FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Janakiraman, V Ojo, L Sheth, S Keller, J Young, H AF Janakiraman, Vanitha Ojo, Linda Sheth, Sheetal Keller, Jennifer Young, Heather TI Membrane sweeping in GBS positive patients: a randomized controlled trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Janakiraman, Vanitha] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ojo, Linda; Sheth, Sheetal; Keller, Jennifer; Young, Heather] George Washington Univ, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 72 BP S41 EP S41 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500073 ER PT J AU Joynt, K Jha, A Lazar, J Janakiraman, V AF Joynt, Karen Jha, Ashish Lazar, Jane Janakiraman, Vanitha TI Comparing the outcomes of low volume and high volume obstetrics providers and hospitals SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Joynt, Karen] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jha, Ashish] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lazar, Jane] Massachusetts Dept Publ Hlth, Boston, MA USA. [Janakiraman, Vanitha] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 614 BP S244 EP S244 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500611 ER PT J AU Kaimal, A Janakiraman, V Newman, K Ecker, J AF Kaimal, Anjali Janakiraman, Vanitha Newman, Katherine Ecker, Jeff TI The rising primary cesarean rate in a low risk population: What is the impact of CNM versus MD care? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Kaimal, Anjali; Janakiraman, Vanitha; Newman, Katherine; Ecker, Jeff] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2011 VL 204 SU 1 MA 544 BP S218 EP S218 DI 10.1016/j.ajog.2010.10.564 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500542 ER PT J AU Kaimal, A Yee, LM Nakagawa, S Kuppermann, M AF Kaimal, Anjali Yee, Lynn M. Nakagawa, Sanae Kuppermann, Miriam TI Predictors of early postpartum sexual activity and relationship to mode of delivery in a diverse population of women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Kaimal, Anjali] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Yee, Lynn M.; Nakagawa, Sanae; Kuppermann, Miriam] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 149 BP S72 EP S72 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500149 ER PT J AU Karumanchi, A Stillman, I McMahon, K Cummings, P Fligner, C Patton, D Easterling, T AF Karumanchi, Ananth Stillman, Isaac McMahon, Kerry Cummings, Peter Fligner, Corrine Patton, Dorothy Easterling, Tom TI What is the physiological role of sFlt-1? Does sFlt-1 control placental invasion at the expense of increasing the risk of developing preeclampsia? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Karumanchi, Ananth; Stillman, Isaac] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [McMahon, Kerry; Cummings, Peter; Fligner, Corrine; Patton, Dorothy; Easterling, Tom] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2011 VL 204 SU 1 MA 766 BP S301 EP S301 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500763 ER PT J AU Kim, M Rotmensch, S Acuna, J Cohavy, O Solt, I Lebovics, I Paster, B Reeder, J Knight, R AF Kim, Matthew Rotmensch, Siegfried Acuna, Joann Cohavy, Offer Solt, Ido Lebovics, Irving Paster, Bruce Reeder, Jens Knight, Rob TI Preliminary observations on the microbial phylogeny of the oral, vaginal, and rectal microbiome in gestational diabetes and healthy pregnancies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Kim, Matthew; Rotmensch, Siegfried] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Los Angeles, CA 90048 USA. [Paster, Bruce] Forsyth Inst, Boston, MA USA. [Paster, Bruce] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Reeder, Jens; Knight, Rob] Univ Colorado, Boulder, CO 80309 USA. NR 0 TC 0 Z9 0 U1 1 U2 14 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 JAN PY 2011 VL 204 SU 1 MA 257 BP S109 EP S110 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500256 ER PT J AU Lim, KH Zera, C Wilkins-Haug, L McElrath, T Rich-Edwards, J Stuart, J Parry, S AF Lim, Kee-Hak Zera, Chloe Wilkins-Haug, Louise McElrath, Thomas Rich-Edwards, Janet Stuart, Jennifer Parry, Samuel TI The association of first trimester body mass index with preeclampsia phenotype SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Lim, Kee-Hak] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Rich-Edwards, Janet] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Stuart, Jennifer] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Parry, Samuel] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 744 BP S292 EP S293 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500741 ER PT J AU Lim, KH McElrath, TF Rich-Edwards, J Pare, E Parry, S AF Lim, Kee-Hak McElrath, Thomas F. Rich-Edwards, Janet Pare, Emanuel Parry, Samuel TI Longitudinal evaluation of circulating angiogenic factors for prediction of preeclampsia in a large contemporary North American cohort SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Lim, Kee-Hak] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [McElrath, Thomas F.; Rich-Edwards, Janet] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Pare, Emanuel; Parry, Samuel] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 4 BP S3 EP S3 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500005 ER PT J AU Rana, S Karumanchi, A Wang, A Powe, C Ecker, J Thadhani, R Levine, R AF Rana, Sarosh Karumanchi, Ananth Wang, Alice Powe, Camille Ecker, Jeffery Thadhani, Ravi Levine, Richard TI Preeclampsia is not independently associated with large for gestational age infants SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Rana, Sarosh; Karumanchi, Ananth] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Wang, Alice] Boston Med Ctr, Boston, MA USA. [Powe, Camille; Ecker, Jeffery; Thadhani, Ravi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Levine, Richard] NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 244 BP S105 EP S105 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500243 ER PT J AU Rana, S Salahuddin, S Hegde, S Lim, KH Karumanchi, A Powe, C AF Rana, Sarosh Salahuddin, Saira Hegde, Saumya Lim, Kee-Hak Karumanchi, Ananth Powe, Camille TI Prospective evaluation of angiogenic proteins as predictors of adverse maternal and fetal outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Rana, Sarosh; Salahuddin, Saira; Hegde, Saumya; Lim, Kee-Hak; Karumanchi, Ananth] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Powe, Camille] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 792 BP S310 EP S310 DI 10.1016/j.ajog.2010.10.814 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500789 ER PT J AU Rhee, J Shahul, S Mitchell, J Mahmood, F Hamar, B Hess, P Rana, S Powe, C AF Rhee, Julie Shahul, Sajid Mitchell, John Mahmood, Feroze Hamar, Benjamin Hess, Philip Rana, Sarosh Powe, Camille TI Myocardial performance index in preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Rhee, Julie; Shahul, Sajid; Mitchell, John; Mahmood, Feroze; Hamar, Benjamin; Hess, Philip; Rana, Sarosh] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Powe, Camille] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Hess, Philip/A-8577-2013 OI Hess, Philip/0000-0002-1206-0102 NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2011 VL 204 SU 1 MA 389 BP S159 EP S159 DI 10.1016/j.ajog.2010.10.408 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500388 ER PT J AU Scholl, J Coletta, J Panda, B Al Ammari, R Kaplan, J Wolfberg, A Tanner, C Iyer, C Heard, A House, M Craigo, S AF Scholl, Jessica Coletta, Jaclyn Panda, Britta Al Ammari, Roa Kaplan, Jeremy Wolfberg, Adam Tanner, Cassandre Iyer, Chitra Heard, Asha House, Michael Craigo, Sabrina TI Obstetric outcomes in cases of first trimester cystic hygroma SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Scholl, Jessica] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Coletta, Jaclyn] Columbia Univ, Med Ctr, New York, NY USA. [Panda, Britta] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Al Ammari, Roa; Kaplan, Jeremy; Wolfberg, Adam; Tanner, Cassandre; Iyer, Chitra; Heard, Asha; House, Michael; Craigo, Sabrina] Tufts Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2011 VL 204 SU 1 MA 704 BP S278 EP S279 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500701 ER PT J AU Silasi, M Rana, S Cohen, B Lim, KH Karumanchi, A Stillman, I Powe, C AF Silasi, Michelle Rana, Sarosh Cohen, Bruce Lim, Kee-Hak Karumanchi, Ananth Stillman, Isaac Powe, Camille TI Trisomy 13 and placental sFlt-1 expression SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Silasi, Michelle; Rana, Sarosh; Cohen, Bruce; Lim, Kee-Hak; Karumanchi, Ananth; Stillman, Isaac] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Powe, Camille] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 778 BP S305 EP S305 DI 10.1016/j.ajog.2010.10.800 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500775 ER PT J AU Smith, NA McElrath, TF Henry, D AF Smith, Nicole A. McElrath, Thomas F. Henry, Dana TI Risk of early severe preeclampsia in singleton and twin pregnancies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [McElrath, Thomas F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Henry, Dana] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 748 BP S294 EP S294 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500745 ER PT J AU Sparks, TN Caughey, AB Rosenstein, MG Cheng, YW Chang, JH Phan, N AF Sparks, Teresa N. Caughey, Aaron B. Rosenstein, Melissa G. Cheng, Yvonne W. Chang, Jin H. Phan, Ngoc TI Is twin chorionicity associatied with preeclampsia? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Sparks, Teresa N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sparks, Teresa N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Caughey, Aaron B.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Rosenstein, Melissa G.; Cheng, Yvonne W.; Chang, Jin H.; Phan, Ngoc] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2011 VL 204 SU 1 MA 612 BP S243 EP S244 DI 10.1016/j.ajog.2010.10.632 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500609 ER PT J AU Torchilin, K Colognato, R Manganini, M Columbo, M Fauza, D Armant, M Bayer-Zwirello, L Zanna, G Grati, F Simoni, G AF Torchilin, Kate Colognato, Renato Manganini, Massimiliano Columbo, Mariaelena Fauza, Dario Armant, Myriam Bayer-Zwirello, Lucy Zanna, Gaia Grati, Francesca Simoni, Giuseppe TI Third trimester amniotic fluid as source of mesenchymal stem cells for regenerative applications SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med C1 [Torchilin, Kate] Biocell Ctr Corp, Medford, MA USA. [Colognato, Renato; Manganini, Massimiliano; Columbo, Mariaelena] Biocell Ctr Corp, Varese, Italy. [Fauza, Dario] Childrens Hosp, Boston, MA 02115 USA. [Armant, Myriam] Immune Dis Inst, Boston, MA USA. [Bayer-Zwirello, Lucy; Zanna, Gaia] St Elizabeth Hosp, Boston, MA USA. [Grati, Francesca; Simoni, Giuseppe] TOMA Adv Biomed Assays SpA, Varese, Italy. RI Colognato, Renato/A-8520-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2011 VL 204 SU 1 MA 857 BP S332 EP S332 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 702WV UT WOS:000285927500854 ER PT J AU Yell, H Smoot, E Schoenfeld, D Schuetz, C Varma, M Markmann, J AF Yell, Heidi Smoot, Elizabeth Schoenfeld, David Schuetz, Christian Varma, Manish Markmann, James TI Geographic Disparities in Access to Deceased Donor Livers SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Congress of the American-Society-of-Transplant-Surgeons CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplant Surg C1 [Yell, Heidi; Smoot, Elizabeth; Schoenfeld, David; Schuetz, Christian; Varma, Manish; Markmann, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2011 VL 11 SU 1 BP 75 EP 75 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 709AD UT WOS:000286406500079 ER PT J AU Varma, MC Tolkoff-Rubin, N Cosimi, AB Elias, N Malik, F Goes, NB Pratt, DS Thiim, M Andersson, K Markmann, JF Hertl, M AF Varma, Manish C. Tolkoff-Rubin, Nina Cosimi, A. Benedict Elias, Nahel Malik, Fahim Goes, Nelson B. Pratt, Daniel S. Thiim, Michael Andersson, Karin Markmann, James F. Hertl, Martin TI Plasmapheresis in Treatment of Fibrosing Cholestatic Hepatitis Due to Recurrent Hepatitis C after Liver Transplant SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Congress of the American-Society-of-Transplant-Surgeons CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplant Surg C1 [Varma, Manish C.; Cosimi, A. Benedict; Elias, Nahel; Markmann, James F.; Hertl, Martin] Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. [Varma, Manish C.; Tolkoff-Rubin, Nina; Cosimi, A. Benedict; Elias, Nahel; Malik, Fahim; Goes, Nelson B.; Pratt, Daniel S.; Thiim, Michael; Andersson, Karin; Markmann, James F.; Hertl, Martin] Harvard Univ, Sch Med, Boston, MA USA. [Tolkoff-Rubin, Nina; Malik, Fahim; Goes, Nelson B.] Massachusetts Gen Hosp, Dept Med, Div Renal, Boston, MA 02114 USA. [Pratt, Daniel S.; Thiim, Michael; Andersson, Karin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2011 VL 11 SU 1 BP 80 EP 80 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 709AD UT WOS:000286406500098 ER PT J AU Yannam, GR Liu, LP Basma, H Ito, R White, P Soto-Gutierrez, A Wang, L Sato, S Tanaka, K Miller, J Duan, FH Kaestner, K Fox, I AF Yannam, Govardhana R. Liu, Liping Basma, Hesham Ito, Ryotaro White, Peter Soto-Gutierrez, Alejandro Wang, Lin Sato, Shintaro Tanaka, Kimiaki Miller, John Duan, Fenghai Kaestner, Klaus Fox, Ira TI Extracellular Microenvironment Is the Dominant Factor in Hepatocyte Proliferation and Function in Advanced Liver Disease SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT Congress of the American-Society-of-Transplant-Surgeons CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplant Surg C1 [Yannam, Govardhana R.; Liu, Liping; Basma, Hesham; Ito, Ryotaro; Sato, Shintaro; Tanaka, Kimiaki; Miller, John] Univ Nebraska Med Ctr, Dept Surg, Omaha, NE USA. [White, Peter; Kaestner, Klaus] Univ Penn, Philadelphia, PA 19104 USA. [Soto-Gutierrez, Alejandro] Massachusetts Gen Hosp, Ctr Engn Med, Surg Serv, Boston, MA 02114 USA. [Wang, Lin; Fox, Ira] UPMC, Dept Surg, Pittsburgh, PA USA. [Wang, Lin; Fox, Ira] UPMC, McGowan Inst Regenerat Med, Pittsburgh, PA USA. [Duan, Fenghai] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2011 VL 11 SU 1 BP 84 EP 84 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 709AD UT WOS:000286406500111 ER PT J AU Boden, E Ahuja, V Moran, C Nguyen, D Mayer, L Snapper, S AF Boden, E. Ahuja, V Moran, C. Nguyen, D. Mayer, L. Snapper, S. TI The Wiskott-Aldrich Syndrome protein alters Treg homeostasis via reduced strength of T cell receptor signaling SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations National Clinical and Research Conference CY DEC 09-12, 2010 CL Hollywood, FL C1 [Boden, E.; Mayer, L.] Mt Sinai Hosp, New York, NY 10029 USA. [Ahuja, V] All India Med Inst, New Delhi, India. [Moran, C.; Nguyen, D.; Snapper, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2011 VL 17 SU 1 BP S3 EP S4 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 693WO UT WOS:000285256300013 ER PT J AU Docktor, M Abramowicz, S Ingram, J Jiang, H Bousvaros, A Paster, B AF Docktor, M. Abramowicz, S. Ingram, J. Jiang, H. Bousvaros, A. Paster, B. TI The oral microbiome in children with inflammatory bowel disease. SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT Advances in Inflammatory Bowel Diseases Crohn's and Colitis Foundations National Clinical and Research Conference CY DEC 09-12, 2010 CL Hollywood, FL C1 [Docktor, M.; Ingram, J.; Jiang, H.; Bousvaros, A.] Childrens Hosp Boston, Dept Pediat Gastroenterol, Boston, MA USA. [Docktor, M.; Paster, B.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Abramowicz, S.] Childrens Hosp Boston, Dept Oral Surg, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2011 VL 17 SU 1 BP S13 EP S13 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 693WO UT WOS:000285256300040 ER PT J AU Kalasapudi, B Shah, S Leleiko, N Lidofsky, S Bright, R Grabert, S Law, M Moniz, H Bancroft, B Patel, M Harris, A Cole, E Merrick, M Flowers, N Sands, B AF Kalasapudi, B. Shah, S. Leleiko, N. Lidofsky, S. Bright, R. Grabert, S. Law, M. Moniz, H. Bancroft, B. Patel, M. Harris, A. Cole, E. Merrick, M. Flowers, N. Sands, B. TI Medical therapy of IBD in the first year after diagnosis: Preliminary results from the Ocean State Crohn's and Colitis Area Registry (OSCCAR). SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations National Clinical and Research Conference CY DEC 09-12, 2010 CL Hollywood, FL C1 [Kalasapudi, B.; Shah, S.; Leleiko, N.; Lidofsky, S.; Bright, R.; Law, M.; Moniz, H.; Bancroft, B.; Patel, M.; Harris, A.] Lifespan, Providence, RI USA. [Kalasapudi, B.; Shah, S.; Leleiko, N.; Lidofsky, S.; Bright, R.; Law, M.; Moniz, H.; Bancroft, B.; Patel, M.; Harris, A.] Brown Univ, Providence, RI 02912 USA. [Grabert, S.; Cole, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merrick, M.] Crohns & Colitis Fdn Amer, New York, NY USA. [Flowers, N.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Sands, B.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2011 VL 17 SU 1 BP S8 EP S9 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 693WO UT WOS:000285256300027 ER PT J AU Kalasapudi, B Shah, S Leleiko, N Lidofsky, S Bright, R Grabert, S Law, M Moniz, H Bancroft, B Patel, M Harris, A Cole, E Merrick, M Flowers, N Sands, B AF Kalasapudi, B. Shah, S. Leleiko, N. Lidofsky, S. Bright, R. Grabert, S. Law, M. Moniz, H. Bancroft, B. Patel, M. Harris, A. Cole, E. Merrick, M. Flowers, N. Sands, B. TI Presenting Symptoms at Diagnosis of Crohn's Disease and Ulcerative Colitis: Results from the Ocean State Crohn's and Colitis Area Registry (OSCCAR) SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT Advances in Inflammatory Bowel Diseases Crohn's and Colitis Foundations National Clinical and Research Conference CY DEC 09-12, 2010 CL Hollywood, FL C1 [Kalasapudi, B.; Shah, S.; Leleiko, N.; Lidofsky, S.; Bright, R.; Law, M.; Moniz, H.; Bancroft, B.; Patel, M.; Harris, A.] Brown Univ, Providence, RI 02912 USA. [Kalasapudi, B.; Shah, S.; Leleiko, N.; Lidofsky, S.; Bright, R.; Law, M.; Moniz, H.; Bancroft, B.; Patel, M.; Harris, A.] Lifespan, Providence, RI USA. [Law, M.; Cole, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merrick, M.] Crohns & Colitis Fdn Amer, New York, NY USA. [Flowers, N.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Sands, B.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2011 VL 17 SU 1 BP S48 EP S48 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 693WO UT WOS:000285256300157 ER PT J AU Sands, B Shah, S Leleiko, N Lidofsky, S Bright, R Grabert, S Law, M Moniz, H Bancroft, B Kalasapudi, B Cole, E Merrick, M Flowers, N Patel, M Harris, A AF Sands, B. Shah, S. Leleiko, N. Lidofsky, S. Bright, R. Grabert, S. Law, M. Moniz, H. Bancroft, B. Kalasapudi, B. Cole, E. Merrick, M. Flowers, N. Patel, M. Harris, A. TI Ocean State Crohn's and Colitis Area Registry (OSCCAR): Incidence of Crohn's disease and ulcerative colitis in a prospective, population-based inception cohort in Rhode Island. SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT Advances in Inflammatory Bowel Diseases Crohns and Colitis Foundations National Clinical and Research Conference CY DEC 09-12, 2010 CL Hollywood, FL C1 [Sands, B.] Mt Sinai Sch Med, New York, NY USA. [Shah, S.; Leleiko, N.; Lidofsky, S.; Bright, R.; Law, M.; Moniz, H.; Bancroft, B.; Kalasapudi, B.; Patel, M.; Harris, A.] Lifespan, Providence, RI USA. [Shah, S.; Leleiko, N.; Lidofsky, S.; Bright, R.; Law, M.; Moniz, H.; Bancroft, B.; Kalasapudi, B.; Patel, M.; Harris, A.] Brown Univ, Providence, RI 02912 USA. [Grabert, S.; Cole, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merrick, M.] Crohns & Colitis Fdn Amer, New York, NY USA. [Flowers, N.] Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2011 VL 17 SU 1 BP S8 EP S8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 693WO UT WOS:000285256300026 ER PT S AU Plourde, E Delgutte, B Brown, EN AF Plourde, Eric Delgutte, Bertrand Brown, Emery N. GP IEEE TI THE RELATIVE IMPORTANCE IN THE AUDITORY NERVE SPIKING OF A NEURON'S INTERNAL DYNAMICS VERSUS AN EXTERNAL INPUT STIMULUS SO 2011 5TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 5th International IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) Conference on Neural Engineering (NER) CY APR 27-MAY 01, 2011 CL Cancun, MEXICO SP Natl Sci Fdn (NSF), Engn Med & Biol Soc (EMBS), IEEE ID TIME-RESCALING THEOREM AB Neuron spiking typically reflects both the intrinsic dynamics of the neuron as well as characteristics of extrinsic stimuli. In this paper, we compare the importance of the neuron's internal dynamics and the spectro-temporal characteristics of an input speech stimulus in a previously developed point process model for auditory nerve spiking. Using a relative deviance measure and Kolmogorov-Smirnov (KS) analysis, we show that, for low spontaneous rate neurons, the spectro-temporal characteristics of the input speech stimulus are much more important than the neuron's internal dynamics and, in fact, sufficient to explain the neuron spiking. However, for higher spontaneous rates, both are shown to be almost equally important to the spiking. The relative importance of one of these two aspects for spiking in the auditory nerve and their relevance in the neuron firing model therefore depends on the spontaneous rate of the neuron. C1 [Plourde, Eric; Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Neurosci Stat Res Lab, Boston, MA 02114 USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Boston, MA 02114 USA. [Delgutte, Bertrand] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02114 USA. RP Plourde, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Neurosci Stat Res Lab, Boston, MA 02114 USA. EM eplourde@mit.edu; Bertrand_Delgutte@meei.harvard.edu; enb@neurostat.mit.edu FU Fonds quebecois de la recherche sur la nature et les technologies; National Institutes of Health [DP1-OD003646] FX This work was supported by the Fonds quebecois de la recherche sur la nature et les technologies and the National Institutes of Health under grant DP1-OD003646 NR 9 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4244-4141-9 J9 I IEEE EMBS C NEUR E PY 2011 BP 9 EP 12 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BYH13 UT WOS:000298735800003 ER PT S AU Pani, D Usai, F Citi, L Raffo, L AF Pani, Danilo Usai, Francesco Citi, Luca Raffo, Luigi GP IEEE TI Real-time processing of tfLIFE neural signals on embedded DSP platforms: a case study SO 2011 5TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 5th International IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) Conference on Neural Engineering (NER) CY APR 27-MAY 01, 2011 CL Cancun, MEXICO SP Natl Sci Fdn (NSF), Engn Med & Biol Soc (EMBS), IEEE ID ACTION-POTENTIALS; RECOGNITION; RECORDINGS AB Spike sorting is a typical neural processing technique aimed at identifying the firing activity of individual neurons. It plays a different role in the processing of the signals coming either from a single electrode or an electrode array. In presence of highly noisy recordings, a preliminary denoising stage is required in order to improve the SNR. Despite the significant number of studies in the field, only a few of them deal with peripheral nervous system (PNS) recordings and often the possibility of a real-time implementation is only hinted without any real implementation study. In this paper, a real-time PNS signal processing and classification technique is presented end evaluated on real electroneurographic signals taken from the sciatic nerve of rats. A state-of-the-art algorithm, composed of a wavelet denoising preprocessing stage followed by a correlation-based spike sorting and a support vector machine, has been adapted to work on-line in order to improve the processing efficiency while preserving at the most its effectiveness. The algorithm provides some level of adaptiveness with respect to an off-line implementation. On average, the correct classification reach 92.24% with isolated errors that can be easily filtered out. Cycle-accurate profiling results on an off-the-shelf Digital Signal Processor demonstrate the real-time performance. C1 [Pani, Danilo; Usai, Francesco; Raffo, Luigi] Univ Cagliari, DIEE Dept Elect & Elect Engn, I-09124 Cagliari, Italy. [Citi, Luca] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Citi, Luca] MIT, Dept Brain & Cognit Sci, Cambridge, MA USA. RP Pani, D (reprint author), Univ Cagliari, DIEE Dept Elect & Elect Engn, I-09124 Cagliari, Italy. EM pani@diee.unica.it; lciti@neurostat.mit.edu RI Raffo, Luigi/E-9713-2012; Citi, Luca/G-2270-2011; Pani, Danilo/C-6832-2009 OI Raffo, Luigi/0000-0001-9683-009X; Citi, Luca/0000-0001-8702-5654; Pani, Danilo/0000-0003-1924-0875 FU Region of Sardinia FX This work is supported by Region of Sardinia, Young Researchers Grant, PO Sardegna FSE 2007-2013, L.R.7/2007 Promotion of the scientific research and technological innovation in Sardinia. The authors wish to thank Prof. Xa vier Na v arro and his team (Universitat Autonoma de Barcelona) for pro viding the data, Dr . Ken Yoshida (Dept. of Biomedical Engineering, University of Purdue, Indianapolis, USA) for the useful suggestions, Francesco Grussu and Daniele Farris for their help in this research work NR 13 TC 6 Z9 6 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4244-4141-9 J9 I IEEE EMBS C NEUR E PY 2011 BP 44 EP 47 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BYH13 UT WOS:000298735800011 ER PT S AU Hebert, P Wolf, MT Campos, M Chakrabarti, S Gail, A Burdick, JW AF Hebert, Paul Wolf, Michael T. Campos, Michael Chakrabarti, Shubhodeep Gail, Alexander Burdick, Joel W. GP IEEE TI An Improved SpikeTrack: An Autonomous Multi-Electrode Control & Recording System SO 2011 5TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 5th International IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) Conference on Neural Engineering (NER) CY APR 27-MAY 01, 2011 CL Cancun, MEXICO SP Natl Sci Fdn (NSF), Engn Med & Biol Soc (EMBS), IEEE AB This paper summarizes an algorithm to autonomously position an extracellular recording electrode so as to first isolate the action potentials of a single neuron in a multi-unit signal, and then re-position the electrode as necessary to optimize and maintain the recording quality of that neuron over an extended recording interval. We first summarize some of the technical advancements of the current algorithm over earlier versions of the "SpikeTrack" recording system in the area of multi-hypothesis cluster tracking method for spike sorting, and a new technique to optimize the signal recording interval. Novel recording experiments in macaque cortex compare the performance of autonomous extracellular recording with that of an experienced neurophysiologist. We found that the algorithm isolates cells better than a human expert. C1 [Hebert, Paul; Burdick, Joel W.] CALTECH, Pasadena, CA 91125 USA. [Wolf, Michael T.] Adv Robot Control Grp, Pasadena, CA 91125 USA. [Campos, Michael] Massachusetts Gen Hosp, Dept NeurSurg, Boston, MA USA. [Chakrabarti, Shubhodeep; Gail, Alexander] Germany Primate Ctr, Sensorimotor Grp, Gottingen, Germany. RP Hebert, P (reprint author), CALTECH, Pasadena, CA 91125 USA. EM paul.hebert@caltech.edu NR 10 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4244-4141-9 J9 I IEEE EMBS C NEUR E PY 2011 BP 360 EP 363 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BYH13 UT WOS:000298735800085 ER PT S AU Berdichevsky, Y Staley, KJ AF Berdichevsky, Yevgeny Staley, Kevin J. GP IEEE TI Multiple-compartment chip for parallel recordings of epileptic activity from organotypic cultures SO 2011 5TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 5th International IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) Conference on Neural Engineering (NER) CY APR 27-MAY 01, 2011 CL Cancun, MEXICO SP Natl Sci Fdn (NSF), Engn Med & Biol Soc (EMBS), IEEE ID EPILEPTOGENESIS; SEIZURES AB Organotypic hippocampal slice culture is an in vitro model of post-traumatic epilepsy. To increase experimental throughput for development of anti-epileptic drugs, we designed a system for parallel recordings of neural activity from several cultures. We recorded spontaneous electrical activity from four organotypic cultures on the same recording chip for more than seven weeks. We confirmed that hippocampal cultures develop spontaneous epileptiform activity. Cultures exhibited a quiet latent period followed by interictal and ictal epileptiform activity. C1 [Berdichevsky, Yevgeny; Staley, Kevin J.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Berdichevsky, Y (reprint author), Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. EM yberdichevsky@partners.org; kstaley@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4244-4141-9 J9 I IEEE EMBS C NEUR E PY 2011 BP 572 EP 575 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BYH13 UT WOS:000298735800137 ER PT S AU Heaton, JT Knox, C Malo, J Hadlock, TA AF Heaton, James T. Knox, Christopher Malo, Juan Hadlock, Tessa A. GP IEEE TI A System for Delivering Mechanical Stimulation to the Rat Whisker Pad during Facial Nerve Regeneration SO 2011 5TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 5th International IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) Conference on Neural Engineering (NER) CY APR 27-MAY 01, 2011 CL Cancun, MEXICO SP Natl Sci Fdn (NSF), Engn Med & Biol Soc (EMBS), IEEE ID MANUAL STIMULATION; VIBRISSAL MUSCLES; RECOVERY; INJURY; REPAIR; MOVEMENTS AB Facial nerve regeneration after transection with immediate neurorrhaphy frequently leads to poor functional recovery in both humans and animal models, and recent advancements in surgical and pharmacologic interventions have had little impact. In contrast, daily passive assistance of whisking movement during the recovery period after facial nerve cut/repair has been shown to dramatically improve facial nerve function in the rodent. Additional studies are needed to understand the mechanisms of this functional enhancement, and to identify optimal stimulation patterns. This report describes a new robotic system for delivering controlled patterns of mechanical whisking assistance after rat facial nerve injury, and provides pilot data of mechanical stimulation treatments that are either preprogrammed (4 or 8 Hz at 65-70 degrees per whisk for 520 minutes per day) or yoked to the rat's whisking behavior from the contralateral (intact) side of the face. C1 [Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, 1 Bowdoin Sq Floor 11, Boston, MA 02114 USA. [Knox, Christopher; Malo, Juan; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Harvard Med Sch, Dept Otolarynol Head & Neck Surgery, Boston, MA 02114 USA. RP Heaton, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, 1 Bowdoin Sq Floor 11, Boston, MA 02114 USA. EM james.heaton@mgh.harvard.edu; tessa_hadlock@meei.harvard.edu FU [R01NS071067] FX This work was supported by R01NS071067 to T. A. Hadlock. We thank James B. Kobler, Ph.D. for his advice and assistance. NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4244-4141-9 J9 I IEEE EMBS C NEUR E PY 2011 BP 629 EP 633 PG 5 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BYH13 UT WOS:000298735800151 ER PT S AU Mallas, G Rosenthal, A Calfon, MA Razansky, RN Mauskapf, A Jaffer, FA Brooks, DH Ntziachristos, V AF Mallas, Georgios Rosenthal, Amir Calfon, Marcella A. Razansky, R. Nika Mauskapf, Adam Jaffer, Farouc A. Brooks, Dana H. Ntziachristos, Vasilis GP IEEE TI Progress on multimodal molecular/anatomical intravascular imaging of coronary vessels combining near infrared fluorescence and ultrasound SO 2011 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 33rd Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 30-SEP 03, 2011 CL Boston, MA SP IEEE, Engn Med & Biol Soc (EMBS) ID OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO; ATHEROSCLEROSIS AB The use of intravascular imaging modalities for the detection and assessment of atherosclerotic plaque is becoming increasingly useful. Current clinical invasive modalities assess the presence of plaque using anatomical information and include Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT). However, such modalities cannot take into account underlying functional biological information, which can however be revealed with the use of molecular imaging. Consequently, intravascular molecular imaging is emerging as a powerful approach. We have developed such a Near-Infrared Fluorescence (NIRF) imaging system and showcased, in both phantom and in-vivo (rabbit) experiments, its potential to successfully detect inflamed atherosclerotic plaques, using appropriate fluorescent probes. Here, we discuss some limitations of the current system and suggest the combined use of the NIRF and IVUS imaging systems as a means for more accurate assessment of atherosclerotic plaque. We include some results and models that showcase the potential power of this kind of hybrid imaging. C1 [Mallas, Georgios; Calfon, Marcella A.; Mauskapf, Adam; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. RP Mallas, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. EM gmallas@partners.org OI Jaffer, Farouc/0000-0001-7980-384X NR 18 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-4122-8 J9 IEEE ENG MED BIO PY 2011 BP 1117 EP 1120 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BYH52 UT WOS:000298810001066 ER PT S AU Meltzner, GS Colby, G Deng, YB Heaton, JT AF Meltzner, Geoffrey S. Colby, Glen Deng, Yunbin Heaton, James T. GP IEEE TI Signal Acquisition and Processing Techniques for sEMG Based Silent Speech Recognition SO 2011 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 33rd Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 30-SEP 03, 2011 CL Boston, MA SP IEEE, Engn Med & Biol Soc (EMBS) AB sEMG based silent speech recognition systems seek to bypass the limitations of acoustic speech recognition by measuring and interpreting muscle activity of the facial and neck musculature involved in speech production. However, this speech recognition modality introduces unique challenges of its own. This paper describes signal acquisition and processing strategies that we have employed to address these challenges during our development of a silent speech recognition system. C1 [Meltzner, Geoffrey S.] BAE Syst Inc, Burlington, MA 01809 USA. [Colby, Glen; Deng, Yunbin] BAE Syst Inc, Burlington, MA 01890 USA. [Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Meltzner, GS (reprint author), BAE Syst Inc, Burlington, MA 01809 USA. EM geoffrey.meltzner@baesystems.com; glen.colby@baesystems.com; yunbin.deng@baesystems.com; james.heaton@mgh.harvard.edu FU United States Defense Advanced Research Projects Agency (DARPA) [W157T-08-C-P021, W15P7T-06-C-P437] FX This study was sponsored by the United States Defense Advanced Research Projects Agency (DARPA) Information Innovation Office (I2O) Program, Advanced Speech Encoding, under contracts W157T-08-C-P021 and W15P7T-06-C-P437. The views and conclusions in this document are those of the authors and should not be interpreted as representing the official policies, either expressly or implied, of DARPA or the U.S. Government. NR 12 TC 3 Z9 3 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-4122-8 J9 IEEE ENG MED BIO PY 2011 BP 4848 EP 4851 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BYH52 UT WOS:000298810003292 ER PT S AU Arney, D Bhatia, K Bhatia, S Sutton, M Rausch, T Karlinsky, J Goldman, JM AF Arney, David Bhatia, Kunal Bhatia, Sanchit Sutton, Michael Rausch, Tracy Karlinsky, Joel Goldman, Julian M. GP IEEE TI Design of an X-Ray/Ventilator Synchronization System in an Integrated Clinical Environment SO 2011 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 33rd Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 30-SEP 03, 2011 CL Boston, MA SP IEEE, Engn Med & Biol Soc (EMBS) AB Patients in an ICU may receive daily chest x-rays. These x-rays are taken manually and may be at different phases of respiration, which limits their clinical usefulness. We examine design issues around automatically synchronizing an x-ray and ventilator in an interoperable manner, including requirements on the individual devices and new safety hazards introduced by connecting them into a system. C1 [Arney, David; Goldman, Julian M.] CIMIT, Med Device Plug & Play Program, Cambridge, MA USA. [Bhatia, Kunal; Bhatia, Sanchit; Sutton, Michael] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Rausch, Tracy] DocBox Inc, Waltham, MA USA. [Karlinsky, Joel] VA Med Center, Waltham, MA USA. [Goldman, Julian M.] Massachusetts Gen Hosp, Med Director Biomed Engn, Cambridge, MA USA. [Goldman, Julian M.] CIMIT, Med Dev Plug & Play program, Cambridge, MA USA. RP Arney, D (reprint author), CIMIT, Med Device Plug & Play Program, Cambridge, MA USA. EM dave@mdpnp.org; kunal@bu.edu; sanchitb@bu.edu; msutton@bu.edu; tracy@docboxinc.com; jmgoldman@partners.org FU CIMIT [XXX]; TATRC [YYY (TBD)] FX This work was supported in part by the CIMIT Grant XXX and TATRC Grant YYY (TBD). NR 8 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-4122-8 J9 IEEE ENG MED BIO PY 2011 BP 8203 EP 8206 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BYH52 UT WOS:000298810006080 ER PT S AU Citi, L Brown, EN Barbieri, R AF Citi, Luca Brown, Emery N. Barbieri, Riccardo BE Murray, A TI A Point Process Local Likelihood Algorithm for Robust and Automated Heart Beat Detection and Correction SO 2011 COMPUTING IN CARDIOLOGY SE Computing in Cardiology Series LA English DT Proceedings Paper CT Conference on Computing in Cardiology CY SEP 18-21, 2011 CL Hangzhou, PEOPLES R CHINA SP European Soc Cardiol, Zhejiang Univ, EMB, IEEE, Drager, Mortara, Philips, Univ Rochester, Telemetr & Holter ECG Warehouse, Physiol Measurement, Mindray, GE Healthcare, Zoll, Edan, GSMA ID RATE-VARIABILITY; INTERBEAT INTERVALS; ARRHYTHMIA AB Robust and automated classification and correction of ECG-derived heart beats are a necessary prerequisite for an accurate real-time estimation of measures of heart rate variability and cardiovascular control. In particular, the low quality of the signal, as well as the presence of recurring arrhythmic events, may significantly affect estimation accuracy. We here present a novel point process based method for a real time R-R interval error detection and correction. Results of detection analysis over data from the benchmark MIT-BIH arrhythmia database demonstrate that the proposed algorithm achieves 99.97% accuracy (98.23% sensitivity, 99.98% specificity and 95.69% positive predictive value), outperforming state-of-the-art algorithms. Further results on simulated data demonstrate the efficacy of the detection and correction method. C1 [Citi, Luca; Brown, Emery N.; Barbieri, Riccardo] Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia, Boston, MA USA. [Citi, Luca; Brown, Emery N.; Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Citi, L (reprint author), Dept Anesthesia Crit Care & Pain Med, 149 13th St, Charlestown, MA 02129 USA. EM lciti@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833 FU National Institutes of Health (NIH) [R01-HL084502, DP1-OD003646] FX This work was supported by National Institutes of Health (NIH) through grants R01-HL084502 (R.B.) and DP1-OD003646 (E.N.B.). NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 978-1-4577-0611-0 J9 COMPUT CARDIOL PY 2011 VL 38 BP 293 EP 296 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications SC Cardiovascular System & Cardiology; Computer Science GA BAP78 UT WOS:000305132500075 ER PT S AU Hamblin, MR AF Hamblin, Michael R. GP IEEE TI Therapeutic applications of light: PDT - the killer; LLLT - the healer SO 2011 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 01-06, 2011 CL Baltimore, MD ID TARGETED PHOTODYNAMIC THERAPY; ANTITUMOR IMMUNITY; WOUND INFECTIONS; IN-VIVO; MICE; MODEL AB Visible and near-infrared light can treat all human diseases. Light plus non-toxic dyes called photodynamic therapy (PDT) can kill cancer cells, pathogens and destroy unwanted tissue. In contrast light alone can reduce inflammation, stimulate healing and tissue repair. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 414, Boston, MA 02114 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 414, 40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvaerd.edu NR 21 TC 0 Z9 0 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-910-7 J9 CONF LASER ELECTR PY 2011 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BXB77 UT WOS:000295612400019 ER PT S AU Lin, CP AF Lin, Charles P. GP IEEE TI Optical Techniques For Tracking Cells In Vivo SO 2011 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 01-06, 2011 CL Baltimore, MD AB I will focus on tracking cancer cells, immune cells, and stem cells in vivo using (i) intravital microscopy for 3D tissue imaging, and (ii) in vivo flow cytometry for detection and quantification of circulating cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Lin, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, 40 Blossom St, Boston, MA 02114 USA. EM lin@helix.mgh.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-910-7 J9 CONF LASER ELECTR PY 2011 PG 1 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BXB77 UT WOS:000295612401081 ER PT S AU Wierwille, J Andrews, P Onozato, M Jiang, J Cable, A Chen, Y AF Wierwille, Jeremiah Andrews, Peter Onozato, Maristela Jiang, James Cable, Alex Chen, Yu GP IEEE TI In Vivo Imaging of Kidney Microcirculation Using Doppler Optical Coherence Tomography SO 2011 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 01-06, 2011 CL Baltimore, MD ID TRANSPLANTATION AB We demonstrated 3D Doppler optical coherence tomography (DOCT) imaging of rat kidney microcirculation within the glomerulus in vivo. Dynamic changes in blood flow were detected under altered physiological conditions demonstrating real-time DOCT imaging. (C) 2011 Optical Society of America C1 [Wierwille, Jeremiah; Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Andrews, Peter] Georgetown Univ, Dept Biochem, Washington, DC 20057 USA. [Onozato, Maristela] Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA. [Jiang, James; Cable, Alex] Thorlabs Inc, Newton, NJ 07860 USA. RP Wierwille, J (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. EM yuchen@umd.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-910-7 J9 CONF LASER ELECTR PY 2011 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BXB77 UT WOS:000295612400035 ER PT S AU Lui, C Carr, CE Rowedder, H Ruvkun, G Zuber, M AF Lui, Clarissa Carr, Christopher E. Rowedder, Holli Ruvkun, Gary Zuber, Maria GP IEEE TI SETG: An Instrument for Detection of Life on Mars Ancestrally Related to Life on Earth SO 2011 IEEE AEROSPACE CONFERENCE SE IEEE Aerospace Conference Proceedings LA English DT Proceedings Paper CT IEEE Aerospace Conference CY MAR 05-12, 2011 CL Big Sky, MT SP IEEE ID BACTERIAL DIVERSITY; NATURAL TRANSFER; VIABLE MICROBES; PCR; SOIL; DNA; PLANETS; IDENTIFICATION; SEDIMENTS; CHLORIDE AB Life on Mars, if it exists, may be related to life on Earth. (12) This common ancestry hypothesis is supported by theoretical and experimental studies of meteoritic exchange between Earth and Mars, exchange that could have spread life between those planets. If so, we can target the basic building blocks of life, DNA or RNA, in our search. We are developing the Search for Extra-Terrestrial Genomes (SETG) instrument with the goal of isolating, extracting, and sequencing nucleic acids in-situ on Mars. Here we outline the major challenges and approaches to achieve this goal, with an emphasis on the sample preparation required to isolate nucleic acids from Mars-like samples. Looking for nucleic acids is not the most general approach to search for life on Mars. However, given the possibility of common ancestry, it is a critical part of any comprehensive life detection strategy, arguably unmatched in its ability to provide a highly sensitive and specific detection and characterization of any life on Mars related to life on Earth. C1 [Lui, Clarissa; Carr, Christopher E.; Zuber, Maria] MIT, Dept Earth Atmospher & Planetary Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Rowedder, Holli; Ruvkun, Gary] Massachusetts General Hosp, Molecular Biol Dept, Boston, MA 02114 USA. RP Lui, C (reprint author), MIT, Dept Earth Atmospher & Planetary Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM clui@mit.edu NR 91 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1095-323X BN 978-1-4244-7351-9 J9 AEROSP CONF PROC PY 2011 PG 12 WC Engineering, Aerospace SC Engineering GA BXL11 UT WOS:000296277200078 ER PT S AU Weller, DS Polimeni, JR Grady, L Wald, LL Adalsteinsson, E Goyal, VK AF Weller, Daniel S. Polimeni, Jonathan R. Grady, Leo Wald, Lawrence L. Adalsteinsson, Elfar Goyal, Vivek K. GP IEEE TI COMBINED COMPRESSED SENSING AND PARALLEL MRI COMPARED FOR UNIFORM AND RANDOM CARTESIAN UNDERSAMPLING OF K-SPACE SO 2011 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech, and Signal Processing (ICASSP) CY MAY 22-27, 2011 CL Prague Congress Ctr, Prague, CZECH REPUBLIC SP Inst Elect & Elect Engineers Signal Processing Soc, IEEE HO Prague Congress Ctr DE Compressed sensing; magnetic resonance imaging; image reconstruction; parallel imaging; sampling patterns ID ROBUST UNCERTAINTY PRINCIPLES AB Both compressed sensing (CS) and parallel imaging effectively reconstruct magnetic resonance images from undersampled data. Combining both methods enables imaging with greater undersampling than accomplished previously. This paper investigates the choice of a suitable sampling pattern to accommodate both CS and parallel imaging. A combined method named SpRING is described and extended to handle random undersampling, and both GRAPPA and SpRING are evaluated for uniform and random undersampling using both simulated and real data. For the simulated data, when the undersampling factor is large, SpRING performs better with random undersampling. However, random undersampling is not as beneficial to SpRING for real data with approximate sparsity. C1 [Weller, Daniel S.; Adalsteinsson, Elfar; Goyal, Vivek K.] MIT, Dept EECS, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Polimeni, Jonathan R.; Wald, Lawrence L.] Massachusetts Gen Hosp, AA Martinos Ctr, Dept Radiol, Charlestown, MA USA. [Polimeni, Jonathan R.; Wald, Lawrence L.] Harvard Med Sch, Dept Radiol, Boston, MA USA. [Grady, Leo] Siemens Corp Res, Dept Image Analyt & Informat, Princeton, NJ USA. RP Weller, DS (reprint author), MIT, Dept EECS, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dweller@mit.edu; jonp@nmr.mgh.harvard.edu; leo.grady@siemens.com; wald@nmr.mgh.harvard.edu; elfar@mit.edu; vgoyal@mit.edu RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU NSF CAREER [CCF-0643836, NIHR01 EB007942, EB006847]; NIH NCRR [P41 RR014075]; NSF Graduate Research Fellowship FX Funding acknowledgements: NSF CAREER Grant CCF-0643836, NIHR01 EB007942 and EB006847, NIH NCRR P41 RR014075, and a NSF Graduate Research Fellowship. The authors also thank Prof. Fa Hsuan Linof the A. A. Martinos Center for the use of hisB1simulator. NR 11 TC 4 Z9 4 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4577-0539-7 J9 INT CONF ACOUST SPEE PY 2011 BP 553 EP 556 PG 4 WC Acoustics; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology SC Acoustics; Engineering; Imaging Science & Photographic Technology GA BXG36 UT WOS:000296062400139 ER PT S AU Cascio, EW Bentefour, EH AF Cascio, Ethan W. Bentefour, E. H. GP IEEE TI The Use of Diodes as Dose and Fluence Probes in the Experimental Beamline at the Francis H. Burr Proton Therapy Center SO 2011 IEEE RADIATION EFFECTS DATA WORKSHOP (REDW) SE IEEE Radiation Effects Data Workshop LA English DT Proceedings Paper CT IEEE Radiation Effects Data Workshop (REDW)/48th IEEE International Nuclear and Space Radiation Effects Conference (NSREC) CY JUL 25-29, 2011 CL Las Vegas, NV SP Inst Elect & Elect Engineers (IEEE), IEEE Nucl & Plasma Sci Soc, Radiat Effects Comm AB We describe the use of rectifier diodes to measure dose, fluence and mean proton energy inside a device under test. The fluence and energy measurements are performed by analyzing pulses induced by individual protons. C1 [Cascio, Ethan W.