferrihydrite showed very small increase in the Fe dissolution when the concentration of external reductant, ascorbate, was doubled, suggesting the surface dynamics being dominated by the interactions between dpa and ferrihydrite. Greater than stoichiometric amounts of Fe were mobilized during dpa dissolution of ferrihydrite assisted by ascorbate and cysteine. This is attributed to the catalytic dissolution of Fe(III) (hydr) oxides by the in situ generated Fe(II) in the presence of a complex former, dpa. (C) 2007 Published by Elsevier Ltd. C1 Los Alamos Natl Lab, Biosci Div, Los Alamos, NM 87545 USA. RP Dhungana, S (reprint author), NIEHS, 111 TW Alexander Dr, Durham, NC 27709 USA. NR 48 TC 11 Z9 11 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0016-7037 J9 GEOCHIM COSMOCHIM AC JI Geochim. Cosmochim. Acta PD DEC 1 PY 2007 VL 71 IS 23 BP 5651 EP 5660 DI 10.1016/j.gca.2007.07.022 PG 10 WC Geochemistry & Geophysics SC Geochemistry & Geophysics GA 237IG UT WOS:000251366800007 ER PT J AU Sherman, ME Madigan, MP Lacey, JV Garcia-Closas, M Potischman, N Carreon, JD Hartge, P Brinton, LA AF Sherman, Mark E. Madigan, M. Patricia Lacey, James V., Jr. Garcia-Closas, Montserrat Potischman, Nancy Carreon, Joseph D. Hartge, Patricia Brinton, Louise A. TI Ovarian volumes among women with endometrial carcinoma: Associations with risk factors and serum hormones SO GYNECOLOGIC ONCOLOGY LA English DT Article DE endometrial carcinoma; hormones; ovary; epidemiology ID BODY-MASS INDEX; ANDROGEN CONCENTRATIONS; POSTMENOPAUSAL WOMEN; STROMAL HYPERPLASIA; STEROID-HORMONES; CANCER; AGE; TESTOSTERONE; ENDOCRINE; OBESITY AB Objectives. Data suggest that post-menopausal women with larger ovaries are at increased risk for endometrial carcinoma; however, analyses comparing ovarian volume to serum hormone levels are limited. Accordingly, we assessed ovarian volumes in relation to serum sex hormone levels among post-menopausal women with endometrial carcinoma who participated in a multi-center case-control study. Methods. Data for established risk and protective factors for endometrial carcinoma were collected via in-person interviews. Ovarian volumes were estimated from pathology reports. Associations between exposures and age-adjusted ovarian volumes were analyzed for 175 cases with available data. For a subset of 135 cases, we analyzed relationships between ovarian volume, adjusted for age and body mass index (BMI), and serum hormone levels by analysis of variance. Results. Ovarian volume declined progressively from 1.83 cm(3) among women ages 55-59 years to 1.23 cm(3) among women age 70 years or older (p-trend=0.02). Larger ovarian volume was associated with early menarche (p-trend=0.03), having given birth (p=0.01), and weakly with elevated BMI (p-trend=0.06). After adjustment, increased ovarian volume was associated with higher estradiol (p-trend=0.007); albumin-bound estradiol (p-trend=0.01); and free estradiol (p-trend=0.006) levels; androstenedione, estrone and estrone sulfate showed similar, though non-significant associations. Conclusions. Among women with endometrial carcinoma, larger ovaries were associated with higher serum levels of estrogens. Further studies examining the role of the ovaries in post-menopausal hormonal carcinogenesis are warranted. Published by Elsevier Inc. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Hormonal Reprod Epidemiol Branch, Rockville, MD 20852 USA. RP Sherman, ME (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Hormonal Reprod Epidemiol Branch, 6120 Execut Blvd, Rockville, MD 20852 USA. EM shermanm@mail.nih.gov RI 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 FU Intramural NIH HHS [Z99 CA999999] NR 27 TC 5 Z9 5 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2007 VL 107 IS 3 BP 431 EP 435 DI 10.1016/j.ygyno.2007.07.061 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 241BP UT WOS:000251632200010 PM 17720234 ER PT J AU Brinton, LA Sakoda, LC Frederiksen, K Sherman, ME Kjaer, SK Graubard, BI Olsen, JH Mellemkjaer, L AF Brinton, Louise A. Sakoda, Lori C. Frederiksen, Kirsten Sherman, Mark E. Kjaer, Susanne K. Graubard, Barry I. Olsen, Jorgen H. Mellemkjaer, Lene TI Relationships of uterine and ovarian tumors to pre-existing chronic conditions SO GYNECOLOGIC ONCOLOGY LA English DT Article DE uterine cancer; ovarian cancer; chronic diseases; risk ID ENDOMETRIAL CANCER-RISK; BODY-MASS INDEX; ESTROGEN REPLACEMENT THERAPY; POPULATION-BASED COHORT; GROWTH-FACTOR SYSTEM; DIABETES-MELLITUS; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; HISTOLOGIC TYPES; BREAST-CANCER AB Objective. Several chronic diseases have been hypothesized to affect the risk of subsequent gynecologic malignancies, possibly through shared hormonal mechanisms. Methods. Using record linkage techniques, we assessed the relationships between hospital and outpatient admissions for gallbladder disease, diabetes, hypertension, thyroid diseases and obesity and the subsequent development of uterine and ovarian cancers in Denmark between 1978 and 1998. Based on a subsample of more than 99,000 women, including 1398 uterine and 2491 ovarian cancers, we derived relative risks (RRs) and 95% confidence intervals (CIs) associated with overall and histology-specific cancer risks after adjustment for age, calendar time and reproductive characteristics. Results. Uterine cancers were related to previous diagnoses of thyroid diseases (RR= 1.52, 95% CI 1.17-1.98) and obesity (2.05, 1.40-3.00). Associations with diabetes were confounded by obesity, but there were some elevations in risk for subjects diagnosed with obesity prior to age 45 (RRs 1.66-1.79). Although the "usual types" of endometrial cancer largely accounted for the observed associations, there was some evidence that uterine sarcomas (n = 137) were related to prior diagnoses of thyroid diseases (2.78, 1.41-5.50). In contrast, ovarian cancers were not strongly related to most documented chronic diseases. Serous carcinomas were associated with gallbladder diseases of short durations, but detection bias or misdiagnosis probably accounts for this association. An association of obesity and endometrioid ovarian cancer was not identified. Conclusions. Uterine cancers, including sarcomas, appear to be influenced by selected chronic diseases. Further attention should focus on possible biologic mechanisms underlying observed associations with thyroid diseases and obesity. Published by Elsevier Inc. C1 [Brinton, Louise A.; Sakoda, Lori C.; Sherman, Mark E.; Graubard, Barry I.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Frederiksen, Kirsten; Kjaer, Susanne K.; Olsen, Jorgen H.; Mellemkjaer, Lene] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. RP Brinton, LA (reprint author), 6120 Executive Blvd,Rm 5018, Rockville, MD 20852 USA. EM Brinton@nih.gov RI Brinton, Louise/G-7486-2015; OI Brinton, Louise/0000-0003-3853-8562; Olsen, Jorgen Helge/0000-0001-9633-5662; Kjaer, Susanne/0000-0002-8347-1398 FU Intramural NIH HHS [Z01 CP010126-11] NR 66 TC 7 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2007 VL 107 IS 3 BP 487 EP 494 DI 10.1016/j.ygyno.2007.08.002 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 241BP UT WOS:000251632200019 PM 17825884 ER PT J AU Shivapurkar, N Sherman, ME Stastny, V Echebiri, C Rader, JS Nayar, R Bonfiglio, TA Gazdar, AF Wang, SS AF Shivapurkar, Narayan Sherman, Mark E. Stastny, Victor Echebiri, Chinyere Rader, Janet S. Nayar, Ritu Bonfiglio, Thomas A. Gazdar, Adi F. Wang, Sophia S. TI Evaluation of candidate methylation markers to detect cervical neoplasia SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cervical cancer; promoter methylation; tumor suppressor genes ID ABERRANT PROMOTER METHYLATION; HYPERMETHYLATED GENES; HEPARAN-SULFATE; MULTIPLE GENES; CANCER; CARCINOMA; TUMOR; SUPPRESSOR; WOMEN; LUNG AB Objective. Studies of cervical cancer and its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3), have identified genes that often show aberrant DNA methylation and therefore represent candidate early detection markers. We used quantitative PCR assays to evaluate methylation in five candidate genes (TNFRSF10C, DAPK1, SOCS3, HS3 ST2 and CDH1) previously demonstrated as inethylated in cervical cancer. Methods. In this analysis, we performed methylation assays for the five candidate genes in 45 invasive cervical cancers, 12 histologically normal cervical specimens, and 23 liquid-based cervical cytology specimens confirmed by expert review as unequivocal demonstrating cytologic high-grade squamous intraepithelial lesions, thus representing the counterparts of histologic CIN3. Results. We found hypermethylation of HS3ST2 in 93% of cancer tissues and 70% of cytology specimens interpreted as CIN3; hypermethylation of CDH1 was found in 89% of cancers and 26% of CIN3 cytology specimens. Methylation of either HS3 ST2 or CDH1 was observed in 100% of cervical cancer tissues and 83% of CIN3 cytology specimens. None of the five genes showed detectable methylation in normal cervical tissues. Conclusion. Our data support further evaluation of HS3ST2 and CDH1 methylation as potential markers of cervical cancer and its precursor lesions. Published by Elsevier Inc. C1 [Shivapurkar, Narayan; Stastny, Victor; Echebiri, Chinyere; Gazdar, Adi F.] Univ Texas SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Pathol, Dallas, TX 75930 USA. [Sherman, Mark E.; Wang, Sophia S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Rader, Janet S.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Nayar, Ritu] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. [Bonfiglio, Thomas A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. RP Wang, SS (reprint author), Univ Texas SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dept Pathol, Dallas, TX 75930 USA. EM wangso@mail.nih.gov FU Intramural NIH HHS [Z01 CP010124-12]; NCI NIH HHS [CA95713, R01 CA094141, R01 CA095713, CA94141] NR 28 TC 42 Z9 43 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2007 VL 107 IS 3 BP 549 EP 553 DI 10.1016/j.ygyno.2007.08.057 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 241BP UT WOS:000251632200028 PM 17894941 ER PT J AU Hurst, SA Reiter-Theil, S Perrier, A Forde, R Slowther, AM Pegoraro, R Danis, M AF Hurst, Samia A. Reiter-Theil, Stella Perrier, Arnaud Forde, Reidun Slowther, Anne-Marie Pegoraro, Renzo Danis, Marion TI Physicians' access to ethics support services in four European countries SO HEALTH CARE ANALYSIS LA English DT Article DE clinical ethics; ethics committees; ethics consultation; Europe; health services accessibility physicians ID CLINICAL ETHICS; NATIONAL-SURVEY; INTENSIVE-CARE; CONSULTATION; COMMITTEES; DIFFICULTIES; EXPERIENCES; EDUCATION; HEALTH AB Clinical ethics support services are developing in Europe. They will be most useful if they are designed to match the ethical concerns of clinicians. We conducted a cross-sectional mailed survey on random samples of general physicians in Norway, Switzerland, Italy, and the UK, to assess their access to different types of ethics support services, and to describe what makes them more likely to have used available ethics support. Respondents reported access to formal ethics support services such as clinical ethics committees (23%), consultation in individual cases (17.6%), and individual ethicists (8.8%), but also to other kinds of less formal ethics support (23.6%). Access to formal ethics support services was associated with work in urban hospitals. Informal ethics resources were more evenly distributed. Although most respondents (81%) reported that they would find help useful in facing ethical difficulties, they reported having used the available services infrequently (14%). Physicians with greater confidence in their knowledge of ethics (P = 0.001), or who had had ethics courses in medical school (P = 0.006), were more likely to have used available services. Access to help in facing ethical difficulties among general physicians in the surveyed countries is provided by a mix of official ethics support services and other resources. Developing ethics support services may benefit from integration of informal services. Development of ethics education in medical school curricula could lead to improved physicians sensititity to ethical difficulties and greater use of ethics support services. Such support services may also need to be more proactive in making their help available. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Geneva, Fac Med, Inst Biomed Eth, Geneva, Switzerland. Univ Basel, Inst Appl Eth & Med Eth, Basel, Switzerland. Univ Hosp Geneva, Gen Internal Med Serv, Geneva, Switzerland. Norwegian Med Assoc, Res Inst, Oslo, Norway. Univ Oslo, Oslo, Norway. Univ Oxford, Ethox Ctr, Headington, England. Fdn Lanza, Padua, Italy. RP Danis, M (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM mdanis@cc.nih.gov RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 NR 47 TC 15 Z9 15 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1065-3058 J9 HEALTH CARE ANAL JI Health Care Anal. PD DEC PY 2007 VL 15 IS 4 BP 321 EP 335 DI 10.1007/s10728-007-0072-6 PG 15 WC Ethics; Health Policy & Services; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Biomedical Social Sciences GA 226HU UT WOS:000250580900005 PM 17943449 ER PT J AU Campbell, MK Resnicow, K Carr, C Wang, T Williams, A AF Campbell, Marci Kramish Resnicow, Ken Carr, Carol Wang, Terry Williams, Alexis TI Process evaluation of an effective church-based diet intervention: Body & soul SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE minority health; health promotion; dietary intervention; motivational interviewing; cancer prevention ID AFRICAN-AMERICAN CHURCHES; RE-AIM FRAMEWORK; HEALTH-PROMOTION; BLACK CHURCHES; LIFE TRIAL; BEHAVIOR; AUTONOMY; FRUIT; FAT; VALIDATION AB Body & Soul has demonstrated effectiveness as a dietary intervention among African American church members. The process evaluation assessed relationships between program exposure and implementation factors and study outcomes and characterized factors important for adoption, implementation, and maintenance. Data sources included participant surveys and qualitative interviews with program staff, church liaisons, and volunteer advisors who conducted motivational interviewing (MI) calls. Outcomes included changes in dietary intake and psychosocial variables. Process variables included program exposure, participation, and dose and perceptions about MI calls. Results showed that attendance at project events, receiving educational materials, and self-reported quality of the MI calls were associated with significantly (p <.05) greater fruit and vegetable intake, decreased fat consumption, and other secondary outcomes. Interviews indicated implementation and sustainability issues and needs including more training to enhance MI implementation as well as ongoing support and resources. The results have implications for future dissemination efforts of Body & Soul. C1 Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NIH, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Campbell, MK (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Nutr, CB 7461, Chapel Hill, NC 27599 USA. EM Marci_Campbell@unc.edu NR 29 TC 44 Z9 45 U1 2 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD DEC PY 2007 VL 34 IS 6 BP 864 EP 880 DI 10.1177/1090198106292020 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 236BU UT WOS:000251278800002 PM 17200096 ER PT J AU Han, PKJ Moser, RP Klein, WMP AF Han, Paul K. J. Moser, Richard P. Klein, William M. P. TI Perceived ambiguity about cancer prevention recommendations: associations with cancer-related perceptions and behaviours in a US population survey SO HEALTH EXPECTATIONS LA English DT Article DE ambiguity; cancer; prevention; health behaviours; perceptions; recommendations ID SHARED DECISION-MAKING; AFRICAN-AMERICAN MEN; PROSTATE-CANCER; BREAST-CANCER; INFORMED-CONSENT; SCREENING MAMMOGRAPHY; RISK INFORMATION; HEALTH-CARE; CHOICE; WOMEN AB Background: Health information reaching the public today is often characterized by what decision theorists have termed 'ambiguity'- i.e. uncertainty regarding the information's reliability, credibility or adequacy. This is a critical problem, as growing research suggests that ambiguity has important effects-promoting pessimistic judgments about risks and potential outcomes of risk-reducing behaviours, and lowering adoption of these behaviours. However, little is known about the public's perceptions of ambiguity in the health information domain, the effects of these perceptions, and the factors that influence these effects. Objective: To examine associations between perceived ambiguity regarding cancer prevention recommendations and prevention-related perceptions and behaviours, and to explore how these associations differ by cancer type. Study design and participants: Cross-sectional analysis of data on 4070 adults participating in the 2005 US Health Information National Trends Survey. Main variables and outcome measures: We examined associations between perceived ambiguity about colon, skin and lung cancer prevention recommendations and two main outcome variables: (i) risk-related cognitions (perceived cancer risk and preventability, cancer-related worry) and (ii) risk-modifying behaviours (colon cancer screening, sunscreen use and smoking abstinence). Results: Perceived ambiguity was inversely associated with perceptions of the preventability of all three cancers, and with cancer-specific risk-modifying behaviours including sigmoidoscopy-colonoscopy testing, sunscreen use and smoking abstinence. Relationships with cancer risk perceptions and worry varied across different cancer types. Conclusions: Perceived ambiguity about cancer prevention recommendations has significant and predictable associations with cancer prevention-related cognitions and behaviours, and some associations differ by cancer type. These findings have implications for future research and communication efforts. C1 NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. RP Han, PKJ (reprint author), NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4091,MSC 7344, Bethesda, MD 20892 USA. EM hanp@mail.nih.gov OI Han, Paul/0000-0003-0165-1940 FU Intramural NIH HHS [Z99 HG999999] NR 62 TC 41 Z9 41 U1 0 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD DEC PY 2007 VL 10 IS 4 BP 321 EP 336 DI 10.1111/j.1369-7625.2007.00456.x PG 16 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 226WC UT WOS:000250618200003 PM 17986069 ER PT J AU Noben-Trauth, K Neely, H Brady, RO AF Noben-Trauth, Konrad Neely, Harold Brady, Roscoe O. TI Normal hearing in alpha-galactosidase A-deficient mice, the mouse model for Fabry disease SO HEARING RESEARCH LA English DT Article DE alpha-galactosidase A; Fabry disease; hearing ID STRAINS AB Fabry disease (OMIM 301500) is a rare X-linked recessive disorder caused by mutations in the alpha-galactosidase gene (Gla). Loss of Gla activity leads to the abnormal accumulation of glycosphingolipids in lysosomes of predominantly vascular endothelial cells. Clinically the disorder presents with angiokeratomas, clouding of the cornea, and renal, cardiac, and cerebrovascular complications. In addition, there is an increased incidence of sensorineural hearing loss in Fabry patients. In this study, we investigated the loss of alpha-galactosidase A activity on hearing function in Gla-deficient mice (Gla(tm1Kul)). Gla mRNA was readily detected in the cochlea of 2- and 12-month old C57BL/6J and C3HeB/FeJ mice. The targeted allele was introgressed to the normal hearing C3HeB/FeJ strain to eliminate confounding genetic background effects. Auditory brain stem responses (ABR) to click, 8-, 16-, and 32 kHz stimuli measured at regular intervals from animals at the N4 backcross generation and from N4F1 hybrids demonstrated normal hearing in hemizygous and homozygous mutant mice up to 76 weeks of age. By histological criteria, the cyto-architecture of the mutant cochlea showed a normal appearance. The data demonstrate that in the mouse the loss of alpha-galactosidase A activity is genetically or biochemically buffered and not sufficient per se to cause an appreciable degree of hearing impairment. Published by Elsevier B.V. C1 [Noben-Trauth, Konrad; Neely, Harold] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20855 USA. [Brady, Roscoe O.] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, 5 Res Court, Rockville, MD 20855 USA. EM nobentk@nidcd.nih.gov FU Intramural NIH HHS NR 18 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD DEC PY 2007 VL 234 IS 1-2 BP 10 EP 14 DI 10.1016/j.heares.2007.08.009 PG 5 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 244WK UT WOS:000251895800002 PM 17933476 ER PT J AU Murphy, E Steenbergen, C AF Murphy, Elizabeth Steenbergen, Charles TI Cardioprotection in females: a role for nitric oxide and altered gene expression SO HEART FAILURE REVIEWS LA English DT Article DE estrogen; mitochondria; nitric oxide ID ESTROGEN-RECEPTOR-BETA; ISCHEMIA-REPERFUSION INJURY; STEAROYL-COA DESATURASE; MYOCARDIAL INFARCT SIZE; HEAT-SHOCK PROTEINS; GENDER-DIFFERENCES; ER-BETA; ISCHEMIA/REPERFUSION INJURY; CARDIOVASCULAR-SYSTEM; ADIPOSE-TISSUE AB A number of epidemiological and animal studies have suggested a cardioprotective role for estrogen. This review will focus on the cardioprotective role of estrogen in ischemia-reperfusion injury. Estrogen binding to receptors can lead to altered gene expression and estrogen has been shown to induce expression of a number of genes that have been suggested to be important in cardioprotection. Estrogen is reported to increase expression of the plasma membrane glucose transporter GLUT4 and to increase carbohydrate metabolism. Estrogen has also been reported to increase mitochondrial biogenesis and to alter mitochondrial generation of reactive oxygen species. Estrogen results in upregulation of cardiac eNOS and nNOS, which have been shown previously to be important mediators of cardioprotection. Nitric oxide has been shown to result in S-nitrosylation and inhibition of the L-type calcium channel, thereby reducing calcium loading during ischemia. Nitric oxide has also been reported to inhibit complex I and inhibition of complex I has been reported to reduce activation of the mitochondrial permeability transition pore. Nitric oxide has been shown to result in activation of the mitochondrial K-ATP channel, which has been shown to be involved in cardioprotection. Estrogen can also activate rapid non-genomic pathways that activate cardioprotective-signaling pathways such as the phosphatidylinositol-3-kinase (PI-3 kinase) pathway which has also been shown to initiate protection. Taken together, estrogen by genomic and non-genomic pathways can result in the initiation of a number of signaling pathways that enhance cardioprotection. C1 NHLBI, Vasc Med Branch, Head Cardiac Physiol Sect, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Murphy, E (reprint author), NHLBI, Vasc Med Branch, Head Cardiac Physiol Sect, Bldg 10,Room 7N112,10 Ctr Dr, Bethesda, MD 20892 USA. EM murphy1@niehs.nih.gov FU NHLBI NIH HHS [R01 HL039752] NR 85 TC 40 Z9 42 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1382-4147 J9 HEART FAIL REV JI Heart Fail. Rev. PD DEC PY 2007 VL 12 IS 3-4 BP 293 EP 300 DI 10.1007/s10741-007-9035-0 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 191ZQ UT WOS:000248170900013 PM 17508281 ER PT J AU Moak, JP Goldstein, DS Eldadah, BA Saleem, A Holmes, C Pechnik, S Sharabi, Y AF Moak, Jeffrey P. Goldstein, David S. Eldadah, Basil A. Saleem, Ahmed Holmes, Courtney Pechnik, Sandra Sharabi, Yehonatan TI Supine low-frequency power of heart rate variability reflects baroreftex function, not cardiac sympathetic innervation SO HEART RHYTHM LA English DT Article DE baroreceptors; fluorodopamine; heart rate variability; power spectral analysis; sympathetic nervous system ID CHRONIC ORTHOSTATIC INTOLERANCE; RATE SPECTRAL-ANALYSIS; NEUROCIRCULATORY ABNORMALITIES; AUTONOMIC MODULATION; PARKINSON-DISEASE; NERVE ACTIVITY; FAILURE; MECHANISMS; HUMANS; NOREPINEPHRINE AB BACKGROUND Power spectral analysis of heart rate variability (HRV) has been used to indicate cardiac autonomic function. High-frequency power relates to respiratory sinus arrhythmia and therefore to parasympathetic cardiovagal tone; however, the relationship of Low-frequency (LF) power to cardiac sympathetic innervation and function has been controversial. Alternatively, LF power might reflect baroreflexive modulation of autonomic outflows. OBJECTIVE We studied normal volunteers and chronic autonomic failure syndrome patients with and without loss of cardiac noradrenergic nerves to examine the relationships of LF power with cardiac sympathetic innervation and baroreflex function. METHODS We compared LF power of HRV in patients with cardiac sympathetic denervation, as indicated by Low myocardial concentrations of 6-[F-18] fluorodopamine-derived radioactivity or low rates of norepinephrine entry into coronary sinus plasma (cardiac norepinephrine spillover) to values in patients with intact innervation, at baseline, during infusion of yohimbine, which increases exocytotic norepinephrine release from sympathetic nerves, or during infusion of tyramine, which increases non-exocytotic release. Baroreflex-cardiovagal slope (BRS) was calculated from the cardiac interbeat interval and systolic pressure during the Valsalva maneuver. RESULTS LF power was unrelated to myocardial 6-[F-18] fluorodopamine-derived radioactivity or cardiac norepinephrine spillover. In contrast, the log of LF power correlated positively with the log of BRS (r = 0.72, P <0.0001). Patients with a tow BRS (<= 3 msec/mm Hg) had tow LF power, regardless of cardiac innervation. Tyramine and yohimbine increased LF power in subjects with normal BRS but not in those with Low BRS. BRS at baseline predicted LF responses to tyramine and yohimbine. CONCLUSION LF power reflects baroreflex function, not cardiac sympathetic innervation. C1 [Moak, Jeffrey P.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Goldstein, David S.; Eldadah, Basil A.; Saleem, Ahmed; Holmes, Courtney; Pechnik, Sandra; Sharabi, Yehonatan] NIH, Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. RP Moak, JP (reprint author), Bldg 10 Room 6N252,10 Ctr Dr,MSC 1620, Bethesda, MD 20892 USA. EM moakj@mail.nih.gov FU Intramural NIH HHS [Z01 NS002979-09] NR 28 TC 75 Z9 75 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD DEC PY 2007 VL 4 IS 12 BP 1523 EP 1529 DI 10.1016/j.hrthm.2007.07.019 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243HC UT WOS:000251786400007 PM 17997358 ER PT J AU Zakhari, S Li, TK AF Zakhari, Samir Li, Ting-Kai TI Determinants of alcohol use and abuse: Impact of quantity and frequency patterns on liver disease SO HEPATOLOGY LA English DT Review ID CHRONIC HEPATITIS-C; METABOLIZING ENZYMES; NATIONAL-HEALTH; USE DISORDERS; RISK; CONSUMPTION; CIRRHOSIS; POLYMORPHISMS; FIBROSIS; DRINKING AB More than 70% of alcohol is consumed by 10% of the population in the United States. Implicit in this statistic is that tremendous variation in the pattern of drinking (quantity, frequency, and duration) exists among alcohol consumers. Individuals who are binge or chronic drinkers will have different health outcomes than social drinkers. Therefore, knowing the pattern of drinking will shed light on how severely individuals are alcohol-dependent and on the extent of liver damage. Thus, these parameters assume particular relevance for the treatment-providing physician. Genetic factors contribute substantially to differences in alcohol metabolism. Variations in the activities of the alcohol-metabolizing enzymes, cytosolic alcohol dehydrogenase and mitochondrial aldehyde dehydrogenase, in part determine blood alcohol concentration, thereby contributing to the predisposition to becoming alcohol-dependent and to susceptibility to alcohol-induced liver damage. Chronic alcohol consumption induces cytochrome P450 2E1, a microsomal enzyme that metabolizes alcohol at high concentrations and also metabolizes medications such as acetaminophen and protease inhibitors. Alcohol metabolism changes the redox state of the liver, which leads to alterations in hepatic lipid, carbohydrate, protein, lactate, and uric acid metabolism. The quantity and frequency of alcohol consumption severely impact the liver in the presence of comorbid conditions such as infection with hepatitis B or C and/or human immunodeficiency virus, type 2 diabetes, hemochromatosis, or obesity and thus have implications with respect to the extent of injury and response to medications. Conclusion: Knowledge of the relationships between the quantity, frequency, and patterns of drinking and alcoholic liver disease is limited. A better understanding of these relationships will guide hepatologists in managing alcoholic liver disease. C1 NIAAA, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Zakhari, S (reprint author), NIAAA, 5635 Fishers Lane, Rm 2031, Bethesda, MD 20892 USA. EM szakhari@mail.nib.gov NR 50 TC 110 Z9 120 U1 4 U2 19 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2007 VL 46 IS 6 BP 2032 EP 2039 DI 10.1002/hep.22010 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 238TY UT WOS:000251471700042 PM 18046720 ER PT J AU Cleary, S Phillips, JK Huynh, TT Pacak, K Fliedner, S Elkahloun, AG Munson, P Worrell, RA Eisenhofer, G AF Cleary, S. Phillips, J. K. Huynh, T-T Pacak, K. Fliedner, S. Elkahloun, A. G. Munson, P. Worrell, R. A. Eisenhofer, G. TI Chromogranin A expression in phaeochromocytomas associated with von Hippel-Lindau syndrome and multiple endocrine neoplasia type SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE chromaffin cells; catecholamines; noradrenaline; adrenaline; granin; exocytosis ID SECRETORY GRANULE BIOGENESIS; PHENYLETHANOLAMINE N-METHYLTRANSFERASE; ADRENAL CHROMAFFIN GRANULES; CATECHOLAMINE RELEASE; TARGETED ABLATION; SOLUBLE-PROTEIN; ON/OFF SWITCH; STORAGE; GENE; IDENTIFICATION AB Chromogranin A (CGA) is a major secretory protein present in the soluble matrix of chromaffin granules of neuroendocrine cells and tumours, such as phaeochromocytomas. CGA has several functions, some of which may be involved in the distinct phenotypic differences of phaeochromocytomas in patients with von Hippel-Lindau (VHL) syndrome compared to multiple endocrine neoplasia type 2 (MEN 2). In this study, we therefore compared tumour and plasma levels of CGA in patients with phaeochromocytorna associated with the two syndromes. We show that phaeochromocytomas from MEN 2 patients express substantially more CGA than tumours from VHL patients at both the mRNA (3-fold greater) and protein (20-fold) level. We further show that relative to increases in plasma catecholamines, patients with phaeochromocytomas associated with MEN 2 have higher plasma concentrations of CGA than those with tumours in VHL syndrome. These data supplement other observations that phaeochromocytomas in VHL compared to MEN 2 patients express lower amounts of catecholamines and other chromaffin granule cargo, such as chromogranin B and neuropeptide Y. Possibly the differences in turnout CGA expression may contribute to differences in secretory vesicle formation and secretion in the two types of tumours. Alternatively the differences in expression in CGA and other secretory constituents may reflect downregulation of the entire regulated secretory pathway in VHL compared to MEN 2 tumours. C1 [Cleary, S.; Phillips, J. K.] Murdoch Univ, Sch Vet & Biomed Sci, Div Hlth Sci, Perth, WA 6150, Australia. [Cleary, S.; Phillips, J. K.] Western Australian Biomed Res Inst, Perth, WA, Australia. [Cleary, S.; Huynh, T-T; Eisenhofer, G.] Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD USA. [Pacak, K.; Fliedner, S.] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. [Elkahloun, A. G.] Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. [Munson, P.] NIH, Math & Stat Inst Hlth, Ctr Informat Technol, Bethesda, MD 20892 USA. [Worrell, R. A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Cleary, S (reprint author), Murdoch Univ, Sch Vet & Biomed Sci, Div Hlth Sci, Perth, WA 6150, Australia. EM S.Cleary@murdoch.edu.au RI Phillips, Jacqueline/G-7901-2011; Fliedner, Stephanie/D-3406-2012 OI Phillips, Jacqueline/0000-0002-4917-7734; FU Intramural NIH HHS NR 33 TC 13 Z9 13 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD DEC PY 2007 VL 39 IS 12 BP 876 EP 883 DI 10.1055/s-2007-993135 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 251GL UT WOS:000252360500006 PM 18046660 ER PT J AU Ain, Q Nazli, S Riazuddin, S Jaleel, AU Riazuddin, SA Zafar, AU Khan, SN Husnain, T GriYth, AJ Ahmed, ZM Friedman, TB Riazuddin, S AF Ain, Quratul Nazli, Sabiha Riazuddin, Saima Jaleel, Ateeq-ul Riazuddin, S. Amer Zafar, Ahmad U. Khan, Shaheen N. Husnain, Tayyab GriYth, Andrew J. Ahmed, Zubair M. Friedman, Thomas B. Riazuddin, Sheikh TI The autosomal recessive nonsyndromic deafness locus DFNB72 is located on chromosome 19p13.3 SO HUMAN GENETICS LA English DT Article ID SYNDROMIC HEARING-LOSS; SYNDROME TYPE 1D; SYNDROME TYPE 1F; PROTOCADHERIN GENE; BINDING-PROTEIN; MUTATIONS; PCDH15; CADHERIN; ALLELES; CDH23 AB We ascertained three consanguineous Pakistani families ( PKDF291, PKDF335 and PKDF793) segregating nonsyndromic recessive hearing loss. The hearing loss segregating in PKDF335 and PKDF793 is moderate to severe, whereas it is profound in PKDF291. The maximum two-point LOD scores are 3.01 ( D19S1034), 3.85 ( D19S894) and 3.71 ( D19S894) for PKDF291, PKDF335 and PKDF793, respectively. Haplotype analyses of the three families define a 1.16 Mb region of overlap of the homozygous linkage intervals bounded by markers D19S216 ( 20.01 cM) and D19S1034 ( 20.75 cM). These results define a novel locus, DFNB72, on chromosome 19p13.3. There are at least 22 genes in the 1.16 Mb interval, including PTPRS, ZNRF4 and CAPS. We identified no pathogenic variants in the exons and flanking intronic sequences of these three genes in affected members of the DFNB72 families. DFNB72 is telomeric to DFNB68, the only other known deafness locus with statistically significant support for linkage to chromosome 19p. C1 Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. Natl Inst Hlth, Sect Human Genet, Mol Genet Lab, Rockville, MD 20850 USA. NIH, Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, Rockville, MD 20850 USA. RP Riazuddin, SA (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd,Thokar Niaz Baig, Lahore 53700, Pakistan. EM riaz@lhr.comsats.net.pk RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015 FU Intramural NIH HHS NR 34 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 2007 VL 122 IS 5 BP 445 EP 450 DI 10.1007/s00439-007-0418-z PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 234EQ UT WOS:000251143900003 PM 17690910 ER PT J AU Lee, KM Lan, Q Kricker, A Purdue, MP Grulich, AE Vajdic, CM Turner, J Whitby, D Kang, D Chanock, S Rothman, N Armstrong, BK AF Lee, Kyoung-Mu Lan, Qing Kricker, Anne Purdue, Mark P. Grulich, Andrew E. Vajdic, Claire M. Turner, Jennifer Whitby, Denise Kang, Daehee Chanock, Stephen Rothman, Nathaniel Armstrong, Bruce K. TI One-carbon metabolism gene polymorphisms and risk of non-Hodgkin lymphoma in Australia SO HUMAN GENETICS LA English DT Article ID 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISMS; ACUTE LYMPHOBLASTIC-LEUKEMIA; METHYLENETETRAHYDROFOLATE REDUCTASE; MALIGNANT-LYMPHOMA; 10-FORMYLTETRAHYDROFOLATE DEHYDROGENASE; LYMPHOPROLIFERATIVE DISORDERS; ALTERS SUSCEPTIBILITY; THYMIDYLATE-SYNTHASE; MULTIPLE-MYELOMA; DNA-REPAIR AB Dysregulation of the one-carbon metabolic pathway, which controls nucleotide synthesis and DNA methylation, may promote lymphomagenesis. We evaluated the association between polymorphisms in one-carbon metabolism genes and risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study in Australia. Cases (n = 561) and controls (n = 506) were genotyped for 14 selected single-nucleotide polymorphisms in 10 genes (CBS, FPGS, FTHFD, MTHFR, MTHFS, MTR, SHMT1, SLC19A1, TCN1, and TYMS). We also conducted a meta-analysis of all studies of Caucasian populations investigating the association between MTHFR Ex5+79C>T (a.k.a., 677C>T) and NHL risk. A global test of 13 genotypes was statistically significant for diffuse large B-cell lymphoma (DLBCL; P = 0.008), but not for follicular lymphoma (FL; P = 0.27) or all NHL (P = 0.17). The T allele at MTHFR Ex5+79 was marginally significantly associated with all NHL (OR = 1.25, 95% CI = 0.98-1.59) and DLBCL (1.36, 0.96-1.93). The T allele at TYMS Ex8+157 was associated with a reduced risk of FL (0.64, 0.46-0.91). An elevated risk of NHL was also observed among carriers of the G allele at FTHFD Ex21+31 (all NHL, 1.31, 1.02-1.69; DLBCL, 1.50, 1.05-2.14). A meta-analysis of 11 studies conducted in Caucasian populations of European origin (4,121 cases and 5,358 controls) supported an association between the MTHFR Ex5+79 T allele and increased NHL risk (additive model, P = 0.01). In conclusion, the results of this study suggest that genetic polymorphisms of one-carbon metabolism genes such as MTHFR and TYMS may influence susceptibility to NHL. C1 Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch,DHHS, Bethesda, MD 20892 USA. Univ Sydney, Sch Publ Hlth, Sydney, NSW, Australia. Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. St Vincents Hosp, Sydney, NSW 2010, Australia. NCI, Frederick, MD 21701 USA. Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. NCI, NIH, Ctr Canc Res, Ctr Adv Technol,Div Canc Epidemiol & Genet Pediat, Bethesda, MD USA. RP Lee, KM (reprint author), Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch,DHHS, 6120 Executive Blvd EPS 8118, Bethesda, MD 20892 USA. EM leekyou@mail.nih.gov RI Kang, Dae Hee/E-8631-2012; Armstrong, Bruce/K-9464-2015; Purdue, Mark/C-9228-2016; OI Armstrong, Bruce/0000-0001-8940-7525; Purdue, Mark/0000-0003-1177-3108; Vajdic, Claire/0000-0002-3612-8298 FU Intramural NIH HHS NR 42 TC 30 Z9 32 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 2007 VL 122 IS 5 BP 525 EP 533 DI 10.1007/s00439-007-0431-2 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 234EQ UT WOS:000251143900012 PM 17891500 ER PT J AU Ottolenghi, C Pelosi, E Tran, J Colombino, M Douglass, E Nedorezov, T Cao, A Forabosco, A Schlessinger, D AF Ottolenghi, Chris Pelosi, Emanuele Tran, Joseph Colombino, Maria Douglass, Eric Nedorezov, Timur Cao, Antonio Forabosco, Antonino Schlessinger, David TI Loss of Wnt4 and Foxl2 leads to female-to-male sex reversal extending to germ cells SO HUMAN MOLECULAR GENETICS LA English DT Article ID GONADAL DEVELOPMENT; OVARIAN DEVELOPMENT; INVERSUS SYNDROME; GENE-EXPRESSION; MAMMALIAN GONAD; SERTOLI-CELLS; DIFFERENTIATION; MOUSE; MICE; TESTIS AB The discovery that the SRY gene induces male sex in humans and other mammals led to speculation about a possible equivalent for female sex. However, only partial effects have been reported for candidate genes experimentally tested so far. Here we demonstrate that inactivation of two ovarian somatic factors, Wnt4 and Foxl2, produces testis differentiation in XX mice, resulting in the formation of testis tubules and spermatogonia. These genes are thus required to initiate or maintain all major aspects of female sex determination in mammals. The two genes are independently expressed and show complementary roles in ovary morphogenesis. In addition, forced expression of Foxl2 impairs testis tubule differentiation in XY transgenic mice, and germ cell-depleted XX mice lacking Foxl2 and harboring a Kit mutation undergo partial female-to-male sex reversal. The results are all consistent with an anti-testis role for Foxl2. The data suggest that the relative autonomy of the action of Foxl2, Wnt4 and additional ovarian factor(s) in the mouse should facilitate the dissection of their respective contributions to female sex determination. C1 NIA, Genet Lab, NIH, IRP, Baltimore, MD 21224 USA. CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. Univ Modena & Reggio Emilia, Dept Mother & Child, Reggio Emilia, Italy. RP Ottolenghi, C (reprint author), NIA, Genet Lab, NIH, IRP, Baltimore, MD 21224 USA. EM chris11@helix.nih.gov OI Pelosi, Emanuele/0000-0003-1890-9821 FU Intramural NIH HHS NR 75 TC 149 Z9 155 U1 0 U2 14 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 DEC 1 PY 2007 VL 16 IS 23 BP 2795 EP 2804 DI 10.1093/hmg/ddm235 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 232RG UT WOS:000251036400002 PM 17728319 ER PT J AU Hishimoto, A Liu, QR Drgon, T Pletnikova, O Walther, D Zhu, XG Troncoso, JC Uhl, GR AF Hishimoto, Akitoyo Liu, Qing-Rong Drgon, Tomas Pletnikova, Olga Walther, Donna Zhu, Xu-Guang Troncoso, Juan C. Uhl, George R. TI Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms SO HUMAN MOLECULAR GENETICS LA English DT Article ID CELL-SURFACE PROTEINS; ALPHA-NEUREXINS; BETA-NEUREXINS; ADDICTION VULNERABILITY; FAMILIAL TRANSMISSION; GENETIC MODIFIER; ADHESION; AUTISM; NEUROLIGINS; BINDING AB Neurexins are cell adhesion molecules that help to specify and stabilize synapses and provide receptors for neuroligins, neurexophilins, dystroglycans and alpha-latrotoxins. We previously reported significant allele frequency differences for single nucleotide polymorphisms (SNPs) in the neurexin 3 (NRXN3) gene in each of two comparisons between individuals who were dependent on illegal substances and controls. We now report work clarifying details of NRXN3's gene structure and variants and documenting association of NRXN3 SNPs with alcohol dependence. We localize this association signal with the vicinity of the NRXN3 splicing site 5 (SS#5). A splicing site SNP, rs8019381, that is located 23 bp from the SS#5 exon 23 donor site displays association with P = 0.0007 (odds ratio = 2.46). Including or excluding exon 23 at SS#5 produces soluble or transmembrane NRXN3 isoforms. We thus examined expression of these NRXN3 isoforms in postmortem human cerebral cortical brain samples from individuals with varying rs8019381 genotypes. Two of the splice variants that encode transmembrane NRXN3 isoforms were expressed at significantly lower levels in individuals with the addiction-associated rs8019381 'T' allele than in CC homozygotes. Taken together with recent reports of NRXN3 association with nicotine dependence and linkage with opiate dependence, these data support roles for NRXN3 haplotypes that alter expression of specific NRXN3 isoforms in genetic vulnerabilities to dependence on a variety of addictive substances. C1 NIDA, Mol Neurobiol Branch, IRP, NIH,DHSS, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, IRP, NIH,DHSS, 333 Cassell Dr,Suite 3510, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 NR 66 TC 63 Z9 63 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 1 PY 2007 VL 16 IS 23 BP 2880 EP 2891 DI 10.1093/hmg/ddm247 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 232RG UT WOS:000251036400009 PM 17804423 ER PT J AU Mathew, SV Law, AJ Lipska, BK Davila-Garcia, MI Zamora, ED Mitkus, SN Vakkalanka, R Straub, RE Weinberger, DR Kleinman, JE Hyde, TM AF Mathew, Shiny V. Law, Amanda J. Lipska, Barbara K. Davila-Garcia, Martha I. Zamora, Eduardo D. Mitkus, Shruti N. Vakkalanka, Radhakrishna Straub, Richard E. Weinberger, Daniel R. Kleinman, Joel E. Hyde, Thomas M. TI alpha 7 nicotinic acetylcholine receptor mRNA expression and binding in postmortem human brain are associated with genetic variation in neuregulin 1 SO HUMAN MOLECULAR GENETICS LA English DT Article ID SPATIAL WORKING-MEMORY; LONG-TERM POTENTIATION; IN-SITU HYBRIDIZATION; ALZHEIMERS-DISEASE; MOUSE-BRAIN; PREFRONTAL CORTEX; CEREBRAL-CORTEX; RAT-BRAIN; AUTORADIOGRAPHIC ANALYSIS; ATYPICAL ANTIPSYCHOTICS AB Studies in cell culture and in animals suggest that neuregulin 1 (NRG1), a probable schizophrenia susceptibility gene, regulates the expression of the alpha 7 nicotinic acetylcholine receptors (nAChRs). We hypothesized that schizophrenia-associated allelic variations within the NRG1 gene, via their effects on NRG1 isoform expression, would be associated with alterations in nAChR a7 receptor levels. We examined the effects of four disease-associated single-nucleotide polymorphisms (SNPs) in the 50 region of the NRG1 gene on nAChR a7 mRNA transcript expression in both the dorsolateral prefrontal cortex (DLPFC) and hippocampus of normal controls and patients with schizophrenia using quantitative real-time PCR. NRG1 risk alleles at SNPs SNP8NRG221132 and rs6994992 predicted significantly lower nAChR a7 mRNA expression in the DLPFC. Haplotypes containing the risk alleles at the above SNPs were also associated with lower expression of nAChR a7 in the DLPFC. The genotype effect for rs6994992 and the haplotype effect were more pronounced within the schizophrenic patient group. To determine whether receptor levels follow that of mRNA expression, we performed receptor binding and autoradiography using [I-125] alpha-bungarotoxin in the DLPFC. Consistent with the mRNA findings, we found a decrease in binding in risk allele carriers of SNP8NRG221132 as compared with heterozygous individuals. Together, these results suggest that the molecular mechanism of the association between NRG1 risk alleles and schizophrenia may include down-regulation of nAChR a7 expression. C1 NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. RP Hyde, TM (reprint author), 10 Ctr Dr,Bldg 10,Room 4N312, Bethesda, MD 20892 USA. EM hydet@mail.nih.gov RI Law, Amanda/G-6372-2012; OI Law, Amanda/0000-0002-2574-1564 FU Intramural NIH HHS; Medical Research Council [G120/997] NR 76 TC 45 Z9 46 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 1 PY 2007 VL 16 IS 23 BP 2921 EP 2932 DI 10.1093/hmg/ddm253 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 232RG UT WOS:000251036400013 PM 17884806 ER PT J AU Louis, GMB Hediger, ML Pena, JB AF Louis, Germaine M. Buck Hediger, Mary L. Pena, Josefa B. TI Intrauterine exposures and risk of endometriosis SO HUMAN REPRODUCTION LA English DT Article DE angiogenesis; cigarette smoking; endometriosis; gynecologic health; intrauterine ID TESTICULAR CANCER; ANGIOGENIC FACTORS; CIGARETTE-SMOKE; FERTILITY; PREECLAMPSIA; CYTOCHROME-P450; PREGNANCY; NICOTINE; TRENDS; GROWTH AB BACKGROUND: Intrauterine environmental exposures have been adversely associated with male reproductive health in contrast to limited investigation of such exposures and female reproductive health. METHODS: To address this research gap, a cohort comprising 84 women aged 18-40 years undergoing laparoscopy was recruited prior to surgery and followed through the post-operative period for endometriosis diagnosis. Women were interviewed about environmental exposures and those of their mothers while pregnant with them (use of alcohol, caffeinated beverages and cigarettes). Endometriosis was diagnosed in 32 women from the laparoscopy cohort; 52 women had no endometriosis visualized. Using unconditional logistic regression, odds ratios (OR) and 95 % confidence intervals (CIs) were estimated for the intrauterine exposures adjusting for potential confounders. RESULTS: No significant associations were seen between intrauterine exposure to alcohol or caffeine and a diagnosis of endometriosis. Adjusting for age, significant reductions in odds of an endometriosis diagnosis were observed for intrauterine cigarette exposure both in the absence (OR 0.22, 95% CI 0.06-0.82) or presence (OR 0.05, 95% CI 0.01-0.42) of women's current smoking. CONCLUSIONS: While speculative, in utero cigarette exposure may be associated with a lower risk of surgically diagnosed adult-onset endometriosis, possibly as a result of alterations in hormonal milieu or pathologic angiogensis. C1 [Louis, Germaine M. Buck; Hediger, Mary L.] NICHHD, Epidemiol Branch, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Pena, Josefa B.] Texas A&M Univ, Hlth Sci Ctr, Sch Rural Publ Hlth, Dept Epidemiol & Biostat, College Stn, TX 77843 USA. RP Louis, GMB (reprint author), NICHHD, Epidemiol Branch, Dept Hlth & Human Serv, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM louisg@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 NR 43 TC 23 Z9 23 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD DEC PY 2007 VL 22 IS 12 BP 3232 EP 3236 DI 10.1093/humrep/dem338 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 248KF UT WOS:000252151500025 ER PT J AU Whitcomb, BW Schisterman, EF Louis, GM AF Whitcomb, Brian W. Schisterman, Enrique F. Louis, Germaine M. TI Gestational age and gestational age-at-delivery: cause, effect, or time-scale? SO HUMAN REPRODUCTION LA English DT Letter C1 [Whitcomb, Brian W.; Schisterman, Enrique F.; Louis, Germaine M.] NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. RP Whitcomb, BW (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Rm 7B03A, Rockville, MD 20852 USA. EM whitcomb@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490 NR 4 TC 1 Z9 1 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD DEC PY 2007 VL 22 IS 12 BP 3267 EP 3267 DI 10.1093/humrep/dem332 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 248KF UT WOS:000252151500037 PM 17940070 ER PT J AU Sullivan, LC Clements, CS Beddoe, T Johnson, D Hoare, HL Lin, J Huyton, T Hopkins, EJ Reid, HH Wilce, MCJ Kabat, J Borrego, F Coligan, JE Rossjohn, J Brooks, AG AF Sullivan, Lucy C. Clements, Craig S. Beddoe, Travis Johnson, Darryl Hoare, Hilary L. Lin, Jie Huyton, Trevor Hopkins, Emma J. Reid, Hugh H. Wilce, Mafthew C. J. Kabat, Juraj Borrego, Francisco Coligan, John E. Rossjohn, Jamie Brooks, Andrew G. TI The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition SO IMMUNITY LA English DT Article ID KILLER-CELL RECEPTORS; ACTIVATING IMMUNORECEPTOR NKG2D; CLASS-I RECOGNITION; HLA-E; CRYSTAL-STRUCTURE; CD94/NKG2 RECEPTORS; INHIBITORY RECEPTOR; MOLECULE QA-1(B); STRUCTURAL BASIS; COMPLEX AB The CD94-NKG2 receptor family that regulates NK and T cells; is unique among the lectin-like receptors encoded within the natural killer cell complex. The function of the CD94-NKG2 receptors is dictated by the pairing of the invariant CD94 polypeptide with specific NKG2 isoforms to form a family of functionally distinct heterodimeric receptors. However, the structural basis for this selective pairing and how they interact with their ligand, HLA-E, is unknown. We describe the 2.5 angstrom resolution crystal structure of CD94-NKG2A in which the mode of dimerization contrasts with that of other homodimeric NK receptors. Despite structural homology between the CD94 and NKG2A subunits, the dimer interface is asymmetric, thereby providing a structural basis for the preferred heterodimeric assembly. Structure-based sequence comparisons of other CD94-NKG2 family members, combined with extensive mutagenesis studies on HLA-E and CD94-NKG2A, allows a model of the interaction between CD94-NKG2A and HLA-E to be established, in which the invariant CD94 chain plays a more dominant role in interacting with HLA-E in comparison to the variable NKG2 chain. C1 [Clements, Craig S.; Beddoe, Travis; Hoare, Hilary L.; Huyton, Trevor; Hopkins, Emma J.; Reid, Hugh H.; Wilce, Mafthew C. J.; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol,Prot Crystallog Unit, ARC Ctr Excellence Struct & Funct Microbial Genom, Clayton, Vic 3800, Australia. [Sullivan, Lucy C.; Johnson, Darryl; Lin, Jie; Brooks, Andrew G.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia. [Kabat, Juraj; Borrego, Francisco; Coligan, John E.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Rossjohn, J (reprint author), Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol,Prot Crystallog Unit, ARC Ctr Excellence Struct & Funct Microbial Genom, Clayton, Vic 3800, Australia. EM jamie.rossjohn@med.monash.edu.au; agbrooks@unimelb.edu.au RI Rossjohn, Jamie/F-9032-2013; Beddoe, Travis/F-3415-2014; OI Rossjohn, Jamie/0000-0002-2020-7522; Sullivan, Lucy/0000-0003-2907-4989; Beddoe, Travis/0000-0003-4550-2277; Brooks, Andrew/0000-0002-4085-9683 NR 43 TC 43 Z9 46 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2007 VL 27 IS 6 BP 900 EP 911 DI 10.1016/j.immuni.2007.10.013 PG 12 WC Immunology SC Immunology GA 245AS UT WOS:000251907300010 PM 18083576 ER PT J AU Swanson, KA Crane, DD Caldwell, HD AF Swanson, Kena A. Crane, Deborah D. Caldwell, Harlan D. TI Chlamydia trachomatis species-specific induction of ezrin tyrosine phosphorylation functions in pathogen entry SO INFECTION AND IMMUNITY LA English DT Article ID PROTEIN DISULFIDE-ISOMERASE; OUTER-MEMBRANE PROTEIN; EPITHELIAL-CELLS; HOST-CELLS; SHIGELLA-FLEXNERI; MAMMALIAN-CELLS; GENOME SEQUENCE; HELA-CELLS; ATTACHMENT; INFECTION AB Chlamydia trachomatis is an obligate intracellular pathogen of humans that exhibits species-specific biological characteristics in its early interactions with host cells that are likely important to pathogenesis. One such characteristic is the tyrosine phosphorylation (Tyr-P) of an similar to 70-kDa polypeptide that occurs only after infection of mammalian cells by human strains. We sought to identify this protein because of its potential significance to the pathogenesis of human chlamydial infections. Using an immunoproteomic approach we identified the host protein ezrin, a member of the ezrin-radixin-moesin (ERM) protein family that serves as a physical link between host cell receptors and the actin cytoskeleton. Confocal microscopy studies showed colocalization of ezrin and actin at the tips and crypts of microvilli, the site of chlamydial attachment and entry, respectively. To demonstrate a functional role for ezrin we infected cells with a dominant-negative (DN) ezrin phenotype or treated cells with ezrin-specific small interfering RNA (siRNA). We found that both DN and siRNA-treated cells were significantly less susceptible to infection by human chlamydial strains. Moreover, we demonstrated that inhibition of infection in ezrin DN cells occurred at the stage of chlamydial entry. We hypothesize that the C. trachomatis-specific Tyr-P of ezrin might relate to an undefined species-specific mechanism of pathogen entry that involves chlamydial specific ligand(s) and host cell coreceptor usage. C1 NIAID, NIH, Intracellular Parasites Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, NIH, Intracellular Parasites Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM hcaldwell@niaid.nih.gov FU Intramural NIH HHS NR 48 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2007 VL 75 IS 12 BP 5669 EP 5677 DI 10.1128/IAI.01096-07 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 236ZF UT WOS:000251341500014 PM 17908813 ER PT J AU Miura, K Zhou, H Muratova, OV Orcutt, AC Giersing, B Miller, LH Long, CA AF Miura, Kazutoyo Zhou, Hong Muratova, Olga V. Orcutt, Andrew C. Giersing, Birgitte Miller, Louis H. Long, Carole A. TI In immunization with Plasmodium falciparum apical membrane antigen 1, the specificity of antibodies depends on the species immunized SO INFECTION AND IMMUNITY LA English DT Article ID APICAL MEMBRANE ANTIGEN-1; MALARIA VACCINE CANDIDATE; BLOOD-STAGE MALARIA; BAY COHORT PROJECT; ERYTHROCYTE INVASION; NATURAL-SELECTION; DOMAIN-III; RECOMBINANT; PROTEIN; AMA-1 AB At least a million people, mainly African children under 5 years old, still die yearly from malaria, and the burden of disease and death has increased. Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is one of the most promising blood-stage malarial vaccine candidates. However, the allelic polymorphism observed in this protein is a potential stumbling block for vaccine development. To overcome the polymorphism- and strain-specific growth inhibition in vitro, we previously showed in a rabbit model that vaccination with a mixture of two allelic forms of PfAMA1 induced parasite growth-inhibitory antisera against both strains of P. falciparum parasites in vitro. In the present study, we have established that, in contrast to a single-allele protein, the antigen mixture elicits primarily antibodies recognizing antigenic determinants common to the two antigens, as judged by an antigen reversal growth inhibition assay (GIA). We also show that a similar reactivity pattern occurs after immunization of mice. By contrast, sera from rhesus monkeys do not distinguish the two alleles when tested by an enzyme-linked immunosorbent assay or by GIA, regardless of whether the immunogen is a single AMA1 protein or the mixture. This is the first report that a malarial vaccine candidate induced different specificities of functional antibodies depending on the animal species immunized. These observations, as well as data available on human immune responses in areas of endemicity, suggest that polymorphism in the AMA1 protein may not be as formidable a problem for vaccine development as anticipated from studies with rabbits and mice. C1 NIH, NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA. RP Miura, K (reprint author), 12441 Parklawn Dr,Twinbrook 2,room 107, Rockville, MD 20852 USA. EM kmiura@niaid.nih.gov FU Intramural NIH HHS NR 47 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2007 VL 75 IS 12 BP 5827 EP 5836 DI 10.1128/IAI.00593-07 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 236ZF UT WOS:000251341500033 PM 17923516 ER PT J AU Stump, AD Pombi, M Goeddel, L Ribeiro, JMC Wilder, JA Torre, AD Besansky, NJ AF Stump, A. D. Pombi, M. Goeddel, L. Ribeiro, J. M. C. Wilder, J. A. Torre, A. D. Besansky, N. J. TI Genetic exchange in 2La inversion heterokaryotypes of Anopheles gambiae SO INSECT MOLECULAR BIOLOGY LA English DT Article DE Anopheles gambiae; chromosomal inversion; gene flux; genetic exchange; recombination ID DROSOPHILA-PSEUDOOBSCURA; CHROMOSOMAL INVERSIONS; RECOMBINATION RATE; SPECIATION; DIFFERENTIATION; POLYMORPHISMS; ADAPTATION; MOSQUITOS; GENOME; MAP AB In the malaria vector Anopheles gambiae, alternative arrangements of chromosome 2 (2La and 2L+(a)) vary in relative frequency along clines of aridity, suggesting the action of natural selection on targets within the inversion. Our long term goal of detecting such targets depends in part on the level of genetic exchange between arrangements. Accordingly, we estimated recombination rates on 2L from the backcross progeny of 2La/+(a) heterokaryotypes and as a control, from 2L+(a) homokaryotypes. In homokaryotypes, the recombination rate was uniform at similar to 2.0 centimorgans per megabase (cM/Mb). In heterokaryotypes, recombination within the rearranged region was reduced to < 0.5 cM/Mb, with slightly higher but nevertheless reduced levels (< 1.0 cM/Mb) flanking the rearrangement. Yet, gene exchange was recorded between nearly all markers, including those very near the distal inversion breakpoint. These results suggest that reduced recombination is a necessary but not sufficient mechanism for genetic isolation between alternative arrangements, and that the targets of natural selection can be identified against the different chromosomal backgrounds. C1 [Stump, A. D.; Goeddel, L.; Besansky, N. J.] Univ Notre Dame, Ctr Global Hlth & Infect Dis, Dept Biol Sci, Notre Dame, IN 46556 USA. [Stump, A. D.; Wilder, J. A.] Williams Coll, Dept Biol, Williamstown, MA 01267 USA. [Pombi, M.; Torre, A. D.] Univ Roma La Sapienza, Dipartimento Sci Sanita Pubbl, Rome, Italy. [Ribeiro, J. M. C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Besansky, NJ (reprint author), Univ Notre Dame, Ctr Global Hlth & Infect Dis, Dept Biol Sci, POB 369,317 Galvin Life Sci Bldg, Notre Dame, IN 46556 USA. EM nbesansk@nd.edu OI Pombi, Marco/0000-0002-4382-9922; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI63508] NR 30 TC 21 Z9 21 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0962-1075 J9 INSECT MOL BIOL JI Insect Mol. Biol. PD DEC PY 2007 VL 16 IS 6 BP 703 EP 709 PG 7 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 242QC UT WOS:000251739500005 PM 18092999 ER PT J AU Belyakov, IM Kozlowski, S Mage, M Ahlers, JD Boyd, LF Margulies, DH Berzofsky, JA AF Belyakov, Igor M. Kozlowski, Steven Mage, Michael Ahlers, Jeffrey D. Boyd, Lisa F. Margulies, David H. Berzofsky, Jay A. TI Role of alpha 3 domain of class I MHC molecules in the activation of high- and low-avidity CD8(+) CTLs SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytotoxic T lymphocytes; MHC class I; avidity; epitope; peptide; TCR ID CYTOTOXIC T-LYMPHOCYTES; MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT VACCINIA VIRUS; PROTECTIVE IMMUNITY; IMMUNOLOGICAL SYNAPSE; MUCOSAL IMMUNIZATION; POXVIRUS INFECTION; VIRAL-INFECTION; NEW-GENERATION AB CD8 can serve as a co-receptor or accessory molecule on the surface of CTL. As a co-receptor, CD8 can bind to the alpha 3 domain of the same MHC class I molecules as the TCR to facilitate TCR signaling. To evaluate the role of the MHC class I molecule alpha 3 domain in the activation of CD8(+) CTL, we have produced a soluble 227 mutant of H-2D(d), with a point mutation in the alpha 3 domain (Glu227 -> Lys). 227 mutant class I-peptide complexes were not able to effectively activate H-2D(d)-restricted CD8 T cells in vitro, as measured by IFN-gamma production by an epitope-specific CD8(+) CTL line. However, the 227 mutant class I-peptide complexes in the presence of another MHC class I molecule (H-2K(b)) (that cannot present the peptide) with a normal alpha 3 domain can induce the activation of CD8(+) CTL. Therefore, in order to activate CD8(+) CTL, the alpha 3 domain of MHC class I does not have to be located on the same molecule with the alpha 1 and alpha 2 domains of MHC class I. A low-avidity CD8(+) CTL line was significantly less sensitive to stimulation by the 227 mutant class I-peptide complexes in the presence of the H-2K(b) molecule. Thus, low-avidity CTL may not be able to take advantage of the interaction between CD8 and the alpha 3 domain of non-presenting class I MHC molecules, perhaps because of a shorter dwell time for the TCR-MHC interaction. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Belyakov, IM (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM igorbelyakov@yahoo.com RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU Intramural NIH HHS NR 70 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 2007 VL 19 IS 12 BP 1413 EP 1420 DI 10.1093/intimm/dxm111 PG 8 WC Immunology SC Immunology GA 232RL UT WOS:000251036900010 PM 17981793 ER PT J AU Jackson, CR Boylan, JA Frye, JG Gherardini, FC AF Jackson, Charlene R. Boylan, Julie A. Frye, Jonathan G. Gherardini, Frank C. TI Evidence of a conjugal erythromycin resistance element in the Lyme disease spirochete Borrelia burgdorferi SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE Borrelia burgdorferi; erythromycin; antimicrobial resistance; conjugation ID MULTIPLE ANTIBIOTIC-RESISTANCE; STREPTOCOCCUS-PNEUMONIAE; ANTIMICROBIAL AGENTS; ESCHERICHIA-COLI; EFFLUX SYSTEM; MACROLIDE; SUSCEPTIBILITY; FAECALIS; RECOMBINATION; CEFTRIAXONE AB We report the identification of isolates of Borrelia burgdorferi strain B31 that exhibit an unusual macrolide-lincosamide (ML) or macrolide-lincosamide-streptogramin A (MLSA) antibiotic resistance pattern. Low-passage isolates were resistant to high levels (>100 mu g/mL) of erythromycin, spiramycin and the lincosamides but were sensitive to dalfopristin, an analogue of streptogramin B. Interestingly, the high-passage erythromycin-resistant strain B31 was resistant to quinupristin, an analogue of streptogramin A (25 mu g/mL). Biochemical analysis revealed that resistance was not due to antibiotic inactivation or energy-dependent efflux but was instead due to modification of ribosomes in these isolates. Interestingly, we were able to demonstrate high-frequency transfer of the resistance phenotype via conjugation from B. burgdorferi to Bacillus subtilis (10(-2)-10(-4)) or Enterococcus fiaecalis (10(-5)). An intergeneric conjugal system in B. burgdorferi suggests that horizontal gene transfer may play a role in its evolution and is a potential too] for developing new genetic systems to study the pathogenesis of Lyme disease. Published by Elsevier B.V. on behalf of International Society of Chemotherapy. C1 [Boylan, Julie A.; Gherardini, Frank C.] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. [Jackson, Charlene R.; Frye, Jonathan G.] USDA, Antimicrobial Resistance Res Unit, ARS, SAA,Russell Res Ctr, Athens, GA 30602 USA. RP Gherardini, FC (reprint author), NIAID, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM fgherardini@niaid.nih.gov RI Frye, Jonathan/I-6382-2013 OI Frye, Jonathan/0000-0002-8500-3395 FU Intramural NIH HHS [Z01 AI000906-06, Z99 AI999999]; NIAID NIH HHS [AI33501] NR 48 TC 8 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD DEC PY 2007 VL 30 IS 6 BP 496 EP 504 DI 10.1016/j.ijantimicag.2007.07.013 PG 9 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 242SE UT WOS:000251745200003 PM 17905571 ER PT J AU Hussain, SP Harris, CC AF Hussain, S. Perwez Harris, Curtis C. TI Inflammation and cancer: An ancient link with novel potentials SO INTERNATIONAL JOURNAL OF CANCER LA English DT Review DE inflammation; microRNA; nitric oxide; cancer ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; MIGRATION INHIBITORY FACTOR; TUMOR-SUPPRESSOR GENE; P53 MUTATION LOAD; CROHNS-DISEASE; PROMOTER METHYLATION; ULCERATIVE-COLITIS; OXIDATIVE STRESS; DNA METHYLATION AB Infection and chronic inflammation contribute to about 1 in 4 of all cancer cases. Mediators of the inflammatory response, e-g., cytokines, free radicals, prostaglandins and growth factors, can induce genetic and epigenetic changes including point mutations in tumor suppressor genes, DNA methylation and post-translational modifications, causing alterations in critical pathways responsible for maintaining the normal cellular homeostasis and leading to the development and progression of cancer. Recent discovery of an interaction between microRNAs and innate immunity during inflammation has further strengthened the association between inflammation and cancer. (C) 2007 Wiley-Liss, Inc. C1 NIH, NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NIH, NCI, Human Carcinogenesis Lab, Bldg 37,Room 3068, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov NR 127 TC 444 Z9 476 U1 5 U2 53 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 2007 VL 121 IS 11 BP 2373 EP 2380 DI 10.1002/ijc.23173 PG 8 WC Oncology SC Oncology GA 226AN UT WOS:000250559600004 PM 17893866 ER PT J AU Garcia-Closas, M Kristensen, V Langerod, A Qi, Y Yeager, M Burdett, L Welch, R Lissowska, J Peplonska, B Brinton, L Gerhard, DS Gram, IT Perou, CM Borresen-Dale, AL Chanock, S AF Garcia-Closas, Montserrat Kristensen, Vessela Langerod, Anita Qi, Ying Yeager, Meredith Burdett, Laurie Welch, Robert Lissowska, Jolanta Peplonska, Beata Brinton, Louise Gerhard, Daniela S. Gram, Inger Torhild Perou, Charles M. Borresen-Dale, Anne-Lise Chanock, Stephen TI Common genetic variation in TP53 and its flanking genes, WDR79 and ATP1B2, and susceptibility to breast cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE TP53; polymorphisms; breast cancer ID HUMAN P53 GENE; INCREASED RISK; POLYMORPHISM; ASSOCIATION; HAPLOTYPES; VARIANTS; OVARIAN; PREDISPOSITION; MUTATIONS; PATTERNS AB Germline mutations in the tumor suppressor gene TP53 are associated with high incidence of early-onset malignancies, and somatic mutations occur in 20-40% of all breast cancer cases. We investigated the association of common genetic variation in TP53 and its flanking genes, WDR79 and ATPIB2, with risk for breast cancer. Single nucleotide polymorphisms (SNPs) identified in a resequence analysis were genotyped in 2 large case-control studies including 731 cases and 1,124 controls from Norway, and 1,995 cases and 2,296 controls from Poland. Analyses of the pooled data showed no SNPs in TP53 to be significantly associated with risk for breast cancer. However, we found a significant and consistent association with risk for a SNP in exon I (R68G) of the 5' neighboring gene WDR79 (rs2287499, OR (95% CI) = 1.08 (0.95-1.23) for CG vs. CC and 1.60 (1.04-2.47) for GG vs. CC, p-trend = 0.01). Stratification by ER and PR status, showed these increases in risk to be limited to ER negative tumors (OR (95% CI) per variant allele: 1.42 (1.18-1.71) p-trend = 0.00009). In addition, 2 TP53 SNPs (rs17887200 Y of STP and rs12951053 in intron 7) showing weak and non-significant overall increases in risk, were also associated with ER negative tumors (1.48 (1.11-1.93) p-trend = 0.01 and 1.29 (1.06-1.58) p-trend = 0.009, respectively). In conclusion, this comprehensive evaluation of common genetic variation in TP53 and its flanking genes found no significant overall associations between SNPs in TP53 and breast cancer risk. However, data suggested that common variation in TP53 or WDR79 could be associated with ER negative breast cancers. (C) 2007 Wiley-Liss, Inc. C1 NIH, NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Natl Hosp Norway, Radiumhosp, Ctr Med, Canc Res Inst,Dept Genet, Oslo, Norway. Univ Oslo, Fac Med, N-0316 Oslo, Norway. NCI, Ctr Adv Technol, Gaithersburg, MD USA. M Sklodowska Curie Inst, Warsaw, Poland. Ctr Canc, Warsaw, Poland. Nofer Inst Occupat Med, Lodz, Poland. NCI, Off Canc Genom, Bethesda, MD 20892 USA. Univ Tromso, Inst Community Med, Tromso, Norway. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol, Chapel Hill, NC 27599 USA. NCI, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Garcia-Closas, M (reprint author), NIH, NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. EM garciacm@exchange.nih.gov RI Peplonska, Beata/F-6004-2010; 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; Perou, Charles/0000-0001-9827-2247 FU NCI NIH HHS [P50-CA58223, R01-CA-101227-01] NR 35 TC 32 Z9 32 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 2007 VL 121 IS 11 BP 2532 EP 2538 DI 10.1002/ijc.22985 PG 7 WC Oncology SC Oncology GA 226AN UT WOS:000250559600024 PM 17683073 ER PT J AU Lenfant, C AF Lenfant, Claude TI Hypertension, one or several guidelines: Does it matter? SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract C1 [Lenfant, Claude] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD DEC 1 PY 2007 VL 122 SU 1 BP 18 EP 18 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 250OP UT WOS:000252310200072 ER PT J AU Yang, M Zhodzishsky, V Crawley, JN AF Yang, Mu Zhodzishsky, Vladimir Crawley, Jacqueline N. TI Social deficits in BTBR T+tf/J mice are unchanged by cross-fostering with C57BL/6J mothers SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE inbred strains of mice; behavioral development; maternal factor; postnatal environment; social interaction; juvenile play; autism ID AUTISM SPECTRUM DISORDERS; ADVERSE CHILDHOOD EXPERIENCES; PITUITARY-ADRENAL AXIS; MATERNAL-CARE; APPROACH BEHAVIORS; NEGATIVE FEEDBACK; MAJOR DEPRESSION; INBRED STRAINS; MESSENGER-RNA; LIFE EVENTS AB Inbred strains of mice are useful model systems for studying the interactions of genetic and environmental contributions during neurodevelopmental stages. We recently reported an inbred strain, BTBR T + tf/J (BTBR), which, as compared to the commonly used C57BL/6J (B6) strain, displays lower social interactions as juveniles, lower social approach in adult ages, and higher levels of repetitive self-grooming throughout developmental stages. The present study investigated whether the early postnatal maternal environment contributes substantially to the unusually low expression of social behaviors and high self-grooming in BTBR as compared to B6. Within 24 h of birth, entire litters of pups were crossfostered to either a dam of the same strain or a dam of the opposite strain. Control litters were left with their own mothers. Offspring were tested for juvenile play at postnatal day 21 1, for sociability at 8 weeks of age in an automated three-chambered social approach test, and for self-grooming at 9-11 weeks of age. Results indicate that deficits in play behaviors in juvenile BTBR pups were not rescued by a 136 maternal environment. Similarly, a BTBR maternal environment did not induce play deficits in 136 pups. Cross-fostering had no effect on sociability scores in adults. The high self-grooming in BTBR and low self-grooming in 136 were not affected by maternal environment. These findings favor a genetic interpretation of the unusual social behaviors and self-grooming traits of BTBR, and support the use of the BTBR inbred strain as a mouse model to study genetic mechanism of autism. Published by Elsevier Ltd on behalf of ISDN. C1 [Yang, Mu; Zhodzishsky, Vladimir; Crawley, Jacqueline N.] NIH, NIMH, Intramural Res Program, Lab Behav Neurosci, Bethesda, MD 20892 USA. RP Yang, M (reprint author), NIH, NIMH, Intramural Res Program, Lab Behav Neurosci, Bldg 35 Room 1C,Mail Code 3730, Bethesda, MD 20892 USA. EM yangmu@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 41 TC 82 Z9 82 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2007 VL 25 IS 8 BP 515 EP 521 DI 10.1016/j.ijdevneu.2007.09.008 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 248OY UT WOS:000252164900004 PM 17980995 ER PT J AU Galanti, K Gluck, ME Geliebter, A AF Galanti, Kochavi Gluck, Marci E. Geliebter, Allan TI Test meal intake in obese binge eaters in relation to impulsivity and compulsivity SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE impulsive; OCD; depression; binge eating disorder; obesity; food intake; loss of control ID RATING DEPRESSION SCALE; EATING DISORDER; GASTRIC CAPACITY; BULIMIA-NERVOSA; PATTERNS; CRITERIA; WOMEN AB Objective: Studies have linked increased impulsivity and compulsivity with bulimia nervosa (BN). Less is known about this relationship in binge eating disorder (BED). Method: Seventy-nine overweight participants (28 male, 65 females) were classified as BED (n = 22), BE (Subthreshold BED, not meeting full criteria for BED) (n = 21), and non-BED (n = 36). Following an 8-hr fast, participants completed psychological scales to assess impulsivity, compulsivity, and depression. They then consumed a liquid test meal until extremely full. Results: Test meal intake (TMI) was significantly greater for both BED and BE than non-BED participants. impulsivity and depression scores were significantly higher in BED and BE than in non-BED participants. Men had significantly higher compulsivity scores than women. Impulsivity correlated significantly with TMI, accounting for 16% of the variance. Conclusion: There was greater impulsivity in BED and BE, compared with non-BED. Moreover, impulsivity was the best predictor of TMI, and may play a larger role in BE than previously realized. (C) 2007 by Wiley Periodicals, Inc. C1 NIDDK, NIH, Phoenix, AZ USA. Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA. Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA. Columbia Univ, New York Obesity Res Ctr, St Lukes Roosevelt Hosp Ctr, New York, NY USA. Columbia Univ, Dept Med, St Lukes Roosevelt Hosp Ctr, New York, NY USA. Columbia Univ, Dept Psychiat, St Lukes Roosevelt Hosp Ctr, New York, NY USA. RP Gluck, ME (reprint author), NIDDK, NIH, Phoenix, AZ USA. EM gmarci@mail.nih.gov FU NIDDK NIH HHS [R01 DK074046-02S1, R01 DK074046, R01 DK074046-01A1, R01 DK074046-01A1S1, R01 DK074046-02, R01 DK074046-02S2, R01 DK074046-03, R01 DK074046-04, R01 DK074046-05] NR 26 TC 52 Z9 52 U1 4 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD DEC PY 2007 VL 40 IS 8 BP 727 EP 732 DI 10.1002/eat.20441 PG 6 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 229OW UT WOS:000250814900008 PM 17683093 ER PT J AU Drel, VR Pacher, P Vareniuk, I Pavlov, IA Ilnytska, O Lyzogubov, VV Bell, SR Groves, JT Obrosova, IG AF Drel, Viktor R. Pacher, Pal Vareniuk, Igor Pavlov, Ivan A. Ilnytska, Olga Lyzogubov, Valeriy V. Bell, Seth R. Groves, John T. Obrosova, Irina G. TI Evaluation of the peroxynitrite decomposition catalyst Fe(III) tetra-mesitylporphyrin octasulfonate on peripheral neuropathy in a mouse model of type 1 diabetes SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE nitrosative stress; nerve conduction; peripheral diabetic neuropathy; peroxynitrite decomposition catalysts; poly(ADP-ribose) polymerase ID POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; ALDOSE REDUCTASE INHIBITION; NERVE CONDUCTION-VELOCITY; ENDONEURIAL BLOOD-FLOW; NITROSATIVE STRESS; OXIDATIVE STRESS; ENDOTHELIAL DYSFUNCTION; VASCULAR REACTIVITY; MICE; RATS AB Whereas the important role of free radicals in diabetes-associated complications is well established, the contributions of the highly reactive oxidant peroxynitrite have not been properly explored. The present study used a pharmacological approach to evaluate the role of peroxynitrite in peripheral diabetic neuropathy. Control and STZ-diabetic mice were maintained with or without treatment with the potent peroxynitrite decomposition catalyst Fe(III) tetramesitylporphyrin octasulfonate (FeTMPS), at doses of 5 or 10 mg/kg/day in the drinking water for 3 weeks after an initial 3 weeks without treatment. Mice with a 6-week duration of diabetes developed clearly manifest motor (MNCV) and sensory nerve conduction velocity (SNCV) deficits, thermal hypoalgesia (paw withdrawal, tail-flick, and hot plate tests), mechanical hypoalgesia (tail pressure Randall-Sellito test), tactile allodynia (flexible von Frey filament test), and similar to 44% loss of intraepidermal nerve fibers. They also had increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in sciatic nerve, grey matter of the spinal cord, and dorsal root ganglion neurons. FeTMPS treatment alleviated or essentially corrected (at a dose of 10 mg/kg/day) MNCV and SNCV deficits, and was associated with less severe small sensory nerve fiber dysfunction and degeneration. Nitrotyrosine and poly(ADP-ribose) immunofluorescence in sciatic nerve, spinal cord, and dorsal root ganglion neurons in peroxynitrite decomposition catalyst-treated diabetic mice was markedly reduced. In conclusion, peroxynitrite contributes to large C1 Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. Princeton Univ, Dept Chem, Princeton, NJ 08544 USA. RP Obrosova, IG (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM obrosoig@pbrc.edu RI Pacher, Pal/B-6378-2008; Drel, Viktor/G-8883-2016 OI Pacher, Pal/0000-0001-7036-8108; Drel, Viktor/0000-0003-4542-0132 FU Intramural NIH HHS [Z01 AA000375-02]; NIDDK NIH HHS [DK 071566-01, R21 DK071566, R21 DK071566-01]; NIGMS NIH HHS [GM 36298, R01 GM036298, R37 GM036298] NR 42 TC 32 Z9 32 U1 3 U2 8 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD DEC PY 2007 VL 20 IS 6 BP 783 EP 792 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 237MB UT WOS:000251376900002 PM 17982684 ER PT J AU Dennison, SK Jacobs, SA Wilson, JW Seeger, J Cescon, TP Raymond, JM Geyer, CE Wolmark, N Swain, SM AF Dennison, Sheri K. Jacobs, Samuel A. Wilson, John W. Seeger, Janell Cescon, Terrence P. Raymond, Jane M. Geyer, Charles E. Wolmark, Norman Swain, Sandra M. TI A phase II clinical trial of ZD1839 (Iressa (TM)) in combination with docetaxel as first-line treatment in patients with advanced breast cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE chemotherapy; clinical trials; adult medical oncology; advanced breast cancer ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; PROGNOSTIC VALUE; MULTICENTER TRIAL; ONCOLOGY-GROUP; SOLID TUMORS; FOLLOW-UP; GEFITINIB; PACLITAXEL AB This was a phase II multi-institutional trial to determine the efficacy and tolerability of gefitinib (Iressa (TM)) and docetaxel as first-line treatment in patients with metastatic breast cancer. All patients had histologically confirmed breast cancer with metastatic disease. They were permitted to have received adjuvant chemotherapy, but no prior docetaxel or prior chemotherapy for metastatic disease. Patients received gefitinib 250 mg once daily and docetaxel 75 mg/m(2) stop every 3 weeks, until tumor progression, toxicity or other reasons for discontinuation. Thirty-three patients were enrolled and received a median of 5 cycles of treatment. The clinical benefit rate was 51.5% (95% CI: 33.5-69.2%). There were 1 confirmed complete response and 12 confirmed partial responses, and the overall objective response rate was 39.4% (95% CI: 22.9-57.9%). Four patients had stable disease for +/- 24 weeks. The median duration of clinical benefit was 10.9 months (95% CI: 6.0-17.6 months). The most common reason for study discontinuation was disease progression (16 patients), followed by toxicity (ten patients). Toxicities were mainly attributable to docetaxel, including >= 3 neutropenia in 43% of patients. The combination of gefitinib and docetaxel is an active regimen in patients with previously untreated metastatic breast cancer, with a clinical benefit rate and toxicity profile in the range of that reported for docetaxel alone. C1 Walter Reed Army Med Ctr, Washington, DC 20307 USA. NSABP, Pittsburgh, PA USA. FRP, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Med, Canc Ctr, Pittsburgh, PA USA. RP Dennison, SK (reprint author), Walter Reed Army Med Ctr, 6900 Georgia Ave NW, Washington, DC 20307 USA. EM dennisonsk@mail.nih.gov OI Swain, Sandra/0000-0002-1320-3830 FU Intramural NIH HHS NR 40 TC 14 Z9 15 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD DEC PY 2007 VL 25 IS 6 BP 545 EP 551 DI 10.1007/s10637-007-9055-6 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 215KS UT WOS:000249807800005 PM 17563856 ER PT J AU Mackenzie, MJ Saltman, D Hirte, H Low, J Johnson, C Pond, G Moore, MJ AF Mackenzie, M. J. Saltman, D. Hirte, H. Low, J. Johnson, C. Pond, G. Moore, M. J. TI A Phase II study of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) and gemcitabine in advanced pancreatic carcinoma. A trial of the Princess Margaret Hospital Phase II consortium SO INVESTIGATIONAL NEW DRUGS LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE triapine; germcitabine; pancreatic; Phase II ID RIBONUCLEOTIDE REDUCTASE INHIBITOR; SOLID TUMORS; CANCER; COMBINATION AB 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine (R), Vion Pharmaceuticals, New Haven, CT) is an inhibitor of the M2 subunit of ribonucleotide reductase (RR). Preclinical testing demonstrates synergy between 3-AP and gemcitabine. Phase I studies of the combination have suggested tolerability and some initial evidence of efficacy. Therefore, a phase II study of gemcitabine plus 3-AP in advanced pancreatic carcinoma was undertaken. In this two-step phase II trial, patients with advanced pancreatic adenocarcinoma who had not received prior chemotherapy for advanced disease were treated with 3-AP 105 mg/m(2) stop given over 2 h. Four hours after the 3-AP infusion was completed, gemcitabine 1,000 mg/m(2) stop was given over 30 min. Both drugs were given on days 1, 8 and 15 of a 28-day cycle. Twenty-six patients were enrolled to the study. One patient withdrew consent prior to receiving any treatment and is excluded from all further analyses. Four patients discontinued treatment due to adverse effects. Grade 3/4 hematological adverse events included neutropenia, thrombocytopenia, lymphopenia, leukopenia and anemia and the most frequent non-hematological adverse events were fatigue and pain. No objective responses were observed. Eleven patients had stable disease (SD). In five of these eleven patients, SD lasted for more than 6 months. The median time to progression was 4.1 months and the 6 month progression-free survival rate was 29%. The median survival was 9.0 months with a 1-year survival of 28.0%. The combination of 3-AP and gemcitabine is associated with moderate toxicity in patients with advanced pancreatic cancer. This two-stage trial was stopped after stage I due to lack of antitumour activity. On the basis of this clinical trial, the combination of gemcitabine and 3-AP at this dose and schedule does not warrant further study in this patient population. C1 London Reg Canc Program, London, ON N6A 4L6, Canada. British Columbia Canc Agcy, Kelowna, BC, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. NCI CTEP, Bethesda, MD USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. RP Mackenzie, MJ (reprint author), London Reg Canc Program, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. EM mary.mackenzie@lhsc.on.ca NR 18 TC 45 Z9 46 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD DEC PY 2007 VL 25 IS 6 BP 553 EP 558 DI 10.1007/s10637-007-9066-3 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 215KS UT WOS:000249807800006 PM 17585372 ER PT J AU Li, R Maminishkis, A Wang, FE Miller, SS AF Li, Rong Maminishkis, Arvydas Wang, Fei E. Miller, Sheldon S. TI PDGF-c and -D induced proliferation/migration of human RPE is abolished by inflammatory cytokines SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PIGMENT EPITHELIAL-CELLS; NITRIC-OXIDE SYNTHASE; GROWTH-FACTOR-BETA; NF-KAPPA-B; PROLIFERATIVE VITREORETINOPATHY; TNF-ALPHA; (R)-ALPHA-LIPOIC ACID; MACULAR DEGENERATION; OXIDATIVE DAMAGE; INTERFERON-GAMMA AB PURPOSE. The role of growth factors and inflammation in regulating retinal pigment epithelial (RPE) function is complex and still poorly understood. The present study investigated human RPE cell proliferation and migration mediated by platelet-derived growth factor (PDGF) and inflammatory cytokines. METHODS. Human fetal RPE (hfRPE) cells were obtained as previously described. Gene expressions of PDGF isoforms and their receptors were detected using real-time PCR. Protein expression, activity, and localization of PDGFR-alpha and-beta were analyzed by Western blot and immunohistochemistry. BrdU incorporation and wound healing assays were used to test the effects of different PDGF isoforms and inflammatory cytokines on hfRPE proliferation and migration. Annexin-V and phalloidin staining were used to detect apoptosis and the actin cytoskeleton, respectively. RESULTS. PDGF-C and PDGF-D proteins are expressed in native human adult RPE, and mRNA levels are up to 100-fold higher than PDGF-A and-B. PDGFR-alpha and-beta proteins are expressed in native adult RPE and hfRPE (mainly localized to the apical membrane). In hfRPE, these receptors can be activated by PDGF-CC and -DD. PDGF-CC, -DD, and -BB significantly increased hfRPE proliferation, whereas PDGF-DD, -BB, and -AB significantly increased cell migration. An inflammatory cytokine mixture (TNF-alpha/IL-1 beta/IFN-gamma) completely inhibited the stimulatory effect of PDGF-BB, -CC, and -DD; in contrast, this mixture stimulated the proliferation of choroidal cells. This inflammatory cytokine mixture also induced apoptosis, significant disruption of actin filaments and zonula occludens (ZO-1), and a decrease in transepithelial resistance. CONCLUSIONS. These results suggest that proinflammatory cytokines in vivo can inhibit the proliferative effect of PDGF on human RPE and, at the same time, stimulate the proliferation of choroidal cells. They also suggest an important role of proinflammatory cytokines in overcoming local proliferative/wound-healing responses, thereby controlling the development of disease processes at the retina/RPE/choroid interface. C1 NIH, NEI, Bethesda, MD 20892 USA. RP Miller, SS (reprint author), NIH, NEI, 31 Ctr Dr,MSC 2510,Room 6A22, Bethesda, MD 20892 USA. EM millers@nei.nih.gov FU Intramural NIH HHS NR 69 TC 34 Z9 40 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2007 VL 48 IS 12 BP 5722 EP 5732 DI 10.1167/iovs.07-0327 PG 11 WC Ophthalmology SC Ophthalmology GA 238MB UT WOS:000251450800048 PM 18055825 ER PT J AU McGowan, I Elliott, J Cortina, G Tanner, K Siboliban, C Adler, A Cho, D Boscardin, WJ Soto-Torres, L Anton, PA AF McGowan, Ian Elliott, Julie Cortina, Galen Tanner, Karen Siboliban, Chomchay Adler, Amy Cho, Daniel Boscardin, W. John Soto-Torres, Lydia Anton, Peter A. TI Characterization of baseline intestinal mucosal indices of injury and inflammation in men for use in rectal microbicide trials (HIV prevention trials network-056) SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE cytokines; gastrointestinal lymphoid tissue; HIV-1; microbicides; mucosa; viral load ID ACTIVE ANTIRETROVIRAL THERAPY; VIRUS TYPE-1 INFECTION; T-CELL DEPLETION; GASTROINTESTINAL-TRACT; TOPICAL MICROBICIDES; ULCERATIVE-COLITIS; CROHNS-DISEASE; TRANSMISSION; ACTIVATION; SAFETY AB Objectives: The purpose of this study was to evaluate the biologic stability of mucosal parameters that might be used as endpoints in phase I rectal safety studies. Methods: Sixteen male participants were enrolled into 4 groups defined by HIV status, viral load, and sexual activity. Each participant underwent 3 flexible sigmoidoscopics at 2-week intervals with collection of blood, intestinal biopsies, and rectal secretions. Intestinal histology, phenotypic characterization of mucosal mononuclear cells, cytokine messenger RNA (mRNA) profiles (RANTES, interferon-gamma [IFN gamma], and interleukin-10), and immunoglobulin secretion were assessed. Intraclass correlation (ICC) was calculated to assess endpoint stability. Results: Qualitative histology demonstrated minimal inflammation in >95% of biopsies and remained stable throughout the study period.]CC for the tissue cytokine mRNA measurements and several T-cell phenotypic markers was >0.7, indicating stability over time. Mucosal CD4 lymphopenia was seen in the HIV-positive participants and was more pronounced in those with higher viral loads. Modest differences were observed for cytokine expression (IFN-gamma) and T-cell phenotype (CD3, CD4, CD8, CD19, CD4/CCR5, and CD4/CD38) between the tissue samples collected at 10 and 30 cm. Conclusions: These data help to provide a rationale for the selection of endpoints for future phase I rectal safety studies. C1 Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA 15213 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Prevent Res, Div Digest Dis, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Biostat, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Natl Inst Allergy & Infect Dis, Bethesda, MD USA. RP McGowan, I (reprint author), Univ Pittsburgh, Magee Womens Res Inst, 204 Croft Ave,Rm B505, Pittsburgh, PA 15213 USA. EM mcgowanim@mail.magee.edu FU NIAID NIH HHS [AI46749/645-12] NR 38 TC 35 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD DEC 1 PY 2007 VL 46 IS 4 BP 417 EP 425 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 231ZH UT WOS:000250987200007 PM 17891044 ER PT J AU Shi, J Zhao, LY Epstein, DH Zhao, CZ Shuai, YL Yan, B Jin, J Lu, L AF Shi, Jie Zhao, Li-Yan Epstein, David H. Zhao, Chengzheng Shuai, Yinliang Yan, Bin Jin, Jun Lu, Lin TI The effect of methadone maintenance on illicit opioid use, human immunodeficiency virus and hepatitis C virus infection, health status, employment, and criminal activity among heroin abusers during 6 months of treatment in China SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE methadone maintenance therapy; HIV infection; HCV infection; health status; severity of dependence; depression; employment activity; criminal activity; heroin abuse; China ID ADDICTION SEVERITY INDEX; LONG-TERM; MEDICAL-TREATMENT; OPIATE ADDICTION; DEPENDENCE; TRIAL; DETOXIFICATION; INSTRUMENT; SCALE AB Purpose:This study was designed to evaluate the effects of methadone maintenance treatment (MMT) on severity of dependence, depression, human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, health status, employment, and criminal activity among heroin abusers after 3 and 6 months of treatment, compared with baseline, in China. Methods: A total of 102 methadone maintenance treatment (MMT) patients (87 men and 15 women; mean age, 36.1 years; standard deviation = 6.9) without major medical or psychiatric comorbidity participated in the experimental procedure. They were given oral methadone (maximum daily dose 80 mg, minimum daily dose 30 mg). Opioid use was assessed by twice-weekly urinalysis; HIV and HCV statu's were assessed by standard blood tests. Questionnaires were administered to assess blood-borne-virus risk behavior, severity of dependence, depression, health status, employment, and criminal activity. Changes over time were evaluated by 1-way analysis of variance (ANOVA) followed by post hoc t tests. Results: Opioid use was reduced from 26.7 days per month at baseline to 0.7 and 0.0 days at 3 and 6 months, respectively. No participant seroconverted to HIV and HCV positivity during the 6 months of MMT. Health status significantly improved, as did severity of dependence, depression, and criminal activity, after 3 and 6 months MMT. Conclusions: The results support the broad beneficial effects of MMT in China. C1 [Zhao, Li-Yan; Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Dept Neuropharmacol, Beijing, Peoples R China. [Shi, Jie; Zhao, Chengzheng] Peking Univ, Natl Inst Drug Dependence, Dept Clin Pharmacol, Beijing, Peoples R China. [Epstein, David H.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. [Shuai, Yinliang; Yan, Bin; Jin, Jun] Beijing Ankang Hosp, Beijing, Peoples R China. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, Dept Neuropharmacol, 38 Xueyuan Rd, Beijing, Peoples R China. EM llu@bjmu.edu.cn NR 39 TC 20 Z9 23 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD DEC PY 2007 VL 1 IS 4 BP 186 EP 190 DI 10.1097/ADM.0b013e318156cc19 PG 5 WC Substance Abuse SC Substance Abuse GA 305GM UT WOS:000256166000003 PM 21768956 ER PT J AU Rubinow, DR Smith, MJ Schenkel, LA Schmidt, PJ Dancer, K AF Rubinow, David R. Smith, Mark J. Schenkel, Linda A. Schmidt, Peter J. Dancer, Kristen TI Facial emotion discrimination across the menstrual cycle in women with Premenstrual Dysphoric Disorder (PMDD) and controls SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE facial emotion; menstrual cycle; premenstrual dysphoric disorder ID MAJOR DEPRESSION; BEHAVIORAL FINDINGS; MOOD DISORDERS; RECOGNITION; EXPRESSIONS; PERCEPTION; SAD; PERSONALITY; PERSISTENCE; CRITERIA AB Background: Depressed patients show mood-congruent errors in the identification of emotion in facial expressions. Errors consist of impaired performance (recognition errors) and negative bias (seeing faces as sadder than they are). This abnormal processing may both reflect and contribute to the negative affective state. In this study, we administered an emotional recognition in facial expression task to women with premenstrual dysphoric disorder (PMDD) to determine whether processing errors similar to those in depression were present and whether they were confined to the luteal phase (i.e., state dependent). Methods: The Facial Discrimination Task (FDT) was administered in the follicular and luteal phases to women with PMDD (n = 28) and asymptomatic controls (n 27). Results: ANOVA with repeated measures identified significantly increased negative judgments (both performance errors and bias) in women with PMDD during the luteal phase (more neutral to sad misjudgments and higher negative bias index) as well as impaired "specificity" of judgments [an inability to discriminate neutral from emotional stimuli] (diagnosis by phase interactions, p<0.05), findings similar to those observed in depression. No menstrual cycle effects were seen in controls, and no differences between patients and controls were seen on a control task (age assessment of pictured subjects). Limitations: The levels of significance obtained were modest and would not withstand correction for multiple comparisons. Conclusion: Women with PMDD display a luteal phase-dependent impairment (negative bias) in the processing of non-verbal affective information. This negative bias may contribute to the generation of negative mood states during the luteal phase and could suggest the presence of dysfunction in those brain regions whose coordinated activity mediates the recognition of emotion in facial expression. (c) 2007 Elsevier B.V All rights reserved. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, NIH, Brain Stimulat Unit, Bethesda, MD USA. RP Rubinow, DR (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10-CRC,Room 6-5340,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. EM david_rabinow@med.unc.edu FU Intramural NIH HHS [Z01 MH002865-02]; NIMH NIH HHS [1 Z01 MH002765-09] NR 31 TC 17 Z9 19 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2007 VL 104 IS 1-3 BP 37 EP 44 DI 10.1016/j.jad.2007.01.031 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 239AJ UT WOS:000251489600004 PM 17367867 ER PT J AU Gernez, Y Tirouvanziam, R Nguyen, KD Herzenberg, LA Krensky, AM Nadeau, KC AF Gernez, Yael Tirouvanziam, Rabindra Nguyen, Khoa D. Herzenberg, Leonard A. Krensky, Alan M. Nadeau, Kari C. TI Altered phosphorylated signal transducer and activator of transcription profile of CD4(+)CD161(+) T cells in asthma: Modulation by allergic status and oral corticosteroids SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergy; atopy; fluorescence-activated cell sorting; immune polarization ID FLOW-CYTOMETRY; AIRWAY INFLAMMATION; PERIPHERAL-BLOOD; ATOPIC ASTHMA; HUMAN NKR-P1A; MECHANISMS; EXPRESSION; PATHWAYS; DISEASE; CD161 AB Background: Asthma is a complex immunologic disorder linked to altered cytokine signaling. Objective: We tested whether asthmatic patients showed any change in cytokine-dependent signal transducer and activator of transcription (STAT) levels, focusing on the central/effector-memory CD4(+)CD161(+) subset, which represents 15% to 25% of circulating T cells. Methods: We quantified intracellular levels of active phosphorylated STAT (phospho-STAT) 1, 3, 5, and 6 by means of flow cytometry, without any activation or expansion. Results: Baseline phospho-STAT1 and phospho-STAT6 levels were increased in CD4(+)CD161(+) T cells from asthmatic patients compared with those from healthy control subjects (by 10- and 8-fold, respectively). This asthma-associated alteration was both subset specific because no change was seen in CD4(+)CD161(-)CD25(+) (regulatory T cells) and CD4(+)CD161(-)CD25(-) subsets and isoform specific because phospho-STAT5 and phospho-STAT3 levels were unchanged. Among asthmatic patients, phospho-STAT1 and phospho-STAT6 levels correlated negatively with each other, suggesting antagonistic regulation. Oral corticosteroid (OCS) treatment significantly decreased phospho-STAT6 and IL-4 levels but not phospho-STAT1 levels. Disease parameters showing significant correlations with phospho-STAT1, phospho-STAT6, or both included age at onset, plasma IgE levels, and levels of the T(H)2 cytokines IL-4 and IL-10 and the T(H)1 cytokine IL-2. Overall, combined phospho-STAT1 and phospho-STAT6 measurements showed excellent predictive value for identifying (1) asthmatic patients versus healthy control subjects, (2) allergic versus nonallergic asthmatic patients, and (3) asthmatic patients taking versus those not taking OCSs. Conclusion: Baseline changes in phospho-STAT1 and phospho-STAT6 levels in blood CD4(+)CD161(+) T cells identify asthmatic patients and mirror their allergic status and response to OCSs. Clinical implications: These results confirm the pathologic importance of activated STAT1 and STAT6 in asthma and suggest their potential use as clinical biomarkers. C1 [Tirouvanziam, Rabindra] Beckman Ctr B013, Stanford, CA 94305 USA. [Gernez, Yael; Herzenberg, Leonard A.] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. [Tirouvanziam, Rabindra; Nguyen, Khoa D.; Nadeau, Kari C.] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [Krensky, Alan M.] NIH, Bethesda, MD USA. RP Tirouvanziam, R (reprint author), Beckman Ctr B013, Stanford, CA 94305 USA. EM tirouvan@stanford.edu RI Tirouvanziam, Rabindra/E-8981-2010 FU NIDDK NIH HHS [R37 DK035008-23] NR 42 TC 18 Z9 20 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2007 VL 120 IS 6 BP 1441 EP 1448 DI 10.1016/j.jaci.2007.08.012 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 241JX UT WOS:000251653800029 PM 17919711 ER PT J AU Shearer, WT Pahwa, S Read, JS Chen, J Wijayawardana, SR Palumbo, P Abrams, EJ Nesheim, SR Yin, W Thompson, B Easley, KA AF Shearer, William T. Pahwa, Savita Read, Jennifer S. Chen, Jian Wijayawardana, Sameera R. Palumbo, Paul Abrams, Elaine J. Nesheim, Stephen R. Yin, Wanrong Thompson, Bruce Easley, Kirk A. TI CD4/CD8 T-cell ratio predicts HIV infection in infants: The National Heart, Lung, and Blood Institute (PC2)-C-2 Study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE CD4/CD8 T-cell ratio; mother-to-child transmission of HIV; HIV infection ID CHILDREN; TRANSMISSION; MORTALITY; THERAPY; AIDS; AGE AB Background: In resource-poor regions of the world, HIV virologic testing is not available. Objective: We sought to evaluate the diagnostic usefulness of the CD4/CD8 T-cell ratio in predicting HIV infection in infants. Methods: Data from the 3- and 9-month visits for non-breastfed infants born to HIV-infected mothers enrolled (1990-1994) in the Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study (mother-to-child transmission of HIV, 17%) were analyzed. Data from the 3-month visit for infants enrolled (1985-1996) in the Perinatal AIDS Collaborative Transmission Study (mother-to-child transmission of HIV, 18%) were used for validation. Results: At 3 months of age, data were available on 79 HIV-infected and 409 uninfected non-breast-fed infants in the Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study. The area under the curve (AUC) of the receiver operating characteristic curve at 3 months was higher for the CD4/CD8 ratio compared with the CD4(+) T-cell count (AUC, 0.83 and 0.75; P = .03). The mean CD4/CD8 ratio at the 3-month visit was 1.7 for HIV-infected infants and 3.0 for uninfected infants. A CD4/CD8 ratio of 2.4 at 3 months of age was almost 2.5 times more likely to occur in an HIV-infected infant compared with an uninfected infant (test sensitivity, 81%; posttest probability of HIV, 33%). Model performance in the Centers for Disease Control and Prevention Perinatal AIDS Collaborative Transmission Study validation test (224 HIV-infected and 1015 uninfected 3-month-old infants) was equally good (AUC, 0.78 for CD4/CD8 ratio). Conclusion: The CD4/CD8 T-cell ratio is a more sensitive predictor of HIV infection in infants than the CD4(+) T-cell count. Clinical implications: The CD4/CD8 T-cell ratio can be used with caution to predict HIV infection in children. C1 [Shearer, William T.] Baylor Coll Med, Dept Pediat, Sect Allergy & Immunol, Houston, TX USA. [Pahwa, Savita] Univ Miami, Miller Sch Med, Dept Microbiol, Coral Gables, FL 33124 USA. [Pahwa, Savita] Univ Miami, Miller Sch Med, Dept Immunol, Coral Gables, FL 33124 USA. [Pahwa, Savita] Univ Miami, Miller Sch Med, Dept Pediat, Coral Gables, FL 33124 USA. [Read, Jennifer S.] NICHHD, Bethesda, MD 20892 USA. [Chen, Jian; Wijayawardana, Sameera R.; Easley, Kirk A.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. [Palumbo, Paul] Dartmouth Med Sch, Hanover, NH USA. [Abrams, Elaine J.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Nesheim, Stephen R.] Emory Univ, Sch Med, Atlanta, GA USA. [Yin, Wanrong; Thompson, Bruce] Clin Trial & Survey Corp, Baltimore, MD USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, 6621 Fannin St MC FC330-01, Houston, TX 77030 USA. EM wtsheare@TexasChildrensHospital.org RI Easley, Kirk/K-6910-2015 OI Easley, Kirk/0000-0003-4419-2617 FU NCRR NIH HHS [M01 RR000188, K01 RR000188, RR0188]; NHLBI NIH HHS [HL079533, R01 HL079533, N01 HR096037, N01 HR096043, R01 HL072705, HL72705, HL96040]; NIAID NIH HHS [AI27551, P30 AI036211, AI41089, U01 AI027551, AI36211, U01 AI041089]; NICHD NIH HHS [HD41983, U01 HD041983]; PHS HHS [P30 A1050409] NR 24 TC 8 Z9 9 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2007 VL 120 IS 6 BP 1449 EP 1456 DI 10.1016/j.jaci.2007.08.037 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 241JX UT WOS:000251653800030 PM 17920669 ER PT J AU Liu, CL Lerch, V Weber, K Schneider, MF Sharp, GB Gorapaju, L Levine, A Sharma, A Gandhi, M Merenstein, D AF Liu, Chenglong Lerch, Virginia Weber, Kathleen Schneider, Michael F. Sharp, Gerald B. Gorapaju, Lakshmi Levine, Alexandra Sharma, Anjali Gandhi, Monica Merenstein, Daniel TI Association between complementary and alternative medicine use and adherence to highly active antiretroviral therapy in the Women's Interagency HIV Study SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; OUTCOMES; LESS; AIDS C1 [Liu, Chenglong; Gorapaju, Lakshmi] Georgetown Univ, Dept Med, Washington, DC 20007 USA. [Lerch, Virginia] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Biostat & Epidemiol, Washington, DC USA. [Weber, Kathleen] John H Stronger Hosp Cook Cty, Hektoen Inst Med, Chicago, IL USA. [Weber, Kathleen] John H Stronger Hosp Cook Cty, CORE Ctr, Chicago, IL USA. [Schneider, Michael F.] Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Sharp, Gerald B.] NIH, Natl Inst Allergy & Infect Dis, Basic Sci Program, Epidemiol Branch, Bethesda, MD 20892 USA. [Sharma, Anjali] Suny Downstate Med Ctr, Div Infect Dis, Brooklyn, NY 11203 USA. [Levine, Alexandra] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Gandhi, Monica] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA. [Merenstein, Daniel] Georgetown Univ, Med Ctr, Dept Family Med, Washington, DC USA. RP Liu, CL (reprint author), Georgetown Univ, Dept Med, 2233 Wisconsin Ave NW,Suite 214, Washington, DC 20007 USA. EM cl278@georgetown.edu FU NCRR NIH HHS [M01-RR-00071, M01-RR00083, M01-RR00079]; NIAID NIH HHS [U01-AI-42590, U01-AI-31834, U01-AI-35004, U01-AI-34994, U01-AI-34989, U01-AI-34993]; NICHD NIH HHS [U01-HD-32632] NR 16 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD DEC PY 2007 VL 13 IS 10 BP 1053 EP 1056 DI 10.1089/acm.2007.0590 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 249RK UT WOS:000252247200003 PM 18166114 ER PT J AU Zhou, ZH Tzioufas, AG Notkins, AL AF Zhou, Zhao-Hua Tzioufas, Athanasios G. Notkins, Abner Louis TI Properties and function of polyreactive antibodies and polyreactive antigen-binding B cells SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT International Workshop on Pathophysiology of Autoimmune Disease CY MAY 25-27, 2007 CL Athens, GREECE DE polyreactive antibody; natural antibody; B cell; autoantibody; bacteria ID MONOCLONAL AUTOANTIBODIES; NATURAL ANTIBODIES; HORROR AUTOTOXICUS; REPERTOIRE; HUMANS; REACT; AUTOIMMUNITY; RECOGNITION; CIRCULATION; MOLECULES AB The advent of hybridoma technology has made it possible to study in-depth individual antibody molecules. These studies have revealed a number of surprises that have and are continuing to change our view, of the immune system. None of these was more surprising than the demonstration that many antibody molecules are polyreactive - that is they can bind to a variety of different and structurally unrelated self- and non-self-foreign antigens. These findings make it clear that self-reactivity is a common and not necessarily forbidden or pathogenic feature of the immune system and that the well-known broad antibacterial activity of natural antibodies is largely due to polyreactive antibodies. In this brief review we will discuss these insights and their impact on basic and clinical immunology. Published by Elsevier Ltd. C1 NIH, Natl Inst Dent & Cranofacial Res, Expt Med Sect, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. RP Notkins, AL (reprint author), NIH, Natl Inst Dent & Cranofacial Res, Expt Med Sect, Oral Infect & Immun Branch, Bldg 30,Rm 106,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 OD999999] NR 42 TC 103 Z9 111 U1 0 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD DEC PY 2007 VL 29 IS 4 BP 219 EP 228 DI 10.1016/j.jaut.2007.07.015 PG 10 WC Immunology SC Immunology GA 236XY UT WOS:000251338000004 PM 17888628 ER PT J AU Milner, J Ward, J Keane-Myers, A Min, B Paul, WE AF Milner, Joshua Ward, Jerrold Keane-Myers, Andrea Min, Booki Paul, William E. TI Repertoire-dependent immunopathology SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT International Workshop on Pathophysiology of Autoimmune Disease CY MAY 25-27, 2007 CL Athens, GREECE DE IL-4; IL-13; IgE; alternatively activated macrophages; eosinophils ID CD4(+) T-CELLS; AUTOIMMUNE GASTRITIS; PROLIFERATION; IL-2; MICE AB In humans, limited T-cell receptor repertoire and lymphopenia are associated with severe eosinophilic inflammatory disease. A model of lymphopenia and reduced T-cell repertoire was created; C57BL/6 Rag2-/- mice received limited (30,000) or large (2 million) numbers of CD4 T-cells. Three to five months post-transfer, mice that had received 30,000 T-cells, but not those that received 2 million, developed fulminant macrophage pneumonia with eosinophilia, Ym 1 deposition. methacholine-induced airway hyperresponsiveness, eosinophilic gastritis and esophagitis. These mice had strikingly elevated serum IgE (in CD3 epsilon-/- hosts) and donor-cells were enriched for IL-4, IL-5 and IL-13 producers. Th2 pathology and serum IgE were enhanced when transferred populations were depleted of CD25+ CD4 Tregs, but was more severe when the effector population was derived from limited as compared to the large effector population. Pretreatment of Rag2-/- mice with 300,000 CD25+ CD4 Tregs prior to effector cell transfer prevented disease while pretreatment with 30,000 did not, despite the fact that there were equal numbers of Tregs in the hosts at the time of transfer of effector cells. Limited repertoire complexity of Tregs may lead to a failure to control immunopathologic responses and limited repertoire complexity of conventional cells may be responsible for the Th2 phenotype. Published by Elsevier Ltd. C1 NIH, Natl Inst Allergy & Infect Dis, Immunol Lab, Bethesda, MD 20892 USA. NIH, Natl Inst Allergy & Infect Dis, Infect Dis Pathogenesis Sect, Comparat Med Branch, Bethesda, MD 20892 USA. NIH, Natl Inst Allergy & Infect Dis, Lab Allerg Dis, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA. RP Paul, WE (reprint author), NIH, Natl Inst Allergy & Infect Dis, Immunol Lab, Bldg 10,Rm 11N311,10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 AI000968-02] NR 27 TC 41 Z9 41 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD DEC PY 2007 VL 29 IS 4 BP 257 EP 261 DI 10.1016/j.jaut.2007.07.019 PG 5 WC Immunology SC Immunology GA 236XY UT WOS:000251338000009 PM 17889507 ER PT J AU Nielsen, HJ Youngren, B Hansen, FG Austin, S AF Nielsen, Henrik J. Youngren, Brenda Hansen, Flemming G. Austin, Stuart TI Dynamics of Escherichia coli chromosome segregation during multifork replication SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LOCALIZATION; COHESION; TERMINUS; ORIGIN; MODEL AB Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive cohesion of sister DNA regions was seen at any growth rate. We conclude that segregation is driven by the progression of the replication forks. C1 NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA. Tech Univ Denmark, Bioctr DTU, Microbial Genom Grp, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. RP Austin, S (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA. EM austin@ncifcrf.gov FU Intramural NIH HHS NR 20 TC 46 Z9 46 U1 0 U2 2 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 DEC PY 2007 VL 189 IS 23 BP 8660 EP 8666 DI 10.1128/JB.01212-07 PG 7 WC Microbiology SC Microbiology GA 238YI UT WOS:000251484100028 PM 17905986 ER PT J AU Greenberg, DE Porcella, SF Zelazny, AM Virtaneva, K Sturdevant, DE Kupko, JJ Barbian, KD Babar, A Dorward, DW Holland, SM AF Greenberg, David E. Porcella, Stephen F. Zelazny, Adrian M. Virtaneva, Kimmo Sturdevant, Dan E. Kupko, John J., III Barbian, Kent D. Babar, Amenah Dorward, David W. Holland, Steven M. TI Genome sequence analysis of the emerging human pathogenic acetic acid bacterium Granulibacter bethesdensis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; A STREPTOCOCCUS TRANSCRIPTOME; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; SIGNAL PEPTIDES; HOST-DEFENSE; SP-NOV.; INFECTION; PREDICTION; VIRULENCE AB Chronic granulomatous disease (CGD) is an inherited immune deficiency characterized by increased susceptibility to infection with Staphylococcus, certain gram-negative bacteria, and fungi. Granulibacter bethesdensis, a newly described genus and species within the family Acetobacteraceae, was recently isolated from four CGD patients residing in geographically distinct locales who presented with fever and lymphadenitis. We sequenced the genome of the reference strain of Granulibacter bethesdensis, which was isolated from lymph nodes of the original patient. The genome contains 2,708,355 base pairs in a single circular chromosome, in which 2,437 putative open reading frames (ORFs) were identified, 1,470 of which share sequence similarity with ORFs in the nonpathogenic but related Gluconobacter oxydans genome. Included in the 967 ORFs that are unique to G. bethesdensis are ORFs potentially important for virulence, adherence, DNA uptake, and methanol utilization. GC% values and best BLAST analysis suggested that some of these unique ORFs were recently acquired. Comparison of G. bethesdensis to other known CGD pathogens demonstrated conservation of some putative virulence factors, suggesting possible common mechanisms involved in pathogenesis in CGD. Geno-typing of the four patient isolates by use of a custom microarray demonstrated genome-wide variations in regions encoding DNA uptake systems and transcriptional regulators and in hypothetical ORFs. G. bethesdensis is a genetically diverse emerging human pathogen that may have recently acquired virulence factors new to this family of organisms. C1 NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIAID, Res Technol Sect, Genom Unit, Rocky Mt Labs,NIH,US Dept Hlth & Human Serv, Hamilton, MT 59840 USA. NIAID, Res Technol Sect, Microscopy Unit, Rocky Mt Labs,NIH,US Dept Hlth & Human Serv, Hamilton, MT 59840 USA. RP Greenberg, DE (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH,US Dept Hlth & Human Serv, 33 North Dr,Room 2W10A-3,MSC 3206, Bethesda, MD 20892 USA. EM degreenberg@mail.nih.gov FU Intramural NIH HHS NR 42 TC 33 Z9 292 U1 0 U2 6 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 DEC PY 2007 VL 189 IS 23 BP 8727 EP 8736 DI 10.1128/JB.00793-07 PG 10 WC Microbiology SC Microbiology GA 238YI UT WOS:000251484100036 PM 17827295 ER PT J AU Hall, KL Robbins, ML Paiva, A Knott, JE Harris, L Mattice, B AF Hall, Kara L. Robbins, Mark L. Paiva, Andrea Knott, J. Eugene Harris, Lorna Mattice, Burton TI Donation intentions among african american college students: Decisional balance and self-efficacy measures SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE organ donation; stages of change; decisional balance; self-efficacy; transtheoretical model ID EXPERT-SYSTEM INTERVENTION; ORGAN DONATION; SMOKING-CESSATION; BEHAVIORS; ATTITUDES; COMPONENT; WOMEN; STAGE; TRANSPLANTATION; WILLINGNESS AB Although the need for transplantation among African Americans is high, their donation rates are disproportionately low. This study describes the development and validation of culturally adapted psychosocial measures, including Transtheoretical Model constructs, Stages of Change, Decisional Balance, and Self-efficacy, related to deceased organ and tissue donation for an African American college population. Exploratory and confirmatory analyses for Decisional Balance and Self-efficacy measures demonstrated factor structures similar to previous studies of other behavioral applications, indicated excellent model fit and showed good internal and external validity. This study developed brief measures with good psychometric properties for an emerging behavior change domain in a new population. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Rhode Isl, Kingston, RI 02881 USA. North Carolina A&T Univ, Greensboro, NC USA. Carolina Donor Serv, Durham, NC USA. RP Hall, KL (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7326,Execut Plaza N,Room 512, Bethesda, MD 20892 USA. EM hallka@mail.nih.gov FU OSTLTS CDC HHS [1H39OT00077] NR 76 TC 15 Z9 15 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD DEC PY 2007 VL 30 IS 6 BP 483 EP 495 DI 10.1007/s10865-007-9121-8 PG 13 WC Psychology, Clinical SC Psychology GA 232KS UT WOS:000251019200004 PM 17674183 ER PT J AU Sauna, ZE Kim, IW Ambudkar, SV AF Sauna, Zuben E. Kim, In-Wha Ambudkar, Suresh V. TI Genomics and the mechanism of P-glycoprotein (ABCB1) SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE ATP-binding cassette; P-glycoprotein; multidrug resistance; ATP hydrolysis; catalytic; transport pathway; single nucleotide polymorphism ID ATP-BINDING CASSETTE; MULTIDRUG-RESISTANCE GENE; CATALYTIC CYCLE; GLUTAMATE RESIDUES; STRUCTURAL BIOLOGY; TRANSPORTER HLYB; DRUG TRANSPORT; A-LOOP; HYDROLYSIS; DOMAIN AB The development of effective clinical interventions against multidrug resistance (MDR) in cancer remains a significant challenge. Single nucleotide polymorphisms (SNPs) contribute to wide variations in how individuals respond to medications and there are several SNPs in human P-glycoprotein (P-gp) that may influence the interactions of drug-substrates with the transporter. Interestingly, even some of the synonymous SNPs have functional consequences for P-gp. It is also becoming increasingly evident that an understanding of the transport pathway of P-gp may be necessary to design effective modulators. In this review we discuss: (1) The potential importance of SNPs (both synonymous and non-synonymous) in MDR and (2) How new concepts that have emerged from structural studies with isolated nucleotide binding domains of bacterial ABC transporters have prompted biochemical studies on P-gp, leading to a better understanding of the mechanism of P-gp mediated transport. Our results suggest that the power-stroke is provided only after formation of the pre-hydrolysis transition-like (E center dot S) state during ATP hydrolysis. C1 [Sauna, Zuben E.; Kim, In-Wha; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bldg 37,Room 2120,37 Convent Dr, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov FU Intramural NIH HHS NR 54 TC 38 Z9 41 U1 1 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD DEC PY 2007 VL 39 IS 5-6 BP 481 EP 487 DI 10.1007/s10863-007-9115-9 PG 7 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 252TC UT WOS:000252468500021 PM 18058211 ER PT J AU Lin, DC Dmitriadis, EK Horkay, F AF Lin, David C. Dmitriadis, Emilios K. Horkay, Farenc TI Robust strategies for automated AFM force curve Analysis-II: Adhesion-influenced indentation of soft, elastic materials SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE adhesive contact; atomic force microscopy; contact mechanics; elasticity; indentation ID POLYMER SURFACES; CONTACT; SPHERES; DEFORMATION; MICROSCOPY; SOLIDS; LOAD AB In the first of this two-part discourse on the extraction of elastic properties from atomic force microscopy (AFM) data, a scheme,for automating the analysis of force-distance curves was introduced and experimentally validated for the Hertzian (i.e., linearly elastic and noninteractive probe-sample pairs) indentation of soft, inhomogeneous materials. In the presence of probe-sample adhesive interactions, which are common especially during retraction of the rigid tip from soft materials, the Hertzian models are no longer adequate. A number of theories (e.g., Johnson-Kendall-Roberts and Derjaguin-Muller-Toporov), covering the full range of sample compliance relative to adhesive force and tip radius, are available for analysis of such data. We incorporated Pietrement and Troyon's approximation (2000, "General Equations Describing Elastic Indentation Depth and Normal Contact Stiffness Versus Load, " J. Colloid Interface Sci., 226(1), pp. 166-171) of the Maugis-Dugdale model into the automated procedure. The scheme developed for the processing of Hertzian data was extended to allow for adhesive contact by applying the Pietrement-Troyon equation. Retraction force-displacement data from the indentation of polyvinyl alcohol gels were processed using the customized software. Many of the retraction curves exhibited strong adhesive interactions that were absent in extension. We compared the values of Young's modulus extracted from the retraction data to the values obtained from the extension data and tom macroscopic uniaxial compression tests. Application of adhesive contact models and the automated scheme to the retraction curves yielded average values of Young's modulus close to those obtained with Hertzian models for the extension curves. The Pietrement-Troyon equation provided a good fit to the data as indicated by small values of the mean-square error. The Maugis-Dugdale theory is capable of accurately modeling adhesive contact between a rigid spherical indenter and a soft, elastic sample. Pietrement and Troyon's empirical equation greatly simplifies the theory and renders it compatible with the general automation strategies that we developed for Hertzian analysis. Our comprehensive algorithm for automated extraction of Young's moduli from AFM indentation data has been expanded to recognize the presence of either adhesive or Hertzian behavior and apply the appropriate contact model. C1 NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. [Dmitriadis, Emilios K.; Horkay, Farenc] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Lin, DC (reprint author), NIH, Lab Integrat & Med Biophys, 9Mem Dr,Bldg 9,Room 1E118, Bethesda, MD 20892 USA. EM lindavid@mail.nih.gov; dimitria@helix.nih.gov; horkay@helix.nih.gov FU Intramural NIH HHS NR 24 TC 53 Z9 53 U1 7 U2 54 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD DEC PY 2007 VL 129 IS 6 BP 904 EP 912 DI 10.1115/1.2800826 PG 9 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 251LD UT WOS:000252374000014 PM 18067395 ER PT J AU Montanaro, L Campoccia, D Pirini, V Ravaioli, S Otto, M Arciola, CR AF Montanaro, Lucio Campoccia, Davide Pirini, Valter Ravaioli, Stefano Otto, Michael Arciola, Carla Renata TI Antibiotic multiresistance strictly associated with IS256 and ica genes in Staphylococcus epidermidis strains from implant orthopedic infections SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE Staphylococcus epidermidis; antibiotic resistance; ica-genes; IS256; aminoglycosides; gentamicin ID GENTAMICIN RESISTANCE TRANSPOSON; POLYSACCHARIDE INTERCELLULAR ADHESIN; SEQUENCE ELEMENT IS256; BIOFILM FORMATION; SLIME PRODUCTION; INSERTION; AUREUS; LOCUS; EXOPOLYSACCHARIDE; DISCRIMINATION AB In this study the presence both of the ica genes, encoding for biofilm exopolysaccharide production, and the insertion sequence IS256, a mobile element frequently associated to transposons, was investigated in relationship with the prevalence of antibiotic resistance among Staphylococcus epidermidis strains. The investigation was conducted on 70 clinical isolates derived from orthopedic implant infections. Among the clinical isolates investigated a dramatic high level of association was found between the presence of ica genes as well as of IS256 and multiple-resistance to all the antibiotics tested (oxacillin, penicillin, gentamicin, erythromycin, clindamycin, chloramphenicol, sulfamethoxazole + trimethoprim, ciprofloxacin, vancomycin). Noteworthy, a striking full association between the presence of IS256 and resistance to gentamicin was found, being none of the IS256-negative strain resistant to this antibiotic. This association is probably because of the link of the corresponding aminoglycoside-resistance genes, and IS256, often co-existing within the same staphylococcal transposon. In conclusion, in orthopedics, the presence of ica genes and that of IS256 in S. epidermidis genome should both be considered as informative markers of clinically relevant strains equipped with greatest and broadest resistance potential to survive to medical treatments. (c) 2007 Wiley Periodicals, Inc. C1 Rizzoli Orthoped Inst, Res Unit Implant Infect, I-40136 Bologna, Italy. Univ Bologna, Dept Expt Pathol, I-40126 Bologna, Italy. NIAID, NIH, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Arciola, CR (reprint author), Rizzoli Orthoped Inst, Res Unit Implant Infect, Via Barbiano 1-10, I-40136 Bologna, Italy. EM carlarenata.arciola@ior.it OI Otto, Michael/0000-0002-2222-4115 NR 32 TC 15 Z9 15 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD DEC 1 PY 2007 VL 83A IS 3 BP 813 EP 818 DI 10.1002/jbm.a.31399 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 228PT UT WOS:000250742700027 PM 17559115 ER PT J AU Mackey, DC Eby, JG Harris, F Taaffe, DR Cauley, JA Tylavsky, FA Harris, TB Lang, TF Cummings, SR AF Mackey, Dawn C. Eby, Jean Gaare Harris, Fran Taaffe, Dennis R. Cauley, Jane A. Tylavsky, Frances A. Harris, Tamara B. Lang, Thomas F. Cummings, Steven R. CA HABCS Grp TI Prediction of clinical non-spine fractures in older black and white men and women with volumetric BMD of the spine and areal BMD of the hip: The health, aging, and body composition study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteoporosis; fracture; BMD; DXA; QCT ID BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; QUANTITATIVE COMPUTED-TOMOGRAPHY; OSTEOPOROTIC FRACTURES; ELDERLY-WOMEN; POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURES; RISK-FACTORS; AGE; DIAGNOSIS AB In a prospective study of 1446 black and white adults 70-79 yr of age (average follow-up, 6.4 yr), vertebral TrvBMD from QCT predicted non-spine fracture in black and white women and black men, but it was not a stronger predictor than total hip aBMD from DXA. Hip aBMD predicted non-spine fracture in black men. Introduction: Areal BMD (aBMD) at multiple skeletal sites predicts clinical non-spine fractures in white and black women and white men. The predictive ability of vertebral trabecular volumetric BMD (TrvBMD) for all types of clinical non-spine fractures has never been tested or compared with hip aBMD. Also, the predictive accuracy of hip aBMD has never been tested prospectively for black men. Materials and Methods: We measured vertebral TrvBMD with QCT and hip aBMD with DXA in 1446 elderly black and white adults (70-79 yr) in the Health, Aging, and Body Composition Study. One hundred fifty-two clinical non-spine fractures were confirmed during an average of 6.4 yr of >95% complete follow-up. We used Cox proportional hazards regression to determine the hazard ratio (HR) and 95% CIs of non-spine fracture per SD reduction in hip aBMD and vertebral TrvBMD. Results: Vertebral TrvBMD and hip aBMD were both associated with risk of non-spine fracture in black and white women and black men. The age-adjusted HR of fracture per SD decrease in BMD was highest in black men (hip aBMD: HR = 2.04, 95 % CI = 1.03, 4.04; vertebral TrvBM D: HR = 3.00, 95 % CI 1.29, 7.00) and lowest in white men (hip aBMD: HR = 1.23, 95 % CI = 0.85, 1.78; vertebral TrvBMD: HR 1.06, 95 % CI = 0.73, 1.54). Adjusted for age, sex, and race, each SD decrease in hip aBMD was associated with a 1.67-fold (95% CI = 1.36. 2.07) greater risk of fracture, and each SD decrease in vertebral TrvBMD was associated with a 1.47-fold (95% CI = 1.18,1.82) greater risk. Combining measurements of hip aBMD and vertebral TrvBMD did not improve fracture prediction. Conclusions: Low BMD measured by either spine QCT or hip DXA predicts non-spine fracture in older black and white women and black men. Vertebral TrvBMD is not a stronger predictor than hip aBMD of non-spine fracture. C1 Calif Pacific Med Ctr, San Francisco Coordinating Ctr, Res Inst, San Francisco, CA 94118 USA. Brigham & Womens Hosp, Harvard Med Sch, Harvard Sch Publ Hlth, Channing Lab, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Queensland, Fac Hlth Sci, Sch Human Movement Studies, Brisbane, Qld, Australia. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. NIA, Lab Epidemiol Demography & Biometry, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Mackey, DC (reprint author), Calif Pacific Med Ctr, San Francisco Coordinating Ctr, Res Inst, San Francisco, CA 94118 USA. RI Lang, Thomas/B-2685-2012; Cauley, Jane/N-4836-2015 OI Lang, Thomas/0000-0002-3720-8038; Cauley, Jane/0000-0003-0752-4408 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2106] NR 31 TC 25 Z9 26 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2007 VL 22 IS 12 BP 1862 EP 1868 DI 10.1359/JBMR-070807 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 236HA UT WOS:000251292400006 PM 17708713 ER PT J AU Oxentenko, AS Vierkant, RA Pardi, DS Farley, DR Dozois, EJ Hartman, TE Hough, DM Petersen, WO Klabunde, CN Sharpe, K Bond, JH Smith, RA Levin, B Pope, JB Schroy, PC Limburg, PJ AF Oxentenko, Amy S. Vierkant, Robert A. Pardi, Darrell S. Farley, David R. Dozois, Eric J. Hartman, Thomas E. Hough, David M. Petersen, Wesley O. Klabunde, Carrie N. Sharpe, Katherine Bond, John H. Smith, Robert A. Levin, Bernard Pope, John B. Schroy, Paul C. Limburg, Paul J. TI Colorectal cancer screening perceptions and practices: Results from a national survey of gastroenterology, surgery and radiology trainees SO JOURNAL OF CANCER EDUCATION LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the American-College-of-Gastroenterology CY OCT 30-NOV 02, 2005 CL Honolulu, HI SP Amer Coll Gastroenterol ID FECAL OCCULT BLOOD; PRIMARY-CARE PHYSICIANS; COLONOSCOPY SURVEILLANCE; CONSENSUS UPDATE; UNITED-STATES; E-MAIL; GUIDELINES; KNOWLEDGE; RISK; POPULATION AB Background. Colorectal cancer (CRC) screening in the United States is suboptimal. We conducted a national survey to learn about CRC screening perceptions and practices among trainees who perform CRC screening tests including those enrolled in Gastroenterology and Hepatology (GIH), General and Colorectal Surgery, and Diagnostic and Abdominal Radiology training programs. Methods. Program directors/administrators (PDs/PAs) from 642 programs were contacted by e-mail with an invitation to forward our survey to trainees in their programs. Participating trainees then completed an anonymous, Web-based questionnaire. Results. A total of 130/642 (20%) PDs/PAs forwarded our survey to their trainees, with responses received from 476 trainees (80 GIH, 261 surgery, 135 radiology). Colonoscopy was felt to be the best CRC screening test at reducing CRC mortality, with patient-related factors perceived as greater barriers than system-related factors. No single guideline was deemed very influential on CRC screening practices by most trainees. A total of 2 of 5 above-average risk patient profiles were not recognized by most trainees. Colonoscopy was selected as the preferred follow-up test for a positive CRC screening test by most trainees. However, 34% of respondents chose an option other than colonoscopy atone for follow-up of a positive fecal occult blood test. Conclusions. Based on data from this national survey of gastroenterology, surgery, and radiology trainees, opportunities exist for curricular changes that may help enhance current perceptions and practices of trainees who perform CRC screening tests. C1 [Oxentenko, Amy S.; Vierkant, Robert A.; Pardi, Darrell S.; Farley, David R.; Dozois, Eric J.; Hartman, Thomas E.; Hough, David M.; Petersen, Wesley O.; Limburg, Paul J.] Mayo Clin, Coll Med, Miles & Shirley Fiterman Ctr Digest Dis, Rochester, MN 55905 USA. [Klabunde, Carrie N.] NCI, Hlth Serv, Bethesda, MD 20892 USA. [Sharpe, Katherine; Smith, Robert A.] Amer Canc Soc, Atlanta, GA 30329 USA. [Bond, John H.] Vet Adm Med Ctr, Minneapolis, MN 55417 USA. [Levin, Bernard] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Pope, John B.] Louisiana State Univ, Shreveport, LA 71105 USA. [Pope, John B.] Boston Univ, Med Ctr, Boston, MA 02215 USA. [Klabunde, Carrie N.] NCI, Econ Branch, Bethesda, MD 20892 USA. RP Limburg, PJ (reprint author), Mayo Clin, Coll Med, Miles & Shirley Fiterman Ctr Digest Dis, 200 1st St SW, Rochester, MN 55905 USA. EM limburg.paul@mayo.edu OI Vierkant, Robert/0000-0001-6242-5221 NR 35 TC 5 Z9 5 U1 1 U2 3 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD WIN PY 2007 VL 22 IS 4 BP 219 EP 226 PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 252RA UT WOS:000252463100004 PM 18067433 ER PT J AU Cannick, GF Horowitz, AM Garr, DR Reed, SG Neville, BW Day, TA Woolson, RF Lackland, DT AF Cannick, Gabrielle F. Horowitz, Alice M. Garr, David R. Reed, Susan G. Neville, Brad W. Day, Terry A. Woolson, Robert F. Lackland, Daniel T. TI Oral cancer prevention and early detection: Using the PRECEDE-PROCEED framework to guide the training of health professional students SO JOURNAL OF CANCER EDUCATION LA English DT Article ID DENTAL STUDENTS; SOUTH-CAROLINA; KNOWLEDGE; OPINIONS; SCHOOLS AB Background. Teaching cancer prevention and detection is important in health professional education. It is desirable to select a comprehensive framework for teaching oral cancer (OC) prevention and detection skills. Methods. The PRECEDE-PROCEED model was used to design a randomized pretest and posttest study of the OC prevention and detection skills of dental students (n = 104). OC knowledge, opinions, and competencies were evaluated. Results. Second year students in the intervention group were more competent than those in the control group. Conclusions. The novel use of PRECEDE-PROCEED sets a precedent for designing a standardized OC curriculum for a wide range of health professional disciplines. C1 [Cannick, Gabrielle F.; Garr, David R.; Reed, Susan G.; Neville, Brad W.; Day, Terry A.; Woolson, Robert F.; Lackland, Daniel T.] Med Univ S Carolina, Charleston, SC 29425 USA. [Horowitz, Alice M.] NIDCR, NIH, Bethesda, MD USA. RP Lackland, DT (reprint author), 135 Cannon St,Suite 303, Charleston, SC 29425 USA. EM lackland@musc.edu FU NIDCR NIH HHS [F30DE017046-01] NR 22 TC 6 Z9 7 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD WIN PY 2007 VL 22 IS 4 BP 250 EP 253 PG 4 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 252RA UT WOS:000252463100009 PM 18067438 ER PT J AU Berrier, AL Yamada, KM AF Berrier, Allison L. Yamada, Kenneth M. TI Cell-matrix adhesion SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID EXTRACELLULAR-MATRIX; LYSYL OXIDASE; FOCAL ADHESIONS; INTEGRIN REGULATION; STRUCTURAL BASIS; CANCER INVASION; MIGRATION; FIBRONECTIN; FIBROBLASTS; MOTILITY AB The complex interactions of cells with extracellular matrix (ECM) play crucial roles in mediating and regulating many processes, including cell adhesion, migration, and signaling during morphogenesis, tissue homeostasis, wound healing, and tumorigenesis. Many of these interactions involve transmembrane integrin receptors. Integrins cluster in specific cell-matrix adhesions to provide dynamic links between extracellular and intracellular environments by bi-directional signaling and by organizing the ECM and intracellular cytoskeletal and signaling molecules. This mini review discusses these interconnections, including the roles of matrix properties such as composition, three-dimensionality, and porosity, the bi-directional functions of cellular contractility and matrix rigidity, and cell signaling. The review concludes by speculating on the application of this knowledge of cell-matrix interactions in the formation of cell adhesions, assembly of matrix, migration, and tumorigenesis to potential future therapeutic approaches. C1 Natl Ctr Minor Hlth & Hlth Dispar, Katrina Visiting Fac Program, Natl Inst Hlth, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, Natl Inst Hlth, Bethesda, MD USA. RP Berrier, AL (reprint author), Bldg 30,Room 426,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM berriera@mail.nih.gov; Kenneth.Yamada@nih.gov OI Yamada, Kenneth/0000-0003-1512-6805 FU Intramural NIH HHS NR 90 TC 457 Z9 464 U1 9 U2 110 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 2007 VL 213 IS 3 BP 565 EP 573 DI 10.1002/jcp.21237 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 227ID UT WOS:000250649500001 PM 17680633 ER PT J AU Grant, P Lougee, L Hirschtritt, M Swedo, SE AF Grant, Paul Lougee, Lorraine Hirschtritt, Matthew Swedo, Susan E. TI An open-label trial of riluzole, a glutamate antagonist, in children with treatment-resistant obsessive-compulsive disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID AGENT RILUZOLE; BEHAVIOR; ADOLESCENTS; MODEL; OCD AB Background: Obsessive-compulsive disorder (OCD) in childhood is often refractory to treatment. Riluzole, a glutamate antagonist, has theoretical support as an alternative pharmacological treatment and has demonstrated possible benefit in some open-label trials in adults with OCD. Methods: Six subjects, ages 8-16 years, were enrolled in a 12-week open-label trial of riluzole for OCD symptoms that had resisted prior treatments. OCD symptoms and adverse effects of drug were monitored. Results: Four of 6 subjects had clear benefit, with reduction of more than 46% (39% overall) on Children's Yale-Brown Obsessive-Compulsive Scale, and "Much Improved" or "Very Much Improved" on the Clinical Global Impressions-Improvement scale. Two subjects had no clinically meaningful change in symptom severity by 12 weeks, but 1 subject improved thereafter. There were no adverse effects of drug sufficient to cause discontinuation or reduction of dose. All subjects elected to continue riluzole after the 12-week trial. Conclusions: Riluzole may be beneficial for treatment-resistant OCD in young subjects and seems well tolerated. A placebo-controlled trial of the drug is planned. C1 [Grant, Paul] NIH, Bethesda, MD 20892 USA. [Grant, Paul; Lougee, Lorraine; Hirschtritt, Matthew; Swedo, Susan E.] NIMH, Pediat & Dev Neuropsychiat Branch, NIH, Bethesda, MD USA. RP Grant, P (reprint author), NIH, Bldg 10,Room 4N208,MSC 1255, Bethesda, MD 20892 USA. EM paul.grant@nih.gov FU Intramural NIH HHS NR 17 TC 105 Z9 109 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD DEC PY 2007 VL 17 IS 6 BP 761 EP 767 DI 10.1089/cap.2007.0021 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QU UT WOS:000252745500003 PM 18315448 ER PT J AU Thouennon, E Elkahloun, AG Guillemot, J Gimenez-Roqueplo, AP Bertherat, J Pierre, A Ghzili, H Grumolato, L Muresan, M Klein, M Lefebvre, H Ouafik, L Vaudry, H Plouin, PF Yon, L Anouar, Y AF Thouennon, Erwan Elkahloun, Abdel G. Guillemot, Johann Gimenez-Roqueplo, Anne-Paule Bertherat, Jerome Pierre, Alice Ghzili, Hafida Grumolato, Luca Muresan, Mihaela Klein, Marc Lefebvre, Herve Ouafik, L'Houcine Vaudry, Hubert Plouin, Pierre-Francois Yon, Laurent Anouar, Youssef TI Identification of potential gene markers and insights into the pathophysiology of pheochromocytoma malignancy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EXPRESSION; ACTIVATION; HEREDITARY; DIAGNOSIS; PROTEIN; ALPHA AB Context: Pheochromocytomas are catecholamine-producing tumors that are generally benign but that can also present as or develop into malignancy. Occurrence of malignant pheochromocytomas can only be asserted by imaging of metastatic lesions. Objectives: We conducted a gene expression profiling of benign and malignant tumors to identify a gene signature that would allow us to discriminate benign from malignant pheochromocytomas and to gain a better understanding of tumorigenic pathways associated with malignancy. Design: A total of 36 patients with pheochromocytoma was studied retrospectively. There were 18 ( nine benign and nine malignant) tumors used for gene expression profiling on pangenomic oligonucleotide microarrays. Results: We identified and validated a set of predictor genes that could accurately distinguish the two tumor subtypes through unsupervised clustering. Most of the differentially expressed genes were down-regulated in malignant tumors, and several of these genes encoded neuroendocrine factors involved in prominent characteristics of chromaffin cell biology. In particular, the expression of two key processing enzymes of trophic peptides, peptidylglycine alpha-amidating monooxygenase and glutaminyl-peptide cyclotransferase, was reduced in malignant pheochromocytomas. Conclusion: The gene expression profiling of benign and malignant pheochromocytomas clearly identified a set of genes that could be used as a prognostic multi-marker and revealed that the expression of several genes encoding neuroendocrine proteins was reduced in malignant compared with benign tumors. C1 Univ Rouen, European Inst Peptide Res, Lab Cellular & Mol Neuroendocrinol, F-76821 Mont St Aignan, France. NIH, NHGRI, Genom Technol Branch, Bethesda, MD 20892 USA. Hop Europeen Georges Pompidou, Dept Genet, F-75015 Paris, France. Inst Cochin, Inst Natl Sante Rech Med, Dept Endocrinol, U567, F-75014 Paris, France. Hop Brabois, Dept Endocrinol, F-54511 Vandoeuvre Les Nancy, France. Univ Aix Marseille 2, Equipe Mixte Inst Natl Sante Rech Med EMI 0359, Lab Expt Cancerol, F-13015 Marseille, France. Univ Paris 05, Hop Europeen Georges Pompidou, Hypertens Unit, F-75015 Paris, France. RP Anouar, Y (reprint author), Univ Rouen, European Inst Peptide Res, Lab Cellular & Mol Neuroendocrinol, F-76821 Mont St Aignan, France. EM youssef.anouar@univ-rouen.fr RI Guillemot, Johann/O-1066-2013; Grumolato, Luca/A-1697-2015; OI Guillemot, Johann/0000-0002-5902-9188; Grumolato, Luca/0000-0001-8231-3032; Klein, Marc/0000-0002-1037-4220 NR 21 TC 40 Z9 42 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2007 VL 92 IS 12 BP 4865 EP 4872 DI 10.1210/jc.2007-1253 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237TQ UT WOS:000251399700056 PM 17878247 ER PT J AU Tan, SY Rosenthal, J Zhao, XQ Francis, RJ Chatterjee, B Sabol, SL Linask, KL Bracero, L Connelly, PS Daniels, MP Yu, Q Omran, H Leatherbury, L Lo, CW AF Tan, Serena Y. Rosenthal, Julie Zhao, Xiao-Qing Francis, Richard J. Chatterjee, Bishwanath Sabol, Steven L. Linask, Kaari L. Bracero, Luciann Connelly, Patricia S. Daniels, Mathew P. Yu, Qing Omran, Heymut Leatherbury, Linda Lo, Cecilia W. TI Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LEFT-RIGHT ASYMMETRY; CARDIOVASCULAR ANOMALIES; NODE MONOCILIA; SITUS-INVERSUS; IMMOTILE CILIA; MICE; MUTATIONS; FLOW; HYDROCEPHALUS; LATERALITY AB Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder associated with ciliary defects and situs inversus totalis, the complete mirror image reversal. of internal organ situs (positioning). A variable incidence of heterotaxy, or irregular organ situs, also has been reported in PCD patients, but it is not known whether this is elicited by the PCD-causing genetic lesion. We studied a mouse model of PCD with a recessive mutation in Dnahc5, a dynein gene commonly mutated in PCD. Analysis of homozygous mutant embryos from 18 litters yielded 25% with normal organ situs, 35% with situs inversus totalis, and 40% with heterotaxy. Embryos with heterotaxy had complex structural heart defects that included discordant atrioventricular and ventricular outflow situs and atrial/pulmonary isomerisms. Variable combinations of a distinct set of cardiovascular anomalies were observed, including superior-inferior ventricles, great artery alignment defects, and interrupted inferior vena cava with azygos continuation. The surprisingly high incidence of heterotaxy led us to evaluate the diagnosis of PCD. PCD was confirmed by EM, which revealed missing outer dynein arms in the respiratory cilia. Ciliary dyskinesia was observed by videomicroscopy. These findings show that Dnabc5 is required for the specification of left-right asymmetry and suggest that the PCD-causing Dnahc5 mutation may also be associated with heterotaxy. C1 NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, NHLBI Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. Univ Childrens Hosp Freiburg, Freiburg, Germany. Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA. RP Lo, CW (reprint author), NHLBI, Dev Biol Lab, NIH, 10 Ctr Dr,MSC 1583, Bethesda, MD 20892 USA. EM loc@nhlbi.nih.gov RI Francis, Richard/P-2524-2015 FU NHLBI NIH HHS [Z01 HL005701] NR 44 TC 54 Z9 56 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2007 VL 117 IS 12 BP 3742 EP 3752 DI 10.1172/JCI33284 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 237SL UT WOS:000251396600023 PM 18037990 ER PT J AU Tang, XW Zhu, YC Han, L Kim, AL Kopelovich, L Bickers, DR Athar, M AF Tang, Xiuwei Zhu, Yucui Han, Lydia Kim, Arianna L. Kopelovich, Levy Bickers, David R. Athar, Mohammad TI CP-31398 restores mutant p53 tumor suppressor function and inhibits UVB-induced skin carcinogenesis in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN CANCER-CELLS; WILD-TYPE P53; DNA-DAMAGE; IN-VIVO; DRUG DEVELOPMENT; APOPTOSIS; GENE; PROTEIN; RESTORATION; ACTIVATION AB Mutations in the tumor suppressor p53 are detectable in over 50% of all human malignancies. Mutant p53 protein is incapable of transactivating its downstream target genes that are required for DNA repair and apoptosis. Chronic exposure to UVB induces p53 mutations and is carcinogenic in both murine and human skin. CP-31398, a styrylquinazoline compound, restores the tumor suppressor functions of mutant forms of p53 in tumor cells. However, its effectiveness in vivo remains unclear. Here, we demonstrate that CP-31398 blocked UVB-induced skin carcinogenesis and was associated with increases in p53, p21, and BclXs. CP-31398 downregulated Bcl2, proliferating nuclear cell antigen, and cychn D1. Activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase also occurred in both tumor and perilesional skin following treatment. CP-31398 induced the expression of p53-dependent target proteins, and this was followed by apoptosis in UVB-irradiated wild-type mice but not in their p53-deficient littermates. Similar effects were observed in human skin carcinoma A431 cells expressing mutant p53. In addition, CP-31398 induced mitochondrial translocation of p53, leading to changes in mitochondrial membrane permeability pore transition (MPT) and consequent cytochrome c release in these cells. Blocking MPT diminished p53 translocation and apoptosis. These studies indicate that reconstituting p53 tumor suppressor functions in vivo by small molecular weight compounds may block the pathogenesis and progression of skin cancer. C1 Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Athar, M (reprint author), Univ Alabama, Dept Dermatol, Volker Hall,Room 509,1670 Univ Blvd, Birmingham, AL 35294 USA. EM mathar@uab.edu FU NCI NIH HHS [CA097249, N01-CN-35105, N01-CN-35109, N01-CN-43300, N01CN35105, N01CN35109, N01CN43300, R01 CA097249, R01 CA105136]; NIAMS NIH HHS [K01 AR048582]; NIEHS NIH HHS [R01 ES015323] NR 61 TC 70 Z9 72 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2007 VL 117 IS 12 BP 3753 EP 3764 DI 10.1172/JCI32481 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 237SL UT WOS:000251396600024 PM 18060030 ER PT J AU Quint, K Porras, C Safaeian, M Gonzalez, P Hildesheim, A Quint, W van Doorn, LJ Silva, S Melchers, W Schiffman, M Rodriguez, AC Wacholder, S Freer, E Cortes, B Herrero, R AF Quint, Koen Porras, Carolina Safaeian, Mahboobeh Gonzalez, Paula Hildesheim, Allan Quint, Wim van Doorn, Leen-Jan Silva, Sandra Melchers, Willem Schiffman, Mark Rodriguez, Ana Cecilia Wacholder, Sholom Freer, Enrique Cortes, Bernal Herrero, Rolando CA Costa Rican Vaccine Trial Grp TI Evaluation of a novel PCR-Based assay for detection and identification of Chlamydia trachomatis serovars in cervical specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; PELVIC INFLAMMATORY DISEASE; OUTER-MEMBRANE PROTEIN; CHLAMYDIA-TRACHOMATIS-OMP1 GENOTYPES; MONOCLONAL-ANTIBODIES; INFECTIONS; PLASMID; POPULATION; ISOLATE; SAMPLES AB The aims of this study were to compare a novel PCR-based Chlamydia trachomatis detection and genotyping (Ct-DT) assay with the FDA-approved, commercially available C. trachomatis detection Hybrid Capture 2 (HC2) assay and to investigate the C. trachomatis serovar distribution among young women in a rural Costa Rican study population. A total of 5,828 sexually active women participating in a community-based trial in Costa Rica were tested for C. trachomatis by HC2. A sample of 1,229 specimens consisting of 100% HC2 C. trachomatis-positive specimens (n = 827) and a random sample of 8% HC2 C. trachomatis-negative specimens (n = 402) were tested with the Ct-DT assay. Agreement between the two assays was determined by the unweighted kappa statistic. Discrepant specimens were tested with a second commercially available test (COBAS TaqMan). The Ct-DT-positive specimens were further analyzed with the Ct-DT genotyping step to investigate the distribution of 14 different C. trachomatis serovars (A, B/Ba, C, D/Da, E, F, G/Ga, H, I/Ia, J, K, L1, L2/L2a, and L3). After accounting for the sampling fraction selected for Ct-DT testing, crude agreement with the HC2 assay was 98% and the kappa was 0.92 (95% confidence interval [CI], 0.89 to 0.97). The 33 discordant samples that were further analyzed with the COBAS TaqMan test showed better agreement with the Ct-DT assay (31/33, P < 0.001). Among the 806 Ct-DT-positive samples, serovar E was the most common serovar (31%), followed by serovars F and D (both 21%) and serovar I (15%). In conclusion, the novel Ct-DT assay permits reliable detection and identification of C. trachomatis serovars. C1 [Quint, Koen; Quint, Wim; van Doorn, Leen-Jan] DDL Diagnost Lab, Voorburg, Netherlands. [Porras, Carolina; Gonzalez, Paula; Silva, Sandra; Rodriguez, Ana Cecilia; Cortes, Bernal; Herrero, Rolando] Fdn INCIENSA, San Jose, Costa Rica. [Safaeian, Mahboobeh; Hildesheim, Allan; Schiffman, Mark; Rodriguez, Ana Cecilia; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Freer, Enrique] Univ Costa Rica, Ctr Invest Estructuras Microscop, San Jose, Costa Rica. [Melchers, Willem] Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, Nijmegen, Netherlands. RP Safaeian, M (reprint author), NCI, Hormonal & Reproduct Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 550, Rockville, MD 20852 USA. EM safaeianm@mail.nih.gov RI Melchers, Willem/C-8819-2015 OI Melchers, Willem/0000-0002-5446-2230 NR 33 TC 19 Z9 19 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2007 VL 45 IS 12 BP 3986 EP 3991 DI 10.1128/JCM.01155-07 PG 6 WC Microbiology SC Microbiology GA 241AT UT WOS:000251630000019 PM 17959760 ER PT J AU Basch, E Iasonos, A Barz, A Culkin, A Kris, MG Artz, D Fearn, P Speakman, J Farquhar, R Scher, HI McCabe, M Schrag, D AF Basch, Ethan Iasonos, Alexia Barz, Allison Culkin, Ann Kris, Mark G. Artz, David Fearn, Paul Speakman, John Farquhar, Rena Scher, Howard I. McCabe, Mary Schrag, Deborah TI Long-term toxicity monitoring via electronic patient-reported outcomes in patients receiving chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 11th Annual International Meeting of the International-Society-of-Pharmacoeconomics-and-Outcomes-Research CY MAY 20-24, 2006 CL Philadelphia, PA SP Int Soc Pharmacoecon & Outcomes Res ID QUALITY-OF-LIFE; ONCOLOGY PRACTICE; CLINICAL-TRIALS; END-POINTS; CANCER; COMMUNICATION AB Purpose In cancer treatment trials, clinicians traditionally report patient toxicity symptoms. Alternatively, patients could provide this information directly. Patients and Methods The Common Terminology Criteria for Adverse Events (CTCAE) is the mandated instrument for tracking patient toxicity symptoms in National Cancer Institute (NCI)-sponsored cancer treatment trials. We adapted CTCAE symptom items into patient language and uploaded these to an online platform. Lung cancer outpatients receiving chemotherapy were invited to self-report selected symptoms at visits via waiting area computers or optional home access. Symptom reports were printed for nurses at visits, but no instructions were given with regard to use of this information. Results From June 2005 through March 2006, 125 patients were invited to participate, and 107 chose to enroll. Mean length of participation was 42 weeks (range, 1 to 71 weeks), by which time 35% died. The average number of clinic visits was 12 (range, 1 to 40 visits). At each consecutive visit, most patients (mean, 78%) logged in without significant attrition. Reasons for failure to log in included having no reminder and having inadequate time. Although 76% of enrollees had home computers, only 15% self-reported from home. Satisfaction with the system was high (90%), but only 51% felt communication was improved. All participating nurses understood the reports and felt this information was useful for clinical decisions, documentation, and discussions. However, only one of seven nurses discussed reports with patients frequently, with insufficient time being the most common barrier to discussions. Conclusion Online patient self-reporting is a feasible long-term strategy for toxicity symptom monitoring during chemotherapy, even among patients with advanced cancer and high symptom burdens. However, without explicit reminders and clinician feedback, patients demonstrated limited voluntary interest in self-reporting between visits. C1 Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Nursing, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Informat Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Off Phys Chief, New York, NY 10021 USA. NCI, Ctr Bioinformat, Rockville, MD USA. RP Basch, E (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. EM basche@mskcc.org OI Kris, Mark/0000-0002-7317-5341 FU NCI NIH HHS [K07 CA124851] NR 27 TC 72 Z9 72 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2007 VL 25 IS 34 BP 5374 EP 5380 DI 10.1200/JCO.2007.11.2243 PG 7 WC Oncology SC Oncology GA 272UL UT WOS:000253885700008 PM 18048818 ER PT J AU Pisters, KMW Evans, WK Azzoli, CG Kris, MG Smith, CA Desch, CE Somerfield, MR Brouwers, MC Darling, G Ellis, PM Gaspar, LE Pass, HI Spigel, DR Strawn, JR Ung, YC Shepherd, FA AF Pisters, Katherine M. W. Evans, William K. Azzoli, Christopher G. Kris, Mark G. Smith, Christopher A. Desch, Christopher E. Somerfield, Mark R. Brouwers, Melissa C. Darling, Gail Ellis, Peter M. Gaspar, Laurie E. Pass, Harvey I. Spigel, David R. Strawn, John R. Ung, Yee C. Shepherd, Frances A. TI Cancer care Ontario and American society of clinical oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I-IIIA resectable non-small-cell lung cancer guideline SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID VINORELBINE PLUS CISPLATIN; DOCTOR-PATIENT COMMUNICATION; RANDOMIZED CONTROLLED-TRIALS; EARLY BREAST-CANCER; POSTOPERATIVE RADIOTHERAPY; COMPUTER-PROGRAM; DECISION-MAKING; POOLED-ANALYSIS; BAD-NEWS; METAANALYSIS AB Purpose To determine the role of adjuvant chemotherapy and radiation therapy in patients with completely resected stage IA-IIIA non-small-cell lung cancer (NSCLC). Methods The Cancer Care Ontario Program in Evidence-Based Care and the American Society of Clinical Oncology convened a Joint Expert Panel in August 2006 to review the evidence and draft recommendations for these therapies. Results Available data support the use of adjuvant cisplatin-based chemotherapy in completely resected NSCLC; however, the strength of the data and consequent recommendations vary by disease stage. Adjuvant radiation therapy appears detrimental to survival in stages IB and II, with a possible modest benefit in stage IIIA. Conclusion Adjuvant cisplatin-based chemotherapy is recommended for routine use in patients with stages IIA, IIB, and IIIA disease. Although there has been a statistically significant overall survival benefit seen in several randomized clinical trials (RCTs) enrolling a range of people with completely resected NSCLC, results of subset analyses for patient populations with stage IB disease were not significant, and adjuvant chemotherapy in stage IB disease is not currently recommended for routine use. To date, very few patients with stage IA NSCLC have been enrolled onto RCTs of adjuvant therapy; adjuvant chemotherapy is not recommended in these cases. Evidence from RCTs demonstrates a survival detriment for adjuvant radiotherapy with limited evidence for a reduction in local recurrence. Adjuvant radiation therapy appears detrimental to survival in stage IB and II, and may possibly confer a modest benefit in stage IIIA. C1 Anderson Canc Ctr, Houston, TX USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NYU, Sch Med, New York, NY USA. Natl Comprehens Canc Network, Jenkintown, PA USA. Amer Soc Clin Oncol, Alexandria, VA USA. Univ Colorado, Denver Hlth Sci Ctr, Denver, CO 80202 USA. NCI, Ctr Canc, Bethesda, MD 20892 USA. Sarah Cannon Can Ctr, Nashville, TN USA. Canc Care Ontario, Toronto, ON, Canada. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada. RP Pisters, KMW (reprint author), ASCO, Canc Policy & Clin Affairs, 1900 Duke St,Suite 200, Alexandria, VA USA. EM guidelines@asco.org RI Mendez, Pedro /J-8955-2016; OI Mendez, Pedro /0000-0001-6713-7907; Kris, Mark/0000-0002-7317-5341 NR 78 TC 185 Z9 194 U1 1 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2007 VL 25 IS 34 BP 5506 EP 5518 DI 10.1200/JCO.2007.14.1226 PG 13 WC Oncology SC Oncology GA 272UL UT WOS:000253885700023 PM 17954710 ER PT J AU Cox, BJ Sareen, J Enns, MW Clara, I Grant, BF AF Cox, Brian J. Sareen, Jitender Enns, Murray W. Clara, Ian Grant, Bridget F. TI The fundamental structure of axis II personality disorders assessed in the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMMON MENTAL-DISORDERS; DRUG-USE DISORDERS; UNITED-STATES; PSYCHIATRIC-DISORDERS; DSM; PREVALENCE; SAMPLE; IV; COMORBIDITY; COOCCURRENCE AB Objective: Little is known about the fundamental structure of core personality disorder psychopathology in the general population. The current study employed confirmatory factor analysis to evaluate competing models of patterns of personality disorder diagnoses in a nationally representative sample. Method: DSM-IV and alternate models of the structure of personality disorder psychopathology were evaluated using data from the National Epidemiologic Survey on Alcohol and Related Conditions conducted between 2001 and 2002 (N=43,093). Dimensional versus categorical representations of DSM-IV personality disorder structure were also tested. Face-to-face interviews were conducted in the United States. Participants were community-based respondents aged 18 years and older. Diagnoses and dimensional scores were made for antisocial, avoidant, dependent, histrionic, obsessive-compulsive, paranoid, and schizoid personality disorders. Results: Multiple goodness-of-fit indicators provided support for a DSM-IV - based hierarchical model of personality disorders. In this model, the individual personality disorders were viewed as belonging to 1 of 3 latent factors or clusters (A, B, or C). In all of the models, the individual personality disorders were allowed to be an indicator for only a single latent cluster, and errors were not allowed to correlate with each other. In turn, these 3 clusters were viewed as comprising a single higher-order '' Axis II personality disorder factor.'' The DSM-IV model was largely invariant across gender, Axis I comorbidity, and treatment-seeking status. A dimensionally based form of assessment of the DSM-IV personality disorders produced excellent goodness-of-fit indicators and produced low Akaike information criterion values (which are indicative of better-fitting models). Conclusions: The results from this confirmatory factor analysis in a large, nationally representative mental health survey supported the DSM-IV hierarchical organization of Axis II personality disorders. This model was significantly superior to viable alternative models of Axis II personality psychopathology. There was also evidence to suggest this model could obtain even stronger support if a dimensionally based form of diagnostic assessment was adopted in place of the dichotomous form of assessment (presence/absence) of personality disorders currently in use in the DSM-IV. C1 [Cox, Brian J.; Sareen, Jitender; Enns, Murray W.] Univ Manitoba, Dept Psychiat, Winnipeg, MB R3T 2N2, Canada. [Cox, Brian J.; Sareen, Jitender; Enns, Murray W.] Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3T 2N2, Canada. [Cox, Brian J.; Clara, Ian] Univ Manitoba, Dept Psychol, Winnipeg, MB R3T 2N2, Canada. [Grant, Bridget F.] NIAAA, Div Intramural Clin & Biol Res, NIH, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. RP Cox, BJ (reprint author), PsycHlth Ctr PZ 430, 771 Bannatyne Ave, Winnipeg, MB R3E 3N4, Canada. EM coxbj@cc.umunitoba.ca NR 37 TC 8 Z9 8 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2007 VL 68 IS 12 BP 1913 EP 1920 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 246ZC UT WOS:000252045900012 PM 18162023 ER PT J AU Wang, PS Schneeweiss, S Setoguchi, S Patrick, A Avorn, J Mogun, H Choudhry, NK Brookhart, MA AF Wang, Philip S. Schneeweiss, Sebastian Setoguchi, Soko Patrick, Amanda Avorn, Jerry Mogun, Helen Choudhry, Niteesh K. Brookhart, M. Alan TI Ventricular arrhythmias and cerebrovascular events in the elderly using conventional and atypical antipsychotic medications SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID CARDIAC-ARREST; RISK; DEATH; DRUGS; THIORIDAZINE; DEMENTIA C1 NIMH, Div Serv Intervent Res, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. RP Wang, PS (reprint author), NIMH, Div Serv Intervent Res, Bethesda, MD 20892 USA. EM wangphi@mail.nih.gov RI Schneeweiss, Sebastian/C-2125-2013 FU NIA NIH HHS [K25 AG027400]; NIMH NIH HHS [R01 MH 069772] NR 18 TC 26 Z9 26 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2007 VL 27 IS 6 BP 707 EP 710 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 234RO UT WOS:000251181600024 PM 18004143 ER PT J AU Bratincsak, A McMullen, D Miyake, S Toth, ZE Hallenbeck, JM Palkovits, M AF Bratincsak, Andras McMullen, David Miyake, Shinichi Toth, Zsuzsanna E. Hallenbeck, John M. Palkovits, Miklos TI Spatial and temporal activation of brain regions in hibernation: c-fos expression during the hibernation bout in thirteen-lined ground squirrel SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE hibernation bout; thermoregulation; c-fos; choroid plexus; ependyma; tanycytes; preoptic nucleus ID SUPRACHIASMATIC NUCLEUS; GENE-EXPRESSION; MESSENGER-RNA; AROUSAL; SYSTEM; SLEEP; CYCLE; RHYTHMS; RAT; RECEPTORS AB Hibernation results in dramatic changes in body temperature and metabolism; however, the central nervous system remains active during deep torpor. By cloning c-fos cDNA from the 13-lined ground squirrel (Spermophilus tridecemlineatus) and using squirrel c-fos mRNA probe for in situ hybridization histochemistry, we systematically analyzed and identified specific brain regions that were activated during six different phases of the hibernation bout. During entrance into torpor, we detected activation of the ventrolateral subdivision of the medial preoptic area ('thermoregulatory center'), and the reticular thalamic nucleus, which is known to inhibit the somatomotor cortex. During torpor, c-fos expression in the cortex was suppressed while the reticular thalamic nucleus remained uniformly active. Throughout torpor the suprachiasmatic nucleus ('biological clock') showed increasing activity, likely participating in phase-change regulation of the hibernation bout. Interestingly, during torpor very strong c-fos activation was seen in the epithelial cells of the choroid plexus and in tanycytes at the third ventricle, both peaking near the beginning of arousal. In arousal, activity of the suprachiasmatic and reticular thalamic nuclei and choroid epithelial cells diminished, while ependymal cells in the lateral and fourth ventricles showed stronger activity. Increasing body temperature during arousal was driven by the activation of neurons in the medial part of the preoptic area. In interbout awake animals, we demonstrated the activation of hypothalamic neurons located in the arcuate nucleus and the dorsolateral hypothalamus, areas involved in food intake. Our observations indicate that the hibernation bout is closely regulated and orchestrated by specific regions of the central nervous system. C1 NIMH, LOG, NIH, Washington, DC 20009 USA. Semmelweis Univ, Neuromorphol Lab, H-1094 Budapest, Hungary. Natl Inst Neurol Disorders & Stroke, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Bratincsak, A (reprint author), NIMH, LOG, NIH, 9000 Rockville Pike,Bldg 49 Rm 5C84, Washington, DC 20009 USA. EM bratiandris@yahoo.com RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU Intramural NIH HHS [Z01 NS002856-17] NR 43 TC 18 Z9 18 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 1 PY 2007 VL 505 IS 4 BP 443 EP 458 DI 10.1002/cne.21507 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 224FP UT WOS:000250433200008 PM 17912746 ER PT J AU Fay, MP Kim, HJ Hachey, M AF Fay, Michael P. Kim, Hyune-Ju Hachey, Mark TI On using truncated sequential probability ratio test boundaries for Monte Carlo implementation of hypothesis tests SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS LA English DT Article DE B-value; bootstrap; permutation; resampling risk; sequential design; sequential probability ratio test ID P-VALUES; PERMUTATION; PARAMETER AB When designing programs or software for the implementation of Monte Carlo (MC) hypothesis tests, we can save computation time by using sequential stopping boundaries. Such boundaries imply stopping resampling after relatively few replications if the early replications indicate a very large or a very small p value. We study a truncated sequential probability ratio test (SPRT) boundary and provide a tractable algorithm to implement it. We review two properties desired of any MC p value, the validity of the p value and a small resampling risk, where resampling risk is the probability that the accept/reject decision will be different than the decision from complete enumeration. We show how the algorithm can be used to calculate a valid p value and confidence intervals for any truncated SPRT boundary. We show that a class of SPRT boundaries is minimax with respect to resampling risk and recommend a truncated version of boundaries in that class by comparing their resampling risk (RR) to the RR of fixed boundaries with the same maximum resample size. We study the lack of validity of some simple estimators of p values and offer a new, simple valid p value for the recommended truncated SPRT boundary. We explore the use of these methods in a practical example and provide the MChtest R package to perform the methods. C1 [Fay, Michael P.] NIAID, Bethesda, MD 20892 USA. [Kim, Hyune-Ju] Syracuse Univ, Dept Math, Syracuse, NY 13244 USA. [Hachey, Mark] Informat Management Serv Inc, Silver Spring, MD 20904 USA. RP Fay, MP (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mfay@niaid.nih.gov; hjkim@syr.edu; HacheyM@imsweb.com OI Fay, Michael P./0000-0002-8643-9625 FU Intramural NIH HHS [Z99 AI999999] NR 23 TC 13 Z9 13 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1061-8600 EI 1537-2715 J9 J COMPUT GRAPH STAT JI J. Comput. Graph. Stat. PD DEC PY 2007 VL 16 IS 4 BP 946 EP 967 DI 10.1198/106186007X257025 PG 22 WC Statistics & Probability SC Mathematics GA 246MG UT WOS:000252010500010 PM 18633453 ER PT J AU Tanofsky-Kraff, M Goossens, L Eddy, KT Ringham, R Goldschmidt, A Yanovski, SZ Braet, C Marcus, MD Wilfley, DE Olsen, C Yanovski, JA AF Tanofsky-Kraff, Marian Goossens, Lien Eddy, Kamryn T. Ringham, Rebecca Goldschmidt, Andrea Yanovski, Susan Z. Braet, Caroline Marcus, Marsha D. Wilfley, Denise E. Olsen, Cara Yanovski, Jack A. TI A multisite investigation of binge eating behaviors in children and adolescents SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE binge eating; loss of control eating; children; adolescents ID WEIGHT-LOSS TREATMENT; BODY-MASS INDEX; DISORDER EXAMINATION; OVERWEIGHT CHILDREN; SELF-REPORT; FEMALE ADOLESCENTS; CHILDHOOD OBESITY; UNITED-STATES; ADULT OBESITY; RISK-FACTORS AB The phenomenology of childhood and adolescent loss of control (LOC) eating is unknown. The authors interviewed 445 youths to assess aspects of aberrant eating. LOC was associated with eating forbidden food before the episode; eating when not hungry; eating alone; and experiencing secrecy, negative emotions, and a sense of "numbing" while eating (ps <.01). Hierarchical cluster analysis revealed a subgroup, most of whom reported LOC eating. Cluster members reported having a trigger initiate episodes, eating while watching television, and having decreased awareness regarding the amount consumed. The authors conclude that aspects of LOC eating during youth are similar to aspects of adult episodes, but a youth-specific presentation may exist. Findings may provide an intervening point to prevent excessive weight gain and eating disorders. C1 [Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Physiol, Bethesda, MD 20814 USA. [Tanofsky-Kraff, Marian; Yanovski, Susan Z.; Yanovski, Jack A.] NICHHD, Unit Growth & Obes, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Goossens, Lien; Braet, Caroline] Univ Ghent, Dept Dev Personal & Social Psychol, B-9000 Ghent, Belgium. [Eddy, Kamryn T.] Boston Univ, Childrens Hosp Boston, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Ringham, Rebecca; Marcus, Marsha D.