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. [Bentefour, E. H.] Ion Beam Applicat SA, Louvain, Belgium. RP Cascio, EW (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM ecascio@partners.org; Hassan.Bentefour@iba-group.com NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2154-0519 BN 978-1-4577-1283-8 J9 IEEE RADIAT EFFECTS PY 2011 BP 13 EP 18 PG 6 WC Physics, Fluids & Plasmas; Physics, Nuclear SC Physics GA BYJ79 UT WOS:000299051900003 ER PT J AU Isaac, C Chertoff, J Lee, B Carnes, M AF Isaac, Carol Chertoff, Jocelyn Lee, Barbara Carnes, Molly TI Do Students' and Authors' Genders Affect Evaluations? A Linguistic Analysis of Medical Student Performance Evaluations SO ACADEMIC MEDICINE LA English DT Article ID PROGRAM DIRECTORS; ACADEMIC MEDICINE; SELECTION PROCESS; DEANS LETTER; RECOMMENDATION; WOMEN; RESIDENTS; ADVANCEMENT; LEADERSHIP; LANGUAGE AB Purpose Recent guidelines for the Medical Student Performance Evaluation (MSPE) have standardized the "dean's letter." The authors examined MSPEs for linguistic differences according to student or author gender. Method This 2009 study analyzed 297 MSPEs for 227 male and 70 female medical students applying to a diagnostic radiology residency program. Text analysis software identified word counts, categories, frequencies, and contexts; factor analysis detected patterns of word categories in student-author gender pairings. Results Analyses showed a main effect for student gender (P=.046) and a group difference for the author-student gender combinations (P=.048). Female authors of male student MSPEs used the fewest "positive emotion" words (P=.006). MSPEs by male authors were shorter than those by females (P=.014). MSPEs for students ranked in the National Resident Matching Program contained more "standout" (P=.002) and "positive emotion" (P=.001) words. There were no differences in the author-gender pairs in the proportion of students ranked, although predominant word categories differed by author and student gender. Factor analysis revealed differences among the author-student groups in patterns of correlations among word categories. Conclusions MSPEs differed slightly but significantly by student and author gender. These differences may derive from societal norms for male and female behaviors and the subsequent linguistic interpretation of these behaviors, which itself may be colored by the observer's gender. Although the differences in MSPEs did not seem to influence students' rankings, this work underscores the need for awareness of the complex effects of gender in evaluating students and guiding their specialty choices. C1 [Isaac, Carol; Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. [Carnes, Molly] Meriter Hosp, Madison, WI USA. [Carnes, Molly] Univ Wisconsin, Dept Med & Psychiat, Sch Med & Publ Hlth, Madison, WI 53715 USA. [Carnes, Molly] Univ Wisconsin, Dept Ind & Syst Engn, Coll Engn, Madison, WI 53715 USA. [Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Women Vet Hlth Program, Madison, WI USA. [Chertoff, Jocelyn] Dartmouth Hitchcock Med Ctr, Dept Diagnost Radiol, Lebanon, NH 03766 USA. [Chertoff, Jocelyn] Dartmouth Hitchcock Med Ctr, Sect Gastrointestinal Radiol, Lebanon, NH 03766 USA. [Chertoff, Jocelyn] Dartmouth Med Sch, Lebanon, NH USA. [Lee, Barbara] Univ S Florida, Louis de la Parte Florida Mental Hlth Inst, Tampa, FL USA. [Lee, Barbara] Hillsborough Cty Publ Sch, Tampa, FL USA. RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM mlcarnes@wisc.edu FU National Institute on Aging [T32 AG00265]; NSF [SBE-0619979]; NIH [RO1 GM088477-01] FX Dr. Isaac was funded by the National Institute on Aging, grant no. T32 AG00265. Dr. Carnes' research on gender and the advancement of women in academic science and engineering is funded by NSF SBE-0619979 and NIH RO1 GM088477-01. Dr. Carnes is employed part-time by the William S. Middleton Veterans Hospital. This is GRECC manuscript number 2010-10. NR 46 TC 16 Z9 16 U1 4 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2011 VL 86 IS 1 BP 59 EP 66 DI 10.1097/ACM.0b013e318200561d PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 700GL UT WOS:000285725900021 PM 21099389 ER PT J AU Iwashyna, TJ Fuld, A Asch, DA Bellini, LM AF Iwashyna, Theodore J. Fuld, Alexander Asch, David A. Bellini, Lisa M. TI The Impact of Residents, Interns, and Attendings on Inpatient Laboratory Ordering Patterns: A Report From One University's Hospitalist Service SO ACADEMIC MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; DIAGNOSTIC-TESTS; PHYSICIAN AWARENESS; QUALITY IMPROVEMENT; BRITISH-COLUMBIA; MEDICAL-CARE; FEEDBACK; COST; INTERVENTION; EDUCATION AB Purpose To examine the laboratory test ordering patterns of interns to determine the effects of more senior residents' and attendings' supervision on trainees' patterns and residents' perceptions of control in test ordering. Method In a 2007 cohort study of 2,066 patients cared for by 85 interns, 56 residents, and 27 attendings on the University of Pennsylvania general medical hospitalist service, the authors studied variation in laboratory test utilization and costs in 10,908 patient-days. Ordinary least squares regression was used to partition variance among supervised and supervising physicians. Interns and residents were surveyed about their perceived control over lab test ordering. Results Forty-five percent (95% confidence interval [CI]: 39-53) of the variation in laboratory test utilization was attributable to interns' ordering, 26% (95% CI: 21-34) to residents, and 9% (95% CI: 7-16) to attendings; 20% (95% CI: 6-25) could not be uniquely attributed to a particular level of the care team. Similar results were obtained for variation in laboratory costs. Interns underestimated their control over laboratory test utilization, residents overestimated their control, and both groups had inaccurate assessments of their utilization relative to peers. Conclusions Attending faculty had relatively little impact on laboratory ordering patterns. This may reflect a consistent baseline impact of attending physicians on laboratory use, but it may also represent a missed opportunity to reduce practice variation and improve patient care. Observing variation in trainee practice patterns in the face of different supervisors represents a new approach to measuring the supervision in clinical settings. C1 [Iwashyna, Theodore J.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Iwashyna, Theodore J.] Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Fuld, Alexander] Dartmouth Hitchcock Med Ctr, Div Hematol Oncol, Lebanon, NH 03766 USA. [Bellini, Lisa M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Asch, DA (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, 3641 Locust Walk, Philadelphia, PA 19104 USA. EM asch@wharton.upenn.edu RI Kim, Hyung Woo /G-7525-2011; OI Asch, David/0000-0002-7970-286X; Iwashyna, Theodore/0000-0002-4226-9310 FU Leonard Davis Institute of Health Economics of the University of Pennsylvania FX This work was supported by a Pilot Grant from the Leonard Davis Institute of Health Economics of the University of Pennsylvania. NR 46 TC 15 Z9 15 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2011 VL 86 IS 1 BP 139 EP 145 DI 10.1097/ACM.0b013e3181fd85c3 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 700GL UT WOS:000285725900035 PM 20938318 ER PT J AU Back, SE Book, SW Santos, AB Brady, KT AF Back, Sudie E. Book, Sarah W. Santos, Alberto B. Brady, Kathleen T. TI Training Physician-Scientists: A Model for Integrating Research Into Psychiatric Residency SO ACADEMIC PSYCHIATRY LA English DT Article ID INSTITUTE; PROGRAM AB Objective: The number of physicians engaged in research careers has declined significantly over the past two decades. Physicians with in-depth experience and formal training in research design, development, implementation, statistical analysis, and interpretation of scientific information are rare. Methods: In response to this shortage, the Medical University of South Carolina (MUSC) launched an NIH-funded research track in 2006 to address the institutional, financial, and regulatory barriers to research training during residency. The primary aim was to incorporate a research track within a 4-year psychiatric residency program for physicians. A secondary goal was to extend recruitment into earlier phases of medical training by offering summer research fellowships to medical and undergraduate students. Results: This article describes the program including core mechanisms of training, recruitment, and outcomes to date. Conclusions: The program provides a model to effectively integrate research training during residency without increasing the number of years of residency training. The training components described herein should be exportable to other psychiatric residency training programs and potentially other specialties of medicine. C1 [Back, Sudie E.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC 29425 USA. [Brady, Kathleen T.] Ralph H Johnson VAMC, Charleston, SC USA. RP Back, SE (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 67 President St,POB 250861, Charleston, SC 29425 USA. EM backs@musc.edu FU NIDA NIH HHS [K23 DA021228, K23 DA021228-03, R25 DA020357, R25 DA020537, R25 DA020537-04] NR 18 TC 19 Z9 19 U1 4 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JAN-FEB PY 2011 VL 35 IS 1 BP 40 EP 45 DI 10.1176/appi.ap.35.1.40 PG 6 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 702TK UT WOS:000285918600009 PM 21209406 ER PT J AU Nishino, M Guo, MY Jackman, DM DiPiro, PJ Yap, JT Ho, TK Hatabu, H Janne, PA Van den Abbeele, AD Johnson, BE AF Nishino, Mizuki Guo, Mengye Jackman, David M. DiPiro, Pamela J. Yap, Jeffrey T. Ho, Tak K. Hatabu, Hiroto Jaenne, Pasi A. Van den Abbeele, Annick D. Johnson, Bruce E. TI CT Tumor Volume Measurement in Advanced Non-small-cell Lung Cancer: Performance Characteristics of an Emerging Clinical Tool SO ACADEMIC RADIOLOGY LA English DT Article DE Lung cancer; computed tomography; tumor volume measurement; interobserver variability; intraobserver variability ID SMALL PULMONARY NODULES; VARIABILITY; MUTATIONS; GEFITINIB; REPRODUCIBILITY; THICKNESS; ERLOTINIB; EVALUATE AB Rationale and Objectives: Determine inter- and intraobserver variability of computed tomography (CT) tumor volume measurements in advanced non-small-cell lung cancer (NSCLC) patients treated in a Phase II clinical trial using chest CT. Materials and Methods: Twenty-three advanced NSCLC patients with a total of 53 measurable lung lesions enrolled in a Phase II, multicenter, open-label clinical trial of erlotinib were retrospectively studied with institutional review board approval. Two radiologists independently measured the tumor size, volume, and CT attenuation coefficient using commercially available volume analysis software. Concordance correlation coefficients (CCCs) and Bland-Altman plots were used to assess inter- and intraobserver agreement. Results: High CCCs (0.949-0.990) were observed in all types of measurements for interobserver agreement. The 95% limits of agreements for volume, unidimensional, and bidimensional measurements were (-26.0%, 18.6%), (-23.1%, 24.4%), and (-34.0%, 48.6%), respectively. Volume measurement had slightly higher CCC and narrower 95% limits of agreement compared to uni- and bidimensional measurements. CCCs for intraobserver agreement were high (range, 0.946-0.996) with CCC for volume being slightly higher than CCCs of uni- and bidimensional measurements. The smaller the tumor volume was, the larger the interobserver difference of CT attenuation. Location, morphology, or adjacent atelectasis had no significant impact on inter- or intraobserver variability. Conclusion: CT tumor volume measurement in advanced NSCLC patients using clinical chest CT and commercially available software demonstrated high inter- and intraobserver agreement, indicating that the method may be used routinely in clinical practice. C1 [Nishino, Mizuki; Guo, Mengye; DiPiro, Pamela J.; Yap, Jeffrey T.; Ho, Tak K.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Jackman, David M.; Jaenne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nishino, Mizuki; DiPiro, Pamela J.; Yap, Jeffrey T.; Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA. EM Mizuki_Nishino@dfci.harvard.edu FU Agfa HealthCare/RSNA; National Institutes of Health [1RO1CA114465-01, 5R21 CA11627-02]; National Cancer Institute [2P50CA090578-06]; Genentech Inc; Doris and William Krupp Research Fund in Thoracic Oncology FX From the Departments of Imaging (M.N., M.G., P.J.D., J.T.Y., T.K.H., A.D.V.d.A.) and Medical Oncology (D.M.J., P.A.J., B.E.J.), Dana-Farber Cancer Institute and Brigham and Women's Hospital, 44 Binney St, Boston, MA 02115; Department of Radiology Brigham and Women's Hospital, Boston, MA (M.N., P.J.D., J.T.Y., H.H.). Received April 14, 2010; accepted August 31, 2010. The investigators were supported by 2009-11 Agfa HealthCare/RSNA Research Scholar Grant (M.N.), Grants 1RO1CA114465-01 (B.E.J., P.A.J.) and 5R21 CA11627-02 (H.H.) from the National Institutes of Health, Grant No. 2P50CA090578-06 (B.E.J, P.A.J.) from the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer, and a grant from Genentech Inc, as well as by the Doris and William Krupp Research Fund in Thoracic Oncology. Address correspondence to: M.N. e-mail: Mizuki_Nishino@dfci.harvard.edu NR 19 TC 31 Z9 31 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2011 VL 18 IS 1 BP 54 EP 62 DI 10.1016/j.acra.2010.08.021 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703YT UT WOS:000286018600008 PM 21036632 ER PT B AU Villasenor, J Berson, DS Kroshinsky, D AF Villasenor, Jennifer Berson, Diane S. Kroshinsky, Daniela BE Shalita, AR DelRosso, JQ Webster, GF TI Combination therapy SO ACNE VULGARIS LA English DT Article; Book Chapter ID ADAPALENE GEL 0.1-PERCENT; ACNE-VULGARIS; BENZOYL PEROXIDE; DOUBLE-BLIND; TOPICAL TREATMENT; CYANOACRYLATE STRIPS; PARALLEL-GROUP; ORAL-THERAPY; MULTICENTER; TRETINOIN C1 [Villasenor, Jennifer] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Berson, Diane S.] Weill Cornell Med Coll, Dept Dermatol, New York, NY USA. [Kroshinsky, Daniela] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Villasenor, J (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 36 TC 1 Z9 1 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND BN 978-1-61631-009-7; 978-1-84184-707-8 PY 2011 BP 105 EP 112 DI 10.3109/9781616310097.003.3 D2 10.3109/9781616310097 PG 8 WC Dermatology SC Dermatology GA BC2XC UT WOS:000351406600012 ER PT B AU Villasenor, J Berson, DS Kroshinsky, D AF Villasenor, Jennifer Berson, Diane S. Kroshinsky, Daniela BE Shalita, AR DelRosso, JQ Webster, GF TI Treatment guidelines in adult women SO ACNE VULGARIS LA English DT Article; Book Chapter ID PLACEBO-CONTROLLED TRIAL; ACNE-VULGARIS; ORAL-CONTRACEPTIVES; ETHINYL ESTRADIOL; SEBACEOUS GLANDS; CYPROTERONE-ACETATE; ANDROGEN METABOLISM; HORMONAL-THERAPY; IMPROVE OUTCOMES; GLOBAL ALLIANCE C1 [Villasenor, Jennifer] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Berson, Diane S.] Weill Cornell Med Coll, Dept Dermatol, New York, NY USA. [Kroshinsky, Daniela] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Villasenor, J (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. NR 54 TC 3 Z9 3 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND BN 978-1-61631-009-7; 978-1-84184-707-8 PY 2011 BP 198 EP 207 DI 10.3109/9781616310097.008.2 D2 10.3109/9781616310097 PG 10 WC Dermatology SC Dermatology GA BC2XC UT WOS:000351406600022 ER PT J AU Castoreno, AB Eggert, US AF Castoreno, Adam B. Eggert, Ulrike S. TI Small Molecule Probes of Cellular Pathways and Networks SO ACS CHEMICAL BIOLOGY LA English DT Article DE Cytokinesis; High content screening; Network; Pathway; Profiling; Rho pathway; Small molecule probes ID CAENORHABDITIS-ELEGANS; CHEMICAL GENETICS; BCR-ABL; INHIBITORS; YEAST; SCREEN; DISCOVERY; CYTOKINESIS; TARGETS; DRUGS AB Small molecules are important not only as therapeutics to treat disease but also as chemical tools to probe complex biological processes. The discovery of novel bioactive small molecules has largely been catalyzed by screening diverse chemical libraries for alterations in specific activities in pure proteins assays or in generating cell-based phenotypes. New approaches are needed to close the vast gap between the ability to study either single proteins or whole cellular processes. This Review focuses on the growing number of studies aimed at understanding In more detail how small molecules perturb particular signaling pathways and larger networks to yield distinct cellular phenotypes. This type of pathway-level analysis and phenotypic profiling provides valuable insight into mechanistic action of small molecules and can reveal off-target effects and improve our understanding of how proteins within a pathway regulate signaling. C1 [Eggert, Ulrike S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Eggert, US (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM ulrike_eggert@dfci.harvard.edu FU National Institutes of Health [R01 GM082834]; Claudia Adams Barr Program; Dana-Farber Cancer Institute FX A.B.C. and U.S.E. were supported by National Institutes of Health grant R01 GM082834, the Claudia Adams Barr Program, and the Dana-Farber Cancer Institute. NR 39 TC 21 Z9 24 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2011 VL 6 IS 1 BP 86 EP 94 DI 10.1021/cb1002976 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 707SJ UT WOS:000286306000009 PM 21087032 ER PT J AU Campbell, J Singh, AK Maria, JPS Kim, Y Brown, S Swoboda, JG Mylonakis, E Wilkinson, BJ Walker, S AF Campbell, Jennifer Singh, Atul K. Maria, John P. Santa, Jr. Kim, Younghoon Brown, Stephanie Swoboda, Jonathan G. Mylonakis, Eleftherios Wilkinson, Brian J. Walker, Suzanne TI Synthetic Lethal Compound Combinations Reveal a Fundamental Connection between Wall Teichoic Acid and Peptidoglycan Biosyntheses in Staphylococcus aureus SO ACS CHEMICAL BIOLOGY LA English DT Article ID BETA-LACTAM RESISTANCE; CELL-WALL; METHICILLIN-RESISTANT; PENICILLIN; BINDING; PATHWAY; ANTIBIOTICS; INFECTIONS; INHIBITORS; POLYMERS AB Methicillin resistance in Staphylococcus aureus depends on the production of mecA, which encodes penicillin-binding protein 2A (PBP2A), an acquired peptidoglycan transpeptidase (TP) with reduced susceptibility to beta-lactam antibiotics. PBP2A cross-links nascent peptidoglycan when the native TPs are inhibited by beta-lactams. Although mecA expression is essential for beta-lactam resistance, it is not sufficient. Here we show that blocking the expression of wall teichoic acids (WTAs) by inhibiting the first enzyme in the pathway, TarO, sensitizes methicillin-resistant S. aureus (MRSA) strains to beta-lactams even though the beta-lactam-resistant transpeptidase, PBP2A, is still expressed. The dramatic synergy between TarO inhibitors and beta-lactams is noteworthy not simply because strategies to overcome MRSA are desperately needed but because neither TarO nor the activities of the native TPs are essential in MRSA strains. The "synthetic lethality" of inhibiting TarO and the native TPs suggests a functional connection between ongoing WTA expression and peptidoglycan assembly in S. aureus. Indeed, transmission electron microscopy shows that S. aureus cells blocked in WTA synthesis have extensive defects in septation and cell separation, indicating dysregulated cell wall assembly and degradation. Our studies imply that WTAs play a fundamental role in S. aureus cell division and raise the possibility that synthetic lethal compound combinations may have therapeutic utility for overcoming antibiotic-resistant bacterial infections. C1 [Campbell, Jennifer; Singh, Atul K.; Maria, John P. Santa, Jr.; Brown, Stephanie; Swoboda, Jonathan G.; Walker, Suzanne] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Singh, Atul K.; Wilkinson, Brian J.] Illinois State Univ, Sch Biol Sci, Normal, IL 61790 USA. [Kim, Younghoon; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Kim, Younghoon; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Walker, S (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. EM suzanne_walker@hms.harvard.edu FU National Institutes of Health [F32AI084316, 1R15AI084006, 5R01GM078477, 1P01AI083214] FX This work was supported by the National Institutes of Health (F32AI084316 to J.C., 1R15AI084006 to B.J.W., 5R01GM078477 to S.W., and 1P01AI083214 to S.W. and E.M.). Methicillin was generously provided by Merck. NR 46 TC 85 Z9 85 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2011 VL 6 IS 1 BP 106 EP 116 DI 10.1021/cb100269f PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 707SJ UT WOS:000286306000012 PM 20961110 ER PT J AU Fass, DM Shah, R Ghosh, B Hennig, K Norton, S Zhao, WN Reis, SA Klein, PS Mazitschek, R Maglathlin, RL Lewis, TA Haggarty, SJ AF Fass, Daniel M. Shah, Rishita Ghosh, Balaram Hennig, Krista Norton, Stephanie Zhao, Wen-Ning Reis, Surya A. Klein, Peter S. Mazitschek, Ralph Maglathlin, Rebecca L. Lewis, Timothy A. Haggarty, Stephen J. TI Short-Chain HDAC Inhibitors Differentially Affect Vertebrate Development and Neuronal Chromatin SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE HDAC inhibitors; hydroxamic acid; valproate; butyrate; phenylbuty-rate; histone acetylation ID HYDROXAMIC ACID-DERIVATIVES; HISTONE DEACETYLASE; VALPROIC ACID; MOUSE MODEL; ALZHEIMERS-DISEASE; MEMORY; ACETYLATION; THERAPY; TARGET; CELLS AB Carboxylic acids with known central nervous system and histone deacetylase (HDAC) inhibitory activities were converted to hydroxamic acids and tested using a suite of in vitro biochemical assays with recombinant HDAC isoforms, cell based assays in human cervical carcinoma HeLa cells and primary cultures from mouse forebrain, and a whole animal (Xenopus laevis) developmental assay. Relative to the parent carboxylic acids two of these analogues exhibited enhanced potency, and one analogue showed altered HDAC isoform selectivity and in vivo activity in the Xenopus assay. We discuss potential uses of these novel hydroxamic acids in studies aimed at determining the utility of HDAC inhibitors as memory enhancers and mood stabilizers. C1 [Fass, Daniel M.; Ghosh, Balaram; Hennig, Krista; Norton, Stephanie; Zhao, Wen-Ning; Reis, Surya A.; Haggarty, Stephen J.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Shah, Rishita; Klein, Peter S.] Univ Penn, Sch Med, Div Hematol Oncol, Dept Med, Philadelphia, PA 19104 USA. [Maglathlin, Rebecca L.; Lewis, Timothy A.] Broad Inst Harvard & MIT, Chem Biol Program, Cambridge, MA 02142 USA. [Fass, Daniel M.; Ghosh, Balaram; Hennig, Krista; Norton, Stephanie; Zhao, Wen-Ning; Mazitschek, Ralph; Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Dept Neurol, Boston, MA 02114 USA. RP Haggarty, SJ (reprint author), Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM haggarty@chgr.mgh.harvard.edu RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X FU National Cancer Institute's Initiative for Chemical Genetics, NIH [N01-CO-12400]; NIH [1RO1MH58324]; NIDA/NIH [5R01DA028301-02]; Stanley Medical Research Institute FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute's Initiative for Chemical Genetics, NIH, under Contract No. N01-CO-12400. P.S.K. is supported by a grant from the NIH (1RO1MH58324). S.J.H is supported by a grant from the NIDA/NIH (5R01DA028301-02) and the Stanley Medical Research Institute. NR 25 TC 23 Z9 23 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD JAN PY 2011 VL 2 IS 1 BP 39 EP 42 DI 10.1021/ml1001954 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 707SL UT WOS:000286306200008 PM 21874153 ER PT J AU Wilbur, DC AF Wilbur, David C. TI Digital Cytology: Current State of the Art and Prospects for the Future SO ACTA CYTOLOGICA LA English DT Review DE Cytology; Telecytology; Telepathology; Digital imaging; Whole slide; Images ID NEEDLE-ASPIRATION SPECIMENS; CERVICAL-VAGINAL SMEARS; VIRTUAL MICROSCOPY; IMMEDIATE EVALUATION; DIAGNOSTIC-ACCURACY; SURGICAL PATHOLOGY; QUALITY-ASSURANCE; TELEPATHOLOGY; TELECYTOLOGY; SLIDE AB The growth of digital methods in pathology is accelerating. Digital images can be used for a variety of applications in cytology, including rapid interpretations, primary diagnosis and second opinions, continuing education and proficiency testing. All of these functions can be performed using small static digital images, real-time dynamic digital microscopy, or whole-slide images. This review will discuss the general principles of digital pathology, its methods and applications to cytologic specimens. As cytologic specimens have unique features compared to histopathology specimens, the key differences will be discussed. Technical and administrative issues in digital pathology applications and the outlook for the future of the field will be presented. Copyright (C) 2011 S. Karger AG, Basel C1 Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilbur, DC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, 55 Fruit St,Warren 120, Boston, MA 02114 USA. EM dwilbur@partners.org NR 64 TC 21 Z9 21 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PY 2011 VL 55 IS 3 BP 227 EP 238 DI 10.1159/000324734 PG 12 WC Pathology SC Pathology GA 759AK UT WOS:000290211400002 PM 21525733 ER PT J AU Ono, JC Wilbur, DC Lee, H Yang, J Krane, JF Bongiovanni, M Faquin, WC AF Ono, J. C. Wilbur, D. C. Lee, H. Yang, J. Krane, J. F. Bongiovanni, M. Faquin, W. C. TI Cytologic Features of Focal Papillary Thyroid Carcinoma Arising within Follicular Adenoma: A Masked Cytomorphologic Analysis of 17 Cases SO ACTA CYTOLOGICA LA English DT Article DE Fine-needle aspiration; Atypia of undetermined significance/follicular lesion of undetermined significance; Thyroid; Papillary thyroid carcinoma; Adenoma ID FINE-NEEDLE-ASPIRATION; SCIENCE CONFERENCE; DIAGNOSIS; BIOPSY; CANCER; NODULES; VARIANT; APPRAISAL; CRITERIA; LESIONS AB Background/Objective: Focal papillary thyroid carcinoma (PTC) arising within a follicular adenoma (PTCFA) represents a clinically significant, but rare, histopathologic subset of papillary carcinomas whose cytologic features have not been well described. This uncommon presentation of PTC may contribute to a subset of thyroid aspirates interpreted as 'atypia of undetermined significance/follicular lesion of undetermined significance' (AUS/FLUS). Study Design: Seventeen fine-needle aspiration biopsy (FNAB) cases diagnosed as 'PTCFA' on corresponding surgical excision were identified from the archival records of 2 large academic medical centers. A control group of 40 FNAB comprised of 20 follicular adenomas (FA) and 20 PTC was identified (based on the corresponding surgical pathology diagnosis) for comparison. All 57 FNAB were reviewed in a masked fashion and scored for a series of 31 cytomorphologic features. The intraclass correlation between diagnostic categories and overall agreement between cytopathologists was statistically evaluated. Results: Aspirates of PTCFA were originally diagnosed as 'negative' (n = 3), 'AUS/FLUS' (n = 7), 'suspicious for a follicular neoplasm' (n = 3), 'suspicious for malignancy' (n = 3), and 'malignant' (n = 1). On masked review, the most common cytomorphologic features of PTCFA were a nonmacrofollicular cytoarchitectural pattern (71%), medium-large cell size (74%), and micronucleoli (79%). Intranuclear pseudoinclusions and a papillary architecture were absent in 85 and 88% of the cases, respectively. Relative to the 2 control groups, the PTCFA cases demonstrated overlapping features between FA and PTC for the majority of the 31 examined cytomorphologic features. Conclusion: PTCFA represent a rare subset of PTC that is difficult to recognize as PTC by FNAB. Most cases exhibit overlapping features between a benign thyroid nodule and conventional PTC, and they are often interpreted as 'AUS/FLUS'. Copyright (C) 2011 S. Karger AG, Basel C1 [Ono, J. C.; Wilbur, D. C.; Faquin, W. C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lee, H.; Yang, J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Ono, J. C.; Wilbur, D. C.; Lee, H.; Yang, J.; Krane, J. F.; Faquin, W. C.] Harvard Univ, Sch Med, Boston, MA USA. [Krane, J. F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Bongiovanni, M.] Inst Pathol, Locarno, Switzerland. [Bongiovanni, M.] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 219,55 Fruit St, Boston, MA 02114 USA. EM wfaquin@partners.org RI Bongiovanni, Massimo/C-3144-2017 OI Bongiovanni, Massimo/0000-0001-9846-6682 NR 29 TC 3 Z9 3 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PY 2011 VL 55 IS 6 BP 531 EP 538 DI 10.1159/000333240 PG 8 WC Pathology SC Pathology GA 867WZ UT WOS:000298486800008 PM 22156462 ER PT J AU Jordan, KW Adkins, CB Cheng, LL Faquin, WC AF Jordan, Kate W. Adkins, Christen B. Cheng, Leo L. Faquin, William C. TI Application of Magnetic-Resonance-Spectroscopy-Based Metabolomics to the Fine-Needle Aspiration Diagnosis of Papillary Thyroid Carcinoma SO ACTA CYTOLOGICA LA English DT Article DE Thyroid cancer; Diagnosis; Magnetic resonance spectroscopy; Metabolomics; Fine-needle aspiration biopsy ID NEOPLASMS; BIOPSY; RESOLUTION; BENIGN AB Objective: This study explores the potential use of high-resolution magic angle spinning proton magnetic resonance spectroscopy as an ancillary diagnostic technique for papillary thyroid carcinoma in thyroid fine-needle aspiration biopsies. The method has already been shown to be effective in the classification of various other nonthyroid cancers. Study Design: Twenty-six samples (13 paired cytologic and histologic samples) from patients being evaluated for thyroid abnormalities at the Massachusetts General Hospital were spectroscopically analyzed, and included: papillary thyroid carcinomas (n = 4), follicular adenomas (n = 4), and normal thyroid samples (n = 5). Metabolic profiles were statistically generated based on the spectroscopy results, which were then correlated with the final cytologic and histologic diagnoses from the same samples to determine the diagnostic capacity of the profiles. Results: Principal component analysis of the tissue samples revealed statistically significant correlations among principal components and various cytologic and histologic features. Canonical score 1, calculated with principal components in correlation with analyzed pathologies, revealed the ability of the metabolic profile to differentiate all three examined histologic tissue groups (ANOVA, p < 0.0001). Applying coefficients of principal components and canonical scores obtained with tissue samples directly onto spectral results of cytology samples, the calculated canonical score 1 also revealed similar trends among the three fine-needle aspiration biopsy groups. In particular, the papillary thyroid carcinoma group exhibited significant differences from both the adenomatous and normal cytology groups (p < 0.0170). Conclusions: The results indicate the potential of high-resolution magic angle spinning proton magnetic resonance spectroscopy as an ancillary marker for papillary thyroid carcinoma in fine-needle aspiration biopsy specimens. Copyright (C) 2011 S. Karger AG, Basel C1 [Faquin, William C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Jordan, Kate W.; Adkins, Christen B.; Cheng, Leo L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Faquin, WC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, WRN 219, Boston, MA 02114 USA. EM wfaquin@partners.org OI Jordan, Kate/0000-0002-3089-2543 FU NIH [CA115746, CA095624]; Massachusetts General Hospital; A.A. Martinos Center for Biomedical Imaging FX The authors acknowledge partial support from NIH grants CA115746 (L. L. C.) and CA095624 (L. L. C), and from Massachusetts General Hospital and the A.A. Martinos Center for Biomedical Imaging. NR 22 TC 9 Z9 9 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5547 EI 1938-2650 J9 ACTA CYTOL JI Acta Cytol. PY 2011 VL 55 IS 6 BP 584 EP 589 DI 10.1159/000333271 PG 6 WC Pathology SC Pathology GA 867WZ UT WOS:000298486800016 PM 22156470 ER PT J AU Akiba, Y Kaunitz, JD AF Akiba, Y. Kaunitz, J. D. TI Luminal chemosensing in the duodenal mucosa SO ACTA PHYSIOLOGICA LA English DT Review DE acid sensor; calcium-sensing receptor; carbonic anhydrase; glutamate receptor; taste receptor; vanilloid receptor ID CALCIUM-SENSING RECEPTOR; GASTRIC-ACID-SECRETION; GLUCAGON-LIKE PEPTIDE-2; BITTER TASTE RECEPTORS; RAT SMALL-INTESTINE; GASTROINTESTINAL-TRACT; BICARBONATE SECRETION; CARBONIC-ANHYDRASES; HCO3-TRANSPORT; PH REGULATION AB The upper gastrointestinal (GI) mucosa is exposed to endogenous and exogenous chemicals, including gastric acid, CO(2) and nutrients. Mucosal chemical sensors are necessary to exert physiological responses such as secretion, digestion, absorption and motility. We propose the mucosal chemosensing system by which luminal chemicals are sensed to trigger mucosal defence mechanisms via mucosal acid sensors and taste receptors. Luminal acid/CO(2) is sensed via ecto- and cytosolic carbonic anhydrases and ion transporters in the epithelial cells and via acid sensors on the afferent nerves in the duodenum and the oesophagus. Gastric acid sensing is differentially mediated via endocrine cell acid sensors and afferent nerves. Furthermore, a luminal l-glutamate signal is mediated via epithelial l-glutamate receptors, including metabotropic glutamate receptors and taste receptor 1 family heterodimers, with activation of afferent nerves and cyclooxygenase, whereas luminal Ca2+ is differently sensed via the calcium-sensing receptor in the duodenum. These luminal chemosensors help to activate mucosal defence mechanisms in order to maintain the mucosal integrity and physiological responses of the upper GI tract. Stimulation of luminal chemosensing in the upper GI mucosa may prevent mucosal injury, affect nutrient metabolism and modulate sensory nerve activity. C1 Brentwood Biomed Res Inst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Vet Affairs Greater Los Angles Healthcare Syst, Los Angeles, CA 90073 USA. RP Akiba, Y (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yakiba@verizon.net FU Ajinomoto Inc., Japan; AstraZeneca [IRUSESOM0424]; Department of Veterans Affairs; NIH-NIDDK [R01 DK54221] FX We thank Drs Misa Mizumori, Maggie Ham, Chikako Watanabe, Takanari Nakano and Joonho Wang for their research contributions. This study was supported by a research grant from Ajinomoto Inc., Japan (Y. Akiba), Investigator-Sponsored Study Program of AstraZeneca IRUSESOM0424 (Y. Akiba), Department of Veterans Affairs Merit Review Award (J. Kaunitz) and NIH-NIDDK R01 DK54221 (J. Kaunitz). NR 75 TC 19 Z9 19 U1 0 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1748-1708 J9 ACTA PHYSIOL JI Acta Physiol. PD JAN PY 2011 VL 201 IS 1 BP 77 EP 84 DI 10.1111/j.1748-1716.2010.02149.x PG 8 WC Physiology SC Physiology GA 692LA UT WOS:000285153100008 PM 20518751 ER PT J AU Kaunitz, JD Akiba, Y AF Kaunitz, J. D. Akiba, Y. TI Purinergic regulation of duodenal surface pH and ATP concentration: implications for mucosal defence, lipid uptake and cystic fibrosis SO ACTA PHYSIOLOGICA LA English DT Review DE alkaline phosphatase; ecto-ATPase; extracellular purines; HCO(3)- secretion; mucosal defence; P2Y receptors ID INTESTINAL ALKALINE-PHOSPHATASE; MALE REPRODUCTIVE-TRACT; BICARBONATE SECRETION; EPITHELIAL-CELLS; HCO3-SECRETION; MUCOCILIARY CLEARANCE; RAT DUODENUM; PSEUDOMONAS-AERUGINOSA; RECEPTOR AGONISTS; AIRWAY EPITHELIA AB The duodenum secretes HCO(3)- as part of a multi-layered series of defence mechanisms against damage from luminal acid. In the 1980s, an alkaline surface layer was measured over the mucosa which correlated with the rate of HCO(3)- secretion. As all biological processes are regulated, we investigated how the alkaline pH of the surface layer was maintained. As the ecto-phosphorylase alkaline phosphatase (AP) is highly expressed in the duodenal brush border, we hypothesized that its extreme alkaline pH optimum (similar to pH 8-9) combined with its ability to hydrolyse regulatory purines such as ATP was part of an ecto-purinergic signalling system, consisting also of brush border P2Y receptors and cystic fibrosis transmembrane regulator-mediated HCO(3)- secretion. Extracellular ATP increases the rate of HCO(3)- secretion through this purinergic system. At high surface pH (pH(s)), AP activity is increased, which then increases the rate of ATP hydrolysis, decreasing surface ATP concentration ([ATP](s)), with a resultant decrease in the rate of HCO(3)- secretion, which subsequently decreases pH(s). This feedback loop is thus hypothesized to regulate pH(s) over the duodenal mucosa, and in several other HCO(3)- secretory organs. As AP activity is directly related to pH(s), and as AP hydrolyses ATP, [ATP](s) and pH(s) are co-regulated. As many essential tissue functions such as ciliary motility and lipid uptake are dependent on [ATP](s), dysregulation of pH(s) and [ATP](s) may help explain the tissue dysfunction characteristic of diseases such as cystic fibrosis. C1 [Kaunitz, J. D.; Akiba, Y.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Kaunitz, J. D.; Akiba, Y.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Kaunitz, J. D.; Akiba, Y.] Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU Department of Veterans Affairs; NIH-NIDDK [R01 DK54221, R21 DK081199] FX We thank Coleen Palileo for her assistance with manuscript preparation. This study was supported by a Department of Veterans Affairs Merit Review Award, NIH-NIDDK R01 DK54221 and R21 DK081199 (J. Kaunitz). NR 56 TC 11 Z9 12 U1 2 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1748-1708 J9 ACTA PHYSIOL JI Acta Physiol. PD JAN PY 2011 VL 201 IS 1 BP 109 EP 116 DI 10.1111/j.1748-1716.2010.02156.x PG 8 WC Physiology SC Physiology GA 692LA UT WOS:000285153100011 PM 20560899 ER PT J AU Papakostas, G AF Papakostas, George TI Stahl's illustrated. Antidepressants SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Book Review C1 [Papakostas, George] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 01224 USA. RP Papakostas, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 01224 USA. EM gpapakostas@partners.org NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JAN PY 2011 VL 123 IS 1 BP 84 EP 84 PG 1 WC Psychiatry SC Psychiatry GA 691RU UT WOS:000285099300017 ER PT J AU Papakostas, G AF Papakostas, George TI Stahl's illustrated. Mood stabilizers SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Book Review C1 [Papakostas, George] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 01224 USA. RP Papakostas, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 01224 USA. EM gpapakostas@partners.org NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JAN PY 2011 VL 123 IS 1 BP 84 EP 84 PG 1 WC Psychiatry SC Psychiatry GA 691RU UT WOS:000285099300016 ER PT B AU Singhal, AB Lo, EH Dalkara, T Moskowitz, MA AF Singhal, Aneesh B. Lo, Eng H. Dalkara, Turgay Moskowitz, Michael A. BE Gonzalez, RG Hirsch, JA Lev, MH Schaefer, PW Schwamm, LH TI Ischemic Stroke: Basic Pathophysiology and Neuroprotective Strategies SO ACUTE ISCHEMIC STROKE: IMAGING AND INTERVENTION, SECOND EDITION LA English DT Article; Book Chapter ID FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN-ACTIVATOR; NITRIC-OXIDE SYNTHASE; BLOOD-BRAIN-BARRIER; RANDOMIZED CONTROLLED-TRIAL; CLOMETHIAZOLE ACUTE STROKE; CENTRAL-NERVOUS-SYSTEM; CORTICAL SPREADING DEPRESSION; PERFUSION COMPUTED-TOMOGRAPHY; OXYGEN-GLUCOSE DEPRIVATION C1 [Singhal, Aneesh B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv & Neuroprotect Res Lab, Boston, MA 02115 USA. [Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA. [Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA USA. [Dalkara, Turgay] Hacettepe Univ, Dept Neurol, Ankara, Turkey. [Moskowitz, Michael A.] Harvard Univ, Sch Med, Charlestown, MA USA. [Moskowitz, Michael A.] Massachusetts Gen Hosp, Ctr Neurosci, Stroke & Neurovasc Regulat Lab, Dept Neurol, Charlestown, MA USA. RP Singhal, AB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv & Neuroprotect Res Lab, Boston, MA 02115 USA. EM asinghal@partners.org NR 272 TC 3 Z9 3 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-12750-2 PY 2011 BP 1 EP 24 DI 10.1007/978-3-642-12751-9_1 D2 10.1007/978-3-642-12751-9 PG 24 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA BSW03 UT WOS:000285942800001 ER PT J AU Moore, AA Blow, FC Hoffing, M Welgreen, S Davis, JW Lin, JC Ramirez, KD Liao, DH Tang, LQ Gould, R Gill, M Chen, O Barry, KL AF Moore, Alison A. Blow, Fred C. Hoffing, Marc Welgreen, Sandra Davis, James W. Lin, James C. Ramirez, Karina D. Liao, Diana H. Tang, Lingqi Gould, Robert Gill, Monica Chen, Oriana Barry, Kristen L. TI Primary care-based intervention to reduce at-risk drinking in older adults: a randomized controlled trial SO ADDICTION LA English DT Article DE Aged; alcohol; comorbidity; intervention; primary care; screening ID BRIEF PHYSICIAN ADVICE; PROBLEMS SURVEY ARPS; ALCOHOL-USE; EPIDEMIOLOGIC SURVEY; HAZARDOUS DRINKING; DRINKERS; CONSUMPTION; PREVALENCE; HARMFUL AB Aims To examine whether a multi-faceted intervention among older at-risk drinking primary care patients reduced at-risk drinking and alcohol consumption at 3 and 12 months. Design Randomized controlled trial. Setting Three primary care sites in southern California. Participants Six hundred and thirty-one adults aged >= 55 years who were at-risk drinkers identified by the Comorbidity Alcohol Risk Evaluation Tool (CARET) were assigned randomly between October 2004 and April 2007 during an office visit to receive a booklet on healthy behaviors or an intervention including a personalized report, booklet on alcohol and aging, drinking diary, advice from the primary care provider and telephone counseling from a health educator at 2, 4 and 8 weeks. Measurements The primary outcome was the proportion of participants meeting at-risk criteria, and secondary outcomes were number of drinks in past 7 days, heavy drinking (four or more drinks in a day) in the past 7 days and risk score. Findings At 3 months, relative to controls, fewer intervention group participants were at-risk drinkers [odds ratio (OR) 0.41; 95% confidence interval (CI) 0.22-0.75]; they reported drinking fewer drinks in the past 7 days [rate ratio (RR) 0.79; 95% CI 0.70-0.90], less heavy drinking (OR 0.46; 95% CI 0.22-0.99) and had lower risk scores (RR 0.77 95% CI 0.63-0.94). At 12 months, only the difference in number of drinks remained statistically significant (RR 0.87; 95% CI 0.76-0.99). Conclusions A multi-faceted intervention among older at-risk drinkers in primary care does not reduce the proportions of at-risk or heavy drinkers, but does reduce amount of drinking at 12 months. C1 [Moore, Alison A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr Med, Dept Psychiat & Biobehav Sci,Dept Med, Los Angeles, CA 90095 USA. [Hoffing, Marc] Desert Oasis Healthcare, Palm Springs, CA USA. [Blow, Fred C.; Barry, Kristen L.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Blow, Fred C.; Barry, Kristen L.] Vet Affairs Natl Serious Mental Illness Treatment, Ann Arbor, MI USA. [Welgreen, Sandra] Kaiser Permanente, Panorama City, CA USA. [Lin, James C.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Lin, James C.] Cheng Ching Hosp, Dept Med, Taichung, Taiwan. [Tang, Lingqi] Univ Calif Los Angeles, Hlth Serv Res Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Gould, Robert] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA. [Gill, Monica] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Chen, Oriana] Northeastern Ohio Univ Coll Med & Pharm, Coll Med, Rootstown, OH 44272 USA. [Chen, Oriana] Northeastern Ohio Univ Coll Med & Pharm, Coll Pharm, Rootstown, OH USA. RP Moore, AA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr Med, Dept Psychiat & Biobehav Sci,Dept Med, 10945 Le Conte Blvd,Suite 2339, Los Angeles, CA 90095 USA. EM aamoore@mednet.ucla.edu FU National Institute of Alcohol Abuse and Alcoholism [R01 AA013937, K23 AA00270, K24 AA15957]; National Institute on Aging [P30AG021684, T35 AG026736, P30AG028748]; National Institute of Mental Health [P30MH082760]; John A. Hartford Foundation FX This study was supported by R01 AA013937, K23 AA00270, and K24 AA15957 (awarded to Dr Moore) from the National Institute of Alcohol Abuse and Alcoholism, P30AG021684 from the National Institute on Aging (Dr Moore), P30MH082760 from the National Institute of Mental Health (Dr Tang), the Medical Student Training in Aging Program, funded by the National Institute on Aging (T35 AG026736), and the John A. Hartford Foundation (Ms Gill and Ms Chen), Special Fellowship in Advanced Geriatrics, Veterans Affairs Greater Los Angeles Healthcare System (Dr Lin). Data management activities were supported by the UCLA Claude Pepper Older Americans Independence Center funded by the National Institute on Aging (P30AG028748). The sponsor provided financial support for the study only and had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the study; or in the preparation, review or approval of the manuscript. We gratefully acknowledge the patients and clinicians at Desert Oasis Healthcare (DOHC), Kaiser Permanente Southern California (KPSC)-Panorama City and Woodland Hills and UCLA Healthcare, without whom this study could not have been completed. We also thank Michael Mason MD for his leadership of this project at SCKP-Woodland Hills, James Miller for his recruiting efforts at DOHC and Eric Zamora BA, who both recruited subjects and conducted countless interviews. We also would like to acknowledge the assistance provided by the UCLA Academic Technology Services Statistical Consulting Group. NR 36 TC 38 Z9 38 U1 8 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD JAN PY 2011 VL 106 IS 1 BP 111 EP 120 DI 10.1111/j.1360-0443.2010.03229.x PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 693DO UT WOS:000285205000018 PM 21143686 ER PT J AU Anacker, AMJ Loftis, JM Kaur, S Ryabinin, AE AF Anacker, Allison M. J. Loftis, Jennifer M. Kaur, Simranjit Ryabinin, Andrey E. TI Prairie voles as a novel model of socially facilitated excessive drinking SO ADDICTION BIOLOGY LA English DT Article DE Alcoholism; c-Fos; circadian activity; ethanol self-administration; Microtus ochrogaster; peer-pressure ID CORTICOTROPIN-RELEASING-FACTOR; INCENTIVE-SENSITIZATION THEORY; VOLUNTARY ETHANOL-CONSUMPTION; NUCLEUS-ACCUMBENS DOPAMINE; EDINGER-WESTPHAL NUCLEUS; ALCOHOL-PREFERRING RATS; INBRED MOUSE STRAINS; C-FOS EXPRESSION; MICROTUS-OCHROGASTER; PARTNER PREFERENCES AB Social relationships strongly affect alcohol drinking in humans. Traditional laboratory rodents do not exhibit social affiliations with specific peers, and cannot adequately model how such relationships impact drinking. The prairie vole is a socially monogamous rodent used to study social bonds. The present study tested the prairie vole as a potential model for the effects of social affiliations on alcohol drinking. Same-sex adult sibling prairie voles were paired for five days, and then either separated into individual cages, or housed in pairs. Starting at the time of separation, the voles received unlimited access to alcohol in a two-bottle choice test versus water. Pair-housed siblings exhibited higher preference for alcohol, but not saccharin, than singly housed voles. There was a significant correlation between the amount of alcohol consumed by each member of a pair when they were housed together (r = 0.79), but not when housed apart (r = 0.20). Following automated analysis of circadian patterns of fluid consumption indicating peak fluid intake before and after the dark phase, a limited access two-hour two-bottle choice procedure was established. Drinking in this procedure resulted in physiologically relevant blood ethanol concentrations and increased Fos immunoreactivity in perioculomotor urocortin containing neurons (but not in nucleus accumbens or central nucleus of the amygdala). The high ethanol preference and sensitivity to social manipulation indicate that prairie voles can serve to model social influences on excessive drinking. C1 [Ryabinin, Andrey E.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Res & Dev Serv, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Res & Dev Serv, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. RP Ryabinin, AE (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Res & Dev Serv, Portland Vet Affairs Med Ctr, 3181 SW Sam Jackson Pk Rd,L470, Portland, OR 97239 USA. EM ryabinin@ohsu.edu FU National Institute of Health [AA016886, AA016647]; [AA007468-22] FX This work was supported by National Institute of Health grants AA016886 and AA016647 to AER, and training grant AA007468-22. We would like to thank Erika Spangler and Zuzzie Kapasova for technical assistance, Drs. Deborah Finn, Matthew Ford, Sue Carter and Larry Young for valuable consultations, Drs. Joseph Lonstein, Phillip Smith and Karen Bales for donating prairie voles for our colony, and the Veterinary Medical Unit at the Portland VA Medical Center for the care and maintenance of our vole colony. NR 76 TC 31 Z9 31 U1 2 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD JAN PY 2011 VL 16 IS 1 BP 92 EP 107 DI 10.1111/j.1369-1600.2010.00234.x PG 16 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 686LU UT WOS:000284698600009 PM 20579002 ER PT B AU Kelly, JF White, WL AF Kelly, John F. White, William L. BE Kelly, JF White, WL TI Recovery Management and the Future of Addiction Treatment and Recovery in the USA SO ADDICTION RECOVERY MANAGEMENT: THEORY, RESEARCH AND PRACTICE SE Current Clinical Psychiatry LA English DT Article; Book Chapter DE Addiction recovery management; Recovery-oriented systems of care; Addiction treatment systems; Alcoholics anonymous; Narcotics anonymous ID SELF-HELP GROUPS; DRUG-USE; OUTPATIENT TREATMENT; ALCOHOL DEPENDENCE; TREATMENT CAREERS; CONTINUING CARE; CLINICAL-TRIAL; USE DISORDERS; OUTCOMES; PERSPECTIVE AB Scientific understanding of addiction as a chronic disorder has increased substantially in the past 15 years stemming from the results of several retrospective and prospective studies. This research has revealed that among individuals with severe alcohol and other drug problems periods of relapse and poor functioning are common over many years and even decades, despite the receipt of intermittent interventions. Because these interventions typically occur only following acute substance-related crises, treatment typically takes the form of acute biopsychosocial stabilization and is delivered in discrete, self-contained, programs that typically end the service relationship shortly after discharge with little focus on providing adequate linkage to continuing care or recovery support. The predominant acute care paradigm is insufficient and mismatched to the realities of the chronic illness of substance dependence. In this chapter, we provide an overview of recovery management (RM) and recovery-oriented systems of care (ROSC) as new guiding paradigms for the future treatment of, and recovery from, severe alcohol and other drug problems. We also summarize notable examples of RM and ROSC implementation efforts at the program, system, city, and state, levels. Results from these efforts provide a foundation for confident optimism that a cost-effective system of care can be successfully established that is well suited to managing the undulating and enduring risks associated with the chronic illness of substance dependence. C1 [Kelly, John F.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. [White, William L.] Chestnut Hlth Syst, Lighthouse Inst, Bloomington, IL USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St Suite 120, Boston, MA 02114 USA. EM jkelly11@partners.org; bill1white@aol.com; jkelly11@partners.org; bill1white@aol.com NR 64 TC 3 Z9 3 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-959-8 J9 CURR CLIN PSYCHIAT PY 2011 BP 303 EP 316 DI 10.1007/978-1-60327-960-4_16 D2 10.1007/978-1-60327-960-4 PG 14 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA BSP79 UT WOS:000285318300016 ER PT J AU Gray, KM LaRowe, SD Watson, NL Carpenter, MJ AF Gray, Kevin M. LaRowe, Steven D. Watson, Noreen L. Carpenter, Matthew J. TI Reactivity to in vivo marijuana cues among cannabis-dependent adolescents SO ADDICTIVE BEHAVIORS LA English DT Article DE Marijuana; Cannabis; Cue reactivity; Craving; Youth; Adolescent ID SMOKERS; RELIABILITY; RESPONSES; VALIDITY; USERS AB Introduction Cannabis dependence is a common but poorly understood condition in adolescents Marijuana craving has been posited as a potential contributing factor to continued use and relapse but relatively few studies have focused on the measurement of craving and reactivity to marijuana cues The present work sought to explore reactivity to marijuana cues within this age group Methods Thirty treatment-seeking cannabis dependent adolescents (age 13-20) completed a cue reactivity session consisting of exposure to and manipulation of in vivo marijuana cues ( joint and lighter) and matching neutral cues (pencil and eraser) in counterbalanced order Subjective craving and physiological reactivity were assessed Results Participants demonstrated increased craving and skin conductance reactivity in response to marijuana cues relative to neutral cues Conclusion In vivo marijuana cues appear to elicit significant subjective and physiological reactivity among treatment seeking cannabis dependent adolescents Further work is needed with a larger sample and with a wider variety of cues (C) 2010 Elsevier Ltd All rights reserved C1 [Gray, Kevin M.; LaRowe, Steven D.; Watson, Noreen L.; Carpenter, Matthew J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [LaRowe, Steven D.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Watson, Noreen L.] Texas Tech Univ, Dept Psychol, Lubbock, TX 79409 USA. [Carpenter, Matthew J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. RP Gray, KM (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,POB 250861, Charleston, SC 29425 USA. FU NIDA [K12DA000357, R01DA026777, K23DA020482]; USPHS [M01RR01070]; Pfizer Inc FX Funding was provided through NIDA grants K12DA000357 (KMG) R01DA026777 (KMG) and K23DA020482 (MJC) and by USPHS grant M01RR01070 The funding agencies had no role in the study design collection analysis or interpretation of the data writing the manuscript or the decision to submit the paper for publication; No conflicts are declared for Dr LaRowe Dr Carpenter or Ms Watson Dr Gray receives research support (medication and placebo supply for NIH funded research) from Pfizer Inc NR 18 TC 16 Z9 16 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JAN-FEB PY 2011 VL 36 IS 1-2 BP 140 EP 143 DI 10.1016/j.addbeh.2010.08.021 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 694VK UT WOS:000285326900022 PM 20851531 ER PT S AU Krevolin, J Liu, JJ Wallen, A Patel, K Dahl, R Hsu, HP Kearney, C Spector, M AF Krevolin, Janet Liu, James J. Wallen, Adam Patel, Kitu Dahl, Rachel Hsu, Hu-Ping Kearney, Cathal Spector, Myron BE Narayan, R Colombo, P Widjaja, S Singh, D TI TISSUE INGROWTH IN RESORBABLE POROUS TISSUE SCAFFOLDS SO ADVANCES IN BIOCERAMICS AND POROUS CERAMICS IV SE Ceramic Engineering and Science Proceedings LA English DT Proceedings Paper CT Symposium on Porous Ceramics - Novel Developments and Applications / Symposium on Next Generation Bioceramics of the 35th International Conference and Exposition on Advanced Ceramics and Composites (ICACC) CY JAN 23-28, 2011 CL Daytona Beach, FL SP Amer Cerm Soc, Engn Ceram Div ID BIOACTIVE GLASS SCAFFOLDS; ENGINEERING APPLICATIONS; IN-VITRO; BONE; REGENERATION; SURFACE; FIBERS AB Highly porous scaffolds fabricated using a proprietary Cross-Linked Microstructure (CLM) process in a resorbable (bioactive) glass composition were subjected to an in vivo animal study to determine and evaluate the feasibility for use as a weight-bearing tissue engineering scaffold. The CLM scaffolds were manufactured by processing resorbable glass fibers to create a cross-linked microstructure of an interconnected open pore network. The fabrication of such novel scaffolds involves pore formation and strengthening sintering techniques which lead to a well defined crosslinked microstructure with desired mechanical properties. A highly interconnected pore network is created by selection and arrangement of pore-formers and fibers. The porosity can be controlled from 20 to 75% with a pore size range from 50 to 750 mu m. The CLM structure in a resorbable composition with open and interconnected porosity exhibits the potential to provide adequate mechanical properties and bioactivity at the same time. In vivo results suggest that new bone has formed in the pores and around the fibers of the CLM implants. There is also evidence of bone formation directly on the surface of the CLM implants, with continuity of the mineral phase between the bone and implant demonstrating direct bonding to the scaffold. An optimized porous CLM resorbable glass scaffold, with a bonded fiber structure and interconnected porosity is promising for applications in orthopedic tissue engineering as it combines high strength and bioactive properties. The potential applications of this high strength, resorbable glass fiber-based scaffold include load-bearing implants for treating problems of the spine and extremities. C1 [Krevolin, Janet; Liu, James J.; Wallen, Adam; Patel, Kitu; Dahl, Rachel] Bio2 Technol, 12-R Cabot Rd, Woburn, MA 01801 USA. [Hsu, Hu-Ping; Kearney, Cathal; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Lab, Boston, MA 02130 USA. RP Krevolin, J (reprint author), Bio2 Technol, 12-R Cabot Rd, Woburn, MA 01801 USA. OI Kearney, Cathal/0000-0002-9514-6517 FU Technologies and the Department of Veterans Affairs [BI02] FX We wish to thank contributing team members at A _ 2 Technologies, including Art O'Dea and Leonard Newton. This work was supported in part by BI02 Technologies and the Department of Veterans Affairs. NR 22 TC 0 Z9 0 U1 0 U2 0 PU AMER CERAMIC SOC PI WESTERVILLE PA 735 CERAMIC PLACE, WESTERVILLE, OH 43081-8720 USA SN 0196-6219 BN 978-1-118-09526-3; 978-1-118-05991-3 J9 CERAM ENG SCI PROC PY 2011 VL 32 BP 25 EP 35 PG 11 WC Materials Science, Ceramics SC Materials Science GA BFF77 UT WOS:000319679100004 ER PT J AU Rubin, MF AF Rubin, Mario F. TI Hypertension Following Kidney Transplantation SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Hypertension; Transplant; Kidney; Proteinuria; Cardiovascular ID RENAL-ARTERY STENOSIS; BLOOD-PRESSURE CONTROL; LAPAROSCOPIC BILATERAL-NEPHRECTOMY; TRANS-LUMINAL ANGIOPLASTY; RENIN-ANGIOTENSIN SYSTEM; CALCIUM-CHANNEL BLOCKERS; LONG-TERM; POSTTRANSPLANT HYPERTENSION; RISK-FACTORS; ALLOGRAFT RECIPIENTS AB The majority of patients become hypertensive following kidney transplantation. Its occurrence is associated not only with increased fatal and nonfatal cardiovascular events but also with decreased allograft survival. This review summarizes the current knowledge of the epidemiology, etiology, pathophysiology, and management of post-transplant hypertension. (C) 2011 by the National Kidney Foundation, Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. RP Rubin, MF (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM mfrubin@partners.org NR 89 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 EI 1548-5609 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD JAN PY 2011 VL 18 IS 1 BP 17 EP 22 DI 10.1053/j.ackd.2010.10.006 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 715FT UT WOS:000286866800005 PM 21224026 ER PT S AU Daniel, C von Boehmer, H AF Daniel, Carolin von Boehmer, Harald BE Rudensky, A Sakaguchi, S TI Extrathymic Generation of Regulatory T Cells-Chances and Challenges for Prevention of Autoimmune Disease SO ADVANCES IN IMMUNOLOGY: REGULATORY T-CELLS, VOL 112 SE Advances in Immunology LA English DT Review; Book Chapter ID THYMIC EPITHELIAL-CELLS; TRANSCRIPTION FACTOR FOXP3; RECEPTOR TRANSGENIC MICE; LIGASE CBL-B; IN-VIVO; DENDRITIC CELLS; NOD MICE; RETINOIC-ACID; CUTTING EDGE; GENE-EXPRESSION AB Fopx3(+) expressing regulatory T cells (Tregs) function as an indispensable cellular constituent of the immune system by establishing and maintaining immunological self-tolerance. T cell receptor (TCR) ligands of high agonist activity, when applied in vivo under sub-immunogenic conditions, convert naive but not activated T cells into stable Tregs expressing Foxp3. Tolerogenic vaccination with strong-agonist mimetopes of self-antigens may function as a safe and highly specific instrument in the prevention of autoimmune disease by promoting self-antigen-specific tolerance. In this review, we address the requirements for generation of dominant tolerance exerted by Foxp3(+) Tregs in autoimmune disease with special focus on type 1 diabetes (T1D). Further understanding of differentiation of T cells into Tregs at the cellular and molecular level will facilitate development of additional tolerogenic vaccination strategies that can be used in prevention as well as therapeutically to combat unwanted immunity. C1 [Daniel, Carolin; von Boehmer, Harald] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Lab Lymphocyte Biol, Boston, MA 02115 USA. [Daniel, Carolin] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [von Boehmer, Harald] Harvard Univ, Harvard Fac Arts & Sci, Cambridge, MA 02138 USA. RP Daniel, C (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Lab Lymphocyte Biol, Boston, MA 02115 USA. RI Daniel, Carolin/M-4624-2014 OI Daniel, Carolin/0000-0003-4698-7069 FU NIAID NIH HHS [NIH-AI-53102] NR 192 TC 9 Z9 9 U1 2 U2 14 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-387827-4 J9 ADV IMMUNOL JI Adv.Immunol. PY 2011 VL 112 BP 177 EP 213 DI 10.1016/B978-0-12-387827-4.00005-X PG 37 WC Immunology SC Immunology GA BYN00 UT WOS:000299395600005 PM 22118409 ER PT S AU Bentley, KL Stranford, S Liao, S Mounzer, RM Ruddle, FH Ruddle, NH AF Bentley, Kevin L. Stranford, Sharon Liao, Shan Mounzer, Rawad M. Ruddle, Frank H. Ruddle, Nancy H. BE Wallach, D Kovalenko, A Feldman, M TI High Endothelial Venule Reporter Mice to Probe Regulation of Lymph Node Vasculature SO ADVANCES IN TNF FAMILY RESEARCH SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 12th Biennial International TNF Conference CY APR, 2009 CL San Lorenzo del Escorial, SPAIN ID LT-ALPHA-BETA; GENE-EXPRESSION; L-SELECTIN; LYMPHOTOXIN; INFLAMMATION; SULFOTRANSFERASE; NEOGENESIS; DEFICIENT; ADDRESSIN; CHEMOKINE C1 [Bentley, Kevin L.; Liao, Shan; Mounzer, Rawad M.; Ruddle, Nancy H.] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, New Haven, CT 06520 USA. [Liao, Shan] Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. [Mounzer, Rawad M.] UPMC, Montefiore Hosp, Dept Internal Med, Pittsburgh, PA 15213 USA. [Ruddle, Frank H.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06510 USA. [Stranford, Sharon] Mt Holyoke Coll, Dept Biol Sci, S Hadley, MA 01075 USA. RP Ruddle, NH (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, 10 Amistad St,POB 208089, New Haven, CT 06520 USA. EM kevin.bentley@yale.edu; stranford@mtholyoke.edu; sliao@steele.mgh.harvard.edu; mounzerr@upmc.edu; frank.ruddle@yale.edu; nancy.ruddle@yale.edu FU National Institutes of Health [R01 DK057731, CA016885, GM09966]; Mount Holyoke College; Lymphatic Research Foundation FX We thank Myriam Hill for figure preparation and Myriam Hill and Daniel Reagan for outstanding technical assistance. This work was supported by U.S. Public Health Service Grants R01 DK057731 and CA016885 (to N.H.R.) and GM09966 (to F.H.R.) from the National Institutes of Health, a Mount Holyoke College Faculty Research Fellowship (to S.S) and a Lymphatic Research Foundation Fellowship (to R.A.M.) NR 18 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-6611-7 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2011 VL 691 BP 35 EP 44 DI 10.1007/978-1-4419-6612-4_4 PG 10 WC Biochemistry & Molecular Biology; Biology; Immunology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Immunology; Research & Experimental Medicine GA BVG74 UT WOS:000291501300006 PM 21153307 ER PT J AU Robinson, CM Paukert, A Kraus-Schuman, CA Snow, AL Kunik, ME Wilson, NL Teri, L Stanley, MA AF Robinson, Christina M. Paukert, Amber Kraus-Schuman, Cynthia A. Snow, A. Lynn Kunik, Mark E. Wilson, Nancy L. Teri, Linda Stanley, Melinda A. TI The involvement of multiple caregivers in cognitive-behavior therapy for anxiety in persons with dementia SO AGING & MENTAL HEALTH LA English DT Article DE cognitive-behavioral therapy; anxiety; dementia ID RANDOMIZED CONTROLLED-TRIAL; ALZHEIMERS-DISEASE; GROUP INTERVENTION; CLINICAL-TRIAL; NURSING-HOME; PEOPLE; CARE; SCALE; PREVALENCE; DEPRESSION AB Objectives: Peaceful Mind, a cognitive-behavioral therapy for treating anxiety in persons with dementia, is a promising new treatment currently under investigation. This article reports results of our examination of a modification of the treatment protocol in two cases that included multiple caregivers in treating two persons with dementia. Method: Two case presentations of the benefits and challenges of including multiple caregivers in treatment are discussed. Treatment outcome data for these cases were collected as part of a larger investigation of Peaceful Mind. Results: The involvement of multiple collaterals resulted in several benefits, including increased family communication, as well as increased opportunities for the practice of new skills. These cases have also presented unique challenges requiring alterations in therapy structure and attention to issues of family conflict. Conclusions: Including multiple collaterals in cognitive-behavioral therapy for treating anxiety in persons with dementia is feasible and may be beneficial in maximizing treatment gains and increasing the family's investment in therapy. C1 [Kunik, Mark E.; Wilson, Nancy L.; Stanley, Melinda A.] VA HSR&D Houston Ctr Excellence, Houston, TX USA. [Robinson, Christina M.] Univ Houston, Dept Psychol, Houston, TX USA. [Paukert, Amber] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Kraus-Schuman, Cynthia A.; Kunik, Mark E.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Snow, A. Lynn] Univ Alabama, Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. [Snow, A. Lynn; Kunik, Mark E.; Stanley, Melinda A.] VA S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA. [Kunik, Mark E.; Wilson, Nancy L.; Stanley, Melinda A.] Baylor Coll Med, Houston, TX 77030 USA. [Teri, Linda] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. RP Stanley, MA (reprint author), VA HSR&D Houston Ctr Excellence, Houston, TX USA. EM mstanley@bcm.tmc.edu FU National Institute of Mental Health [R34-MH078925]; VA HSR&D Houston Center of Excellence [HFP90-020] FX This study was supported by Grant R34-MH078925 from the National Institute of Mental Health awarded to the last author. It is also based upon work supported in part by the VA HSR&D Houston Center of Excellence (HFP90-020). NR 37 TC 3 Z9 4 U1 4 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 EI 1364-6915 J9 AGING MENT HEALTH JI Aging Ment. Health PY 2011 VL 15 IS 3 BP 291 EP 298 DI 10.1080/13607860903493374 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 748QC UT WOS:000289404500002 PM 21491216 ER PT J AU O'Rourke, N Claxton, A Chou, PHB Smith, JZ Hadjistavropoulos, T AF O'Rourke, Norm Claxton, Amy Chou, Pak Hei Benedito Smith, JuliAnna Z. Hadjistavropoulos, Thomas TI Personality trait levels within older couples and between-spouse trait differences as predictors of marital satisfaction SO AGING & MENTAL HEALTH LA English DT Article DE discrepancy analyses; long-term marriage; marital satisfaction; older adults; personality ID LONG-TERM MARRIAGES; ENDURING MARRIAGES; 5-FACTOR MODEL; LIFE-COURSE; WOMEN WANT; QUALITY; DISSOLUTION; ADJUSTMENT; STABILITY; MIDDLE AB In this study of 125 older couples married for an average of 34 years, multilevel models were computed to simultaneously examine intra-couple personality trait averages and between-spouse trait similarity as predictors of marital satisfaction. Our findings suggest that higher intra-couple levels of extraversion predict marital satisfaction, both husbands and wives. In addition, between-spouse similarity in openness to experience appears associated with higher levels of marital satisfaction as reported by husbands; concomitantly, between-spouse similarity in agreeableness predicts wives' marital satisfaction. With respect to openness (husbands) and agreeableness (wives), it did not matter which spouse within couples reported higher or lower trait levels. The most notable finding to emerge from this study is that neuroticism is not associated with marital satisfaction, neither husbands nor wives. This result stands in contrast to previously reported findings - the vast majority of prior research conducted with dating and newlywed couples. Conflicting results may reflect the degree to which neuroticism determines divorce within the first years of married life, adaptation to the foibles of one's spouse over time, overreliance on younger samples in marriage and family research, or some combination of these alternate explanations. C1 [O'Rourke, Norm] Simon Fraser Univ, Dept Gerontol, Vancouver, BC, Canada. [Claxton, Amy] Univ Washington, Sch Med, VA Puget Sound Healthcare Syst, Seattle, WA USA. [Chou, Pak Hei Benedito] Univ Victoria, Ctr Aging, Victoria, BC, Canada. [Smith, JuliAnna Z.] Univ Massachusetts Amherst, Ctr Res Families, Amherst, MA USA. [Hadjistavropoulos, Thomas] Univ Regina, Dept Psychol, Regina, SK S4S 0A2, Canada. RP O'Rourke, N (reprint author), Simon Fraser Univ, Dept Gerontol, Vancouver Campus, Vancouver, BC, Canada. EM ORourke@sfu.ca RI Hadjistavropoulos, Thomas /D-5976-2011; OI O'Rourke, Norm/0000-0001-5100-427X; Hadjistavropoulos, Thomas /0000-0002-8586-0450 FU Social Sciences and Humanities Research Council of Canada (SSHRC) [410-2005-2328]; Canadian Institutes of Health Research (CIHR) [127915, 136727] FX Support for this study was provided by the Social Sciences and Humanities Research Council of Canada (SSHRC #410-2005-2328) and from the Canadian Institutes of Health Research (CIHR #127915 & 136727), each awarded to Dr O'Rourke. NR 57 TC 2 Z9 2 U1 1 U2 10 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 EI 1364-6915 J9 AGING MENT HEALTH JI Aging Ment. Health PY 2011 VL 15 IS 3 BP 344 EP 353 DI 10.1080/13607863.2010.519324 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 748QC UT WOS:000289404500008 PM 21491219 ER PT J AU Feil, DG Lukman, R Simon, B Walston, A Vickrey, B AF Feil, Denise G. Lukman, Revana Simon, Barbara Walston, Amy Vickrey, Barbara TI Impact of dementia on caring for patients' diabetes SO AGING & MENTAL HEALTH LA English DT Article DE cognitive impairment; comorbidity; caregivers; quality of care ID RANDOMIZED CONTROLLED-TRIAL; BLOOD-GLUCOSE CONTROL; COGNITIVE IMPAIRMENT; ALZHEIMER-DISEASE; OLDER-ADULTS; CAREGIVER SUPPORT; GLYCEMIC CONTROL; CHRONIC ILLNESS; PRIMARY-CARE; MANAGEMENT AB Objective: To explore caregivers' challenges and quality-of-life issues managing diabetes in patients with dementia. Method: We conducted six focus groups with 21 caregivers of patients with dementia and type 2 diabetes. Focus groups were digitally recorded, transcribed, and translated using a software coding system. Emergent themes were identified and confirmed. Results: Three themes emerged. (1) Memory loss was the first identified cause of self-care neglect leading to caregiver intervention. (2) Behavioral and psychological symptoms of dementia (BPSD) disrupted the daily diabetes care routine, with 'denial' of having diabetes or memory loss (anosognosia) being the most disruptive. (3) Caregivers reported that caring for both diabetes and dementia was highly burdensome, felt overwhelmed with BPSD, and wanted more support from family and patients' healthcare providers. Conclusion: Caregivers of patients with dementia and diabetes face extraordinary challenges managing both conditions and the accompanying BPSD. Their identified need for a greater response from the healthcare system should be tested in quality improvement programs for this overlooked yet rapidly growing population. C1 [Feil, Denise G.; Simon, Barbara; Vickrey, Barbara] Vet Affairs Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Sepulveda, CA USA. [Feil, Denise G.; Vickrey, Barbara] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Feil, Denise G.; Lukman, Revana; Walston, Amy; Vickrey, Barbara] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Feil, DG (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Sepulveda, CA USA. EM denise.feil@va.gov FU Veterans' Administration Health Services; West Los Angeles Veterans' Administration Department of Research and Development FX This study was supported by funding from a Veterans' Administration Health Services Research Career Development Award and from the West Los Angeles Veterans' Administration Department of Research and Development. NR 44 TC 6 Z9 6 U1 1 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PY 2011 VL 15 IS 7 BP 894 EP 903 DI 10.1080/13607863.2011.569485 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 881KI UT WOS:000299482500011 PM 21547750 ER PT J AU Betancourt, TS Rubin-Smith, JE Beardslee, WR Stulac, SN Fayida, I Safren, S AF Betancourt, Theresa S. Rubin-Smith, Julia E. Beardslee, William R. Stulac, Sara N. Fayida, Ildephonse Safren, Steven TI Understanding locally, culturally, and contextually relevant mental health problems among Rwandan children and adolescents affected by HIV/AIDS SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE Rwanda; HIV/AIDS; children and adolescents; mental health; qualitative research ID NORTHERN UGANDA; RURAL UGANDA; IRRITABILITY; COMORBIDITY; GENOCIDE; DEPRESSION; HOUSEHOLDS; DISORDERS; COUNTRIES; SYMPTOMS AB In assessing the mental health of HIV/AIDS-affected children and adolescents in Sub-Saharan Africa, researchers often employ mental health measures developed in other settings. However, measures derived from standard Western psychiatric criteria are frequently based on conceptual models of illness or terminology that may or may not be an appropriate for diverse populations. Understanding local perceptions of mental health problems can aid in the selection or creation of appropriate measures. This study used qualitative methodologies (Free Listing, Key Informant interviews, and Clinician Interviews) to understand local perceptions of mental health problems facing HIV/AIDS-affected youth in Rwinkwavu, Rwanda. Several syndrome terms were identified by participants: agahinda kenshi, kwiheba, guhangayika, ihahamuka, umushiha, and uburara. While these local syndromes share some similarities with Western mood, anxiety, and conduct disorders, they also contain important culture-specific features and gradations of severity. Our findings underscore the importance of understanding local manifestations of mental health syndromes when conducting mental health assessments and when planning interventions for HIV/AIDS-affected children and adolescents in diverse settings. C1 [Betancourt, Theresa S.; Rubin-Smith, Julia E.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Francois Xavier Bagnoud Ctr Hlth & Human Rights, Boston, MA 02115 USA. [Beardslee, William R.] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Stulac, Sara N.; Fayida, Ildephonse] Partners In Hlth, Mental Hlth Program, Rwinkwavu, Rwanda. [Safren, Steven] Harvard Univ, Sch Med, Boston, MA USA. [Safren, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Betancourt, TS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Francois Xavier Bagnoud Ctr Hlth & Human Rights, 665 Huntington Ave, Boston, MA 02115 USA. EM Theresa_Betancourt@harvard.edu FU NIMH NIH HHS [K01 MH077246-01A2, 1K01MH077246-01A2, K01 MH077246] NR 47 TC 25 Z9 25 U1 2 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2011 VL 23 IS 4 BP 401 EP 412 DI 10.1080/09540121.2010.516333 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 731OK UT WOS:000288118800002 PM 21271393 ER PT J AU Venkatesh, KK Srikrishnan, AK Safren, SA Triche, EW Thamburaj, E Prasad, L Lurie, MN Kumar, MS Kumarasamy, N Solomon, S Mayer, KH AF Venkatesh, Kartik K. Srikrishnan, A. K. Safren, Steven A. Triche, Elizabeth W. Thamburaj, E. Prasad, Lakshmi Lurie, Mark N. Kumar, M. Suresh Kumarasamy, N. Solomon, Suniti Mayer, Kenneth H. TI Sexual risk behaviors among HIV-infected South Indian couples in the HAART era: implications for reproductive health and HIV care delivery SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; AIDS; sexual behavior; HAART; India ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; SERODISCORDANT COUPLES; DISCORDANT COUPLES; SECONDARY PREVENTION; POSITIVE WOMEN; HOMOSEXUAL-MEN; ALCOHOL-USE; CONDOM USE; CHALLENGES AB The current study examines sexual behaviors among HIV-infected Indians in primary care, where access to highly active antiretroviral therapy (HAART) has recently increased. Between January and April 2008, we assessed the sexual behaviors of 247 HIV-infected South Indians in care. Multivariable logistic regression models were used to determine predictors of being in a HIV-seroconcordant primary relationship, being sexually active, and reporting unprotected sex. Over three-fourths (80%) of participants were HAART-experienced. Among the 58% of participants who were currently in a seroconcordant relationship, one-third were serodiscordant when enrolling into care. Approximately two-thirds (63.2%) of participants were sexually active; 9.0% reported unprotected sex. In the multivariable analyses, participants who were in a seroconcordant primary relationship were more likely to have children, use alcohol, report unprotected sex, and have been enrolled in care for >12 months. Sexually active participants were more likely to be on HAART, have a prior tuberculosis diagnosis, test Herpes simplex type 2 antibody seropositive, and have low general health perceptions. Participants who reported unprotected sex were more likely to be in a seroconcordant relationship, be childless, want to have a child, and use alcohol. We did not document an association between HAART and unprotected sex. Among HIV-infected Indians in primary care, predictors of unprotected sex included alcohol use and desire for children. Prevention interventions for Indian couples should integrate reproductive health and alcohol use counseling at entry into care. C1 [Venkatesh, Kartik K.; Triche, Elizabeth W.; Lurie, Mark N.; Mayer, Kenneth H.] Brown Univ, Dept Community Hlth, Alpert Med Sch, Providence, RI 02912 USA. [Srikrishnan, A. K.; Thamburaj, E.; Prasad, Lakshmi; Kumar, M. Suresh; Kumarasamy, N.; Solomon, Suniti] YR Gaitonde Ctr AIDS Res & Educ YRGCARE, Madras, Tamil Nadu, India. [Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat Behav Med, Massachusetts Gen Hosp, Boston, MA USA. [Safren, Steven A.; Mayer, Kenneth H.] Fenway Community Hlth, Boston, MA USA. [Mayer, Kenneth H.] Brown Univ, Div Infect Dis, Dept Med, Alpert Med Sch,Miriam Hosp, Providence, RI 02912 USA. RP Mayer, KH (reprint author), Brown Univ, Dept Community Hlth, Alpert Med Sch, Providence, RI 02912 USA. EM Kenneth_Mayer@brown.edu RI Triche, Elizabeth/I-4986-2014 FU FIC NIH HHS [D43 TW000237, D43 TW000237-16, D43TW00237]; NIAID NIH HHS [P30 AI042853, P30 AI042853-10, P30AI042853]; NIMH NIH HHS [F30 MH079738-01A2, F30 MH079738, F30 MH079738-01, F30 MH079738-05] NR 52 TC 11 Z9 11 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2011 VL 23 IS 6 BP 722 EP 733 DI 10.1080/09540121.2010.525616 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 764FT UT WOS:000290615500010 PM 21293990 ER PT J AU Curran, GM Pyne, J Fortney, JC Gifford, A Asch, SM Rimland, D Rodriguez-Barradas, M Monson, TP Kilbourne, AM Hagedorn, H Atkinson, JH AF Curran, Geoffrey M. Pyne, Jeffrey Fortney, John C. Gifford, Allen Asch, Stephen M. Rimland, David Rodriguez-Barradas, Maria Monson, Thomas P. Kilbourne, Amy M. Hagedorn, Hilde Atkinson, Joseph H. TI Development and implementation of collaborative care for depression in HIV clinics SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE depression; health services; HIV ID QUALITY-IMPROVEMENT; COST-EFFECTIVENESS; ANTIRETROVIRAL THERAPY; QUERI SERIES; INFECTION; MANAGEMENT; MORTALITY; RISK; AIDS; DISSEMINATION AB We sought to develop and implement collaborative depression care in human immunodeficiency virus (HIV) clinics in a project called HIV Translating Initiatives for Depression into Effective Solutions (HITIDES). Here we describe: (i) the formative evaluation (FE) conducted prior to implementation; (ii) the process used to adapt the primary care collaborative care model for depression to specialty HIV clinics; and (iii) the intervention itself. The overall design of HITIDES was a multi-site randomized trial in United States Department of Veterans Affairs (VA) HIV clinics comparing the depression collaborative care intervention to usual depression care. Qualitative methods were used for the FEs and informed the evidence-based quality improvement (EBQI) methods that were used for adapting and implementing the intervention. Baseline assessments were completed by 249 depressed HIV participants. Summaries of respective key informant interviews with eight HIV patients who were receiving depression treatment and 25 HIV or mental health (MH) providers were presented to each site. EBQI methods were used to tailor the HITIDES intervention to each site while maintaining true to the evidence base for depression collaborative care. EBQI methods provided a useful framework for intervention adaptation and implementation. The HITIDES study provides the opportunity to evaluate collaborative depression care in a specialty physical health clinic setting with a population that has a high prevalence of depression and MH comorbidity. C1 [Curran, Geoffrey M.; Pyne, Jeffrey; Fortney, John C.; Monson, Thomas P.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72114 USA. [Gifford, Allen; Atkinson, Joseph H.] Bedford Vet Affairs Med Ctr, Bedford, MA USA. [Asch, Stephen M.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Rimland, David] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Rodriguez-Barradas, Maria] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kilbourne, Amy M.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Hagedorn, Hilde] Minneapolis Vet Affairs Healthcare Ctr, Minneapolis, MN USA. RP Curran, GM (reprint author), Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72114 USA. EM currangeoffreym@uams.edu NR 51 TC 9 Z9 9 U1 4 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2011 VL 23 IS 12 BP 1626 EP 1636 DI 10.1080/09540121.2011.579943 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 881KA UT WOS:000299481400013 PM 21714689 ER PT J AU Oursler, KK Goulet, JL Crystal, S Justice, AC Crothers, K Butt, AA Rodriguez-Barradas, MC Favors, K Leaf, D Katzel, LI Sorkin, JD AF Oursler, Krisann K. Goulet, Joseph L. Crystal, Stephen Justice, Amy C. Crothers, Kristina Butt, Adeel A. Rodriguez-Barradas, Maria C. Favors, Knachelle Leaf, David Katzel, Leslie I. Sorkin, John D. TI Association of Age and Comorbidity with Physical Function in HIV-Infected and Uninfected Patients: Results from the Veterans Aging Cohort Study SO AIDS PATIENT CARE AND STDS LA English DT Article ID MYOCARDIAL-INFARCTION; MEDICAL CONDITIONS; NEGATIVE VETERANS; CIGARETTE-SMOKING; MEN; DISEASE; RISK; HEALTH; IMPACT; DISABILITY AB HIV clinical care now involves prevention and treatment of age-associated comorbidity. Although physical function is an established correlate to comorbidity in older adults without HIV infection, its role in aging of HIV-infected adults is not well understood. To investigate this question we conducted cross-sectional analyses including linear regression models of physical function in 3227 HIV-infected and 3240 uninfected patients enrolled 2002-2006 in the Veterans Aging Cohort Study-8-site (VACS-8). Baseline self-reported physical function correlated with the Short Form-12 physical subscale (rho = 0.74, p < 0.001), and predicted survival. Across the age groups decline in physical function per year was greater in HIV-infected patients (beta(coef) -0.25, p < 0.001) compared to uninfected patients (beta(coef) -0.08, p = 0.03). This difference, although statistically significant (p < 0.01), was small. Function in the average 50-year old HIV-infected subject was equivalent to the average 51.5-year-old uninfected subject. History of cardiovascular disease was a significant predictor of poor function, but the effect was similar across groups. Chronic pulmonary disease had a differential effect on function by HIV status (Delta beta(coef) -3.5, p = 0.03). A 50-year-old HIV-infected subject with chronic pulmonary disease had the equivalent level of function as a 68.1-year-old uninfected subject with chronic pulmonary disease. We conclude that age-associated comorbidity affects physical function in HIV-infected patients, and may modify the effect of aging. Longitudinal research with markers of disease severity is needed to investigate loss of physical function with aging, and to develop age-specific HIV care guidelines. C1 [Oursler, Krisann K.; Favors, Knachelle; Katzel, Leslie I.; Sorkin, John D.] Univ Maryland, Sch Med, Dept Med, Vet Affairs Maryland Healthcare Syst, Baltimore, MD 21201 USA. [Goulet, Joseph L.; Justice, Amy C.] Yale Univ, Sch Med & Publ Hlth, Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Crystal, Stephen] Rutgers State Univ, Ctr Hlth Serv Res Pharmacotherapy Chron Dis Manag, Inst Hlth, New Brunswick, NJ 08903 USA. [Crothers, Kristina] Univ Washington, Seattle, WA 98195 USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. [Leaf, David] Univ Calif Los Angeles, Sch Med, Greater Los Angeles Vet Affairs Healthcare Syst L, Los Angeles, CA 90024 USA. [Katzel, Leslie I.; Sorkin, John D.] Baltimore Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. RP Oursler, KK (reprint author), Univ Maryland, Sch Med, Dept Med, Vet Affairs Maryland Healthcare Syst, 10 N Greene St BVAMC, Baltimore, MD 21201 USA. EM koursler@grecc.umaryland.edu OI Goulet, Joseph/0000-0002-0842-804X; Crothers, Kristina/0000-0001-9702-0371 FU National Institutes of Health (NIH) [K23AG024896, U01AA13566, R01HL090342, R01MH058984]; University of Maryland Claude D. Pepper Older Americans Independence Center [P60AG 028747]; Department of Veterans Affairs Baltimore Geriatric Research, Clinical and Education Center FX Supported by the National Institutes of Health (NIH) K23AG024896 (K.K.O.); U01AA13566 (A.C.J.); R01HL090342 (K.C.); R01MH058984 (S.C.); University of Maryland Claude D. Pepper Older Americans Independence Center P60AG 028747 (K.K.O., L.I.K., J.D.S., K.F.), and Department of Veterans Affairs Baltimore Geriatric Research, Clinical and Education Center (L.I.K., J.D.S.). NR 36 TC 45 Z9 45 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JAN PY 2011 VL 25 IS 1 BP 13 EP 20 DI 10.1089/apc.2010.0242 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 704PW UT WOS:000286065900003 PM 21214375 ER PT J AU Chu, J Sloan, CE Freedberg, KA Yazdanpanah, Y Losina, E AF Chu, Jennifer Sloan, Caroline E. Freedberg, Kenneth A. Yazdanpanah, Yazdan Losina, Elena TI Drug efficacy by direct and adjusted indirect comparison to placebo: An illustration by Mycobacterium avium complex prophylaxis in HIV SO AIDS RESEARCH AND THERAPY LA English DT Article AB Background: Our goal was to illustrate a method for making indirect treatment comparisons in the absence of head-to-head trials, by portraying the derivation of published efficacies for prophylaxis regimens of HIV-related opportunistic infections. Results: We identified published results of randomized controlled trials from the United States in which HIV-infected patients received rifabutin, azithromycin, clarithromycin, or placebo for prophylaxis against Mycobacterium avium complex (MAC). We extracted the number of subjects, follow-up time, primary MAC events, mean CD4 count, and proportion of subjects on mono or dual antiretroviral therapy (ART) from each study. We derived the efficacy of each drug using adjusted indirect comparisons and, when possible, by direct comparisons. Five articles satisfied our inclusion criteria. Using direct comparison, we estimated the efficacies of rifabutin, clarithromycin, and azithromycin compared to placebo to be 53% (95% CI, 48-61%), 66% (95% CI, 61-74%), and 66% (95% CI, 60-81%), respectively. Using adjusted indirect calculations, the efficacy of rifabutin compared to placebo ranged from 41% to 44%. The adjusted indirect efficacies of clarithromycin and azithromycin were estimated to be 73% and 72%, respectively. Conclusions: Accurate estimates of specific drug dosages as compared to placebo are important for policy and implementation research. This study illustrates a simple method of adjusting for differences in study populations by using indirect comparisons in the absence of head-to-head HIV clinical trials. C1 [Chu, Jennifer; Sloan, Caroline E.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Freedberg, Kenneth A.; Losina, Elena] Harvard Univ, Ctr AIDS Res, Sch Med, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. [Yazdanpanah, Yazdan] Ctr Hosp Tourcoing, Fac Med Lille, Tourcoing, France. RP Chu, J (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. EM jchu6@partners.org FU National Institute of Allergy and Infectious Diseases [R37 AI042006, R01 AI058736, K24 AI062476] FX This study was supported by the National Institute of Allergy and Infectious Diseases (R37 AI042006, R01 AI058736, K24 AI062476). NR 24 TC 1 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-6405 J9 AIDS RES THER JI Aids Res. Ther. PY 2011 VL 8 AR 14 DI 10.1186/1742-6405-8-14 PG 6 WC Infectious Diseases SC Infectious Diseases GA V27LK UT WOS:000208614500014 PM 21388558 ER PT J AU Ivers, LC Appleton, SC Wang, BX Jerome, JG Cullen, KA Fawzi, MCS AF Ivers, Louise C. Appleton, Sasha C. Wang, Bingxia Jerome, J. Gregory Cullen, Kimberly A. Fawzi, Mary C. Smith TI HIV-free survival and morbidity among formula-fed infants in a prevention of mother-to-child transmission of HIV program in rural Haiti SO AIDS RESEARCH AND THERAPY LA English DT Article DE HIV; prevention of mother-to-child transmission; breastfeeding; formula; resource-poor setting; Haiti AB Background: Partners In Health (PIH) works with the Ministry of Health to provide comprehensive health services in Haiti. Between 1994 and 2009, PIH recommended exclusive formula feeding in the prevention of mother-to-child transmission (PMTCT) of HIV program and provided support to implement this strategy. We conducted this study to assess HIV-free survival and prevalence of diarrhea and malnutrition among infants in our PMTCT program in rural Haiti where exclusive formula feeding was supported. Methods: We reviewed medical charts of PMTCT mother-infant pairs at PIH between November 2004 and August 2006 through a retrospective longitudinal study and cross-sectional survey. We performed household surveys for each pair and at control households matched by infant's age and gender. Results: 254 mother-infant pairs were included. 15.3% of infants were low birth weight; most births occurred at home (68.8%). 55.9% of households had no latrine; food insecurity was high (mean score of 18; scale 0-27, SD = 5.3). HIV-free survival at 18 months was 90.6%. Within the cohort, 9 children (3.5%) were HIV-infected and 17 (6.7%) died. Community controls were more likely to be breastfed (P = 0.003) and more likely to introduce food early (P = 0.003) than PMTCT-program households. There was no difference in moderate malnutrition (Z score <= 2 SD) between PMTCT and community groups after controlling for guardian's education, marital status, and food insecurity (OR = 1.05; 95% CI: 0.67, 1.64; P = 0.84). Diarrhea was 2.9 times more prevalent among community children than PMTCT infants (30.3% vs. 12.2%; P < 0.0001). Conclusions: In a PIH-supported program in rural Haiti that addressed socioeconomic barriers to ill-health, breast milk substitution was safe, acceptable and feasible for PMTCT for HIV-infected women choosing this option. C1 [Ivers, Louise C.