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. [Goldschmidt, Andrea; Wilfley, Denise E.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63130 USA. [Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Olsen, Cara] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Physiol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM mtanofsky@usuhs.mil RI Goldschmidt, Andrea/B-2951-2008; OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NHLBI NIH HHS [T32 HL007456]; NICHD NIH HHS [R01 HD038425, HD38425, R01 HD036904, Z01 HD-00641, Z01 HD000641]; NIDDK NIH HHS [DK46204, P30 DK046204]; NIMH NIH HHS [5F31MH071019, F31 MH071019, K24 MH070446] NR 94 TC 71 Z9 71 U1 12 U2 29 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2007 VL 75 IS 6 BP 901 EP 913 DI 10.1037/0022-006X.75.6.901 PG 13 WC Psychology, Clinical SC Psychology GA 241BD UT WOS:000251631000007 PM 18085907 ER PT J AU Tian, J Atkinson, NL Portnoy, B Gold, RS AF Tian, Jing Atkinson, Nancy L. Portnoy, Barry Gold, Robert S. TI A systematic review of evaluation in formal Continuing Medical Education SO JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS LA English DT Review DE continuing; education; medical; literature review; evaluation studies; randomized controlled trial ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PHYSICIANS; LOW-BACK-PAIN; HEALTH-CARE; GENERAL-PRACTITIONERS; CONSOLIDATION WORKSHOPS; COMMUNICATION-SKILLS; TRAINING-PROGRAM; CANCER; OUTCOMES AB Introduction: Physicians spend a considerable amount of time in Continuing Medical Education (CME) to maintain their medical licenses. CME evaluation studies vary greatly in evaluation methods, levels of evaluation, and length of follow-up. Standards for CME evaluation are needed to enable comparison among different studies and to detect factors influencing CME evaluation. Methods: A review of the CME evaluation literature was conducted on primary research studies published from January 2000 to January 2006. Studies assessing only satisfaction with CME were excluded, as were studies where fewer than 50% of the participants were practicing physicians. Thirty-two studies were included in the analyses. Determinations were made about evaluation methods, outcome measures, and follow-up assessment. Results: Only 2 of 32 reviewed studies addressed all evaluation levels: physician changes in knowledge and attitudes (level 2), practices (level 3), and improved patient health status (level 4). None of the studies using self-developed instruments (n = 10) provided reliability and validity information. Only 6 studies used validated scales. Twenty studies had a follow-up period of 6 months or less, and 11 had a follow-up period between 1 and 2 years. Discussion: A gold standard for evaluating the effectiveness of CME would include assessment of all 4 levels of evaluation. A valid, reliable, and adaptable CME evaluation questionnaire addressing variables in the second level is needed to allow comparison of effectiveness across CME interventions. A minimum 1-year postintervention follow-up period may also be indicated to investigate the sustainability of intervention outcomes. C1 Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. Univ Maryland, Publ Hlth Informat Res Lab, College Pk, MD 20742 USA. NIH, Off Dis Prevent, Off Director, Rockville, MD USA. Univ Maryland, Coll Hlth & Human Performance, College Pk, MD 20742 USA. RP Tian, J (reprint author), Univ Maryland, Dept Publ & Community Hlth, Suite 2387 Valley Dr, College Pk, MD 20742 USA. EM tianjing@umd.edu NR 48 TC 44 Z9 47 U1 2 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1912 J9 J CONTIN EDUC HEALTH JI J. Contin. Educ. Health Prof. PD WIN PY 2007 VL 27 IS 1 BP 16 EP 27 DI 10.1002/chp.089 PG 12 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 152EP UT WOS:000245344100003 PM 17385741 ER PT J AU Nowjack-Raymer, RE Sheiham, A AF Nowjack-Raymer, R. E. Sheiham, A. TI Numbers of natural teeth, diet, and nutritional status in US adults SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE teeth; diet; nutrition; vitamins; health disparities ID NUTRIENT INTAKE; ORAL-HEALTH; NATIONAL-HEALTH; AMERICAN DIET; UNITED-STATES; DENTAL STATUS; FOOD; VEGETABLES; IMPACT; FRUIT AB Evidence that dental status affects diet is equivocal. The hypothesis of this study was that diet was affected by dental status. The objective was to assess the relationship between numbers of teeth and diet and nutritional status in US adult civilians without prostheses. We examined 6985 NHANES (1988-1994) participants. Data included socio-economics, demographics, dental status, and diet and nutritional status. Dietary data were obtained from food frequency questionnaires and 24-hour dietary recall. Serum levels of beta carotene, folate, and vitamin C were measured with isocratic high-performance liquid chromatography. The population was classified by numbers of teeth. Covariance and Satterthwaite F-adjusted statistical comparisons were made between tooth groupings and the fully dentate population. Multilinear regression models adjusted for covariates. People with fewer than 28 teeth had significantly lower intakes of carrots, tossed salads, and dietary fiber than did fully dentate people, and lower serum levels for beta carotene, folate, and vitamin C. Dental status significantly affects diet and nutrition. C1 Natl Inst Dent & Craniofacial Res, Hlth Disparities Res Program, Clin Res Ctr, NIH DHHS, Bethesda, MD 20892 USA. UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England. RP Nowjack-Raymer, RE (reprint author), Natl Inst Dent & Craniofacial Res, Hlth Disparities Res Program, Clin Res Ctr, NIH DHHS, 45 Ctr Dr,Room 4AS-43F, Bethesda, MD 20892 USA. EM Ruth.Nowjack-Raymer@nih.gov NR 32 TC 60 Z9 64 U1 7 U2 20 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2007 VL 86 IS 12 BP 1171 EP 1175 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 234JI UT WOS:000251157000005 PM 18037650 ER PT J AU Neiderhiser, JA Reiss, D Lichtenstein, P Spotts, EL Ganiban, J AF Neiderhiser, Jenae A. Reiss, David Lichtenstein, Paul Spotts, Erica L. Ganiban, Jody TI Father-adolescent relationships and the role of genotype-environment correlation SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE parenting; genotype-environment correlation; twins; family ID DEVELOPMENTAL PSYCHOPATHOLOGY; ANTISOCIAL-BEHAVIOR; CHILD RELATIONSHIPS; FAMILY ENVIRONMENT; TWIN ZYGOSITY; MOTHER-CHILD; PARENT; ADJUSTMENT; INTERPLAY; SYMPTOMS AB This study uses 2 samples of adolescents and parents-the child-based Nonshared Environment in Adolescent Development project (NEAD; D. Reiss, J. M. Neiderhiser, E. Hetherington, & R. Plomin, 2000; N = 395 families) and the parent-based Twin and Offspring Study in Sweden (TOSS; N = 909 twin family pairs)-to investigate passive and evocative genotype-environment correlation (rGE) on fathering. Both samples used the same measures of positivity, negativity, control, and monitoring. A previous report examining mothering found evidence for passive rGE for positivity and monitoring, and evocative rGE for negativity and control, although both types of rGE were suggested in many cases. The current report focuses on fathering. Father reports of positivity and control are influenced by evocative rGE, whereas father reports of negativity and monitoring are influenced by both passive and evocative rGE. Adolescent reports of father's positivity and negativity were influenced by both evocative and passive rGE, and control and monitoring by passive rGE. The most notable difference in findings for fathers and mothers is for positivity and the presence of rGE for father's control and monitoring. These findings and their implications are discussed. C1 [Neiderhiser, Jenae A.; Reiss, David] George Washington Univ, Ctr Family Res, Washington, DC 20052 USA. [Lichtenstein, Paul] Karolinska Inst, Stockholm, Sweden. [Spotts, Erica L.] NIA, Behav & Social Res Program, Bethesda, MD 20892 USA. [Ganiban, Jody] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. RP Neiderhiser, JA (reprint author), Penn State Univ, Dept Psychol, 222 Moore Bldg, University Pk, PA 16802 USA. EM jenaemn@psu.edu OI lichtenstein, paul/0000-0003-3037-5287 NR 65 TC 51 Z9 53 U1 2 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD DEC PY 2007 VL 21 IS 4 BP 560 EP 571 DI 10.1037/0893-3200.21.4.560 PG 12 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 243BY UT WOS:000251771100002 PM 18179328 ER PT J AU Chan, PC Fu, PP AF Chan, Po-Chuen Fu, Peter P. TI Toxicity of Panax genseng - An herbal medicine and dietary supplement SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE ginseng dietary supplement; NTP; chronic tumorigenicity bioassay ID GINSENG EXTRACT G115; ST-JOHNS-WORT; IN-VITRO; DIGESTIVE-TRACT; EMBRYO CULTURE; RED-GINSENG; CELLS; GINSENOSIDES; RATS; SAPONINS AB Ginseng is one of the most popular herbal dietary supplements in the U.S. market, with five to six million persons using it even before the recent boom in the herbal supplement industry. Ginsana (G115 ginseng), a standardized extract of Panax ginseng (Asian ginseng, also called Chinese or Korean ginseng) controls half of this market. Numerous reports of adverse effects from products containing ginseng have been filed with the U.S. Food and Drug Administration (FDA). The literature also documents "ginseng abuse syndrome" among regular users. The chronic effects of ginseng are not well characterized. Because of its significant human exposure and little information on toxicity is available, Panax ginseng has been nominated by the U.S. National Institutes of Health (NIH) to the U.S. National Toxicology Program (NTP) for assessing its carcinogenic potential. In this review, we discuss the environmental occurrence, purported therapeutic effects, biological effects, and toxicity of ginseng, with focus on Panax ginseng. To demonstrate how NTP chronic tumorigenicity bioassays are conducted, the tumorigenicity bioassay of Panax ginseng is detailed described. C1 [Chan, Po-Chuen] NIEHS, Res Triangle Pk, NC 27709 USA. [Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chan, PC (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM chanp@niehs.nih.gov; peter.fu@fda.hhs.gov NR 76 TC 7 Z9 7 U1 2 U2 18 PU BUREAU FOOD DRUG ANALYSIS PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2007 VL 15 IS 4 BP 416 EP 427 PG 12 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 252GS UT WOS:000252435600010 ER PT J AU Papavramidou, N Fee, E Christopoulou-Aletra, H AF Papavramidou, Niki Fee, Elizabeth Christopoulou-Aletra, Helen TI Jaundice in the Hippocratic Corpus SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 6th World Congress of the HepatoPancreato-Billiary-Association CY JUN, 2004 CL Washington, DC SP Hepato Pancreato Billiary Assoc DE Icterus; Hippocratic Corpus; history of liver diseases; ancient medicine AB The Hippocratic physicians were among the first who described jaundice ( icterus). The Hippocratic Corpus has numerous appearances of the condition, where its etiology, description, prognosis, and treatment are provided. The connection made between the liver and jaundice was remarkable, bearing in mind that the Hippocratic physicians had not performed dissections and that their medical views were based on observation. The Hippocratic doctors described five kinds of jaundice. The etiology was, as in most cases of diseases mentioned in the Hippocratic Corpus, "humoral" imbalance. The diagnosis and prognosis were based on the color of the skin, the urine, the feces, and several other factors, such as the season of the year during which the disease first appeared or the coexisting diseases. The treatment, finally, consisted of herbal medications, baths, diet, and blood-letting, depending on the type of jaundice in question. Finally, an attempt is made to correlate modern diseases with the Hippocratic types of jaundice. C1 Aristotle Univ Thessaloniki, Sch Med, Hist Med Div, GR-54006 Thessaloniki, Greece. Natl Lib Med, Hist Med Div, Natl Inst Hlth, Bethesda, MD 20894 USA. RP Papavramidou, N (reprint author), 30 Koritsas St, Thessaloniki, Greece. EM papavramidou@hotmail.com NR 2 TC 5 Z9 6 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD DEC PY 2007 VL 11 IS 12 BP 1728 EP 1731 DI 10.1007/s11605-007-0281-1 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 231BW UT WOS:000250922500027 PM 17896166 ER PT J AU Shackelton, LA Hoelzer, K Parrish, CR Holmes, EC AF Shackelton, Laura A. Hoelzer, Karin Parrish, Colin R. Holmes, Edward C. TI Comparative analysis reveals frequent recombination in the parvoviruses SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID PORCINE PARVOVIRUS; ALEUTIAN DISEASE; EXPERIMENTAL-INFECTION; VIRUS-INFECTION; MINK; PERSISTENT; IDENTIFICATION; REPLICATION; B19; MUSCLE AB Parvoviruses are small single-stranded DNA viruses that are ubiquitous in nature. Infections with both autonomous and helper-virus dependent parvoviruses are common in both human and animal populations, and many animals are host to a number of different parvoviral species. Despite the epidemiological importance of parvoviruses, the presence and role of genome recombination within or among parvoviral species has not been well characterized. Here we show that natural recombination may be widespread in these viruses. Different genome regions of both porcine parvoviruses and Aleutian mink disease viruses have conflicting phylogenetic histories, providing evidence for recombination within each of these two species. Further, the rodent parvoviruses show complex evolutionary histories for separate genomic regions, suggesting recombination at the interspecies level. C1 [Shackelton, Laura A.; Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. [Hoelzer, Karin; Parrish, Colin R.] Cornell Univ, Coll Vet Med, JA Baker Inst, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. [Holmes, Edward C.] NIH, Fogarty Intl Ctr, Bethesda, MD 20892 USA. RP Shackelton, LA (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. EM las53@psu.edu RI Hoelzer, Karin/A-8230-2010; OI Holmes, Edward/0000-0001-9596-3552 FU NIGMS NIH HHS [GM080533-01, R01 GM080533, R01 GM080533-01] NR 41 TC 55 Z9 60 U1 0 U2 9 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 2007 VL 88 BP 3294 EP 3301 DI 10.1099/vir.0.83255-0 PN 12 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 240WS UT WOS:000251619500011 PM 18024898 ER PT J AU Aaskov, J Buzacott, K Field, E Lowry, K Berlioz-Arthaud, A Holmes, EC AF Aaskov, John Buzacott, Katie Field, Emma Lowry, Kym Berlioz-Arthaud, Alain Holmes, Edward C. TI Multiple recombinant dengue type 1 viruses in an isolate from a dengue patient SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HEPATITIS-C-VIRUS; NATURAL-POPULATIONS; FLAVIVIRUS VACCINES; POLIOVIRUS; TRANSMISSION; EMERGENCE; EVOLUTION; POLYMERASE; MECHANISMS; SEROTYPE-3 AB Between 2000 and 2004, dengue virus type 1 (DENV-1) genotypes I and 11 from Asia were introduced into the Pacific region and co-circulated in some localities. Envelope protein gene sequences of DENV-1 from 12 patients infected on the island of New Caledonia were obtained, five of which carried genotype I viruses and six, genotype 11 viruses. One patient harboured a mixed infection, containing viruses assigned to both genotypes I and 11, as well as a number of inter-genotypic recombinants. This is the first report of a population of dengue viruses isolated from a patient containing both parental and recombinant viruses. C1 [Aaskov, John; Buzacott, Katie; Field, Emma; Lowry, Kym] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia. [Berlioz-Arthaud, Alain] Inst Pasteur, Noumea, New Caledonia. [Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Intl Ctr, Bethesda, MD 20892 USA. RP Aaskov, J (reprint author), Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia. EM j.aaskov@qut.edu.au OI Holmes, Edward/0000-0001-9596-3552 FU Wellcome Trust NR 40 TC 33 Z9 34 U1 1 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 2007 VL 88 BP 3334 EP 3340 DI 10.1099/vir.0.83122-0 PN 12 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 240WS UT WOS:000251619500016 PM 18024903 ER PT J AU Maurer, JR Ryu, J Beck, G Moss, J Lee, JC Finlay, G Brown, K Chapman, J McMahan, J Olson, E Ruoss, S Sherer, S AF Maurer, Janet R. Ryu, Jay Beck, Gerald Moss, Joel Lee, Jar-Chi Finlay, Geraldine Brown, Kevin Chapman, Jeffrey McMahan, June Olson, Eric Ruoss, Stephen Sherer, Susan CA Natl Heart Lung Blood Inst LAM Reg TI Lung transplantation in the management of patients with lymphangioleiomyomatosis: Baseline data from the NHLBI LAM registry SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID PULMONARY LYMPHANGIOLEIOMYOMATOSIS AB Background: In 1997, the National Heart, Lung, and Blood Institute of the National Institutes of Health established a Registry to better characterize the demographic, clinical, physiologic and radiographic features of patients with lymphangioleiomyomatosis (LAM). Herein we report data collected at enrollment from patients who had either undergone transplant prior to enrollment, underwent transplant during the 5-year study, or were evaluated/wait-listed for lung transplant during the 5-year study. Methods: The LAM Registry enrolled patients from six clinical centers between August 1998 and October 2001. On entry, patients filled-out questionnaires covering their medical history, symptoms, treatment and quality of life (SF-36 and St. George's Respiratory Questionnaire). Enrollees underwent blood laboratory work and testing for arterial blood gases and pulmonary function. Follow-up was done at 6-month and/or yearly intervals. Diagnoses were confirmed by biopsy or typical clinical presentation plus computerized tomography (CT) findings confirmed by independent expert radiologists. A total of 243 women were enrolled. Of these, 13 (5.3%) had been transplanted at time of entry (Group A), 21 (8.6%) were transplanted during the study (Group B), and 48 (19.8%) were either wait-listed for transplant or underwent evaluation after enrollment during the study period (Group C). The remaining 161 (66.3%) registrants were neither considered for nor listed for transplant during the Registry period (Group D). Results: One-third of patients in a large sample of LAM patients had either been transplanted or were being considered for transplant. At enrollment, patients who had already been transplanted and those not in need of transplant (Groups A and D) had better pulmonary function and quality-of-life scores compared l with patients who subsequently underwent lung transplant during the Registry period (Group B). Conclusions: In this large Registry of LAM patients, lung transplantation appears to be associated both with significantly improved lung function and quality of life compared with patients with advanced disease. J Heart Lung Transplant 2007;26:1293-9. Copyright (c) 2007 by the International Society for Heart and Lung Transplantation. C1 [Maurer, Janet R.] Hlth Dialog Inc, Provider Serv & Coaching Ctr, Scottsdale, AZ USA. [Ryu, Jay; Olson, Eric] Div Pulm & Crit Care Med, Mayo Clin, Rochester, MN USA. [Beck, Gerald; Lee, Jar-Chi; McMahan, June; Sherer, Susan] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Moss, Joel] NIH, NHLBI, Bethesda, MD 20892 USA. [Finlay, Geraldine] Tufts Univ New England Med Ctr, Boston, MA USA. [Brown, Kevin] Natl Jewish Ct, Pulm Sci & Crit Care Med, Denver, CO USA. [Chapman, Jeffrey] Dept Pulm Allergy & Crit Care, Dept Pulm, Cleveland Clin Fdn, Cleveland, OH USA. [Ruoss, Stephen] Stanford Univ, Med Ctr, Div Pulm & Crit Care Med, Palo Alto, CA USA. RP Maurer, JR (reprint author), Hlth Dialog Inc, 16425 N Pima Rd, Scottsdale, AZ 85260 USA. EM maurerj99@msn.com FU Intramural NIH HHS [Z01 HL002541-12]; NHLBI NIH HHS [U01 HL58440, U01 HL058440, U01 HL058440-04, U01 HL058440-03, U01 HL058440-05] NR 9 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 2007 VL 26 IS 12 BP 1293 EP 1299 DI 10.1016/j.healun.2007.09.013 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 246FS UT WOS:000251993500010 PM 18096481 ER PT J AU Shata, MT Barrett, A Shire, NJ Abdelwahab, SF Sobhy, M Daef, E El-Kamary, SS Hashem, M Engle, RE Purcell, RH Emerson, SU Strickland, GT Sherman, KE AF Shata, M. T. Barrett, A. Shire, N. J. Abdelwahab, S. F. Sobhy, M. Daef, E. El-Kamary, S. S. Hashem, M. Engle, R. E. Purcell, R. H. Emerson, S. U. Strickland, G. T. Sherman, K. E. TI Characterization of hepatitis E-specific cell-mediated immune response using IFN-gamma ELISPOT assay SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article; Proceedings Paper CT 12th International Symposium on Viral Hepatitis and Liver Disease CY JUL 01-05, 2006 CL Paris, FRANCE SP Pan Amer Soc Clin Virol, European Soc Clin Virol DE HEV; ELISPOT; immunity; hepatitis E; cell-mediated; diagnosis ID LINKED-IMMUNOSORBENT-ASSAY; IMMUNOGLOBULIN-M ANTIBODIES; RURAL EGYPTIAN COMMUNITIES; T-LYMPHOCYTE RESPONSES; ACUTE VIRAL-HEPATITIS; E VIRUS HEV; BLOOD-DONORS; ENZYME-IMMUNOASSAY; DETECTABLE VIREMIA; C VIRUS AB in developing countries, hepatitis E (HEV) and hepatitis A (HAV) are the major causes of acute viral hepatitis with similar feco-oral modes of transmission. In contrast to the high seroprevalence of hepatitis A infection, a low seroprevalence of HEV among children in endemic areas has been reported. These data suggest the possibility that silent HEV infection is undiagnosed by the current available methods. Many of the serological tests used for HEV diagnosis have poor specificity and are unable to differentiate among different genotypes of HEV Moreover, the RT-PCR used for HEV isolation is only valid for a brief period during the acute stage of infection. Cell-mediated immune (CMI) responses are highly sensitive, and long lasting after sub-clinical infections as shown in HCV and HIV. Our objective was to develop a quantitative assay for cell-mediated immune (CMI) responses in HEV infection as a surrogate marker for HEV exposure in silent infection. Quantitative assessment of the CMI responses in HEV will also help us to evaluate the role of CMI in HEV morbidity. In this study, an HEV-specific interferon-gamma (IFN-gamma) ELISPOT assay was optimized to analyze HEV-specific CMI responses. We used peripheral blood mononuclear cells (PBMC) and sera from experimentally infected chimpanzees and from seroconverted and control human subjects to validate the assay. The HEV-specific IFNI-gamma ELISPOT responses correlated strongly and significantly with anti-HEV ELISA positive/negative results (rho=0.73, p=0.02). Moreover, fine specificities of HEV-specific T cell responses could be identified using overlapping HEV ORF2 peptides. (C) 2007 Elsevier B.V. All rights reserved. C1 Univ Cincinnati, Med Ctr, Div Digest Dis, Dept Internal Med,Viral Immunol Lab, Cincinnati, OH 45267 USA. Univ Maryland, Int Hlth Div, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NIH, NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Shata, MT (reprint author), Univ Cincinnati, Med Ctr, Div Digest Dis, Dept Internal Med,Viral Immunol Lab, MSB 6360,231 Albert B Sabin Way,POB 670595, Cincinnati, OH 45267 USA. EM mohamed.shata@uc.edu RI Abdelwahab, Sayed/P-1481-2016 OI Abdelwahab, Sayed/0000-0002-9636-7485 FU Intramural NIH HHS; NIAID NIH HHS [R21 AI067868, U01 AI058372]; NIDDK NIH HHS [K24 DK070528]; Wellcome Trust [059113/Z/99/A, 059113/Z/99/Z] NR 58 TC 24 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 1 PY 2007 VL 328 IS 1-2 BP 152 EP 161 DI 10.1016/j.jim.2007.08.014 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 239AV UT WOS:000251490900016 PM 17905301 ER PT J AU Kamala, T AF Kamala, T. TI Hock immunization: A humane alternative to mouse footpad injections SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE footpad immunization; alternative; hock immunization; CFA; IACUC regulations; immune response ID LINKED GENETIC-CONTROL; LYMPH-NODE ASSAY; IMMUNE-RESPONSE; POPLITEAL LYMPH; T-CELLS; E-ALPHA; MICE; OVALBUMIN; RESPONSIVENESS; RECOGNITION AB Footpad injection is a commonly used immunization method in mice. Being relatively easy to do with well-characterized lymphatic drainage, it has become a very useful immunization protocol to study local immune responses in draining lymph nodes. However, its disadvantages include use of only hind feet as a routine site of immunization since mice use their fore feet for food handling, and exacerbation of inflammation and swelling at the injection site leading to unrelieved pain and distress since feet are weight-bearing structures. With increasingly stringent Institutional guidelines for animal manipulations, there is increasing need for more humane protocols. A novel immunization protocol involving injection into the hock, the lateral tarsal region just above the ankle, a non-weight bearing structure draining to the same lymph node as the footpad, retains the advantages of footpad immunization without its drawbacks. This study, comparing immune responses between footpad and hock immunization in six different inbred mouse strains to two different protein antigens and a heat-killed bacterium, shows that hock immunization is a better alternative to footpad immunization, inducing comparable immune responses and being considerably more humane. (C) 2007 Elsevier B.V. All rights reserved. C1 NIH, NIAID, LCMI, Bethesda, MD 20892 USA. RP Kamala, T (reprint author), NIH, NIAID, LCMI, Blgd 4,Room 3,9000 Rockvill Pike, Bethesda, MD 20892 USA. EM tkamala@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000581-19] NR 31 TC 34 Z9 37 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 1 PY 2007 VL 328 IS 1-2 BP 204 EP 214 DI 10.1016/j.jim.2007.08.004 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 239AV UT WOS:000251490900022 PM 17804011 ER PT J AU Ohta, A Lukashev, D Jackson, EK Fredholm, BB Sitkovsky, M AF Ohta, Akio Lukashev, Dmitriy Jackson, Edwin K. Fredholm, Bertil B. Sitkovsky, Michail TI 1,3,7-trimethylxanthine (Caffeine) may exacerbate acute inflammatory liver injury by weakening the physiological immunosuppressive mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID A-INDUCED HEPATITIS; A(2A) ADENOSINE RECEPTORS; CONCANAVALIN-A; T-CELLS; IMMUNE-RESPONSE; MICE; COFFEE; ACTIVATION; CIRRHOSIS; INHIBITION AB The genetic elimination of A2A adenosine receptors (A2AR) was shown to disengage the critical immunosuppressive mechanism and cause the dramatic exacerbation of acute inflammatory tissue damage by T cells and myeloid cells. This prompted the evaluation of the proinflammatory vs the anti-inflammatory effects of the widely consumed behavioral drug caffeine, as the psychoactive effects of caffeine are mediated largely by its antagonistic action on A2AR in the brain. Because caffeine has other biochemical targets besides A2AR, it was important to test whether the consumption of caffeine during an acute inflammation episode would lead to the exacerbation of immune-mediated tissue damage. We examined acute and chronic treatment with caffeine for its effects on acute liver inflammation. It is shown that caffeine at lower doses (10 and 20 mg/kg) strongly exacerbated acute liver damage and increased levels of proinflammatory cytokines. Because caffeine did not enhance liver damage in A2AR-deficient mice, we suggest that the potentiation of liver inflammation was mediated by interference with the A2AR-mediated tissue-protecting mechanism. In contrast, a high dose of caffeine (100 mg/kg) completely blocked both liver damage and proinflammatory cytokine responses through an A2AR-independent mechanism. Furthermore, caffeine administration exacerbated liver damage even when mice consumed caffeine chronically, although the extent of exacerbation was less than in "naive" mice that did not consume caffeine before. This study suggests an unappreciated "man-made" immunological pathogenesis whereby consumption of the food-, beverage-, and medication-derived adenosine receptor antagonists may modify an individual's inflammatory status and lead to excessive organ damage during acute inflammation. C1 Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. NIH, NIAID, Immunol Lab, Bethesda, MD 20892 USA. Univ Pittsburgh, Ctr Clin Pharmacol, Pittsburgh, PA 15261 USA. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. RP Ohta, A (reprint author), Northeastern Univ, New England Inflammat & Tissue Protect Inst, 360 Huntington Ave,113 Mugar Hlth Sci Bldg, Boston, MA 02115 USA. EM a.ohta@neu.edu RI Lukashev, Dmitriy/F-8133-2010 FU Intramural NIH HHS; NCCIH NIH HHS [AT002788]; NCI NIH HHS [CA111985, CA112561] NR 55 TC 37 Z9 37 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2007 VL 179 IS 11 BP 7431 EP 7438 PG 8 WC Immunology SC Immunology GA 237MK UT WOS:000251378300030 PM 18025187 ER PT J AU Chattopadhyay, G Khan, AQ Sen, G Colino, J Dubois, W Rubtsov, A Torres, RM Potter, M Snapper, CM AF Chattopadhyay, Gouri Khan, Abdul Q. Sen, Goutam Colino, Jesus duBois, Wendy Rubtsov, Anatoly Torres, Raul M. Potter, Michael Snapper, Clifford M. TI Transgenic expression of BCl-X-L or bcl-2 by murine B cells enhances the in vivo antipolysaccharide, but not antiprotein, response to intact Streptococcus pneumoniae SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FAS-MEDIATED APOPTOSIS; RECEPTOR CROSS-LINKING; IG ISOTYPE RESPONSES; MARGINAL-ZONE; GERMINAL CENTER; ANTIGEN RECEPTOR; T-CELLS; DIFFERENTIAL REGULATION; HUMORAL IMMUNITY; MICE AB IgG antipolysaccharide (PS) and antiprotein responses to Streptococcus pneumoniae (Pn) are both CD4(+) T cell dependent. However, the primary IgG anti-PS response terminates more quickly, uses a shorter period of T cell help, fails to generate memory, and is more dependent on membrane Ig (mlg) signaling. We thus determined whether this limited anti-PS response to Pn reflected a greater propensity of PS-specific B cells to undergo apoptosis. We used mice that constitutively expressed the antiapoptotic protein Bcl-x(L) or Bcl-2 as a B cell-specific transgene. Both transgenic (Tg) mice exhibited increased absolute numbers of splenic B-1 and peritoneal B-1b and B-2 cells, subsets implicated in anti-PS responses, but not in marginal zone B (MZB) cells. Both Tg mouse strains elicited, in an apparently Fas-independent manner, a more prolonged and higher peak primary IgM and IgG anti-PS, but not antiprotein, response to Pn, but without PS-specific memory. A similar effect was not observed using purified PS or pneumococcal conjugate vaccine. In vitro, both splenic MZB and follicular Tg B cells synthesized DNA at markedly higher levels than their wild-type counterparts, following mIg cross-linking. This was associated with increased clonal expansion and decreased apoptosis. Using Lsc(-/-) mice, the Pn-induced IgG response specific for the capsular PS was found to be almost entirely dependent on MZB cells. Collectively, these data suggest that apoptosis may limit mIg-dependent clonal expansion of PS-specific B cells during a primary immune response to an intact bacterium, as well as decrease the pool of PS-responding B cell subsets. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NCI, Genet Lab, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80207 USA. Natl Jewish Med & Res Ctr, Integrated Dept Immunol, Denver, CO 80207 USA. RP Snapper, CM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM csnapper@usuhs.mil FU NIAID NIH HHS [1 R01 AI49192, R01 AI052157] NR 76 TC 23 Z9 23 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 DEC 1 PY 2007 VL 179 IS 11 BP 7523 EP 7534 PG 12 WC Immunology SC Immunology GA 237MK UT WOS:000251378300040 PM 18025197 ER PT J AU Wang, HS Feng, JX Qi, CF Li, ZY Morse, HC Clarke, SH AF Wang, Hongsheng Feng, Jianxun Qi, Chen-Feng Li, Zhaoyang Morse, Herbert C., III Clarke, Stephen H. TI Transitional B cells lose their ability to receptor edit but retain their potential for positive and negative selection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID V(D)J RECOMBINASE ACTIVITY; LIGHT-CHAIN GENES; ANTIGEN-RECEPTOR; ALLELIC EXCLUSION; RAG2 EXPRESSION; BONE-MARROW; LYMPHOCYTES; MICE; TOLERANCE; ENGAGEMENT AB Ligation of B cell receptors on immature bone marrow B cells, either by an endogenous Ag or by an anti-B cell receptor Ab induces secondary V(D)J gene rearrangements, termed receptor editing. Whether the same signal induces receptor editing in transitional B cells is not clear. In this study, we examined the responses of immature and transitional B cells from V(H)12V kappa 1A Ig transgenic mice to stimulation with an anti-Ig beta Ab. Our results demonstrated that immature B cells stimulated with a low concentration of anti-Ig beta Ab, mimicking Ag stimulation, underwent receptor editing both in vivo and in vitro, as evidenced by the detection of dsDNA breaks at J kappa recombination signal sequences, whereas transitional B cells did not. The lack of dsDNA breaks in transitional B cells contrasts with their increased expression of RAG1 and RAG2, suggesting a novel mechanism that may prevent rearrangements. Furthermore, treatment of transitional B cells with high concentrations of anti-Ig beta Abs induced apoptosis, whereas low concentrations induced differentiation. Our results support the idea that transitional B cells lose the capacity to edit, but are sensitive to positive and negative selection. C1 NIH, NIAID, Immunopathol Lab, Rockville, MD 20852 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. RP Wang, HS (reprint author), NIH, NIAID, 5640 Fishers Lane, Rockville, MD 20852 USA. EM wanghongs@niaid.nih.gov; shl@med.unc.edu OI Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS; NIAID NIH HHS [AI29576, AI43587] NR 46 TC 13 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 DEC 1 PY 2007 VL 179 IS 11 BP 7544 EP 7552 PG 9 WC Immunology SC Immunology GA 237MK UT WOS:000251378300042 PM 18025199 ER PT J AU Morens, DM Fauci, AS AF Morens, David M. Fauci, Anthony S. TI Reply to Brundage and Shanks SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID INFLUENZA C1 NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, Natl Inst Hlth, 6700B Rockledge Dr Rm 3258,MSC 7630, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 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 DEC 1 PY 2007 VL 196 IS 11 BP 1718 EP 1719 DI 10.1086/522356 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 231RE UT WOS:000250965900022 ER PT J AU Shin, EC Seifert, U Urban, S Truong, KT Feinstone, SM Rice, CM Kloetzel, PM Rehermann, B AF Shin, Eui-Cheol Seifert, Ulrike Urban, Sabrina Truong, Kim-Thuy Feinstone, Stephen M. Rice, Charles M. Kloetzel, Peter-M. Rehermann, Barbara TI Proteasome activator and antigen-processing aminopeptidases are regulated by virus-induced type I interferon in the hepatitis C virus-infected liver SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID MHC CLASS-I; CELLULAR IMMUNE-RESPONSES; CD8(+) T-CELLS; VIRAL CLEARANCE; GAMMA; IMMUNOPROTEASOMES; PERSISTENCE; GENERATION; PEPTIDES; EPITOPES AB Many components of the class I antigen-processing pathway are thought to be regulated solely by interferon-gamma (IFN-gamma). Herein, we report type I IFN-mediated induction of proteasome activator (PA28) subunits alpha and beta, endoplasmic reticulum aminopeptidase 1 (ERAP1), ERAP2, and leucine aminopeptidase (LAP). This mechanism was initiated by either synthetic RNA (poly(I-C)) or by hepatitis C virus (HCV) RNA-mediated induction of type I IFN and abrogated by blocking of type I IFN. In serial liver biopsies of chimpanzees with acute HCV infection, increases in PA28 subunit and aminopeptidase mRNA levels correlated with intrahepatic type I IFN responses and preceded intrahepatic IFN-gamma responses by several weeks. Thus, viral RNA-induced type I IFN regulates the antigen-processing machinery early during viral infection and prior to IFN-gamma response. This mechanism may contribute to the high effectiveness of type I IFN-based therapies if administered early during acute HCV infection. C1 [Shin, Eui-Cheol; Truong, Kim-Thuy; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Seifert, Ulrike; Urban, Sabrina; Kloetzel, Peter-M.] Humboldt Univ, Charite, Inst Biochem, D-10117 Berlin, Germany. [Feinstone, Stephen M.] US FDA, Ctr Biol Evaluat & Res, Lab Hepatatis Viruses, Bethesda, MD 20892 USA. [Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011 FU Intramural NIH HHS; NCI NIH HHS [CA85883-01] NR 28 TC 18 Z9 18 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD DEC PY 2007 VL 27 IS 12 BP 985 EP 990 DI 10.1089/jir.2007.0039 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 248WD UT WOS:000252187000002 PM 18184038 ER PT J AU Olasz, EB Roh, J Yee, CL Arita, K Akiyama, M Shimizu, H Vogel, JC Yancey, KB AF Olasz, Edit B. Roh, Jooyoung Yee, Carole L. Arita, Ken Akiyama, Masashi Shimizu, Hiroshi Vogel, Jonathan C. Yancey, Kim B. TI Human bullous pemphigoid antigen 2 transgenic skin elicits specific IgG in wild-type mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID BENIGN EPIDERMOLYSIS-BULLOSA; COLLAGENOUS TRANSMEMBRANE PROTEINS; T-CELLS; HERPES-GESTATIONIS; IN-VIVO; EXTRACELLULAR DOMAIN; BASEMENT-MEMBRANE; PASSIVE TRANSFER; GRAFT-REJECTION; DEFICIENT MICE AB Bullous pemphigoid antigen 2 (BPAG2) is targeted by autoantibodies in patients with bullous pemphigoid (BP), and absent in patients with one type of epidermolysis bullosa (OMIM #226650). A keratin 14 promoter construct was used to produce transgenic (Tg) mice appropriately expressing human BPAG2 (hBPAG2) in murine epidermal basement membrane ( BM). Grafts of Tg skin placed on gender-matched, syngeneic wild type (Wt) or major histocompatibility complex I (MHC I)-/- mice elicited IgG that bound human epidermal BM and BPAG2. Production of such IgG in grafted mice was prompt (detectable within 16 +/- 2 days), robust (titer >= 1,280), durable (present >= 380 days), and correlated with the involution and loss of Tg skin grafts. MHC II-/- mice grafted with Tg skin did not develop anti-hBPAG2 IgG or graft loss indicating that MHC II:CD4+ T cell interactions were crucial for these responses. Tg skin grafts on Wt mice developed neutrophil-rich infiltrates, dermal edema, subepidermal blisters, and deposits of immunoreactants in epidermal BM. This model shows fidelity to alterations seen in patients with BP, has relevance to immune responses that may arise in patients with epidermolysis bullosa following BPAG2 gene replacement, and can be used to identify interventions that may block production of IgG against proteins in epidermal BM. C1 Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. Univ Texas SW Med Ctr Dallas, Dept Dermatol, Dallas, TX 75390 USA. NIH, NCI, Dermatol Branch, DCS, Bethesda, MD USA. Hokkaido Univ, Grad Sch Med, Dept Dermatol, Sapporo, Hokkaido, Japan. RP Yancey, KB (reprint author), Univ Texas SW Med Ctr Dallas, Dept Dermatol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM kim.yancey@utsouthwestern.edu FU NIAMS NIH HHS [R01 AR048982-03, R01 AR048982, R01 AR048982-01A1, R01 AR048982-05, R01 AR048982-02, R01 AR048982-04] NR 41 TC 22 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2007 VL 127 IS 12 BP 2807 EP 2817 DI 10.1038/sj.jid.5700970 PG 11 WC Dermatology SC Dermatology GA 235XB UT WOS:000251266500017 PM 17657247 ER PT J AU Trempus, CS Dang, H Humble, MM Wei, SJ Gerdes, MJ Morris, RJ Bortner, CD Cotsarelis, G Tennant, RW AF Trempus, Carol S. Dang, Hong Humble, Margaret M. Wei, Sung-Jen Gerdes, Michael J. Morris, Rebecca J. Bortner, Carl D. Cotsarelis, George Tennant, Raymond W. TI Comprehensive microarray transcriptome profiling of CD34-enriched mouse keratinocyte stem cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID HAIR FOLLICLE BULGE; ENRICHMENT; EXPRESSION; NICHE; SKIN C1 Natl Inst Environm Hlth, Mol Toxicol Lab, Canc Biol Grp, Res Triangle Pk, NC USA. Alpha Gamma Technol Inc, Raleigh, NC USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, Bethesda, MD 20892 USA. Columbia Univ, Dept Dermatol, Med Ctr, New York, NY 10027 USA. Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC USA. Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. RP Trempus, CS (reprint author), Natl Inst Environm Hlth, Mol Toxicol Lab, Canc Biol Grp, Res Triangle Pk, NC USA. EM trempus@niehs.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA97957] NR 18 TC 12 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2007 VL 127 IS 12 BP 2904 EP 2907 DI 10.1038/sj.jid.5700917 PG 4 WC Dermatology SC Dermatology GA 235XB UT WOS:000251266500028 PM 17581618 ER PT J AU Oh, YK Joo, KW Lee, JW Jeon, US Lim, CS Han, JS Knepper, MA Na, KY AF Oh, Yun Kyu Joo, Kwon Wook Lee, Jay Wook Jeon, Un Sil Lim, Chun Soo Han, Jin Suk Knepper, Mark A. Na, Ki Young TI Altered renal sodium transporter expression in an animal model of type 2 diabetes mellitus SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Article DE diabetic nephropathies; rats; inbred OLETF; sodium-hydrogen exchanger 3; bumetanide sensitive NaK2Cl cotransporter; thiazide sensitive Nacl cotransporter; epithelial sodium channel ID BLOOD-PRESSURE; ZUCKER RATS; ENAC; CHANNEL; COMPLICATIONS; COTRANSPORTER; HYPERTENSION; ABUNDANCE; SALT; ALDOSTERONE AB Hemodynamic factors play an important role in the development and/or progression of diabetic nephropathy. We hypothesized that renal sodium transporter dysregulation might contribute to the hemodynamic alterations in diabetic nephropathy. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as an animal model for type 2 diabetes. Long Evans Tokushima (LETO) rats were used as controls. Renal sodium transporter regulation was investigated by semiquantitative immunoblotting and immunohistochemistry of the kidneys of 40-week-old animals. The mean serum glucose level in OLETF rats was increased to 235+/-25 mg/dL at 25 weeks, and the hyperglycemia continued up to the end of 40 weeks. Urine protein/creatinine ratios were 10 times higher in OLETF rats than in LETO rats. At 40th week, the abundance of the epithelial sodium channel (ENaC) beta-subunit was increased in OLETF rats, but the abundance of the ENaC gamma-subunit was decreased. No significant differences were observed in the ENaC alpha-subunit or other major sodium transporters. Immunohistochemistry for the ENaC beta-subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC gamma-subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC beta-subunit upregulation and ENaC gamma-subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance. C1 [Oh, Yun Kyu; Joo, Kwon Wook; Lee, Jay Wook; Jeon, Un Sil; Lim, Chun Soo; Han, Jin Suk; Na, Ki Young] Seoul Natl Univ, Coll Med, Seoul Natl Univ Bundang Hosp, Dept Internal Med, Songnam 463707, South Korea. [Oh, Yun Kyu; Lim, Chun Soo] Seoul Natl Univ, Boramae Hosp, Dept Internal Med, Seoul, South Korea. [Knepper, Mark A.] Natl Inst Hlth, Kidney & Electrolyte Metab Lab, Bethesda, MD USA. RP Na, KY (reprint author), Seoul Natl Univ, Coll Med, Seoul Natl Univ Bundang Hosp, Dept Internal Med, 300 Gumi Dong, Songnam 463707, South Korea. EM kyna@snubh.org RI Lim, Chun Soo/J-5624-2012; Oh, Yun Kyu/J-5542-2012; Han, Jin-Suk/J-5711-2012; Na, Ki Young/J-5456-2012; Joo, Kwon Wook/J-5675-2012 NR 24 TC 4 Z9 5 U1 0 U2 1 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD DEC PY 2007 VL 22 IS 6 BP 1034 EP 1041 DI 10.3346/jkms.2007.22.61034 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 248AC UT WOS:000252122700017 PM 18162719 ER PT J AU Rajesh, M Pan, H Mukhopadhyay, P Batkai, S Osei-Hyiaman, D Hasko, G Liaudet, L Gao, B Pacher, P AF Rajesh, Mohanraj Pan, Hao Mukhopadhyay, Partha Batkai, Sandor Osei-Hyiaman, Douglas Hasko, Gyoergy Liaudet, Lucas Gao, Bin Pacher, Pal TI Pivotal Advance: Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE endothelial activation; adhesion; inflammation; TNF-alpha ID ISCHEMIA-REPERFUSION INJURY; CB2 RECEPTOR; ENDOCANNABINOID SYSTEM; ENDOTHELIAL-CELLS; LIVER-TRANSPLANTATION; N-ACYLETHANOLAMINES; MYOCARDIAL-ISCHEMIA; ADHESION MOLECULES; CEREBRAL-ISCHEMIA; NITRIC-OXIDE AB In this study, we have investigated the role of the cannabinoid CB2 (CB2) receptor in an in vivo mouse model of hepatic ischemia/reperfusion (I/R) injury. In addition, we have assessed the role of the CB2 receptor in TNF-alpha-induced ICAM-1 and VCAM-1 expression in human liver sinusoidal endothelial cells (HLSECs) and in the adhesion of human neutrophils to HLSECs in vitro. The potent CB2 receptor agonist HU-308, given prior to the induction of I/R, significantly attenuated the extent of liver damage (measured by serum alanine aminotransferase and lactate dehydrogenase) and decreased serum and tissue TNF-alpha, MIP-1 alpha, and MIP-2 levels, tissue lipid peroxidation, neutrophil infiltration, DNA fragmentation, and caspase 3 activity. The protective effect of HU-308 against liver damage was also preserved when given right after the ischemic episode. HU-308 also attenuated the TNF-alpha-induced ICAM-1 and VCAM-1 expression in HLSECs, which expressed CB2 receptors, and the adhesion of human neutrophils to HLSECs in vitro. These findings suggest that selective CB2 receptor agonists may represent a novel, protective strategy against I/R injury by attenuating oxidative stress, inflammatory response, and apoptosis. C1 NIH, NIAAA, Lab Physiol Studies, Sect Oxidat Stress & Tissue Injury, Bethesda, MD 20892 USA. NIH, NIAAA, Lab Physiol Studies, Sect Liver Biol, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Dept Surg, Newark, NJ 07103 USA. Univ Hosp, Dept Intens Care Med, Lausanne, Switzerland. RP Pacher, P (reprint author), NIH, NIAAA, Lab Physiol Studies, Sect Oxidat Stress & Tissue Injury, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Batkai, Sandor/G-3889-2010; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z01 AA000375-02, Z99 AA999999] NR 59 TC 75 Z9 77 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC 1 PY 2007 VL 82 IS 6 BP 1382 EP 1389 DI 10.1189/jlb.0307180 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 235OI UT WOS:000251243800004 PM 17652447 ER PT J AU Rosenberg, HF Pacher, P AF Rosenberg, Helene F. Pacher, Pal TI Endocannabinoids, cannabinoid receptors and inflammatory stress: an interview with Dr. Pal Pacher SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID CB2; INJURY; BRAIN; BINDS C1 NIH, NIAAA, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIH, NIAAA, Lab Allerg Dis, Bldg 10, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 18 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC 1 PY 2007 VL 82 IS 6 BP 1390 EP 1392 DI 10.1189/jlb.1307180 PG 3 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 235OI UT WOS:000251243800005 ER PT J AU Norris, HH Peterson, ME Stebbins, CC McConchie, BW Bundoc, VG Trivedi, S Hodges, MG Anthony, RM Urban, JF Long, EO Keane-Myers, AM AF Norris, Hillary H. Peterson, Mary E. Stebbins, Chris C. McConchie, Brittany W. Bundoc, Virgilio G. Trivedi, Shweta Hodges, Marcus G. Anthony, Robert M. Urban, Joseph F., Jr. Long, Eric O. Keane-Myers, Andrea M. TI Inhibitory receptor gp49B regulates eosinophil infiltration during allergic inflammation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE mouse asthma model; helminth ID NATURAL-KILLER-CELLS; MAST-CELLS; AIRWAY HYPERRESPONSIVENESS; IMMUNOGLOBULIN SUPERFAMILY; NEGATIVE REGULATION; ASTHMA; DISEASE; PROTEIN; EXPRESSION; IL-13 AB gp49B, an Ig-like receptor, negatively regulates the activity of mast cells and neutrophils through cytoplasmic immunoreceptor tyrosine-based inhibition motifs. To characterize the role of gp49B further in vivo, gp49B-deficient mice were tested in two allergic models. Responses to ragweed (RW) challenge in the lung and conjunctiva were assessed in models of allergic inflammation and during an infection with parasitic larvae of the nematode Ascaris suum. Infiltration by inflammatory cells into the lung during allergic responses was under negative control of the inhibitory receptor gp49B. Furthermore, an increase in conjunctival inflammation with a predominance of eosinophils, neutrophils, and degranulated mast cells was observed in RW-sensitized, gp49B-deficient mice, which had been challenged in the eye, as compared with C57BL/6 wild-type (WT) controls. Finally, an increase in allergic inflammation in the lungs of A. suum-infected, RW-sensitized mice was observed upon RW challenge, as compared with C57BL/6 WT controls. The observed influx of eosinophils into mucus membranes is characteristic of allergic asthma and allergic conjunctivitis and may contribute to airway hyper-responsiveness, airway remodeling, and mucus production. Expression of gp49B was detected on peripheral eosinophils of control mice and on eosinophils from lungs of mice treated with RW, suggesting a role for gp49B on eosinophils in dampening allergic inflammatory responses. C1 NIH, NIAAA, Immunogenet Lab, Rockville, MD USA. USDA, ARS, Human Nutr Res Ctr, Nutrient Requirements & Funct Lab, Beltsville, MD 20705 USA. RP Keane-Myers, AM (reprint author), NIH, NIAAA, Lab Allerg Dis, Room 125,12441 Parklawn Dr, Rockville, MD 20852 USA. EM akeane@niaid.nih.gov RI Long, Eric/G-5475-2011; OI Long, Eric/0000-0002-7793-3728; Urban, Joseph/0000-0002-1590-8869 FU Intramural NIH HHS NR 55 TC 12 Z9 12 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC 1 PY 2007 VL 82 IS 6 BP 1531 EP 1541 DI 10.1189/jlb.1106667 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 235OI UT WOS:000251243800021 PM 17761953 ER PT J AU Kim, I Ahn, SH Inagaki, T Choi, M Ito, S Guo, GL Kliewer, SA Gonzalez, FJ AF Kim, Insook Ahn, Sung-Hoon Inagaki, Takeshi Choi, Mihwa Ito, Shinji Guo, Grace L. Kliewer, Steven A. Gonzalez, Frank J. TI Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine SO JOURNAL OF LIPID RESEARCH LA English DT Article DE FXR; FGF15; CYP7A1; CYP8B1; liver-specific FXR null mice; intestine-specific FXR null mice ID SOLUTE TRANSPORTER-ALPHA; SALT EXPORT PUMP; NUCLEAR RECEPTOR; FEEDBACK-REGULATION; LIPID HOMEOSTASIS; GENE-EXPRESSION; FXR; MICE; ACTIVATION; BETA AB Bile acid concentrations are controlled by a feedback regulatory pathway whereby activation of the farnesoid X receptor (FXR) represses transcription of both the CYP7A1 gene, encoding the rate-limiting enzyme in the classic bile acid synthesis pathway, and the CYP8B1 gene, required for synthesis of cholic acid. The tissue-specific roles of FXR were examined using liver- and intestinespecific FXR-null models. FXR deficiency in either liver (Fxr Delta(L)) or intestine (Fxr Delta(IE)) increased bile acid pool size. Treatment with the FXR-selective agonist GW4064 significantly repressed CYP7A1 in Fxr Delta(L) mice but not Fxr Delta(IE) mice, demonstrating that activation of FXR in intestine but not liver is required for short-term repression of CYP7A1 in liver. This intestinal-specific effect of FXR is likely mediated through induction of the hormone FGF15, which suppresses CYP7A1. In comparison to CYP7A1, FXR-mediated repression of CYP8B1 was more dependent on the presence of FXR in liver and less dependent on its presence in intestine. Consistent with these findings, recombinant FGF15 repressed CYP7A1 mRNA levels without affecting CYP8B1 expression. These data provide evidence that FXR-mediated repression of bile acid synthesis requires the complementary actions of FXR in both liver and intestine and reveal mechanistic differences in feedback repression of CYP7A1 and CYP8B1. C1 NCI, Natl Inst Hlth, Met Lab, Bethesda, MD 20892 USA. Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA. RP Gonzalez, FJ (reprint author), NCI, Natl Inst Hlth, Met Lab, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI inagaki, takeshi/J-8802-2013 OI inagaki, takeshi/0000-0003-1711-8286 FU Intramural NIH HHS NR 40 TC 201 Z9 204 U1 1 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 2007 VL 48 IS 12 BP 2664 EP 2672 DI 10.1194/jlr.M700330-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 232TD UT WOS:000251041500015 PM 17720959 ER PT J AU Lin, YH Salem, N AF Lin, Yu Hong Salem, Norman, Jr. TI Whole body distribution of deuterated linoleic and alpha-linolenic acids and their metabolites in the rat SO JOURNAL OF LIPID RESEARCH LA English DT Article DE docosahexaenoic acid; arachidonic acid; polyunsaturated fatty acid; fatty acid metabolism; stable isotope; gas liquid chromatography-mass spectrometry; essential fatty acid ID POLYUNSATURATED FATTY-ACIDS; TROUT ONCORHYNCHUS-MYKISS; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; GUINEA-PIG; BRAIN PHOSPHOLIPIDS; SUCKLING RATS; ADULT RATS; LIVER; LIPIDS AB Little is known about the uptake or metabolism of essential fatty acids (EFAs) in various mammalian organs. Thus, the distribution of deuterated alpha-linolenic acid (18:3n-3) and linoleic acid ( 18:2n-6) and their metabolites was studied using a stable isotope tracer technique. Rats were orally administered a single dose of a mixture ( 20 mg each) of ethyl D5-18:3n-3 and D5-18:2n-6, and 25 tissues per animal were analyzed for D5-labeled PUFAs at 4, 8, 24, 96, 168, 240, 360, and 600 h after dosing. Plasma, stomach, and spleen contained the highest concentrations of labeled precursors at the earliest time points, whereas other internal organs and red blood cells reached their maximal concentrations at 8 h. The time-course data were consistent with liver metabolism of EFAs, but local metabolism in other tissues could not be ruled out. Brain, spinal cord, heart, testis, and eye accumulated docosahexaenoic acid with time, whereas skin accumulated mainly 20: 4n-6. On average, similar to 16-18% of the D5-18:3n-3 and D5-18:2n-6 initial dosage was eventually accumulated in tissues, principally in adipose, skin, and muscle. Approximately 6.0% of D5-18:3n-3 and 2.6% of D5-18:2n-6 were elongated/desaturated and stored, mainly in muscle, adipose, and the carcass. The remaining 78% of both precursors was apparently catabolized or excreted. C1 Natl Inst Hlth, Natl Inst Alcohol Abuse & Alcoholism, Lab Membrane Biochem & Biophys, Sect Nutr Neurosci, Bethesda, MD 20892 USA. RP Salem, N (reprint author), Natl Inst Hlth, Natl Inst Alcohol Abuse & Alcoholism, Lab Membrane Biochem & Biophys, Sect Nutr Neurosci, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov FU Intramural NIH HHS NR 52 TC 43 Z9 44 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 2007 VL 48 IS 12 BP 2709 EP 2724 DI 10.1194/jlr.M700369-JLR200 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 232TD UT WOS:000251041500020 PM 17876057 ER PT J AU Guttman, MA Ozturk, C Raval, AN Raman, VK Dick, AJ DeSilva, R Karmarkar, P Lederman, RJ McVeigh, ER AF Guttman, Michael A. Ozturk, Cenghizhan Raval, Amish N. Raman, Venkatesh K. Dick, Alexander J. DeSilva, Ranil Karmarkar, Parag Lederman, Robert J. McVeigh, Elliot R. TI Interventional cardiovascular procedures guided by real-time MR imaging: An interactive interface using multiple slices, adaptive projection modes and live 3D renderings SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE interventional MRI; real-time MRI; image guided interventions; catheterization; user interface ID MESENCHYMAL STEM-CELLS; CATHETER-TRACKING; STEADY-STATE; SWINE; FLUOROSCOPY; RESOLUTION; TRUEFISP; GUIDANCE; TSENSE; COIL AB Purpose: To develop and test a novel interactive real-time MRI environment that facilitates image-guided cardiovascular interventions. Materials and Methods: Color highlighting of device-mounted receiver coils, accelerated imaging of multiple slices, adaptive projection modes, live three-dimensional (3D) renderings and other interactive features were utilized to enhance navigation of devices and targeting of tissue. Results: Images are shown from several catheter-based interventional procedures performed in swine that benefit from this custom interventional MRI interface. These include endograft repair of aortic aneurysm, balloon septostomy of the cardiac interatrial septum, angioplasty and stenting, and endomyocardial cell injection, all using active catheters containing MRI receiver coils. Conclusion: Interactive features not available on standard clinical scanners enhance real-time MRI for guiding cardiovascular interventional procedures. C1 [Guttman, Michael A.; McVeigh, Elliot R.] NHLBI, NIH, Div Intramural Res, Cardiac Energet Lab, Bethesda, MD 20892 USA. [Ozturk, Cenghizhan; Raval, Amish N.; Raman, Venkatesh K.; Dick, Alexander J.; DeSilva, Ranil; Karmarkar, Parag; Lederman, Robert J.] NHLBI, NIH, Div Intramural Res, Cardiovasc Branch, Bethesda, MD 20892 USA. RP Guttman, MA (reprint author), NHLBI, NIH, Div Intramural Res, Cardiac Energet Lab, 10 Ctr Dr,Bldg 10,Rm B1D416, Bethesda, MD 20892 USA. EM mguttman@nih.gov RI Ozturk, Cengizhan/A-6177-2016; OI Ozturk, Cengizhan/0000-0002-6966-0774; lederman, robert/0000-0003-1202-6673 FU Intramural NIH HHS [Z01 HL005062-05]; NHLBI NIH HHS [Z01-HL005062-04, Z01 HL004608, Z01 HL005062, Z01-HL004608-06] NR 33 TC 32 Z9 32 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD DEC PY 2007 VL 26 IS 6 BP 1429 EP 1435 DI 10.1002/jmri.21199 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 246MW UT WOS:000252012100008 PM 17968897 ER PT J AU Lyne, JC Gatehouse, PD Assomull, RG Smith, GC Kellman, P Firmin, DN Pennell, DJ AF Lyne, Jonathan C. Gatehouse, Peter D. Assomull, Ravi G. Smith, Gillian C. Kellman, Peter Firmin, David N. Pennell, Dudley J. TI Direct comparison of myocardial perfusion cardiovascular magnetic resonance sequences with parallel acquisition SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI; myocardial perfusion; first-pass; gadolinium contrast agent ID POSITRON-EMISSION-TOMOGRAPHY; STATE FREE PRECESSION; 1ST-PASS PERFUSION; GRADIENT-ECHO; CONTRAST; MRI; RESERVE; MULTISECTION; COVERAGE; TSENSE AB Purpose: To directly compare the three main myocardial perfusion cardiovascular magnetic resonance (CMR) sequences incorporating parallel acquisition methods. Materials and Methods: In 15 subjects (12 men, 57 +/- 15.7 years) referred for diagnostic coronary angiography, we acquired first-pass perfusion images (0.1 mmol/kg gadolinium-DTPA) at rest and during adenosine (140 mu g/kg/min) on three separate occasions using three sequences incorporating parallel acquisition methods and approximately equivalent spatiotemporal resolution: hybrid echo planar imaging (hEPI). steady-state free precession (SSFP), and gradient echo imaging (GRE). We calculated the contrast-to-noise ratio (CNR) of each scan and blinded observers scored the presence and severity of artifacts (1, worst to 4, best), diagnostic confidence (0, low to 2, high), transmurality, area, and epicardial vessel territory of perfusion defects. Results: CNR was greatest with SSFP and least with hEPI (13.15 vs 7.85 P < 0.001). The most artifacts were recorded with SSFP and least with hEPI (2.00 vs 3.03 P < 0.001). Observers were significantly more confident in reporting hEPI images (1.6 hEPI vs 0.9 SSFP, P < 0.001). Results for GRE were intermediate for all assessments. Conclusion: The hEPI sequence scored best for diagnostic performance despite the SSFP sequence having greater CNR. This trial favors hEPI for clinical myocardial perfusion CMR and suggests CNR should not be the sole criterion used to gauge the best candidate sequence. C1 [Lyne, Jonathan C.; Gatehouse, Peter D.; Assomull, Ravi G.; Smith, Gillian C.; Firmin, David N.; Pennell, Dudley J.] Royal Brompton Hosp, CMR Unit, London SW3 6NP, England. [Kellman, Peter] NHLBI, NIH, DHHS, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Pennell, DJ (reprint author), Royal Brompton Hosp, CMR Unit, Sydney St, London SW3 6NP, England. EM d.pennell@rbht.nhs.uk OI Gatehouse, Peter/0000-0002-0260-4719 NR 34 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD DEC PY 2007 VL 26 IS 6 BP 1444 EP 1451 DI 10.1002/jmri.21167 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 246MW UT WOS:000252012100010 PM 17968886 ER PT J AU Alves, S Woods, A Tabet, JC AF Alves, Sandra Woods, Amina Tabet, Jean Claude TI Charge state effect on the zwitterion influence on stability of non-covalent interaction of single-stranded DNA with peptides SO JOURNAL OF MASS SPECTROMETRY LA English DT Article; Proceedings Paper CT 25th Informal Meeting on Mass Spectrometry (IMMS) CY MAY 06-10, 2007 CL Nyiregyhaza Sosto, HUNGARY SP Natl Sci Council, Taiwan, Natl Sun Yat Sen Univ, Org Prohibition Chem Weapons, State Off Nucl Safety, Minist Educ, Youth & Sports DE noncovalent complexes; salt bridge interaction; ESI mass spectrometry ID ASSISTED-LASER-DESORPTION/IONIZATION; GAS-PHASE ACIDITIES; COLLISION-INDUCED DISSOCIATION; IONIZATION MASS-SPECTROMETRY; ELECTROSPRAY-IONIZATION; PROTON AFFINITY; WATER-MOLECULES; AMINO-ACIDS; MALDI-TOF; ELECTROSTATIC INTERACTIONS AB Negative ion ESI mass spectrometry was used to study the gas-phase stability and dissociation pathways of peptide-DNA complexes. We show that bradykinin and three modified peptides containing the basic residue arginine or lysine form stable interactions with single-stranded oligonucleotides. ESI-MS/MS, of complexes of (T) under bar ((8) under bar) with PPGFSPFRR resulted in a major dissociation pathway through cleavage of the peptide covalent bond. The stability of the complex is due to electrostatic interaction between the negatively charged phosphate group and the basic side chain of the arginine and lysine residues as demonstrated by Vertes et al. and Woods et al. In fact, the present work establishes the role played by zwitterions on complex stabilisation. The presence of protons in nucleobase and/or amino acid contributes in reinforcing the strength of the salt bridge (SB) interaction. The zwitterionic form of the most basic of amino acid residues, arginine, is assumed to form a strong SB interaction to the negatively charged phosphate groups of DNA. This non-covalent complex is stable enough to withstand disruption of the non-covalent interaction and to first break the covalent bond. Moreover, the dependence of fragmentation patterns upon the complex charge state is explained by the fact that the net number of negative charges modulates the number of zwitterionic sites, which stabilise the complexes. Finally, the weak influence of the nucleobase is assumed by the existence of competition for proton addition between the nucleobase and the R/K side chain leading to a decrease in the stabilisation of the SB interaction. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Alves, Sandra; Tabet, Jean Claude] Univ Paris 06, UMR 7613, BP45, Lab Chim Struct Organ & Biol, F-75252 Paris 4, France. [Woods, Amina] NIDA, IRP, NIH, Baltimore, MD 21224 USA. RP Tabet, JC (reprint author), Univ Paris 06, UMR 7613, BP45, Lab Chim Struct Organ & Biol, 4 Pl Jussieu, F-75252 Paris 4, France. EM tabet@ccr.jussieu.fr NR 71 TC 13 Z9 13 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD DEC PY 2007 VL 42 IS 12 BP 1613 EP 1622 DI 10.1002/jms.1359 PG 10 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 253IM UT WOS:000252511900010 PM 18085569 ER PT J AU Kusanovic, JP Romero, R Hassan, SS Gotsch, F Edwin, S Chaiworapongsa, T Erez, O Mittal, P Mazaki-Tovi, S Soto, E Than, NG Friel, LA Yoon, BH Espinoza, J AF Kusanovic, Juan Pedro Romero, Roberto Hassan, Sonia S. Gotsch, Francesca Edwin, Samuel Chaiworapongsa, Tinnakorn Erez, Offer Mittal, Pooja Mazaki-Tovi, Shali Soto, Eleazar Than, Nandor Gabor Friel, Lara A. Yoon, Bo Hyun Espinoza, Jimmy TI Maternal serum soluble CD30 is increased in normal pregnancy, but decreased in preeclampsia and small for gestational age pregnancies SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE preeclampsia; sCD30; Th2 immune response; small for gestational age neonate; SGA ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; BLOOD MONONUCLEAR-CELLS; RECURRENT SPONTANEOUS-ABORTION; UTERINE ARTERY DOPPLER; CIRCULATING ANGIOGENIC FACTORS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HEALTHY NULLIPAROUS WOMEN; BED SPIRAL ARTERIES; T-HELPER CYTOKINES AB Objective. Women with preeclampsia and those who deliver small for gestational age (SGA) neonates are characterized by intravascular inflammation (T helper 1 (Th1)-biased immune response). There is controversy about the T helper 2 (Th2) response in preeclampsia and SGA. CD30, a member of the tumor necrosis factor receptor superfamily, is preferentially expressed in vitro and in vivo by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) has been proposed to be an index of Th2 immune response. The objective of this study was to determine whether the maternal serum concentration of sCD30 changes with normal pregnancy, as well as in mothers with preeclampsia and those who deliver SGA neonates. Methods. This cross-sectional study included patients in the following groups: (1) non-pregnant women (N=49); (2) patients with a normal pregnancy (N=89); (3) patients with preeclampsia (N=100); and (4) patients who delivered an SGA neonate (N=78). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests with post-hoc analysis were used for comparisons. A p value <0.05 was considered statistically significant. Results. (1) The median sCD30 serum concentration of pregnant women was significantly higher than that of non-pregnant women (median 29.7 U/mL, range 12.2-313.2 vs. median 23.2 U/mL, range 14.6-195.1, respectively; p=0.01). (2) Patients with preeclampsia had a significantly lower median serum concentration of sCD30 than normal pregnant women (median 24.7 U/mL, range 7.6-71.2 vs. median 29.7 U/mL, range 12.2-313.2, respectively; p < 0.05). (3) Mothers with SGA neonates had a lower median concentration of sCD30 than normal pregnant women (median 23.4 U/mL, range 7.1-105.3 vs. median 29.7 U/mL, range 12.2-313.2, respectively; p < 0.05). (4) There was no significant correlation (r=-0.059, p=0.5) between maternal serum sCD30 concentration and gestational age (19-38 weeks) in normal pregnant women. Conclusions. (1) Patients with preeclampsia and those who deliver an SGA neonate had a significantly lower serum concentration of sCD30 than normal pregnant women. (2) This finding is consistent with the view that preeclampsia and SGA are associated with a polarized Th1 immune response and, perhaps, a reduced Th2 response. C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Hassan, Sonia S.; Chaiworapongsa, Tinnakorn; Mittal, Pooja; Mazaki-Tovi, Shali; Soto, Eleazar; Friel, Lara A.; Espinoza, Jimmy] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM nichdprbchiefstaff@mail.nih.gov RI Yoon, Bo Hyun/H-6344-2011 FU Intramural NIH HHS [Z99 HD999999, Z01 HD002400-16] NR 186 TC 23 Z9 24 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD DEC PY 2007 VL 20 IS 12 BP 867 EP 878 DI 10.1080/14767050701482993 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 248JW UT WOS:000252150600004 PM 17853188 ER PT J AU Santolaya-Forgas, J Edwin, S Zeiter, K Pitt, A Pineles, B Tarca, AL Espinoza, J Kusanovic, JP Erez, O Wolf, R Romero, R AF Santolaya-Forgas, Joaquin Edwin, Samuel Zeiter, Katie Pitt, Adam Pineles, Beth Tarca, Adi L. Espinoza, Jimmy Kusanovic, Juan Pedro Erez, Offer Wolf, Roman Romero, Roberto TI The timed-pregnant baboon animal model can be used for determining the role of soluble vascular endothelial growth factor receptors 1 and 2 during development SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE angiogenesis; FLK1; FLT1; placental vascularization; vascular endothelial growth factor; VEGF-receptors ID ENDOTHELIAL GROWTH-FACTOR; MATERNAL SERUM; HUMAN PLACENTA; VEGF; PREECLAMPSIA; EXPRESSION; RECEPTORS; FETAL; VASCULOGENESIS; ANGIOGENESIS AB Background During pregnancy, mechanisms that allow for regulation of continuous fetal and placental vasculogenesis with prevention of maternal neo-vascularization remain elusive. The vascular endothelial growth factor (VEGF) biological system has a key role during vasculogenesis. The aims of this study were to validate a bioassay for soluble vascular endothelial growth factor receptors 1 and 2 (sVEGFR-1 and sVEGFR-2) in baboon plasma and to determine the maternal and fetal plasma concentration of these receptors at the end of the baboon pregnancy. Methods Maternal peripheral blood samples were obtained from eight baboons (Papio anubis) prior to elective cesarean section and from the umbilical cord after the fetuses were delivered. Spike and recovery experiments at various concentrations in pooled baboon maternal plasma were used to validate a human quantitative sandwich immunoassay for sVEGFR-1 and -2. Concentrations of sVEGFR-1 and -2 were then determined in maternal and fetal plasma samples. Results No significant correlations were observed between sVEGFR-1 or -2 concentrations in maternal and fetal circulations. The concentration of sVEGFR-1 was at least 30 times greater and that of sVEGFR-2 approximately two times greater, in maternal than in cord plasma (both P < 0.01). Conclusions These findings suggest that baboons can be used to study the regulation of vasculogenesis during pregnancy. C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, DHHS, Perinatol Res Branch, NIH, Detroit, MI USA. Univ Oklahoma, Hlth Sci Ctr, Biol Resource Lab, Norman, OK 73019 USA. RP Santolaya-Forgas, J (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Fetal Med & Prenatal Genet, 75 Francis St, Boston, MA 02115 USA. EM jsantolaya@partners.org FU NCRR NIH HHS [R24 RR016556, P40 RR012317] NR 30 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD DEC PY 2007 VL 36 IS 6 BP 370 EP 374 DI 10.1111/j.1600-0684.2006.00205.x PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 225YC UT WOS:000250553200006 PM 17976042 ER PT J AU Mattison, JA Ottinger, MA Powell, D Longo, DL Ingram, DK AF Mattison, Julie A. Ottinger, Mary Ann Powell, Douglas Longo, Dan L. Ingram, Donald K. TI Endometriosis: clinical monitoring and treatment procedures in rhesus Monkeys SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE dysmenorrhea; estrogen; gonadal hormones; Macaca mulatta ID PROGESTERONE-RECEPTOR ANTAGONISTS; MACACA-MULATTA; BABOONS; DIOXIN; SERUM; MACAQUES; ESTROGEN; THERAPY; WOMEN; CYCLE AB The National Institute on Aging (NIA) sponsored a workshop on September 8, 2004, to discuss the incidence, diagnosis, and clinical treatment of endometriosis in rhesus monkey colonies. Because of the growing number of aging studies using rhesus monkeys, this disease has become more prevalent as monkeys are living into advanced ages in captivity. The objective of the workshop was to gather information from various NIA-supported aging rhesus colonies on the incidence, clinical manifestations, indicators for early detection, and possible treatment options for endometriosis. Participants outlined a course of action for the effective management of this disease that would best maintain the integrity of long-term aging studies. C1 NIA, Lab Expt Gerontol, Anim Ctr, NIH, Poolesville, MD USA. Univ Maryland, Dept Avian & Anim Sci, College Pk, MD 20742 USA. NIH, Off Res Serv, Div Vet Resources, Poolesville, MD USA. NIA, Off Sci Director, NIH, Baltimore, MD USA. NIA, Lab Expt Gerontol, NIH, Baltimore, MD USA. RP Mattison, JA (reprint author), 16701 Elmer Sch Rd,Bldg 103, Dickerson, MD 20842 USA. EM mattisonj@mail.nih.gov FU Intramural NIH HHS NR 35 TC 11 Z9 11 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD DEC PY 2007 VL 36 IS 6 BP 391 EP 398 DI 10.1111/j.1600-0684.2006.00208.x PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 225YC UT WOS:000250553200010 PM 17976046 ER PT J AU Moscarelli, M Rupp, A AF Moscarelli, Massimo Rupp, Agnes TI Untitled SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Editorial Material C1 [Moscarelli, Massimo] Int Ctr Mental Hlth Policy & Econ, Milan, Italy. [Moscarelli, Massimo] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Rupp, Agnes] NIMH, Econ Programme, Div Epidemiol & Serv Res, Rockville, MD 20857 USA. RP Moscarelli, M (reprint author), Int Ctr Mental Hlth Policy & Econ, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT CTR MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD DEC PY 2007 VL 10 IS 4 BP 163 EP 164 PG 2 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA 245LV UT WOS:000251937200001 ER PT J AU Combs, CA Smirnov, AV Riley, JD Gandjbakhche, AH Knutson, JR Balaban, RS AF Combs, Christian A. Smirnov, Aleksandr V. Riley, Jason D. Gandjbakhche, Amir H. Knutson, Jay R. Balaban, Robert S. TI Optimization of multiphoton excitation microscopy by total emission detection using a parabolic light reflector SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE brain; GFP; light collection; trans-fluorescence; two-photon microscopy ID 2-PHOTON MICROSCOPY; OPTICAL-PROPERTIES; FLUORESCENCE MICROSCOPY; BRAIN-TISSUE; IN-VIVO; SCATTERING; CELLS; ANIMALS; RANGE; VITRO AB We have constructed a device that maximizes the probability of collecting all of the scattered and ballistic light isotropically generated at the focal spot of multiphoton excited emissions (MPE) to optimize the signal-to-noise ratio (SNR) for micro-imaging. This was accomplished by optically coupling a parabolic reflector (that surrounds the sample and top of the objective) to a pair of collimating lenses (above the sample) that redirects emitted light to a separate detector. These additional optics, combined with the objective, allow the total emission detection (TED) condition to be approached. Numerical simulations suggest an approximately 10-fold improvement in SNR with TED. Comparisons between the objective detection and TED reveal an enhancement of 8.9 in SNR (77% of predicted) for GFP-labelled brain slices and similar results for fluorescent beads. This increase in SNR can be used to improve time resolution, reduce laser power requirements/photodynamic damage, and, in certain cases, detection depth, for MPE imaging techniques. C1 NHLBI, Light Microscopy Facil, Natl Inst Hlth, Bethesda, MD 20892 USA. NHLBI, Mol Biophys Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. NICHD, Lab Integrat & Med Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Combs, CA (reprint author), NHLBI, Light Microscopy Facil, Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA. EM combsc@nih.gov RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 32 TC 20 Z9 20 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD DEC PY 2007 VL 228 IS 3 BP 330 EP 337 DI 10.1111/j.1365-2818.2007.01851.x PG 8 WC Microscopy SC Microscopy GA 235RG UT WOS:000251251400008 PM 18045327 ER PT J AU Lopez-Lazaro, M Willmore, E Jobson, A Gilroy, KL Curtis, H Padget, K Austin, CA AF Lopez-Lazaro, Miguel Willmore, Elaine Jobson, Andrew Gilroy, Kathryn L. Curtis, Hannah Padget, Kay Austin, Caroline A. TI Curcumin induces high levels of topoisomerase I- and II DNA complexes in K562 leukemia cells SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID CLEAVABLE COMPLEXES; CHEMOPREVENTIVE AGENT; DOWN-REGULATION; CANCER-THERAPY; KAPPA-B; APOPTOSIS; INDUCTION; INHIBITION; MECHANISM; BETA AB Recent data suggest that curcumin, a phytochemical with cancer chemopreventive potential, might be useful in the treatment of several solid and hematological malignancies. DNA topoisomerases (topos) are the target of several drugs commonly used in cancer chemotherapy. These drugs induce topo-DNA complexes with either topo I or topo II; then cellular processing converts these complexes into permanent DNA strand breaks that trigger cell death. Using the TARDIS in vivo assay, this study shows for the first time that curcumin induces topo I and topo II ((alpha and beta)-DNA complexes in K562 leukemia cells. A comparative analysis revealed that the levels of these complexes were higher than those induced by several standard topo I and topo II inhibitors at equitoxic doses. Curcumin-induced topo I and topo II-DNA complexes were prevented by the antioxidant N-acetylcysteine; this suggests that, unlike the standard topo inhibitors, reactive oxygen species may mediate the formation of these complexes. Overall, this work shows that curcumin is capable of inducing topo-DNA complexes in cells with both topo I and topo II and increases the evidence suggesting that this dietary agent has potential to be tested in cancer chemotherapy. C1 [Lopez-Lazaro, Miguel; Willmore, Elaine; Jobson, Andrew; Gilroy, Kathryn L.; Curtis, Hannah; Padget, Kay; Austin, Caroline A.] Univ Newcastle Upon Tyne, Sch Med, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Lopez-Lazaro, Miguel] Univ Seville, Fac Pharm, Dept Pharmacol, Seville, Spain. [Willmore, Elaine] Univ Newcastle Upon Tyne, Sch Med, No Inst Canc Res, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Jobson, Andrew] NIH, Natl Canc Inst, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Austin, CA (reprint author), Univ Newcastle Upon Tyne, Sch Med, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM caroline.austin@ncl.ac.uk RI Willmore, Elaine/B-4350-2009 NR 51 TC 36 Z9 36 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD DEC PY 2007 VL 70 IS 12 BP 1884 EP 1888 DI 10.1021/np070332i PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 246ZK UT WOS:000252046700009 PM 18076140 ER PT J AU Reimold, M Smolka, MN Zimmer, A Batra, A Knobel, A Solbach, C Mundt, A Smoltczyk, HU Goldman, D Mann, K Reischl, G Machulla, HJ Bares, R Heinz, A AF Reimold, M. Smolka, M. N. Zimmer, A. Batra, A. Knobel, A. Solbach, C. Mundt, A. Smoltczyk, H. U. Goldman, D. Mann, K. Reischl, G. Machulla, H. -J. Bares, R. Heinz, A. TI Reduced availability of serotonin transporters in obsessive-compulsive disorder correlates with symptom severity - a [C-11]DASB PET study SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE 5-HTT; OCD; SERT; 5-HTTLPR; thalamus ID POSITRON-EMISSION-TOMOGRAPHY; I-123 BETA-CIT; NONHUMAN-PRIMATES; HEALTHY HUMANS; DOPAMINE; BINDING; SPECT; GENOTYPE; ALCOHOL; BRAIN AB Reduced availability of brainstem serotonin transporters (5-HTT) has been observed in vivo in obsessive-compulsive disorder (OCD). However, results vary and may be influenced by competition with endogenous serotonin. Using positron emission tomography (PET) and [C-11]DASB, a specific 5-HTT ligand that showed no competition with serotonin for 5-HTT binding in vitro, we tested the hypothesis that 5-HTT availability is reduced in OCD patients and correlated with OCD severity. Methods. 5-HTT availability in the thalamus and the midbrain was measured in nine drug-free OCD patients and compared with 19 healthy controls, matched for the individual combination of 5-HTT genotype, gender and smoking status. OCD severity was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS). Results. 5-HTT availability was significantly reduced in the thalamus and midbrain of OCD patients. Age and 5-HTT in the thalamus explained 83% of OCD severity in patients that were drug-free for at least 1 year. Conclusion. This PET study confirms a central role of the serotonergic system, particularly the thalamus in the pathogenesis of obsessive compulsive disorder. C1 Charite Univ Med Ctr, Dept Psychiat & Psychotherapy, Berlin, Germany. Univ Tubingen, Dept Nucl Med, Tubingen, Germany. Univ Heidelberg, Cent Inst Mental Hlth, Dept Addict Behav & Addict Res, D-6800 Mannheim, Germany. Univ Tubingen, Dept Psychiat, Tubingen, Germany. Univ Med Ctr, CCM, Dept Psychiat & Psychotherapy, Charite, Berlin, Germany. Univ Tubingen, Dept Radiopharm, Tubingen, Germany. NIH, Natl Inst Alcohol Abuse & Alcoholism, Bethesda, MD 20892 USA. RP Heinz, A (reprint author), Charite Univ Med Ctr, Dept Psychiat & Psychotherapy, Campus Charite Mitte,Chariteplatz 1, Berlin, Germany. EM andreas.heinz@charite.de RI Smolka, Michael/B-4865-2011; Goldman, David/F-9772-2010; OI Smolka, Michael/0000-0001-5398-5569; Goldman, David/0000-0002-1724-5405; Mundt, Adrian P/0000-0001-8763-4601 NR 53 TC 43 Z9 43 U1 4 U2 9 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD DEC PY 2007 VL 114 IS 12 BP 1603 EP 1609 DI 10.1007/s00702-007-0785-6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 237NS UT WOS:000251382200013 PM 17713719 ER PT J AU Rushing, EJ Cooper, PB Quezado, M Begnami, M Crespo, A Smirniotopoulos, JG Ecklund, J Olsen, C Santi, M AF Rushing, Elisabeth J. Cooper, Patrick B. Quezado, Martha Begnami, Maria Crespo, Ana Smirniotopoulos, James G. Ecklund, James Olsen, Cara Santi, Mariarita TI Subependymoma revisited: clinicopathological evaluation of 83 cases SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE central nervous system; CISH; CT; ependymoma; MRI; subependymoma ID SYMPTOMATIC SUBEPENDYMOMA; MR MANIFESTATIONS; IMAGING FEATURES; 14 TUMORS; EPENDYMOMAS; CT; NEOPLASMS AB Object Subependymomas are rare ependymal neoplasms. To date, a large clinicopathologic study of these benign neoplasms treated with modern neurosurgical techniques has not been reported. Methods Eighty-three cases of subependymoma were retrieved from the files of the Armed Forces Institute of Pathology. Clinicopathological features were reviewed; chromogenic in situ hybridization analysis for chromosome 22 was performed (n = 8), and patient follow-up was obtained (n = 34). Overall, the patients included 68 males and 15 females, 1.5 to 85 years of age (mean, 51.0 years). Twenty-seven cases were discovered at autopsy and the remaining were surgical specimens (n = 56). Tumors arose in the posterior fossa (n = 43), lateral ventricles (n = 37), spinal cord (2) and only one arose in the temporal horn. Tumors ranged in size from 2.0 mm to 60 mm in greatest dimension (mean, 23.0 mm). Eighteen-percent (15/83) of subependymomas exhibited a mixed histologic pattern; that is, subependymoma together with another glial tumor. The most common mixture (13/15) was subependymoma and ependymoma. Surgical excision was used in all symptomatic patients; 10 patients received radiation. Four patients developed a recurrence due to incomplete excision. All patients were without evidence of disease at the last follow-up: alive (n = 28) or dead (n = 8). Conclusions Age is the only variable found to be significantly associated with survival. Currently, surgical methods result in an excellent long-term clinical outcome. Subependymomas do not appear to be associated with NF2 mutations. C1 Armed Forces Inst Pathol, Dept Neuropathol, Washington, DC 20306 USA. Armed Forces Inst Pathol, Dept Ophthalm Pathol, Washington, DC 20306 USA. Walter Reed Army Med Ctr, Natl Capitol Consortium, Dept Neurosurg, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Radiol Pathol, Washington, DC 20306 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol Sci, Bethesda, MD 20814 USA. Natl Childrens Hosp, Med Ctr, Dept Pathol, Washington, DC USA. RP Rushing, EJ (reprint author), Armed Forces Inst Pathol, Dept Neuropathol, Washington, DC 20306 USA. EM rushinge@afip.osd.mil RI Smirniotopoulos, James/D-3726-2011; Begnami, Maria/D-9663-2012 OI Begnami, Maria/0000-0003-0848-7813 NR 26 TC 33 Z9 36 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 2007 VL 85 IS 3 BP 297 EP 305 DI 10.1007/s11060-007-9411-6 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 231AY UT WOS:000250920000010 PM 17569000 ER PT J AU Soundarapandian, MM Wu, D Zhong, XF Petralia, RS Peng, LS Tu, WH Lu, YM AF Soundarapandian, Mangala M. Wu, Di Zhong, Xiaofen Petralia, Ronald S. Peng, Lisheng Tu, Weihong Lu, Youming TI Expression of functional Kir6.1 channels regulates glutamate release at CA3 synapses in generation of epileptic form of seizures SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE excitotoxicity; K-ATP channels; seizure ID K-ATP CHANNELS; SENSITIVE POTASSIUM CHANNELS; FOREBRAIN ISCHEMIA; METABOLIC SENSORS; CELL-DEATH; KAINATE; EXOCYTOSIS; NEURONS; CAMP; EXCITABILITY AB The Kir6.1 channels are a subtype of ATP-sensitive inwardly rectifying potassium (K-ATP) channels that play an essential role in coupling the cell's metabolic events to electrical activity. In this study, we show that functional Kir6.1 channels are located at excitatory pre-synaptic terminals as a complex with type-1 Sulfonylurea receptors (SUR1) in the hippocampus. The mutant mice with deficiencies in expressing the Kir6.1 or the SUR1 gene are more vulnerable to generation of epileptic form of seizures, compared to wild-type controls. Whole-cell patch clamp recordings demonstrate that genetic deletion of the Kir6.1/SUR1 channels enhances glutamate release at CA3 synapses. Hence, expression of functional Kir6.1/SUR1 channels inhibits seizure responses and possibly acts via limiting excitatory glutamate release. C1 Univ Cent Florida, Burnett Coll Biomed Sci, Biomed Sci Ctr, Orlando, FL 32816 USA. NIH, Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, Bethesda, MD 20892 USA. RP Lu, YM (reprint author), Univ Cent Florida, Burnett Coll Biomed Sci, Biomed Sci Ctr, Orlando, FL 32816 USA. EM youming@mail.ucf.edu FU Intramural NIH HHS; NINDS NIH HHS [5R01NS5051383] NR 30 TC 27 Z9 28 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2007 VL 103 IS 5 BP 1982 EP 1988 DI 10.1111/j.1471-4159.2007.04883.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 231YN UT WOS:000250985200026 PM 17883401 ER PT J AU Ikeda, T Hikosaka, O AF Ikeda, Takuro Hikosaka, Okihide TI Positive and negative modulation of motor response in primate superior colliculus by reward expectation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SACCADIC EYE-MOVEMENTS; DORSOLATERAL PREFRONTAL CORTEX; INHIBITORY BURST NEURONS; TARGET SELECTION; VISUAL RESPONSES; CAUDATE-NUCLEUS; BASAL GANGLIA; ELECTRICAL-STIMULATION; ORBITOFRONTAL CORTEX; PARIETAL CORTEX AB Positive and negative modulation of motor response in primate superior colliculus by reward expectation. J Neurophysiol 98: 3163-3170, 2007. First published October 10, 2007; doi:10.1152/jn.00975.2007. Expectation of reward is crucial for goal-directed behavior of animals. However, little is known about how reward information is used in the brain at the time of action. We investigated this question by recording from single neurons in the macaque superior colliculus (SC) while the animal was performing a memory-guided saccade task with an asymmetrical reward schedule. The SC is an ideal structure to ask this question because it receives inputs from many brain areas including the prefrontal cortex and the basal ganglia where reward information is thought to be encoded and sends motor commands to the brain stem saccade generators. We found two groups of SC neurons that encoded reward information in the presaccadic period: positive reward-coding neurons that showed higher activity when reward was expected and negative reward-coding neurons that showed higher activity when reward was not expected. The positive reward-coding usually started even before a cue for target position was presented, whereas the negative reward-coding was largely restricted to the presaccadic period. The two kinds of reward-coding may be useful for the animal to select an appropriate behavior in a complex environment. C1 [Ikeda, Takuro] Natl Inst Physiol Sci, Dept Dev Physiol, Okazaki, Aichi 4448585, Japan. [Ikeda, Takuro] Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Kawaguchi, Japan. [Ikeda, Takuro] Tamagawa Univ, Brain Sci Res Ctr, Res Inst, Tokyo, Japan. [Hikosaka, Okihide] Natl Inst Hlth, Sensorimotor Res Lab, Bethesda, MD USA. [Ikeda, Takuro; Hikosaka, Okihide] Juntendo Univ, Sch Med, Dept Physiol, Tokyo, Japan. RP Ikeda, T (reprint author), Natl Inst Physiol Sci, Dept Dev Physiol, Okazaki, Aichi 4448585, Japan. EM taikeda-ns@umin.ac.jp NR 60 TC 20 Z9 20 U1 2 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2007 VL 98 IS 6 BP 3163 EP 3170 DI 10.1152/jn.00975.2007 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 243DS UT WOS:000251775700005 PM 17928551 ER PT J AU Smith, JC Abdala, APL Koizumi, H Rybak, IA Paton, JFR AF Smith, J. C. Abdala, A. P. L. Koizumi, H. Rybak, I. A. Paton, J. F. R. TI Spatial and functional architecture of the mammalian brain stem respiratory network: A hierarchy of three oscillatory mechanisms SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PRE-BOTZINGER COMPLEX; PERSISTENT SODIUM CURRENT; DECREMENTING EXPIRATORY NEURONS; MODELING NEURAL MECHANISMS; INSPIRATORY OFF-SWITCH; RHYTHM GENERATION; PACEMAKER NEURONS; IN-VITRO; SYNAPTIC MECHANISMS; MEMBRANE-PROPERTIES AB Spatial and functional architecture of the mammalian brain stem respiratory network: a hierarchy of three oscillatory mechanisms. J Neurophysiol 98: 3370-3387, 2007. First published October 3, 2007; doi:10.1152/jn.00985.2007. Mammalian central pattern generators (CPGs) producing rhythmic movements exhibit extremely robust and flexible behavior. Network architectures that enable these features are not well understood. Here we studied organization of the brain stem respiratory CPG. By sequential rostral to caudal transections through the pontine-medullary respiratory network within an in situ perfused rat brain stem-spinal cord preparation, we showed that network dynamics reorganized and new rhythmogenic mechanisms emerged. The normal three-phase respiratory rhythm transformed to a two-phase and then to a one-phase rhythm as the network was reduced. Expression of the three-phase rhythm required the presence of the pons, generation of the two-phase rhythm depended on the integrity of Botzinger and pre-Botzinger complexes and interactions between them, and the one-phase rhythm was generated within the pre-Botzinger complex. Transformation from the three-phase to a two-phase pattern also occurred in intact preparations when chloride-mediated synaptic inhibition was reduced. In contrast to the three-phase and two-phase rhythms, the one-phase rhythm was abolished by blockade of persistent sodium current (I-NaP). A model of the respiratory network was developed to reproduce and explain these observations. The model incorporated interacting populations of respiratory neurons within spatially organized brain stem compartments. Our simulations reproduced the respiratory patterns recorded from intact and sequentially reduced preparations. Our results suggest that the three-phase and two-phase rhythms involve inhibitory network interactions, whereas the one-phase rhythm depends on I-NaP. We conclude that the respiratory network has rhythmogenic capabilities at multiple levels of network organization, allowing expression of motor patterns specific for various physiological and pathophysiological respiratory behaviors. C1 [Smith, J. C.; Koizumi, H.] Natl Inst Hlth, NINDS, Cellular & Syst Neurobiol Sect, Bethesda, MD USA. [Abdala, A. P. L.; Paton, J. F. R.] Univ Bristol, Sch Med Sci, Inst Heart, Dept Physiol, Bristol, Avon, England. [Rybak, I. A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA USA. RP Smith, JC (reprint author), NIH, NINDS, Porter Neurosci Res Ctr, Cellular & Syst Neurobiol Sect, Bldg 35,Rm 3C-917,35 Convent Dr, Bethesda, MD 20892 USA. EM jsmith@helix.nih.gov RI Abdala, Ana Paula/G-9104-2014; OI Abdala, Ana Paula/0000-0001-6051-2591; Paton, Julian/0000-0001-7410-2913 FU Intramural NIH HHS; NINDS NIH HHS [R01 NS048844, R01 NS048844-01A2, R01 NS048844-02, R01 NS057815, R01 NS057815-01, R01 NS057815-02] NR 73 TC 200 Z9 201 U1 1 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2007 VL 98 IS 6 BP 3370 EP 3387 DI 10.1152/jn.00985.2007 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 243DS UT WOS:000251775700024 PM 17913982 ER PT J AU Zhang, D Zeldin, DC Blackshear, PJ AF Zhang, Donghui Zeldin, Darryl C. Blackshear, Perry J. TI Regulatory factor X4 variant 3: A transcription factor involved in brain development and disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Review DE regulatory factor X; hydrocephalus; midline; brain development ID DNA-BINDING; FACTOR RFX4; IDENTIFICATION; HYDROCEPHALUS; EXPRESSION; PROTEIN; MOUSE; GENE; DIFFERENTIATION; DEFICIENCY AB Regulatory factor X4 variant 3 (RFX4_v3) is a recently identified transcription factor specifically expressed in the brain. Gene disruption in mice demonstrated that interruption of a single allele (heterozygous, +/-) prevented formation of the subcommissural organ (SCO), resulting in congenital hydrocephalus, whereas interruption of two alleles (homozygous, -/-) caused fatal failure of dorsal midline brain structure formation. These mutagenesis studies implicated RFX4_v3 in early brain development as well as the genesis of the SCO. Rfx4_v3 deficiency presumably causes abnormalities in brain by altering the expression levels of many genes that are crucial for brain morphogenesis, such as the signaling components in the Wnt, bone morphogenetic protein, and retinoic acid pathways. RFX4_v3 might affect these critical signaling pathways in brain development. Cx3cl1, a chemokine gene highly expressed in brain, was identified as a direct target for RFX4_v3, indicating that RFX4_v3 possesses trans-acting activity to stimulate gene expression. RFX4_v3 is highly expressed in the suprachiasmatic nucleus and might be involved in regulating the circadian clock. One haplotype in RFX4_v3 gene is linked to a higher risk of bipolar disorder, suggesting that this protein might contribute to the pathogenesis of the disease. This Mini-Review describes our current knowledge about RFX4_v3, an important protein that appears to be involved in many aspects of brain development and disease. (C) 2007 Wiley-Liss, Inc. C1 [Zhang, Donghui; Blackshear, Perry J.] Natl Inst Hlth, Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC USA. [Zhang, Donghui; Zeldin, Darryl C.] Natl Inst Hlth, Natl Inst Environm Hlth Sci, Lab Respirat Biol, Res Triangle Pk, NC USA. [Zhang, Donghui; Zeldin, Darryl C.; Blackshear, Perry J.] Natl Inst Hlth, Natl Inst Environm Hlth Sci, Off Clin Res, Res Triangle Pk, NC USA. [Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med Biochem, Durham, NC USA. RP Blackshear, PJ (reprint author), NIEHS, A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM black009@niehs.nih.gov FU Intramural NIH HHS [Z01 ES101583-05] NR 29 TC 9 Z9 10 U1 0 U2 3 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 DEC PY 2007 VL 85 IS 16 BP 3515 EP 3522 DI 10.1002/jnr.21356 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 243EP UT WOS:000251778200002 PM 17510980 ER PT J AU Milhorat, TH Bolognese, PA Nishikawa, M McDonnell, NB Francomano, CA AF Milhorat, Thomas H. Bolognese, Paolo A. Nishikawa, Misao McDonnell, Nazli B. Francomano, Clair A. TI Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and Chiari malformation Type I in patients with hereditary disorders of connective tissue SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE Chiari malformation; connective tissue disorders; cranial settling; craniocervical instability; Ehlers-Danlos syndrome; joint hypermobility ID EHLERS-DANLOS-SYNDROME; TRAUMATIC OCCIPITOVERTEBRAL DISSOCIATION; RHEUMATOID-ARTHRITIS; CRANIOVERTEBRAL JUNCTION; CRANIOCERVICAL JUNCTION; OCCIPITOCERVICAL FUSION; RADIOLOGIC-DIAGNOSIS; LATERAL RADIOGRAPHS; RETROODONTOID MASS; POSTERIOR-FOSSA AB Object. Chiari malformation Type I (CM-I) is generally regarded as a disorder of the paraxial mesoderm. The authors report an association between CM-I and hereditary disorders of connective tissue (HDCT) that can present with lower brainstem symptoms attributable to occipitoatlantoaxial hypermobility and cranial settling. Methods. The prevalence of HDCT was determined in a prospectively accrued cohort of 2813 patients with CM-I. All patients underwent a detailed medical and neuroradiological workup that included an assessment of articular mobility. Osseous structures composing the craniocervical junction were investigated morphometrically using reconstructed 3D computed tomography and plain x-ray images in 114 patients with HDCT/CM-I, and the results were compared with those obtained in patients with CM-I (55 cases) and healthy control individuals (55 cases). Results. The diagnostic criteria for Ehlers-Danlos syndrome and related HDCT were met in 357 (12.7%) of the 2813 cases. Hereditability was generally compatible with a pattern of autosomal dominant transmission with variable expressivity. The diagnostic features of HDCT/CM-I were distinguished from those of CM-I by clinical stigmata of connective tissue disease, a greater female preponderance (8:1 compared with 3: 1, p < 0.001), and a greater incidence of lower brainstem symptoms (0.41 compared with 0.11, p < 0.001), retroodontoid pannus formation (0.71 compared with 0.11, p < 0.001), and hypoplasia of the oropharynx (0.44 compared with 0.02, p < 0.001). Measurements of the basion-dens interval, basion-atlas interval, atlas-dens interval, dens-atlas interval, clivusatlas angle, clivus-axis angle, and atlas-axis angle were the same in the supine and upright positions in healthy control individuals and patients with CM-1. In patients with HDCT/CM-1, there was a reduction of the basion-dens interval (3.6 mm, p < 0.001), an enlargement of the basion-atlas interval (3.0 mm, p < 0.001), and a reduction of the clivus-axis angle (10.8 degrees, p < 0.001), clivus-atlas angle (5.8 degrees, p < 0.001), and atlas-axis angle (5.3 degrees, p < 0.001) on assumption of the upright position. These changes were reducible by cervical traction or returning to the supine position. Conclusions. The identification of HDCT in 357 patients with CM-I establishes an association between two presumably unrelated mesodermal disorders. Morphometric evidence in this cohort-cranial settling, posterior gliding of the occipital condyles, and reduction of the clivus-axis angle, clivus-atlas angle, and atlas-axis angle in the upright position-suggests that hypermobility of the occipitoatlantal and atlantoaxial joints contributes to retroodontoid pannus formation and symptoms referable to basilar impression. C1 N Shore LIJ Hlth Syst, Harvey Cushing Inst Neurosci, Chiari Inst, Dept Neurosurg, Manhasset, NY 11030 USA. NIA, NIH, Baltimore, MD 21224 USA. Greater Baltimore Med Ctr, Harvey Inst Med Genet, Baltimore, MD USA. RP Milhorat, TH (reprint author), N Shore LIJ Hlth Syst, Harvey Cushing Inst Neurosci, Chiari Inst, Dept Neurosurg, 300 Community Dr, Manhasset, NY 11030 USA. EM Milhorat@nshs.edu FU Intramural NIH HHS NR 54 TC 57 Z9 58 U1 2 U2 6 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD DEC PY 2007 VL 7 IS 6 BP 601 EP 609 DI 10.3171/SPI-07/12/601 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 239LN UT WOS:000251519900004 PM 18074684 ER PT J AU Timmers, HJLM Carrasquillo, JA Whatley, M Eisenhofer, G Chen, CC Ling, A Linehan, WM Pinto, PA Adams, KT Pacak, K AF Timmers, Henri J. L. M. Carrasquillo, Jorge A. Whatley, Millie Eisenhofer, Graeme Chen, Clara C. Ling, Alexander Linehan, W. Marston Pinto, Peter A. Adams, Karen T. Pacak, Karel TI Usefulness of standardized uptake values for distinguishing adrenal glands with pheochromocytoma from normal adrenal glands by use of 6-F-18-fluorodopamine PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE 6-F-18-fluorodopamine; pheochromocytoma; paraganglioma; PET ID POSITRON-EMISSION-TOMOGRAPHY; METASTATIC PHEOCHROMOCYTOMA; LOCALIZATION; SUPERIORITY AB 6-F-18-Fluorodopamine (F-18-FDA) PET is a highly sensitive tool for the localization of pheochromocytoma (PHEO). The aim of this study was to establish cutoff values for pathologic and physiologic adrenal gland tracer uptake. Methods: F-18-FDA PET with CT coregistration was performed in 14 patients (10 men and 4 women; age [mean +/- SD], 42.9 +/- 13.3 y) with unilateral adrenal gland PHEO and in 13 control subjects (5 men and 8 women; age, 51.7 +/- 12.5 y) without PHEO. Standardized uptake values (SUVs) were compared between adrenal glands with PHEO and normal left adrenal glands in control subjects. Results: F-18-FDA accumulation was observed in all adrenal glands with PHEO and in 6 of 13 control adrenal glands (P = 0.02). The SUV was higher in adrenal glands with PHEO (mean +/- SD, 16.1 +/- 6.1) than in F-18-FDA-positive control adrenal glands (7.7 +/- 1.4) (P = 0.005). SUV cutoffs for distinguishing between adrenal glands with PHEO and normal adrenal glands were 7.3 (100% sensitivity) and 10.1 (100% specificity). Conclusion: The SUVs of adrenal focion F-18-FDA PET facilitate the distinction between adrenal glands with PHEO and normal adrenal glands. C1 [Timmers, Henri J. L. M.; Adams, Karen T.; Pacak, Karel] NICHHD, Reproduct & Adult Endocrinol Program, Bethesda, MD 20892 USA. [Timmers, Henri J. L. M.] Univ Nijmegen St Radboud Hosp, Med Ctr, Dept Endocrinol, NL-6500 HB Nijmegen, Netherlands. [Carrasquillo, Jorge A.; Whatley, Millie; Chen, Clara C.] NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. [Eisenhofer, Graeme] NIH, NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. [Ling, Alexander] Natl Inst Hlth, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD USA. [Linehan, W. Marston; Pinto, Peter A.] Natl Inst Hlth, Natl Canc Inst, Canc Res Ctr, Urolog Oncol Branch, Bethesda, MD USA. RP Pacak, K (reprint author), NICHHD, Reproduct & Adult Endocrinol Program, 10 Ctr Dr,Bldg 10,CRC,Rm 1-E 3140,MC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 FU Intramural NIH HHS NR 14 TC 17 Z9 17 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2007 VL 48 IS 12 BP 1940 EP 1944 DI 10.2967/jnumed.107.043281 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258UN UT WOS:000252895100010 PM 18006611 ER PT J AU Brown, AK Fujita, M Fujimura, Y Liow, JS Stabin, M Ryu, YH Imaizumi, M Hong, J Pike, VW Innis, RB AF Brown, Amira K. Fujita, Masahiro Fujimura, Yota Liow, Jeih-San Stabin, Michael Ryu, Yong H. Imaizumi, Masao Hong, Jinsoo Pike, Victor W. Innis, Robert B. TI Radiation dosimetry and biodistribution in monkey and man of C-11-PBR28: A PET radioligand to image inflammation SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE translocator protein (18 kDa); source organ; C-11-PBR28; PET ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; PROTEIN 18 KDA; BRAIN; LIGANDS; BINDING; DAA1106; TISSUE; RAT AB C-11-PBR28 ([methyl-C-11]N-acetyl-N-(2-methoxybenzyl)-2phenoxy-5-pyridinamine) is a recently developed radioligand to image peripheral benzodiazepine receptors (PBRs) in brain. The aim of this study was to estimate the human radiation doses of C-11-PBR28 based on biodistribution data in monkeys and humans. In addition, we scanned 1 human subject who fortuitously behaved as if he lacked the PBR binding protein. Methods: Whole-body PBR images were acquired after intravenous bolus administration of C-11-PBR28 in 7 healthy humans (651 +/- 111 MBq) and 2 rhesus monkeys (370 +/- 59.9MBq). One monkey was scanned after receptor blockade with PK 11195 (10.7 mg/kg intravenously). Results: For typical subjects (subjects 1 - 6), the 3 organs with highest exposure were those with the high PBR densities (kidneys, spleen, and lungs), and the effective dose was 6.6 mu Sv/MBq. The unusual subject (subject 7) had 60% - 90% less uptake in these 3 organs, resulting in 28% lower effective dose. The activity in the baseline monkey scans was greater than that in humans for organs with high PBR densities. For this reason, the human effective dose was overestimated by 60% with monkey biodistribution data. The monkey with receptor blockade had an overall distribution qualitatively similar to that of the unusual human subject (subject 7), with decreased exposure to lungs, kidney, and spleen. Conclusion: The effective dose of C-11-PBR28 was modest and was similar to that of several other C-11-radioligands. Lack of receptor binding in the unusual human subject and in the monkey with receptor blockade decreased exposure to organs with high PER densities and enhanced uptake in excretory and metabolic pathways. C1 [Brown, Amira K.; Fujita, Masahiro; Fujimura, Yota; Liow, Jeih-San; Ryu, Yong H.; Imaizumi, Masao; Hong, Jinsoo; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Stabin, Michael] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN USA. [Ryu, Yong H.] Yonsei Univ, Coll Med, Dept Nucl Med, Seoul, South Korea. RP Brown, AK (reprint author), NIMH, Mol Imaging Branch, 31 Ctr Dr,Room B2-B34, Bethesda, MD 20892 USA. EM amirabrown@mail.nih.gov FU Intramural NIH HHS NR 18 TC 83 Z9 83 U1 0 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2007 VL 48 IS 12 BP 2072 EP 2079 DI 10.2967/jnumed.107.044842 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258UN UT WOS:000252895100027 PM 18006619 ER PT J AU Wang, INE Shan, J Choi, R Oh, S Kepler, CK Chen, FH Lu, HH AF Wang, I-Ning E. Shan, Jing Choi, Rene Oh, Seongcheol Kepler, Christopher K. Chen, Faye H. Lu, Helen H. TI Role of osteoblast-fibroblast interactions in the formation of the ligament-to-bone interface SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE fibrocartilage; interface; enthesis; co-culture; fibroblasts ID MEDIAL COLLATERAL LIGAMENT; MESENCHYMAL STEM-CELLS; TENDON GRAFT; IN-VITRO; POSTNATAL-DEVELOPMENT; X COLLAGEN; RAT KNEE; TUNNEL; RECONSTRUCTION; INSERTION AB The anterior cruciate ligament (ACL) inserts into bone through a characteristic fibrocartilagenous interface, which is essential for load transfer between soft and hard tissues. This multi-tissue interface is lost post ACL reconstruction, and the lack of an anatomic fibrocartilage interface between graft and bone remains the leading cause of graft failure. Currently, the mechanism of interface formation is not known. As a fibrocartilage-like tissue is found within the bone tunnel post ACL reconstruction, we hypothesize that fibroblast-osteoblast interactions at the graft-to-bone junction play a role in fibrocartilage formation. To test this hypothesis, a co-culture model permitting osteoblast-fibroblast communications was used to determine the effects of heterotypic interactions on cell phenotype and the development of fibrocartilage-relevant markers in vitro. It was found that co-culture decreased cell proliferation and osteoblast-mediated mineralization, while inducing fibroblast-mediated mineralization. Moreover, the expression of interface-relevant markers such as collagen type II and aggrecan were detected. Our findings suggest that osteoblast- fibroblast interactions may lead to cell trans-differentiation and eventual fibrocartilage formation. These results provide new insight into the mechanism of fibrocartilage formation, which are critical for interface tissue engineering and achieving biological fixation of soft tissue grafts to bone. (C) 2007 Orthopaedic Research Society. C1 Columbia Univ, Dept Biomed Engn, Biomat & Interface Tissue Engn Lab, New York, NY 10027 USA. NIAMSD, NIH, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branc, Bethesda, MD 20892 USA. Columbia Univ, Coll Dent Med, New York, NY 10032 USA. RP Lu, HH (reprint author), Columbia Univ, Dept Biomed Engn, Biomat & Interface Tissue Engn Lab, 1210 Amsterdam Ave,351 Engn Terrace Bldg, New York, NY 10027 USA. EM hl2052@columbia.edu FU NIAMS NIH HHS [AR052402-01A1] NR 34 TC 56 Z9 58 U1 0 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD DEC PY 2007 VL 25 IS 12 BP 1609 EP 1620 DI 10.1002/jor.20475 PG 12 WC Orthopedics SC Orthopedics GA 234QR UT WOS:000251179300009 PM 17676622 ER PT J AU Mustapha, IZ Debrey, S Oladubu, M Ugarte, R AF Mustapha, Indra Z. Debrey, Sarah Oladubu, Michael Ugarte, Richard TI Markers of systemic bacterial exposure in periodontal disease and cardiovascular disease risk: A systematic review and meta-analysis SO JOURNAL OF PERIODONTOLOGY LA English DT Review DE cardiovascular disease; C-reactive protein; immunoglobulins; periodontal disease; periodontitis; stroke ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; SERUM ANTIBODY-LEVELS; PORPHYROMONAS-GINGIVALIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ISCHEMIC-STROKE; ATHEROSCLEROSIS RISK; ADULT PERIODONTITIS; HOST RESPONSE; INFLAMMATION AB Background: Recent meta-analyses reported a weak association between periodontal disease (PD) on clinical examination and cardiovascular disease (CVD). Systemic bacterial exposure from periodontitis, which correlates poorly with the clinical examination, has been proposed as the more biologically pertinent risk factor. The purpose of this study was to review and analyze the association between PD with elevated systemic bacterial exposure and CVD. Methods: We searched in the PubMed, Cochrane Controlled Trials Register, EMBASE, and SCOPUS databases for all literature examining PD and CVD. From 10 selected publications, we extracted 12 cohort (N = 5) and cross-sectional (N = 7) studies and included 11 of these in a meta-analysis. With stratified analyses, this resulted in 14 analyses of coronary heart disease (CHD; N = 7), stroke (N = 4), and carotid intima-medial thickening (CIMT; N = 3) as a measure of early atherosclerosis. Systemic bacterial exposure was measured by periodontal bacterial burden (N=1), periodontitis-specific serology (N= 12), or C-reactive protein (N = 1). Results: Periodontal disease with elevated markers of systemic bacterial exposure was associated strongly with CHD compared to subjects without PD, with a summary odds ratio of 1.75 (95% confidence interval (CI): 1.32 to 2.34; P < 0.001). This group was not associated with CVD events or with stroke but was associated with a significant increase in mean CIMT (0.03 mm; 95% CI: 0.02 to 0.04). Conclusion: Periodontal disease with elevated bacterial exposure is associated with CHD events and early atherogenesis (CIMT), suggesting that the level of systemic bacterial exposure from periodontitis is the biologically pertinent exposure with regard to atherosclerotic risk. C1 [Mustapha, Indra Z.] Howard Univ, Dept Periodontol, Washington, DC 20059 USA. [Debrey, Sarah] NIH, Struct Neurosci Unit, Bethesda, MD USA. [Oladubu, Michael] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Ugarte, Richard] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. RP Mustapha, IZ (reprint author), 701 Pennsylvania Ave NW 1028, Washington, DC 20004 USA. EM imustaph@jhsph.edu FU NCRR NIH HHS [1KL2RR025006-01] NR 49 TC 123 Z9 131 U1 2 U2 12 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD DEC PY 2007 VL 78 IS 12 BP 2289 EP 2302 DI 10.1902/jop.2007.070140 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 245PA UT WOS:000251946300009 PM 18052701 ER PT J AU Ryder, AG Costa, PT Bagby, RM AF Ryder, Andrew G. Costa, Paul T., Jr. Bagby, R. Michael TI Evaluation of the SCID-II personality disorder traits for DSM-IV: Coherence, discrimination, relations with general personality traits, and functional impairment SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID 5 FACTOR MODEL; INTERNAL CONSISTENCY; 5-FACTOR MODEL; COOCCURRENCE; CRITERIA; OVERLAP; CLPS AB The utility of the DSM personality disorder (PD) system remains a concern. The strategy employed represents one approach designed to evaluate and improve the diagnostic efficiency of the SCID-II PDs. Using a sample of 203 patients, SCID-II PD items - based on the criterion sets of the 10 DSM-lV PDs - were evaluated with respect to (a) convergent validity; (b) divergent validity; (c) relation to general personality traits; and (d) association with functional impairment. Only Borderline PD items were satisfactory on all four evaluation criteria. Histrionic and Obsessive-Compulsive PD items met criteria for convergent and divergent validity and relation to personality dimensions of the Five-Factor Model of Personality (FFM) but were not related to functional impairment, suggesting they might be reconsidered as disorders. Schizotypal PD items met three of the four criteria but showed no relation to FFM dimensions, suggesting that it may be a candidate for reassignment to Axis I. C1 [Bagby, R. Michael] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. [Ryder, Andrew G.] Concordia Univ, Montreal, PQ, Canada. [Costa, Paul T., Jr.] NIA, Bethesda, MD 20892 USA. RP Bagby, RM (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, 250 Coll St, Toronto, ON M5T 1R8, Canada. EM michael_bagby@camh.net RI Ryder, Andrew/A-1108-2008; OI Ryder, Andrew/0000-0003-3041-7168; Costa, Paul/0000-0003-4375-1712 NR 23 TC 12 Z9 13 U1 0 U2 6 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD DEC PY 2007 VL 21 IS 6 BP 626 EP 637 DI 10.1521/pedi.2007.21.6.626 PG 12 WC Psychiatry SC Psychiatry GA 239YN UT WOS:000251554300004 PM 18072864 ER PT J AU Minton, AP AF Minton, Allen P. TI The effective hard particle model provides a simple, robust, and broadly applicable description of nonideal Behavior in concentrated solutions of bovine serum albumin and other nonassociating proteins SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE protein-protein interaction; excluded volume; osmotic pressure; light scattering; sedimentation equilibrium ID OSMOTIC-PRESSURE; LIGHT-SCATTERING; CHALLENGES; HEMOGLOBIN; EQUILIBRIA; DEPENDENCE; PH AB Published data on the concentration dependence of osmotic pressure of solutions of bovine serum albumin in 0.15 M NaCl at concentrations up to greater than 400 g/L are shown to be described to within experimental uncertainty by a simple one-parameter model in which protein molecules are represented by effective hard spherical particles. The volume of the effective hard particle reflects both steric and electrostatic repulsion and thus varies with pH and ionic strength. The pH dependence of the effective volume is shown to agree well with that previously obtained from analysis of the concentration dependence of sedimentation equilibrium and static light scattering. (c) 2007 Wiley-Liss, Inc. C1 NIH, NIDDKD, US Dept Hlth & Human Serv, Lab Biochem & Genet,Sect Phys Biochem, Bethesda, MD 20892 USA. RP Minton, AP (reprint author), NIH, NIDDKD, US Dept Hlth & Human Serv, Lab Biochem & Genet,Sect Phys Biochem, Bldg 8,Room 226, Bethesda, MD 20892 USA. EM minton@helix.nih.gov OI Minton, Allen/0000-0001-8459-1247 NR 19 TC 39 Z9 39 U1 1 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD DEC PY 2007 VL 96 IS 12 BP 3466 EP 3469 DI 10.1002/jps.20964 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 236XW UT WOS:000251337800025 PM 17588257 ER PT J AU Zhao, Y Valdez, GR Fekete, EM Rivier, JE Vale, WW Rice, KC Weiss, F Zorrilla, EP AF Zhao, Y. Valdez, G. R. Fekete, E. M. Rivier, J. E. Vale, W. W. Rice, K. C. Weiss, F. Zorrilla, E. P. TI Subtype-selective corticotropin-releasing factor receptor Agonists exert contrasting, but not opposite, effects on anxiety-related Behavior in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SOCIAL-INTERACTION TEST; HORMONE RECEPTOR-2; MOTOR-ACTIVITY; UROCORTIN-III; STRESS; MICE; CRF; ANTAGONIST; PEPTIDE; NEUROENDOCRINE AB The corticotropin-releasing factor (CRF) system mediates stress responses. Extrahypothalamic CRF1 receptor activation has anxiogenic-like properties, but anxiety-related functions of CRF2 receptors remain unclear. The present study determined the effects of intracerebroventricular administration of a CRF2 agonist, urocortin 3, on behavior of male Wistar rats in the shock-probe, social interaction, and defensive withdrawal tests of anxiety-like behavior. Equimolar doses of stressin(1)-A, a novel CRF1 agonist, were administered to separate rats. The effects of pyrazolo[1,5-a]-1,3,5-triazin-4-amine,8-[4-(bromo)-2-chlorophenyl]- N,N-bis(2-methoxyethyl)-2,7-dimethyl-(9Cl) (MJL-1-109-2), a CRF1 antagonist, on behavior in the shock probe test also were studied. Stressin(1)-A increased anxiety-like behavior in the social interaction and shock-probe tests. Stressin(1) -A elicited behavioral activation and defensive burying at lower doses (0.04 nmol), but it increased freezing, grooming, and mounting at 25-fold higher (1-nmol) doses. Conversely, systemic administration of MJL-1-109-2 (10 mg/kg) had anxiolytic-like effects in the shock-probe test. Unlike stressin(1)-A or MJL-1-109-2, i.c.v. urocortin 3 infusion did not alter anxiety-like behavior in the shock-probe test across a range of doses that reduced locomotion and rearing and increased grooming. Urocortin 3 also did not decrease social interaction, but it decreased anxiety-like behavior in the defensive withdrawal test at a 2-nmol dose. Thus, i.c.v. administration of CRF1 and CRF2 agonists produced differential, but not opposite, effects on anxiety-like behavior. Urocortin 3 (i.c.v.) did not consistently decrease or increase anxiety-like behavior, the latter unlike effects seen previously after local microinjection of CRF2 agonists into the septum or raphe. With increasing CRF1 activation, however, the behavioral expression of anxiety qualitatively changes from "coping" to "noncoping" and offensive, agonistic behaviors. C1 Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. Scripps Res Inst, Harold L Dorris Neurol Res Inst, La Jolla, CA USA. Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA USA. Grand Valley State Univ, Dept Psychol, Allendale, MI 49401 USA. Univ Pecs, Sch Med, Inst Physiol, Pecs, Hungary. Natl Inst Drug Abuse, Chem Biol Res Brach, Natl Inst Hlth, Bethesda, MD USA. Salk Inst Biol Studies, Peptide Biol Lab, La Jolla, CA USA. RP Zhao, Y (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, SP30-2400,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU Intramural NIH HHS; NIAAA NIH HHS [AA006420]; PHS HHS [NIDDK 64871, NIDDK 26741] NR 42 TC 48 Z9 49 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2007 VL 323 IS 3 BP 846 EP 854 DI 10.1124/jpet.107.123208 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 231RO UT WOS:000250966900012 PM 17855476 ER PT J AU Zhang, HM Zhou, HY Chen, SR Gautam, D Wess, J Pan, HL AF Zhang, Hong-Mei Zhou, Hong-Yi Chen, Shao-Rui Gautam, Dinesh Wess, Jurgen Pan, Hui-Lin TI Control of Glycinergic input to spinal dorsal horn neurons by distinct muscarinic receptor subtypes revealed using knockout mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACETYLCHOLINE-RECEPTOR; CHOLINERGIC RECEPTORS; AUTORADIOGRAPHIC LOCALIZATION; CHOLINESTERASE INHIBITION; GABA(B) RECEPTORS; GABAERGIC INPUTS; CORD; RAT; ANTAGONISTS; ANALGESIA AB Muscarinic acetylcholine receptors (mAChRs) play an important role in the tonic regulation of nociceptive transmission in the spinal cord. However, how mAChR subtypes contribute to the regulation of synaptic glycine release is unknown. To determine their role, glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded in lamina II neurons by using whole-cell recordings in spinal cord slices of wild-type (WT) and mAChR subtype knockout (KO) mice. In WT mice, the mAChR agonist oxotremorine-M dose-dependently decreased the frequency of sIPSCs in most neurons, but it had variable effects in other neurons. In contrast, in M3-KO mice, oxotremorine-M consistently decreased the glycinergic sIPSC frequency in all neurons tested, and in M2/M4 double-KO mice, it always increased the sIPSC frequency. In M-2/M-4 double-KO mice, the potentiating effect of oxotremorine-M was attenuated by higher concentrations in some neurons through activation of GABA B receptors. In pertussis toxin-treated WT mice, oxotremorine-M also consistently increased the sIPSC frequency. In M-2-KO and M-4-KO mice, the effect of oxotremorine-M on sIPSCs was divergent because of the opposing functions of the M-3 subtype and the M-2 and M-4 subtypes. This study demonstrates that stimulation of the M-2 and M-4 subtypes inhibits glycinergic inputs to spinal dorsal horn neurons of mice, whereas stimulation of the M-3 subtype potentiates synaptic glycine release. Furthermore, GABA(B) receptors are involved in the feedback regulation of glycinergic synaptic transmission in the spinal cord. This study revealed distinct functions of mAChR subtypes in controlling glycinergic input to spinal dorsal horn neurons. C1 Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Pain Med, Unit 110, Houston, TX 77030 USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Zhang, HM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Pain Med, Unit 110, 1515 Holcombe Blvd, Houston, TX 77030 USA. RI Zhou, Hong-Yi/A-5619-2010 FU NIGMS NIH HHS [GM64830]; NINDS NIH HHS [NS45602] NR 41 TC 7 Z9 10 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2007 VL 323 IS 3 BP 963 EP 971 DI 10.1124/jpet.107.127795 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 231RO UT WOS:000250966900025 PM 17878406 ER PT J AU Low, N Cui, LH Merikangas, KR AF Low, Nancy Cui, Lihong Merikangas, Kathleen R. TI Spousal concordance for substance use and anxiety disorders SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE spousal concordance; assortative mating; psychiatric genetics; substance abuse/dependence disorders; anxiety disorders ID FAMILY HISTORY METHOD; PSYCHIATRIC-DISORDERS; ALCOHOL-USE; SOCIAL-ADJUSTMENT; COMMUNITY SAMPLE; MARRIED-COUPLES; UNITED-STATES; PERSONALITY; POPULATION; SIMILARITY AB Assortative mating - the tendency for mate selection to occur on the basis of similar traits - plays an essential role in understanding the genetic contribution to psychiatric illness. It also carries significant impact on clinical prognosis and is an important mechanism explaining spousal concordance. This study uses a family study design ascertaining 225 probands with substance abuse/dependence, anxiety disorders. and controls to address: (1) is there spousal concordance or cross-concordance for substance use and/or anxiety disorders? (2) Is the spousal concordance or cross-concordance associated with worse clinical outcomes? (3) What is the mechanism of the concordance or cross-concordance? Results show a high magnitude of spousal concordance for substance use disorders with a third of the substance probands' spouses also substance dependent. In contrast, there was no spousal concordance for anxiety disorders. Couples were also concordant for having "no disorders." Both substance use and anxiety disorder concordance were associated with poorer global functioning and persistent illness. Assortative mating is a likely mechanism for spousal concordance given the elevated rate of substance use disorders among the relatives of spouses' of substance probands. Implications for family/genetic studies and the transmission of substance use disorders and "no disorders" include: (1) at the individual level, spousal concordance influences probands' course of illness, couples marital functioning, and offspring's genetic and environmental context; and (2) at the population level, it shifts the general distribution of substance use disorders and "no disorders" by reducing the "average" couple concordance and increasing the number concordant and discordant couples at extremes of the distribution. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIMH, Sect Dev Genet Epidemiol, Mood & Anxiety Disorders Program, Intramural Res Program,NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Low, N (reprint author), NIMH, Sect Dev Genet Epidemiol, Mood & Anxiety Disorders Program, Intramural Res Program,NIH,Dept Hlth & Human Serv, 35 Convent Dr MSC 3720, Bethesda, MD 20892 USA. EM Nancy.Low@nih.gov NR 70 TC 21 Z9 21 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD DEC PY 2007 VL 41 IS 11 BP 942 EP 951 DI 10.1016/j.jpsychires.2006.11.003 PG 10 WC Psychiatry SC Psychiatry GA 213LU UT WOS:000249669700007 PM 17204289 ER PT J AU Tsuji, Y Kimura, T Akamatsu, T Hirose, K Okai, T Komaki, G AF Tsuji, Yumiko Kimura, Takehiko Akamatsu, Tatsuya Hirose, Kazuhiro Okai, Takashi Komaki, Gen TI The role of clinical psychologist working in the obstetrics and gynecology: Based on the experience of 12 years SO JOURNAL OF PSYCHOSOMATIC OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 [Kimura, Takehiko; Okai, Takashi] Showa Univ, Dept Obstet & Gynecol, Tokyo, Japan. [Hirose, Kazuhiro] Chiba Nishi Gen Hosp, Dept Obstet & Gynecol, Chiba, Japan. [Komaki, Gen] NIMH, Natl Ctr Neurol & Psychiat, Dept Psychosomat Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0167-482X J9 J PSYCHOSOM OBST GYN JI J. Psychosomat. Obstet. Gynecol. PD DEC PY 2007 VL 28 SU 1 BP 86 EP 86 PG 1 WC Psychology, Clinical; Obstetrics & Gynecology; Psychiatry SC Psychology; Obstetrics & Gynecology; Psychiatry GA 258GA UT WOS:000252855200233 ER PT J AU Vitiello, B Kratochvil, CJ Silva, S Curry, J Reinecke, M Pathak, S Waslick, B Hughes, CW Prentice, ED May, DE March, JS AF Vitiello, Benedetto Kratochvil, Christopher J. Silva, Susan Curry, John Reinecke, Mark Pathak, Sanjeev Waslick, Bruce Hughes, Carroll W. Prentice, Ernest D. May, Diane E. March, John S. TI Research knowledge among the participants in the Treatment for Adolescents with Depression Study (TADS) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE depression; treatment; ethics ID RANDOMIZED CONTROLLED-TRIALS; INFORMED-CONSENT; CLINICAL-RESEARCH; CHILDREN; PARENTS; PSYCHOPHARMACOLOGY; ATTITUDES; QUALITY AB Objective: We examined the extent to which parents and adolescents participating in the Treatment for Adolescents With Depression Study (TADS) understood key aspects of the study. Method: TADS was a clinical trial comparing the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), their combination, and placebo in 439 adolescents (112-17 years old) with major depressive disorder. Six weeks after starting treatment, adolescents and their parents were asked to complete a questionnaire about critical elements of the trial. Results: Completion rate was 67.2% for adolescents (N = 295) and 73.6% for parents (N = 323). More than 90% of the completers knew of the main purpose of the trial, possible assignment to placebo, and their right to withdraw participation at any time. However, about one third overall (and 49% in the CBT group) described TADS as "education" rather than "research." Of 12 questions, the mean number of correct answers was 10.3 (SID 1.7) among adolescents and 11.2 (SD 1.2) among parents (p < .0001). The most frequently stated reason for TADS participation was the pursuit of high-quality care. Conclusions: Most parents and adolescents were well-informed research participants. Difficulties in appreciating the research nature of the trial, however, emerged, especially among participants assigned to psychotherapy. Parents were overall better informed than adolescents. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. Univ Nebraska Med Ctr, Omaha, NE 68198 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Northwestern Univ, Evanston, IL 60208 USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA. Baystate Med Ctr, Springfield, MA 01199 USA. RP Vitiello, B (reprint author), NIMH, Div Serv & Intervent Res, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov RI Espinosa, Daniel/B-7285-2012 FU NIMH NIH HHS [N01 MH80008] NR 26 TC 10 Z9 10 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2007 VL 46 IS 12 BP 1642 EP 1650 DI 10.1097/chi.0b013e318153f8c7 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 234DV UT WOS:000251141800013 PM 18030086 ER PT J AU Pennington, JAT Stumbo, PJ Murphy, SP Mcnutt, SW Eldridge, AL McCabe-Sellers, BJ Chenard, CA AF Pennington, Jean A. T. Stumbo, Phyllis J. Murphy, Suzanne P. Mcnutt, Suzanne W. Eldridge, Alison L. McCabe-Sellers, Beverly J. Chenard, Catherine A. TI Food composition data: The foundation of dietetic practice and research SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Review ID NUTRIENT DATA-BASES; COMPOSITION DATABASES; DIETARY-SUPPLEMENTS; NIH OFFICE; NUTRITION; SYSTEM; SOFTWARE; VALUES; RESTAURANTS; VEGETABLES AB Food composition databases and dietary assessment systems are important tools for food and nutrition professionals. The availability and accessibility of data have improved over time along with the technology to convert the information into useful formats for planning diets, writing educational materials, counseling patients, and conducting research. Primary sources of food composition data include government, academic, and other institutional databases; the food industry; and scientific literature. Changes in the marketplace affect food availability and composition and affect the accuracy and adequacy of food composition databases. Improvements in both food composition data and in dietary assessment methods have worked synergistically to improve estimates of dietary intake. The development of databases for food frequency assessment systems requires special considerations for data aggregation for each food or food grouping in the questionnaires. Considerations for selecting a dietary assessment system include appropriateness of the data for the intended audience or purpose, efficiency of the search strategy for retrieving data, content and format of summary information, and cost. Needs for food composition data vary depending on dietetic practice area; however, most food and nutrition professionals will benefit from becoming more informed about food composition data, exploring new ways to educate themselves about databases and database systems, and advocating for what is most needed in dietetic practice. C1 [Pennington, Jean A. T.] Natl Inst Hlth, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. [Stumbo, Phyllis J.; Chenard, Catherine A.] Univ Iowa, Gen Clin Res Ctr, Iowa City, IA USA. [Murphy, Suzanne P.] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Mcnutt, Suzanne W.] Westat Corp, Salt Lake City, UT USA. [Eldridge, Alison L.] Gen Mills Bell Inst Hlth & Nutr, Div Nutr Sci, Minneapolis, MN USA. [McCabe-Sellers, Beverly J.] USDA ARS, Lower Mississippi Delta Nutr Intervent Res Initia, Little Rock, AR USA. RP Pennington, JAT (reprint author), Natl Inst Hlth, Div Nutr Res Coordinat, 6707 Democracy Blvd,Room 629, Bethesda, MD 20892 USA. EM Jpl57d@nih.gov NR 87 TC 27 Z9 27 U1 0 U2 12 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 2007 VL 107 IS 12 BP 2105 EP 2113 DI 10.1016/j.jada.2007.09.004 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 239ZY UT WOS:000251558000013 PM 18060896 ER PT J AU Mazzaglia, G Roti, L Corsini, G Colombini, A Maciocco, G Marchionni, N Buiatti, E Ferrucci, L Di Bari, M AF Mazzaglia, Giampiero Roti, Lorenzo Corsini, Giacomo Colombini, Angela Maciocco, Gavino Marchionni, Niccolo Buiatti, Eva Ferrucci, Luigi Di Bari, Mauro TI Screening of older community-dwelling people at risk for death and hospitalization: The assistenza socio-sanitaria in italia project SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE elderly; mortality; hospitalization; screening ID ELDERLY-PEOPLE; DEPRESSIVE SYMPTOMS; FUNCTIONAL DECLINE; MORTALITY; VALIDATION; ADMISSION; TRIAL; INDEX; CARE; COMORBIDITY AB OBJECTIVES: To develop and validate mortality and hospitalization prognostic tools based upon information readily available to primary care physicians (PCPs). DESIGN: Population-based cohort study. Baseline predictors were patient demographics, a seven-item questionnaire on functional status and general health, use of five or more drugs, and previous hospitalization. SETTING: Community-based study. PARTICIPANTS: Prognostic indexes were developed in 2,470 subjects and validated in 2,926 subjects, all community-dwelling, aged 65 and older, and randomly sampled from the rosters of 98 PCPs in Florence, Italy. MEASUREMENTS: Fifteen-month mortality and hospitalization. RESULTS: Two scores were derived from logistic regression models and used to stratify participants into four groups. With Model 1, based upon the seven-item questionnaire, mortality rate ranged from 0.8% in the lowest-risk group (0-1 point) to 9.4% in the highest risk group (>= 3 points), and hospitalization rate ranged from 12.4% to 29.3%; area under the receiver operating characteristic curves ( AUC) was 0.75 and 0.60, respectively. With Model 2, considering also drug use and previous hospitalization, mortality and hospitalization rates ranged from 0.3% to 8.2% and from 8.1% to 29.7%, for the lowest-risk to the highest-risk group; the AUC increased significantly only for hospitalization (0.67). CONCLUSION: Prediction of death and hospitalization in older community-dwelling people can be easily obtained with two indexes using information promptly available to PCPs. These tools might be useful for guiding clinical care and targeting interventions to reduce the need for hospital care in older persons. C1 Univ Florence, Dept Crit Care Med & Surg, Unit Gerontol & Geriatr, I-50141 Florence, Italy. Reg Agcy Healthcare Syst, Unit Geriatr, Florence, Italy. Univ Florence, Dept Publ Hlth, Florence, Italy. Azienda Osped Univ Careggi, Florence, Italy. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Di Bari, M (reprint author), Univ Florence, Dept Crit Care Med & Surg, Unit Gerontol & Geriatr, Via Oblate 4, I-50141 Florence, Italy. EM dibari@unifi.it RI DI BARI, MAURO/J-1524-2012 FU Intramural NIH HHS [Z99 AG999999] NR 41 TC 27 Z9 27 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2007 VL 55 IS 12 BP 1955 EP 1960 DI 10.1111/j.1532-5415.2007.01446.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 238FV UT WOS:000251433700008 PM 17944891 ER PT J AU Kamijo, Y Hora, K Kono, K Takahashi, K Higuchi, M Ehara, T Kiyosawa, K Shigematsu, H Gonzalez, FJ Aoyama, T AF Kamijo, Yuji Hora, Kazuhiko Kono, Keiichi Takahashi, Kyoko Higuchi, Makoto Ehara, Takashi Kiyosawa, Kendo Shigematsu, Hidekazu Gonzalez, Frank J. Aoyama, Toshifumi TI PPAR alpha protects proximal tubular cells from acute fatty acid toxicity SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; RAT-LIVER MITOCHONDRIA; BETA-OXIDATION ENZYMES; FACTOR-KAPPA-B; TUBULOINTERSTITIAL DAMAGE; BINDING PROTEIN; OBESE RATS; IN-VITRO; APOPTOSIS; EXPRESSION AB Fatty acids bound to albumin are filtered through glomeruli, reabsorbed by proximal tubular epithelial cells, and metabolized. Because albumin serves as a carrier, an increase in delivery of fatty acids to the proximal tubule may occur in proteinuric states, possibly leading to toxic effects. At present, the contribution of fatty acids to tubulointerstitial damage and the mechanisms underlying this toxicity remain unclear. We recently found that the transcription factor peroxisome proliferator-activated receptor a (PPAR alpha) regulates fatty acid metabolism in proximal tubules, so we tested its role in tubular damage under proteinuric conditions. We induced protein-overload nephropathy in Ppara-null or wildtype (WT) mice by injecting fatty acids bound to BSA. Ppara-null mice exhibited greater renal dysfunction from severe proximal tubular injury than WT mice. Kidneys from Ppara-null mice injected with albumin alone showed little injury. Acute tubular injury was associated with deranged fatty acid homeostasis, increased oxidative stress, increased apoptosis, and activation of NF kappa B signaling. These results suggest a role for fatty acids in proteinuria-associated tubular toxicity, as well as a protective role for PPARa. Modulation of PPARa may be a future therapeutic option for tubular toxicity from fatty acids. C1 [Kamijo, Yuji; Kono, Keiichi; Takahashi, Kyoko; Aoyama, Toshifumi] Shinshu Univ, Sch Med, Dept Metabol Regulat, Inst Aging & Adaptat, Matsumoto, Nagano 3908621, Japan. [Kamijo, Yuji; Hora, Kazuhiko; Kono, Keiichi; Takahashi, Kyoko; Higuchi, Makoto; Kiyosawa, Kendo] Shinshu Univ, Sch Med, Dept Internal Med, Matsumoto, Nagano 3908621, Japan. [Ehara, Takashi; Shigematsu, Hidekazu] Shinshu Univ, Sch Med, Dept Pathol, Matsumoto, Nagano 3908621, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Kamijo, Y (reprint author), Shinshu Univ, Sch Med, Dept Metabol Regulat, Inst Aging & Adaptat, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. EM yujibeat@hsp.md.shinshu-u.ac.jp NR 47 TC 42 Z9 43 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2007 VL 18 IS 12 BP 3089 EP 3100 DI 10.1681/ASN.2007020238 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 241AG UT WOS:000251628700012 PM 17978304 ER PT J AU Cai, B Dunson, DB AF Cai, Bo Dunson, David B. TI Bayesian multivariate isotonic regression splines: Applications to carcinogenicity studies SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE factor model; functional data analysis; monotone curves; multiple outcomes; seemingly unrelated regression; tumor data ID SEEMINGLY UNRELATED REGRESSIONS; NONPARAMETRIC REGRESSION; LONGITUDINAL DATA; VARIABLE SELECTION; TUMOR-INCIDENCE; BODY-WEIGHT; MODELS; CURVES AB In many applications, interest focuses on assessing the relationship between a predictor and a multivariate outcome variable, and there may be prior knowledge about the shape of the regression curves. For example, regression functions that relate dose of a possible risk factor to different adverse outcomes can often be assumed to be nondecreasing. In such cases, interest focuses on (1) assessing evidence of an overall adverse effect, (2) determining which outcomes are most affected, and (3) estimating outcome-specific regression curves. This article proposes a Bayesian approach for addressing this problem, motivated by multi site tumor data from carcinogenicity experiments. A multivariate smoothing spline model is specified, that accommodates dependency in the multiple curves through a hierarchical Markov random field prior for the basis coefficients, while also allowing for residual correlation. A Gibbs sampler is proposed for posterior computation, and the approach is applied to data on body weight and tumor occurrence. C1 [Cai, Bo] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Dunson, David B.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. RP Cai, B (reprint author), Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. EM bocai@gwm.sc.edu; dunson1@niehs.nih.gov NR 31 TC 13 Z9 13 U1 1 U2 9 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2007 VL 102 IS 480 BP 1158 EP 1171 DI 10.1198/016214506000000942 PG 14 WC Statistics & Probability SC Mathematics GA 243WY UT WOS:000251829200011 ER PT J AU Peddada, SD Dinse, GE Kissling, GE AF Peddada, Shyamal D. Dinse, Gregg E. Kissling, Grace E. TI Incorporating historical control data when comparing tumor incidence rates SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE cancer bioassay; carcinogenicity experiment; National Toxicology Program; order-restricted inference; poly-3; quantal response; survival adjustment ID QUANTAL-RESPONSE TEST; TREND TESTS; CONTROL INFORMATION; BINARY DATA; CARCINOGENICITY; PROPORTIONS AB Animal carcinogenicity studies, such as those conducted by the U.S. National Toxicology Program (NTP), focus on detecting trends in tumor rates across dose groups. Over time, the NTP has compiled vast amounts of data on tumors in control animals. Currently, this information is used informally, without the benefit of statistical tests for carcinogenicity that directly incorporate historical data on control animals. This article proposes a survival-adjusted test for detecting dose-related trends in tumor incidence rates, which incorporates data on historical control rates and formally accounts for variation in these rates among studies. An extensive simulation, based on a wide range of realistic situations, demonstrates that the proposed test performs well compared with the current NTP test. which does not incorporate historical control data. In particular, our test can aid in interpreting the occurrence of a few tumors in treated animals that are rarely seen in controls. One such example, which motivates our work, concerns the analysis of histiocytic sarcoma in the NTP's 2-year cancer bioassay of benzophenone. Whereas the occurrence of three histiocytic sarcomas in female rats was not significant according to the current NTP testing procedure (p =.074), it was highly significant (p =.004) when control data from six recent historical studies were included and our test was applied to the combined data. C1 [Peddada, Shyamal D.; Dinse, Gregg E.; Kissling, Grace E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Peddada, SD (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM peddada@niehs.nih.gov; dinse@niehs.nih.gov; kissling@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 FU Intramural NIH HHS [Z01 ES101744-04] NR 31 TC 11 Z9 11 U1 1 U2 8 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2007 VL 102 IS 480 BP 1212 EP 1220 DI 10.1198/016214506000001356 PG 9 WC Statistics & Probability SC Mathematics GA 243WY UT WOS:000251829200015 PM 20396669 ER PT J AU Shen, Y Qin, J Costantino, JR AF Shen, Yu Qin, Jing Costantino, Joseph R. TI Inference of tamoxifen's effects on prevention of breast cancer from a randomized controlled trial SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE cancer prevention; cure rate model; National Surgical Adjuvant Breast and Bowel Project Trial; semiparametric model; tamoxifen ID SURGICAL ADJUVANT BREAST; LONG-TERM SURVIVORS; SEMIPARAMETRIC MODELS; MIXTURE-MODELS; FRACTION; OUTCOMES AB The largest randomized, double-blind, placebo-controlled chemoprevention trial, the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Trial (NSABP-BCPT), evaluated the efficacy of tamoxifen in preventing breast cancer among women at high risk of developing the disease. The trial has reported a reduction of breast cancer incidence for the tamoxifen group; however, the effect of tamoxifen on the time to diagnosis of the disease over the 6-year follow-up of the trial has not been fully explored in the literature. We propose a flexible semiparametric model to assess the effects of tamoxifen on the incidence of breast cancer as well as time to diagnosis of the disease separately in the framework of a cure rate model. We used an estimating equation approach to estimating the unknown parameters and assessed the semiparametric model assumption with a test based on the area between two survival curves. In the NSABP-BCPT data, we found that tamoxifen has a substantial effect in reducing invasive breast cancer events in estrogen receptor (ER)-positive tumors, but has no effect on ER-negative tumors. Among women diagnosed with ER-positive breast cancer during study follow-up, there was little difference in terms of time to diagnosis between the two arms. However, tamoxifen may advance the time to breast cancer diagnosis for ER-negative breast cancer, whereas the incidence of ER-negative tumors is similar in the two treatment arms. C1 [Shen, Yu] MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Qin, Jing] Howard Hughes Med Inst, Natl Inst All & Infect Dis, Bethesda, MD 20817 USA. [Costantino, Joseph R.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA. RP Shen, Y (reprint author), MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. EM yshen@tndanderson.org; jingqin@niaid.nih.gov; costan@nsabp.pitt.edu OI Shen, Yu/0000-0002-3899-7868 FU NCI NIH HHS [U10 CA037377, R01 CA079466-07, U10 CA069974, R01 CA079466] NR 33 TC 7 Z9 7 U1 1 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2007 VL 102 IS 480 BP 1235 EP 1244 DI 10.1198/016214506000001446 PG 10 WC Statistics & Probability SC Mathematics GA 243WY UT WOS:000251829200017 PM 19662105 ER PT J AU Gallas, BD Pennello, GA Myers, KJ AF Gallas, Brandon D. Pennello, Gene A. Myers, Kyle J. TI Multireader multicase variance analysis for binary data SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID DORFMAN-BERBAUM-METZ; OPERATING CHARACTERISTIC ANALYSIS; CHARACTERISTIC ROC DATA; MRMC METHOD; MODEL; VALIDATION AB Multireader multicase (MRMC) variance analysis has become widely utilized to analyze observer studies for which the summary measure is the area under the receiver operating characteristic (ROC) curve. We extend MRMC variance analysis to binary data and also to generic study designs in which every reader may not interpret every case. A subset of the fundamental moments central to MRMC variance analysis of the area under the ROC curve (AUC) is found to be required. Through multiple simulation configurations, we compare our unbiased variance estimates to naive estimates across a range of study designs, average percent correct, and numbers of readers and cases. C1 [Gallas, Brandon D.; Pennello, Gene A.; Myers, Kyle J.] US FDA, Natl Inst Biomed Imaging & Bioengn, Ctr Derices & Radiol Hlth, Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. RP Gallas, BD (reprint author), US FDA, Natl Inst Biomed Imaging & Bioengn, Ctr Derices & Radiol Hlth, Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. EM brandon.gallas@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 15 TC 17 Z9 17 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD DEC PY 2007 VL 24 IS 12 BP B70 EP B80 DI 10.1364/JOSAA.24.000B70 PG 11 WC Optics SC Optics GA 248BP UT WOS:000252126600008 PM 18059916 ER PT J AU Park, S Barrett, HH Clarkson, E Kupinski, MA Myers, KJ AF Park, Subok Barrett, Harrison H. Clarkson, Eric Kupinski, Matthew A. Myers, Kyle J. TI Channelized-ideal observer using Laguerre-Gauss channels in detection tasks involving non-Gaussian distributed lumpy backgrounds and a Gaussian signal SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID DETECTION PERFORMANCE; OBJECTIVE ASSESSMENT; IMAGE QUALITY; NOISE; MODEL AB We investigate a channelized-ideal observer (CIO) with Laguerre-Gauss (LG) channels to approximate ideal-observer performance in detection tasks involving non-Gaussian distributed lumpy backgrounds and a Gaussian signal. A Markov-chain Monte Carlo approach is employed to determine the performance of both the ideal observer and the CIO using a large number of LG channels. Our results indicate that the CIO with LG channels can approximate ideal-observer performance within error bars, depending on the imaging system, object, and channel parameters. The CIO also outperforms a channelized-Hotelling observer using the same channels. In addition, an alternative approach for estimating the CIO is investigated. This approach makes use of the characteristic functions of channelized data and employs an approximation method to the area under the receiver operating characteristic curve. The alternative approach provides good estimates of the performance of the CIO with five LG channels. However, for large channel cases, more efficient computational methods need to be developed for the CIO to become useful in practice. (C) 2007 Optical Society of America. C1 [Park, Subok; Myers, Kyle J.] US FDA, Natl Inst Biomed Imaging & Bioengn, CDRH, Lab Assessment Med Imaging Syst,Div Imaging & App, Silver Spring, MD 20993 USA. [Barrett, Harrison H.; Clarkson, Eric; Kupinski, Matthew A.] Univ Arizona, Ctr Opt Sci, Tucson, AZ 85724 USA. [Barrett, Harrison H.; Clarkson, Eric; Kupinski, Matthew A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Park, S (reprint author), US FDA, Natl Inst Biomed Imaging & Bioengn, CDRH, Lab Assessment Med Imaging Syst,Div Imaging & App, Silver Spring, MD 20993 USA. EM stibok.park@fda.hhs.gov FU Intramural NIH HHS; NIBIB NIH HHS [R37 EB000803, P41EB002035, R37EB000803, P41 EB002035-09, P41 EB002035, R37 EB000803-17] NR 19 TC 27 Z9 27 U1 1 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD DEC PY 2007 VL 24 IS 12 BP B136 EP B150 DI 10.1364/JOSAA.24.00B136 PG 15 WC Optics SC Optics GA 248BP UT WOS:000252126600014 PM 18059906 ER PT J AU Kupinski, MA Watson, AB Siewerdsen, JH Myers, KJ Eckstein, M AF Kupinski, Matthew A. Watson, Andrew B. Siewerdsen, Jeffrey H. Myers, Kyle J. Eckstein, Miguel TI Image quality - Introduction SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Editorial Material C1 [Kupinski, Matthew A.] Univ Arizona, Coll Opt sci, Tucson, AZ 85721 USA. [Kupinski, Matthew A.] Univ Arizona, Dept Radiol, Tucson, AZ 85721 USA. [Watson, Andrew B.] NASA, Ames Res Ctr, Vis Grp, Moffett Field, CA 94035 USA. [Siewerdsen, Jeffrey H.] Univ Toronto, Div Biophys & Bioimaging, Toronto, ON M5G 2M9, Canada. [Myers, Kyle J.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. [Eckstein, Miguel] Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA. RP Kupinski, MA (reprint author), Univ Arizona, Coll Opt sci, Tucson, AZ 85721 USA. EM mkupinski@optics.arizona.edu; andrew.b.watson@nasa.gov; jsiewerd@uhnres.utoronto.ca; kyle.myers@fda.hhs.gov; eckstein@psych.ucsb.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD DEC PY 2007 VL 24 IS 12 PG 1 WC Optics SC Optics GA 248BP UT WOS:000252126600001 ER PT J AU Velazquez, EJ Lee, KL O'Connor, CM Oh, JK Bonow, RO Pohost, GM Feldman, AM Mark, DB Panza, JA Sopko, G Rouleau, JL Jones, RH AF Velazquez, Eric J. Lee, Kerry L. O'Connor, Christopher M. Oh, Jae K. Bonow, Robert O. Pohost, Gerald M. Feldman, Arthur M. Mark, Daniel B. Panza, Julio A. Sopko, George Rouleau, Jean L. Jones, Robert H. CA STICH Investigators TI The rationale and design of the Surgical Treatment for Ischemic Heart Failure (STICH) trial SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; CORONARY-ARTERY-DISEASE; REVERSIBLE MYOCARDIAL DYSFUNCTION; SYSTOLIC DYSFUNCTION; GUIDELINE UPDATE; RANDOMIZED TRIAL; CLINICAL-TRIALS; REVASCULARIZATION; VIABILITY; SURVIVAL AB Objectives: The rationale and design of the Surgical Treatment for Ischemic Heart Failure trial is described. Before the Surgical Treatment for Ischemic Heart Failure trial, less than 1000 patients with ischemic cardiomyopathy had been studied in randomized comparisons of medical therapy versus coronary artery bypass grafting. Trial data reflect how these therapies were delivered more than 20 years ago and do not indicate the relative benefits of medical therapy versus coronary artery bypass grafting in contemporary practice. Methods: Randomization of consenting patients with heart failure, left ventricular ejection fraction of 0.35 or less, and coronary artery disease is based on whether patients are judged by attending physicians to be candidates only for coronary artery bypass grafting or can be treated with medical therapy without coronary artery bypass grafting, Patients eligible for surgical ventricular reconstruction because of significant anterior wall akinesis or dyskinesis but ineligible for medical therapy are randomly assigned to coronary artery bypass grafting with or without surgical ventricular reconstruction. Patients eligible for medical therapy are randomly assigned between medical therapy only and medical therapy with coronary artery bypass grafting. Patients eligible for all 3 are randomly assigned evenly to medical therapy only, medical therapy and coronary artery bypass grafting, or medical therapy and coronary artery bypass grafting and surgical ventricular reconstruction. Major substudies will examine quality of life, cost-effectiveness, changes in left ventricular volumes, effect of myocardial viability, selected biomarkers, and selected polymorphisms on treatment differences. Results: Enrollment is now complete in both STICH hypotheses. Follow-up will continue until sufficient end points are available to address both hypotheses with at least 90% power. The primary outcome of hypothesis 2 is expected to be reported in 2009. The primary outcome of hypothesis I is expected to be reported in 2011. Conclusions: The Surgical Treatment for Ischernic Heart Failure trial is a National Heart, Lung, and Blood Institute-funded multicenter international randomized trial addressing 2 specific primary hypotheses: (1) coronary artery bypass grafting, with intensive medical therapy improves long-term survival compared with survival with medical therapy alone, and (2) in patients with anterior left ventricular dysfunction, surgical ventricular reconstruction to a more not-mal left ventricular size plus coronary artery bypass grafting improves survival free of subsequent hospitalization for cardiac cause when compared with that with coronary artery bypass grafting alone. C1 Duke Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Duke Clin Res Inst, Durham, NC 27715 USA. Northwestern Univ, Feinber Sch Med, Dept Med, Div Cardiol, Chicago, IL 60611 USA. Mayo Clin, Div Cardiol, Rochester, MN USA. Univ So Calif, Dept Med, Keck Sch Med, Div Cardiovasc Med, Los Angeles, CA USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Div Cardiol, Philadelphia, PA 19107 USA. Washington Hosp Ctr, Div Cardiol, Washington, DC 20010 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. Duke Univ, Med Ctr, Dept Surg, Div Cardiothorac Surg, Durham, NC 27710 USA. RP Velazquez, EJ (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27715 USA. EM eric.velazquez@duke.edu OI Mark, Daniel/0000-0001-6340-8087 FU NHLBI NIH HHS [R01 HL105853, U01 HL069013, U01 HL069015] NR 37 TC 91 Z9 97 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2007 VL 134 IS 6 BP 1540 EP 1547 DI 10.1016/j.jtcvs.2007.05.069 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 235OM UT WOS:000251244200023 PM 18023680 ER PT J AU Parekh, DJ Ankerst, DP Troyer, D Srivastava, S Thompson, IM AF Parekh, Dipen J. Ankerst, Donna Pauler Troyer, Dean Srivastava, Sudhir Thompson, Ian M. TI Biomarkers for prostate cancer detection SO JOURNAL OF UROLOGY LA English DT Review DE prostate; prostatic neoplasms, tumor markers; biological; validation studies [publication type]; prostate-specific antigen ID MULTICENTER CLINICAL-TRIAL; STEM-CELL ANTIGEN; HUMAN KALLIKREIN-2; GSTP1 METHYLATION; PERIPHERAL-BLOOD; MEMBRANE ANTIGEN; MICROARRAY DATA; SAMPLE-SIZE; MEN; MARKERS AB Purpose: The limitations of prostate specific antigen as a biomarker for prostate cancer screening, characterized by low sensitivity for acceptable false-positive rates, are well known. New markers that differentiate indolent from aggressive cancers to decrease potential the over treatment of prostate cancer are needed. We reviewed current and potential biomarkers for prostate cancer detection. Materials and Methods: A literature search was performed to identify established and emerging biomarkers for prostate cancer detection. Recent suggested guidelines by the Early Detection Research Network for phases of biomarker studies were interpreted for use in prostate cancer and the existing status of marker studies were reviewed with respect to these phases of study. Results: Advances in high throughput bench research, including high dimensional genomic, proteomic and autoantibody signatures, have the potential to improve the operating characteristics of prostate specific antigen but they are undergoing reproducibility and multicenter validation studies. None of the prostate specific antigen derivatives or isoforms, such as prostate specific antigen density, velocity or percent complexed prostate specific antigen, improve operating characteristics enough to likely replace prostate specific antigen. Prostate stem cell antigen, alpha-methyl coenzyme-A racemase, PCA3, early prostate cancer antigen, human kallikrein 2 and hepsin are promising markers that are currently undergoing validation. Conclusions: The process of discovering novel biomarkers to replace or augment the existing best marker, prostate specific antigen, requires standardized phases of evaluation and validation. Several biomarkers are currently on the cusp of initial validation studies. C1 Univ Texas, Hlth Sci Ctr, Dept Urol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. NCI, Early Detect & Res Network, Bethesda, MD 20892 USA. RP Parekh, DJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Urol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM parekhd@uthscsa.edu FU NCI NIH HHS [U01-CA86402] NR 48 TC 52 Z9 57 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2007 VL 178 IS 6 BP 2252 EP 2259 DI 10.1016/j.juro.2007.08.055 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 230AO UT WOS:000250847900005 PM 17936845 ER PT J AU Carter, HB Kettermann, A Warlick, C Metter, EJ Landis, P Walsh, PC Epstein, JI AF Carter, H. Ballentine Kettermann, Anna Warlick, Christopher Metter, E. Jeffrey Landis, Patricia Walsh, Patrick C. Epstein, Jonathan I. TI Expectant management of prostate cancer with curative intent: An update of the Johns Hopkins experience SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; follow-up studies; age factors ID ACTIVE SURVEILLANCE; MEN; THERAPY; TIMES AB Purpose: We updated our experience with a strategy of expectant treatment for men with stage T1c prostate cancer and evaluated predictors of disease intervention. Materials and Methods: A total of 407 men with a median age of 65.7 years (range 45.8 to 81.5) with stage T1c (99.8%) or T2a (0.2%) prostate cancer suspected of harboring small volume prostate cancer based on needle biopsy findings and prostate specific antigen density have been followed in a prospective, longitudinal surveillance program with a median followup of 2.8 years (range 0.4 to 12.5). A recommendation for treatment was made if disease progression was suggested by unfavorable followup needle biopsy findings (Gleason pattern 4 or 5, greater than 2 biopsy cores with cancer or greater than 50% involvement of any core with cancer). Cox proportional hazards regression was used to evaluate the affect of multiple covariates on the outcome of curative intervention. Results: Of 407 men 239 (59%) men remained on active surveillance at a median followup of 3.4 years (range 0.43 to 12.5), 103 (25%) underwent curative intervention at a median of 2.2 years after diagnosis (range 0.96 to 7.39) and 65 (16%) were either lost to followup (12), withdrew from the program (45), or died of causes other than prostate cancer (8). Older age at diagnosis (p = 0.011) and an earlier date of diagnosis (p = 0.001) were significantly associated with curative intervention. Conclusions: Recognizing that over treatment of prostate cancer is prevalent, especially among elderly patients, a program of careful selection and monitoring of older men who are likely to harbor small volume, low grade disease may be a rational alternative to the active treatment of all. C1 Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA. Johns Hopkins Univ Hosp, Dept Urol, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. RP Carter, HB (reprint author), Johns Hopkins Univ Hosp, Dept Urol, James Buchanan Brady Urol Inst, 145 Marburg Bldg,600 N Wolfe St, Baltimore, MD 21287 USA. EM hcarter@jhmi.edu FU NCI NIH HHS [P50 CA058236] NR 15 TC 210 Z9 218 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2007 VL 178 IS 6 BP 2359 EP 2364 DI 10.1016/j.juro.2007.08.039 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 230AO UT WOS:000250847900030 PM 17936806 ER PT J AU LaMere, BJ Kornegay, J Fetterman, B Sadorra, M Shieh, J Castle, PE AF LaMere, Brandon J. Kornegay, Janet Fetterman, Barbara Sadorra, Mark Shieh, Jen Castle, Philip E. CA PaP Cohort Study Grp TI Human papillomavirus genotyping after denaturation of specimens for Hybrid Capture 2 testing: Feasibility study for the HPV persistence and progression cohort SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE cervical cancer; human papillomavirus (HPV); HPV genotypes; cervical precancer; cervical intraepithelial neoplasia grade 3 (CIN3); screening; PCR ID COSTA-RICA; CERVICAL PRECANCER; WOMEN; RISK; CANCER; DNA; ABNORMALITIES; POPULATION; GUANACASTE; TYPE-16 AB Human papillomavirus (HPV) genotyping could be clinically useful, depending on the results of large, prospective studies like the HPV persistence and progression (PaP) cohort. The cohort is based on genotyping and follow-up of Hybrid Capture-positive women at Kaiser Permanente, Northern California. HPV DNA testing by Hybrid Capture 2 requires denaturation with alkali, possibly damaging the DNA for optimal PCR-based genotyping. A feasibility study was conducted on paired aliquots of anonymized specimens from 100 women with low-grade intraepithelial lesion cytology. Test aliquots were left in denaturant for 10 or 18 h at 4 degrees C and then neutralized; comparison aliquots were not denatured but diluted to match the timing, temperature, concentration and salt conditions of the treated specimens. The masked aliquots were tested using a commercialized PCR-based assay that detects of 37 HPV genotypes. There was no overall effect of treatment on test positivity or number of types. HPV16 was marginally more likely to be detected in untreated versus treated aliquots (P = 0.09) but HPV45 was marginally more likely to be detected in treated than untreated aliquots (P=0.07), suggesting that these differences represented chance (intra-test variability). It can be concluded that residual Hybrid Capture-positive specimens can be genotyped by PCR after Hybrid Capture 2 processing. Published by Elsevier B.V. C1 [Castle, Philip E.] Natl Canc Inst, Div Canc Epidemiol, NIH, DHHS, Bethesda, MD USA. [LaMere, Brandon J.; Fetterman, Barbara; Shieh, Jen] Kaiser Permanente No California, Reg Lab, Berkeley, CA USA. [Kornegay, Janet; Sadorra, Mark] Roche Mol Syst, Alameda, CA USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5004,MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU Intramural NIH HHS [Z01 CP010124-12, Z99 CA999999] NR 20 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD DEC PY 2007 VL 146 IS 1-2 BP 80 EP 85 DI 10.1016/j.jviromet.2007.06.001 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 241HV UT WOS:000251648400011 PM 17673302 ER PT J AU Lai, CJ Goncalvez, AP Men, R Wernly, C Donau, O Engle, RE Purcell, RH AF Lai, Ching-Juh Goncalvez, Ana P. Men, Ruhe Wernly, Claire Donau, Olivia Engle, Ronald E. Purcell, Robert H. TI Epitope determinants of a chimpanzee dengue virus type 4 (DENV-4) -neutralizing antibody and protection against DENV-4 challenge in mice and rhesus monkeys by passively transferred humanized antibody SO JOURNAL OF VIROLOGY LA English DT Article ID BORNE ENCEPHALITIS-VIRUS; WEST-NILE-VIRUS; DENGUE TYPE-4 VIRUS; IMMUNOGLOBULIN G1 ANTIBODY; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; MEMBRANE-FUSION; FAB FRAGMENTS; YELLOW-FEVER; DOMAIN-III AB The chimpanzee monoclonal antibody (MAb) 5H2 is specific for dengue virus type 4 (DENV-4) and neutralizes the virus at a high titer in vitro. The epitope detected by the antibody was mapped by sequencing neutralization escape variants of the virus. One variant contained a Lys(174)-Glu substitution and another contained a Pro(176)-Leu substitution in domain I of the DENV-4 envelope protein (E). These mutations reduced binding affinity for the antibody 18- to >100-fold. Humanized immunoglobulin G (IgG) 5112, originally produced from an expression vector, has been shown to be a variant containing a nine-amino-acid deletion in the Fc region which completely ablates antibody-dependent enhancement of DENV replication in vitro. The variant MAb, termed IgG 5H2 AD, is particularly attractive for exploring its protective capacity in vivo. Passive transfer of IgG 5H2 Delta D at 20 mu g/mouse afforded 50% protection of suckling mice against challenge with 25 50% lethal doses of mouse neurovirulent DENV-4 strain H241. Passive transfer of antibody to monkeys was conducted to demonstrate proof of concept for protection against DENV challenge. Monkeys that received 2 mg/kg of body weight of IgG 5H2 AD were completely protected against 100 50% monkey infectious doses (MID,,) of DENV-4, as indicated by the absence of viremia and seroconversion. A DENV-4 escape mutant that contained a Lys(174)-Glu substitution identical to that found in vitro was isolated from monkeys challenged with 10(6) MID50 of DENV-4. This substitution was also present in all naturally occurring isolates belonging to DENV-4 genotype III. These studies have important implications for possible antibody-mediated prevention of DENV infection. C1 NIH, Infect Dis Lab, Bethesda, MD 20892 USA. NIH, Mol Viral Biol Sect, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. NIH, Natl Inst Allergy & Infect Dis, Infect Dis Lab, Bethesda, MD 20892 USA. RP Lai, CJ (reprint author), NIH, Infect Dis Lab, 50 S Dr MSC 8005, Bethesda, MD 20892 USA. EM clai@niaid.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [P41 RR-01081, P41 RR001081] NR 55 TC 46 Z9 51 U1 0 U2 3 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 DEC PY 2007 VL 81 IS 23 BP 12766 EP 12774 DI 10.1128/JVI.01420-07 PG 9 WC Virology SC Virology GA 236VC UT WOS:000251330500006 PM 17881450 ER PT J AU Gustchina, E Louis, JM Lam, SN Bewley, CA Clore, GM AF Gustchina, Elena Louis, John M. Lam, Son N. Bewley, Carole A. Clore, G. Marius TI A monoclonal fab derived from a human nonimmune phage library reveals a new epitope on gp41 and neutralizes diverse human immunodeficiency virus type 1 strains SO JOURNAL OF VIROLOGY LA English DT Article ID TRIMERIC COILED-COIL; ENVELOPE GLYCOPROTEIN; HIV-1 ENTRY; QUANTITATIVE-ANALYSIS; PEPTIDE INHIBITOR; ATOMIC-STRUCTURE; MEMBRANE-FUSION; CELL-FUSION; ANTIBODY; DESIGN AB A monoclonal Fab (Fab 3674) selected from a human nonimmune phage library by panning against the chimeric construct NccG-gp41 (which comprises an exposed coiled-coil trimer of gp41 N helices fused in the helical phase onto the minimal thermostable ectodomain of gp41) is described. Fab 3674 is shown to neutralize diverse laboratory-adapted B strains of human immunodeficiency virus type 1 (HIV-1) and primary isolates of subtypes A, B, and C in an Env-pseudotyped-virus neutralization assay, albeit with reduced potency (approximately 25-fold) compared to that of 2F5 and 4E10. Alamine scanning mutagenesis maps a novel epitope to a shallow groove on the N helices of gp41 that is exposed between two C helices in the fusogenic six-helix bundle conformation of gp41. Bivalent Fab 3674 and the C34 peptide (a potent fusion inhibitor derived from the C helix of gp41) are shown to act at similar stages of the fusion reaction and to neutralize HIV-1 synergistically, providing additional evidence that the epitope of Fab 3674 is new and distinct from the binding site of C34. C1 NIH, NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NIH, NIDDKD, Chem Phys Lab, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIH, NIDDK, Bioorgan Chem Lab, Bldg 10, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov; mariusc@mail.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU Intramural NIH HHS NR 45 TC 30 Z9 31 U1 1 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 DEC PY 2007 VL 81 IS 23 BP 12946 EP 12953 DI 10.1128/JVI.01260-07 PG 8 WC Virology SC Virology GA 236VC UT WOS:000251330500024 PM 17898046 ER PT J AU Parrish, S Moss, B AF Parrish, Susan Moss, Bernard TI Characterization of a second vaccinia virus mRNA-decapping enzyme conserved in poxviruses SO JOURNAL OF VIROLOGY LA English DT Article ID GENE-EXPRESSION; D10 PROTEIN; SEQUENCE; INFECTION; CELLS; HDCP2; HOST AB Vaccinia virus (VACV) encodes enzymes that cap the 5' end of viral mRNAs, which enhances their stability and translation. Nevertheless, recent studies demonstrated that the VACV D10 protein (VACV-WR_115) decaps mRNA, an enzymatic activity not previously shown to be encoded by a virus. The decapping activity of D10 is dependent on a Nudix hydrolase motif that is also present in the VACV D9 protein (VACV-WR_114), which shares 25% sequence identity with D10. Here, we showed that a purified recombinant VACV D9 fusion protein also decaps mRNA and that this activity was abolished by point mutations in the Nudix hydrolase motif. Decapping was specific for a methylated cap attached to RNA and resulted in the liberation Of m(7) GDP. D9 differed from D10 in requiring a longer capped RNA substrate for optimal activity, having greater sensitivity to inhibition by uncapped RNA, and having lower sensitivity to inhibition by nucleotide cap analogs unattached to RNA. Since D9 is expressed early in infection and D10 late, we suggest that the two proteins enhance mRNA turnover and manipulate gene expression in a complementary and overlapping manner. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33,Room 1E13C-1,33 North Dr,MSC 3210, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 21 TC 38 Z9 40 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 DEC PY 2007 VL 81 IS 23 BP 12973 EP 12978 DI 10.1128/JVI.01668-07 PG 6 WC Virology SC Virology GA 236VC UT WOS:000251330500027 PM 17881455 ER PT J AU Harker, J Bukreyev, A Collins, PL Wang, B Openshaw, PJM Tregoning, JS AF Harker, James Bukreyev, Alexander Collins, Peter L. Wang, Belinda Openshaw, Peter J. M. Tregoning, John S. TI Virally delivered Cytokines alter the immune response to future lung infections SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY-SYNCYTIAL-VIRUS; T-CELLS; AIRWAY HYPERRESPONSIVENESS; LYMPHOCYTE-RESPONSES; IN-VIVO; INTERLEUKIN-4; EXPRESSION; MICE; DISEASE; BRONCHIOLITIS AB Respiratory syncytial virus (RSV) is an important cause of infant morbidity and mortality worldwide and is increasingly recognized to have a role in the development and exacerbation of chronic lung diseases. There is no effective vaccine, and we reasoned that it might be possible to skew the immune system towards beneficial nonpathogenic responses by selectively priming protective T-cell subsets. We therefore tested recombinant RSV (rRSV) candidates expressing prototypic murine Th1 (gamma interferon [IFN-gamma]) or Th2 (interleukin-4 [IL-4]) cytokines, with detailed monitoring of responses to subsequent infections with RSV or (as a control) influenza A virus. Although priming with either recombinant vector reduced viral load during RSV challenge, enhanced weight loss and enhanced pulmonary influx of RSV-specific CD8(+) T cells were observed after challenge in mice primed with rRSV/IFN-gamma. By contrast, rRSV/IL-4-primed mice were protected against weight loss during secondary challenge but showed airway eosinophillia. When rRSV/IL-4-primed mice were challenged with influenza virus, weight loss was attenuated but was again accompanied by marked airway eosinophillia. Thus, immunization directed toward enhancement of Th1 responses reduces viral load but is not necessarily protective against disease. Counter to expectation, Th2-biased responses were more beneficial but also influenced the pathological effects of heterologous viral challenge. C1 Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Asthma UK Ctr Allerg Mech Asthma, London W2 1PG, England. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Dept Resp Med, MRC, London W2 1PG, England. RP Openshaw, PJM (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Resp Med, MRC, Paddington Campus,Norfolk Pl, London W2 1PG, England. EM p.openshaw@imperial.ac.uk OI Tregoning, John/0000-0001-8093-8741 FU Intramural NIH HHS; Wellcome Trust [071381/Z/03/Z] NR 34 TC 16 Z9 16 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 DEC PY 2007 VL 81 IS 23 BP 13105 EP 13111 DI 10.1128/JVI.01544-07 PG 7 WC Virology SC Virology GA 236VC UT WOS:000251330500041 PM 17855518 ER PT J AU Miyagij, E Opi, S Takeuchi, H Khan, M Goila-Gaur, R Kao, S Strebel, K AF Miyagij, Eri Opi, Sandrine Takeuchi, Hiroaki Khan, Mohammad Goila-Gaur, Ritu Kao, Sandra Strebel, Klaus TI Enzymatically active APOBEC3G is required for efficient inhibition of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID VIF PROTEIN; ANTIVIRAL ACTIVITY; HIV-1 VIRIONS; REVERSE TRANSCRIPTION; VIRAL-RNA; SOR GENE; DNA; DEGRADATION; INFECTIVITY; HYPERMUTATION AB APOBEC3G (APO3G) is a cellular cytidine deaminase with potent antiviral activity. Initial studies of the function of APO3G demonstrated extensive mutation of the viral genome, suggesting a model in which APO3G's antiviral activity is due to hypermutation of the viral genome. Recent studies, however, found that deaminase-defective APO3G mutants transiently expressed in virus-producing cells exhibited significant antiviral activity, suggesting that the antiviral activity of APO3G could be dissociated from its deaminase activity. To directly compare the antiviral activities of wild-type (wt) and deaminase-defective APO3G, we used two approaches: (i) we titrated wt and deaminase-defective APO3G in transient-transfection studies to achieve similar levels of virus-associated APO3G and (ii) we constructed stable cell lines and selected clones expressing comparable amounts of wt and deaminase-defective APO3G. Viruses produced under these conditions were tested for viral infectivity. The results from the two approaches were consistent and suggested that the antiviral activity of deaminase-defective APO3G was significantly lower than that of wt APO3G. We conclude that efficient inhibition of vif-defective human immunodeficiency virus type 1 requires catalytically active APO3G. C1 [Miyagij, Eri; Opi, Sandrine; Takeuchi, Hiroaki; Khan, Mohammad; Goila-Gaur, Ritu; Kao, Sandra; Strebel, Klaus] NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bldg 4,Room 310,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM kstrebel@nih.gov RI Takeuchi, Hiroaki/F-9728-2012 FU Intramural NIH HHS NR 45 TC 105 Z9 105 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 DEC PY 2007 VL 81 IS 24 BP 13346 EP 13353 DI 10.1128/JVI.01361-07 PG 8 WC Virology SC Virology GA 239XR UT WOS:000251552100007 PM 17928335 ER PT J AU Duvall, MG Lore, K Blaak, H Ambrozak, DA Adams, WC Santos, K Geldmacher, C Mascola, JR McMichael, AJ Jaye, A Whittle, HC Rowland-Jones, SL Koup, RA AF Duvall, Melody G. Lore, Karin Blaak, Hetty Ambrozak, David A. Adams, William C. Santos, Kathlyn Geldmacher, Christof Mascola, John R. McMichael, Andrew J. Jaye, Assan Whittle, Hilton C. Rowland-Jones, Sarah L. Koup, Richard A. TI Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; POLYCHROMATIC FLOW-CYTOMETRY; DC-SIGN; INTRAVAGINAL INOCULATION; 1-INFECTED INDIVIDUALS; PRODUCTIVE INFECTION; REVERSE TRANSCRIPTS; LANGERHANS CELLS; TRANS-INFECTION; PLASMA VIREMIA AB Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) has been documented in vivo and may be an important contributor to HIV-1 transmission and pathogenesis. HIV-1-specific CD4(+) T cells respond to HIV antigens presented by HIV-1-infected DCs and in this process become infected, thereby providing a mechanism through which HIV-1-specific CD4(+) T cells could become preferentially infected in vivo. HIV-2 disease is attenuated with respect to HIV-1 disease, and host immune responses are thought to be contributory. Here we investigated the susceptibility of primary myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to infection by HIV-2. We found that neither CCR5-tropic primary HIV-2 isolates nor a lab-adapted CXCR4-tropic HIV-2 strain could efficiently infect mDCs or pDCs, though these viruses could infect primary CD4(+) T cells in vitro. HIV-2-exposed mDCs were also incapable of transferring virus to autologous CD4(+) T cells. Despite this, we found that HIV-2-specific CD4(+) T cells contained more viral DNA than memory CD4(+) T cells of other specificities in vivo. These data suggest that either infection of DCs is not an important contributor to infection of HIV-2-specific CD4(+) T cells in vivo or that infection of DCs by HIV-2 occurs at a level that is undetectable in vitro. The frequent carriage of HIV-2 DNA within HIV-2-specific CD4(+) T cells, however, does not appear to be incompatible with preserved numbers and functionality of HIV-2-specific CD4(+) T cells in vivo, suggesting that additional mechanisms contribute to maintenance of HIV-2-specific CD4(+) T-cell help in vivo. C1 [Duvall, Melody G.; Lore, Karin; Ambrozak, David A.; Adams, William C.; Santos, Kathlyn; Geldmacher, Christof; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Duvall, Melody G.; McMichael, Andrew J.; Rowland-Jones, Sarah L.] Univ Oxford, Weatherall Inst Mol Med, MRC, Human Immunol Unit, Oxford OX3 9DS, England. [Lore, Karin; Adams, William C.] Karolinska Inst, Dept Med, Ctr Infect Med, Stockholm, Sweden. [Blaak, Hetty] Erasmus MC, Dept Virol, Rotterdam, Netherlands. [Mascola, John R.] NIAID, Core Virol Lab BSL 3, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Jaye, Assan; Whittle, Hilton C.; Rowland-Jones, Sarah L.] MRC Labs Fajara, Banjul, Gambia. RP Koup, RA (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3022,Bldg 40,Room 3502, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov FU Medical Research Council [MC_U137884180, MC_U190081958] NR 81 TC 26 Z9 26 U1 0 U2 4 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 DEC PY 2007 VL 81 IS 24 BP 13486 EP 13498 DI 10.1128/JVI.00976-07 PG 13 WC Virology SC Virology GA 239XR UT WOS:000251552100021 PM 17913821 ER PT J AU Geldmacher, C Gray, C Nason, M Currier, JR Haule, A Njovu, L Geis, S Hoffmann, O Maboko, L Meyerhans, A Cox, J Hoelscher, M AF Geldmacher, Christof Gray, Clive Nason, Martha Currier, Jeffrey R. Haule, Antelmo Njovu, Lilian Geis, Steffen Hoffmann, Oliver Maboko, Leonard Meyerhans, Andreas Cox, Josephine Hoelscher, Michael TI A high viral burden predicts the loss of CD8 T-cell responses specific for subdominant Gag epitopes during chronic human immunodeficiency virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; MBEYA REGION; CLASS-I; IMMUNODOMINANT REGIONS; LYMPHOCYTE RESPONSES; DISEASE PROGRESSION; IMMUNE-RESPONSES; SUBTYPE-C; TYPE-1; VIREMIA AB Human immunodeficiency virus (HIV)-specific CD8 T-cell responses targeting products encoded within the Gag open reading frame have frequently been associated with better viral control and disease outcome during the chronic phase of HIV infection. To further clarify this relationship, we have studied the dynamics of Gag-specific CD8 T-cell responses in relation to plasma viral load and time since infection in 33 chronically infected subjects over a 9-month period. High baseline viral loads were associated with a net loss of breadth (P < 0.001) and a decrease in the total magnitude of the Gag-specific T-cell response in general (P = 0.03). Most importantly, the baseline viral load predicted the subsequent change in the breadth of Gag recognition over time (P < 0.0001, r(2) = 0.41). Compared to maintained responses, lost responses were low in magnitude (P < 0.0001) and subdominant in the hierarchy of Gag-specific responses. The present study indicates that chronic exposure of the human immune system to high levels of HIV viremia is a determinant of virus-specific CD8 T-cell loss. C1 [Geldmacher, Christof; Nason, Martha] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Geldmacher, Christof; Haule, Antelmo; Njovu, Lilian; Geis, Steffen; Hoffmann, Oliver; Maboko, Leonard] Referral Hosp, Mbeya Med Res Programme, Mbeya, Tanzania. [Hoelscher, Michael] Univ Munich, Dept Trop Med & Infect Dis, D-80799 Munich, Germany. [Currier, Jeffrey R.; Cox, Josephine] US Mil HIV Res Program, Rockville, MD 20851 USA. [Gray, Clive] Natl Inst Communicable Dis, Johannesburg, South Africa. [Meyerhans, Andreas] Univ Saarland, Inst Virol, D-66421 Homburg, Germany. RP Geldmacher, C (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM geldmacherc@mail.nih.gov RI Hoelscher, Michael/D-3436-2012; Meyerhans, Andreas/D-3382-2014 OI Meyerhans, Andreas/0000-0003-0620-5317 NR 36 TC 9 Z9 9 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 DEC PY 2007 VL 81 IS 24 BP 13809 EP 13815 DI 10.1128/JVI.01566-07 PG 7 WC Virology SC Virology GA 239XR UT WOS:000251552100052 PM 17898052 ER PT J AU Gambhira, R Karanam, B Jagu, S Roberts, JN Buck, CB Bossis, I Alphs, H Culp, T Christensen, ND Roden, RBS AF Gambhira, Ratish Karanam, Balasubramanyam Jagu, Subhashini Roberts, Jeffrey N. Buck, Christopher B. Bossis, Ioannis Alphs, Hannah Culp, Timothy Christensen, Neil D. Roden, Richard B. S. TI A protective and broadly cross-neutralizing epitope of human papillomavirus L2 SO JOURNAL OF VIROLOGY LA English DT Article ID MINOR CAPSID PROTEIN; COTTONTAIL RABBIT PAPILLOMAVIRUS; BOVINE PAPILLOMAVIRUS; VACCINATION; INFECTION; IMMUNIZATION; ANTIBODIES; CATTLE; RESPONSES; PEPTIDES AB We generated a monoclonal antibody, RG-1, that binds to highly conserved L2 residues 17 to 36 and neutralizes human papillomavirus 16 (HPV16) and HPV18. Passive immunotherapy with RG-1 was protective in mice. Antiserum to the HPV16 L2 peptide comprising residues 17 to 36 (peptide 17-36) neutralized pseudoviruses HPV5, HPV6, HPV16, HPV 18, HPV31, HPV 45, HPV 52, HPV 58, bovine papillomavirus 1, and HPV11 native virions. Depletion of HPV16 L2 peptide 17-36-reactive antibodies from cross-neutralizing rabbit and human L2-specific sera abolished cross-neutralization and drastically reduced neutralization of the cognate type. This cross-neutralization of diverse HPVs associated with cervical cancer, genital warts, and epidermodysplasia verruciformis suggests the possibility of a broadly protective, peptide-based vaccine. C1 [Gambhira, Ratish; Karanam, Balasubramanyam; Jagu, Subhashini; Bossis, Ioannis; Alphs, Hannah; Roden, Richard B. S.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. [Roden, Richard B. S.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA. [Roden, Richard B. S.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21231 USA. [Roberts, Jeffrey N.; Buck, Christopher B.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. [Culp, Timothy; Christensen, Neil D.] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA USA. RP Roden, RBS (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Room 308,Canc Res Bldg 2,1550 Orleans St, Baltimore, MD 21231 USA. EM roden@jhmi.edu OI Buck, Christopher/0000-0003-3165-8094 FU Intramural NIH HHS; NCI NIH HHS [P50 CA098252] NR 22 TC 119 Z9 123 U1 0 U2 4 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 DEC PY 2007 VL 81 IS 24 BP 13927 EP 13931 DI 10.1128/JVI.00936-07 PG 5 WC Virology SC Virology GA 239XR UT WOS:000251552100064 PM 17928339 ER PT J AU Edwards, S Tureck, R Fredrick, M Huang, XK Zhang, J Barnhart, K AF Edwards, Scott Tureck, Richard Fredrick, Margaret Huang, Xiangke Zhang, Jun Barnhart, Kurt TI Patient acceptability of manual versus electric vacuum aspiration for early pregnancy loss SO JOURNAL OF WOMENS HEALTH LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the American-Society-for-Reproductive-Medicine/51st Annual Meeting of the Canadian-Fertility-and-Andrology-Society CY OCT 15-19, 2005 CL Montreal, CANADA SP Amer Soc Reprod Med, Canadian Fertil & Androl Soc ID INCOMPLETE ABORTION; TRIMESTER ABORTION; MANAGEMENT; PAIN; TERMINATION; MISCARRIAGE; DEPRESSION; TRIAL; TIME AB Objective: To compare the safety, efficacy, postprocedure quality of life, and acceptability of manual vacuum aspiration (MVA) performed as an outpatient with electric vacuum aspiration (EVA) performed in a hospital in women experiencing a first-trimester miscarriage. Methods: From a randomized multicenter trial comparing misoprostol with vacuum aspiration for first-trimester loss, data were extracted comparing the safety, efficacy, and acceptability of MVA in an office setting with local anesthesia with EVA in an operating room environment with spinal or general anesthesia or monitored anesthesia care (MAC). Results: One hundred fifty-seven women underwent EVA or MVA. Efficacy and safety were similar in both groups. Physical and emotional role functioning scores were better in patients undergoing MVA (p = 0.01), and fewer patients undergoing MVA missed work or required help at home (p < 0.01). However, pain severity scores were better in the EVA arm of the study (p = 0.03). There was a trend toward fewer MVA patients recommending or using this procedure again. Conclusions: In patients with early pregnancy loss, treatment with MVA as an outpatient with local anesthesia is an effective and safe alternative to EVA performed in a hospital with conscious sedation or spinal or general anesthesia. Treatment in the outpatient setting allows for a better physical and emotional quality of life postprocedure. C1 [Edwards, Scott; Tureck, Richard; Barnhart, Kurt] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Barnhart, Kurt] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Fredrick, Margaret; Huang, Xiangke] Clin Trials & Surveys Corp, Baltimore, MD USA. [Zhang, Jun] NICHHD, NIH, Epidemiol Branch, Bethesda, MD 20892 USA. RP Edwards, S (reprint author), Univ Penn, Dept Obstet & Gynecol, 3701 Market St, Philadelphia, PA 19104 USA. EM sedwards@obgyn.upenn.edu FU NICHD NIH HHS [N01-HD-1-3321, N01-HD-1-3322, N01-HD-1-3323, N01-HD-1-3324, N01-HD-1-3325] NR 24 TC 18 Z9 18 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD DEC PY 2007 VL 16 IS 10 BP 1429 EP 1436 DI 10.1089/jwh.2007.0362 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 248MW UT WOS:000252158400006 PM 18062758 ER PT J AU Ix, J Shlipak, M Sarnak, M Beck, G Greene, T Wang, X Kusek, J Collins, A Levey, A Menon, V AF Ix, J. H. Shlipak, M. G. Sarnak, M. J. Beck, G. J. Greene, T. Wang, X. Kusek, J. W. Collins, A. J. Levey, A. S. Menon, V. TI Fetuin-A is not associated with mortality in chronic kidney disease SO KIDNEY INTERNATIONAL LA English DT Article DE cardiovascular disease; chronic kidney disease; calcium; mortality ID CORONARY-ARTERY CALCIFICATION; BEAM COMPUTED-TOMOGRAPHY; C-REACTIVE PROTEIN; VASCULAR CALCIFICATION; CARDIOVASCULAR-DISEASE; RENAL-DISEASE; GLYCOPROTEIN/FETUIN-A; DIALYSIS PATIENTS; CALCIUM SCORE; FOLLOW-UP AB Fetuin-A is a serum protein that inhibits vascular calcification such that lower levels are associated with a higher prevalence of vascular calcification and mortality risk among end-stage renal disease populations. We analyzed data of 822 persons in the Modification of Diet in Renal Disease study, a randomized, controlled trial of persons with predominantly non-diabetic stage 3 -4 chronic kidney disease (CKD). Serum fetuin-A levels were measured in baseline serum. Survival status and cause of death were determined by the National Death Index. Cox proportional hazard models evaluated the association of fetuin-A levels with all-cause and cardiovascular mortality. Glomerular filtration ranged from 13 to 55 ml per min per 1.73m(2). During a median follow-up of 9.5 years, 25% of persons died from any cause and 12% died from a cardiovascular cause. Compared to the lowest tertile, no association was found between the highest fetuin-A tertile and all-cause or cardiovascular mortality. Similarly, no association was found between fetuin-A as a continuous variable and all-cause or cardiovascular mortality. Our study shows that serum fetuin-A levels are not related to all-cause or cardiovascular mortality among persons with predominantly non-diabetic stage 3 or 4 CKD. C1 Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA. Univ Calif San Diego, Div Nephrol & Hypertens, Vet Affairs Healthcare Syst, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Med, Vet Affairs Heathcare Syst, San Diego, CA USA. Vet Affairs San Diego Healthcare Syst, Dept Med, San Diego, CA USA. Tufts Univ New England Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA. Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. Univ Utah, Dept Med, Div Clin Epidemiol, Salt Lake City, UT 84112 USA. NIH, Bethesda, MD 20892 USA. Hennepin Cty Med Ctr, Dept Med, Div Nephrol, Minneapolis, MN 55415 USA. RP Ix, J (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, Vet Affairs San Diego Healthcare Syst, 3350 La Jolla Village Dr,Box 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu NR 37 TC 27 Z9 27 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2007 VL 72 IS 11 BP 1394 EP 1399 DI 10.1038/sj.ki.5002549 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 231NR UT WOS:000250955900020 PM 17882149 ER PT J AU Seshadri, S Wolf, PA AF Seshadri, Sudha Wolf, Philip A. TI Lifetime risk of stroke and dementia: current concepts, and estimates from the Framingham Study SO LANCET NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; UNITED-STATES; HIP FRACTURE; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; FACTOR BURDEN; CANCER; AGE; MORTALITY; TRENDS AB The main neurological causes of morbidity and mortality are stroke and dementia. We contend that the most relevant and readily communicated risk estimate for stroke and dementia is lifetime risk, which is the probability of someone of a given age and sex developing a condition during their remaining lifespan. Lifetime risk estimates describe the population burden; however, they can be refined with risk-stratified models to enable individual risk prediction. Community-based data on a group of North Americans of European descent indicate that the lifetime risk of stroke for a middle-aged woman is 1 in 5 and for a middle-aged man is 1 in 6. The lifetime risk of stroke was equal to the lifetime risk of dementia and equal to or greater than the lifetime risk of Alzheimer's disease (1 in 5 and 1 in 10 for women and men, respectively), and the lifetime risk of stroke or dementia was greater than 1 in 3. Thus, the lifetime burden attributable to common neurological disease is immense. C1 [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Seshadri, Sudha; Wolf, Philip A.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St, B-602, Boston, MA 02118 USA. EM suseshad@bu.edu FU NHLBI NIH HHS [N01-HC-25195]; NIA NIH HHS [AG08122, AG16495]; NINDS NIH HHS [NS17950] NR 59 TC 102 Z9 104 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD DEC PY 2007 VL 6 IS 12 BP 1106 EP 1114 DI 10.1016/S1474-4422(07)70291-0 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 239UI UT WOS:000251543100017 PM 18031707 ER PT J AU Katki, HA Gail, MH Greene, MH AF Katki, Hormuzd A. Gail, Mitchell H. Greene, Mark H. TI Breast-cancer risk in BRCA-mutation-negative women from BRCA-mutatio-positive families SO LANCET ONCOLOGY LA English DT Editorial Material ID PHENOCOPIES; GENES; MODEL C1 [Katki, Hormuzd A.; Gail, Mitchell H.; Greene, Mark H.] Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Biostat Branch, Bethesda, MD 20892 USA. RP Greene, MH (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Biostat Branch, Bethesda, MD 20892 USA. EM greenem@mail.nih.gov RI Katki, Hormuzd/B-4003-2015 NR 11 TC 7 Z9 7 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD DEC PY 2007 VL 8 IS 12 BP 1042 EP 1043 DI 10.1016/S1470-2045(07)70348-0 PG 2 WC Oncology SC Oncology GA 242YR UT WOS:000251762600002 PM 18054868 ER PT J AU Pavletic, SZ Zhou, G Sobocinski, K Marti, G Doney, K DiPersio, J Feremans, W Foroni, L Goodman, S Prentice, G LeMaistre, C Bandini, G Ferrant, A Jacobsen, N Khouri, J Gale, RP Wiestner, A Giralt, S Montserrat, E Chan, WC Bredeson, C AF Pavletic, S. Z. Zhou, G. Sobocinski, K. Marti, G. Doney, K. DiPersio, J. Feremans, W. Foroni, L. Goodman, S. Prentice, G. LeMaistre, C. Bandini, G. Ferrant, A. Jacobsen, N. Khouri, J. Gale, R. P. Wiestner, A. Giralt, S. Montserrat, E. Chan, W. C. Bredeson, C. CA CIBMTR TI Genetically identical twin transplantation for chronic lymphocytic leukemia SO LEUKEMIA LA English DT Article DE hematopoietic stem cell transplantation; identical twin; CLL ID STEM-CELL TRANSPLANTATION; MARROW TRANSPLANTATION; ALLOGENEIC TRANSPLANTATION; BLOOD; LYMPHOMA; GENE; ABNORMALITIES; MALIGNANCIES; OVERCOME; CANCER AB We identified 19 persons with B-cell chronic lymphocytic leukemia (CLL) who received genetically identical twin blood cell or bone marrow transplants after high-dose conditioning. Ten are alive (eight disease-free) with a median follow-up of 89 months (range, 31-171 months); 5-year relapse rate was 50% (95% confidence interval (CI), 26-73%). Estimated 5-year survival and disease-free survival were 61% (95% CI, 37-82%) and 45% (95% CI, 23-68%). In two of four patients tested at 12 and 21 months by polymerase chain reaction no evidence of residual CLL was detected post-transplant. In one recipient who relapsed at 6 years, molecular studies showed a different CLL clone from that detected pretransplant. This clone was subsequently identified in the donor suggesting transfer of occult leukemia at the time of transplant. Genetically identical twin transplants can result in long-term disease-free survival and molecular remissions, these data suggest the potential for CLL control in the absence of allogeneic graft-versus-leukemia effect. The case of leukemia transfer indicates the need for careful evaluation of donors prior to graft collection. C1 Ctr Canc Res, Natl Canc Inst, Bethesda, MD USA. Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, Milwaukee, WI USA. US FDA, Div Cell & Gene Therapies, CBER, Bethesda, MD USA. Univ Washington, Dept Med, Seattle, WA USA. Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO USA. Erasme Univ Hosp, Clin Hematol, Brussels, Belgium. UCL, Royal Free Hosp, Sch Med, Dept Haematol, London, England. Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol & Oncol, Nashville, TN USA. Texas Transplant Inst, Div Adult Stem Cell Transplantat, San Antonio, TX USA. Sant Orsola Univ Hosp, Inst Hematol, Dept Hematol Oncol, Bologna, Italy. Catholic Univ Louvain, Clin Univ St Luc, Dept Hematol, Brussels, Belgium. Rigshosp Univ Hosp, Dept Hematol, Copenhagen, Denmark. Univ Texas MD Anderson Canc Ctr Houston, Dept Stem Cell Transplantat, Houston, TX 77030 USA. NHLBI, Natl Inst Hlth, Bethesda, MD USA. Univ Barcelona, Hosp & Clin, Inst Hematol & Oncol, Dept Hematol,IDIBAPS, Barcelona, Spain. Med Coll Wisconsin, Div Neoplast Dis, Milwaukee, WI USA. RP Pavletic, SZ (reprint author), NCI, Graft Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, 9000 Rockville Pike,10 Ctr Dr, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov FU Intramural NIH HHS NR 29 TC 14 Z9 14 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2007 VL 21 IS 12 BP 2452 EP 2455 DI 10.1038/sj.leu.2404928 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 234CY UT WOS:000251139500008 PM 17728782 ER PT J AU Kajiguchi, T Chung, E Lee, S Stine, A Kiyoi, H Naoe, T Levis, MJ Neckers, L Trepel, JB AF Kajiguchi, T. Chung, E. J. Lee, S. Stine, A. Kiyoi, H. Naoe, T. Levis, M. J. Neckers, L. Trepel, J. B. TI FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells SO LEUKEMIA LA English DT Article DE FLT3 AML; beta-catenin; tyrosine phosphorylation ID INTERNAL TANDEM DUPLICATION; UBIQUITIN-PROTEASOME PATHWAY; COLON-CARCINOMA CELLS; CONSTITUTIVE ACTIVATION; HEMATOLOGIC MALIGNANCIES; HEMATOPOIETIC-CELLS; SIGNALING PATHWAY; MULTIPLE-MYELOMA; KINASE INHIBITOR; CYCLIN D1 AB Deregulated accumulation of nuclear beta-catenin enhances transcription of beta-catenin target genes and promotes malignant transformation. Recently, acute myeloid leukemia (AML) cells with activating mutations of FMS-like tyrosine kinase-3 (FLT3) were reported to display elevated beta-catenin-dependent nuclear signaling. Tyrosine phosphorylation of beta-catenin has been shown to promote its nuclear localization. Here, we examined the causal relationship between FLT3 activity and beta-catenin nuclear localization. Compared to cells with wild-type FLT3 (FLT3-WT), cells with the FLT3 internal tandem duplication (FLT3-ITD) and tyrosine kinase domain mutation (FLT3-TKD) had elevated levels of tyrosine-phosphorylated beta-catenin. Although beta-catenin was localized mainly in the cytoplasm in FLT3-WT cells, it was primarily nuclear in FLT3-ITD cells. Treatment with FLT3 kinase inhibitors or FLT3 silencing with RNAi decreased beta-catenin tyrosine phosphorylation and nuclear localization. Conversely, treatment of FLT3-WT cells with FLT3 ligand increased tyrosine phosphorylation and nuclear accumulation of beta-catenin. Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML. C1 Nagoya Univ, Grad Sch Med, Dept Infect Dis, Nagoya, Aichi 4668560, Japan. Natl Canc Inst, Natl Inst Hlth, Urol Oncol Branch, Bethesda, MD USA. Natl Canc Inst, Natl Inst Hlth, Med Oncol Branch, Bethesda, MD USA. Sidney Kimmel Comprehens Canc Ctr John hopkins, Baltimore, MD USA. Nagoya Univ, Grad Sch Med, Dept Hematol Oncol, Nagoya, Aichi, Japan. RP Kajiguchi, T (reprint author), Nagoya Univ, Grad Sch Med, Dept Infect Dis, 65 Tsurumai-cho, Nagoya, Aichi 4668560, Japan. EM tomokaji@med.nagoya-u.ac.jp FU Intramural NIH HHS NR 48 TC 26 Z9 27 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2007 VL 21 IS 12 BP 2476 EP 2484 DI 10.1038/sj.leu.2404923 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 234CY UT WOS:000251139500012 PM 17851558 ER PT J AU Catchpoole, D Lail, A Guo, D Chen, QR Khan, J AF Catchpoole, Daniel Lail, Andy Guo, Dachuan Chen, Qing-Rong Khan, Javed TI Gene expression profiles that segregate patients with childhood acute lymphoblastic leukaemia: An independent validation study identifies that endoglin associates with patient outcome SO LEUKEMIA RESEARCH LA English DT Article DE acute lymphoblastic leukaemia; cDNA microarray; gene expression profiles; validation; endoglin AB In this report, we determine whether genes identified in a previously reported cDNA microarray investigation of childhood acute lymphoblastic leukaemia (ALL) diagnostic bone marrow have the same distinguishing power in an independently derived cDNA microarray dataset from an equivalent but distinct patient cohort. Genes previously reported as discriminatory, generally were unable to distinguish ALL lymphocyte lineages, the presence of the Tel-AML1 translocation and patient risk stratification. An artificial neural network identified endoglin, which was reported in the initial study as a potential lineage marker, was actually better at identifying ALL patients with poor outcome. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Catchpoole, Daniel; Lail, Andy; Guo, Dachuan] Childrens Hosp, Oncol Res Unit, Tumour Bank, Westmead, NSW 2145, Australia. [Chen, Qing-Rong; Khan, Javed] Ctr Adv Technol, Natl Inst Hlth, Natl Canc Inst, Pediat Oncol Branch,Oncogenom Sect, Gaithersburg, MD 20877 USA. RP Catchpoole, D (reprint author), Childrens Hosp, Oncol Res Unit, Tumour Bank, Locked Bag 4001, Westmead, NSW 2145, Australia. EM danielc@chw.edu.au RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 8 TC 9 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD DEC PY 2007 VL 31 IS 12 BP 1741 EP 1747 DI 10.1016/j.leukres.2007.04.021 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 240FZ UT WOS:000251573900018 PM 17572488 ER PT J AU Day, NE Gail, MH AF Day, Nick E. Gail, Mitchell H. TI Norman Breslow, an architect of modern biostatistics SO LIFETIME DATA ANALYSIS LA English DT Biographical-Item C1 [Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. [Day, Nick E.] Univ Cambridge, Cambridge, England. RP Day, NE (reprint author), NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. EM gailm@epndce.nci.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD DEC PY 2007 VL 13 IS 4 BP 435 EP 438 DI 10.1007/s10985-007-9052-2 PG 4 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 245WZ UT WOS:000251970800002 PM 17763972 ER PT J AU Chatterjee, N Chen, YH AF Chatterjee, Nilanjan Chen, Yi-Hau TI A semiparametric pseudo-score method for analysis of two-phase studies with continuous phase-I covariates SO LIFETIME DATA ANALYSIS LA English DT Article; Proceedings Paper CT Conference on Statistical Methods for Emerging Issues in Observational Studies and Epidemiology CY AUG 04, 2006 CL Univ Washington, Seattle, WA HO Univ Washington DE case-control sampling; Kernel smoothing; locally weighted least square; measurement error; validation design ID 2-STAGE CASE-CONTROL; LOGISTIC-REGRESSION; MEASUREMENT ERROR; MODELS; PARAMETERS; ESTIMATORS; EXPOSURE; DISEASE; DESIGN AB Two-phase study designs can reduce cost and other practical burdens associated with large scale epidemiologic studies by limiting ascertainment of expensive covariates to a smaller but informative sub-sample (phase-II) of the main study (phase-I). During the analysis of such studies, however, subjects who are selected at phase-I but not at phase-II, remain informative as they may have partial covariate information. A variety of semi-parametric methods now exist for incorporating such data from phase-I subjects when the covariate information can be summarized into a finite number of strata. In this article, we consider extending the pseudo-score approach proposed by Chatterjee et al. (J Am Stat Assoc 98:158-168, 2003) using a kernel smoothing approach to incorporate information on continuous phase-I covariates. Practical issues and algorithms for implementing the methods using existing software are discussed. A sandwich-type variance estimator based on the influence function representation of the pseudo-score function is proposed. Finite sample performance of the methods are studies using simulated data. Advantage of the proposed smoothing approach over alternative methods that use discretized phase-I covariate information is illustrated using two-phase data simulated within the National Wilms Tumor Study (NWTS). C1 [Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. [Chen, Yi-Hau] Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. EM chattern@mail.nih.gov; yhchen@stat.sinica.edu.tw NR 22 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD DEC PY 2007 VL 13 IS 4 BP 607 EP 622 DI 10.1007/s10985-007-9066-9 PG 16 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 245WZ UT WOS:000251970800016 PM 18004656 ER PT J AU Oyler, NA Tycko, R AF Oyler, Nathan A. Tycko, Robert TI Conformational constraints in solid-state NMR of uniformly labeled polypeptides from double single-quantum-filtered rotational echo double resonance SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE NMR; C-13; N-15; protein structure; magic-angle spinning; amyloid; dipolar recoupling ID ANISOTROPY CORRELATION NMR; BETA-AMYLOID PEPTIDE; TORSION ANGLE PHI; DIHEDRAL ANGLES; CHEMICAL-SHIFT; AMINO-ACIDS; FIBRILS; SPECTROSCOPY; RESIDUES; FRAGMENT AB A solid-state nuclear magnetic resonance (NMR) technique is described for obtaining constraints on the backbone conformation of a protein or peptide that is prepared with uniform N-15,C-13 labeling of consecutive pairs of amino acids or of longer segments. The technique, called double single-quantum-filtered rotational echo double resonance (DSQ-REDOR), uses frequency-selective REDOR to prepare DSQ coherences involving directly bonded backbone (CO)-C-13 and (NH)-N-15 sites, to dephase these coherences under longer-range (NH)-N-15-(CO)-C-13 dipole-dipole couplings in a conformationally dependent manner, and to convert the remaining DSQ coherences to detectable transverse C-13-spin polarization. The efficacy of DSQ-REDOR is demonstrated in experiments on two isotopically labeled samples, the helical peptide MB(i + 4)EK and the amyloid-forming peptide A beta(11-25). Published in 2007 by John Wiley & Sons, Ltd. C1 [Oyler, Nathan A.; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU Intramural NIH HHS NR 31 TC 5 Z9 5 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD DEC PY 2007 VL 45 SU S BP S101 EP S106 DI 10.1002/mrc.2110 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 268OD UT WOS:000253588200014 PM 18157809 ER PT J AU Fleming, LE Jerez, E Stephan, WB Cassedy, A Bean, JA Reich, A Kirkpatrick, B Backer, L Nierenberg, K Watkins, S Hollenbeck, J Weisman, R AF Fleming, Lora E. Jerez, Eva Stephan, Wendy Blair Cassedy, Amy Bean, Judy A. Reich, Andrew Kirkpatrick, Barbara Backer, Lorraine Nierenberg, Kate Watkins, Sharon Hollenbeck, Julie Weisman, Richard TI Evaluation of Harmful algal bloom outreach activities SO MARINE DRUGS LA English DT Article DE Poison Information Centers; Harmful algal bloom (HAB); outreach and education; Florida red tide; ciguatera fish poisoning; blue green algae; cyanobacteria; brevetoxins; ciguatoxins; human health effects; neurotoxic shellfish poisoning (NSP); paralytic shellfish poisoning (PSP); Solutions to Avoid Red Tide (START); Karenia brevis ID FLORIDA RED TIDE; AEROSOLIZED BREVETOXINS; HUMAN HEALTH; EXPOSURES; EVENTS; TOXINS AB With an apparent increase of harmful algal blooms (HABs) worldwide, healthcare providers, public health personnel and coastal managers are struggling to provide scientifically-based appropriately-targeted HAB outreach and education. Since 1998, the Florida Poison Information Center-Miami, with its 24 hour/365 day/year free Aquatic Toxins Hotline (1-888-232-8635) available in several languages, has received over 25,000 HAB-related calls. As part of HAB surveillance, all possible cases of HAB-related illness among callers are reported to the Florida Health Department. This pilot study evaluated an automated call processing menu system that allows callers to access bilingual HAB information, and to speak directly with a trained Poison Information Specialist. The majority (68%) of callers reported satisfaction with the information, and many provided specific suggestions for improvement. This pilot study, the first known evaluation of use and satisfaction with HAB educational outreach materials, demonstrated that the automated system provided useful HAB-related information for the majority of callers, and decreased the routine informational call workload for the Poison Information Specialists, allowing them to focus on callers needing immediate assistance and their healthcare providers. These results will lead to improvement of this valuable HAB outreach, education and surveillance tool. Formal evaluation is recommended for future HAB outreach and educational materials. C1 [Fleming, Lora E.; Hollenbeck, Julie] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF, NIEHS Oceans & Human Hlth Ctr, Miami, FL 33136 USA. [Jerez, Eva; Stephan, Wendy Blair; Weisman, Richard] Univ Miami, Miller Sch Med, Dept Pediat, S Florida Poison Informat Ctr, Miami, FL 33136 USA. [Jerez, Eva; Stephan, Wendy Blair; Weisman, Richard] Jackson Hlth Syst, Miami, FL 33136 USA. [Cassedy, Amy; Bean, Judy A.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45244 USA. [Reich, Andrew; Watkins, Sharon] Florida Dept Hlth, Aquat Toxins Grp, Tallahassee, FL 32399 USA. [Kirkpatrick, Barbara; Nierenberg, Kate] Mote Marine Lab, Sarasota, FL 34236 USA. [Backer, Lorraine] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. RP Fleming, LE (reprint author), Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Clin Res Bldg,10th Floor R 669,1120 NW 14th St, Miami, FL 33136 USA. EM lfleming@med.miami.edu FU NIEHS NIH HHS [P01 ES010594, P01 ES010594-07, P30 ES005705, P50 ES012736] NR 29 TC 13 Z9 14 U1 2 U2 11 PU MOLECULAR DIVERSITY PRESERVATION INT PI BASEL PA MATTHAEUSSTRASSE 11, CH-4057 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD DEC PY 2007 VL 5 IS 4 BP 208 EP 219 DI 10.3390/md504208 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 247HC UT WOS:000252068000007 PM 18463727 ER PT J AU Gurarie, D McKenzie, FE AF Gurarie, David McKenzie, F. Ellis TI A stochastic model of immune-modulated malaria infection and disease in children SO MATHEMATICAL BIOSCIENCES LA English DT Article DE malaria; Stochastic; infection; disease; immunity; transmission ID PLASMODIUM-FALCIPARUM PARASITEMIA; BLOOD-STAGE DYNAMICS; TRANSMISSION INTENSITY; AFRICA; ANEMIA; LEVEL AB We develop a simple three-state stochastic description of individual malaria infections that relates dynamics of disease and immune status to age and previous exposure, under different intensities of transmission. We apply the resulting individual-based community models to examine the effects of drug treatment and vaccination on the frequency and severity of disease in ensembles of children. The several broad qualitative similarities between our results and field observations include potential rebound effects following intervals of drug treatment. (C) 2007 Elsevier Inc. All rights reserved. C1 [Gurarie, David] Case Western Reserve Univ, Dept Math, Cleveland, OH 44106 USA. [McKenzie, F. Ellis] Natl Inst Hlth, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Gurarie, D (reprint author), Case Western Reserve Univ, Dept Math, Cleveland, OH 44106 USA. EM David.Gurarie@case.edu; mckenzel@mail.nih.gov OI Gurarie, David/0000-0002-5314-7888 FU FIC NIH HHS [R01 TW001543, R01 TW001543-05S1]; Intramural NIH HHS [Z99 TW999999] NR 25 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD DEC PY 2007 VL 210 IS 2 BP 576 EP 597 DI 10.1016/j.mbs.2007.07.001 PG 22 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 245HX UT WOS:000251926800011 PM 17709118 ER PT J AU Landgren, O Katzmann, JA Hsing, AW Pfeiffer, RM Kyle, RA Yeboah, ED Biritwum, RB Tettey, Y Adjei, AA Larson, DR Dispenzieri, A Melton, LJ Goldin, LR McMaster, ML Caporaso, NE Rajkumar, SV AF Landgren, Ola Katzmann, Jerry A. Hsing, Ann W. Pfeiffer, Ruth M. Kyle, Robert A. Yeboah, Edwapd D. Biritwum, Richard B. Tettey, Yao Adjei, Andrew A. Larson, Dirk R. Dispenzieri, Angela Melton, L. Joseph, III Goldin, Lynn R. McMaster, Mary L. Caporaso, Neil E. Rajkumar, S. Vincent TI Prevalence of monoclonal Gammopathy of undetermined significance among men in Ghana SO MAYO CLINIC PROCEEDINGS LA English DT Article ID MULTIPLE-MYELOMA; ADULT-POPULATION; UNITED-STATES; VETERANS; RISK AB OBJECTIVES: To determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma (MM), in Ghanaian men vs white men and to test for evidence to support an underlying race-related predisposition of the 2-fold higher prevalence of MGUS In African Americans vs whites. PARTICIPANTS AND METHODS: Between September 1, 2004, and September 30, 2006, 917 men (50-74 years) underwent In-person interviews and physical examinations. Serum samples from all participants were analyzed by electrophoresis performed on agarose gel; any serum sample with a discrete or localized band was subjected to immunofixation. Age-adjusted and standardized (to the 2000 world population) prevalence estimates of MGUS and 95% confidence Intervals (Cis) were computed In the Ghanaian men and compared with MGUS prevalence in 7996 white men from Minnesota. Associations between selected characteristics and MGUS prevalence were assessed by the Fisher exact test and logistic regression models. RESULTS: Of the 917 study participants, 54 were found to have MGUS, yielding an age-adjusted prevalence of 5.84 (95% Cl, 4.277.40) per 100 persons. No significant variation was found by age group, ethnicity, education status, or prior infectious diseases. The concentration of monoclonal immunoglobulin was undetectable In 41 (76%) of the 54 MGUS cases, less than 1 g/dL in 10 patients (19%), and J. g/dL or more in only 3 patients (43%). Compared with white men, the age-adjusted prevalence of MGUS was 1.97-fold (95% Cl, 1.94-2.00) higher In Ghanaian men. CONCLUSION: The prevalence of MGUS In Ghanaian men was twice that in white men, supporting the hypothesis that racerelated genetic susceptibility could explain the higher rates of MGUS in black populations. An improved understanding of MGUS and MM pathophysiology would facilitate the development of strategies to prevent progression of MGUS to MM. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. Univ Ghana, Sch Med, Accra, Ghana. RP Landgren, O (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Bldg EPS Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; OI Rajkumar, S. Vincent/0000-0002-5862-1833; Dispenzieri, Angela/0000-0001-8780-9512 FU Intramural NIH HHS; NCI NIH HHS [CA107-476-03, CA62242] NR 20 TC 74 Z9 75 U1 0 U2 1 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD DEC PY 2007 VL 82 IS 12 BP 1468 EP 1473 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 237OI UT WOS:000251384300005 PM 18053453 ER PT J AU Kagawa-Singer, M Pourat, N Breen, N Coughlin, S McLean, TA McNeel, TS Ponce, NA AF Kagawa-Singer, Marjorie Pourat, Nadereh Breen, Nancy Coughlin, Steven McLean, Teresa Abend McNeel, Timothy S. Ponce, Ninez A. TI Breast and cervical cancer screening rates of subgroups of Asian American women in california SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE breast cancer; cervical cancer; Asian American; mammography; Papanicolaou test ID PACIFIC ISLANDER; UNITED-STATES; POPULATION; SURVIVAL AB Although breast and cervical cancer screening rates for Asian American (AA) women are the lowest of any ethnic group in California, few causes for this are known. The authors used the 2001 California Health Interview Survey, conducted in five Asian languages, to conduct the first evaluation of Pap and mammography screening rates for a representative sample of 2,239 AA women. Wide variations in screening rates were found among the seven different subgroups of AA women studied: adjusted Pap test use ranged from 81% (Filipina Americans) to 61% (Vietnamese Americans). Mammography rates ranged from 78% (Japanese Americans) to 53% (Korean Americans). Disaggregating the AA data and using separate multivariate logistic regressions revealed that different factors were independently associated with the low screening rates for each subgroup. The measurement of additional contextual information is needed to identify structural barriers and community resources to provide clearer guidance for the design of effective screening promotion programs for AA subpopulations. C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Natl Canc Inst, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RP Kagawa-Singer, M (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA. EM mkagawa@ucla.edu OI Ponce, Ninez/0000-0001-5151-6718 FU NCI NIH HHS [1 K07 CA100097] NR 43 TC 55 Z9 55 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD DEC PY 2007 VL 64 IS 6 BP 706 EP 730 DI 10.1177/1077558707304638 PG 25 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 233KT UT WOS:000251090500005 PM 17804823 ER PT J AU Riley, J Hassan, M Chernomordik, V Gandjbakhche, A AF Riley, Jason Hassan, Moinuddin Chernomordik, Victor Gandjbakhche, Amir TI Choice of data types in time resolved fluorescence enhanced diffuse optical tomography SO MEDICAL PHYSICS LA English DT Article ID TURBID MEDIUM; LIFETIME; TISSUE; RECONSTRUCTION; SYSTEM AB In this paper we examine possible data types for time resolved fluorescence enhanced diffuse optical tomography (FDOT). FDOT is a particular case of diffuse optical tomography, where our goal is to analyze fluorophores deeply embedded in a turbid medium. We focus on the relative robustness of the different sets of data types to noise. We use an analytical model to generate the expected temporal point spread function (TPSF) and generate the data types from this. Varying levels of noise are applied to the TPSF before generating the data types. We show that local data types are more robust to noise than global data types, and should provide enhanced information to the inverse problem. We go on to show that with a simple reconstruction algorithm, depth and lifetime (the parameters of interest) of the fluorophore are better reconstructed using the local data types. Further we show that the relationship between depth and lifetime is better preserved for the local data types, suggesting they are in some way not only more robust, but also self-regularizing. We conclude that while the local data types may be more expensive to generate in the general case, they do offer clear advantages over the standard global data types. C1 [Riley, Jason; Hassan, Moinuddin; Chernomordik, Victor; Gandjbakhche, Amir] NICHHD, Lab Integrat & Med Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Riley, J (reprint author), NICHHD, Lab Integrat & Med Biophys, Natl Inst Hlth, Bldg 9, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 29 TC 15 Z9 15 U1 0 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2007 VL 34 IS 12 BP 4890 EP 4900 DI 10.1118/1.2804775 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 245BT UT WOS:000251910200034 PM 18196814 ER PT J AU Carlson, O Martin, B Stote, KS Golden, E Maudsley, S Najjar, SS Ferrucci, L Ingram, DK Longo, DL Rumpler, WV Baer, DJ Egan, J Mattson, MP AF Carlson, Olga Martin, Bronwen Stote, Kim S. Golden, Erin Maudsley, Stuart Najjar, Samer S. Ferrucci, Luigi Ingram, Donald K. Longo, Dan L. Rumpler, William V. Baer, David J. Egan, Josephine Mattson, Mark P. TI Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; INSULIN SENSITIVITY; NEUROTROPHIC FACTOR; DIETARY RESTRICTION; METABOLIC SYNDROME; DIABETES-MELLITUS; LEPTIN RESISTANCE; PLASMA-GLUCOSE; BLOOD-PRESSURE; TOLERANCE TEST AB An unresolved issue in the field of diet and health is if and how changes in meal frequency affect energy metabolism in humans. We therefore evaluated the influence of reduced meal frequency without a reduction in energy intake on glucose metabolism in normal-weight, healthy male and female subjects. The study was a randomized crossover design, with two 8-week treatment periods (with an intervening 11-week off-diet period) in which subjects consumed all of their calories for weight maintenance distributed in either 3 meals or I meal per day (consumed between 4:00 Pm and 8:00 Pm). Energy metabolism was evaluated at designated time points throughout the study by pet-forming morning oral glucose tolerance tests and measuring levels of glucose, insulin, glucagon, leptin, ghrelin, adiponectin, resistin, and brain-derived neurotrophic factor (BDNF). Subjects consuming I meal per day exhibited higher morning fasting plasma glucose levels, greater and more sustained elevations of plasma glucose concentrations, and a delayed insulin response in the oral glucose tolerance test compared with subjects consuming 3 meals per day. Levels of ghrelin were elevated in response to the I-meal-per-day regimen. Fasting levels of insulin, leptin, ghrelin, adiponectin, resistin, and BDNF were not significantly affected by meal frequency. Subjects consuming a single large daily meal exhibit elevated fasting glucose levels and impaired morning glucose tolerance associated with a delayed insulin response during a 2-month diet period compared with those consuming 3 meals per day. The impaired glucose tolerance was reversible and was not associated with alterations in the levels of adipokines or BDNF. (c) 2007 Elsevier Inc. All rights reserved. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Clin Invest Lab, Intramural Res Program, Diabet Sect, Baltimore, MD 21224 USA. USDA, Beltsville Human Nutr Res Ctr, Agr Res Serv, Beltsville, MD 20705 USA. NIA, Cardiovasc Sci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Immunol Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000315-07, Z99 AG999999] NR 37 TC 32 Z9 32 U1 1 U2 21 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2007 VL 56 IS 12 BP 1729 EP 1734 DI 10.1016/j.metabol.2007.07.018 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237BM UT WOS:000251347600020 PM 17998028 ER PT J AU Bharti, S Inoue, H Bharti, K Hirsch, DS Nie, Z Yoon, HY Artym, V Yamada, KA Mueller, SC Barr, VA Randazzo, PA AF Bharti, Sanita Inoue, Hiroki Bharti, Kapil Hirsch, Dianne S. Nie, Zhongzhen Yoon, Hye-Young Artym, Vira Yamada, Kenneth A. Mueller, Susette C. Barr, Valarie A. Randazzo, Paul A. TI Src-dependent phosphorylation of ASAP1 regulates podosomes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; FOCAL-ADHESION KINASE; BREAST-CANCER INVASION; HIV-1 NEF PROTEIN; SH3 DOMAIN; MEMBRANE CURVATURE; CRYSTAL-STRUCTURE; COMPLEX; EXPRESSION; RECEPTORS AB Invadopodia are Src-induced cellular structures that are thought to mediate tumor invasion. ASAP1, an Arf GTPase-activating protein (GAP) containing Src homology 3 (SH3) and Bin, amphiphysin, and RVS161/167 (BAR) domains, is a substrate of Src that controls invadopodia. We have examined the structural requirements for ASAP1-dependent formation of invadopodia and related structures in NIH 3T3 fibroblasts called podosomes. We found that both predominant splice variants of ASAP1 (ASAP1a and ASAP1b) associated with invadopodia and podosomes. Podosomes were highly dynamic, with rapid turnover of both ASAP1 and actin. Reduction of ASAP1 levels by small interfering RNA blocked formation of invadopodia and podosomes. Podosomes were formed in NIH 3T3 fibroblasts in which endogenous ASAP1 was replaced with either recombinant ASAP1a or ASAP1b. ASAP1 mutants that lacked the Src binding site or GAP activity functioned as well as wild-type ASAP1 in the formation of podosomes. Recombinant ASAP1 lacking the BAR domain, the SH3 domain, or the Src phosphorylation site did not support podosome formation. Based on these results, we conclude that ASAP1 is a critical target of tyrosine kinase signaling involved in the regulation of podosomes and invadopodia and speculate that ASAP1 may function as a coincidence detector of simultaneous protein association through the ASAP1 SH3 domain and phosphorylation by Src. C1 NCI, Ctr Canc Res, Lab Cellular & Mol Biol, Bethesda, MD USA. NINDS, Mammalian Dev Sect, Bethesda, MD USA. US FDA, Bethesda, MD USA. NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Georgetown Univ, Washington, DC USA. RP Randazzo, PA (reprint author), Ctr Canc Res, Lab Cellular & Mol Biol, CCR, Bldg 37,Rm 4118, Bethesda, MD 20892 USA. EM Randazzo@helix.nih.gov OI Yamada, Kenneth/0000-0003-1512-6805 FU Intramural NIH HHS NR 37 TC 56 Z9 56 U1 2 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 DEC PY 2007 VL 27 IS 23 BP 8271 EP 8283 DI 10.1128/MCB.01781-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 239OH UT WOS:000251527100020 PM 17893324 ER PT J AU Balagopalan, L Barr, VA Sommers, CL Barda-Saad, M Goyal, A Isakowitz, MS Samelson, LE AF Balagopalan, Lakshmi Barr, Valarie A. Sommers, Connie L. Barda-Saad, Mira Goyal, Amrita Isakowitz, Matthew S. Samelson, Lawrence E. TI c-Cbl-mediated regulation of LAT-nucleated signaling complexes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID T-CELL-RECEPTOR; PHOSPHOTYROSINE-BINDING DOMAIN; NEGATIVE REGULATION; ANTIGEN RECEPTOR; TYROSINE PHOSPHORYLATION; UBIQUITIN LIGASES; RING FINGER; ACTIVATION; PROTEIN; FAMILY AB The engagement of the T-cell receptor (TCR) causes the rapid recruitment of multiple signaling molecules into clusters with the TCR. Upon receptor activation, the adapters LAT and SLP-76, visualized as chimeric proteins tagged with yellow fluorescent protein, transiently associate with and then rapidly dissociate from the TCR. Previously, we demonstrated that after recruitment into signaling clusters, SLP-76 is endocytosed in vesicles via a lipid raft-dependent pathway that requires the interaction of the endocytic machinery with ubiquitylated proteins. In this study, we focus on LAT and demonstrate that signaling clusters containing this adapter are internalized into distinct intracellular compartments and dissipate rapidly upon TCR activation. The internalization of LAT was inhibited in cells expressing versions of the ubiquitin ligase c-Cbl mutated in the RING domain and in T cells from mice lacking c-Cbl. Moreover, c-Cbl RING mutant forms suppressed LAT ubiquitylation and caused an increase in cellular LAT levels, as well as basal and TCR-induced levels of phosphorylated LAT. Collectively, these data indicate that following the rapid formation of signaling complexes upon TCR stimulation, c-Cbl activity is involved in the internalization and possible downregulation of a subset of activated signaling molecules. C1 NCI, Cellular & Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Canc Res Ctr, NIH, Bldg 37,Rm 2066, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov FU Intramural NIH HHS NR 52 TC 62 Z9 64 U1 0 U2 2 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 DEC PY 2007 VL 27 IS 24 BP 8622 EP 8636 DI 10.1128/MCB.00467-07 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 239OJ UT WOS:000251527300018 PM 17938199 ER PT J AU Tenno, M Ohtsubo, K Hagen, FK Ditto, D Zarbock, A Schaerli, P von Andrian, UH Ley, K Le, D Tabak, LA Marth, JD AF Tenno, Mari Ohtsubo, Kazuaki Hagen, Fred K. Ditto, David Zarbock, Alexander Schaerli, Patrick von Andrian, Ulrich H. Ley, Klaus Le, Dzung Tabak, Lawrence A. Marth, Jamey D. TI Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FAMILIAL TUMORAL CALCINOSIS; UDP-N-ACETYLGALACTOSAMINE; CORE-2 BRANCHING BETA-1,6-N-ACETYLGLUCOSAMINYLTRANSFERASE; SELECTIN-DEFICIENT MICE; LINKED GLYCOSYLATION; BOVINE COLOSTRUM; CDNA CLONING; B-LYMPHOCYTE; EXPRESSION; BIOSYNTHESIS AB Core-type protein O glycosylation is initiated by pollypeptide N-acetylgalactosamine (GalNAc) transferase (ppGalNAcT) activity and produces the covalent linkage of serine and threonine residues of proteins. More than a dozen ppGalNAcTs operate within multicellular organisms, and they differ with respect to expression patterns and substrate selectivity. These distinctive features imply that each ppGalNAcT may differentially modulate regulatory processes in animal development, physiology, and perhaps disease. We found that ppGalNAcT-1 plays key roles in cell and glycoprotein selective functions that modulate the hematopoietic system. Loss of ppGalNAcT-1 activity in the mouse results in a bleeding disorder which tracks with reduced plasma levels of blood coagulation factors V, VII, VIII, IX, X, and XII. ppGalNAcT-1 further supports leukocyte trafficking and residency in normal homeostatic physiology as well as during inflammatory responses, in part by providing a scaffold for the synthesis of sellectin ligands expressed by neutrophils and endothellial cells of peripheral lymph nodes. Animals lacking ppGalNAcT4 are also markedly impaired in immunoglobulin G production, coincident with increased germinal center B-cell apoptosis and reduced levels of plasma B cells. These findings reveal that the initiation of protein 0 glycosylation by ppGalNAcT-1 provides a distinctive repertoire of advantageous functions that support vascular responses and humoral immunity. C1 Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cell & Mol Med, La Jolla, CA 92093 USA. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Univ Munster, Dept Anesthesiol & Crit Care Med, Munster, Germany. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA USA. Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA. NIDDKD, Sect Biol Chem, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA. RP Marth, JD (reprint author), Univ Calif San Diego, Howard Hughes Med Inst, 9500 Gilman Dr,MC0625, La Jolla, CA 92093 USA. EM jmarth@ucsd.edu RI von Andrian, Ulrich/A-5775-2008 FU NIDDK NIH HHS [DK48247, R01 DK048247] NR 68 TC 59 Z9 61 U1 0 U2 6 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 DEC PY 2007 VL 27 IS 24 BP 8783 EP 8796 DI 10.1128/MCB.01204-07 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 239OJ UT WOS:000251527300031 PM 17923703 ER PT J AU Curcio, MJ Kenny, AE Moore, S Garfinkel, DJ Weintraub, M Gamache, ER Scholes, DT AF Curcio, M. Joan Kenny, Alison E. Moore, Sharon Garfinkel, David J. Weintraub, Matthew Gamache, Eric R. Scholes, Derek T. TI S-phase checkpoint pathways stimulate the mobility of the retrovirus-like transposon Ty1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST RETROTRANSPOSON TY1; DNA-REPLICATION STRESS; VIRUS-LIKE PARTICLES; DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE; DAMAGE CHECKPOINT; GENOME STABILITY; HOMOLOGOUS RECOMBINATION; ELEMENT TRANSPOSITION; REVERSE-TRANSCRIPTASE AB The mobility of the Tyl retrotransposon in the yeast Saccharomyces cerevisiae is restricted by a large collection of proteins that preserve the integrity of the genome during replication. Several of these repressors of Tyl transposition (Rtt)/genome caretakers are orthologs of mammalian retroviral restriction factors. In rtt/genome caretaker mutants, levels of Tyl cDNA and mobility are increased; however, the mechanisms underlying Tyl hypermobility in most rtt mutants are poorly characterized. Here, we show that either or both of two S-phase checkpoint pathways, the replication stress pathway and the DNA damage pathway, partially or strongly stimulate Tyl mobility in 19 rtt/genome caretaker mutants. In contrast, neither checkpoint pathway is required for Tyl hypermobility in two rtt mutants that are competent for genome maintenance. In rtt101 Delta mutants, hypermobility is stimulated through the DNA damage pathway components Rad9, Rad24, Mec1, Rad53, and Dun I but not Chk1. We provide evidence that Tyl cDNA is not the direct target of the DNA damage pathway in rtt101 Delta mutants; instead, levels of Tyl integrase and reverse transcriptase proteins, as well as reverse transcriptase activity, are significantly elevated. We propose that DNA lesions created in the absence of Rtt/genome caretakers trigger S-phase checkpoint pathways to stimulate Tyl reverse transcriptase activity. C1 Wadsworth Ctr, Ctr Med Sci, Lab Dev Genet, Albany, NY 12201 USA. Natl Canc Inst, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Curcio, MJ (reprint author), Wadsworth Ctr, Ctr Med Sci, Lab Dev Genet, POB 2002, Albany, NY 12201 USA. EM curcio@wadsworth.org OI Curcio, M. Joan/0000-0001-5361-3909 FU NIGMS NIH HHS [R01 GM052072, R29 GM052072, GM52072] NR 96 TC 22 Z9 22 U1 0 U2 1 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 DEC PY 2007 VL 27 IS 24 BP 8874 EP 8885 DI 10.1128/MCB.01095-07 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 239OJ UT WOS:000251527300039 PM 17923678 ER PT J AU Rogozin, IB Wolf, YI Carmel, L Koonin, EV AF Rogozin, Igor B. Wolf, Yuri I. Carmel, Liran Koonin, Eugene V. TI Analysis of rare amino acid replacements supports the coelomata clade SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE phylogenetic analysis; cladistics; rare genomic changes; coelomata; ecdysozoa ID EUKARYOTIC GENOMES; ANIMAL PHYLOGENY; ECDYSOZOA; NEMATODE AB The recent analysis of a novel class of rare genomic changes, RGC_CAMs (after conserved amino acids - multiple substitutions), supported the Coelomata clade of animals as opposed to the Ecdysozoa clade (Rogozin et al. 2007). A subsequent reanalysis, with the sequences from the sea anemone Nematostella vectensis included in the set of outgroup species, suggested that this result was an artifact caused by reverse amino replacements and claimed support for Ecdysozoa (Irimia et al. 2007). We show that the internal branch connecting the sea anemone to the bilaterian animals is extremely short, resulting in a weak statistical support for the Coelomata clade. Direct estimation of the level of homoplasy, combined with taxon sampling with different sets of outgroup species, reinforces the support for Coelomata, whereas the effect of reversals is shown to be relatively minor. C1 [Rogozin, Igor B.; Wolf, Yuri I.; Carmel, Liran; Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Carmel, Liran/A-9681-2008 FU Intramural NIH HHS NR 21 TC 19 Z9 21 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD DEC PY 2007 VL 24 IS 12 BP 2594 EP 2597 DI 10.1093/molbev/msm218 PG 4 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 244LX UT WOS:000251868500001 PM 17921482 ER PT J AU Andres, AM de Hemptinne, C Bertranpetit, J AF Andres, Aida M. de Hemptinne, Coralie Bertranpetit, Jaume TI Heterogeneous rate of protein evolution in serotonin genes SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE serotonin; 5-HT; conservation; evolutionary rate; functional pathway; gene family ID CONSERVED SEQUENCES; MAXIMUM-LIKELIHOOD; ADAPTIVE EVOLUTION; POSITIVE SELECTION; SIMPLE DEPENDENCE; 5-HT1E RECEPTOR; GENOMES; MOUSE; DISPENSABILITY; SUBSTITUTION AB Serotonin (5-hydroxytryptamine) is a neurotransmitter crucial for cardiovascular, gastrointestinal, and brain function. It is also involved in several aspects of behavior and associated with a variety of personality disorders in humans. Its dual role as a crucial element in vital physiological functions (strictly evolutionary conserved) and in traits that differ substantially across species makes the evolution of serotonin function particularly interesting. We studied the evolution of serotonin function through the identification of the selective forces shaping the evolution of genes in its functional pathway in primates and rodents. Serotonin genes are highly conserved and show no signals of positive selection, suggesting functional constraint as the main force driving their evolution. They show, nevertheless, considerable differences in constraint between primates and rodents, with some genes showing dramatic differences between the 2 groups. These genes most likely represent cases of functional divergence between primates and rodents and point out to the relevance of using closely related species in gene-based evolutionary studies to avoid the effect of unrecognized functional differences between distant species. Within each group (rodents or primates), genes also show heterogeneity in evolution. Genes from the same gene family (with structure and function alike) tend to evolve at a similar rate, but this is not always the case. A few serotonin genes show substantial differences in constraint with the rest of members of their family, suggesting the presence of important and unrecognized functional differences among the genes, which may be involved in species-specific evolution. C1 [Andres, Aida M.; de Hemptinne, Coralie; Bertranpetit, Jaume] Univ Pompeu Fabra, Unit Biol Evolut, Barcelona, Spain. RP Andres, AM (reprint author), NHGRI, Natl Inst Hlth, Genome Technol Branch, Bethesda, MD 20892 USA. EM andresa@mail.nih.gov RI Bertranpetit, Jaume/F-8550-2012; Andres, Aida/B-4088-2014 OI Bertranpetit, Jaume/0000-0003-0100-0590; Andres, Aida/0000-0002-8590-9672 NR 46 TC 13 Z9 13 U1 3 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD DEC PY 2007 VL 24 IS 12 BP 2707 EP 2715 DI 10.1093/molbev/msm202 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 244LX UT WOS:000251868500012 PM 17884826 ER PT J AU Culp, WD Tsagozis, P Burgio, M Russell, P Pisa, P Garland, D AF Culp, W. David Tsagozis, Panagiotis Burgio, Michael Russell, Paul Pisa, Pavel Garland, Donita TI Interference of macrophage migration inhibitory factor expression in a mouse melanoma inhibits tumor establishment by up-regulating thrombospondin-1 SO MOLECULAR CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; GENE FAMILY; FACTOR MIF; ENDOTHELIAL-CELLS; ANGIOGENESIS; CANCER; PROTEIN; MEMBER; IDENTIFICATION; ACTIVATION AB Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with proinflammatory, proangiogenic, and protumorigenic properties. The molecular mechanisms underlying the role of MIF in tumorigenesis and angiogenesis are not well understood. To address these roles, an interfering MIF (iMIF) RNA was stably introduced into the B16-F10 mouse melanoma cell line, reducing MIF mRNA expression 1.6-fold and MIF protein expression 2.8-fold relative to control cells. When iMIF cells were subcutaneously injected into C57131L/6 mice, tumor establishment was significantly delayed and there was a marked absence of intratumoral vasculature in iMIF tumors relative to controls. A comparative gene expression analysis of iMIF and control melanoma cell lines revealed that thrombospondin-1 (TSP-1) mRNA expression was up-regulated 88-fold in the iMIF cells by real-time PCR. A 2-fold increase in TSP-1 protein levels was observed in iMIF cell culture supernatants. These results strongly suggest that the delayed tumor establishment and reduced vasculature in iMIF melanomas are linked to the up-regulation of the antiangiogenic TSP-1. They further define a novel function of MIF as a regulator of TSP-1 in a mouse melanoma model. C1 [Culp, W. David; Burgio, Michael; Russell, Paul; Garland, Donita] NEI, NIH, Bethesda, MD 20892 USA. [Culp, W. David; Tsagozis, Panagiotis; Pisa, Pavel] Karolinska Hosp & Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, Stockholm, Sweden. RP Garland, D (reprint author), Univ Penn, FM Kirby Ctr Mol Ophthalmol, Scheie Eye Inst, 306 Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA. EM garland1@mail.med.upenn.edu FU Intramural NIH HHS NR 37 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2007 VL 5 IS 12 BP 1225 EP 1231 DI 10.1158/1541-7786.MCR-07-0229 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 250JK UT WOS:000252295800001 PM 18171979 ER PT J AU Li, Z Tan, F Thiele, CJ AF Li, Zhijie Tan, Fei Thiele, Carol J. TI Inactivation of glycogen synthase kinase-3 beta contributes to brain-derived neutrophic factor/TrkB-induced resistance to chemotherapy in neuroblastoma cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NEUROTROPHIC FACTOR ACTIVATION; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; INDUCED APOPTOSIS; SURVIVAL; DEATH; AKT; PROMOTES; PHOSPHORYLATION AB Elucidating signaling pathways that mediate cell survival or apoptosis will facilitate the development of targeted therapies in cancer. In neuroblastoma tumors, brain-derived neurotrophic factor (BDNF) and its receptor TrkB are associated with poor prognosis. Our previous studies have shown that BDNF activation of TrkB induces resistance to chemotherapy via activation of phosphoinositide-3-kinase (PI3K)/Akt pathway. To study targets of PI3K/ Akt that mediate protection from chemotherapy, we focused on glycogen synthase kinase-3 beta (GSK-beta), which is a known modulator of apoptosis. We used pharmacologic and genetic methods to study the role of GSK-3 beta in the BDNF/TrkB/PI3K/Akt protection of neuroblastoma from chemotherapy. BDNF activation of TrkB induced the Akt-dependent phosphorylation of GSK-3 beta, resulting in its inactivation. Treatment of neuroblastoma cells with inhibitors of GSK-3 beta, LiCl, GSK-3 beta inhibitor VII, kenpaullone, or a GSK-3 beta -targeted small interfering RNA (siRNA) resulted in a 15% to 40% increase in neuroblastoma cell survival after cytotoxic treatment. Transfection of neuroblastoma cells with a constitutively active GSK-3 beta S9A9 caused a 10% to 15% decrease in cell survival. Using real-time, dynamic measurements of cell survival, we found that 6 to 8 h after etoposide treatment was the period during which critical events regulating the induction of cell death or BDNF/TrkB-induced protection occurred. During this period, etoposide treatment was associated with the dephosphorylation and activation of GSK-3 beta in the mitochondria that was blocked by BDNF activation of TrkB. These data indicate that the inactivation of GSK-3 beta contributes to the BDNF/TrkB/PI3K/Akt protection of neuroblastoma cells from chemotherapy. C1 [Li, Zhijie; Tan, Fei; Thiele, Carol J.] NCI, NIH, Canc Res Ctr, Cell & Mol Biol Sect,Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Thiele, CJ (reprint author), NCI, NIH, Canc Res Ctr, Cell & Mol Biol Sect,Pediat Oncol Branch, 10 Ctr Dr MSC-1928 Bldg 10-CRC 1-3940, Bethesda, MD 20892 USA. EM ct47a@nih.gov FU Intramural NIH HHS NR 40 TC 27 Z9 28 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3113 EP 3121 DI 10.1158/1535-7163.MCT-07-0133 PG 9 WC Oncology SC Oncology GA 245HS UT WOS:000251926300004 PM 18089706 ER PT J AU Takagi, K Dexheimer, TS Redon, C Sordet, O Agama, K Lavielle, G Pierre, A Bates, SE Pommier, Y AF Takagi, Kazutaka Dexheimer, Thomas S. Redon, Christophe Sordet, Olivier Agama, Keli Lavielle, Gilbert Pierre, Alain Bates, Susan E. Pommier, Yves TI Novel E-ring camptothecin keto analogues (S38809 and S39625) are stable, potent, and selective topoisomerase I inhibitors without being substrates of drug efflux transporters SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID DNA CLEAVAGE COMPLEXES; ANTITUMOR-ACTIVITY; COVALENT COMPLEX; MAMMALIAN-CELLS; HISTONE H2AX; SERINE 139; DERIVATIVES; RESISTANCE; PHOSPHORYLATION; CYTOTOXICITY AB Camptothecin (CPT) analogues are powerful anticancer agents but are chemically unstable due to their alpha-hydroxylactone six-membered E-ring structure, which is essential for trapping topoisomerase I (Top1)-DNA cleavage complexes. To stabilize the E-ring, CPT keto analogues with a five-membered E-ring lacking the oxygen of the lactone ring (S38809 and S39625) have been synthesized. S39625 has been selected for advanced preclinical development based on its promising activity in tumor models. Here, we show that both keto analogues are active against purified Top1 and selective against Top 1 in yeast and human cancer cells. The keto analogues show improved cytotoxicity toward colon, breast, and prostate cancer cells and leukemia cells compared with CPT. The drug-induced Top1-DNA cleavage complexes induced by the keto analogues show remarkable persistence both with purified Top1 and in cells following 1-h drug treatments. Moreover, we find that S39625 is not a substrate for either the ABCB1 (multidrug resistance/1/P-glycoprotein) or ABCG2 (mitoxantrone resistance/breast cancer resistance protein) drug efflux transporters, which sets S39625 apart from the clinically used CPT analogues topotecan or SN-38 (active metabolite of irinotecan). Finally, we show that nanomolar concentrations of S38809 or S39625 induce intense and persistent histone gamma-H2AX. The chemical stability of the keto analogues and the ability of S39625 to produce high levels of persistent Top1-DNA cleavage complex and its potent antiproliferative activity against human cancer cell lines make S39625 a promising new anticancer drug candidate. Histone gamma-H2AX could be used as a biomarker for the upcoming clinical trials of S39625. C1 [Takagi, Kazutaka; Dexheimer, Thomas S.; Redon, Christophe; Sordet, Olivier; Agama, Keli; Pommier, Yves] NCI, Ctr Canc Res, Lab Mol Pharmacol, Bethesda, MD 20892 USA. [Bates, Susan E.] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD USA. [Lavielle, Gilbert; Pierre, Alain] Inst Rech Int Servier, Croissy Sur Seine, France. RP Pommier, Y (reprint author), NCI, Ctr Canc Res, Lab Mol Pharmacol, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Sordet, Olivier/M-3271-2014 FU Intramural NIH HHS NR 49 TC 29 Z9 33 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3229 EP 3238 DI 10.1158/1535-7163.MCT-07-0441 PN 1 PG 10 WC Oncology SC Oncology GA 245HS UT WOS:000251926300016 PM 18089716 ER PT J AU Henrich, CJ Robey, RW Bokesch, HR Bates, SE Shukla, S Ambudkar, SV Dean, M McMahon, JB AF Henrich, Curtis J. Robey, Robert W. Bokesch, Heidi R. Bates, Susan E. Shukla, Suneet Ambudkar, Suresh V. Dean, Michael McMahon, James B. TI New inhibitors of ABCG2 identified by high-throughput screening SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CANCER RESISTANCE PROTEIN; ANTICANCER DRUG SCREEN; ACUTE-MYELOID-LEUKEMIA; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; ORAL BIOAVAILABILITY; MONOCLONAL-ANTIBODY; BRAIN PENETRATION; FUMITREMORGIN-C; IN-VITRO AB In order to identify novel inhibitors of the ATP-binding cassette transporter, ABCG2, a high-throughput assay measuring the accumulation of the ABCG2 substrate pheophorbide a in ABCG2-overexpressing NCI-H460 MX20 cells was used to screen libraries of compounds. Out of a library of 7,325 natural products and synthetic compounds from the National Cancer Institute/Developmental Therapeutics Program collection, 18 were found to inhibit ABCG2 at 10 mu mol/L. After eliminating flavonoids and compounds of limited availability from the 18 original compounds, 10 of the 11 remaining compounds reversed mitoxantrone resistance in NCI-H460/MX20 cells and prevented ABCG2-mediated BODIPY-prazosin transport in ABCG2-transfected HEK293 cells, confirming an interaction with ABCG2. Based on the activity profiles and the availability of materials, five inhibitors were examined for their ability to compete with [1251] iodoarylazidoprazosin labeling of ABCG2, increase binding of the anti-ABCG2 antibody 5D3, and prevent P-glycoprotein or multidrug resistance protein 1-mediated transport. At a concentration of 20 mu mol/L, all of the compounds reduced iodoarylazidoprazosin labeling by 50% to 80% compared with controls. All five compounds also increased 5133 labeling of ABCG2, indicating that these compounds are inhibitors but not substrates of ABCG2. None of the compounds affected P-glycoprotein-mediated rhodamine 123 transport, whereas three affected multidrug resistance protein-1-mediated calcein transport at 25 [mu mol/L, suggesting that the compounds are relatively specific for ABCG2. These five novel inhibitors of ABCG2 activity may provide a basis for further investigation of ABCG2 function and its relevance in multidrug resistance. C1 [Henrich, Curtis J.; Bokesch, Heidi R.] Sci Applicat Int Corp Frederick Inc, NCI, Frederick, MD 21702 USA. [Henrich, Curtis J.; Bokesch, Heidi R.; McMahon, James B.] NCI, Mol Targets Dev Program, Frederick, MD USA. [Dean, Michael] NCI, Lab Genom Divers, Frederick, MD USA. [Robey, Robert W.; Bates, Susan E.] Med Oncol Branch, Bethesda, MD USA. [Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Bethesda, MD USA. RP Henrich, CJ (reprint author), Sci Applicat Int Corp Frederick Inc, NCI, Bldg 560,Rm 32-63A, Frederick, MD 21702 USA. EM henrichc@ncifcrf.gov RI shukla, suneet/B-4626-2012; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS [Z01 BC005725-15, Z01 BC010030-12, Z01 BC010622-04]; NCI NIH HHS [N01CO12400] NR 35 TC 31 Z9 31 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3271 EP 3278 DI 10.1158/1535-7163.MCT-07-0352 PN 1 PG 8 WC Oncology SC Oncology GA 245HS UT WOS:000251926300021 PM 18089721 ER PT J AU Shukla, S Wu, CP Nandigama, K Ambudkar, SV AF Shukla, Suneet Wu, Chung-Pu Nandigama, Krishnamachary Ambudkar, Suresh V. TI The naphthoquinones, vitamin K3 and its structural analogue plumbagin, are substrates of the multidrug resistance-linked ATP binding cassette drug transporter ABCG2 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BREAST-CANCER CELLS; HUMAN P-GLYCOPROTEIN; IN-VITRO; ANTICANCER ACTIVITY; OXIDATIVE STRESS; LEUKEMIA-CELLS; MITOMYCIN-C; PHASE-I; PROTEIN; MENADIONE AB Vitamin K3 (menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of vitamins K1 and K2, which are essential for blood clotting. The naturally occurring structural analogue of this vitamin, plumbagin (5-hydroxymenadione), is known to modulate cellular proliferation, apoptosis, carcinogenesis, and radioresistance. We here report that both vitamin K3 and plumbagin are substrates of the multidrug resistance-linked ATP binding cassette drug transporter, ABCG2. Vitamin K3 and plumbagin specifically inhibited the ABCG2-mediated efflux of mitoxantrone but did not have any effect on the ABCB1-mediated efflux of rhodamine 123. This inhibition of ABCG2 function was due to their interaction at the substrate-binding site(s). Vitamin K3 and plumbagin inhibited the binding of [1251] iodoarylazidoprazosin, a substrate of ABCG2, to this transporter in a concentration-dependent manner with IC50 values of 7.3 and 22.6 mu mol/L, respectively, but had no effect on the binding of the photoaffinity analogue to ABCB1. Both compounds stimulated ABC132-mediated ATP hydrolysis and also inhibited the mitoxantrone-stimulated ATPase activity of the ABCG2 transporter, but did not have any significant effect on the ATPase activity of ABCB1. In a cytotoxicity assay, ABCG2-expressing HEK cells were 2.8- and 2.3-fold resistant to plumbagin and vitamin K3, respectively, compared with the control cells, suggesting that they are substrates of this transporter. Collectively, these data show for the first time that vitamin K3 is a substrate of the ABCG2 transporter. Thus, ABCG2 may have a role in the regulation of vitamin K3 levels in the body. In addition, vitamin K3 and its structural derivative, plumbagin, could potentially be used to modulate ABCG2 function. C1 [Ambudkar, Suresh V.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Shukla, Suneet; Wu, Chung-Pu; Nandigama, Krishnamachary; Ambudkar, Suresh V.] NIH, NCI, Canc Res Ctr, Cell Biol Lab,Dept Hlth & Human Serv, Bethesda, MD USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, MSC 4254 37 Convent Dr, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov RI shukla, suneet/B-4626-2012 FU Intramural NIH HHS [Z01 BC010030-11] NR 44 TC 33 Z9 33 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3279 EP 3286 DI 10.1158/1535-7163.MCT-07-0564 PN 1 PG 8 WC Oncology SC Oncology GA 245HS UT WOS:000251926300022 PM 18065489 ER PT J AU Wu, CP Shulkla, S Calcagno, AM Hall, MD Gottesman, MM Ambudkar, SV AF Wu, Chung-Pul Shulkla, Suneet Calcagno, Anna Maria Hall, Matthew D. Gottesman, Michael M. Ambudkar, Suresh V. TI Evidence for dual mode of action of a thiosemicarbazone, NSC73306: a potent substrate of the multidrug resistance-linked ABCG2 transporter SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID HUMAN P-GLYCOPROTEIN; BREAST-CANCER CELLS; ATP HYDROLYSIS; ACQUIRED MUTATIONS; DRUG-RESISTANCE; STEM-CELLS; PROTEIN; OVEREXPRESSION; GENE; MITOXANTRONE AB Multidrug resistance due to reduced drug accumulation is a phenomenon predominantly caused by the overexpression of members of the ATP-binding cassette (ABC) transporters, including ABCB1 (P-glycoprotein), ABCG2, and several ABCC family members [multidrug resistance associated protein (MRP)]. We previously reported that a thiosemicarbazone derivative, NSC73306, is cytotoxic to carcinoma cells that overexpress functional P-glycoprotein, and it resensitizes these cells to chemotherapeutics. In this study, we investigated the effect of NSC73306 on cells overexpressing other ABC drug transporters, including ABCG2, MRP1, MRP4, and MRP5. Our findings showed that NSC73306 is not more toxic to cells that overexpress these transporters compared with their respective parental cells, and these transporters do not confer resistance to NSC73306 either. In spite of this, we observed that NSC73306 is a transport substrate for ABCG2 that can effectively inhibit ABCG2-mediated drug transport and reverse resistance to both mitoxantrone and topotecan in ABCG2-expressing cells. Interactions between NSC73306 and the ABCG2 drug-binding site(s) were confirmed by its stimulatory effect on ATPase activity (140-150 nmol/L concentration required for 50% stimulation) and by inhibition of [1251] iodoarylazidoprazosin photolabeling (50% inhibition at 250-400 nmol/L) of the substrate-binding site(s). Overall, NSC73306 seems to be a potent modulator of ABCG2 that does not interact with MRP1, MRP4, or MRP5. Collectively, these data suggest that NSC73306 can potentially be used, due to its dual mode of action, as an effective agent to overcome drug resistance by eliminating P-glycoprotein-overexpressing cells and by acting as a potent modulator that resensitizes ABCG2-expressing cancer cells to chemotherapeutics. C1 [Ambudkar, Suresh V.] NCI, Bethesda, MD 20892 USA. [Wu, Chung-Pul; Shulkla, Suneet; Calcagno, Anna Maria; Hall, Matthew D.; Gottesman, Michael M.; Ambudkar, Suresh V.] NCI, NIH, Ctr Canc Res, Cell Biol Lab, Bethesda, MD USA. RP Ambudkar, SV (reprint author), NCI, Bldg 37,Rm 2120,MSC 4256,37 Convent Dr, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov RI Hall, Matthew/B-2132-2010; Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU Intramural NIH HHS [Z01 BC010030-11] NR 49 TC 48 Z9 48 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3287 EP 3296 DI 10.1158/1535-7163.MCT-07-2005 PN 1 PG 10 WC Oncology SC Oncology GA 245HS UT WOS:000251926300023 PM 18089722 ER PT J AU Martin, SE Pommier, Y Caplen, NJ AF Martin, Scott E. Pommier, Yves Caplen, Natasha J. TI RNAi screening identifies TAK1 as a potential target for the enhanced efficacy of traditional cytotoxic agents in breast cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Martin, Scott E.; Pommier, Yves; Caplen, Natasha J.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3331S EP 3331S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000004 ER PT J AU Sun, HY Nikolovska-Coleskal, Z Lu, JF Meagher, JL Yang, CY Qiu, S Krajewski, K Roller, PP Stuckey, J Yi, H Wang, SM AF Sun, Haiying Nikolovska-Coleskal, Zaneta Lu, Jianfeng Meagher, Jennifer L. Yang, Chao-Yie Qiu, Su Krajewski, Krzysztof Roller, Peter P. Stuckey, Jeanne Yi, Han Wang, Shaomeng TI Design, synthesis, and evaluation of bivalent conformationally constrained Smac mimetics that concurrently targeting both BIR2 and BIR3 domain of XIAP SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Sun, Haiying; Nikolovska-Coleskal, Zaneta; Lu, Jianfeng; Meagher, Jennifer L.; Yang, Chao-Yie; Qiu, Su; Stuckey, Jeanne; Yi, Han; Wang, Shaomeng] Univ Michigan, Ann Arbor, MI 48109 USA. [Krajewski, Krzysztof; Roller, Peter P.] NCI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3331S EP 3331S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000003 ER PT J AU Sridhar, SS Mackenzie, MJ Hotte, SJ Mukherjee, SD Murray, N Tannock, IF Haider, MA Chen, EX Wang, L Srinivasan, R Ivy, SP Moore, MJ AF Sridhar, Srikala S. Mackenzie, Mary J. Hotte, Sebastien J. Mukherjee, Som D. Murray, Nevin Tannock, Ian F. Haider, Masoom A. Chen, Eric X. Wang, Lisa Srinivasan, Ranuka Ivy, S. Percy Moore, Malcolm J. TI AZD2171 (Cediranib) is active in first line metastatic renal cell carcinoma (RCC): Interim results of a phase II trial. A trial of the PMH Phase II Consortium SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Sridhar, Srikala S.; Tannock, Ian F.; Haider, Masoom A.; Chen, Eric X.; Wang, Lisa; Srinivasan, Ranuka; Moore, Malcolm J.] Princess Margaret Hosp, Toronto, ON, Canada. [Mackenzie, Mary J.] London Reg Canc Ctr, Toronto, ON, Canada. [Hotte, Sebastien J.; Mukherjee, Som D.] Juravinski Canc Ctr, Hamilton, ON, Canada. [Murray, Nevin] BC Canc Agncy, Vancouver, BC, Canada. [Ivy, S. Percy] Natl Canc Inst, CTEP, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3337S EP 3338S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000023 ER PT J AU Penson, RT Berlin, ST Krasner, CN Roche, M Tyburski, KA Belden, SE Daniels, GH Garg, RK Ivy, P Matulonis, UA AF Penson, Richard T. Berlin, Suzanne T. Krasner, Carolyn N. Roche, Maria Tyburski, Karin A. Belden, Sarah E. Daniels, Gilbert H. Garg, Rajesh K. Ivy, Percy Matulonis, Ursula A. TI Thyroid toxicity with the VEGF/PDGF receptor TKI AZD-2171 (Recentin (TM)) in a phase II study of recurrent mullerian tumors SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Penson, Richard T.; Krasner, Carolyn N.; Roche, Maria; Belden, Sarah E.; Daniels, Gilbert H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Berlin, Suzanne T.; Tyburski, Karin A.; Matulonis, Ursula A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Garg, Rajesh K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ivy, Percy] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3339S EP 3339S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000029 ER PT J AU Puzanov, I Flaherty, KT Atkins, MB McDermott, DF Wright, JJ Vermeulen, W Harlacker, K Hsu, A Rothenberg, ML Sosman, JA AF Puzanov, Igor Flaherty, Keith T. Atkins, Michael B. McDermott, David F. Wright, John J. Vermeulen, Wendy Harlacker, Kathleen Hsu, Arlene Rothenberg, Mace L. Sosman, Jeffrey A. TI Final results of a phase I trial of sorafenib and bevacizumab in patients with metastatic renal cell cancer (mRCC) SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Puzanov, Igor; Vermeulen, Wendy; Rothenberg, Mace L.; Sosman, Jeffrey A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Flaherty, Keith T.; Harlacker, Kathleen] Univ Penn, Philadelphia, PA 19104 USA. [Atkins, Michael B.; McDermott, David F.; Hsu, Arlene] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wright, John J.] Natl Canc Inst, CTEP, Bethesda, MD USA. RI Puzanov, Igor/A-7179-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3340S EP 3341S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000032 ER PT J AU Pastorino, F Di Paolo, D Piccardi, F Nico, B Ribatti, D Daga, A Baio, G Neumaiers, CE Brignole, C Marimpietri, D Loi, M Poignan, G Cilli, M Wu, LJ Lepekhin, EA Ponzoni, M AF Pastorino, Fabio Di Paolo, Daniela Piccardi, Federica Nico, Beatrice Ribatti, Domenico Daga, Antonio Baio, Gabriella Neumaiers, Carlo E. Brignole, Chiara Marimpietri, Danilo Loi, Monica Poignan, Gabriella Cilli, Michele Wu, Lirzi J. Lepekhin, Eugene A. Ponzoni, Mirco TI Antitumor effects of NGR-peptide targeted liposomal doxorubicin against human solid tumors SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Pastorino, Fabio; Di Paolo, Daniela; Brignole, Chiara; Marimpietri, Danilo; Loi, Monica; Poignan, Gabriella; Ponzoni, Mirco] G Gaslini Childrens Hosp, Genoa, Italy. [Piccardi, Federica] IST Natl Inst Canc Res, Anim Res Facil, Genoa, Italy. [Nico, Beatrice; Ribatti, Domenico] Univ Bari, Dept Human Anat, Bari, Italy. [Daga, Antonio] IST Natl Inst Canc Res, Gene Transfer Lab, Genoa, Italy. [Baio, Gabriella; Neumaiers, Carlo E.] Natl Canc Inst, Dept Radiol, Genoa, Italy. [Wu, Lirzi J.] Ambrilia Biopharma Inc, Verdun, PQ, Canada. RI Baio, Gabriella/M-7621-2015; Di Paolo, Daniela/J-7681-2016 OI Baio, Gabriella/0000-0002-8397-5318; Di Paolo, Daniela/0000-0001-7264-6888 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3341S EP 3341S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000034 ER PT J AU Du, X Nagata, S Ise, T Stetler-Stevenson, M Pastan, I AF Du, Xing Nagata, Satoshi Ise, Tomoko Stetler-Stevenson, Maryalice Pastan, Ira TI FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia and B-cell non-Hodgkin's lymphoma as a target of immunotoxins SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Du, Xing; Nagata, Satoshi; Ise, Tomoko; Pastan, Ira] NIH, NCI, LMB, Bethesda, MD USA. [Stetler-Stevenson, Maryalice] NIH, NCI, LP, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3352S EP 3353S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000067 ER PT J AU Feng, Y Zhu, Z Xiao, X Weitman, SD Dimitrov, DS AF Feng, Yang Zhu, Zhongyu Xiao, Xiaodong Weitman, Steven D. Dimitrov, Dimiter S. TI Depleting soluble ligand (IGF-II) in solid tumor (human breast cancer xenograft) by ligand-specific human monoclonal antibody SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Feng, Yang; Zhu, Zhongyu; Xiao, Xiaodong; Dimitrov, Dimiter S.] NCI, NIH, Frederick, MD USA. [Weitman, Steven D.] Syst Med Inc, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3354S EP 3354S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000071 ER PT J AU Weldon, JE Xiang, L Fitzgerald, D Pastan, I AF Weldon, John E. Xiang, Laiman Fitzgerald, David Pastan, Ira TI Improved design of pseudomonas exotoxin A-based immunotoxins SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Weldon, John E.] Natl Canc Inst, Natl Inst Gen Med Sci, Bethesda, MD USA. [Xiang, Laiman; Fitzgerald, David; Pastan, Ira] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3358S EP 3358S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000085 ER PT J AU Leopoldino, AM Squarize, CH Matos, FA Tajara, EH Gutkind, JS AF Leopoldino, Andreia M. Squarize, Cristiane H. Matos, Flavia A. Tajara, Eloiza H. Gutkind, J. Silvio CA Grp GENCAPO TI New marker in oral cancer and insights in regulation of PTEN phosphorylation SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Leopoldino, Andreia M.; Matos, Flavia A.] Univ Sao Paulo, Fac Ciencias Farmaceut, Depto Anal Clin Toxicol & Bromatol, Ribeirao Preto, Brazil. [Squarize, Cristiane H.; Gutkind, J. Silvio] Natl Inst Hlth, Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. [Tajara, Eloiza H.] Fac Med, Sao Paulo, Brazil. [Grp GENCAPO] Head & Neck Genome Project, Sao Paulo, Brazil. RI Gutkind, J. Silvio/A-1053-2009; Leopoldino, Andreia/E-9926-2012; Tajara, Eloiza/G-7586-2012 OI Leopoldino, Andreia/0000-0002-8313-4754; Tajara, Eloiza/0000-0002-2603-2057 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3368S EP 3369S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000117 ER PT J AU Remondo, C Cereda, V Franzusoff, A Schlom, J Tsang, KY AF Remondo, Cinzia Cereda, Vittore Franzusoff, Alex Schlom, Jeffrey Tsang, Kwong Yok TI Analysis of the ability of recombinant yeast (Saccharomyces cerevisiae)vector encoding carcinoembrionic antigen (CEA) to infect dendritic cells and activate antigen-specific T-cell responses SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Remondo, Cinzia; Cereda, Vittore; Schlom, Jeffrey; Tsang, Kwong Yok] NIH, NCI, Bethesda, MD USA. [Franzusoff, Alex] GlobeImmune Inc, Louisville, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3368S EP 3368S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000115 ER PT J AU Wansley, EK Chakraborty, M Hance, KW Bernstein, MB Guo, Z Quick, D Franzusoff, A Mostbock, S Sabzevari, H Greiner, JW Schlom, J Hodge, JW AF Wansley, Elizabeth K. Chakraborty, Mala Hance, Kenneth W. Bernstein, Michael B. Guo, Zhimin Quick, Deborah Franzusoff, Alex Mostbock, Sven Sabzevari, Helen Greiner, John W. Schlom, Jeffrey Hodge, James W. TI Vaccination of CEA-transgenic mice with a recombinant Saccharomyces cerevisiae-CEA vaccine breaks immune tolerance and elicits therapeutic antitumor responses SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Wansley, Elizabeth K.; Chakraborty, Mala; Hance, Kenneth W.; Bernstein, Michael B.; Mostbock, Sven; Sabzevari, Helen; Greiner, John W.; Schlom, Jeffrey; Hodge, James W.] NCI, NIH, Bethesda, MD USA. [Guo, Zhimin; Quick, Deborah] GlobeImmune Inc, Louisville, CO USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3368S EP 3368S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000116 ER PT J AU Frech, MS Torre, K Robinson, GW Furth, PA AF Frech, Maria S. Torre, Kathleen Robinson, Gertraud W. Furth, Priscilla A. TI Loss of cyclin D1 in concert with deregulated estrogen receptor alpha expression induces a DNA damage response and interrupts mammary gland morphogenesis SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Frech, Maria S.; Torre, Kathleen; Furth, Priscilla A.] George Washington Univ, Washington, DC 20052 USA. [Robinson, Gertraud W.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3369S EP 3369S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000119 ER PT J AU Monks, A Hollingshead, M Stotler, H Divellbiss, R Hose, CD AF Monks, Anne Hollingshead, Melinda Stotler, Howard Divellbiss, Raymond Hose, Curtis D. TI Human tumor cell lines in vitro provide a relevant model for topotecan-induced transcriptional changes in analogous xenografts SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Monks, Anne; Hollingshead, Melinda; Stotler, Howard; Divellbiss, Raymond; Hose, Curtis D.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3375S EP 3375S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000134 ER PT J AU Shoemaker, RH Hose, CD Pezzoli, P Vansant, G Sehested, M Monforte, J Monks, A AF Shoemaker, Robert H. Hose, Curtis D. Pezzoli, Patrick Vansant, Gordon Sehested, Maxwell Monforte, Joseph Monks, Anne TI Defining a set of genes dysregulated in response to the HDAC inhibitor PXD101 (belinostat) SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Shoemaker, Robert H.; Hose, Curtis D.; Monks, Anne] NCI, Frederick, MD 21701 USA. [Pezzoli, Patrick; Vansant, Gordon; Monforte, Joseph] Althea Technol Inc, San Diego, CA USA. [Sehested, Maxwell] TopoTarget AS, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3377S EP 3377S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000139 ER PT J AU Peethambaram, PP Burton, JK Oberg, AL Gomez-Dahl, LC Isham, CR Tibodeau, JD Chomjak, TL Colevas, AD Wright, JJ Erlichman, C Bible, KC AF Peethambaram, Prema P. Burton, Jill K. Oberg, Ann L. Gomez-Dahl, Leigh C. Isham, Crescent R. Tibodeau, Jennifer D. Chomjak, Tamra L. Colevas, A. Dimitrios Wright, John J. Erlichman, Charles Bible, Keith C. TI A phase 2 trial of flavopiridol and cisplatin in platinum-resistant ovarian cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Peethambaram, Prema P.; Burton, Jill K.; Oberg, Ann L.; Gomez-Dahl, Leigh C.; Isham, Crescent R.; Tibodeau, Jennifer D.; Chomjak, Tamra L.; Erlichman, Charles; Bible, Keith C.] Mayo Clin, Rochester, MN USA. [Colevas, A. Dimitrios] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. [Wright, John J.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3380S EP 3381S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000150 ER PT J AU Gulley, JL Arlen, PM Madan, R Lechleider, RL Dahut, WL Lowy, I Schlom, J AF Gulley, James L. Arlen, Philip M. Madan, Ravi Lechleider, Robert L. Dahut, William L. Lowy, Israel Schlom, Jeffrey TI Phase I Trial of a PSA based vaccine and ipilimumab in patients (pts) with metastatic castrate resistant prostate cancer (CRPC) SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Gulley, James L.; Arlen, Philip M.; Madan, Ravi; Lechleider, Robert L.; Dahut, William L.; Schlom, Jeffrey] NCI, Bethesda, MD USA. [Lowy, Israel] Medarex, Princeton, NJ USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3381S EP 3381S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000152 ER PT J AU O'Bryant, CL Leong, S Camidge, DR Gore, L Diab, S Gustafson, DL Call, J Spratlin, J Zwiebel, JA Eckhardt, SG AF O'Bryant, Cindy L. Leong, Stephen Camidge, D. Ross Gore, Lia Diab, Sami Gustafson, Dan L. Call, Justin Spratlin, Jennifer Zwiebel, James A. Eckhardt, S. Gail TI A phase 1 study of belinostat (PXD101) in combination with bortezomib in patients with advanced solid tumors and lymphoma SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [O'Bryant, Cindy L.; Leong, Stephen; Camidge, D. Ross; Gore, Lia; Diab, Sami; Call, Justin; Spratlin, Jennifer; Eckhardt, S. Gail] Univ Colorado, Ctr Canc, Aurora, CO USA. [Gustafson, Dan L.] Colorado State Univ, Ft Collins, CO USA. [Zwiebel, James A.] NCI Canc Therapy Evaluat Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3384S EP 3384S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000159 ER PT J AU Mackay, HJ Hirte, H Covens, A MacAlpine, K Wang, L Tsao, M Pan, J Zweibel, J Oza, AM AF Mackay, Helen J. Hirte, Hal Covens, Al MacAlpine, Katrina Wang, Lisa Tsao, Ming Pan, James Zweibel, James Oza, Amit M. TI A phase II trial of the histone deacetylase inhibitor Belinostat (PXD101) in patients with platinum resistant epithelial ovarian tumors and micropapillary/borderline (LMP) ovarian tumors. A trial of the PMH Phase II Consortium SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Mackay, Helen J.; MacAlpine, Katrina; Wang, Lisa; Tsao, Ming; Pan, James; Oza, Amit M.] Princess Margaret Hosp, Toronto, ON, Canada. [Hirte, Hal] Juravinski Canc Ctr, Hamilton, ON, Canada. [Covens, Al] Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. [Zweibel, James] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3388S EP 3388S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000170 ER PT J AU Rao, VA Agama, K Holbeck, S Pommier, Y AF Rao, V. Ashutosh Agama, Keli Holbeck, Susan Pommier, Yves TI Batracylin,8-aminoisoindolo[1,2-b]quinazolin-10(12H)-one (NSC 320846), a dual inhibitor of DNA topoisomerases I and III: Molecular mechanisms and gamma-H2AX as a biomarker of DNA damage SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Rao, V. Ashutosh; Agama, Keli; Holbeck, Susan; Pommier, Yves] NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3392S EP 3393S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000181 ER PT J AU McMahon, J AF McMahon, James TI NCI's molecular targets development program (MTDP) SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [McMahon, James] Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3403S EP 3403S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000215 ER PT J AU Houghton, PJ Maris, JM Friedman, HS Keir, ST Lock, RB Carol, H Gorlick, R Kolb, EA Keshlava, N Reynolds, CP Morton, CL Smith, MA AF Houghton, Peter J. Maris, John M. Friedman, Henry S. Keir, Stephen T. Lock, Richard B. Carol, Hernan Gorlick, Richard Kolb, E. Anders Keshlava, Nino Reynolds, C. Patrick Morton, Christopher L. Smith, Malcolm A. TI Pediatric preclinical testing program (PPTP) evaluation of the fully human anti-IGF-1R antibody SCH 717454 SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Houghton, Peter J.; Morton, Christopher L.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Maris, John M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Friedman, Henry S.; Keir, Stephen T.] Duke Univ, Durham, NC USA. [Lock, Richard B.; Carol, Hernan] Childrens Canc Inst, Randwick, NSW, Australia. [Gorlick, Richard; Kolb, E. Anders] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Keshlava, Nino; Reynolds, C. Patrick] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RI Carol, Hernan/F-5750-2013 OI Carol, Hernan/0000-0002-9443-8032 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3405S EP 3405S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000221 ER PT J AU Long, J Nikolovska-Coleska, Z Jiang, F Shangary, S Roller, PP Wang, S AF Long, Jianting Nikolovska-Coleska, Zaneta Jiang, Feng Shangary, Sanjeev Roller, Peter P. Wang, Shaomeng TI Development and validation of mitochondria-based functional assays to investigate the mechanism of small-molecule inhibitors of Bcl-2/Bcl-xL/Mcl-1 (BH3 mimetics) in cell-free systems SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Long, Jianting; Nikolovska-Coleska, Zaneta; Jiang, Feng; Shangary, Sanjeev; Wang, Shaomeng] Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Ann Arbor, MI 48109 USA. [Roller, Peter P.] NIH, Natl Canc Inst, Med Chem Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3406S EP 3406S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000223 ER PT J AU Takagi, K Dexheimer, TS Redon, C Sordet, O Agama, K Lavielle, G Pierre, A Robey, RW Bates, S Pommier, Y AF Takagi, Kazutaka Dexheimer, Thomas S. Redon, Christophe Sordet, Olivier Agama, Keli Lavielle, Gilbert Pierre, Alain Robey, Robert W. Bates, Susan Pommier, Yves TI Novel E-ring camptothecin-keto-analogs (S38809 and S39625) are stable, potent, and selective topoisomerase I inhibitors without being substrates of drug efflux transporters SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Takagi, Kazutaka; Dexheimer, Thomas S.; Redon, Christophe; Sordet, Olivier; Agama, Keli; Pommier, Yves] NCI, CCR, Mol Pharmacol Lab, Bethesda, MD USA. [Robey, Robert W.; Bates, Susan] NCI, CCR, Expt Transplantat & Immunol Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3423S EP 3423S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000276 ER PT J AU Cao, X Plasencia, C Yamada, R Burke, TR Neamati, N AF Cao, Xuefei Plasencia, Carmen Yamada, Roppei Burke, Terrence R., Jr. Neamati, Nouri TI Molecular mechanism of salicylhydrazide class of compounds SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Cao, Xuefei; Plasencia, Carmen; Yamada, Roppei; Neamati, Nouri] Univ So Calif, Los Angeles, CA USA. [Burke, Terrence R., Jr.] NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3432S EP 3432S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000302 ER PT J AU Vidal, L Hirte, H Fleming, GF Sugimoto, A Morgan, RJ Biagi, J Wang, L Dickl, C Ivy, P Oza, AM AF Vidal, L. Hirte, H. Fleming, G. F. Sugimoto, A. Morgan, R. J. Biagi, J. Wang, L. Dickl, C. Ivy, P. Oza, A. M. TI A phase 2 study of AZD2171 in recurrent or persistent ovarian, peritoneal or fallopian tube cancer. A study of the PMH, Chicago, and California Phase II Consortia SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Vidal, L.; Wang, L.; Oza, A. M.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Hirte, H.] Jravinsky Canc Ctr, Hamilton, ON, Canada. [Fleming, G. F.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Sugimoto, A.] London Reg Canc Ctr, London, ON N6A 4L6, Canada. [Morgan, R. J.] City Hope Natl Canc Ctr, Duarte, CA USA. [Biagi, J.] Kingston Reg Canc Ctr, Toronto, ON, Canada. [Ivy, P.] NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3433S EP 3433S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000305 ER PT J AU Rapisarda, A Hollingshead, M Raffeld, M Gehrs, B Borgel, S Carter, J Bonomi, C Shoemaker, R Melillo, G AF Rapisarda, Annamaria Hollingshead, Melinda Raffeld, Mark Gehrs, Bradley Borgel, Suzanne Carter, John Bonomi, Carrie Shoemaker, Robert Melillo, Giovanni TI Synergistic antitumor activity of Bevacizumab in combination with HIF-1 inhibition SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Rapisarda, Annamaria; Melillo, Giovanni] NCI, SAIC, Frederick, MD USA. [Hollingshead, Melinda; Borgel, Suzanne; Carter, John; Bonomi, Carrie] NCI, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Frederick, MD 21701 USA. [Raffeld, Mark; Gehrs, Bradley] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Shoemaker, Robert] NCI, Dev Therapeut Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3438S EP 3438S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000319 ER PT J AU Michelin, R Johnson, C Oladeinde, F Kinyua, A Leitner, W Knox, N Lobban, K Shureiqi, I Jenkins, M Whittaker, J AF Michelin, Ruei Johnson, Cynthia Oladeinde, Frederick Kinyua, Antony Leitner, Wolfgang Knox, Nathaniel Lobban, Kathleen Shureiqi, Imad Jenkins, Marshell Whittaker, Joseph TI B22 Apoptosis induced in PaCa-2 cancer cells with novel Bacillus fermented extract SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Michelin, Ruei] Morgan State Univ, Sch Med, IUHS, Baltimore, MD 21239 USA. [Johnson, Cynthia; Oladeinde, Frederick; Kinyua, Antony; Knox, Nathaniel; Jenkins, Marshell; Whittaker, Joseph] Morgan State Univ, Baltimore, MD 21239 USA. [Leitner, Wolfgang] NCI, NIH, Bethesda, MD 20892 USA. [Lobban, Kathleen] Univ W Indies, Univ Technol, Kingston 7, Jamaica. [Shureiqi, Imad] Univ Texas MD Anderson Canc Clin, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3440S EP 3440S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000323 ER PT J AU DiPaolo, JA Aquino, G Alvarez-Salas, LM AF DiPaolo, Joseph A. Aquino, Giulliano Alvarez-Salas, Luis M. TI Triplex systems of ribozymes for inhibition of human papillomavirus type 16 (HPV-16). SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [DiPaolo, Joseph A.] NCI, Bethlehem, PA USA. [Aquino, Giulliano; Alvarez-Salas, Luis M.] CINVESTAV, Mexico City, DF, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3448S EP 3448S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000352 ER PT J AU Grubbs, CJ Bode, AM Steele, VE Juliana, MM Lubet, RA AF Grubbs, Clinton J. Bode, Ann M. Steele, Vernon E. Juliana, M. Margaret Lubet, Ronald A. TI Preventive effects of the EGFR inhibitor Iressa on chemically-induced urinary bladder cancers: Histopathological and biochemical endpoints. SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Grubbs, Clinton J.; Juliana, M. Margaret] Univ Alabama, Chemoprevent Ctr, Birmingham, AL USA. [Bode, Ann M.] Hormel Inst, Austin, MN USA. [Steele, Vernon E.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3452S EP 3452S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000366 ER PT J AU Guirouilh-Barbat, J Takagi, K Von Hoff, DD Pommier, Y AF Guirouilh-Barbat, Jose Takagi, Kazutaka Von Hoff, Daniel D. Pommier, Yves TI PNU-166196 induces DNA damage measured by histone H2AX phosphorylation independently of the nucleotide excision repair pathways. SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Guirouilh-Barbat, Jose; Takagi, Kazutaka; Pommier, Yves] Canc Res Ctr, NCI, Bethesda, MD USA. [Von Hoff, Daniel D.] Translat Res Inst, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3456S EP 3457S PN 2 PG 2 WC Oncology SC Oncology GA 245WH UT WOS:000251969000378 ER PT J AU Dhani, NC Cohen, SJ Bjarnason, GA Kollmannsberger, C Virik, K Brown, J Wang, L Oza, A Chen, A Moore, MJ AF Dhani, Neesha C. Cohen, Steven J. Bjarnason, Georg A. Kollmannsberger, Christian Virik, Kiran Brown, Jasmine Wang, Lisa Oza, Amit Chen, Alice Moore, Malcolm J. TI A Phase II trial of VEGF-Trap in previously treated patients with metastatic colorectal cancer (PHL 050). A study of the PMH Phase II Consortium. SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Dhani, Neesha C.; Brown, Jasmine; Wang, Lisa; Oza, Amit; Moore, Malcolm J.] Princess Margaret Hosp, Toronto, ON, Canada. [Cohen, Steven J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Bjarnason, Georg A.] Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. [Kollmannsberger, Christian] British Columbia Canc Agcy, Vancouver, BC, Canada. [Virik, Kiran] QEII Hlth Sci Ctr, Halifax, NS, Canada. [Chen, Alice] NIH, NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3459S EP 3459S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000385 ER PT J AU Traynor, AM Dubey, S Eickhoff, L Kolesar, JM Schell, K Groteluschen, DL Marcotte, SM Hallahan, CM Weeks, HR Zwiebel, J Schiller, JH AF Traynor, Anne M. Dubey, Sarita Eickhoff, Lens Kolesar, Jill M. Schell, Kathleen Groteluschen, David L. Marcotte, Sarah M. Hallahan, Courtney M. Weeks, Hilary R. Zwiebel, James Schiller, Joan H. TI Vorinostat (NSC 701852) in patients (pts) with relapsed non-small cell lung cancer (NSCLC): A Wisconsin Oncology Network phase II study. SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Traynor, Anne M.; Eickhoff, Lens; Kolesar, Jill M.; Schell, Kathleen; Marcotte, Sarah M.; Hallahan, Courtney M.; Weeks, Hilary R.] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. [Dubey, Sarita] Univ Calif San Francisco, Ctr Canc, San Francisco, CA USA. [Groteluschen, David L.] Green Bay Oncol, Green Bay, WI USA. [Zwiebel, James] NCI, Bethesda, MD USA. [Schiller, Joan H.] Univ Texas, Southwestern Canc Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3463S EP 3463S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000395 ER PT J AU Traini, R Margulies, I Kreitman, RJ AF Traini, Roberta Margulies, Inger Kreitman, Robert J. TI Stability and proteolysis of immunotoxins in patient urine after treatment. SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Traini, Roberta; Margulies, Inger; Kreitman, Robert J.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3464S EP 3464S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000398 ER PT J AU Houghton, PJ Maris, JM Courtright, J Friedman, HS Keir, ST Lock, RB Carol, H Gorlick, R Kolb, EA Keshelava, N Reynolds, CP Morton, CL Smith, MA AF Houghton, Peter J. Maris, John M. Courtright, Joshua Friedman, Henry S. Keir, Stephen T. Lock, Richard B. Carol, Hernan Gorlick, Richard Kolb, E. Anders Keshelava, Nino Reynolds, C. Patrick Morton, Christopher L. Smith, Malcolm A. TI Pediatric preclinical testing program (PPTP) evaluation of the EGFR and ErbB2 inhibitor lapatinib SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Houghton, Peter J.; Morton, Christopher L.] St Jude Childrens Hosp, Memphis, TN USA. [Maris, John M.; Courtright, Joshua] Childrens Hosp Philadelphia, Philadelphia, PA USA. [Friedman, Henry S.; Keir, Stephen T.] Duke Univ, Durham, NC 27706 USA. [Lock, Richard B.; Carol, Hernan] Childrens Canc Inst, Randwick, NSW, Australia. [Gorlick, Richard] Albert Einstein Coll Med, New York, NY USA. [Kolb, E. Anders] duPont Hosp Children, Wilmington, DE USA. [Keshelava, Nino; Reynolds, C. Patrick] Childrens Hosp Los Angeles, Los Angeles, CA USA. [Smith, Malcolm A.] NCI, CTEP, Bethesda, MD USA. RI Carol, Hernan/F-5750-2013 OI Carol, Hernan/0000-0002-9443-8032 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3471S EP 3471S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000417 ER PT J AU Kramer-Marek, G Kiesewetter, DO Martiniova, L Rodriguez, Y Capala, J AF Kramer-Marek, Gabriela Kiesewetter, Dale O. Martiniova, Lucia Rodriguez, Yesenia Capala, Jacek TI F-18-Z(HER2)-Affibody: A new tracer for molecular imaging of HER2-expressing tumors by PET SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Kramer-Marek, Gabriela; Rodriguez, Yesenia; Capala, Jacek] NCI, NIH, Bethesda, MD USA. [Kiesewetter, Dale O.] NIBIB, NIH, Bethesda, MD USA. [Martiniova, Lucia] NICHHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3478S EP 3478S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000438 ER PT J AU Giubellino, A Jenkins, L Vasselli, J Appella, E Burke, TR Bottaro, DP AF Giubellino, Alessio Jenkins, Lisa Vasselli, James Appella, Ettore Burke, Terrence R., Jr. Bottaro, Donald P. TI Novel insight into the mechanism of action and selectivity of the Grb2 Src homology 2 domain binding antagonist C90 SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Giubellino, Alessio; Jenkins, Lisa; Vasselli, James; Appella, Ettore; Burke, Terrence R., Jr.; Bottaro, Donald P.] NCI, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010; Burke, Terrence/N-2601-2014 OI Bottaro, Donald/0000-0002-5057-5334; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3496S EP 3496S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000492 ER PT J AU Ramanathan, RK Egorin, MJ Erlichman, C Remick, SC Ramalingam, S Ivy, SP Ten Eyck, C Holleran, JL Naret, CI Belani, CP AF Ramanathan, Ramesh K. Egorin, Merrill J. Erlichman, Charles Remick, Scot C. Ramalingam, Suresh Ivy, S. Percy Ten Eyck, Cyntha Holleran, Julianne L. Naret, Cindy I. Belani, Chandra P. TI Phase I, pharmacokinetic (PK), and pharmacodynamic (PD) study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, (17DMAG, NSC 707545), an inhibitor of heat shock protein 90 (HSP90), in patients with advanced solid tumors: Final results SO MOLECULAR CANCER THERAPEUTICS LA English DT Meeting Abstract C1 [Ramanathan, Ramesh K.] TGen, Scottsdale, AZ USA. [Egorin, Merrill J.; Ramalingam, Suresh; Holleran, Julianne L.; Naret, Cindy I.; Belani, Chandra P.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. [Erlichman, Charles; Ten Eyck, Cyntha] Mayo Clin, Rochester, MN USA. [Remick, Scot C.] Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA. [Ivy, S. Percy] NCI, Canc Therapy & Evaluat Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD DEC PY 2007 VL 6 IS 12 BP 3500S EP 3500S PN 2 PG 1 WC Oncology SC Oncology GA 245WH UT WOS:000251969000506 ER EF