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Ivers, Louise C.; Appleton, Sasha C.; Cullen, Kimberly A.; Fawzi, Mary C. Smith] Partners Hlth, Boston, MA USA. [Ivers, Louise C.; Fawzi, Mary C. Smith] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Wang, Bingxia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jerome, J. Gregory] Zanmi Lasante, Cange, Haiti. RP Ivers, LC (reprint author), Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA. EM livers@pih.org FU NIAID [K23 AI063998]; David Rockefeller Center for Latin American Studies [205071790] FX The study was supported in part by NIAID (K23 AI063998 to LCI) and by the David Rockefeller Center for Latin American Studies (The Impact of Prevention of Mother-to-Child Transmission of HIV (PMTCT) Program in rural Haiti, 205071790 to LCI). We thank Jessica Teng for literature review and assistance with preparation of the figures and manuscript, Jessica Hart for contribution to literature review and Cate Oswald for assistance with data collection and cleaning. We also thank ZL staff as well as participants in the study. NR 34 TC 5 Z9 5 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-6405 J9 AIDS RES THER JI Aids Res. Ther. PY 2011 VL 8 AR 37 DI 10.1186/1742-6405-8-37 PG 11 WC Infectious Diseases SC Infectious Diseases GA V27LK UT WOS:000208614500037 PM 21992146 ER PT J AU Evans, DA Grodstein, F Loewenstein, D Kaye, J Weintraub, S AF Evans, Denis A. Grodstein, Francine Loewenstein, David Kaye, Jeffrey Weintraub, Sandra TI Reducing case ascertainment costs in US population studies of Alzheimer's disease, dementia, and cognitive impairment-Part 2 SO ALZHEIMERS & DEMENTIA LA English DT Article; Proceedings Paper CT Conference on Prevalence and Trends of Alzheimers Disease and Other Age-Related Cognitive Impairment CY MAR 19-20, 2009 CL Washington, DC DE Alzheimer's disease; Dementia; Cognitive impairment; Cognitive function; Cognitive assessment; Technology; Monitoring system ID MINI-MENTAL STATE; SEMANTIC INTERFERENCE; OLDER-ADULTS; MEMORY IMPAIRMENT; APOLIPOPROTEIN-E; DECLINE; VARIABILITY; EDUCATION; ELDERS; INDIVIDUALS AB Dementia of the Alzheimer's type (DAT) is a major public health threat in developed countries where longevity has been extended to the eighth decade of life. Estimates of prevalence and incidence of DAT vary with what is measured, be it change from a baseline cognitive state or a clinical diagnostic endpoint, such as Alzheimer's disease. Judgment of what is psychometrically "normal" at the age of 80 years implicitly condones a decline from what is normal at the age of 30. However, because cognitive aging is very heterogeneous, it is reasonable to ask "Is 'normal for age' good enough to screen for DAT or its earlier precursors of cognitive impairment?" Cost containment and accessibility of ascertainment methods are enhanced by well-validated and reliable methods such as screening for cognitive impairment by telephone interviews. However, focused assessment of episodic memory, the key symptom associated with DAT, might be more effective at distinguishing normal from abnormal cognitive aging trajectories. Alternatively, the futuristic "Smart Home," outfitted with unobtrusive sensors and data storage devices, permits the moment-to-moment recording of activities so that changes that constitute risk for DAT can be identified before the emergence of symptoms. (C) 2011 The Alzheimer's Association. All rights reserved. C1 [Evans, Denis A.] Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA. [Evans, Denis A.] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Grodstein, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Grodstein, Francine] Brigham & Womens Hosp, Boston, MA 02115 USA. [Loewenstein, David] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Loewenstein, David] Mt Sinai Med Ctr, Wien Ctr Alzheimers Dis & Memory Disorders, Miami, FL USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. [Kaye, Jeffrey] Portland VA Med Ctr, Portland, OR USA. [Weintraub, Sandra] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Weintraub, Sandra] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA. RP Evans, DA (reprint author), Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA. EM Denis_Evans@rush.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [P30 AG008017-15, P30 AG008017, P30 AG013854, P30 AG013854-10, P30 AG024978, P30 AG024978-08, P30AG008017, P30AG013854, P30AG024978, R01 AG011101, R01 AG011101-17, R01 AG024059, R01 AG024059-05, R01 AG024215, R01 AG024215-05, R01AG011101, R01AG024059, R01AG024215] NR 88 TC 17 Z9 17 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2011 VL 7 IS 1 BP 110 EP 123 DI 10.1016/j.jalz.2010.11.008 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 716XJ UT WOS:000287006500011 PM 21255748 ER PT J AU Barnes, DE Lee, SJ AF Barnes, Deborah E. Lee, Sei J. TI Predicting Alzheimer's risk: Why and how? SO ALZHEIMERS RESEARCH & THERAPY LA English DT Editorial Material AB Because the pathologic processes that underlie Alzheimer's disease (AD) appear to start 10 to 20 years before symptoms develop, there is currently intense interest in developing techniques to accurately predict which individuals are most likely to become symptomatic. Several AD risk prediction strategies - including identification of biomarkers and neuroimaging techniques and development of risk indices that combine traditional and non-traditional risk factors - are being explored. Most AD risk prediction strategies developed to date have had moderate prognostic accuracy but are limited by two key issues. First, they do not explicitly model mortality along with AD risk and, therefore, do not differentiate individuals who are likely to develop symptomatic AD prior to death from those who are likely to die of other causes. This is critically important so that any preventive treatments can be targeted to maximize the potential benefit and minimize the potential harm. Second, AD risk prediction strategies developed to date have not explored the full range of predictive variables (biomarkers, imaging, and traditional and non-traditional risk factors) over the full preclinical period (10 to 20 years). Sophisticated modeling techniques such as hidden Markov models may enable the development of a more comprehensive AD risk prediction algorithm by combining data from multiple cohorts. As the field moves forward, it will be critically important to develop techniques that simultaneously model the risk of mortality as well as the risk of AD over the full preclinical spectrum and to consider the potential harm as well as the benefit of identifying and treating high-risk older patients. C1 [Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94118 USA. [Barnes, Deborah E.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Med, Div Geriatr, Program Aging Century, San Francisco, CA 94118 USA. [Lee, Sei J.] San Francisco VA Med Ctr, Med Serv, San Francisco, CA 94121 USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94118 USA. EM deborah.barnes@ucsf.edu FU NIA NIH HHS [K23 AG040779] NR 10 TC 3 Z9 3 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2011 VL 3 IS 6 AR 33 DI 10.1186/alzrt95 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V27JB UT WOS:000208608400003 PM 22126363 ER PT J AU Shirk, SD Mitchell, MB Shaughnessy, LW Sherman, JC Locascio, JJ Weintraub, S Atri, A AF Shirk, Steven D. Mitchell, Meghan B. Shaughnessy, Lynn W. Sherman, Janet C. Locascio, Joseph J. Weintraub, Sandra Atri, Alireza TI A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery SO ALZHEIMERS RESEARCH & THERAPY LA English DT Article DE Alzheimer's disease; cognitive aging; MCI; memory; norms AB Introduction: With the recent publication of new criteria for the diagnosis of preclinical Alzheimer's disease (AD), there is a need for neuropsychological tools that take premorbid functioning into account in order to detect subtle cognitive decline. Using demographic adjustments is one method for increasing the sensitivity of commonly used measures. We sought to provide a useful online z-score calculator that yields estimates of percentile ranges and adjusts individual performance based on sex, age and/or education for each of the neuropsychological tests of the National Alzheimer's Coordinating Center Uniform Data Set (NACC, UDS). In addition, we aimed to provide an easily accessible method of creating norms for other clinical researchers for their own, unique data sets. Methods: Data from 3,268 clinically cognitively-normal older UDS subjects from a cohort reported by Weintraub and colleagues (2009) were included. For all neuropsychological tests, z-scores were estimated by subtracting the raw score from the predicted mean and then dividing this difference score by the root mean squared error term (RMSE) for a given linear regression model. Results: For each neuropsychological test, an estimated z-score was calculated for any raw score based on five different models that adjust for the demographic predictors of SEX, AGE and EDUCATION, either concurrently, individually or without covariates. The interactive online calculator allows the entry of a raw score and provides five corresponding estimated z-scores based on predictions from each corresponding linear regression model. The calculator produces percentile ranks and graphical output. Conclusions: An interactive, regression-based, normative score online calculator was created to serve as an additional resource for UDS clinical researchers, especially in guiding interpretation of individual performances that appear to fall in borderline realms and may be of particular utility for operationalizing subtle cognitive impairment present according to the newly proposed criteria for Stage 3 preclinical Alzheimer's disease. C1 [Shirk, Steven D.; Mitchell, Meghan B.; Shaughnessy, Lynn W.; Sherman, Janet C.; Locascio, Joseph J.; Atri, Alireza] Massachusetts Gen Hosp, Dept Neurol, Memory Disorders Unit, Boston, MA 02114 USA. [Shirk, Steven D.; Mitchell, Meghan B.; Shaughnessy, Lynn W.; Sherman, Janet C.; Locascio, Joseph J.; Atri, Alireza] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Shirk, Steven D.; Mitchell, Meghan B.; Shaughnessy, Lynn W.; Atri, Alireza] Edith Nourse Rogers Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Bedford, MA 01730 USA. [Shaughnessy, Lynn W.] Massachusetts Mental Hlth Ctr, Dept Psychiat, Jamaica Plain, MA 02130 USA. [Shaughnessy, Lynn W.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Weintraub, Sandra] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA. RP Atri, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, Memory Disorders Unit, 15 Parkman St,WACC 715, Boston, MA 02114 USA. EM atri@nmr.mgh.harvard.edu OI Atri, Alireza/0000-0003-4405-6973 FU National Institute on Aging [U01 AG016976]; NIA [K23AG027171] FX We would like to acknowledge the National Alzheimer's Coordinating Center (NACC) funded by the National Institute on Aging (U01 AG016976), PI W. Kukull. The Clinical, Administrative, and Biostatistics and Bioinformatics Cores of the Massachusetts Alzheimer's Disease Research Center (NIA 5 P50AG05134 Growdon and Hyman), and the Bedford Division of the New England Geriatric Research Education and Clinical Center (GRECC) at the ENRM Veterans Administration (VA) Hospital.; We would also like to particularly acknowledge Michael Sachs, Ms. Catherine Crosby, Dr. Rebecca England, Dr. Dorene Rentz, Dr. John Growdon and Dr. Liang Yap (MGH Memory Disorders Unit and MA Alzheimer's Disease Research Center) for providing significant assistance, guidance, resources and/or helpful comments. Finally, and most importantly, we express our deep gratitude for the commitment of the NACC UDS study participants without whose generous contribution and dedication this research would not be possible. This study was funded by NIA K23AG027171 (Atri). NR 14 TC 27 Z9 27 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2011 VL 3 IS 6 AR 32 DI 10.1186/alzrt94 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V27JB UT WOS:000208608400002 PM 22078663 ER PT J AU Chin, CT Chen, AY Wang, TY Alexander, KP Mathews, R Rumsfeld, JS Cannon, CP Fonarow, GC Peterson, ED Roe, MT AF Chin, Chee Tang Chen, Anita Y. Wang, Tracy Y. Alexander, Karen P. Mathews, Robin Rumsfeld, John S. Cannon, Christopher P. Fonarow, Gregg C. Peterson, Eric D. Roe, Matthew T. CA ACTION Registry GWTG Res TI Risk adjustment for in-hospital mortality of contemporary patients with acute myocardial infarction: The Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry (R)-Get With The Guidelines (GWTG)(TM) acute myocardial infarction mortality model and risk score SO AMERICAN HEART JOURNAL LA English DT Article ID ST-SEGMENT ELEVATION; TRIAL; PREDICTORS; CARE AB Background Accurate risk adjustment is needed to guide quality improvement initiatives and research to improve care of patients with acute myocardial infarction (MI). We developed and validated a model to predict the risk of in-hospital mortality for contemporary patients with acute MI treated in routine clinical practice. Methods The Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry (R)-Get With The Guidelines (GWTG)(TM) database of patients with acute MI was used to derive (n = 65,668 from 248 US sites) and validate (n = 16,336) a multivariable logistic regression model to predict the likelihood of in-hospital mortality (4.9% in each cohort). Results Factors with the highest independent significance in terms of mortality prediction included age, baseline serum creatinine, systolic blood pressure, troponin elevation, heart failure and/or cardiogenic shock at presentation, ST-segment changes, heart rate, and prior peripheral arterial disease. The model showed very good discrimination, with c statistics of 0.85 and 0.84 in the derivation and validation cohorts, respectively. The model calibrated well overall and in key patient subgroups including males versus females, age < 75 versus >= 75 years, diabetes versus no diabetes, and ST-elevation MI versus non-ST-elevation MI. The ACTION Registry (R)-GWTG (TM) in-hospital mortality risk score was also developed from the model. Patients with a risk score of <= 40 had an observed mortality rate of < 4% compared with those with a risk score of 41-50 (12%) and risk scores > 50 (34%). Conclusion The ACTION Registry (R)-GWTG (TM) in-hospital mortality model and risk score represent simple, accurate risk adjustment tools for contemporary patients with acute MI. (Am Heart J 2011;161:113-122.e2.) C1 [Chin, Chee Tang; Chen, Anita Y.; Wang, Tracy Y.; Alexander, Karen P.; Mathews, Robin; Peterson, Eric D.; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC USA. [Chin, Chee Tang] Natl Heart Ctr Singapore, Singapore, Singapore. [Rumsfeld, John S.] Univ Colorado, Denver, CO 80202 USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Roe, MT (reprint author), 2400 Pratt St, Durham, NC 27705 USA. EM roe00001@mc.duke.edu FU Society of Chest Pain Centers; American College of Emergency Physicians; Society of Hospital Medicine; Bristol-Myers Squibb/Sanofi Pharmaceuticals FX ACTION Registry (R)-GWTG (TM) is an initiative of the American College of Cardiology Foundation and the American Heart Association with partnering support from the Society of Chest Pain Centers, the American College of Emergency Physicians, and the Society of Hospital Medicine. The registry is sponsored in part by the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. NR 20 TC 65 Z9 67 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2011 VL 161 IS 1 DI 10.1016/j.ahj.2010.10.004 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 695MZ UT WOS:000285376200012 PM 21167342 ER PT J AU Wang, TY Peterson, ED Ou, FS Nallamothu, BK Rumsfeld, JS Roe, MT AF Wang, Tracy Y. Peterson, Eric D. Ou, Fang-Shu Nallamothu, Brahmajee K. Rumsfeld, John S. Roe, Matthew T. CA Natl Cardiovasc Data Registry TI Door-to-balloon times for patients with ST-segment elevation myocardial infarction requiring interhospital transfer for primary percutaneous coronary intervention: A report from the National Cardiovascular Data Registry SO AMERICAN HEART JOURNAL LA English DT Article ID ASSOCIATION TASK-FORCE; PRIMARY ANGIOPLASTY; IMMEDIATE THROMBOLYSIS; HEART-ASSOCIATION; AMERICAN-COLLEGE; REPERFUSION; CARE; THERAPY; SYSTEMS; TIMELINESS AB Background National initiatives have reduced door-to-balloon (DTB) times for direct-arrival ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). However, STEMI patients requiring interhospital transfer for primary PCI are often excluded from public performance assessments of this quality metric. Methods We compared DTB time improvements between 2005 and 2007 for 29,248 transfer (25%) and 86,382 direct-arrival STEMI patients treated with primary PCI at 790 hospitals in the National Cardiovascular Data Catheterization PCI Registry. Among the 165 hospitals that submitted data for >= 10 patients per year, we examined the correlation between hospital-level changes in transfer and direct-arrival DTB times. Results Although DTB times decreased significantly over time for both groups, transfer STEMI patients had longer DTB times (median 149 vs 79 minutes, P < .0001), few received PCI <= 90 minutes (10% vs 63%, P < .0001), and the adjusted rate of DTB time improvement was slower (5% vs 9% relative decrease per year, P < .001) compared with direct-arrival patients. Larger annual transfer volume (not necessarily for primary PCI) was associated with greater improvement in transfer DTB times. However, there was no correlation between hospitals that improved direct-arrival DTB times and those that improved transfer DTB times (r = 0.094, P = .23). Conclusions Although there has been modest temporal improvement in DTB times, transfer patients still rarely achieve benchmark standards. Hospitals that had greater improvements in direct-arrival DTB times were not necessarily those with greater improvements in transfer DTB times. These results highlight the need for targeted system and policy approaches to improve DTB time for transferred primary PCI patients. (Am Heart J 2011;161:76-83.e1.) C1 [Wang, Tracy Y.; Peterson, Eric D.; Ou, Fang-Shu; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC 27705 USA. [Nallamothu, Brahmajee K.] Univ Michigan, Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA. [Rumsfeld, John S.] Univ Colorado, Denver VA Med Ctr, Denver, CO 80202 USA. RP Wang, TY (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM tracy.wang@duke.edu FU Medicines Company, Parsippany, NJ; Sanofi; Schering-Plough (Merck), Whitehouse Station, NJ; Heartscape, Bothell, WA; Eli Lilly; Indianapolis; IN/Daiichi Sankyo Alliance, Parsippany, NJ; Bristol-Myers Squibb, New York, NY; Bristol-Myers Squibb/Sanofi, Bridgewater, NJ; Daiichi-Sankyo, Parsippany, NJ; Indianapolis, IN; Portola Pharmaceuticals, San Francisco, CA; KAI Pharmaceuticals, San Francisco, CA; Schering-Plough (Merck) Whitehouse Station, NJ; Sanofi-Aventis, Bridgewater, NJ; Bridgewater, NJ/BMS, New York, NY FX TY Wang: research grants from the Medicines Company, Parsippany, NJ, Sanofi, Bridgewater, NJ/BMS Partnership, New York, NY, Schering-Plough (Merck), Whitehouse Station, NJ, Heartscape, Bothell, WA, and Eli Lilly, Indianapolis, IN/Daiichi Sankyo Alliance, Parsippany, NJ.; ED Peterson: research grants from Bristol-Myers Squibb, New York, NY, Bristol-Myers Squibb/Sanofi, Bridgewater, NJ.; MT Roe: research grants from Daiichi-Sankyo, Parsippany, NJ, Eli Lilly, Indianapolis, IN, Portola Pharmaceuticals, San Francisco, CA, KAI Pharmaceuticals, San Francisco, CA, Schering-Plough (Merck) Whitehouse Station, NJ, Sanofi-Aventis, Bridgewater, NJ; consultant for KAI Pharmaceuticals, San Francisco, CA, Schering-Plough; Clinical Events Committees for Genentech, San Francisco, CA, Novartis, Basel, Switzerland; speakers bureau for Schering-Plough. NR 32 TC 35 Z9 36 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JAN PY 2011 VL 161 IS 1 DI 10.1016/j.ahj.2010.10.001 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 695MZ UT WOS:000285376200007 PM 21167337 ER PT J AU Courtwright, A AF Courtwright, Andrew TI Shared Health Governance and the Problem of Stability SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Internal Med, Womens Hlth Associates, Boston, MA 02114 USA. RP Courtwright, A (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Womens Hlth Associates, Yawkey 4B,55 Fruit St, Boston, MA 02114 USA. EM acourtwright@partners.org NR 6 TC 2 Z9 2 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 7 BP 47 EP 49 DI 10.1080/15265161.2011.566667 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 799IS UT WOS:000293281000016 PM 21745084 ER PT J AU Huddle, TS AF Huddle, Thomas S. TI Clarifying the Dispute over Academic-Industry Relationships SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID CONFLICTS-OF-INTEREST C1 [Huddle, Thomas S.] UAB Sch Med, Birmingham, AL 35294 USA. [Huddle, Thomas S.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Huddle, TS (reprint author), UAB Sch Med, 1530 3rd Ave S, Birmingham, AL 35294 USA. EM thuddle@uab.edu NR 8 TC 3 Z9 3 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JAN PY 2011 VL 11 IS 1 BP 47 EP 49 DI 10.1080/15265161.2010.534540 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 717LV UT WOS:000287047300018 PM 21240812 ER PT J AU Cochrane, T Bianchi, MT AF Cochrane, Thomas Bianchi, Matt T. TI "Take My Organs, Please": A Section of My Living Will SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Cochrane, Thomas] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Bianchi, Matt T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cochrane, T (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St,Tower 5D EMG, Boston, MA 02115 USA. EM tcochrane@partners.org NR 3 TC 1 Z9 1 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 8 BP 56 EP 58 DI 10.1080/15265161.2011.583326 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 806VO UT WOS:000293843800022 PM 21806445 ER PT J AU Shalowitz, DI Ecker, JL AF Shalowitz, David I. Ecker, Jeffrey L. TI Research in Pregnancy: Back to First Principles SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Shalowitz, David I.; Ecker, Jeffrey L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shalowitz, DI (reprint author), Founders 420,55 Fruit St, Boston, MA 02114 USA. EM dshalowitz@partners.org OI Shalowitz, David/0000-0002-5189-4687 NR 5 TC 2 Z9 2 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 5 BP 56 EP 57 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 756ZN UT WOS:000290053400022 PM 21534155 ER PT J AU Antin, JH Emmert-Buck, MR Aplin, AE Cheng, SY Cryns, VL Wang, DS AF Antin, Joseph H. Emmert-Buck, Michael R. Aplin, Andrew E. Cheng, Sheue-yann Cryns, Vincent L. Wang, Dengshun TI Launching of American Journal of Cancer Research SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Editorial Material C1 [Antin, Joseph H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA. [Emmert-Buck, Michael R.; Cheng, Sheue-yann] NCI, Bethesda, MD 20892 USA. [Aplin, Andrew E.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Cryns, Vincent L.] Northwestern Univ, Chicago, IL 60611 USA. [Wang, Dengshun] Univ Wisconsin, Madison, WI USA. RP Antin, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2011 VL 1 IS 1 BP I EP I PG 1 WC Oncology SC Oncology GA V30ZL UT WOS:000208853800001 ER PT J AU Dawson, MR Chae, SS Jain, RK Duda, DG AF Dawson, Michelle R. Chae, Sung-Suk Jain, Rakesh K. Duda, Dan G. TI Direct evidence for lineage-dependent effects of bone marrow stromal cells on tumor progression SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Myeloid; mesenchymal; bone marrow-derived cells; tumor; metastasis AB We sought to characterize the function of bone marrow stromal cell (BMSC) populations in tumor progression. Because this function may depend on the cell-lineage and mouse strain heterogeneity, we first characterized ex vivo the BMSCs harvested from C57BL/6 versus FVB mice and established their in vivo function in tumor growth and metastasis experiments. All plastic-adherent BMSCs expressed platelet-derived growth factor receptor beta (PDGFR beta) and stem cell antigen 1 (Sca1), consistent with a mesenchymal precursor phenotype, as well as CD80. Moreover, these BMSCs were capable of differentiation along mesenchymal lineage into adipocytes, osteoblasts, chondrocytes or myofibroblasts. However, further phenotypic analysis detected a distinct populations of myeloid (CD11b(+)) precursor cells amongst the ex vivo expanded BMSCs -with specific surface marker phenotypes and gene expression pattern. When co-implanted with metastatic cancer cells, all the BMSCs persisted and integrated into tumor stroma, but only myeloid BMSCs significantly promoted tumor growth and metastasis. These data demonstrate the differential effect of BMSCs sub-populations on tumor progression. These results may have important implications for anti-tumor therapy and for the use of mesenchymal BMSCs as cell-based therapies. C1 [Dawson, Michelle R.; Chae, Sung-Suk; Jain, Rakesh K.; Duda, Dan G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Steele Lab Tumor Biol, Boston, MA USA. RP Duda, DG (reprint author), Massachusetts Gen Hosp, Steele Lab, 100 Blossom St,Cox 734, Boston, MA 02114 USA. EM duda@steele.mgh.harvard.edu FU National Cancer Institute [P01-CA80124, R01-CA115767, R01-CA85140, R01-CA126642, T32-CA73479]; Federal Share Proton Beam Program [R21-CA139168]; ACS [RSG-11-073-01TBG]; Spiro Research Awards FX We wish to acknowledge the outstanding technical assistance of J Kahn, S Roberge and P Huang with animal models, and the statistical support from M Ancukiewicz. Grant support: National Cancer Institute grants P01-CA80124, R01-CA115767, R01-CA85140, R01-CA126642 and T32-CA73479 (RKJ), Federal Share Proton Beam Program grants (RKJ and DGD), and R21-CA139168 (DGD), and ACS grant RSG-11-073-01TBG and Spiro Research Awards (DGD). NR 23 TC 23 Z9 23 U1 0 U2 2 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2011 VL 1 IS 2 BP 144 EP 154 PG 11 WC Oncology SC Oncology GA V30ZM UT WOS:000208853900002 PM 21822499 ER PT J AU Ahmadi, N Nabavi, V Hajsadeghi, F Flores, F French, WJ Mao, SS Shavelle, D Ebrahimi, R Budoff, M AF Ahmadi, Naser Nabavi, Vahid Hajsadeghi, Fereshteh Flores, Ferdinand French, William J. Mao, Song S. Shavelle, David Ebrahimi, Ramin Budoff, Matthew TI Mortality Incidence of Patients With Non-Obstructive Coronary Artery Disease Diagnosed by Computed Tomography Angiography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HISTOLOGY INTRAVASCULAR ULTRASOUND; ACUTE MYOCARDIAL-INFARCTION; CLINICAL PRESENTATION; PLAQUE COMPOSITION; VULNERABLE PLAQUE; PROGNOSTIC VALUE; ATHEROSCLEROSIS; SEVERITY; LESIONS; QUANTIFICATION AB It was previously reported that event-free survival rates of symptomatic patients with coronary artery disease (CAD) diagnosed by computed tomographic angiography decreased incrementally from normal coronary arteries to obstructive CAD. The aim of this study was to investigate the clinical outcomes of symptomatic patients with nonobstructive CAD with luminal stenoses of 1% to 49% on the basis of coronary plaque morphology in an outpatient setting. Among 3,499 consecutive symptomatic subjects who underwent computed tomographic angiography, 1,102 subjects with nonobstructive CAD (mean age 59 +/- 14 years, 69.9% men) were prospectively followed for a mean of 78 +/- 12 months. Coronary plaques were defined as noncalcified, mixed, and calcified per patient. Multivariate Cox proportional-hazards models were developed to predict all-cause mortality. The death rate of patients with nonobstructive CAD was 3.1% (34 deaths). The death rate increased incrementally from calcified plaque (1.4%) to mixed plaque (3.3%) to noncalcified plaque (9.6%), as well as from single- to triple-vessel disease (p < 0.001). In subjects with mixed or calcified plaques, the death rate increased with the severity of coronary artery calcium from 1 to 9 to >= 400. The risk-adjusted hazard ratios of all-cause mortality in patients with nonobstructive CAD were 3.2 (95% confidence interval 1.3 to 8.0, p = 0.001) for mixed plaques and 7.4 (95% confidence interval 2.7 to 20.1, p = 0.0001) for noncalcified plaques compared with calcified plaques. The areas under the receiver-operating characteristic curve to predict all-cause mortality were 0.75 for mixed and 0.86 for noncalcified coronary lesions. In conclusion, this study demonstrates that the presence of noncalcified and mixed coronary plaques provided incremental value in predicting all-cause mortality in symptomatic subjects with nonobstructive CAD independent of age, gender, and conventional risk factors. (c) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:10-16) C1 [Ahmadi, Naser; Nabavi, Vahid; Hajsadeghi, Fereshteh; Flores, Ferdinand; French, William J.; Mao, Song S.; Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Ebrahimi, Ramin] Univ Calif Los Angeles, Sch Med, Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. [Ahmadi, Naser; Shavelle, David] Univ So Calif, Los Angeles, CA USA. RP Budoff, M (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. EM mbudoff@labiomed.org NR 27 TC 43 Z9 43 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2011 VL 107 IS 1 BP 10 EP 16 DI 10.1016/j.amjcard.2010.08.034 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 705KI UT WOS:000286126900003 PM 21146679 ER PT J AU Kimball, AB Bensimon, AG Guerin, A Yu, AP Wu, EQ Okun, MM Bao, YJ Gupta, SR Mulani, PM AF Kimball, Alexa B. Bensimon, Arielle G. Guerin, Annie Yu, Andrew P. Wu, Eric Q. Okun, Martin M. Bao, Yanjun Gupta, Shiraz R. Mulani, Parvez M. TI Efficacy and Safety of Adalimumab among Patients with Moderate to Severe Psoriasis with Co-Morbidities Subanalysis of Results from a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial SO AMERICAN JOURNAL OF CLINICAL DERMATOLOGY LA English DT Article ID QUALITY-OF-LIFE; SEVERE PLAQUE PSORIASIS; REPORTED OUTCOMES; COMORBIDITIES; IMPACT; ARTHRITIS; EPIDEMIOLOGY; DEPRESSION; CONSENSUS AB Background: Psoriasis is associated with a variety of major physical and mental co-morbidities. Objective: To assess the incremental burden of co-morbidities on patient-reported outcomes and evaluate the efficacy and safety of adalimumab in psoriasis patients with co-morbidities. Study Design: Data were obtained from the initial 16-week, double-blind treatment period of REVEAL (Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis triAL), a randomized, multicenter, phase III clinical trial. Intervention: Patients with moderate to severe psoriasis were randomized in a 2:1 ratio to receive adalimumab 80 mg (two 40 mg injections administered subcutaneously) at baseline followed by one 40 mg injection every other week from week 1 to week 15 or placebo. Main Outcome Measures: Clinical severity (Psoriasis Area and Severity Index [PAST]) and patient-reported outcomes (Dermatology Life Quality Index [DLQI], Short Form 36 [SF-36] health survey, Work Productivity and Activity Impairment [WPAI] questionnaire) were assessed during the trial. The effect of selected co-morbidities (i.e. hypertension, psoriatic arthritis, hyperlipidemia, obesity, depression, other forms of arthritis, diabetes mellitus, and other cardiovascular diseases) on patient-reported outcomes was evaluated using multivariate analysis of covariance models. Subgroup analyses were performed by comorbidity type to statistically compare the clinical efficacy, patient-reported outcome benefits, and safety of adalimumab with placebo in the presence of these conditions. Results: Study co-morbidities were each independently associated with significantly greater impairment on at least one general patient-reported outcome measured at baseline (all p<0.05), with the exception of hyperlipidemia. During the 16-week study, adalimumab patients demonstrated significantly greater PAST 75 response rates (defined as a reduction of at least 75% in PAST scores from baseline) compared with placebo patients for all co-morbidity subgroups. Adalimumab provided consistent improvements in DLQI, SF-36 Physical Component Summary and Mental Component Summary scores, and WPAI total scores from baseline to week 16 within comorbidity subgroups. Rates of serious adverse events (AEs), serious infectious AEs, and AEs leading to discontinuation were comparable between adalimumab and placebo for patients with co-morbidities. Conclusions: Co-morbidities were associated with additionally impaired health-related quality of life and work productivity in patients with psoriasis. Adalimumab significantly improved efficacy and patient-reported outcomes and was well tolerated in patients with co-morbidities. C1 [Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bensimon, Arielle G.; Guerin, Annie; Yu, Andrew P.; Wu, Eric Q.] Anal Grp, Boston, MA USA. [Okun, Martin M.; Bao, Yanjun; Gupta, Shiraz R.; Mulani, Parvez M.] Abbott Labs, Abbott Pk, IL 60064 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Abbott Laboratories FX This analysis was funded by Abbott Laboratories. Alexa Kimball is an investigator and consultant for Abbott, Amgen, and Centocor, and Arielle Bensimon, Annie Guerin, Andrew Yu, and Eric Wu are employees of Analysis Group, Inc., an organization contracted by Abbott Laboratories to perform this analysis. Martin Okun, Yanjun Bao, and Parvez Mulani are employees of Abbott Laboratories and own stock and/or stock options in Abbott Laboratories. Shiraz Gupta is a former employee of Abbott Laboratories. Arbor Communications, Inc. provided editorial assistance on behalf of Abbott Laboratories. NR 25 TC 22 Z9 23 U1 2 U2 8 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-0561 J9 AM J CLIN DERMATOL JI Am. J. Clin. Dermatol. PY 2011 VL 12 IS 1 BP 51 EP 62 DI 10.2165/11530640-000000000-00000 PG 12 WC Dermatology SC Dermatology GA 697RO UT WOS:000285534000006 PM 21110526 ER PT J AU Choi, KM Yannakoulia, M Park, MS Cho, GJ Kim, JH Lee, SH Hwang, TG Yang, SJ Kim, TN Yoo, HJ Baik, SH Kim, SM Mantzoros, CS AF Choi, Kyung M. Yannakoulia, Mary Park, Min S. Cho, Geum J. Kim, Jung H. Lee, Seung H. Hwang, Taik G. Yang, Sei J. Kim, Tai N. Yoo, Hye J. Baik, Sai H. Kim, Seon M. Mantzoros, Christos S. TI Serum adipocyte fatty acid-binding protein, retinol-binding protein 4, and adiponectin concentrations in relation to the development of the metabolic syndrome in Korean boys: a 3-y prospective cohort study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; INSULIN-RESISTANCE; OBESE CHILDREN; CHILDHOOD OBESITY; ADOLESCENTS; RETINOL-BINDING-PROTEIN-4; OVERWEIGHT; INFLAMMATION; WOMEN; AP2 AB Background: Adipocyte fatty acid-binding protein (A-FABP), retinol-binding protein 4 (RBP4), and adiponectin have been associated with insulin resistance and the metabolic syndrome in adults. Objective: We evaluated the association of A-FABP, RBP4, and adiponectin with the metabolic syndrome in Korean boys. Design: In this prospective cohort study, 159 boys participated in a school-based health examination and were followed up after 3 y. The metabolic syndrome in children was defined by using the pediatric adaptation of the National Cholesterol Education Program criteria. Results: Compared with normal-weight participants, overweight children had significantly higher A-FABP (23.6 +/- 8.2 compared with 12.8 +/- 5.1 mu g/L, P<0.001) and RBP4 (69.3 +/- 17.1 compared with 59.7 +/- 15.3 mu g/mL, P = 0.001) concentrations and significantly lower adiponectin concentrations (11.5 +/- 5.4 compared with 18.1 +/- 8.4 mu g/mL, P<0.001). Baseline A-FABP concentrations were significantly higher in children who developed the metabolic syndrome than in those who did not, whereas adiponectin concentrations were significantly lower. Baseline RBP4 concentrations were not significantly different between the 2 groups. Multiple logistic regression analysis showed that only A-FABP was an independent predictor of the development of the metabolic syndrome after adjustment for Tanner stage, insulin resistance, body mass index, sleep duration, and physical activity (odds ratio: 17.3; 95% CI: 1.25, 239.76; highest compared with lowest tertile), whereas the significant association between adiponectin and the metabolic syndrome observed by using bivariate analysis reflects, in part, an underlying association with obesity. Conclusion: A-FABP predicts the development of the metabolic syndrome independently of pubertal status, adiposity, and insulin resistance in Korean boys. Am J Clin Nutr 2011;93:19-26. C1 [Choi, Kyung M.; Kim, Tai N.; Yoo, Hye J.; Baik, Sai H.] Korea Univ, Coll Med, Dept Internal Med, Div Endocrinol & Metab, Seoul 136705, South Korea. [Yannakoulia, Mary; Kim, Seon M.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Park, Min S.] Korea Univ, Coll Med, Dept Biostat, Seoul 136705, South Korea. [Cho, Geum J.; Hwang, Taik G.] Guro Gu Publ Hlth Ctr, Seoul, South Korea. [Kim, Jung H.] Eulji Hosp, Dept Family Med, Seoul, South Korea. [Lee, Seung H.; Kim, Seon M.] Korea Univ, Coll Med, Dept Family Med, Seoul 136705, South Korea. [Yannakoulia, Mary] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Publ Hlth, Beth Israel & Deaconess Med Ctr, Med Sch,Div Endocrinol Diabet & Metab, 330 Brookline Ave, Boston, MA 02215 USA. EM ksmpdh@korea.ac.kr; cmantzor@bidmc.harvard.edu FU Korean government [R01-2007-000-20546-0]; Beth Israel Deaconess Medical Center [10526]; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases [DK58785, DK79929, DK81913, AG032030]; Beth Israel Deaconess Medical Center FX Supported by the Seoul R&BD Program, the Korea Science and Engineering Foundation (grant no. R01-2007-000-20546-0 from the Korean government to KMC), the Korean Seoul City Research and Business Development Program (grant no. 10526 to SMK), a discretionary grant from Beth Israel Deaconess Medical Center, and the National Institutes of Health (DK58785, DK79929, DK81913, and AG032030). The Mantzoros Laboratory is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grants DK58785, DK79929, DK81913, and AG032030) and by a discretionary grant from Beth Israel Deaconess Medical Center (to CSM). NR 48 TC 32 Z9 36 U1 2 U2 10 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2011 VL 93 IS 1 BP 19 EP 26 DI 10.3945/ajcn.2010.29667 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 696PJ UT WOS:000285453500005 PM 21106915 ER PT J AU Kim, JY Dzik, WH Dighe, AS Lewandrowski, KB AF Kim, Ji Yeon Dzik, Walter H. Dighe, Anand S. Lewandrowski, Kent B. TI Utilization Management in a Large Urban Academic Medical Center A 10-Year Experience SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Utilization management; Cost containment; Intervention; Laboratory test; Blood components ID GEOGRAPHIC-VARIATION; LABORATORY MEDICINE; COST; CARE; PHYSICIANS; TESTS; RATES; RATIONALE; HOSPITALS; SERVICES AB Management of laboratory test utilization presents an ongoing challenge. Most studies reported in the literature have described efforts to control one or a few tests, but the results cannot be generalized to a broader utilization management strategy. Herein we report our experiences with an organizational utilization management program during a 10-year period. Cumulatively, our program has achieved significant success, saving millions of dollars in blood components and reducing inpatient tests per discharge by 26%. Highlights from our experiences include the importance of implementing an institutional organizational structure to support utilization management, the central role fulfilled by clinical pathologists as leaders of the program, the ability to obtain timely utilization data, and careful selection of the most appropriate implementation tools tailored to the unique circumstances of each utilization management initiative. C1 [Lewandrowski, Kent B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Gray 5 Chem, Boston, MA 02114 USA. NR 44 TC 48 Z9 48 U1 1 U2 3 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2011 VL 135 IS 1 BP 108 EP 118 DI 10.1309/AJCP4GS7KSBDBACF PG 11 WC Pathology SC Pathology GA 697TB UT WOS:000285538700014 PM 21173132 ER PT J AU Roh, MH Jo, VY Stelow, EB Faquin, WC Zou, KH Alexander, EK Larsen, PR Marqusee, E Benson, CB Frates, MC Gawande, A Moore, FD Cibas, ES AF Roh, Michael H. Jo, Vickie Y. Stelow, Edward B. Faquin, William C. Zou, Kelly H. Alexander, Erik K. Larsen, P. Reed Marqusee, Ellen Benson, Carol B. Frates, Mary C. Gawande, Atul Moore, Francis D., Jr. Cibas, Edmund S. TI The Predictive Value of the Fine-Needle Aspiration Diagnosis "Suspicious for a Follicular Neoplasm, Hurthle Cell Type" in Patients With Hashimoto Thyroiditis SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Thyroid; Fine-needle aspiration; Hurthle; Follicular neoplasm; Atypia of undetermined significance; Cytology Hashimoto thyroiditis; Lymphocytic thyroiditis ID CANCER; CARCINOMA; LESIONS; GLAND; MALIGNANCY; BIOPSY; TUMORS; RISK AB A fine-needle aspiration sample composed exclusively of Hurthle cells is interpreted as "suspicious for a follicular neoplasm, Hurthle cell type" (SFNHCT). Because some nonneoplastic Hurthle cell proliferations in Hashimoto thyroiditis (HT) mimic this cytologic pattern, we examined the positive predictive value (PPV) for malignancy of SFNHCT in patients with HT Between 1992 and 2007, 401 patients with cytologic findings of SFNHCT were identified at 3 institutions. Histologic follow-up was available for 287 (71.6%), and malignancy was diagnosed in 69 (24.0%). Malignancy was present in 2 (PPV = 9.5%) of 21 patients with HT compared with 67 (PPV = 25.2%) of 266 patients without HT (P = .081). Although the difference in the rate of malignancy between the HT and non-HT cohorts did not reach statistical significance, the lower risk of malignancy in the HT cohort more closely approximates the risk of cases interpreted as "atypia of undetermined significance." For this reason, it might be appropriate for Hurthle cell-only aspirates from patients with HT to be categorized as either atypia of undetermined significance or SFNHCT. C1 [Roh, Michael H.] Univ Michigan, Dept Pathol, Sch Med, Ann Arbor, MI 48109 USA. [Jo, Vickie Y.; Stelow, Edward B.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Faquin, William C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faquin, William C.; Cibas, Edmund S.] Harvard Univ, Sch Med, Boston, MA USA. [Zou, Kelly H.] Pfizer, Specialty Care Business Unit, New York, NY USA. [Alexander, Erik K.; Larsen, P. Reed; Marqusee, Ellen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Benson, Carol B.; Frates, Mary C.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Gawande, Atul; Moore, Francis D., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Cibas, Edmund S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Roh, MH (reprint author), Univ Michigan, Dept Pathol, Sch Med, 2G332 UH,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. OI Gawande, Atul/0000-0002-1824-9176 FU NIDDK NIH HHS [R01 DK036256] NR 22 TC 19 Z9 19 U1 0 U2 6 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 2011 VL 135 IS 1 BP 139 EP 145 DI 10.1309/AJCP0RW2WMDUAKGK PG 7 WC Pathology SC Pathology GA 697TB UT WOS:000285538700018 PM 21173136 ER PT J AU Sonnenberg, A Faigel, DO AF Sonnenberg, Amnon Faigel, Douglas O. TI The Endoscopist's Influence on Endoscopic Test Characteristics SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. [Faigel, Douglas O.] Mayo Clin, Scottsdale, AZ USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 7 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2011 VL 106 IS 1 BP 10 EP 13 DI 10.1038/ajg.2010.297 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 717CS UT WOS:000287021200004 PM 21212751 ER PT J AU Farzanfar, R Locke, SE Heeren, TC Stevens, A Vachon, L Nguyen, MKT Friedman, RH AF Farzanfar, Ramesh Locke, Steven E. Heeren, Timothy C. Stevens, Allison Vachon, Louis Mai Khoa Thi Nguyen Friedman, Robert H. TI Workplace Telecommunications Technology to Identify Mental Health Disorders and Facilitate Self-Help or Professional Referrals SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Automated Mental Health Assessment; Workplace Mental Health Assessment; Computers in Mental Health Assessment; Behavioral Telehealth; Prevention Research ID WELL-BEING INDEX; TELEPHONE INTERVIEW; RATING-SCALE; PRIMARY-CARE; COMPUTER; REPLICATION; VALIDATION; OUTCOMES; STRESS; IMPACT AB Purpose. Test the feasibility and impact of an automated workplace mental health assessment and intervention. Design. Efficacy was evaluated in a randomized control trial comparing employees who received screening and intervention with those who received only screening. Setting. Workplace. Subjects. 463 volunteers from Boston Medical Center, Boston University, and EMC and other employed adults, among whom 164 were randomized to the intervention (N = 87) and control (N = 77) groups. Intervention. The system administers a panel of telephonic assessment instruments followed by tailored information, education, and referrals. Measures. The Work Limitation Questionnaire, the Medical Outcomes Questionnaire Short Form-12, the Patient Health Questionnaire-9, question 10 from the Patient Health Questionnaire to measure functional impairment, and the Perceived Stress Scale-4 and questions written by study psychiatrists to measure emotional (listless and social support respectively. The WHO-Five Well-being Index was administered to measure overall well-being. Analysis. Independent sample Nests and chi(2) tests as well as mean change were used to compare the data. Results. No significant differences on 16 of the 20 comparisons at 3- and 6-month time points. The intervention group showed a significant improvement in depression (p <= .05) at 3 months and on two Work Limitation Questionnaire subscales, the Mental-Interpersonal Scale (p <= .05) and the Time and Scheduling Scale (p <= .05), at 3 and 6 months respectively with a suggestive improvement in mental health at 6 months (p <= .10). Conclusions. This is a potentially fruitful area for research with important implications for workplace behavioral interventions. (Am J Health Promot. 2011;25[3]:207-216.) C1 [Farzanfar, Ramesh] Boston Univ, Med Ctr, Sch Med, Med Informat Syst Unit, Boston, MA 02118 USA. [Locke, Steven E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Heeren, Timothy C.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Stevens, Allison; Mai Khoa Thi Nguyen] Massachusetts Gen Hosp, Charlestown, MA USA. [Vachon, Louis] Boston Univ, Sch Med, Boston, MA 02118 USA. [Friedman, Robert H.] Boston Univ, Med Informat Syst Unit, Boston, MA 02215 USA. [Friedman, Robert H.] Boston Med Ctr, Boston, MA USA. RP Farzanfar, R (reprint author), Boston Univ, Med Ctr, Sch Med, Med Informat Syst Unit, 801 Massachusetts Ave,2nd Floor, Boston, MA 02118 USA. EM rfarzanf@bu.du OI Friedman, Robert/0000-0002-9440-2443; Heeren, Timothy/0000-0001-5643-3559 FU NCCDPHP CDC HHS [R01 DP000116] NR 39 TC 5 Z9 5 U1 0 U2 7 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JAN-FEB PY 2011 VL 25 IS 3 BP 207 EP 216 DI 10.4278/ajhp.100118-QUAN-14 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 714EM UT WOS:000286790300010 PM 21192751 ER PT J AU Ashby, DM McMahon, PO AF Ashby, Daniel M. McMahon, Patrick O. TI Need for changes, in the residency practice model SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 [Ashby, Daniel M.; McMahon, Patrick O.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [McMahon, Patrick O.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ashby, DM (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Carnegie 180, Baltimore, MD 21287 USA. EM dashby@jhmi.edu NR 6 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JAN 1 PY 2011 VL 68 IS 1 BP 19 EP 19 DI 10.2146/ajhp100374 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858BZ UT WOS:000297772200005 PM 21164061 ER PT J AU Njoroge, JN El Khoudary, SR Fried, LF Barinas-Mitchell, E Sutton-Tyrrell, K AF Njoroge, Jennifer N. El Khoudary, Samar R. Fried, Linda F. Barinas-Mitchell, Emma Sutton-Tyrrell, Kim TI High Urinary Sodium Is Associated With Increased Carotid Intima-Media Thickness in Normotensive Overweight and Obese Adults SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; carotid IMT; hypertension; obesity; sodium; vascular remodeling ID DENSITY-LIPOPROTEIN CHOLESTEROL; LARGE ARTERY STRUCTURE; HIGH-SALT DIET; BLOOD-PRESSURE; HYPERTENSION; WOMEN; SERUM; MEN; DISTENSIBILITY; INTERSALT AB BACKGROUND Increased dietary sodium has been reported to increase cardiovascular disease (CVD) risk, perhaps through blood pressure (BP)-independent vascular remodeling. Carotid intima-media thickness (IMT) is an accepted measure of structural vascular remodeling and a strong predictor of CVD. This study aimed to determine whether urinary sodium is positively associated with carotid IMT in normotensive overweight and obese adults. METHODS We evaluated baseline data from 258 participants in the Slow Adverse Vascular Effects (SAVE) clinical trial. Urinary sodium was measured from one 24-h urine collection from each individual. Carotid IMT was measured using high-resolution B-mode ultrasonography. Participants were categorized into quartiles of urinary sodium. RESULTS There was a significant positive trend with greater IMT associated with increasing urinary sodium quartile in univariate linear regression (P = 0.047). This trend was significant when adjusting for age, sex, race, and systolic BP (SBP) (P = 0.03) as well as in a fully adjusted model (P = 0.04). In pairwise comparisons, the highest urinary sodium quartile had a significantly greater mean IMT (0.62 mm) than the lowest urinary sodium quartile (0.59 mm) after adjustment for age, sex, race, and SBP (P = 0.04). This comparison lost significance after the addition of BMI. CONCLUSIONS In our community-based sample of normotensive overweight and obese adults, we observed a significant positive trend in carotid IMT with increasing quartile of urinary sodium. If the ongoing clinical trial confirms this relationship between sodium and carotid IMT, it would lend support to efforts to decrease sodium intake in overweight and obese individuals. C1 [Njoroge, Jennifer N.; El Khoudary, Samar R.; Fried, Linda F.; Barinas-Mitchell, Emma; Sutton-Tyrrell, Kim] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Univ Dr Div, Pittsburgh, PA USA. RP Sutton-Tyrrell, K (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. EM Tyrrell@edc.pitt.edu OI El Khoudary Abushaban, Samar/0000-0003-2913-0821; Barinas-Mitchell, Emma/0000-0002-7280-7781 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01 HL077525-01A2, T32 HL083825-01] FX This independent investigator-promoted research was supported by grants R01 HL077525-01A2 and T32 HL083825-01 from the National Heart, Lung, and Blood Institute of the National Institutes of Health. We acknowledge Janice Sabatine, Avanti Strategies, Cranberry Township, Pennsylvania, for writing and editing assistance. NR 36 TC 18 Z9 20 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2011 VL 24 IS 1 BP 70 EP 76 DI 10.1038/ajh.2010.113 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 697GS UT WOS:000285501800012 PM 20508622 ER PT J AU Cherniack, M Henning, R Merchant, JA Punnett, L Sorensen, GR Wagner, G AF Cherniack, Martin Henning, Rob Merchant, James A. Punnett, Laura Sorensen, Glorian R. Wagner, Gregory TI Statement on National WorkLife Priorities SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Editorial Material DE WorkLife Initiative; employee health; health promotion; occupational health; workplace; health policy ID HEALTH PROMOTION PROGRAMS; FINANCIAL IMPACT; BEHAVIOR-CHANGE; OCCUPATIONAL-HEALTH; PHYSICAL-ACTIVITY; INTERVENTION; TRIALS; SAFETY; JOB; DIRECTIONS AB The National Institute for Occupational Safety and Health (NIOSH) WorkLife Initiative (WLI) [http://www. cdc. gov/niosh/worklife] seeks to promote workplace programs, policies, and practices that result in healthier, more productive employees through a focus simultaneously on disease prevention, health promotion, and accommodations to age, family, and life stage. The Initiative incorporates the Institute's foundational commitment to workplaces free of recognized hazards into broader consideration of the factors that affect worker health and wellbeing. Workplace hazards, such as physical demands, chemical exposures, and work organization, often interact with non-work factors such as family demands and health behaviors to increase health and safety risks. New workplace interventions being tested by the first three NIOSH WLI Centers of WorkLife Excellence are exploring innovative models for employee health programs to reduce the human, social, and economic costs of compromised health and quality of life. Many parties in industry, labor, and government share the goals of improving employee health while controlling health care costs. NIOSH convened a workshop in 2008 with representatives of the three Centers of Excellence to develop a comprehensive, long-range strategy for advancing the WorkLife Initiative. The recommendations below fall into three areas: practice, research, and policy. Responding to these recommendations would permit the WorkLife Center system to establish a new infrastructure for workplace prevention programs by compiling and disseminating the innovative practices being developed and tested at the Centers, and elsewhere. The WLI would also extend the customary scope of NIOSH by engaging with multiple NIH Institutes that are already generating research-topractice programs involving the working-age population, in areas such as chronic disease prevention and management. Research to Practice (r2p) is a concept focused on the translation of research findings, technologies, and information into evidence-based prevention practices and products that are adopted in the workplace or other "real-world'' settings. NIOSH's goal is to overcome the translational issues that now prevent state-of-the-art occupational health, health promotion, and chronic disease research findings from benefiting working age populations immediately, regardless of workplace size, work sector, or region of the country. Am. J. Ind. Med. 54: 10-20, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Punnett, Laura] Univ Massachusetts, Dept Work Environm, Lowell, MA 01854 USA. [Punnett, Laura] Univ Massachusetts, Ctr Women & Work, Lowell, MA 01854 USA. [Cherniack, Martin] Univ Connecticut, Ctr Hlth, Ergon Technol Ctr, Farmington, CT USA. [Henning, Rob] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Merchant, James A.] Univ Iowa, Dept Occupat & Environm Hlth, Iowa City, IA USA. [Merchant, James A.] Univ Iowa, HealthierWorkforce Ctr Excellence, Iowa City, IA USA. [Sorensen, Glorian R.] Harvard Univ, Sch Publ Hlth, Ctr Work Hlth & Wellbeing, Boston, MA 02115 USA. [Sorensen, Glorian R.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Wagner, Gregory] NIOSH, Washington, DC USA. RP Punnett, L (reprint author), Univ Massachusetts, Dept Work Environm, 1 Univ Ave, Lowell, MA 01854 USA. EM laura_punnett@uml.edu OI Punnett, Laura/0000-0001-9270-9946 FU NIOSH CDC HHS [U19 OH008861, 1U19 OH008857, 1U19 OH008868, 3U19 OH008861] NR 51 TC 10 Z9 10 U1 6 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JAN PY 2011 VL 54 IS 1 BP 10 EP 20 DI 10.1002/ajim.20900 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 693FX UT WOS:000285211100002 PM 20949545 ER PT J AU Milunsky, JM Maher, TM Zhao, GP Wang, ZY Mulliken, JB Chitayat, D Clemens, M Stalker, HJ Bauer, M Burch, M Chenier, S Cunningham, ML Drack, AV Janssens, S Karlea, A Klatt, R Kini, U Klein, O Lachmeijer, AM Megarbane, A Mendelsohn, NJ Meschino, WS Mortier, GR Parkash, S Ray, CR Roberts, A Roberts, A Reardon, W Schnur, RE Smith, R Splitt, M Tezcan, K Whiteford, ML Wong, DA Zori, R Lin, AE AF Milunsky, Jeff M. Maher, Tom M. Zhao, Geping Wang, Zhenyuan Mulliken, John B. Chitayat, David Clemens, Michele Stalker, Heather J. Bauer, Mislen Burch, Michele Chenier, Sebastien Cunningham, Michael L. Drack, Arlene V. Janssens, Sandra Karlea, Audrey Klatt, Regan Kini, Usha Klein, Ophir Lachmeijer, Augusta M. Megarbane, Andre Mendelsohn, Nancy J. Meschino, Wendy S. Mortier, Geert R. Parkash, Sandhya Ray, C. Renai Roberts, Angharad Roberts, Amy Reardon, Willie Schnur, Rhonda E. Smith, Rosemarie Splitt, Miranda Tezcan, Kamer Whiteford, Margo L. Wong, Derek A. Zori, Roberto Lin, Angela E. TI Genotype-Phenotype Analysis of the Branchio-Oculo-Facial Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE branchio-oculo-facial syndrome; cleft lip/palate; mutation analysis; neurocristopathy; TFAP2A ID CHARGE SYNDROME; INTERSTITIAL DELETION; MOLECULAR ANALYSES; INNER-EAR; TFAP2A; PATIENT; AP-2 AB Branchio-oculo-facial syndrome (BOFS; OMIM# 113620) is a rare autosomal dominant craniofacial disorder with variable expression. Major features include cutaneous and ocular abnormalities, characteristic facies, renal, ectodermal, and temporal bone anomalies. Having determined that mutations involving TFAP2A result in BOFS, we studied a total of 30 families (41 affected individuals); 26/30 (87%) fulfilled our cardinal diagnostic criteria. The original family with the 3.2Mb deletion including the TFAP2A gene remains the only BOFS family without the typical CL/P and the only family with a deletion. We have identified a hotspot region in the highly conserved exons 4 and 5 of TFAP2A that harbors missense mutations in 27/30 (90%) families. Several of these mutations are recurrent. Mosaicism was detected in one family. To date, genetic heterogeneity has not been observed. Although the cardinal criteria for BOFS have been based on the presence of each of the core defects, an affected family member or thymic remnant, we documented TFAP2A mutations in three (10%) probands in our series without a classic cervical cutaneous defect or ectopic thymus. Temporal bone anomalies were identified in 3/5 patients investigated. The occurrence of CL/P, premature graying, coloboma, heterochromiairides, and ectopic thymus, are evidence for BOFS as a neurocristopathy. Intrafamilial clinical variability can be marked. Although there does not appear to be mutation-specific genotype-phenotype correlations at this time, more patients need to be studied. Clinical testing for TFAP2A mutations is now available and will assist geneticists in confirming the typical cases or excluding the diagnosis in atypical cases. (C) 2010 Wiley-Liss, Inc. C1 [Milunsky, Jeff M.; Maher, Tom M.; Zhao, Geping; Wang, Zhenyuan] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA. [Milunsky, Jeff M.] BUSM, Dept Pediat Genet & Genom, Boston, MA USA. [Mulliken, John B.] Childrens Hosp, Dept Plast Surg, Boston, MA 02115 USA. [Chitayat, David; Klatt, Regan; Reardon, Willie] Hosp Sick Children, Dept Pediat, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Clemens, Michele] UPMC, Magee Womens Hosp, Dept Genet, Pittsburgh, PA USA. [Stalker, Heather J.; Burch, Michele; Zori, Roberto] Univ Florida, Dept Pediat, Div Genet, Gainesville, FL USA. [Bauer, Mislen] Miami Childrens Hosp, Div Genet & Metab, Miami, FL USA. [Chenier, Sebastien] CHU St Justine, Div Med Genet, Montreal, PQ, Canada. [Cunningham, Michael L.] Univ Washington, Dept Pediat, Seattle Childrens Craniofacial Ctr, Seattle, WA 98195 USA. [Drack, Arlene V.; Ray, C. Renai] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA. [Janssens, Sandra] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium. [Karlea, Audrey; Tezcan, Kamer] Kaiser Permanente, Dept Genet, Oakland, CA USA. [Kini, Usha] Churchill Hosp, Dept Clin Genet, Oxford OX3 7LJ, England. [Klein, Ophir] Univ Calif San Francisco, Dept Pediat, Div Med Genet, San Francisco, CA 94143 USA. [Lachmeijer, Augusta M.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet & Human Genet, Amsterdam, Netherlands. [Megarbane, Andre] St Joseph Univ, Med Genet Unit, Beirut, Lebanon. [Megarbane, Andre] Univ Aix Marseille 2, INSERM, UMR D910, Marseille, France. [Mendelsohn, Nancy J.] Childrens Hosp & Clin Minnesota, Dept Genet, Minneapolis, MN USA. [Meschino, Wendy S.] Univ Toronto, Dept Paediat, Genet Program, N York Gen Hosp, Toronto, ON M5S 1A1, Canada. [Mortier, Geert R.] Univ Antwerp Hosp, Dept Med Genet, Antwerp, Belgium. [Parkash, Sandhya] IWK Hlth Ctr, Maritime Med Genet Serv, Halifax, NS, Canada. [Roberts, Angharad] Univ London Imperial Coll Sci Technol & Med, London, England. [Roberts, Amy] Childrens Hosp, Cardiovasc Genet Program, Boston, MA 02115 USA. [Schnur, Rhonda E.] Cooper Univ Hosp, Div Genet, Dept Pediat, Robert Wood Johnson Med Sch, Camden, NJ USA. [Smith, Rosemarie] Maine Med Ctr, Div Genet, Dept Pediat, Portland, ME 04102 USA. [Splitt, Miranda] Int Ctr Life, No Genet Serv, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England. [Whiteford, Margo L.] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Wong, Derek A.] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA. [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA. RP Milunsky, JM (reprint author), Boston Univ, Sch Med, Ctr Human Genet, 700 Albany St,Room 408, Boston, MA 02118 USA. EM jmilunsk@bu.edu RI Mortier, Geert/D-2542-2012; OI Klein, Ophir/0000-0002-6254-7082; Wong, Derek/0000-0002-7762-2276 NR 23 TC 28 Z9 29 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2011 VL 155A IS 1 BP 22 EP 32 DI 10.1002/ajmg.a.33783 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 702IZ UT WOS:000285889100004 PM 21204207 ER PT J AU Crane, J Fagerness, J Osiecki, L Gunnell, B Stewart, SE Pauls, DL Scharf, JM AF Crane, Jacquelyn Fagerness, Jesen Osiecki, Lisa Gunnell, Boyd Stewart, S. Evelyn Pauls, David L. Scharf, Jeremiah M. CA Tourette Syndrome Int Consortium G TI Family-Based Genetic Association Study of DLGAP3 in Tourette Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE tic disorders; SAPAP3; gene; glutamate; trichotillomania ID OBSESSIVE-COMPULSIVE DISORDER; TRANSPORTER GENE; HAPLOTYPE; SLC1A1; OCD; TRICHOTILLOMANIA; EXPRESSION; SAPAP3; GENOME; SNPS AB Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder that is familial and highly heritable. Although genetic influences are thought to play a significant role in the development of TS, no definite TS susceptibility genes have been identified to date. TS is believed to be genetically related to both obsessive-compulsive disorder (OCD) and grooming disorders (GD) such as trichotillomania (TTM). SAP90/PSD95-associated protein 3 (SAPAP3/DLGAP3) is a post-synaptic scaffolding protein that is highly expressed in glutamatergic synapses in the striatum and has recently been investigated as a candidate gene in both OCD and GD studies. Given the shared familial relationship between TS, OCD and TTM, DLGAP3 was evaluated as a candidate TS susceptibility gene. In a family-based sample of 289 TS trios, 22 common single nucleotide polymorphisms (SNPs) in the DLGAP3 region were analyzed. Nominally significant associations were identified between TS and rs11264126 and two haplotypes containing rs11264126 and rs12141243. Secondary analyses demonstrated that these results cannot be explained by the presence of comorbid OCD or TTM in the sample. Although none of these results remained significant after correction for multiple hypothesis testing, DLGAP3 remains a promising candidate gene for TS. (C) 2010 Wiley-Liss, Inc. C1 [Crane, Jacquelyn; Fagerness, Jesen; Osiecki, Lisa; Gunnell, Boyd; Stewart, S. Evelyn; Pauls, David L.; Scharf, Jeremiah M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Crane, Jacquelyn; Fagerness, Jesen; Osiecki, Lisa; Gunnell, Boyd; Stewart, S. Evelyn; Pauls, David L.; Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Massachusetts Gen Hosp, Dept Neurol, Movement Disorders Unit, Boston, MA 02114 USA. [Scharf, Jeremiah M.] Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Tourette Syndrome Int Consortium G] Tourette Syndrome Assoc, Bayside, NY USA. RP Scharf, JM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Richard B Simches Res Bldg,185 Cambridge St,6th F, Boston, MA 02114 USA. EM jscharf@partners.org RI Citations, TLC SAB/C-4006-2011; Stewart, Evelyn/K-6961-2014; OI Barr, Cathy/0000-0003-0361-0106; Stewart, S. Evelyn/0000-0002-0994-6383 FU American Academy of Neurology Foundation; NIH [MH-085057, NS-40024, NS-16648]; Tourette Syndrome Association (TSA); TSAICG FX Grant sponsor: American Academy of Neurology Foundation; Grant sponsor: NIH; Grant numbers: MH-085057, NS-40024, NS-16648; Grant sponsor: Tourette Syndrome Association (TSA).; Members of the Tourette Syndrome Association International Consortium for Genetics (TSAICG), listed alphabetically by city: D. Cath and P. Heutink, Departments of Psychiatry and Human Genetics, Free University Medical Center, Amsterdam, The Netherlands; M. Grados, H. S. Singer, and J.T. Walkup, Departments of Psychiatry and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD; J.M. Scharf, C. Illmann, D. Yu, J. Platko, S. Santangelo, S. E. Stewart, and D. L. Pauls, Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital Harvard Medical School, Boston, MA; N.J. Cox, Departments of Medicine and Human Genetics, University of Chicago, Chicago, IL; S. Service, D. Keen-Kim, C. Sabatti, and N. Freimer, Departments of Psychiatry, Human Genetics and Statistics, U. C. L. A. Medical School, Los Angeles, CA; M. M. Robertson, Department of Mental Health Sciences, University College London, Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, England; G. A. Rouleau, J.-B. Riviere, S. Chouinard, F. Richer, P. Lesperance, and Y. Dion, University of Montreal, Montreal, Quebec, Canada; R. A. King, J. R. Kidd, A. J. Pakstis, J. F. Leckman, and K. K. Kidd, Department of Genetics and the Child Study Center, Yale University School of Medicine, New Haven, CT; R. Kurlan, P. Como, and D. Palumbo, Department of Neurology, University of Rochester School of Medicine, Rochester, NY; A. Verkerk, B. A. Oostra, Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands; W. McMahon, M. Leppert, and H. Coon, Departments of Psychiatry and Human Genetics, University of Utah School of Medicine, Salt Lake City, UT; C. Mathews, Department of Psychiatry, University of California, San Francisco, San Francisco, CA; P. Sandor and C. L. Barr, Department of Psychiatry, The Toronto Hospital and University of Toronto, Toronto, Ontario, Canada. The TSAICG is grateful to all the families with Gilles de la Tourette syndrome who generously agreed to be part of this study. Furthermore, the members of the Consortium are deeply indebted to the Tourette Syndrome Association and in particular to Ms. Judit Ungar, TSA president and Ms. Sue Levi-Pearl, TSA Director of Medical and Scientific Programs. Both have dedicated their professional lives to the understanding and treatment of Tourette syndrome. Without their support and guidance, this study would not have been possible. This work was supported by an American Academy of Neurology Foundation grant and NIH grant MH-085057 to J.M.S. as well as NIH grant NS-16648 to D. L. P. and NIH grant NS-40024 to D.L.P. and the TSAICG. NR 34 TC 33 Z9 34 U1 2 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN PY 2011 VL 156B IS 1 BP 108 EP 114 DI 10.1002/ajmg.b.31134 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 702JL UT WOS:000285890300014 PM 21184590 ER PT J AU Peralta, CA Katz, R Shlipak, M Dubin, R DeBoer, I Jenny, N Fitzpatrick, A Koro, C Kestenbaum, B Ix, J Sarnak, M Cushman, M AF Peralta, Carmen A. Katz, Ronit Shlipak, Michael Dubin, Ruth DeBoer, Ian Jenny, Nancy Fitzpatrick, Annette Koro, Carol Kestenbaum, Bryan Ix, Joachim Sarnak, Mark Cushman, Mary TI Kidney Function Decline in the Elderly: Impact of Lipoprotein-Associated Phospholipase A(2) SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Chronic kidney disease; Elderly; Estimated GFR; Kidney decline; Lipoprotein-associated phospholipase A(2) ID GLOMERULAR-FILTRATION-RATE; ACTIVATING-FACTOR ACETYLHYDROLASE; LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; SERUM CYSTATIN-C; RENAL-FUNCTION; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; OLDER-ADULTS; DYSFUNCTION AB Background: Whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with kidney function decline has not been well studied. Methods: We investigated associations of Lp-PLA(2) antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as >= 3 ml/min/1.73 m(2) per year. We stratified by baseline preserved GFR (>= 60 ml/min/1.73 m(2)). Results: Mean age was 72 +/- 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m(2) (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA(2) antigen, eGFRcys decline was faster among persons in the second, beta-0.31 (95% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles -0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp-PLA(2) antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA(2) activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m(2)) at baseline. Conclusion: Higher levels of Lp-PLA(2) antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression. Copyright (C) 2011 S. Karger AG, Basel C1 [Peralta, Carmen A.; Shlipak, Michael] San Francisco VA Med Ctr, San Francisco, CA USA. [Peralta, Carmen A.; Shlipak, Michael; Dubin, Ruth] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Katz, Ronit; DeBoer, Ian; Fitzpatrick, Annette; Kestenbaum, Bryan] Univ Washington, Seattle, WA 98195 USA. [Jenny, Nancy; Cushman, Mary] Univ Vermont, Coll Med, Burlington, VT USA. [Koro, Carol] GlaxoSmithKline Inc, Collegeville, PA USA. [Ix, Joachim] Univ Calif San Diego, La Jolla, CA 92093 USA. [Sarnak, Mark] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Peralta, CA (reprint author), 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu FU National Heart, Lung, and Blood Institute [U01 HL080295]; National Institute of Neurological Disorders and Stroke; GlaxoSmithKline (GSK); [N01-HC-85079]; [N01-HC-85086]; [N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222]; [N01-HC-75150]; [N01-HC-45133]; [RO1 AG 027002]; [K23SK082793] FX CHS is supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. This project is also supported by RO1 AG 027002 (Sarnak) and K23SK082793 (Peralta). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm.; This study is supported by a grant from GlaxoSmithKline (GSK). Dr. Koro is an employee at GSK. Drs. Peralta, Cushman, and Fitzpatrick have funding from GSK. The funding sources did not have a role in the design, analysis or approval of the manuscript. NR 35 TC 5 Z9 5 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2011 VL 34 IS 6 BP 512 EP 518 DI 10.1159/000333045 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 867XA UT WOS:000298486900004 PM 22056971 ER PT J AU Thadhani, R Appelbaum, E Chang, YC Pritchett, Y Bhan, I Agarwal, R Zoccali, C Wanner, C Lloyd-Jones, D Cannata, J Thompson, T Audhya, P Andress, D Zhang, WY Ye, J Packham, D Singh, B Zehnder, D Manning, WJ Pachika, A Solomon, SD AF Thadhani, Ravi Appelbaum, Evan Chang, Yuchiao Pritchett, Yili Bhan, Ishir Agarwal, Rajiv Zoccali, Carmine Wanner, Christoph Lloyd-Jones, Donald Cannata, Jorge Thompson, Taylor Audhya, Paul Andress, Dennis Zhang, Wuyan Ye, Jun Packham, David Singh, Bhupinder Zehnder, Daniel Manning, Warren J. Pachika, Ajay Solomon, Scott D. TI Vitamin D Receptor Activation and Left Ventricular Hypertrophy in Advanced Kidney Disease SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Chronic kidney disease; Left ventricular hypertrophy; Vitamin D receptor ID MAJOR CARDIOVASCULAR EVENTS; CARDIAC TROPONIN-T; HEMODIALYSIS-PATIENTS; PROGNOSTIC IMPLICATIONS; NATRIURETIC PEPTIDE; DIALYSIS PATIENTS; MAINTENANCE HEMODIALYSIS; DIASTOLIC DYSFUNCTION; STANDARDS COMMITTEE; OF-ECHOCARDIOGRAPHY AB Background: In chronic kidney disease (CKD), left ventricular hypertrophy (LVH) is prevalent and is associated with increased cardiovascular morbidity and mortality. Vitamin D receptor (VDR) activation attenuates LVH progression in animal models. Methods: PRIMO is a multinational, randomized, double-blinded trial with oral paricalcitol in subjects with stages 3-4 CKD, mild-to-moderate LVH and an LV ejection fraction > 50%. The primary endpoint is change in the left ventricular mass index (LVMI) compared with placebo after 48 weeks of treatment. The main secondary endpoints are changes in diastolic function parameters. In this paper, we report baseline characteristics from this study. Results: LVMI was 33.0 +/- 7.5 g/m(2.7) for males and 30.8 +/- 7.2 g/m(2.7) for females (p = 0.04). LVMI correlated with systolic blood pressure (r = 0.24), urine albumin creatinine ratio (r = 0.39), troponin T (r = 0.29), high-sensitivity C-reactive protein (r = 0.25) and plasma levels of B-type brain natriuretic peptide (r = 0.22); all p < 0.01. In multiple linear regression, each remained independently associated with LVMI. The early diastolic velocity of the lateral mitral annulus (E') was 8.1 +/- 2.4 cm/s. E' was inversely correlated with age in univariate (r = -0.14, p = 0.04) and multivariable (p = 0.02) analysis. Conclusion: Among 227 multinational subjects with stages 3-4 CKD, baseline LVMI correlates with baseline blood pressure, urine albumin creatinine ratio and cardiac biomarkers, and baseline diastolic function correlates with age. This research was funded by Abbott Laboratories; ClinicalTrials.gov No. NCT00497146. Copyright (C) 2011 S. Karger AG, Basel C1 [Thadhani, Ravi; Chang, Yuchiao; Bhan, Ishir; Thompson, Taylor; Ye, Jun] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Appelbaum, Evan; Manning, Warren J.] Harvard Univ, Sch Med, PERFUSE CMR Core Lab, Boston, MA USA. [Appelbaum, Evan; Manning, Warren J.] Harvard Univ, Sch Med, Div Cardiovasc, Beth Israel Deaconess Med Ctr,Dept Med, Boston, MA USA. [Pritchett, Yili; Audhya, Paul; Andress, Dennis; Zhang, Wuyan] Indiana Univ, Sch Med, Abbott Labs, Indianapolis, IN USA. [Agarwal, Rajiv] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. [Zoccali, Carmine] Nephrol Dialysis & Transplantat Unit, Reggio Di Calabria, Italy. [Zoccali, Carmine] CNR, IBIM Clin Epidemiol & Pathophysiol Renal Dis, Reggio Di Calabria, Italy. [Wanner, Christoph] Univ Wurzburg, Univ Hosp, Dept Med, Div Nephrol, Wurzburg, Germany. [Lloyd-Jones, Donald] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. [Cannata, Jorge] Univ Hosp, Cent Asturias, Serv Metab Oseo & Mineral, Oviedo, Spain. [Packham, David] Austin Hosp, Melbourne Renal Res Grp, Reservoir Private Hosp, Royal Melbourne Hosp,Dept Nephrol, Melbourne, Vic, Australia. [Singh, Bhupinder] SW Kidney Inst, Tempe, AZ USA. [Zehnder, Daniel] Univ Warwick, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Manning, Warren J.] Harvard Univ, Sch Med, Dept Radiol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Pachika, Ajay; Solomon, Scott D.] Harvard Univ, Sch Med, Div Cardiovasc, Brigham & Womens Hosp, Boston, MA USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Dept Med, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu RI Lloyd-Jones, Donald/C-5899-2009; Solomon, Scott/I-5789-2013; Cannata-Andia, Jorge/L-2260-2013; OI Zoccali, Carmine/0000-0002-6616-1996 FU Abbott Laboratories; Abbott FX R.T. is supported by a research grant from Abbott Laboratories. R.A. has received honoraria for serving on the speaker's bureau and steering committees of Abbott Laboratories. C.W. serves on an advisory board for Abbott and has received research support, speakers fees and travel support from Abbott. Y.P., P.A. and D.A. are employees of Abbott Laboratories. NR 64 TC 19 Z9 20 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2011 VL 33 IS 2 BP 139 EP 149 DI 10.1159/000323551 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 733CK UT WOS:000288237800006 PM 21242674 ER PT J AU Jotwani, V Scherzer, R Choi, A Szczech, L Polak, JF Kronmal, RA Grunfeld, C Shlipak, M AF Jotwani, Vasantha Scherzer, Rebecca Choi, Andy Szczech, Lynda Polak, Joseph F. Kronmal, Richard A. Grunfeld, Carl Shlipak, Michael TI Reduced Kidney Function and Preclinical Atherosclerosis in HIV-Infected Individuals: The Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Cystatin C; Intima-medial thickness; HIV; Atherosclerosis; Cardiovascular disease; Kidney ID ALL-CAUSE MORTALITY; CYSTATIN-C; CARDIOVASCULAR EVENTS; SERUM CREATININE; MEDIA THICKNESS; DISEASE; ASSOCIATION; INTIMA; ALBUMINURIA; OUTCOMES AB Background/Aims: Reduced kidney function and albuminuria are associated with higher risk for cardiovascular disease (CVD) and mortality in HIV-infected individuals. We investigated whether reduced estimated glomerular filtration rate (eGFR) and albuminuria are associated with subclinical vascular disease, as assessed by carotid intima-medial thickness (cIMT). Methods: Cross-sectional analysis of 476 HIV-infected individuals without clinical evidence of CVD enrolled in the Fat Redistribution and Metabolic Change in HIV infection (FRAM) study, using multivariable linear regression. eGFR(Cys) and eGFR(Cr) were calculated from cystatin C and creatinine levels. Albuminuria was defined as a positive urine dipstick (>= 1+) or urine albumin-to-creatinine ratio >= 30 mg/g. Common and internal cIMT were measured by high-resolution B-mode ultrasound. Results: In unadjusted analyses, eGFR(Cys) and eGFR(Cr) were strongly associated with common and internal cIMT. Each 10 ml/min/1.73 m(2) decrease in eGFR(Cys) and eGFR(cr), was associated with a 0.008 mm higher common cIMT (p = 0.003, p = 0.01) and a 0.024 and 0.029 mm higher internal cIMT (p = 0.003), respectively. These associations were eliminated after adjustment for age, gender, and race. Albuminuria showed little association with common or internal cIMT in all models. Conclusions: In HIV-infected individuals without prior CVD, reduced kidney function and albuminuria were not independently associated with subclinical vascular disease, as assessed by cIMT. These results suggest that research should focus on searching for novel mechanisms by which kidney disease confers cardiovascular risk in HIV-infected individuals. copyright (C) 2011 S. Karger AG, Basel C1 [Jotwani, Vasantha; Scherzer, Rebecca; Choi, Andy; Grunfeld, Carl; Shlipak, Michael] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Jotwani, Vasantha; Scherzer, Rebecca; Choi, Andy; Grunfeld, Carl; Shlipak, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Szczech, Lynda] Duke Univ, Med Ctr, Durham, NC USA. [Polak, Joseph F.] Tufts Med Ctr, Boston, MA USA. [Kronmal, Richard A.] Univ Washington, Seattle, WA 98195 USA. RP Shlipak, M (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu FU NIH [RO1-DK57508, HL74814, HL53359]; NIH GCRC [M01-RR00036, RR00051, RR00052, RR00054, RR00083, RR0636, RR00865, UL1 RR024131, P30 DK 026687-269012]; Veterans Affairs Medical Centers of Atlanta, District of Columbia, New York, and San Francisco FX Supported by NIH grants RO1-DK57508, HL74814, and HL53359, and NIH GCRC grants M01-RR00036, RR00051, RR00052, RR00054, RR00083, RR0636, RR00865, UL1 RR024131, and P30 DK 026687-269012, the Albert L. and Janet A. Schultz Supporting Foundation, and with resources and the use of facilities of the Veterans Affairs Medical Centers of Atlanta, District of Columbia, New York, and San Francisco. NR 25 TC 5 Z9 5 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2011 VL 33 IS 5 BP 453 EP 460 DI 10.1159/000327606 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 767FQ UT WOS:000290841100009 PM 21508633 ER PT J AU Jhamb, M Pike, F Ramer, S Argyropoulos, C Steel, J Dew, MA Weisbord, SD Weissfeld, L Unruh, M AF Jhamb, Manisha Pike, Francis Ramer, Sarah Argyropoulos, Christos Steel, Jennifer Dew, Mary Amanda Weisbord, Steven D. Weissfeld, Lisa Unruh, Mark TI Impact of Fatigue on Outcomes in the Hemodialysis (HEMO) Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE End-stage renal disease; Fatigue; Vitality; Health-related quality of life ID QUALITY-OF-LIFE; DIALYSIS PATIENTS; MAINTENANCE HEMODIALYSIS; HEALTH-STATUS; INTERLEUKIN-6; METAANALYSIS; MORTALITY; SYMPTOMS; TRIAL; SERUM AB Background: Fatigue is a common debilitating symptom in chronic kidney disease patients on maintenance hemodialysis. However, little is known about its pathogenesis and association with survival. Methods: This study examines the correlates and outcomes of fatigue among 1,798 hemodialysis patients enrolled in the HEMO study. Fatigue was assessed using the SF-36 vitality scale. Multivariable analysis was used to assess independent associations of demographic and clinical characteristics with baseline fatigue and longitudinal changes in fatigue. The association of fatigue with all-cause and cause-specific mortality and cardiac hospitalizations was also assessed. Results: Higher index of coexistent diseases (ICED) score, diabetes, non-African-American race, lower serum albumin, use of medications for sleep and poor sleep quality were found to be significantly associated with more fatigue at baseline. In longitudinal analyses, patients who were older, had been on dialysis longer, had higher ICED score, and reported using medications for sleep were more likely to experience worsening fatigue, whereas higher serum albumin was strongly associated with an improvement in level of fatigue. A 10-point increase in vitality score was associated with 10% increase in mean survival (p < 0.0001). Conclusions: Demographic and clinical factors have significant associations with fatigue, which itself predicts mortality. Improving fatigue in the end-stage renal disease population may positively impact patient well-being and survival. Copyright (C) 2011 S. Karger AG, Basel C1 [Unruh, Mark] Univ Pittsburgh, Sch Med, Med Ctr, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Pike, Francis; Dew, Mary Amanda; Weissfeld, Lisa] Univ Pittsburgh, Med Ctr, Dept Biostat, Pittsburgh, PA 15213 USA. [Steel, Jennifer; Dew, Mary Amanda] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. [Steel, Jennifer] Univ Pittsburgh, Sch Med, Liver Canc Ctr, Dept Surg,Starzl Transplantat Inst, Pittsburgh, PA 15213 USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare, Renal Sect, Pittsburgh, PA USA. [Weisbord, Steven D.] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Unruh, M (reprint author), Univ Pittsburgh, Sch Med, Med Ctr, Renal Electrolyte Div, 200 Lothrop St,PUH C-1111, Pittsburgh, PA 15213 USA. EM unruh@pitt.edu RI Jhamb, Manisha/E-4169-2013; OI Argyropoulos, Christos/0000-0002-9679-7805 FU NIDDK NIH HHS [R01 DK077785] NR 32 TC 24 Z9 27 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2011 VL 33 IS 6 BP 515 EP 523 DI 10.1159/000328004 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 780BG UT WOS:000291825500007 PM 21555875 ER PT J AU Johnson, JM Moonis, G Green, GE Carmody, R Burbank, HN AF Johnson, J. M. Moonis, G. Green, G. E. Carmody, R. Burbank, H. N. TI Syndromes of the First and Second Branchial Arches, Part 1: Embryology and Characteristic Defects SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID CONGENITAL AURAL ATRESIA; CLEFT-LIP; TREACHER-COLLINS; NASAL MASSES; INNER-EAR; CT; MIDDLE; PALATE; DIAGNOSIS; MALFORMATIONS AB A variety of congenital syndromes affecting the face occur due to defects involving the first and second BAs. Radiographic evaluation of craniofacial deformities is necessary to define aberrant anatomy, plan surgical procedures, and evaluate the effects of craniofacial growth and surgical reconstructions. High-resolution CT has proved vital in determining the nature and extent of these syndromes. The radiologic evaluation of syndromes of the first and second BAs should begin first by studying a series of isolated defects: CL with or without CP, micrognathia, and EAC atresia, which compose the major features of these syndromes and allow more specific diagnosis. After discussion of these defects and the associated embryology, we proceed to discuss the VCFS, PRS, ACS, TCS, Stickler syndrome, and HFM. C1 [Johnson, J. M.; Burbank, H. N.] Fletcher Allen Hlth Care, Div Neuroradiol, Burlington, VT USA. [Johnson, J. M.; Burbank, H. N.] Fletcher Allen Hlth Care, Dept Radiol, Burlington, VT USA. [Moonis, G.] Beth Israel Deaconess Med Ctr, Dept Radiol, Div Neuroradiol, Boston, MA 02215 USA. [Moonis, G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Green, G. E.] Univ Michigan, Dept Pediat Otolaryngol, Ann Arbor, MI 48109 USA. [Carmody, R.] Univ Arizona, Dept Radiol, Div Neuroradiol, Tucson, AZ 85724 USA. RP Johnson, JM (reprint author), Dept Radiol, 111 Colchester Ave, Burlington, VT 05401 USA. EM Jason.Johnson@vtmednet.org NR 39 TC 10 Z9 10 U1 2 U2 9 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2011 VL 32 IS 1 BP 14 EP 19 DI 10.3174/ajnr.A2072 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 717BC UT WOS:000287016200003 PM 20299437 ER PT J AU Lindsay, RW Edwards, C Smitson, C Cheney, ML Hadlock, TA AF Lindsay, Robin W. Edwards, Colin Smitson, Chris Cheney, Mack L. Hadlock, Tessa A. TI A systematic algorithm for the management of lower lip asymmetry SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID MARGINAL MANDIBULAR BRANCH; DEPRESSOR MUSCLE MECHANISM; FACIAL-NERVE PARALYSIS; MICROSURGICAL STRATEGIES; NEGLECTED TARGET; BOTULINUM TOXIN; REANIMATION; RESTORATION AB Purpose: An asymmetric smile, caused by loss of function of the lip depressors, can be functionally and cosmetically debilitating. Although some surgeons report excellent results with muscle transfer to the lower lip, many facial reanimation surgeons find that dynamic techniques do not consistently address the lower lip. Our objectives were to retrospectively review our outcomes after treatment of the asymmetric lower lip, and to propose a progressive, stepwise algorithm for the management of lower lip asymmetry in facial paralysis. Material/Methods: Retrospective chart review was performed on all patients treated in a multidisciplinary facial nerve center with lower lip asymmetry over an eighteen month period. Treatment ranged from a temporary trial of lidocaine, to chemodenervation with botulinum toxin, to pedicled digastric muscle transfer, and/or resection of the nonparetic depressor labii inferioris (DLI). Results: Fifty-seven patients were treated with chemodenervation with botulinum toxin, four with anterior belly of the digastric transfer, and 3 with DLI resection. All patients with DLI resection had undergone chemodenervation to the contralateral lower lip with botulinum toxin and were pleased with the appearance of their smile. Conclusions: We have found that lower lip asymmetry is optimally managed by adherence to a standardized protocol that offers patients insight into the likely outcome of chemodenervation or surgery and progresses systematically from the reversible to the irreversible. We present our algorithm for the management of the asymmetric lower lip, which reflects this graduated approach and has resulted in high patient satisfaction. Published by Elsevier Inc. C1 [Lindsay, Robin W.; Edwards, Colin; Smitson, Chris; Cheney, Mack L.; Hadlock, Tessa A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Lindsay, Robin W.; Edwards, Colin; Smitson, Chris; Cheney, Mack L.; Hadlock, Tessa A.] Harvard Univ, Sch Med, Boston, MA USA. [Lindsay, Robin W.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. RP Lindsay, RW (reprint author), Natl Naval Med Ctr, Dept Otolaryngol Head & Neck Surg, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM robin_lindsay@meei.harvard.edu NR 13 TC 15 Z9 15 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD JAN-FEB PY 2011 VL 32 IS 1 BP 1 EP 7 DI 10.1016/j.amjoto.2009.08.011 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 695KY UT WOS:000285370200001 PM 20015805 ER PT J AU Yang, N Mosher, R Seo, S Beebe, D Friedl, A AF Yang, Ning Mosher, Rachel Seo, Songwon Beebe, David Friedl, Andreas TI Syndecan-1 in Breast Cancer Stroma Fibroblasts Regulates Extracellular Matrix Fiber Organization and Carcinoma Cell Motility SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HEPARAN-SULFATE CHAINS; FIBRONECTIN MATRIX; ESTROGEN-RECEPTOR; INTEGRIN ACTIVATION; IN-VIVO; MIGRATION; EXPRESSION; BINDING; ALPHA(V)BETA(3); POLYMERIZATION AB Stromal fibroblasts of breast carcinomas frequently express the cell surface proteoglycan syndecan-1 (Sdc1). In human breast carcinoma samples, stromal Sdc1 expression correlates with an organized, parallel, extracellular matrix (ECM) fiber architecture. To examine a possible link between stromal Sdc1 and the fiber architecture, we generated bioactive cell-free three-dimensional ECMs from cultures of Sdc1-positive and Sdc1-negative murine and human mammary fibroblasts (termed ECM-Sdc1 and ECM-mock, respectively). Indeed, ECM-Sdc1 showed a parallel fiber architecture that contrasted markedly with the random fiber arrangement of ECM-mock. When breast carcinoma cells were seeded into the fibroblast-free ECMs, ECM-Sdc1, but not ECM-mock, promoted their attachment, invasion, and directional movement. We further evaluated the contribution of the structural/compositional modifications in ECM-Sdc1 on carcinoma cell behavior. By microcontact printing of culture surfaces, we forced the Sdc1-negative fibroblasts to produce ECM with parallel fiber organization, mimicking the architecture observed in ECM-Sdc1. We found that the fiber topography governs carcinoma cell migration directionality. Conversely, an elevated fibronectin level in ECM-Sdc1 was responsible for the enhanced attachment of the breast carcinoma cells. These observations suggest that Sdc1 expression in breast carcinoma stromal fibroblasts promotes the assembly of an architecturally abnormal ECM that is permissive to breast carcinoma directional migration and invasion. (An: J Pathol 2011, 178:325-335; DOI: 10.1016/j.ajpath.2010.11.039) C1 [Friedl, Andreas] Univ Wisconsin, Dept Pathol & Lab Med, Wisconsin Inst Med Res WIMR 6051, Madison, WI 53705 USA. [Mosher, Rachel; Beebe, David] Univ Wisconsin, Dept Biomed Engn, Coll Engn, Madison, WI 53705 USA. [Seo, Songwon] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53705 USA. [Friedl, Andreas] William S Middleton Mem Vet Adm Med Ctr, Lab Med Serv, Madison, WI USA. RP Friedl, A (reprint author), Univ Wisconsin, Dept Pathol & Lab Med, Wisconsin Inst Med Res WIMR 6051, 1111 Highland Ave, Madison, WI 53705 USA. EM afriedl@wisc.edu FU National Institutes of Health [RO1 CA107012] FX Supported by the National Institutes of Health (grant RO1 CA107012). NR 61 TC 47 Z9 48 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2011 VL 178 IS 1 BP 325 EP 335 DI 10.1016/j.ajpath.2010.11.039 PG 11 WC Pathology SC Pathology GA 710EM UT WOS:000286493700035 PM 21224069 ER PT J AU Thrower, EC Yuan, JZ Usmani, A Liu, YN Jones, C Minervini, SN Alexandre, M Pandol, SJ Guha, S AF Thrower, Edwin C. Yuan, Jingzhen Usmani, Ashar Liu, Yannan Jones, Courtney Minervini, Samantha N. Alexandre, Martine Pandol, Stephen J. Guha, Sushovan TI A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE PKD/PKD1 inhibitor CRT0066101; zymogen activation; amylase secretion; cell injury ID ACTIVATION LOOP SER(744); KAPPA-B ACTIVATION; ZYMOGEN ACTIVATION; IN-VIVO; C-EPSILON; MEDIATED PHOSPHORYLATION; POTENT INHIBITOR; PHORBOL ESTERS; PKC-DELTA; GO 6976 AB Novel protein kinase C isoforms (PKC delta and epsilon) mediate early events in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC delta and epsilon in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-kappa B in acute pancreatitis. For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. We pretreated isolated rat pancreatic acinar cells with CRT0066101 and a commercially available inhibitor Go6976 (10 mu M). This was followed by stimulation for 60 min with high concentrations of cholecystokinin (CCK, 0.1 mu M), carbachol (CCh, 1 mM), or bombesin (10 mu M) to induce initial events of pancreatitis. PKD/PKD1 phosphorylation and activity were measured as well as zymogen activation, amylase secretion, cell injury and NF-kappa B activation. CRT0066101 dose dependently inhibited secretagogue-induced PKD/PKD1 activation and autophosphorylation at Ser-916 with an IC(50) similar to 3.75-5 mu M but had no effect on PKC-dependent phosphorylation of the PKD/PKD1 activation loop (Ser-744/748). Furthermore, CRT0066101 reduced secretagogue-induced zymogen activation and amylase secretion. Go6976 reduced zymogen activation but not amylase secretion. Neither inhibitor affected basal zymogen activation or secretion. CRT0066101 did not affect secretagogue-induced cell injury or changes in cell morphology, but it reduced NF-kappa B activation by 75% of maximal for CCK- and CCh-stimulated acinar cells. In conclusion, CRT0066101 is a potent and specific PKD family inhibitor. Furthermore, PKD/PKD1 is a potential mediator of zymogen activation, amylase secretion, and NF-kappa B activation induced by a range of secretagogues in pancreatic acinar cells. C1 [Thrower, Edwin C.; Usmani, Ashar; Jones, Courtney; Minervini, Samantha N.; Alexandre, Martine] Dept Internal Med, Sect Digest Dis, West Haven, CT USA. [Thrower, Edwin C.; Usmani, Ashar; Jones, Courtney; Minervini, Samantha N.; Alexandre, Martine] Vet Adm Connecticut Healthcare, West Haven, CT USA. [Thrower, Edwin C.; Usmani, Ashar; Jones, Courtney; Minervini, Samantha N.; Alexandre, Martine] Yale Univ, Sch Med, New Haven, CT USA. [Yuan, Jingzhen; Liu, Yannan; Pandol, Stephen J.] Vet Affairs Greater Los Angeles Hlth Care Syst, So Calif Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. [Yuan, Jingzhen; Liu, Yannan; Pandol, Stephen J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Guha, Sushovan] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX USA. RP Thrower, EC (reprint author), Vet Adm Med Ctr, 950 Campbell Ave,Bldg 4, West Haven, CT 06516 USA. EM edwin.thrower@yale.edu FU National Institutes of Health (NIH) [DK69702, 5P30CA16672]; National Institute on Alcohol Abuse and Alcoholism [5 P60 AA11999]; MD Anderson Cancer Center; McNair Foundation; Tsukamoto FX This work was supported by a National Institutes of Health (NIH) Grant R21 (DK69702 to E. C. Thrower) USC-UCLA Research Center for Alcoholic Liver and Pancreatic Injury Grant (5 P60 AA11999 from the National Institute on Alcohol Abuse and Alcoholism; Tsukamoto; to S. J. Pandol), MD Anderson Cancer Center Physician Scientist Program Award (to S. Guha), McNair Foundation Scholar Award (to S. Guha), and NIH 5P30CA16672 (Career Development Award to S. Guha). NR 43 TC 14 Z9 14 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JAN PY 2011 VL 300 IS 1 BP G120 EP G129 DI 10.1152/ajpgi.00300.2010 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 700LV UT WOS:000285744300012 PM 20947701 ER PT J AU Chen, YW Chenier, I Chang, SY Tran, S Ingelfinger, JR Zhang, SL AF Chen, Yun-Wen Chenier, Isabelle Chang, Shiao-Ying Tran, Stella Ingelfinger, Julie R. Zhang, Shao-Ling TI High glucose promotes nascent nephron apoptosis via NF-kappa B and p53 pathways SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article ID OXIDATIVE STRESS; DIABETIC COMPLICATIONS; TUBULAR APOPTOSIS; CONGENITAL-MALFORMATIONS; EPITHELIAL-CELLS; URETERAL BUD; ACTIVATION; MICE; KIDNEY; GENE AB Chen YW, Chenier I, Chang SY, Tran S, Ingelfinger JR, Zhang SL. High glucose promotes nascent nephron apoptosis via NF-kappa B and p53 pathways. Am J Physiol Renal Physiol 300: F147-F156, 2011. First published October 20, 2010; doi:10.1152/ajprenal.00361.2010.-A hyperglycemic environment in utero reduces kidney size and nephron number due to nascent nephron apoptosis. However, the underlying mechanisms are incompletely understood. The present study investigated whether the nascent nephron apoptosis promoted by high glucose is mediated via the transcription factor NF-kappa B and p53 signaling pathways. Neonatal mouse kidneys from the offspring of nondiabetic, diabetic, and insulin-treated diabetic dams were used for in vivo studies, and MK4 cells, an embryonic metanephric mesenchymal (MM) cell line, were used for in vitro studies. Neonatal kidneys of the offspring of diabetic mothers exhibited an increased number of apoptotic cells and reactive oxygen species (ROS) generation, enhanced NF-kappa B activation, and nuclear translocation of its subunits (p50 and p65 subunits) as well as phosphorylation (Ser 15) of p53 compared with kidneys of offspring of nondiabetic mothers. Insulin treatment of diabetic dams normalized these parameters in the offspring. In vitro, high-glucose (25 mM) induced ROS generation and significantly increased MK4 cell apoptosis and caspase-3 activity via activation of NF-kappa B pathway, with p53 phosphorylation and nuclear translocation compared with normal glucose (5 mM). These changes in a high-glucose milieu were prevented by transient transfection of small interfering RNAs for dominant negative I kappa B alpha or IKK or p53. Our data demonstrate that high glucose-induced nascent nephron apoptosis is mediated, at least in part, via ROS generation and the activation of NF-kappa B and p53 pathways. C1 [Chen, Yun-Wen; Chenier, Isabelle; Chang, Shiao-Ying; Tran, Stella; Zhang, Shao-Ling] Univ Montreal, CRCHUM, Hop Hotel Dieu, Montreal, PQ H2W 1T7, Canada. [Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. RP Zhang, SL (reprint author), Univ Montreal, CRCHUM, Hop Hotel Dieu, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T7, Canada. EM shao.ling.zhang@umontreal.ca FU Canadian Institutes of Health Research [MOP86450] FX This research was supported by grants from the Canadian Institutes of Health Research (MOP86450 to S.-L. Zhang). NR 53 TC 10 Z9 11 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2011 VL 300 IS 1 BP F147 EP F156 DI 10.1152/ajprenal.00361.2010 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 703FP UT WOS:000285964000018 PM 20962117 ER PT J AU Mariappan, MM D'Silva, K Lee, MJ Sataranatarajan, K Barnes, JL Choudhury, GG Kasinath, BS AF Mariappan, Meenalakshmi M. D'Silva, Kristin Lee, Myung Ja Sataranatarajan, Kavithalakshmi Barnes, Jeffrey L. Choudhury, Goutam Ghosh Kasinath, Balakuntalam S. TI Ribosomal biogenesis induction by high glucose requires activation of upstream binding factor in kidney glomerular epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ribosomal deoxyribonucleic acid transcription; diabetic kidney disease; hypertrophy; mammalian target of rapamycin; ribonucleic acid; polymerase I ID MESSENGER-RNA TRANSLATION; POLYMERASE-I; DIABETIC-NEPHROPATHY; PROTEIN-SYNTHESIS; GENE-TRANSCRIPTION; RENAL HYPERTROPHY; CARDIAC MYOCYTES; HIGH INSULIN; GROWTH; PHOSPHORYLATION AB Mariappan MM, D'Silva K, Lee MJ, Sataranatarajan K, Barnes JL, Choudhury GG, Kasinath BS. Ribosomal biogenesis induction by high glucose requires activation of upstream binding factor in kidney glomerular epithelial cells. Am J Physiol Renal Physiol 300: F219-F230, 2011. First published October 13, 2010; doi:10.1152/ajprenal.00207.2010.-Diabetes promotes protein synthesis to induce kidney hypertrophy and increase renal matrix proteins. Increased capacity for mRNA translation by way of ribosomal biogenesis facilitates sustained stimulation of protein synthesis. We tested the hypothesis that high glucose induces ribosomal biogenesis as indicated by an increase in rRNA synthesis in the setting of augmented protein synthesis. High glucose (30 mM) increased global protein synthesis, expression of matrix proteins, laminin gamma 1 and fibronectin, and rDNA transcription in glomerular epithelial cells (GECs) compared with 5 mM glucose. High glucose induced Ser(388) phosphorylation of upstream binding factor (UBF), an rDNA transcription factor, along with increased phosphorylation of Erk and p70S6 kinase. Inactivation of Erk and p70S6 kinase either by their respective chemical inhibitors or by expression of their inactive mutant constructs blocked high-glucose-induced UBF phosphorylation. High glucose reduced nuclear content of p19ARF and promoted dissolution of inactive UBF-p19ARF complex. High glucose also promoted association of UBF with RPA194, a subunit of RNA polymerase I. Inhibition of Erk, p70S6 kinase, and UBF1 by transfecting GECs with their respective inactive mutants abolished laminin gamma 1 synthesis, protein synthesis, and rDNA transcription. Renal cortex from type 1 diabetic rats and type 2 diabetic db/db mice showed increased phosphorylation of UBF, Erk, and p70S6 kinase coinciding with renal hypertrophy and onset of matrix accumulation. Our data suggest that augmented ribosome biogenesis occurs in an UBF-dependent manner during increased protein synthesis induced by high glucose in the GECs that correlates with UBF activation and renal hypertrophy in rodents with type 1 and type 2 diabetes. C1 [Mariappan, Meenalakshmi M.; D'Silva, Kristin; Lee, Myung Ja; Sataranatarajan, Kavithalakshmi; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Barnes, Jeffrey L.; Choudhury, Goutam Ghosh; Kasinath, Balakuntalam S.] S Texas Vet Healthcare Syst, Vet Affairs Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. RP Mariappan, MM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM malini@uthscsa.edu FU National Institutes of Health [DK-077295, RC2AG-036613, DK-050190, DK-080106]; National Institute of Diabetes and Digestive and Kidney Diseases O'Brien Kidney Center; Veterans Affairs (VA) Medical Research Service; Juvenile Diabetes Research Foundation [3-2007-245, 1-2008-185]; VA Research Career Scientist Award FX This study was supported by the National Institutes of Health Grants DK-077295 and RC2AG-036613 to B. S. Kasinath, DK-050190 to G. G. Choudhury, and DK-080106 to J. L. Barnes; a National Institute of Diabetes and Digestive and Kidney Diseases O'Brien Kidney Center Grant (B. S. Kasinath); the Veterans Affairs (VA) Medical Research Service (B. S. Kasinath, G. G. Choudhury, and J. L. Barnes); and Juvenile Diabetes Research Foundation Grants 3-2007-245 to M. M. Mariappan/B. S. Kasinath and 1-2008-185 to G. G. Choudhury. G. G. Choudhury is a recipient of VA Research Career Scientist Award. NR 46 TC 11 Z9 11 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2011 VL 300 IS 1 BP F219 EP F230 DI 10.1152/ajprenal.00207.2010 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 703FP UT WOS:000285964000025 PM 20943765 ER PT J AU Zhuang, ZJ Marshansky, V Breton, S Brown, D AF Zhuang, Zhenjie Marshansky, Vladimir Breton, Sylvie Brown, Dennis TI Is caveolin involved in normal proximal tubule function? Presence in model PT systems but absence in situ SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE kidney; cell culture; isolated tubules; endocytosis ID ACUTE-RENAL-FAILURE; RAT-KIDNEY; EPITHELIAL-CELLS; PLASMA-MEMBRANE; ANGIOTENSIN-II; ATPASE; RECEPTOR; ENDOCYTOSIS; INTERNALIZATION; LOCALIZATION AB Zhuang Z, Marshansky V, Breton S, Brown D. Is caveolin involved in normal proximal tubule function? Presence in model PT systems but absence in situ. Am J Physiol Renal Physiol 300: F199-F206, 2011. First published October 27, 2010; doi:10.1152/ajprenal.00513.2010.-Kidney proximal tubule (PT) cells are specialized for the uptake and transport of ions, solutes, peptides, and proteins. These functions are often regulated by hormones that signal at the cell surface and are internalized by clathrin-mediated endocytosis. However, the caveolin/caveolae pathway has also been implicated in normal PT function, often based on data from isolated PTs or PT cells in culture. Although we reported previously that caveolae and caveolin 1 are not detectable in PTs in vivo, reports of caveolin expression and function in PT cells appear periodically in the literature. Therefore, we reexamined caveolin expression in PTs in vivo, in isolated "purified" PTs following collagenase digestion, and in cultured PT cells. Caveolin 1 and 2 protein, mRNA, or immunofluorescence was undetectable in PTs in vivo, but PT cell cultures expressed caveolin 1 and/or 2. Furthermore, caveolin 1 and 2 mRNAs were detected in isolated PTs along with the endothelial markers CD31 and ICAM1. In contrast, no caveolin or endothelial marker mRNAs were detectable in samples isolated from snap-frozen kidneys by laser cut microdissection, which eliminates contamination by other cell types. We conclude 1) caveolin 1 and 2 are not normally expressed by PT cells in situ, 2) caveolin expression is "activated" in cultured PT cells, 3) contamination with non-PT, caveolin-expressing cells is a potential source of caveolin 1 and 2 that must be taken into account when isolated PTs are used in studies to correlate expression of these proteins with PT function. C1 [Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Simches Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Simches Res Bldg,185 Cambridge St,CPZN 8150, Boston, MA 02114 USA. EM brown.dennis@mgh.harvard.edu FU National Institutes of Health (NIH) [R37-DK-42956, DK-38452]; Boston Area Diabetes and Endocrinology Research Center [NIH DK-57521]; Center for the Study of Inflammatory Bowel Disease [NIH DK-43351] FX This work was supported by National Institutes of Health (NIH) Grants R37-DK-42956 (to D. Brown) and DK-38452 (to S. Breton and V. Marshansky). The Microscopy Core Facility of the Program in Membrane Biology received additional support from the Boston Area Diabetes and Endocrinology Research Center (NIH DK-57521) and from the Center for the Study of Inflammatory Bowel Disease (NIH DK-43351). NR 56 TC 17 Z9 18 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2011 VL 300 IS 1 BP F199 EP F206 DI 10.1152/ajprenal.00513.2010 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 703FP UT WOS:000285964000023 PM 20980408 ER PT J AU Sorensen, G Landsbergis, P Hammer, L Amick, BC Linnan, L Yancey, A Welch, LS Goetzel, RZ Flannery, KM Pratt, C AF Sorensen, Glorian Landsbergis, Paul Hammer, Leslie Amick, Benjamin C., III Linnan, Laura Yancey, Antronette Welch, Laura S. Goetzel, Ron Z. Flannery, Kelly M. Pratt, Charlotte CA Workshop Working Grp Worksite Chro TI Preventing Chronic Disease in the Workplace: A Workshop Report and Recommendations SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID WORKSITE HEALTH-PROMOTION; DUAL-EARNER COUPLES; RE-AIM FRAMEWORK; FAMILY-CONFLICT; UNITED-STATES; BEHAVIOR-CHANGE; SOCIOECONOMIC-STATUS; OCCUPATIONAL-HEALTH; WELLNESS-PROGRAMS; PHYSICAL-ACTIVITY AB Chronic disease is the leading cause of death in the United States. Risk factors and work conditions can be addressed through health promotion aimed at improving individual health behaviors; health protection, including occupational safety and health interventions; and efforts to support the work family interface. Responding to the need to address chronic disease at worksites, the National Institutes of Health and the Centers for Disease Control and Prevention convened a workshop to identify research priorities to advance knowledge and implementation of effective strategies to reduce chronic disease risk. Workshop participants outlined a conceptual framework and corresponding research agenda to address chronic disease prevention by integrating health promotion and health protection in the workplace. (Am J Public Health. 2011;101:S196-S207. doi:10.2105/AJPH.2010.300075) C1 [Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02215 USA. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Landsbergis, Paul] SUNY Downstate Sch Publ Hlth, Brooklyn, NY USA. [Hammer, Leslie] Portland State Univ, Portland, ME USA. [Amick, Benjamin C., III] Univ Texas Hlth Sci Ctr San Antonio, Sch Publ Hlth, San Antonio, TX 78229 USA. [Linnan, Laura] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Yancey, Antronette] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Welch, Laura S.] Ctr Construct Res & Training, Silver Spring, MD USA. [Goetzel, Ron Z.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Pratt, Charlotte] NHLBI, NIH, Bethesda, MD 20892 USA. [Flannery, Kelly M.] Univ Maryland, Baltimore, MD 21201 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Glorian_Sorensen@dfci.harvard.edu FU National Cancer Institute [5 K05 CA108663-05]; National Institute for Occupational Safety and Health [5U19 OH008861-04]; National Heart, Lung and Blood Institute; National Institute of Occupational Safety and Health; Centers for Disease Control and Prevention; National Institute for Child Health and Human Development FX We thank the National Heart, Lung and Blood Institute; the National Institute of Occupational Safety and Health; the Centers for Disease Control and Prevention; the National Institute for Child Health and Human Development; and the National Cancer Institute for their support. Glorian Sorensen's contributions were funded by the National Cancer Institute (grant 5 K05 CA108663-05) and the National Institute for Occupational Safety and Health (grant 5U19 OH008861-04). NR 157 TC 37 Z9 37 U1 7 U2 37 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PY 2011 VL 101 SU 1 BP S196 EP S207 DI 10.2105/AJPH.2010.300075 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 849QU UT WOS:000297141000030 PM 21778485 ER PT J AU Hart, JE Garshick, E Dockery, DW Smith, TJ Ryan, L Laden, F AF Hart, Jaime E. Garshick, Eric Dockery, Douglas W. Smith, Thomas J. Ryan, Louise Laden, Francine TI Long-Term Ambient Multipollutant Exposures and Mortality SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE air pollutants/adverse effects; cardiovascular diseases/mortality; nitrogen dioxide; sulfur dioxide; particulate matter ID PARTICULATE AIR-POLLUTION; TRUCKING INDUSTRY WORKERS; LUNG-CANCER; RAILROAD WORKERS; DIESEL EXHAUST; CARDIOPULMONARY MORTALITY; UNITED-STATES; 6 CITIES; COHORT; DISEASE AB Rationale. Population-based studies have demonstrated associations between ambient air pollution exposures and mortality, but few have been able to adjust for occupational exposures. Additionally, two studies have observed higher risks in individuals with occupational dust, gas, or fume exposure. Objectives: We examined the association of ambient residential exposure to particulate matter less than 10 mu m in diameter (PM10), particulate matter less than 2.5 mu m in diameter (PM2.5), NO2, SO2, and mortality in 53,814 men in the U.S. trucking industry. Methods: Exposures for PM10, NO2, and SO2 at each residential address were assigned using models combining spatial smoothing and geographic covariates. PM2.5 exposures in 2000 were assigned from the nearest available monitor. Single and multipollutant Cox proportional hazard models were used to examine the association of an interquartile range (IQR) change (6 mu g/m(3) for PM10, 4 mu g/m(3) for PM2.5, 4ppb for SO2, and 8ppb for NO2) and the risk of all-cause and cause-specific mortality. Measurements and Main Results: An IQR change in ambient residential exposures to PM10 was associated with a 4.3% (95% confidence interval [CI], 1.1-7.7%) increased risk of all-cause mortality. The increase for an IQR change in SO2 was 6.9% (95% CI, 2.3-11.6%), for NO2 was 8.2% (95% CI, 4.5-12.1%), and for PM2.5 was 3.9% (95% CI, 1.0-6.9%). Elevated associations with cause-specific mortality (lung cancer, cardiovascular and respiratory disease) were observed for PM2.5, SO2, and NO2, but not PM10. None of the pollutants were confounded by occupational exposures. In multipollutant models, overall, the associations were attenuated, most strongly for PM10. In sensitivity analyses excluding long-haul drivers, who spend days away from home, larger hazard ratios were observed. Conclusions: In this population of men, residential ambient air pollution exposures were associated with mortality. C1 [Hart, Jaime E.; Dockery, Douglas W.; Smith, Thomas J.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Hart, Jaime E.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Ryan, Louise] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hart, Jaime E.; Garshick, Eric; Laden, Francine] Harvard Univ, Sch Med, Boston, MA USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. RP Hart, JE (reprint author), 181 Longwood Ave, Boston, MA 02115 USA. EM jaime.hart@channing.harvard.edu RI Smith, Thomas/A-9640-2010; Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU National Institutes of Health/National Cancer Institute [R01 CA90792]; National Institute of Environmental Health Sciences [T3-2 ES007069-29]; NIEHS [ES000002]; National Institutes of Health (NIH); Department of Veterans Affairs; National Institute of Environmental Health Sciences (NIEHS) FX Supported by grant R01 CA90792 from the National Institutes of Health/National Cancer Institute, National Institute of Environmental Health Sciences T3-2 ES007069-29 (J.E.H.) and NIEHS Center grant ES000002.; J.E.H. is an employee of Brigham and Women's Hospital and received more than $100,001 in salary funding from a number of National Institutes of Health (NIH) grants. E.G. received $10,001-$50,000 from Libby Medical Plan for advice on pulmonary disease, lectures, and more than $100,001 from the NIH and more than $100,001 from the Department of Veterans Affairs for peer-reviewed research grants. D.W.D. received more than $100,001 from the National Institute of Environmental Health Sciences (NIEHS) in sponsored grants (Center for-Environmental Health), up to $1,000 from the EPA for serving, on a science advisory board; and more than $100,001 from the Health Effects Institute in sponsored grants for air pollution research. T.J.S. received $10,001-$50,000 from Patton Boggs LLB for providing legal advice unrelated to this manuscript, $10,001-$50,000 from Patton Boggs LLB for serving as an expert witness on an accidental dust exposure case, and more than $100,001 from the NIEHS in research grants. L.R. received up to $1,000 from CRC press for royalties on a coauthored book. F.L. received more than $100,001 from the NIH in sponsored grants. NR 49 TC 47 Z9 49 U1 2 U2 34 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 1 PY 2011 VL 183 IS 1 BP 73 EP 78 DI 10.1164/rccm.200912-1903OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 705RM UT WOS:000286155600013 PM 20656944 ER PT J AU De Ferrari, GM Van de Werf, F Armstrong, P Bode, C Lewis, BS Tricoci, P Guo, J Contant, C Newby, K Giugliano, RP AF De Ferrari, G. M. Van de Werf, F. Armstrong, P. Bode, C. Lewis, B. S. Tricoci, P. Guo, J. Contant, C. Newby, K. Giugliano, R. P. TI Contrast induced nephropathy predicts later mortality among patients with non-ST-segment elevation acute coronary syndrome undergoing PCI: a sub-analysis from the EARLY ACS study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [De Ferrari, G. M.] Fdn IRCCS Policlin San Mat, Dept Cardiol, Pavia, Italy. [Van de Werf, F.] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Armstrong, P.] Univ Alberta, Edmonton, AB, Canada. [Bode, C.] Univ Freiburg Klinikum, Freiburg, Germany. [Lewis, B. S.] Lady Davis Carmel Med Ctr, Haifa, Israel. [Tricoci, P.] Duke Clin Res Durham, Durham, NC USA. [Giugliano, R. P.] TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2011 VL 183 BP 657 EP 657 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29TI UT WOS:000208770305083 ER PT J AU Shinagare, AB Ramaiya, NH Jagannathan, JP Fennessy, FM Taplin, ME Van den Abbeele, AD AF Shinagare, Atul B. Ramaiya, Nikhil H. Jagannathan, Jyothi P. Fennessy, Fiona M. Taplin, Mary-Ellen Van den Abbeele, Annick D. TI Metastatic Pattern of Bladder Cancer: Correlation With the Characteristics of the Primary Tumor SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE bladder cancer; metastasis; pattern; transitional cell carcinoma ID TRANSITIONAL-CELL-CARCINOMA; UROTHELIAL CARCINOMA; URINARY-BLADDER; METHOTREXATE; VINBLASTINE; DOXORUBICIN; STATISTICS; CYSTECTOMY; EXPRESSION; CISPLATIN AB OBJECTIVE. The purpose of this study was to evaluate the metastatic pattern of muscle-invasive bladder cancer and to correlate the findings with the characteristics of the primary tumor. MATERIALS AND METHODS. From a clinic population of 392 patients with muscle-invasive (pT2-4) bladder cancer seen at our institution from January 2004 through December 2009, we studied the cases of 150 consecutively registered patients with pathologically proven metastatic disease. The metastasis-free intervals and metastatic patterns of different T categories were compared by Kruskal-Wall is test and Freeman-Halton extension of Fisher's exact test. Patients were divided into two histologic categories, those with transitional cell carcinoma and those with atypical histologic features. The metastasis-free interval and metastatic pattern of these two groups were compared by Mann-Whitney test and Fisher's exact test. RESULTS. The study group consisted of 150 patients (116 men [77%], 34 women [23%]; median age, 64 years). The transitional cell carcinoma group consisted of 94 (63%) patients and the atypical histologic features group of 56 (37%) patients. The most common metastatic sites were lymph nodes (104 patients, 69%), bone (71 patients, 47%), lung (55 patients, 37%), liver (39 patients, 26%), and peritoneum (24 patients, 16%). Patients with tumors of a more advanced T category had shorter metastasis-free intervals (p = 0.001, df = 2). There was no significant difference in the metastatic patterns of tumors in the different T categories. Patients with atypical histologic features had a shorter median metastasis-free interval (3 months; range, 0-29 months) than patients with transitional cell carcinoma (12 months; range, 0-192 months) (p = 0.0001). Patients with atypical histologic features had a significantly higher incidence of peritoneal metastasis (p < 0.0002). CONCLUSION. Lymph nodes, bones, lung, liver, and peritoneum are the most common sites of metastasis from bladder cancer. Tumors in a more advanced T category and those with atypical histologic features metastasize earlier. Tumors with atypical histologic features also have a higher frequency of peritoneal metastasis. C1 [Shinagare, Atul B.; Ramaiya, Nikhil H.; Jagannathan, Jyothi P.; Fennessy, Fiona M.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Taplin, Mary-Ellen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA. EM ashinagare@partners.org NR 34 TC 27 Z9 29 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2011 VL 196 IS 1 BP 117 EP 122 DI 10.2214/AJR.10.5036 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703YV UT WOS:000286018800016 PM 21178055 ER PT J AU Forman, HP Norbash, A Beauchamp, NJ Thrall, JH Larson, DB Kazerooni, EA Hricak, H Monsees, B Javitt, MC Crowe, JK AF Forman, Howard P. Norbash, Alexander Beauchamp, Norman J., Jr. Thrall, James H. Larson, David B. Kazerooni, Ella A. Hricak, Hedvig Monsees, Barbara Javitt, Marcia C. Crowe, John K. TI Masters of Radiology Panel Discussion: Models for Health Care Performance in Radiology-How Do We Measure Our Productivity and Ourselves? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE communications; metrics; productivity C1 [Forman, Howard P.] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA. [Norbash, Alexander] Boston Univ, Med Ctr, Dept Radiol, Boston, MA 02118 USA. [Beauchamp, Norman J., Jr.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Larson, David B.] Cincinnati Childrens Hosp, Med Ctr, Dept Radiol, Cincinnati, OH USA. [Kazerooni, Ella A.] Univ Michigan Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. [Hricak, Hedvig] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Monsees, Barbara] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, Breast Imaging Sect, St Louis, MO 63110 USA. [Javitt, Marcia C.] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. [Crowe, John K.] Scottsdale Med Imaging, Scottsdale, AZ USA. RP Forman, HP (reprint author), Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA. EM howard.forman@yale.edu OI Norbash, Alexander/0000-0003-2986-2563; Hricak, Hedvig/0000-0003-2240-9694 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2011 VL 196 IS 1 BP 130 EP 135 DI 10.2214/AJR.10.5611 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703YV UT WOS:000286018800018 PM 21178057 ER PT J AU Goldberg-Stein, S Liu, B Hahn, PF Lee, SI AF Goldberg-Stein, Shlomit Liu, Bob Hahn, Peter F. Lee, Susanna I. TI Body CT During Pregnancy: Utilization Trends, Examination Indications, and Fetal Radiation Doses SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; fetal imaging; pregnancy; radiation dose; utilization trends ID ACUTE APPENDICITIS; EXPOSURE; DIAGNOSIS; PATIENT; FETUS AB OBJECTIVE. The objective of our study was to analyze body CT utilization trends, indications, fetal radiation doses, and scanning parameters associated with high fetal radiation doses (defined as > 30 mGy). MATERIALS AND METHODS. A retrospective review of all chest and abdominopelvic CT examinations performed between 1998 and 2005 of patients known to be pregnant was conducted. Demographics, gestational age, examination indication, and scan parameters were recorded. Fetal radiation dose was calculated for those abdominopelvic examinations with direct fetal irradiation. RESULTS. From a database of more than 170,000 chest and more than 180,000 abdominopelvic CT examinations, 74 chest and 86 abdominopelvic examinations of pregnant patients were identified. Chest CT use increased on average 75%/y/1,000 deliveries in pregnancy versus 19%/y increase in all patients (p = 0.2700). Abdominopelvic CT utilization increase was on average 22%/y/1,000 deliveries in pregnant patients versus 13%/y increase in all patients (p = 0.1865). The most common indication for chest CT during pregnancy was suspected pulmonary embolism (85%, 63/74) and for abdominopelvic CT, suspected appendicitis (58%, 50/86). The average fetal dose from abdominopelvic CT was 24.8 mGy (range, 6.7-56 mGy); one examination exceeded the 50-mGy threshold for increased risk of childhood cancer. Scanning parameters associated with a dose of more than 30 mGy were a pitch of less than 1 (p = 0.0080) and more than one series acquisition (p = 0.0136). CONCLUSION. Growth of CT during pregnancy reflects the trend of increased CT utilization in the general population. Avoiding use of CT in pregnant patients with suspected appendicitis would significantly decrease fetal radiation exposure. Abdominopelvic CT during pregnancy should be carefully planned and monitored so as not to exceed the fetal radiation dose for negligible risk. C1 [Goldberg-Stein, Shlomit; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Radiol Phys, Boston, MA 02114 USA. [Hahn, Peter F.; Lee, Susanna I.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Goldberg-Stein, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Radiol Phys, 55 Fruit St,White 270, Boston, MA 02114 USA. EM sgoldberg-stein@partners.org NR 25 TC 20 Z9 21 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 EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2011 VL 196 IS 1 BP 146 EP 151 DI 10.2214/AJR.10.4271 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703YV UT WOS:000286018800021 PM 21178060 ER PT J AU Cronin, CG Prakash, P Gervais, DA Hahn, PF Arellano, R Guimares, A Mueller, PR AF Cronin, Carmel G. Prakash, Priyanka Gervais, Debra A. Hahn, Peter F. Arellano, Ronald Guimares, Alexander Mueller, Peter R. TI Imaging-Guided Suprapubic Bladder Tube Insertion: Experience in the Care of 549 Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE bladder outlet obstruction; neurogenic bladder; suprapubic tube ID TRANSURETHRAL CATHETERIZATION; BOWEL PERFORATION; CYSTOSTOMY; DRAINAGE; MANAGEMENT; SURGERY; INJURIES; RISK AB OBJECTIVE. Symptomatic bladder outlet obstruction and neurogenic bladder are common conditions that frequently necessitate suprapubic insertion of a bladder tube. The purpose of this study was to describe an experience with minimally invasive imaging-guided percutaneous suprapubic bladder tube placement and the clinical and technical success and complications encountered. MATERIALS AND METHODS. A total of 585 primary suprapubic bladder tube insertions and 439 exchanges of suprapubic bladder tubes were performed on 549 patients (469 men, 80 women; mean age, 66 years; range, 15-106 years). The details of percutaneous tube placement (indication, tube type, size at insertion and change, and method of insertion) were retrospectively recorded. RESULTS. The technical success rate for primary suprapubic bladder tube insertion was 99.6% (547/549) and for exchanges was 92.3% (405/439). The clinical success rate for primary insertion was 98.1% (572/583), and symptoms were unresolved in 1.9% (11/583). Minor complications occurred in 7.2% (42/583) of cases at tube insertion and in 4.8% (21/439) at exchange. There was one major complication (a patient needed surgery because the small bowel was traversed by a catheter), and there was no procedure-related mortality. CONCLUSION. Radiologic imaging-guided percutaneous suprapubic bladder tube placement is a safe and effective procedure. C1 [Cronin, Carmel G.; Prakash, Priyanka; Gervais, Debra A.; Hahn, Peter F.; Arellano, Ronald; Guimares, Alexander; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Cronin, CG (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 21 TC 7 Z9 7 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2011 VL 196 IS 1 BP 182 EP 188 DI 10.2214/AJR.10.4520 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703YV UT WOS:000286018800026 PM 21178065 ER PT J AU Arellano, RS Gervais, DA Mueller, PR AF Arellano, Ronald S. Gervais, Debra A. Mueller, Peter R. TI CT-Guided Drainage of Abdominal Abscesses: Hydrodissection to Create Access Routes for Percutaneous Drainage SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE abscess; CT; hydrodissection; percutaneous drainage ID RADIOFREQUENCY ABLATION; DIVERTICULITIS; MEDIASTINUM; SALINE; AID; CO2 AB OBJECTIVE. The purpose of this article is to determine the clinical effectiveness of CT-guided injection of 0.9% saline solution into the retroperitoneal space to create access routes for imaging-guided percutaneous abscess drainage. MATERIALS AND METHODS. Between January 2005 and December 2008, a radiology database was searched to identify patients who underwent CT-guided percutaneous drainage of abdominal abscesses using injection of 0.9% saline solution into the retroperitoneal space to displace vital structures and create access routes for percutaneous drainage. Patient sex and age and the cause, size, and location of the abscess were recorded. The volume of 0.9% saline solution used to displace the structures was recorded. Technical success of creating an access route and procedural success in completing percutaneous drainage were evaluated. Complications were recorded. RESULTS. Twelve patients (three men and nine women; mean age, 57 years; range, 26-84 years) with 12 abscesses underwent CT-guided percutaneous abscess drainage after injection of 0.9% saline solution into the retroperitoneum to displace structures and create an access route for drainage. The structures displaced using this technique included the ascending colon (n = 4), descending colon (n = 3), sigmoid colon (n = 2), duodenum (n = 2), and stomach (n = 1). The mean volume of 0.9% saline solution used to displace vital structures was 225 mL (range, 60-250 mL). Technical success was achieved in all 12 cases (100%). Procedural success was achieved in 11 (92%) of 12 cases. CONCLUSION. CT-guided injection of 0.9% saline solution into the retroperitoneal space is associated with a high technical success rate for displacing vital structures and creating a percutaneous access route for imaging-guided drainage of abdominal abscesses. C1 [Arellano, Ronald S.; Gervais, Debra A.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Arellano, RS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM rarellano@partners.org NR 15 TC 14 Z9 14 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2011 VL 196 IS 1 BP 189 EP 191 DI 10.2214/AJR.10.4731 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703YV UT WOS:000286018800027 PM 21178066 ER PT J AU Boland, GWL AF Boland, Giles W. L. TI Adrenal Imaging: Why, When, What, and How? Part 2. What Technique? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE adrenal; CT; MRI; PET/CT characterization C1 [Boland, Giles W. L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Boland, Giles W. L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org NR 10 TC 9 Z9 10 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2011 VL 196 IS 1 BP W1 EP W5 DI 10.2214/AJR.10.4205 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V32SY UT WOS:000208972100001 PM 21178019 ER PT J AU Medverd, JR Pugsley, JM Harley, JD Bhargava, P AF Medverd, Jonathan R. Pugsley, Jeffrey M. Harley, John D. Bhargava, Puneet TI Lateral Approach for Radiocarpal Wrist Arthrography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE arthrography; arthrography technique; CT arthrography; MR arthrography; wrist; wrist injuries; wrist joint AB OBJECTIVE. We describe a technique of radiocarpal arthrography using the lateral approach. This technique may be used as an alternative to conventional dorsal techniques. CONCLUSION. Radiocarpal injection using the lateral approach can be considered as an alternative to conventional dorsal approaches in the evaluation of wrist pain and instability. C1 [Medverd, Jonathan R.; Harley, John D.; Bhargava, Puneet] Univ Washington, Dept Radiol, VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. [Pugsley, Jeffrey M.] Univ Washington, Dept Radiol, Diagnost Radiol Residency Program, Seattle, WA 98108 USA. RP Medverd, JR (reprint author), Univ Washington, Dept Radiol, VA Puget Sound Hlth Care Syst, Seattle Div, 1660 South Columbian Way S 114 RAD, Seattle, WA 98108 USA. EM jmed@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 8 TC 2 Z9 2 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2011 VL 196 IS 1 BP W58 EP W60 DI 10.2214/AJR.10.4900 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V32SY UT WOS:000208972100009 PM 21178032 ER PT J AU Deshpande, V Gupta, R Sainani, N Sahani, DV Virk, R Ferrone, C Khosroshahi, A Stone, JH Lauwers, GY AF Deshpande, Vikram Gupta, Rajib Sainani, Nisha Sahani, Dushyant V. Virk, Renu Ferrone, Cristina Khosroshahi, Arezou Stone, John H. Lauwers, Gregory Y. TI Subclassification of Autoimmune Pancreatitis: A Histologic Classification With Clinical Significance SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE autoimmune pancreatitis; subclassification; IgG4 ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; IGG4-POSITIVE PLASMA-CELLS; DISEASE; DIAGNOSIS; LYMPHADENOPATHY; INFILTRATION; CHOLANGITIS; CARCINOMA; FEATURES; SUBTYPES AB Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of the pancreas. Examination of pancreatic resection specimens from patients with AIP has shown that there are 2 subclasses of this disease. However, there is no widely accepted pathologic classification scheme and the clinical significance of such a classification remains to be established. In this study, we revisited the subclassification of AIP and examine whether this provides clinically and prognostically meaningful information. We evaluated 29 pancreatic resection specimens from patients with AIP. Demographic, clinical, and imaging data were recorded, as was evidence of extrapancreatic manifestations. In addition to a detailed and semiquantitative histologic evaluation, immunohistochemistry for IgG4 was performed on pancreatic and extrapancreatic tissues. We also evaluated 48 consecutive cases of chronic pancreatitis, not otherwise specified. The resected specimens could readily be subclassified into 2 subtypes: type 1 (n = 11) and type 2 (n = 18). In comparison with patients with type 2 disease, patients with type 1 disease were significantly more likely to be males (P = 0.09), older (P = 0.02), and present with jaundice (P = 0.01), and less likely to be associated with abdominal pain (P = 0.04). On imaging, the pancreatic tail cut-off sign was exclusively seen in patients with type 2 disease (4 of 10 cases). Hypercellular inflamed interlobular stroma was unique to type 1 pattern (91%), whereas significant ductal injury in the form of micro-abscesses and ductal ulceration was almost exclusively seen in type 2 pattern (78%). Eight of 10 patients with a type 1 pattern had evidence of a systemic disease. Three patients with type 2 disease had recurrent episodes of pancreatitis after their pancreatic resection. In comparison with the cohort of chronic pancreatitis, not otherwise specified, type 2 AIP cases were less likely to be associated with a history of alcohol abuse, and showed significantly more foci of periductal inflammation and neutrophilic microabscesses. Our review of pancreatic resection specimens shows 2 histologically distinct forms of AIP. Our data support the concept that type 1 AIP is a systemic disease and is the pancreatic manifestation of IgG4-related systemic disease. Type 2 disease is confined to the pancreas. The intensity of the periductal inflammatory infiltrate and the presence of ductal neutrophilic abscesses are features that assist in distinguishing type 2 AIP from chronic pancreatitis, not otherwise specified. Although imperfect, clinical and imaging features may help distinguish the 2 subtypes of AIP. On the basis of these significant differences between the 2 types of AIP, we advocate the position that all subsequent studies attempt to substratify their patients into these 2 groups. C1 [Deshpande, Vikram; Gupta, Rajib; Virk, Renu; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sainani, Nisha; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ferrone, Cristina] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Khosroshahi, Arezou; Stone, John H.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol, Boston, MA 02114 USA. [Khosroshahi, Arezou; Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2-55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 30 TC 76 Z9 81 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2011 VL 35 IS 1 BP 26 EP 35 DI 10.1097/PAS.0b013e3182027717 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 695YV UT WOS:000285409900003 PM 21164284 ER PT J AU DeLair, D Oliva, E Kobel, M Macias, A Gilks, CB Soslow, RA AF DeLair, Deborah Oliva, Esther Koebel, Martin Macias, Antonio Gilks, C. Blake Soslow, Robert A. TI Morphologic Spectrum of Immunohistochemically Characterized Clear Cell Carcinoma of the Ovary: A Study of 155 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE clear cell carcinoma; ovary; HNF-1 beta; morphology; immunohistochemistry; hepatocyte nuclear factor ID HEPATOCYTE NUCLEAR FACTOR-1-BETA; DISTINCT-HISTOLOGIC-TYPE; GRADE SEROUS CARCINOMA; POOR-PROGNOSIS; ADENOCARCINOMA; TUMOR; ENDOMETRIOSIS; EXPRESSION; RESISTANCE; NEOPLASMS AB Establishing a diagnosis of ovarian clear cell carcinoma (O-CCC) can be subject to significant interobserver variation. Accurately diagnosing this tumor is important because of its chemoresistance and reported association with Lynch syndrome. The spectrum of the morphologic features of O-CCC has not been well described in a series composed of immunohistochemically characterized cases. A total of 155 cases diagnosed as O-CCC were retrieved from the files of 3 institutions to analyze architectural and cytologic features. The immunohistochemical features of these cases have been reported earlier. A comprehensive list of features was recorded, including, but not limited to, architectural patterns, nuclear appearance, cytoplasmic characteristics, and mitotic index. Between 1 and 13 slides were available for review for each case. The cases were divided into 2 groups based on morphologic characteristics, those with features shared by the large majority (the first group, n = 138) and those that showed unusual characteristics (second group, n = 17). Tumors in the first group typically showed a mixture of architectural patterns, the most frequent being papillary and tubulocystic. Papillae, usually small and round and lacking hierarchical branching and tufting or stratification of more than 3 cells, were present at least focally in almost 3 of 4 cases. The cell shape was predominantly cuboidal, not columnar. Nuclear pleomorphism and prominent nucleoli were frequently present, but never diffusely. Clear cytoplasm was found in nearly every case and hobnail cells were common. Mitoses exhibited a range from 0 to 13 with an average of 3 to 4 per 10 high power fields. The second group of tumors showed numerous unusual morphologic characteristics, despite the presence of clear cytoplasm, including those typically seen in other ovarian epithelial tumors, such as serous and endometrioid carcinoma. Eighty-nine percent of tumors from the first group showed the expected "O-CCC immunophenotype" [hepatocyte nuclear factor (HNF) positive, and estrogen receptor (ER), progesterone receptor (PR), Wilms tumor 1 (WT1) and p53 negative], whereas 4% of tumors showed HNF positivity along with focal ER or PR expression. Seven percent of tumors were not immunoreactive with these markers. Twenty-nine percent of tumors in the second group showed the O-CCC immunophenotype, whereas 24% of tumors were p53 positive, 5% of tumors were WT1 positive, and the remaining cases were negative for all markers. Ninety-seven percent (112 of 117) of HNF-positive tumors in this series were classical O-CCC. Therefore, O-CCC has characteristic morphologic features and a specific, if not unique, immunophenotype in the vast majority of the cases. Clear cell-rich tumors with features that depart from the classical morphologic appearances described herein should suggest the possibility of an alternative diagnosis. C1 [DeLair, Deborah; Macias, Antonio; Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. [Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Gilks, C. Blake] Univ Calgary, Dept Pathol, Calgary, AB, Canada. RP Soslow, RA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA. EM soslowr@mskcc.org RI Kobel, Martin/A-7373-2011; OI Soslow, Robert/0000-0002-7269-5898; Kobel, Martin/0000-0002-6615-2037 NR 22 TC 46 Z9 52 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2011 VL 35 IS 1 BP 36 EP 44 DI 10.1097/PAS.0b013e3181ff400e PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 695YV UT WOS:000285409900004 PM 21164285 ER PT J AU Coco, DP Goldblum, JR Hornick, JL Lauwers, GY Montgomery, E Srivastava, A Wang, H Odze, RD AF Coco, Dominique P. Goldblum, John R. Hornick, Jason L. Lauwers, Gregory Y. Montgomery, Elizabeth Srivastava, Amitabh Wang, Helen Odze, Robert D. TI Interobserver Variability in the Diagnosis of Crypt Dysplasia in Barrett Esophagus SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE intraepithelial neoplasia; GERD; pathology; columnar metaplasia ID ADENOCARCINOMA; REPRODUCIBILITY; LESIONS AB Recent morphologic and molecular evidence suggests that dysplasia in Barrett esophagus (BE) begins in the bases of the crypts [crypt dysplasia (CD)] and progresses with time to involve the upper portions of the crypts and surface epithelium. The aim of this study was to evaluate the criteria and reproducibility of diagnosing CD among 6 gastrointestinal pathologists, all with research interest in BE. Six gastrointestinal pathologists evaluated 2 clinical study sets, the first consisting of 40 BE cases [BE: 10, CD: 9, low-grade dysplasia (LGD): 10, high-grade dysplasia (HGD); 9, and intramucosal adenocarcinoma; 2] and the second consisting of 63 cases (BE: 16, CD: 15, LGD: 15, HGD: 15, and intramucosal adenocarcinoma: 2), at least 4 months apart. In between evaluations, all of the pathologists met at 1 hospital (consensus conference) to review the areas of disagreement and establish more objective criteria. Overall, the level of agreement for all cases was moderate (kappa = 0.44), and the level of agreement did not change significantly after evaluation of the second study set. The highest levels of agreement were obtained for lesions at the low and high end of the spectrum (BE without dysplasia and HGD). Overall, the degree of agreement for CD was moderate after both the first and second study set review (kappa = 0.44 and 0.46, respectively). However, the degree of agreement for CD was higher than that obtained for LGD in both study sets. In the first study set, 4 or more pathologists agreed with the original CD diagnosis in 78% of cases, and this value did not change significantly after review of the second study set. The observers agreed that characteristic features of CD include the presence of unequivocal dysplastic cells, similar in appearance to traditional LGD, involving any part, or all of the length, of the crypt in the absence of intercrypt surface epithelial involvement. Rare cases of CD may show high-grade cytologic features composed of markedly enlarged nuclei with increased nuclear/cytoplasmic ratio, eosinophilic cytoplasm, irregular nuclear membranes, and loss of polarity. The findings in this study suggest that CD can be diagnosed reliably with a moderate level of interobserver agreement. Long-term and multi-institutional studies should be carried out to further determine the biological and clinical significance and natural history of CD in patients with BE. C1 [Odze, Robert D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Wang, Helen] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldblum, John R.] Cleveland Clin, Cleveland, OH 44106 USA. [Montgomery, Elizabeth] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Srivastava, Amitabh] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Odze, RD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM rodze@partners.org OI Coco, Dominique/0000-0002-8448-2267 NR 12 TC 37 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2011 VL 35 IS 1 BP 45 EP 54 DI 10.1097/PAS.0b013e3181ffdd14 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 695YV UT WOS:000285409900005 PM 21164286 ER PT J AU Dailey, NJM Young, EJ AF Dailey, Natalie J. M. Young, Edward J. TI Candida glabrata Spinal Osteomyelitis SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Candida glabrata; Torulopsis glabrata; Osteomyelitis; Disseminated infection ID TORULOPSIS-GLABRATA; VERTEBRAL OSTEOMYELITIS; INVASIVE CANDIDIASIS; CASPOFUNGIN; ALBICANS AB Invasive disease caused by Candida spp. is being appreciated with increased frequency especially associated with widespread use of immunosuppressive drug therapy. We report a case of spinal osteomyelitis and epidural abscess caused by Candida glabrata occurring in a patient who had been diagnosed with candidemia 3 months before that patient was treated with fluconazole. The infection was successfully treated with amphotericin B, but the patient eventually required surgical intervention for spondylolisthesis with impingement on the cauda equina. C1 Baylor Coll Med, Med Serv, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Dailey, NJM (reprint author), N Carolina Div Publ Hlth, 1902 Mail Serv Ctr, Raleigh, NC 27669 USA. EM janine.dailey@dhhs.nc.gov NR 18 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2011 VL 341 IS 1 BP 78 EP 82 DI 10.1097/MAJ.0b013e3181f6c6ea PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 716MQ UT WOS:000286973800016 PM 21030857 ER PT J AU Mannello, F Raffetto, JD AF Mannello, Ferdinando Raffetto, Joseph D. TI Matrix metalloproteinase activity and glycosaminoglycans in chronic venous disease: the linkage among cell biology, pathology and translational research SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Review DE Matrix metalloproteinase; glycosaminoglycan; chronic venous disease; inflammation; venous ulcer; leukocyte; fibroblast; dermatan sulphate; varicose vein; tissue inhibitor of MMP AB Primary chronic venous disease (CVD) is an inflammatory pathology involving an erratic structural remodeling in the venous well leading to vascular incompetence and the development of varicose vein, characterized by altered collagen and elastin content. In the early steps of varicose vein formation is crucial the role of MMP/TIMP balance, implicated in both ECM and vascular degradation during inflammation processes in early and late stages of venous diseases. Although several pharmacological and surgical strategies are being utilized in the management of varicose vein and CVD with variable success and recurrence rate, inhibition of MMP through glycosaminoglycans may represent a novel therapeutic intervention to limit the progression of varicose vein to CVD and leg ulceration, suggesting possible opportunity to prevent future morbidity and enhancing clinical benefits and quality of life. C1 [Mannello, Ferdinando] Univ Carlo Bo, Cell Biol Unit, Dept Biomol Sci, Clin Biochem Sect, I-61029 Urbino, PU, Italy. [Raffetto, Joseph D.] VA Boston Healthcare Syst, Div Vasc Surg, West Roxbury, MA USA. [Raffetto, Joseph D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Mannello, F (reprint author), Univ Carlo Bo, Cell Biol Unit, Dept Biomol Sci, Clin Biochem Sect, Via O Ubaldini 7, I-61029 Urbino, PU, Italy. EM ferdinando.mannello@uniurb.it OI Mannello, Ferdinando/0000-0001-8112-6139 NR 82 TC 29 Z9 32 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2011 VL 3 IS 2 BP 149 EP 158 PG 10 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA V28QF UT WOS:000208694600004 PM 21416057 ER PT J AU Lee, G Gardner, BK Elashoff, DA Purcell, CM Sandha, HS Mao, JT Krysan, K Lee, JM Dubinett, SM AF Lee, Gina Gardner, Brian K. Elashoff, David A. Purcell, Colleen M. Sandha, Harpavan S. Mao, Jenny T. Krysan, Kostyantyn Lee, Jay M. Dubinett, Steven M. TI Elevated levels of CXC chemokine connective tissue activating peptide (CTAP)-III in lung cancer patients SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Article DE Lung cancer; connective tissue activating peptide (CTAP)-III; neutrophil activating peptide (NAP)-2; CXC chemokines AB Despite advances in treatments, lung cancer has been the leading cause of cancer-related deaths in the United States for the past several decades. Recent findings from the National Lung Screening Trial reveal that low-dose helical computed tomography (CT) scan screening of high-risk individuals reduces lung cancer mortality. This suggests that early detection is of key importance to improving patient outcome. However, of those screened with CT scans, 25% had positive scans that require further follow-up studies which often involve more radiation exposure and invasive tests to reduce false positive results. The purpose of this study was to identify candidate plasma biomarkers to aid in diagnosis of lung cancer in at-risk individuals. We found increased expression of the CXC chemokine connective tissue-activating peptide (CTAP)-III from plasma specimens of lung cancer patients compared to at-risk control subjects. Identification of the peptide was confirmed by the addition of an anti-NAP-2 antibody that recognizes CTAP-III and NAP-2. We also quantified and verified the increased levels of plasma CTAP-III with ELISA in patients with lung cancer (mean +/- SD, 1859 +/- 1219 ng/mL) compared to controls (698 +/- 434 ng/mL; P<0.001). Our findings demonstrate elevated plasma levels of CTAP-III occur in lung cancer patients. Further studies are required to determine if this chemokine could be utilized in a blood-based biomarker panel for the diagnosis of lung cancer. C1 [Lee, Gina; Gardner, Brian K.; Elashoff, David A.; Purcell, Colleen M.; Sandha, Harpavan S.; Krysan, Kostyantyn; Lee, Jay M.; Dubinett, Steven M.] Univ Calif Los Angeles, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Lee, Gina; Gardner, Brian K.; Elashoff, David A.; Purcell, Colleen M.; Sandha, Harpavan S.; Krysan, Kostyantyn; Dubinett, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Lee, Jay M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Lee, Gina; Gardner, Brian K.; Dubinett, Steven M.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Mao, Jenny T.] New Mexico Vet Affairs Healthcare Syst, Dept Med, Albuquerque, NM USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. EM bgardner@mednet.ucla.edu; SDubinett@mednet.ucla.edu FU National Institutes of Health [U01 CA152751, 1 P50 CA90388]; LUNGevity Foundation; Medical Research Funds from the Department of Veterans Affairs FX This work was supported by the National Institutes of Health U01 CA152751 and 1 P50 CA90388, the LUNGevity Foundation, and Medical Research Funds from the Department of Veterans Affairs. NR 31 TC 3 Z9 3 U1 0 U2 1 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2011 VL 3 IS 3 BP 226 EP 233 PG 8 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA V28QG UT WOS:000208694700001 PM 21654877 ER PT J AU Orloff, SL Hwee, YK Kreklywich, C Andoh, TF Hart, E Smith, PA Messaoudi, I Streblow, DN AF Orloff, S. L. Hwee, Y. -K. Kreklywich, C. Andoh, T. F. Hart, E. Smith, P. A. Messaoudi, I. Streblow, D. N. TI Cytomegalovirus Latency Promotes Cardiac Lymphoid Neogenesis and Accelerated Allograft Rejection in CMV Naive Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Chronic rejection; cytomegalovirus; latency; transplant vascular sclerosis ID TRANSPLANT VASCULAR SCLEROSIS; APOE KNOCKOUT MICE; RAT SMALL-BOWEL; T-CELLS; MEMORY INFLATION; RENAL-ALLOGRAFT; HEART-TRANSPLANTS; RISK-FACTORS; INFECTION; DISEASE AB Human cytomegalovirus (HCMV) infection is associated with the acceleration of transplant vascular sclerosis (TVS) and chronic allograft rejection (CR). HCMV-negative recipients of latently HCMV infected donor grafts are at highest risk for developing CMV disease. Using a rat heart transplant CR model, we have previously shown that acute rat CMV (RCMV) infection following transplantation significantly accelerates both TVS and CR. Here, we report that RCMV-naive recipients of heart allografts from latently RCMV-infected donors undergo acceleration of CR with similar kinetics as acutely infected recipients. In contrast to acutely infected recipients, treatment of recipients of latently infected donor hearts with ganciclovir did not prevent CR or TVS. We observed the formation of tertiary lymphoid structures (TLOs) containing macrophages and T cells in latently infected hearts prior to transplantation but not in uninfected rats. Moreover, pathway analysis of gene expression data from allografts from latently infected donors indicated an early and sustained production of TLO-associated genes compared to allografts from uninfected donors. We conclude that RCMV-induced TLO formation and alteration of donor tissue T cell profiles prior to transplantation in part mediate the ganciclovir-insensitive rejection of latently infected donor allografts transplanted into naive recipients by providing a scaffold for immune activation. C1 [Orloff, S. L.; Hwee, Y. -K.; Kreklywich, C.; Andoh, T. F.; Streblow, D. N.] Portland VA Med Ctr, Portland, OR USA. [Orloff, S. L.; Hwee, Y. -K.; Kreklywich, C.; Andoh, T. F.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR USA. [Orloff, S. L.; Kreklywich, C.; Smith, P. A.; Messaoudi, I.; Streblow, D. N.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR USA. [Orloff, S. L.; Kreklywich, C.; Hart, E.; Smith, P. A.; Messaoudi, I.; Streblow, D. N.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR USA. RP Streblow, DN (reprint author), Portland VA Med Ctr, Portland, OR USA. EM streblow@ohsu.edu FU Department of Veterans Affairs; National Institutes of Health [HL 66238-01, HL083194, HL 088603]; AHA FX This work was supported by research grants to S.L. Orloff from the Department of Veterans Affairs and from the National Institutes of Health (HL 66238-01) and grants from the National Institutes of Health to D.N. Streblow (HL083194) and J.A. Nelson (HL 088603). D.N. Streblow and I. Messaoudi are supported by AHA Scientist Development Grants. NR 50 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2011 VL 11 IS 1 BP 45 EP 55 DI 10.1111/j.1600-6143.2010.03365.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 700ZG UT WOS:000285783500010 PM 21199347 ER PT J AU Pedrelli, P Bitran, S Shyu, I Baer, L Guidi, J Tucker, DD Vitali, M Fava, M Zisook, S Farabaugh, AH AF Pedrelli, Paola Bitran, Stella Shyu, Irene Baer, Lee Guidi, Jenny Tucker, Dorothy D. Vitali, Mario Fava, Maurizio Zisook, Sidney Farabaugh, Amy H. TI Compulsive Alcohol Use and Other High-Risk Behaviors among College Students SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID BINGE-DRINKING; UNIVERSITY-STUDENTS; GAMBLING ACTIVITIES; HARVARD-SCHOOL; YOUNG-ADULTS; MARIJUANA; PATTERNS; GENDER; MODELS; TRENDS AB The association between heavy alcohol consumption and risky behaviors has been amply investigated among college students. However, less is known with regard to types of drinking behaviors associated with high-risk activities. The present study extends this area of research by examining the relationship between compulsive drinking and hazardous behaviors in this population. Nine hundred and four college students completed measures on compulsive drinking and other risky behaviors in the context of mental health screenings at three campuses. Results showed that in males, compulsive drinking increased the risk for compulsive street drugs use, compulsive prescription drugs use, compulsive sexual activities, and gambling. Among females, compulsive drinking increased the risk for compulsive street drugs use, and compulsive sexual activities. These findings suggest that inquiring about compulsive drinking among college students may have great utility in identifying those at greater risk for other risky behaviors. The high co-occurrence of compulsive drinking, illicit substances, compulsive sexual activities, and gambling in college students suggests the need for comprehensive programs addressing high-risk behaviors together. (Am J Addict 2010;00:1-7). C1 [Pedrelli, Paola] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress & Clin Res Program, Boston, MA 02114 USA. [Guidi, Jenny] Univ Bologna, Dept Psychol, Bologna, Italy. [Tucker, Dorothy D.] Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. [Tucker, Dorothy D.] Vanderbilt Univ, Dept Psychiat, Nashville, TN 37240 USA. [Tucker, Dorothy D.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Vitali, Mario] Univ Roma La Sapienza, Dept Clin Med, Rome, Italy. [Zisook, Sidney] Univ Calif San Diego, San Diego VA Healthcare Syst, San Diego, CA 92103 USA. RP Pedrelli, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress & Clin Res Program, 6th Fl, Boston, MA 02114 USA. EM ppedrelli@partners.org NR 34 TC 7 Z9 8 U1 4 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JAN-FEB PY 2011 VL 20 IS 1 BP 14 EP 20 DI 10.1111/j.1521-0391.2010.00090.x PG 7 WC Substance Abuse SC Substance Abuse GA 700NM UT WOS:000285750600003 PM 21175916 ER PT J AU Ballenger, JF Best, SR Metzler, TJ Wasserman, DA Mohr, DC Liberman, A Delucchi, K Weiss, DS Fagan, JA Waldrop, AE Marmar, CR AF Ballenger, James F. Best, Suzanne R. Metzler, Thomas J. Wasserman, David A. Mohr, David C. Liberman, Akiva Delucchi, Kevin Weiss, Daniel S. Fagan, Jeffrey A. Waldrop, Angela E. Marmar, Charles R. TI Patterns and Predictors of Alcohol Use in Male and Female Urban Police Officers SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CRITICAL INCIDENT EXPOSURE; PERITRAUMATIC DISSOCIATION; SOCIAL DESIRABILITY; OCCUPATIONAL STRESS; SCREENING-TEST; RISK-FACTORS; SCALE; PERSONNEL; CONSUMPTION AB In a large sample of urban police officers, 18.1% of males and 15.9% of females reported experiencing adverse consequences from alcohol use and 7.8% of the sample met criteria for lifetime alcohol abuse or dependence. Female officers had patterns of alcohol use similar to male officers and substantially more than females in the general population. Critical incident exposure and posttraumatic stress disorder (PTSD) symptoms were not associated with level of alcohol use. Greater psychiatric symptoms were related to adverse consequences from alcohol use. There was a noteworthy gender by work stress interaction: greater routine work stress related to lower current alcohol use in female officers. (Am J Addict 2010;00:1-9). C1 [Ballenger, James F.; Best, Suzanne R.; Metzler, Thomas J.; Wasserman, David A.; Mohr, David C.; Waldrop, Angela E.; Marmar, Charles R.] Dept Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [Metzler, Thomas J.; Delucchi, Kevin; Weiss, Daniel S.; Waldrop, Angela E.; Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Liberman, Akiva] Natl Inst Justice, Washington, DC USA. [Fagan, Jeffrey A.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. RP Waldrop, AE (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116P, San Francisco, CA 94121 USA. EM angela.waldrop@ucsf.edu FU NCRR NIH HHS [UL1 RR025741]; NICHD NIH HHS [RL1 HD058295]; NIMH NIH HHS [R01 MH056350, R01 MH056350-03S1] NR 38 TC 11 Z9 12 U1 3 U2 16 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JAN-FEB PY 2011 VL 20 IS 1 BP 21 EP 29 DI 10.1111/j.1521-0391.2010.00092.x PG 9 WC Substance Abuse SC Substance Abuse GA 700NM UT WOS:000285750600004 PM 21175917 ER PT J AU Simpson, TL Galloway, C Rosenthal, CF Bush, KR McBride, B Kivlahan, DR AF Simpson, Tracy L. Galloway, Christopher Rosenthal, Christina F. Bush, Kristen R. McBride, Brittney Kivlahan, Daniel R. TI Daily Telephone Monitoring Compared with Retrospective Recall of Alcohol Use among Patients in Early Recovery SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID ECOLOGICAL MOMENTARY ASSESSMENT; TIMELINE FOLLOW-BACK; DRINKING PATTERNS; REACTIVITY; CONSUMPTION; RELIABILITY; VARIABLES; VALIDITY; DRUG AB Most studies comparing frequent self-monitoring protocols and retrospective assessments of alcohol use find good correspondence, but have excluded participants with significant comorbidity and/or social instability, and some have included abstainers. We evaluated the correspondence between measures of alcohol use based on daily interactive voice response (IVR) telephone monitoring and a 28-day modification of the Form-90 (Form-28). Participants were 25 outpatients with alcohol use disorder and significant PTSD symptomatology. Overall correlations between the IVR and Form-28 on days drinking and total standard drink units (SDUs) were strong for the entire sample and the subsample of drinkers (n = 7). Day-to-day correspondence between IVR and Form-28 was modest, but much stronger for the most recent week assessed than for the prior 3 weeks. Finally, the drinkers reported significantly greater total SDUs and heavy drinking days on the Form-28 than via IVR. The results indicate a need for further refinement of IVR methodology for treatment seeking populations as well as caution when retrospectively assessing drinking over time periods longer than a week among these individuals. (Am J Addict 2010;00:1-6). C1 [Simpson, Tracy L.; Bush, Kristen R.; McBride, Brittney; Kivlahan, Daniel R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Simpson, Tracy L.; Kivlahan, Daniel R.] VISN 20 Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Simpson, Tracy L.; Bush, Kristen R.; McBride, Brittney; Kivlahan, Daniel R.] Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Simpson, Tracy L.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Simpson, Tracy L.; Rosenthal, Christina F.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. [Galloway, Christopher] San Francisco VA Med Ctr, San Francisco, CA USA. RP Simpson, TL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,ATC-116-S, Seattle, WA 98108 USA. EM Tracy.Simpson@va.gov NR 31 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JAN-FEB PY 2011 VL 20 IS 1 BP 63 EP 68 DI 10.1111/j.1521-0391.2010.00094.x PG 6 WC Substance Abuse SC Substance Abuse GA 700NM UT WOS:000285750600009 PM 21175922 ER PT J AU Sherman, A Bowser, R Grasso, D Power, B Milligan, C Jaffa, M Cudkowicz, M AF Sherman, Alex Bowser, Robert Grasso, Daniela Power, Breen Milligan, Carol Jaffa, Matthew Cudkowicz, Merit TI Proposed BioRepository platform solution for the ALS research community SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE ALS; BioRepository; BioBank; biomarkers AB ALS is a rare disorder whose cause and pathogenesis is largely unknown (1). There is a recognized need to develop biomarkers for ALS to better understand the disease, expedite diagnosis and to facilitate therapy development. Collaboration is essential to obtain a sufficient number of samples to allow statistically meaningful studies. The availability of high quality biological specimens for research purposes requires the development of standardized methods for collection, long-term storage, retrieval and distribution of specimens. The value of biological samples to scientists and clinicians correlates with the completeness and relevance of phenotypical and clinical information associated with the samples (2,3). While developing a secure Web-based system to manage an inventory of multi-site BioRepositories, algorithms were implemented to facilitate ad hoc parametric searches across heterogeneous data sources that contain data from clinical trials and research studies. A flexible schema for a barcode label was introduced to allow association of samples to these data. The ALSBank (TM) BioRepository platform solution for managing biological samples and associated data is currently deployed by the Northeast ALS Consortium (NEALS). The NEALS Consortium and the Massachusetts General Hospital (MGH) Neurology Clinical Trials Unit (NCTU) support a network of multiple BioBanks, thus allowing researchers to take advantage of a larger specimen collection than they might have at an individual institution. Standard operating procedures are utilized at all collection sites to promote common practices for biological sample integrity, quality control and associated clinical data. Utilizing this platform, we have created one of the largest virtual collections of ALS-related specimens available to investigators studying ALS. C1 [Sherman, Alex; Grasso, Daniela; Power, Breen; Jaffa, Matthew; Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Trial Unit, Charlestown, MA 02129 USA. [Bowser, Robert] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Milligan, Carol] Wake Forest Univ, Bowman Gray Sch Med, Dept Neurobiol & Anat, Winston Salem, NC USA. RP Sherman, A (reprint author), Massachusetts Gen Hosp, Neurol Clin Trial Unit, 149 13th St,Room 2274, Charlestown, MA 02129 USA. EM avsherman@partners.org FU TREAT ALS FX The ALS Association partially funded this effort through a TREAT ALS grant. The authors thank Michael Benatar of the Department of Neurology, Emory University School of Medicine for his active participation in the ALSBank (TM) virtual BioRepository project and his constructive critique of this manuscript. NR 13 TC 5 Z9 5 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD JAN PY 2011 VL 12 IS 1 BP 11 EP 16 DI 10.3109/17482968.2010.539233 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 724UN UT WOS:000287601800002 PM 21128868 ER PT J AU Voight, BF AF Voight, Benjamin F. BE Zeggini, E Morris, A TI Delineating Signals from Association Studies SO ANALYSIS OF COMPLEX DISEASE ASSOCIATION STUDIES: A PRACTICAL GUIDE LA English DT Article; Book Chapter ID GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUSCEPTIBILITY LOCI; TYROSINE-PHOSPHATASE; IRF5 POLYMORPHISMS; FUNCTIONAL VARIANT; COMMON DISEASES; COMPLEX TRAITS; RARE VARIANTS; RISK LOCI C1 [Voight, Benjamin F.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA USA. RP Voight, BF (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA. NR 49 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-375143-0 PY 2011 BP 277 EP 293 DI 10.1016/B978-0-12-375142-3.10017-3 PG 17 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA BGD25 UT WOS:000322375500017 ER PT J AU Pfab, F Winhard, M Nowak-Machen, M Napadow, V Irnich, D Pawlik, M Bein, T Hansen, E AF Pfab, Florian Winhard, Martina Nowak-Machen, Martina Napadow, Vitaly Irnich, Dominik Pawlik, Michael Bein, Thomas Hansen, Ernil TI Acupuncture in Critically III Patients Improves Delayed Gastric Emptying: A Randomized Controlled Trial SO ANESTHESIA AND ANALGESIA LA English DT Article ID FUNCTIONAL GASTROINTESTINAL DISORDERS; EARLY PARENTERAL-NUTRITION; ILL PATIENTS; ELECTRICAL-STIMULATION; ACUPOINT STIMULATION; POINT STIMULATION; ENTERAL NUTRITION; HEALTHY-SUBJECTS; CRITICAL-CARE; MODULATION AB BACKGROUND: Malnutrition remains a severe problem in the recovery of critically ill patients and leads to increased in-hospital morbidity and in-hospital stay. Even though early enteral nutrition has been shown to improve overall patient outcomes in the intensive care unit (ICU), tubefeed administration is often complicated by delayed gastric emptying and gastroesophageal reflux. Acupuncture has been successfully used in the treatment and prevention of perioperative nausea and vomiting. In this study we evaluated whether acupuncture can improve gastric emptying in comparison with standard promotility drugs in critically ill patients receiving enteral feeding. METHODS: Thirty mechanically ventilated neurosurgical ICU patients with delayed gastric emptying, defined as a gastric residual volume (GRV) >500 mL for >= 2 days, were prospectively and randomly assigned to either the acupoint stimulation group (ASG; bilateral transcutaneous electrical acupoint stimulation at Neiguan, PC-6) or the conventional promotility drug treatment group (DTG) over a period of 6 days (metoclopramide, cisapride, erythromycin). Patients in the ASG group did not receive any conventional promotility drugs. Successful treatment (feeding tolerance) was defined as GRV ,200 mL per 24 hours. RESULTS: Demographic and hemodynamic data were similar in both groups. After 5 days of treatment, 80% of patients in the ASG group successfully developed feeding tolerance versus 60% in the DTG group. On treatment day 1, GRV decreased from 970 +/- 87 mL to 346 +/- 71 mL with acupoint stimulation (P = 0.003), whereas patients in the DTG group showed a significant increase in GRV from 903 +/- 60 mL to 1040 +/- 211 mL (P = 0.015). In addition, GRV decreased and feeding balance (defined as enteral feeding volume minus GRV) increased in more patients in the ASG group (14 of 15) than in the DTG group (7 of 15; P = 0.014). On treatment day 1, the mean feeding balance was significantly higher in the ASG group (121 +/- 128 mL) than in the DTG group (-727 +/- 259 mL) (P = 0.005). Overall, the feeding balance improved significantly on all days of treatment in comparison with the DTG group. Patients in the DTG group did not show an increase in feeding balance until day 6. CONCLUSIONS: We introduce a new protocol for acupuncture administration in the critical care setting. We demonstrated that this protocol was more effective than standard promotility medication in the treatment of delayed gastric emptying in critically ill patients. Acupoint stimulation at Neiguan (PC-6) may be a convenient and inexpensive option (with few side effects) for the prevention and treatment of malnutrition in critically ill patients. (Anesth Analg 2011;112:150-5) C1 [Pfab, Florian; Winhard, Martina; Pawlik, Michael; Bein, Thomas; Hansen, Ernil] Univ Hosp Regensburg, Dept Anesthesiol, D-93053 Regensburg, Germany. [Pfab, Florian; Napadow, Vitaly] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Boston, MA 02115 USA. [Nowak-Machen, Martina] Harvard Univ, Brigham & Womens Hosp, Dept Anesthesiol, Sch Med, Boston, MA 02115 USA. [Irnich, Dominik] Univ Munich, Dept Anesthesiol, Munich, Germany. RP Hansen, E (reprint author), Univ Hosp Regensburg, Dept Anesthesiol, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. EM ernil.hansen@klinik.uni-regensburg.de FU Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany FX The study was funded by the Department of Anesthesiology, University Hospital Regensburg, Regensburg, Germany. NR 36 TC 17 Z9 21 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2011 VL 112 IS 1 BP 150 EP 155 DI 10.1213/ANE.0b013e3181fdfac8 PG 6 WC Anesthesiology SC Anesthesiology GA 696PQ UT WOS:000285454300024 PM 21081772 ER PT J AU Ishizawa, Y AF Ishizawa, Yumiko TI General Anesthetic Gases and the Global Environment SO ANESTHESIA AND ANALGESIA LA English DT Article ID NITROUS-OXIDE N2O; VOLATILE ANESTHETICS; HALOGENATED ANESTHETICS; ATMOSPHERIC LIFETIMES; STRATOSPHERIC OZONE; ISOFLURANE; XENON; CLIMATE; SEVOFLURANE; DESFLURANE AB General anesthetics are administered to approximately 50 million patients each year in the United States. Anesthetic vapors and gases are also widely used in dentists' offices, veterinary clinics, and laboratories for animal research. All the volatile anesthetics that are currently used are halogenated compounds destructive to the ozone layer. These halogenated anesthetics could have potential significant impact on global warming. The widely used anesthetic gas nitrous oxide is a known greenhouse gas as well as an important ozone-depleting gas. These anesthetic gases and vapors are primarily eliminated through exhalation without being metabolized in the body, and most anesthesia systems transfer these gases as waste directly and unchanged into the atmosphere. Little consideration has been given to the ecotoxicological properties of gaseous general anesthetics. Our estimation using the most recent consumption data indicates that the anesthetic use of nitrous oxide contributes 3.0% of the total emissions in the United States. Studies suggest that the influence of halogenated anesthetics on global warming will be of increasing relative importance given the decreasing level of chlorofluorocarbons globally. Despite these nonnegligible pollutant effects of the anesthetics, no data on the production or emission of these gases and vapors are publicly available. The primary goal of this article is to critically review the current data on the potential effects of general anesthetics on the global environment and to describe possible alternatives and new technologies that may prevent these gases from being discharged into the atmosphere. (Anesth Analg 2011;112:213-7) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Ishizawa, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St Gray Bigelow 444, Boston, MA 02114 USA. EM yishizawa@partners.org NR 37 TC 18 Z9 20 U1 2 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2011 VL 112 IS 1 BP 213 EP 217 DI 10.1213/ANE.0b013e3181fe02c2 PG 5 WC Anesthesiology SC Anesthesiology GA 696PQ UT WOS:000285454300033 PM 21048097 ER PT J AU Schmidt, U Eikermann, M AF Schmidt, Ulrich Eikermann, Matthias TI Organizational Aspects of Difficult Airway Management Think Globally, Act Locally SO ANESTHESIOLOGY LA English DT Editorial Material ID PRACTICE GUIDELINES; ANESTHESIOLOGISTS; COMPLICATIONS; INTUBATION C1 [Schmidt, Ulrich] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmidt, U (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM meikermann@partners.org NR 10 TC 12 Z9 14 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2011 VL 114 IS 1 BP 3 EP 6 DI 10.1097/ALN.0b013e318201c6ff PG 4 WC Anesthesiology SC Anesthesiology GA 697UB UT WOS:000285542700002 PM 21139498 ER PT J AU Edlow, BL Wainger, BJ Rathmell, JP Rost, NS AF Edlow, Brian L. Wainger, Brian J. Rathmell, James P. Rost, Natalia S. TI It Is Time to Abandon Atlanto-Axial Joint Injections: Do No Harm! Reply SO ANESTHESIOLOGY LA English DT Letter C1 [Rost, Natalia S.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. EM nrost@partners.org NR 3 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2011 VL 114 IS 1 BP 224 EP 224 DI 10.1097/ALN.0b013e318201d522 PG 1 WC Anesthesiology SC Anesthesiology GA 697UB UT WOS:000285542700041 ER PT J AU Reiner, T Keliher, EJ Earley, S Marinelli, B Weissleder, R AF Reiner, Thomas Keliher, Edmund J. Earley, Sarah Marinelli, Brett Weissleder, Ralph TI Synthesis and In Vivo Imaging of a F-18-Labeled PARP1 Inhibitor Using a Chemically Orthogonal Scavenger-Assisted High-Performance Method SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cancer therapy; chemically orthogonal conjugation; in vivo imaging; positron emission tomography; scavenger resin ID POSITRON-EMISSION-TOMOGRAPHY; POLY(ADP-RIBOSE) POLYMERASE-1; LIVING CELLS; CHEMISTRY; ONCOLOGY; CANCER C1 [Reiner, Thomas; Keliher, Edmund J.; Earley, Sarah; Marinelli, Brett; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu OI Reiner, Thomas/0000-0002-7819-5480 FU NIH [P50 CA86355, RO1 EB-010011]; Deutschen Akademie der Wissenschaften Leopoldina [LPDS 2009-24] FX We thank Dr. Ralph Mazitschek and Dr. Neal Devaraj for helpful discussions. This research was supported in part by the NIH (grants P50 CA86355 and RO1 EB-010011). T.R. received a stipend from the Deutschen Akademie der Wissenschaften Leopoldina (LPDS 2009-24). NR 22 TC 55 Z9 55 U1 1 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 8 BP 1922 EP 1925 DI 10.1002/anie.201006579 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 727XJ UT WOS:000287836200035 PM 21328671 ER PT J AU Zhang, ZD Kolodziej, AF Greenfield, MT Caravan, P AF Zhang, Zhaoda Kolodziej, Andrew F. Greenfield, Matthew T. Caravan, Peter TI Heteroditopic Binding of Magnetic Resonance Contrast Agents for Increased Relaxivity SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE fibrin; gadolinium; magnetic resonance imaging; peptides; rotational dynamics ID MRI; THROMBUS; EP-2104R C1 [Zhang, Zhaoda; Caravan, Peter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Caravan, P (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Institute of Biomedical Imaging and Bioengineering [R01EB009062] FX This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering, R01EB009062. NR 20 TC 18 Z9 18 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 11 BP 2621 EP 2624 DI 10.1002/anie.201007689 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 730MO UT WOS:000288037600034 PM 21370351 ER PT J AU Subtelny, AO Hartman, MCT Szostak, JW AF Subtelny, Alexander O. Hartman, Matthew C. T. Szostak, Jack W. TI Optimal Codon Choice Can Improve the Efficiency and Fidelity of N-Methyl Amino Acid Incorporation into Peptides by In-Vitro Translation SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE amino acids; codon-anticodon recognition; directed evolution; peptidomimetics; translational fidelity ID SITE-SPECIFIC INCORPORATION; NONNATURAL RESIDUES; ESCHERICHIA-COLI; TRANSFER-RNAS; SPECIFICITY; PROTEIN C1 [Subtelny, Alexander O.; Hartman, Matthew C. T.; Szostak, Jack W.] Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. [Subtelny, Alexander O.; Hartman, Matthew C. T.; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Hartman, Matthew C. T.] Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 USA. [Hartman, Matthew C. T.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23284 USA. [Subtelny, Alexander O.] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Szostak, JW (reprint author), Howard Hughes Med Inst, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute; Harvard College FX We thank Drs. A. Bell, Y. Guillen, K. Josephson, C.-W. Lin, F. Seebeck, D. Treco, R. Green, and U. RajBhandary for reagents and useful discussions. This work was supported by the Howard Hughes Medical Institute, and A.O.S. was supported in part by the Harvard College Research Program. NR 19 TC 6 Z9 6 U1 1 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 14 BP 3164 EP 3167 DI 10.1002/anie.201007686 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 740LR UT WOS:000288796600006 PM 21381166 ER PT J AU Yoon, TJ Lee, H Shao, HL Weissleder, R AF Yoon, Tae-Jong Lee, Hakho Shao, Huilin Weissleder, Ralph TI Highly Magnetic Core-Shell Nanoparticles with a Unique Magnetization Mechanism SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE biosensors; iron; magnetic properties; magnetic resonance imaging; nanoparticles ID MONODISPERSE FE NANOPARTICLES; IRON NANOPARTICLES; PARTICLES; CELLS C1 [Yoon, Tae-Jong; Lee, Hakho; Shao, Huilin; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Lee, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu FU National Institute of Health [2R01-EB004626, U54-CA119349]; TPEN [HHSN268201000044C] FX The authors thank C. Ross (MIT) for her generous support in magnetic measurements; R. Zhang, G. Wojtkiewicz, J. Figueiredo, J. Chen and M. Nahrendorf for their assistance in MRI; N. Sergeyev for synthesizing CLIO; D. Issadore, M. Liong and E. Keliher for helpful discussions; Y. Fisher-Jeffes for reviewing the manuscript. This work was supported by National Institute of Health Grants 2R01-EB004626, U54-CA119349, and TPEN contract (HHSN268201000044C). NR 16 TC 57 Z9 58 U1 6 U2 49 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 20 BP 4663 EP 4666 DI 10.1002/anie.201100101 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 764VW UT WOS:000290663600020 PM 21495138 ER PT J AU Budin, G Yang, KS Reiner, T Weissleder, R AF Budin, Ghyslain Yang, Katherine S. Reiner, Thomas Weissleder, Ralph TI Bioorthogonal Probes for Polo-like Kinase 1 Imaging and Quantification SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cancer; cell cycle; cycloaddition; live cell imaging; polo-like kinase ID BOX DOMAIN; PLK1 SUBSTRATE; PROPHASE; PHOSPHORYLATION; DIVISION; CDC25C; CELLS; TEAM C1 [Budin, Ghyslain; Yang, Katherine S.; Reiner, Thomas; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu OI Reiner, Thomas/0000-0002-7819-5480 FU National Institutes of Health (NIH) [RO1EB010011, T32-CA79443]; German Academy of Sciences Leopoldina [LPDS 2009-24] FX This work was supported by the National Institutes of Health (NIH) grant number RO1EB010011, K.S. was supported by a NIH grant T32-CA79443 and T.R. was supported by a grant from the German Academy of Sciences Leopoldina (LPDS 2009-24). We thank Joshua Dunham and Alex Zaltsman for image processing, and Dr. Robert Yang and Prof. Peter Sorger for assistance with cellWoRx and Image Rail. NR 24 TC 37 Z9 37 U1 1 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 40 BP 9378 EP 9381 DI 10.1002/anie.201103273 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 835XZ UT WOS:000296071700018 PM 21948435 ER PT J AU Chauhan, VP Popovic, Z Chen, O Cui, J Fukumura, D Bawendi, MG Jain, RK AF Chauhan, Vikash P. Popovic, Zoran Chen, Ou Cui, Jian Fukumura, Dai Bawendi, Moungi G. Jain, Rakesh K. TI Fluorescent Nanorods and Nanospheres for Real-Time In Vivo Probing of Nanoparticle Shape-Dependent Tumor Penetration SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cancer; imaging agents; luminescence; microscopy; nanoparticles ID EXTRACELLULAR-MATRIX; SEEDED GROWTH; DIFFUSION; LIPOSOMES; TRANSPORT; PARTICLES; XENOGRAFT; DELIVERY; IMPROVES; MICROENVIRONMENT C1 [Popovic, Zoran; Chen, Ou; Cui, Jian; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Chauhan, Vikash P.; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chauhan, Vikash P.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Chauhan, Vikash P.] Harvard Univ, Harvard Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Bawendi, MG (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mgb@mit.edu; jain@steele.mgh.harvard.edu RI Chauhan, Vikash/H-8172-2013 OI Chauhan, Vikash/0000-0001-9126-2302 FU U.S. National Cancer Institute [R01-CA126642, R01-CA085140, R01-CA115767, P01-CA080124, R01-CA096915]; U.S. Department of Defense [W81XWH-10-1-0016]; MIT-Harvard NIH Center for Cancer Nanotechnology Excellenc [1U54-CA119349]; MIT DCIF [CHE-980806, DBI-9729592]; ISN [W911NF-07-D-0004]; NSF [DMR-0117795] FX We thank Debby Pheasant (BIF Facility, MIT), Julia Kahn (MGH), and Sylvie Roberge (MGH) for technical assistance. This research was supported by the U.S. National Cancer Institute grants R01-CA126642 (R.K.J. and M.G.B.), R01-CA085140, R01-CA115767 (R.K.J.), P01-CA080124 (R.K.J. and D. F.), R01-CA096915 (D. F.); by the U.S. Department of Defense Breast Cancer Research Program Innovator Award W81XWH-10-1-0016 (R.K.J.); by the MIT-Harvard NIH Center for Cancer Nanotechnology Excellence 1U54-CA119349 (M. G. B.); by the MIT DCIF CHE-980806, DBI-9729592; by the ISN W911NF-07-D-0004 (M. G. B); by the NSF-MRSEC program (DMR-0117795) via the use of its shared user facilities. NR 35 TC 136 Z9 138 U1 4 U2 87 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2011 VL 50 IS 48 BP 11417 EP 11420 DI 10.1002/anie.201104449 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 859GC UT WOS:000297863900021 PM 22113800 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS Summary SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Editorial Material; Book Chapter C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 1 EP 5 PG 5 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700001 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS Introduction SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Editorial Material; Book Chapter ID YERSINIA-PESTIS; EVOLUTION; PLAGUE; TSG101 C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 7 EP 13 PG 7 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700002 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Evaluation of Current and Future TMT-Used Animal Models SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID EBOLA-VIRUS-INFECTION; MARBURG HEMORRHAGIC-FEVER; VERVET MONKEY DISEASE; HUMAN ANTHRAX VACCINE; GUINEA-PIGS; BACILLUS-ANTHRACIS; FRANCISELLA-TULARENSIS; DRUG DEVELOPMENT; CYNOMOLGUS MACAQUES; PRIMATE MODELS C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 115 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 15 EP 37 PG 23 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700003 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Ethical and Regulatory Challenges in the Development of Countermeasures SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID VACCINE; CONSENT; ANTHRAX C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 39 EP 49 PG 11 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700004 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Developing New Animal Models for Biodefense Research SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID ANTHRAX C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 51 EP 59 PG 9 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700005 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Alternative Approaches to Animal Testing for Biodefense Countermeasures SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID MONKEYPOX VIRUS; NONHUMAN-PRIMATES; GENE-EXPRESSION; COMPLEX; RESPONSES; SMALLPOX; DESIGN; TRAITS; CELLS; HEMAGGLUTININ C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 61 EP 76 PG 16 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700006 ER PT S AU Marder, SR Roth, B Sullivan, PF Scolnick, EM Nestler, EJ Geyer, MA Welnberger, DR Karayiorgou, M Guidotti, A Gingrich, J Akbarian, S Buchanan, RW Lieberman, JA Conn, PJ Haggarty, SJ Law, AJ Campbell, B Krystal, JH Moghaddam, B Saw, A Caron, MG George, SR Allen, JA Solis, M AF Marder, Stephen R. Roth, Bryan Sullivan, Patrick F. Scolnick, Edward M. Nestler, Eric J. Geyer, Mark A. Welnberger, Daniel R. Karayiorgou, Maria Guidotti, Alessandro Gingrich, Jay Akbarian, Schahram Buchanan, Robert W. Lieberman, Jeffrey A. Conn, P. Jeffrey Haggarty, Stephen J. Law, Amanda J. Campbell, Brian Krystal, John H. Moghaddam, Bita Saw, Akira Caron, Marc G. George, Susan R. Allen, John A. Solis, Michelle BE Braaten, D TI Advancing drug discovery for schizophrenia SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE schizophrenia; genetics; GWAS; neuronal function; small molecules; therapeutics ID METHYLATION; PSYCHIATRY; DISORDERS; INDUCTION; CELLS AB Sponsored by the New York Academy of Sciences and with support from the National Institute of Mental Health, the Life Technologies Foundation, and the Josiah Macy Jr. Foundation, "Advancing Drug Discovery for Schizophrenia" was held March 9-11 at the New York Academy of Sciences in New York City. The meeting, comprising individual talks and panel discussions, highlighted basic, clinical, and translational research approaches, all of which contribute to the overarching goal of enhancing the pharmaceutical armamentarium for treating schizophrenia. This report surveys work by the vanguard of schizophrenia research in such topics as genetic and epigenetic approaches; small molecule therapeutics; and the relationships between target genes, neuronal function, and symptoms of schizophrenia. C1 [Marder, Stephen R.] Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA 90095 USA. [Marder, Stephen R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Roth, Bryan; Allen, John A.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Scolnick, Edward M.] Broad Inst MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Scolnick, Edward M.] Harvard Univ, Cambridge, MA 02138 USA. [Nestler, Eric J.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Geyer, Mark A.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Welnberger, Daniel R.; Haggarty, Stephen J.; Law, Amanda J.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Karayiorgou, Maria; Lieberman, Jeffrey A.] Columbia Univ, Dept Psychiat, New York, NY USA. [Karayiorgou, Maria; Gingrich, Jay] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Guidotti, Alessandro] Univ Illinois, Chicago, IL USA. [Akbarian, Schahram] Univ Massachusetts, Sch Med, Res Inst, Worcester, MA USA. [Akbarian, Schahram] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Worcester, MA USA. [Buchanan, Robert W.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Campbell, Brian; Allen, John A.] Pfizer Neurosci, Groton, CT USA. [Krystal, John H.] Yale Univ, Sch Med, New Haven, CT USA. [Moghaddam, Bita] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. [Saw, Akira] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Saw, Akira] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Caron, Marc G.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. [George, Susan R.] Univ Toronto, Dept Med, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [George, Susan R.] Univ Toronto, Dept Pharmacol, Ctr Addict & Mental Hlth, Toronto, ON, Canada. RP Marder, SR (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA 90095 USA. RI Conn, Peter/D-7848-2012; Law, Amanda/G-6372-2012; Allen, John/D-6141-2011; OI Haggarty, Stephen J./0000-0002-7872-168X; Law, Amanda/0000-0002-2574-1564 FU NIDA NIH HHS [R01 DA007223]; NIMH NIH HHS [R01 MH095088]; NINDS NIH HHS [R01 NS031373] NR 20 TC 14 Z9 14 U1 0 U2 7 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-853-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1236 BP 30 EP 43 DI 10.1111/j.1749-6632.2011.06216.x PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BYL80 UT WOS:000299291300003 PM 22032400 ER PT S AU Dimond, P Carlson, K Bouvier, M Gerard, C Xu, L Covic, L Agarwal, A Ernst, OP Janz, JM Schwartz, TW Gardella, TJ Milligan, G Kuliopulos, A Sakmar, TP Hunt, SW AF Dimond, Patricia Carlson, Kenneth Bouvier, Michel Gerard, Craig Xu, Lei Covic, Lidija Agarwal, Anika Ernst, Oliver P. Janz, Jay M. Schwartz, Thue W. Gardella, Thomas J. Milligan, Graeme Kuliopulos, Athan Sakmar, Thomas P. Hunt, Stephen W., III BE Braaten, D Cooney, RE TI G protein-coupled receptor modulation with pepducins: moving closer to the clinic SO ANNALS MEETING REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE pepducins; G protein-coupled receptors; transmembrane signaling; allosteric modulation; meeting report ID PARATHYROID-HORMONE RECEPTOR; RESONANCE ENERGY-TRANSFER; BREAST-CANCER CELLS; OVARIAN-CANCER; ANTIANGIOGENIC THERAPY; BARIATRIC SURGERY; SIGNALING SYSTEM; TUMOR-GROWTH; ACTIVATION; METASTASIS AB At the 2nd Pepducin Science Symposium held in Cambridge, Massachusetts, on November 4-5, 2010, investigators working in G protein-coupled receptor (GPCR) research convened to discuss progress since last year's inaugural conference. This year's symposium focused on increasing knowledge of the structure and function of this ubiquitous superfamily of membrane receptors and their potential modulation for disease treatment. Presentations also focused on how GPCR mechanisms might be exploited to treat diseases with pepducins, novel synthetic lipopeptide pharmacophores that modulate heptahelical GPCR activity. While the multiple roles of GPCRs in physiological and pathophysiological processes offer significant opportunities for novel drug development, the global nature of their activity challenges drug-specific and validated target identification. This year's conference highlighted advances in understanding of GPCR agonist and antagonist ligand-binding motifs, their ligand-independent functions, structure-activity relationships (SARs), and evolving unique methods to probe GPCR structure and function. Study results summarized at the meeting also provided evidence for evolving views of how signaling mechanisms work through these receptors. C1 [Carlson, Kenneth; Janz, Jay M.; Hunt, Stephen W., III] Anchor Therapeut Inc, Cambridge, MA 02142 USA. [Dimond, Patricia] BioInsight Commun, Eastham, MA USA. [Bouvier, Michel] Univ Montreal, Dept Biochem, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada. [Xu, Lei] Harvard Univ, Sch Med, Dept Pediat, Div Resp Dis,Childrens Hosp, Boston, MA 02115 USA. [Covic, Lidija; Agarwal, Anika; Kuliopulos, Athan] Tufts Univ, Sch Med, Mol Oncol Res Inst, Div Hematol Oncol,Tufts Med Ctr,Dept Med, Boston, MA 02111 USA. [Covic, Lidija; Agarwal, Anika; Kuliopulos, Athan] Tufts Univ, Sch Med, Mol Oncol Res Inst, Div Hematol Oncol,Tufts Med Ctr,Dept Biochem, Boston, MA 02111 USA. [Ernst, Oliver P.] Univ Toronto, Dept Biochem, Toronto, ON, Canada. [Ernst, Oliver P.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Schwartz, Thue W.] Univ Copenhagen, Mol Pharmacol Lab, Copenhagen, Denmark. [Gardella, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Milligan, Graeme] Univ Glasgow, Dept Mol Pharmacol, Glasgow, Lanark, Scotland. [Sakmar, Thomas P.] Rockefeller Univ, Lab Mol Biol & Biochem, New York, NY 10021 USA. RP Hunt, SW (reprint author), Anchor Therapeut Inc, 67 Rogers St, Cambridge, MA 02142 USA. EM shunt@anchortx.com RI Milligan, Graeme/F-9426-2011; Bouvier, Michel/H-2758-2014; Sakmar, Thomas/D-1833-2015 OI Milligan, Graeme/0000-0002-6946-3519; Bouvier, Michel/0000-0003-1128-0100; Sakmar, Thomas/0000-0002-2836-8953 FU Anchor Therapeutics FX Patricia Dimond is an employee of BioInsight Communications and a contractor to Anchor Therapeutics. Athan Kuliopulos and Lidija Covic are co-founders of Anchor Therapeutics. Athan Kuliopulos, Lidija Covic, Thomas P. Sakmar, Thue W. Schwartz, and Graeme Milligan serve on the scientific advisory board of Anchor Therapeutics. Athan Kuliopulos, Thomas P. Sakmar, and Michel Bouvier have had, or do now receive research funding from Anchor Therapeutics. Kenneth Carlson, Jay M. Janz, and Stephen W. Hunt III are employees of Anchor Therapeutics. NR 46 TC 21 Z9 23 U1 0 U2 12 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-837-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1226 BP 34 EP 49 DI 10.1111/j.1749-6632.2011.06039.x PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BVP52 UT WOS:000292220300003 PM 21615752 ER PT J AU Banerji, A Rudders, SA Corel, B Garth, AP Clark, S Camargo, CA AF Banerji, Aleena Rudders, Susan A. Corel, Blanka Garth, Alisha P. Clark, Sunday Camargo, Carlos A., Jr. TI Predictors of hospital admission for food-related allergic reactions that present to the emergency department SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID ANAPHYLACTIC REACTIONS; BIPHASIC ANAPHYLAXIS; CLINICAL PREDICTORS; MANAGEMENT; CHILDREN; FATALITIES; COMMUNITY AB Background: Guidelines do not provide specific hospitalization criteria for patients presenting to the emergency department (ED) with food-related allergic reactions. Objective: To determine predictors of hospital admission for ED patients with food-related allergic reactions. Methods: We performed a medical record review at 3 academic centers of patients presenting to the ED for food-related allergic reactions (International Classification of Diseases, Ninth Revision, Clinical Modification codes 693.1, 995.0, 995.1, 995.3, 995.7, 995.60-995.69, 558.3, 692.5, and 708.X) between January 1, 2001, and December 31, 2006. We focused on patient demographics, medical history, food triggers, clinical presentation, pre-ED and ED management with a specific focus on epinephrine treatment, and disposition. Predictors of hospital admission were determined using multivariable logistic regression. Results: Through random sampling and appropriate weighting, the 1,112 cases reviewed represented a study cohort of 2,583 patients. Most patients (80%) were discharged from the ED. The age and sex of patients admitted to the hospital and those discharged were similar. Multivariable analysis identified 3 factors associated with a higher likelihood of hospital admission: meeting the criteria for food-related anaphylaxis (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.23-4.33), pre-ED epinephrine treatment (OR, 6.65; 95% CI, 3.04-14.57), and epinephrine treatment within 1 hour of ED triage (OR, 3.78; 95% CI, 1.68-8.50). Patients with food-related allergic reactions triggered by shellfish were less likely to be admitted to the hospital (OR, 0.23; 95% CI, 0.08-0.68). Conclusions: Most patients presenting to the ED with food-related allergic reactions are discharged. Several patient factors were independently associated with hospital admission in ED patients with food-related allergic reactions. Ann Allergy Asthma Immunol. 2011;106:42-48. C1 [Banerji, Aleena; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Rudders, Susan A.] Childrens Hosp, Div Allergy & Immunol, Boston, MA 02115 USA. [Corel, Blanka; Garth, Alisha P.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Banerji, A (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, 55 Fruit St,Cox 201, Boston, MA 02114 USA. EM abanerji@partners.org FU Dey; National Institutes of Health [NRSA T32-A1-007512] FX This project was partly supported by an investigator-initiated research grant from Dey (Dr Camargo) and by training grant NRSA T32-A1-007512 from the National Institutes of Health (Dr Rudders). NR 26 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JAN PY 2011 VL 106 IS 1 BP 42 EP 48 DI 10.1016/j.anai.2010.10.011 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 707PA UT WOS:000286297300008 PM 21195944 ER PT J AU Chen, Z Purdon, PL Harrell, G Pierce, ET Walsh, J Brown, EN Barbieri, R AF Chen, Zhe Purdon, Patrick L. Harrell, Grace Pierce, Eric T. Walsh, John Brown, Emery N. Barbieri, Riccardo TI Dynamic Assessment of Baroreflex Control of Heart Rate During Induction of Propofol Anesthesia Using a Point Process Method SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Baroreflex control; Baroreflex sensitivity; Heart rate variability; Hemodynamics; Point processes; Adaptive filters; Volterra series; Closed-loop feedback control; Cardiovascular system ID CARDIOVASCULAR VARIABILITY SIGNALS; OBSTRUCTIVE SLEEP-APNEA; GENERAL-ANESTHESIA; BLOOD-PRESSURE; SYSTEM-IDENTIFICATION; PARAMETER-ESTIMATION; COHERENCE FUNCTION; HEALTHY-SUBJECTS; HUMANS; MODEL AB In this article, we present a point process method to assess dynamic baroreflex sensitivity (BRS) by estimating the baroreflex gain as focal component of a simplified closed-loop model of the cardiovascular system. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by linear and bilinear bivariate regressions on both the previous R-R intervals (RR) and blood pressure (BP) beat-to-beat measures. The instantaneous baroreflex gain is estimated as the feedback branch of the loop with a point-process filter, while the RR -> BP feedforward transfer function representing heart contractility and vasculature effects is simultaneously estimated by a recursive least-squares filter. These two closed-loop gains provide a direct assessment of baroreflex control of heart rate (HR). In addition, the dynamic coherence, cross bispectrum, and their power ratio can also be estimated. All statistical indices provide a valuable quantitative assessment of the interaction between heartbeat dynamics and hemodynamics. To illustrate the application, we have applied the proposed point process model to experimental recordings from 11 healthy subjects in order to monitor cardiovascular regulation under propofol anesthesia. We present quantitative results during transient periods, as well as statistical analyses on steady-state epochs before and after propofol administration. Our findings validate the ability of the algorithm to provide a reliable and fast-tracking assessment of BRS, and show a clear overall reduction in baroreflex gain from the baseline period to the start of propofol anesthesia, confirming that instantaneous evaluation of arterial baroreflex control of HR may yield important implications in clinical practice, particularly during anesthesia and in postoperative care. C1 [Chen, Zhe; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Chen, Zhe; Purdon, Patrick L.; Harrell, Grace; Pierce, Eric T.; Walsh, John; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Chen, Z (reprint author), MIT, Dept Brain & Cognit Sci, 43 Vassar St,Bldg 46-6057, Cambridge, MA 02139 USA. EM zhechen@mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056 FU NIH [R01-HL084502, K25-NS05758, DP2-OD006454, T32NS048005, DP1-OD003646, R01-DA015644]; CRC [RR025758] FX The research was supported by NIH Grants R01-HL084502 (R. B.), K25-NS05758 (P. L. P.), DP2-OD006454 (P. L. P.), T32NS048005 (G. H.), DP1-OD003646 (E.N.B.), and R01-DA015644 (E.N.B.), as well as a CRC UL1 Grant RR025758 (P. L. P.). The authors thank L. Citi, K. Habeeb, R. Merhar, A. Salazar, and C. Tavares for assistance in collecting and preprocessing the data used in our experiments. We also thank the valuable comments from three reviewers that help to improve the manuscript. Preliminary results of this study have been reported in Proceedings of IEEE ICASSP'09, Taiwan.17 NR 63 TC 15 Z9 15 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 EI 1573-9686 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JAN PY 2011 VL 39 IS 1 BP 260 EP 276 DI 10.1007/s10439-010-0179-z PG 17 WC Engineering, Biomedical SC Engineering GA 719OB UT WOS:000287213100023 PM 20945159 ER PT J AU Gandy, S Wustman, B AF Gandy, Sam Wustman, Brandon TI New Pathway Links gamma-Secretase to Inflammation and Memory While Sparing Notch SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; IN-VIVO; MUTATIONS; RECEPTOR; NSAIDS C1 [Gandy, Sam] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Gandy, Sam] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Gandy, Sam] James J Peters VA Med Ctr, Alzheimers Dis Res Ctr, New York, NY USA. [Wustman, Brandon] Amicus Therapeut, La Jolla, CA USA. RP Gandy, S (reprint author), Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. FU NIA NIH HHS [P01 AG10491, P01 AG010491-14, P01 AG010491]; NINDS NIH HHS [R01 NS075685] NR 22 TC 1 Z9 1 U1 0 U2 2 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 JAN PY 2011 VL 69 IS 1 BP 5 EP 7 DI 10.1002/ana.22310 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 714ZS UT WOS:000286850800005 PM 21280069 ER PT J AU Wei, Y Yemisci, M Kim, HH Yung, LM Shin, HK Hwang, SK Guo, SZ Qin, T Alsharif, N Brinkmann, V Liao, JK Lo, EH Waeber, C AF Wei, Ying Yemisci, Muge Kim, Hyung-Hwan Yung, Lai Ming Shin, Hwa Kyoung Hwang, Seo-Kyoung Guo, Shuzhen Qin, Tao Alsharif, Nafiseh Brinkmann, Volker Liao, James K. Lo, Eng H. Waeber, Christian TI Fingolimod Provides Long-Term Protection in Rodent Models of Cerebral Ischemia SO ANNALS OF NEUROLOGY LA English DT Article ID RELAPSING MULTIPLE-SCLEROSIS; REPERFUSION INJURY; SPHINGOSINE-1-PHOSPHATE RECEPTORS; LYMPHOCYTE EGRESS; ORAL FINGOLIMOD; BRAIN-INJURY; WILD-TYPE; FTY720; STROKE; SPHINGOSINE AB Objective: The sphingosine-1-phosphate (S1P) receptor agonist fingolimod (FTY720), that has shown efficacy in advanced multiple sclerosis clinical trials, decreases reperfusion injury in heart, liver, and kidney. We therefore tested the therapeutic effects of fingolimod in several rodent models of focal cerebral ischennia. To assess the translational significance of these findings, we asked whether fingolimod improved long-term behavioral outcomes, whether delayed treatment was still effective, and whether neuroprotection can be obtained in a second species. Methods: We used rodent models of middle cerebral artery occlusion and cell-culture models of neurotoxicity and inflammation to examine the therapeutic potential and mechanisms of neuroprotection by fingolimod. Results: In a transient mouse model, fingolimod reduced infarct size, neurological deficit, edema, and the number of dying cells in the core and periinfarct area. Neuroprotection was accompanied by decreased inflammation, as fingolimod-treated mice had fewer activated neutrophils, microglia/macrophages, and intercellular adhesion molecule-1 (ICAM-1)-positive blood vessels. Fingolimod-treated mice showed a smaller infarct and performed better in behavioral tests up to 15 days after ischemia. Reduced infarct was observed in a permanent model even when mice were treated 4 hours after ischemic onset. Fingolimod also decreased infarct size in a rat model of focal ischemia. Fingolimod did not protect primary neurons against glutamate excitotoxicity or hydrogen peroxide, but decreased ICAM-1 expression in brain endothelial cells stimulated by tumor necrosis factor alpha. Interpretation: These findings suggest that anti-inflammatory mechanisms, and possibly vasculoprotection, rather than direct effects on neurons, underlie the beneficial effects of fingolimod after stroke. S1P receptors are a highly promising target in stroke treatment. ANN NEUROL 2011;69:119-129 C1 [Wei, Ying; Yemisci, Muge; Yung, Lai Ming; Shin, Hwa Kyoung; Guo, Shuzhen; Qin, Tao; Alsharif, Nafiseh; Lo, Eng H.; Waeber, Christian] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Kim, Hyung-Hwan; Hwang, Seo-Kyoung; Liao, James K.] Brigham & Womens Hosp, Dept Vasc Med Res, Cambridge, MA USA. [Kim, Hyung-Hwan] Jungwon Univ, Int Res Ctr Biosci & Biotechnol, Goesan, South Korea. [Brinkmann, Volker] Novartis Inst Biomed Res, Basel, Switzerland. [Brinkmann, Volker] Novartis Inst Autoimmun, Basel, Switzerland. [Brinkmann, Volker] Novartis Inst Transplantat & Inflammat, Basel, Switzerland. RP Shin, HK (reprint author), Pusan Natl Univ, Sch Korean Med, Gyeongsangnam Do 626870, South Korea. RI Ji, Haofeng/G-6206-2012; YEMISCI, MUGE/I-9928-2013; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU National Institute of Neurological Disorders and Stroke [R01NS049263, P01NS55104, R37NS37074, R01NS53560]; National Heart, Lung and Blood Institute [HL052233] FX This study was supported by National Institute of Neurological Disorders and Stroke grants R01NS049263 (C.W.), P01NS55104 (E.H.L. and C.W.), R37NS37074 (E.H.L.), R01NS53560 (E.H.L.), and National Heart, Lung and Blood Institute grant HL052233 (J.K.L.). NR 49 TC 101 Z9 105 U1 1 U2 24 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 JAN PY 2011 VL 69 IS 1 BP 119 EP 129 DI 10.1002/ana.22186 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 714ZS UT WOS:000286850800018 PM 21280082 ER PT J AU Whitmer, RA Quesenberry, CP Zhou, JF Yaffe, K AF Whitmer, Rachel A. Quesenberry, Charles P., Jr. Zhou, Jufen Yaffe, Kristine TI Timing of Hormone Therapy and Dementia: The Critical Window Theory Revisited SO ANNALS OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; HEALTH INITIATIVE MEMORY; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; POPULATION; BRAIN; RISK; STEROIDS; NEURONS AB Objective: Although previous research has shown that initiation of postmenopausal estrogen hormone therapy (HT) in late life increases risk of dementia, animal studies and some observational studies have suggested that midlife use of HT may be beneficial; however, this has not been rigorously investigated in large population-based studies. Our objective was to compare HT use in midlife with that in late life on risk of dementia among 5,504 postmenopausal female members of an integrated healthcare delivery system. Methods: HT use was determined at midlife (mean age, 48.7 years) from a survey in 1964 and in late life (mean age, 76 years) using pharmacy databases from 1994 to 1998. Risk of dementia diagnosis was evaluated with inpatient and outpatient diagnoses made in Neurology, Neuropsychology, and Internal Medicine from 1999 to 2008. Cox proportional hazard models were used to examine effects of HT use at different times on dementia risk with adjustment for age, education, race, body mass index, number of children, and comorbidities. Results: A total of 1,524 women (27%) were diagnosed with dementia during the follow-up period. Compared to women never on HT, those taking HT only at midlife had a 26% decreased risk (multivariate adjusted hazards ratio [aHR], 0.74; 95% confidence interval [CI], 0.58-0.94), whereas those taking HT only in late life had a 48% increased risk (aHR, 1.48; 95% CI, 1.10-1.98), and women taking HT at both mid and late life had a similar risk of dementia (aHR, 1.02; 95% CI, 0.78-1.34). Interpretation: These findings suggest that use of HT in midlife only may protect against cognitive impairment, whereas HT initiation in late life could have deleterious effects. ANN NEUROL 2011;69:163-169 C1 [Whitmer, Rachel A.; Quesenberry, Charles P., Jr.; Zhou, Jufen] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Whitmer, RA (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM raw@dor.kaiser.org FU Kaiser Permanente Community Benefits; National Institutes of Health [NIA AG021918, NIA AG 031155]; NIA; Orgnanon FX This study was supported by Kaiser Permanente Community Benefits (R.A.W.) and National Institutes of Health (NIA AG021918, K.Y.; NIA AG 031155, K.Y.).; K.Y. has held board membership for Pfizer and Medivation, has grants pending from NIA and Orgnanon, and has received honoraria from Novartis. NR 23 TC 83 Z9 87 U1 1 U2 7 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 JAN PY 2011 VL 69 IS 1 BP 163 EP 169 DI 10.1002/ana.22239 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 714ZS UT WOS:000286850800022 PM 21280086 ER PT J AU Foley, AR Hu, Y Zou, YQ Yang, MC Medne, L Leach, M Conlin, LK Spinner, N Shaikh, TH Falk, M Neumeyer, AM Bliss, L Tseng, BS Winder, TL Bonnemann, CG AF Foley, A. Reghan Hu, Ying Zou, Yaqun Yang, Michele Medne, Livija Leach, Meganne Conlin, Laura K. Spinner, Nancy Shaikh, Tamim H. Falk, Marni Neumeyer, Ann M. Bliss, Laurie Tseng, Brian S. Winder, Thomas L. Boennemann, Carsten G. TI Large Genomic Deletions: A Novel Cause of Ullrich Congenital Muscular Dystrophy SO ANNALS OF NEUROLOGY LA English DT Article ID COLLAGEN TYPE-VI; BETHLEM MYOPATHY; VONWILLEBRAND-FACTOR; GLOBULAR DOMAINS; COL6A1; MUTATIONS; SEQUENCE; CHAINS; GENES AB Two mutational mechanisms are known to underlie Ullrich congenital muscular dystrophy (UCMD): heterozygous dominant negatively-acting mutations and recessively-acting loss-of-function mutations. We describe large genomic deletions on chromosome 21q22.3 as a novel type of mutation underlying recessively inherited UCMD in 2 families. Clinically unaffected parents carrying large genomic deletions of COL6A1 and COL6A2 also provide conclusive evidence that haploinsufficiency for COL6A1 and COL6A2 is not a disease mechanism for Bethlem myopathy. Our findings have important implications for the genetic evaluation of patients with collagen VI related myopathies as well as for potential therapeutic interventions for this patient population. C1 [Boennemann, Carsten G.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH,Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Foley, A. Reghan; Hu, Ying; Zou, Yaqun; Yang, Michele; Medne, Livija; Leach, Meganne; Boennemann, Carsten G.] Univ Penn, Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Medne, Livija; Conlin, Laura K.; Falk, Marni] Univ Penn, Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Spinner, Nancy] Univ Penn, Childrens Hosp Philadelphia, Div Pathol, Philadelphia, PA 19104 USA. [Foley, A. Reghan] UCL, Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England. [Foley, A. Reghan] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Yang, Michele; Shaikh, Tamim H.] Univ Colorado Denver, Dept Pediat, Aurora, CO USA. [Spinner, Nancy; Shaikh, Tamim H.; Falk, Marni; Boennemann, Carsten G.] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Neumeyer, Ann M.; Bliss, Laurie; Tseng, Brian S.] Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Winder, Thomas L.] Prevent Genet, Marshfield, WI USA. RP Bonnemann, CG (reprint author), NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH,Porter Neurosci Res Ctr, Bldg 35,Room 2A-116,MSC 35 Convent Dr, Bethesda, MD 20892 USA. EM carsten.bonnemann@nih.gov FU NIH/NIAMS [R01AR051999]; MDA USA [MDA3896]; NIH/NIGMS [GM081519] FX This research was supported by grants from NIH/NIAMS (R01AR051999 to C.G.B.) and from MDA USA (MDA3896 to C.G.B.); NIH/NIGMS grant (GM081519 to T.H.S.). NR 19 TC 11 Z9 13 U1 0 U2 4 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 JAN PY 2011 VL 69 IS 1 BP 206 EP 211 DI 10.1002/ana.22283 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 714ZS UT WOS:000286850800028 PM 21280092 ER PT J AU Maturo, S Tse, SM Kinane, TB Hartnick, CJ AF Maturo, Stephen Tse, Sze Man Kinane, T. Bernard Hartnick, Christopher J. TI Initial Experience Using Propranolol as an Adjunctive Treatment in Children With Aggressive Recurrent Respiratory Papillomatosis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE papilloma; pediatric airway; propranolol ID INTRALESIONAL CIDOFOVIR; BETA-BLOCKERS; HEMANGIOMAS; GROWTH; SAFETY; INDOLE-3-CARBINOL; INJECTIONS; CARCINOMA; INFANCY; ASTHMA AB We performed a retrospective chart review with a 6-month follow-up to examine the initial use of propranolol as an adjunctive treatment in children with severe recurrent respiratory papillomatosis. This is the first such report. Two of 3 children with severe recurrent respiratory papillomatosis demonstrated a response to oral propranolol therapy, as evidenced by an improved voice and by an increased time between surgical interventions. One child demonstrated no response to propranolol, and medication was halted. Both children who demonstrated a response had undergone more than 10 surgical interventions in the previous year, along with prior treatment including surgical excision and adjuvant therapy. Both children more than doubled the interval between treatments after propranolol administration, and the parents of both children noted marked improvement of the child's voice as measured by their Pediatric Voice-Related Quality of Life score (from 40 to 67.5 in one child and from 27 to 60 in the other child). No child experienced hypoglycemia or blood pressure abnormalities. We conclude that initial use of propranolol as an adjunctive measure in severe recurrent respiratory papillomatosis shows it to have some efficacy in delaying surgical intervention and improving voice. Previous reports have demonstrated relatively safe use of propranolol in children with hemangiomas. Further studies are needed to determine the long-term effectiveness, dosing strategies, and side-effect profile of propranolol for treatment of recurrent respiratory papillomatosis C1 [Maturo, Stephen; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Tse, Sze Man; Kinane, T. Bernard] Massachusetts Gen Hosp Children, Dept Pulm Med, Boston, MA USA. RP Maturo, S (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 26 TC 6 Z9 6 U1 1 U2 3 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD JAN PY 2011 VL 120 IS 1 BP 17 EP 20 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 712DS UT WOS:000286645500003 PM 21370676 ER PT J AU Zhang, ZH Tendulkar, A Sun, K Saloner, DA Wallace, AW Ge, LA Guccione, JM Ratcliffe, MB AF Zhang, Zhihong Tendulkar, Amod Sun, Kay Saloner, David A. Wallace, Arthur W. Ge, Liang Guccione, Julius M. Ratcliffe, Mark B. TI Comparison of the Young-Laplace Law and Finite Element Based Calculation of Ventricular Wall Stress: Implications for Postinfarct and Surgical Ventricular Remodeling SO ANNALS OF THORACIC SURGERY LA English DT Article ID ENDOVENTRICULAR PATCH PLASTY; CANINE LEFT-VENTRICLE; MYOCARDIAL-INFARCTION; ACTIVE CONTRACTION; CARDIAC-MUSCLE; ANEURYSM; HEART; MECHANICS; DEVICE; MODEL AB Background. Both the Young-Laplace law and finite element (FE) based methods have been used to calculate left ventricular wall stress. We tested the hypothesis that the Young-Laplace law is able to reproduce results obtained with the FE method. Methods. Magnetic resonance imaging scans with non-invasive tags were used to calculate three-dimensional myocardial strain in 5 sheep 16 weeks after anteroapical myocardial infarction, and in 1 of those sheep 6 weeks after a Dor procedure. Animal-specific FE models were created from the remaining 5 animals using magnetic resonance images obtained at early diastolic filling. The FE-based stress in the fiber, cross-fiber, and circumferential directions was calculated and compared to stress calculated with the assumption that wall thickness is very much less than the radius of curvature (Young-Laplace law), and without that assumption (modified Laplace). Results. First, circumferential stress calculated with the modified Laplace law is closer to results obtained with the FE method than stress calculated with the YoungLaplace law. However, there are pronounced regional differences, with the largest difference between modified Laplace and FE occurring in the inner and outer layers of the infarct borderzone. Also, stress calculated with the modified Laplace is very different than stress in the fiber and cross-fiber direction calculated with FE. As a consequence, the modified Laplace law is inaccurate when used to calculate the effect of the Dor procedure on regional ventricular stress. Conclusions. The FE method is necessary to determine stress in the left ventricle with postinfarct and surgical ventricular remodeling (Ann Thorac Surg 2011; 91: 150-6) (C) 2011 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratcliffe@med.va.gov FU National Institutes of Health [R01-HL-77921, R01-HL-63348] FX This study was supported by National Institutes of Health grant R01-HL-77921 (Dr. Guccione), and R01-HL-63348 (Dr. Ratcliffe). This support is gratefully acknowledged. NR 34 TC 23 Z9 23 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JAN PY 2011 VL 91 IS 1 BP 150 EP 156 DI 10.1016/j.athoracsur.2010.06.132 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 695ZM UT WOS:000285411700029 PM 21172505 ER PT S AU Badylak, SF Taylor, D Uygun, K AF Badylak, Stephen F. Taylor, Doris Uygun, Korkut BE Yarmush, ML Duncan, JS Gray, ML TI Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 13 SE Annual Review of Biomedical Engineering LA English DT Review; Book Chapter DE organ engineering; extracellular matrix; decellularization; regenerative medicine; three-dimensional scaffold; tissue engineering ID MESENCHYMAL STEM-CELLS; SMALL-INTESTINAL SUBMUCOSA; PORCINE HEART-VALVES; ACUTE LIVER-FAILURE; EXTRACELLULAR-MATRIX; IN-VITRO; AMNIOTIC-FLUID; BONE-MARROW; ENDOTHELIAL-CELLS; BASEMENT-MEMBRANE AB The definitive treatment for end-stage organ failure is orthotopic transplantation. However, the demand for transplantation far exceeds the number of available donor organs. A promising tissue-engineering/regenerative-medicine approach for functional organ replacement has emerged in recent years. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. However, significant challenges for three-dimensional organ engineering approach remain. This manuscript describes the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding bioreactor design to support this approach. Critical challenges and future directions are also discussed. C1 [Badylak, Stephen F.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Badylak, Stephen F.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15219 USA. [Taylor, Doris] Univ Minnesota, Ctr Cardiovasc Repair, Minneapolis, MN 55455 USA. [Taylor, Doris] Univ Minnesota, Dept Integrat Biol & Physiol, Minneapolis, MN 55455 USA. [Uygun, Korkut] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Uygun, Korkut] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Uygun, Korkut] Shriners Hosp Children, Boston, MA 02114 USA. RP Badylak, SF (reprint author), Univ Pittsburgh, Dept Surg, 497 Scaife Hall, Pittsburgh, PA 15213 USA. EM badylaks@upmc.edu; dataylor@umn.edu; uygun.korkut@mgh.harvard.edu OI Badylak, Stephen/0000-0003-3555-0689 FU NHLBI NIH HHS [1U01HL100407-0]; NIDDK NIH HHS [DK080942] NR 165 TC 292 Z9 308 U1 26 U2 226 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1523-9829 BN 978-0-8243-3513-7 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2011 VL 13 BP 27 EP 53 DI 10.1146/annurev-bioeng-071910-124743 PG 27 WC Engineering, Biomedical SC Engineering GA BWP48 UT WOS:000294443000002 PM 21417722 ER PT S AU Deisboeck, TS Wang, ZH Macklin, P Cristini, V AF Deisboeck, Thomas S. Wang, Zhihui Macklin, Paul Cristini, Vittorio BE Yarmush, ML Duncan, JS Gray, ML TI Multiscale Cancer Modeling SO ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 13 SE Annual Review of Biomedical Engineering LA English DT Review; Book Chapter DE cancer systems biology; discrete; continuum; hybrid; clinical translation; personalized medicine ID EPIDERMAL-GROWTH-FACTOR; TUMOR-INDUCED ANGIOGENESIS; CELL LUNG-CANCER; SEMANTIC WEB TECHNOLOGIES; AGENT-BASED MODEL; SYSTEMS BIOLOGY; FACTOR RECEPTOR; NONLINEAR SIMULATION; PARAMETER-ESTIMATION; IN-VITRO AB Simulating cancer behavior across multiple biological scales in space and time, i.e., multiscale cancer modeling, is increasingly being recognized as a powerful tool to refine hypotheses, focus experiments, and enable more accurate predictions. A growing number of examples illustrate the value of this approach in providing quantitative insights in the initiation, progression, and treatment of cancer. In this review, we introduce the most recent and important multiscale cancer modeling works that have successfully established a mechanistic link between different biological scales. Biophysical, biochemical, and biomechanical factors are considered in these models. We also discuss innovative, cutting-edge modeling methods that are moving predictive multiscale cancer modeling toward clinical application. Furthermore, because the development of multiscale cancer models requires a new level of collaboration among scientists from a variety of fields such as biology, medicine, physics, mathematics, engineering, and computer science, an innovative Web-based infrastructure is needed to support this growing community. C1 [Deisboeck, Thomas S.; Wang, Zhihui] Harvard Univ, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Macklin, Paul] Univ Dundee, Div Math, Dundee DD1 4HN, Scotland. [Cristini, Vittorio] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Cristini, Vittorio] Univ New Mexico, Dept Chem & Biomed Engn, Albuquerque, NM 87131 USA. RP Deisboeck, TS (reprint author), Harvard Univ, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu RI Cristini, Vittorio/N-3540-2013; OI Macklin, Paul/0000-0002-9925-0151 FU NCI NIH HHS [1U54CA143907, 1U54CA143837, 1U54CA149196, CA 113004, U54 CA143837, U54 CA143907, U54 CA149196, U56 CA113004] NR 122 TC 114 Z9 114 U1 5 U2 63 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1523-9829 BN 978-0-8243-3513-7 J9 ANNU REV BIOMED ENG JI Annu. Rev. Biomed. Eng. PY 2011 VL 13 BP 127 EP 155 DI 10.1146/annurev-bioeng-071910-124729 PG 29 WC Engineering, Biomedical SC Engineering GA BWP48 UT WOS:000294443000006 PM 21529163 ER PT S AU Chauhan, VP Stylianopoulos, T Boucher, Y Jain, RK AF Chauhan, Vikash P. Stylianopoulos, Triantafyllos Boucher, Yves Jain, Rakesh K. BE Prausnitz, JM TI Delivery of Molecular and Nanoscale Medicine to Tumors: Transport Barriers and Strategies SO ANNUAL REVIEW OF CHEMICAL AND BIOMOLECULAR ENGINEERING, VOL 2 SE Annual Review of Chemical and Biomolecular Engineering LA English DT Review; Book Chapter DE cancer; microenvironment; drug resistance; normalization ID INTERSTITIAL FLUID PRESSURE; ENDOTHELIAL GROWTH-FACTOR; HERPES-SIMPLEX-VIRUS; FLUORESCENCE CORRELATION SPECTROSCOPY; HUMAN OSTEOSARCOMA XENOGRAFTS; HUMAN ADENOCARCINOMA LS174T; SOLID TUMORS; IN-VIVO; BLOOD-FLOW; EXTRACELLULAR-MATRIX AB Tumors are similar to organs, with unique physiology giving rise to an unusual set of transport barriers to drug delivery. Cancer therapy is limited by nonuniform drug delivery via blood vessels, inhomogeneous drug transport into tumor interstitium from the vascular compartment, and hindered transport through tumor interstitium to the target cells. Four major abnormal physical and physiological properties contribute to these transport barriers. Accumulated solid stress compresses blood vessels to diminish the drug supply to many tumor regions. Immature vasculature with high viscous and geometric resistances and reduced pressure gradients leads to sluggish and heterogeneous blood flow in tumors to further limit drug supply. Nonfunctional lymphatics coupled with highly permeable blood vessels result in elevated hydrostatic pressure in tumors to abrogate convective drug transport from blood vessels into and throughout most of the tumor tissue. Finally, a dense structure of interstitial matrix and cells serves as a tortuous, viscous, and steric barrier to diffusion of therapeutic agents. In this review, we discuss the origins and implications of these barriers. We then highlight strategies for overcoming these barriers by modulating either drug properties or the tumor microenvironment itself to enhance the delivery and effectiveness of drugs in tumors. C1 [Chauhan, Vikash P.; Stylianopoulos, Triantafyllos; Boucher, Yves; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Chauhan, Vikash P.; Stylianopoulos, Triantafyllos; Boucher, Yves; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chauhan, Vikash P.] Harvard Univ, Harvard Sch Engn & Appl Sci, Cambridge, MA 02138 USA. RP Chauhan, VP (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Chauhan, Vikash/H-8172-2013; OI Chauhan, Vikash/0000-0001-9126-2302; Stylianopoulos, Triantafyllos/0000-0002-3093-1696 FU NCI NIH HHS [P01-CA80124, R01-CA115767, R01-CA126642, R01-CA85140, R01-CA98706, T32-CA73479] NR 122 TC 162 Z9 163 U1 14 U2 90 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1947-5438 BN 978-0-8243-5202-8 J9 ANNU REV CHEM BIOMOL JI Annu. Rev. Chem. Biomol. Eng. PY 2011 VL 2 BP 281 EP 298 DI 10.1146/annurev-chembioeng-061010-114300 PG 18 WC Chemistry, Applied; Engineering, Chemical SC Chemistry; Engineering GA BVV09 UT WOS:000292859600014 PM 22432620 ER PT S AU Berthiaume, F Maguire, TJ Yarmush, ML AF Berthiaume, Francois Maguire, Timothy J. Yarmush, Martin L. BE Prausnitz, JM TI Tissue Engineering and Regenerative Medicine: History, Progress, and Challenges SO ANNUAL REVIEW OF CHEMICAL AND BIOMOLECULAR ENGINEERING, VOL 2 SE Annual Review of Chemical and Biomolecular Engineering LA English DT Review; Book Chapter DE artificial organs; skin; cartilage; liver; stem cells ID EMBRYONIC STEM-CELLS; AUTOLOGOUS CHONDROCYTE IMPLANTATION; HUMAN ARTICULAR CHONDROCYTES; FULMINANT HEPATIC-FAILURE; HUMAN EPIDERMAL-CELLS; TERM-FOLLOW-UP; IN-VITRO; BIOARTIFICIAL LIVER; CARTILAGE DEFECTS; SKIN SUBSTITUTES AB The past three decades have seen the emergence of an endeavor called tissue engineering and regenerative medicine in which scientists, engineers, and physicians apply tools from a variety of fields to construct biological substitutes that can mimic tissues for diagnostic and research purposes and can replace (or help regenerate) diseased and injured tissues. A significant portion of this effort has been translated to actual therapies, especially in the areas of skin replacement and, to a lesser extent, cartilage repair. A good amount of thoughtful work has also yielded prototypes of other tissue substitutes such as nerve conduits, blood vessels, liver, and even heart. Forward movement to clinical product, however, has been slow. Another offshoot of these efforts has been the incorporation of some new exciting technologies (e.g., microfabrication, 3D printing) that may enable future breakthroughs. In this review we highlight the modest beginnings of the field and then describe three application examples that are in various stages of development, ranging from relatively mature (skin) to ongoing proof-of-concept (cartilage) to early stage (liver). We then discuss some of the major issues that limit the development of complex tissues, some of which are fundamentals-based, whereas others stem from the needs of the end users. C1 [Berthiaume, Francois; Maguire, Timothy J.; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Berthiaume, F (reprint author), Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. EM ireis@sbi.org NR 167 TC 112 Z9 118 U1 28 U2 261 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1947-5438 BN 978-0-8243-5202-8 J9 ANNU REV CHEM BIOMOL JI Annu. Rev. Chem. Biomol. Eng. PY 2011 VL 2 BP 403 EP 430 DI 10.1146/annurev-chembioeng-061010-114257 PG 28 WC Chemistry, Applied; Engineering, Chemical SC Chemistry; Engineering GA BVV09 UT WOS:000292859600019 PM 22432625 ER PT S AU Loh, YH Yang, L Yang, JC Li, H Collins, JJ Daley, GQ AF Loh, Yuin-Han Yang, Lin Yang, Jimmy Chen Li, Hu Collins, James J. Daley, George Q. BE Chakravarti, A Green, E TI Genomic Approaches to Deconstruct Pluripotency SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 12 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE transcription regulation; epigenetics; histone modifications; DNA methylation; pluripotent stem cells ID EMBRYONIC STEM-CELLS; TRANSCRIPTIONAL REGULATORY CIRCUITRY; PROTEIN-INTERACTION NETWORK; CONTROLS DNA METHYLATION; PRIMORDIAL GERM-CELLS; HISTONE H3 LYSINE-9; SELF-RENEWAL; GENE-EXPRESSION; CHROMATIN-STRUCTURE; MOUSE DEVELOPMENT AB Embryonic stem cells (ESCs) first derived from the inner cell mass of blastocyst-stage embryos have the unique capacity of indefinite self-renewal and potential to differentiate into all somatic cell types. Similar developmental potency can be achieved by reprogramming differentiated somatic cells into induced pluripotent stem cells (iPSCs). Both types of pluripotent stem cells provide great potential for fundamental studies of tissue differentiation, and hold promise for disease modeling, drug development, and regenerative medicine. Although much has been learned about the molecular mechanisms that underlie pluripotency in such cells, our understanding remains incomplete. A comprehensive understanding of ESCs and iPSCs requires the deconstruction of complex transcription regulatory networks, epigenetic mechanisms, and biochemical interactions critical for the maintenance of self-renewal and pluripotency. in this review, we will discuss recent advances gleaned from application of global "omics" techniques to dissect the molecular mechanisms that define the pluripotent state. C1 [Loh, Yuin-Han; Yang, Lin; Yang, Jimmy Chen; Daley, George Q.] Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Loh, Yuin-Han; Yang, Lin; Yang, Jimmy Chen; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Loh, Yuin-Han; Yang, Lin; Yang, Jimmy Chen; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Loh, Yuin-Han; Yang, Lin; Yang, Jimmy Chen; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02115 USA. [Li, Hu; Collins, James J.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Li, Hu; Collins, James J.] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA. [Li, Hu; Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Collins, James J.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. RP Loh, YH (reprint author), Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI Loh, Yuin-Han/E-1096-2014 OI Loh, Yuin-Han/0000-0002-4715-6454 FU Howard Hughes Medical Institute; NHLBI NIH HHS [RC2-HL102815, RC2 HL102815, U01 HL100001, U01-HL-100001]; NIDCR NIH HHS [RL1 DE019021, RL1DE019021]; NIDDK NIH HHS [R01 DK059279, R01 DK070055, R01-DK59279, R01-DK70055] NR 140 TC 24 Z9 25 U1 1 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3712-4 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2011 VL 12 BP 165 EP 185 DI 10.1146/annurev-genom-082410-101506 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA BXD58 UT WOS:000295819900008 PM 21801025 ER PT S AU Gonzalez, SF Degn, SE Pitcher, LA Woodruff, M Heesters, BA Carroll, MC AF Gonzalez, Santiago F. Degn, Soren E. Pitcher, Lisa A. Woodruff, Matthew Heesters, Balthasar A. Carroll, Michael C. BE Paul, WE Littman, DR Yokoyama, WM TI Trafficking of B cell Antigen in Lymph Nodes SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 29 SE Annual Review of Immunology LA English DT Review; Book Chapter DE fibroblast reticular cells; follicular dendritic cells; conduits; dendritic cells; complement receptors CD21 and CD35 ID FOLLICULAR DENDRITIC CELLS; HUMORAL IMMUNE-RESPONSE; COMPLEMENT-DEPENDENT TRANSPORT; SUBCAPSULAR SINUS MACROPHAGES; HIGH ENDOTHELIAL VENULES; GERMINAL-CENTERS; SYNAPSE FORMATION; IN-VIVO; CLONAL-SELECTION; CONDUIT SYSTEM AB The clonal selection theory first proposed by Macfarlane Burnet is a cornerstone of immunology (1). At the time, it revolutionized the thinking of immunologists because it provided a simple explanation for lymphocyte specificity, immunological memory, and elimination of self-reactive clones (2). The experimental demonstration by Nossal & Lederberg (3) that B lymphocytes bear receptors for a single antigen raised the central question of where B lymphocytes encounter antigen. This question has remained mostly unanswered until recently. Advances in techniques such as multiphoton intravital microscopy (4, 5) have provided new insights into the trafficking of B cells and their antigen. In this review, we summarize these advances in the context of our current view of B cell circulation and activation. C1 [Gonzalez, Santiago F.; Pitcher, Lisa A.; Woodruff, Matthew; Carroll, Michael C.] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Gonzalez, Santiago F.; Pitcher, Lisa A.; Woodruff, Matthew; Carroll, Michael C.] Childrens Hosp, Program Mol & Cellular Med, Boston, MA 02115 USA. [Gonzalez, Santiago F.; Pitcher, Lisa A.; Woodruff, Matthew; Carroll, Michael C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Degn, Soren E.] Aarhus Univ, Dept Med Microbiol & Immunol, Grad Sch Hlth Sci, DK-8000 Aarhus C, Denmark. [Degn, Soren E.] Aarhus Univ, Danish Grad Sch Immunol, DK-8000 Aarhus C, Denmark. [Woodruff, Matthew; Carroll, Michael C.] Harvard Univ, Grad Program Immunol, Cambridge, MA 02138 USA. [Heesters, Balthasar A.] Univ Utrecht, Grad Program Life Sci, NL-3508 TC Utrecht, Netherlands. RP Gonzalez, SF (reprint author), Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. EM carroll@idi.harvard.edu OI Degn, Soren/0000-0001-5409-045X FU NHLBI NIH HHS [5T32HL066987-09]; NIAID NIH HHS [1 PO1 AI078897, 5 RO1 AI039246, 5 RO1 AI067706, T32 AI07498] NR 105 TC 48 Z9 50 U1 0 U2 16 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3029-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2011 VL 29 BP 215 EP 233 DI 10.1146/annurev-immunol-031210-101255 PG 19 WC Immunology SC Immunology GA BUP23 UT WOS:000289959200009 PM 21219172 ER PT S AU Bashirova, AA Thomas, R Carrington, M AF Bashirova, Arman A. Thomas, Rasmi Carrington, Mary BE Paul, WE Littman, DR Yokoyama, WM TI HLA/KIR Restraint of HIV: Surviving the Fittest SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 29 SE Annual Review of Immunology LA English DT Review; Book Chapter DE CTL; escape mutations; NK cells; GWAS; host genetics; viral evolution ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; HLA CLASS-I; NATURAL-KILLER-CELLS; MHC CLASS-I; EXPOSED UNINFECTED INDIVIDUALS; LONG-TERM NONPROGRESSORS; NK-CELLS; VIRAL LOAD; DISEASE PROGRESSION AB Multiple epidemiological studies have demonstrated associations between the human leukocyte antigen (HLA) loci and human immunodeficiency virus (HIV) disease, and more recently the killer cell immunoglobulin-like (KIR) locus has been implicated in differential responses to the virus. Genome-wide association studies have convincingly shown that the HLA class I locus is the most significant host genetic contributor to the variation in HIV control, underscoring a central role for CD8 T cells in resistance to the virus. However, both genetic and functional data indicate that part of the HLA effect on HIV is due to interactions between KIR and HLA genes, also implicating natural killer cells in defense against viral infection and viral expansion prior to initiation of an adaptive response. We review the HLA and KIR associations with HIV disease and the progress that has been made in understanding the mechanisms that explain these associations. C1 [Bashirova, Arman A.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA. Harvard Univ, Boston, MA 02129 USA. NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Bashirova, AA (reprint author), Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02129 USA. EM Arman.Bashirova@nih.gov; thomasrasmi@mail.nih.gov; carringm@mail.nih.gov FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS; NCI NIH HHS [HHSN261200800001E]; PHS HHS [HHSN261200800001E] NR 153 TC 68 Z9 69 U1 0 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3029-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2011 VL 29 BP 295 EP 317 DI 10.1146/annurev-immunol-031210-101332 PG 23 WC Immunology SC Immunology GA BUP23 UT WOS:000289959200012 PM 21219175 ER PT S AU Gostissa, M Alt, FW Chiarle, R AF Gostissa, Monica Alt, Frederick W. Chiarle, Roberto BE Paul, WE Littman, DR Yokoyama, WM TI Mechanisms that Promote and Suppress Chromosomal Translocations in Lymphocytes SO ANNUAL REVIEW OF IMMUNOLOGY, VOL 29 SE Annual Review of Immunology LA English DT Review; Book Chapter DE antigen receptor genes; DNA double-strand breaks; nonhomologous end-joining; DSB repair; lymphoma ID CLASS-SWITCH RECOMBINATION; DOUBLE-STRAND-BREAK; INDUCED CYTIDINE DEAMINASE; DNA-LIGASE-IV; END-JOINING PATHWAY; B-CELL LYMPHOMAS; ANTIBODY DIVERSIFICATION ENZYME; 3' REGULATORY REGION; HEAVY-CHAIN LOCUS; V(D)J RECOMBINATION AB Recurrent chromosomal translocations are characteristic features of many types of cancers, especially lymphomas and leukemias. Several basic mechanistic factors are required for the generation of most translocations. First, DNA double-strand breaks (DSBs) must be present simultaneously at the two participating loci. Second, the two broken loci must either be in proximity or be moved into proximity to be joined. Finally, cellular DNA repair pathways must be available to join the two broken loci to complete the translocation. These mechanistic factors can vary in different normal and mutant cells and, as a result, substantially influence the frequency at which particular translocations are generated in a given cell type. Ultimately, however, appearance of recurrent oncogenic translocations in tumors is, in most cases, strongly influenced by selection for the translocated oncogene during the tumorigenesis process. In this review, we discuss in depth the factors and pathways that contribute to the generation of translocations in lymphocytes and other cell types. We also discuss recent findings regarding mechanisms that underlie the appearance of recurrent translocations in tumors. C1 [Gostissa, Monica; Alt, Frederick W.; Chiarle, Roberto] Childrens Hosp Boston, Howard Hughes Med Inst, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Gostissa, Monica; Alt, Frederick W.; Chiarle, Roberto] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Gostissa, Monica; Alt, Frederick W.; Chiarle, Roberto] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Chiarle, Roberto] Univ Turin, Dept Biomed Sci & Human Oncol, I-10126 Turin, Italy. [Chiarle, Roberto] Univ Turin, CERMS, I-10126 Turin, Italy. RP Gostissa, M (reprint author), Childrens Hosp Boston, Howard Hughes Med Inst, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu OI CHIARLE, Roberto/0000-0003-1564-8531 FU NCI NIH HHS [5P01 CA109901-05, P01 CA109901, 5P01 CA92625-09]; Associazione Italiana per la Ricerca sul Cancro NR 175 TC 75 Z9 78 U1 0 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0732-0582 BN 978-0-8243-3029-3 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2011 VL 29 BP 319 EP 350 DI 10.1146/annurev-immunol-031210-101329 PG 32 WC Immunology SC Immunology GA BUP23 UT WOS:000289959200013 PM 21219174 ER PT S AU Abrahm, JL AF Abrahm, Janet L. BE Caskey, CT TI Advances in Palliative Medicine and End-of-Life Care SO ANNUAL REVIEW OF MEDICINE, VOL 62, 2011 SE Annual Review of Medicine LA English DT Review; Book Chapter DE palliative care; quality of life; methadone; neuropathic pain; CINV; delirium; POLST ID ADVANCED CANCER-PATIENTS; TRANSDERMAL BUPRENORPHINE; TREATMENT PREFERENCES; COMMUNICATION-SKILLS; CLINICAL-ONCOLOGY; AMERICAN-SOCIETY; MENTAL-HEALTH; NEAR-DEATH; PAIN; ASSOCIATIONS AB Palliative care improves the quality and cost-effectiveness of adult and pediatric patient care, and it decreases unwanted hospitalizations and aggressive care at the end of life. National palliative care quality standards and preferred practices can be used for benchmarking by institutions, health care systems, and accrediting bodies. Pain and symptom management and the management of delirium for patients is now possible for the vast majority of patients, even those with advanced disease. However, because of shortages of specialists providing "tertiary" palliative care, significant improvements are needed in generalist-level palliative care among oncologists, intensivists, and specialists caring for patients with advanced cardiac, pulmonary, renal, and hepatic diseases. POLST (Physician Orders for Life-Sustaining Treatment) forms are a major advance in end-of-life care. They enable patients' advance directives to be valid wherever they are cared for (home, hospital, or nursing facility). C1 [Abrahm, Janet L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Adult Palliat Care, Boston, MA 02115 USA. [Abrahm, Janet L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Abrahm, JL (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Adult Palliat Care, 75 Francis St, Boston, MA 02115 USA. EM jabrahm@partners.org NR 46 TC 9 Z9 10 U1 1 U2 10 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0562-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2011 VL 62 BP 187 EP 199 DI 10.1146/annurev-med-050509-163946 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BTS32 UT WOS:000287956900014 PM 21054172 ER PT S AU Laubach, J Richardson, P Anderson, K AF Laubach, Jacob Richardson, Paul Anderson, Kenneth BE Caskey, CT TI Multiple Myeloma SO ANNUAL REVIEW OF MEDICINE, VOL 62, 2011 SE Annual Review of Medicine LA English DT Review; Book Chapter DE autologous stem cell transplantation; lenalidomide; bortezomib ID LENALIDOMIDE PLUS DEXAMETHASONE; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; REDUCES SKELETAL EVENTS; LIGHT-CHAIN ANALYSIS; HIGH-DOSE THERAPY; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; PROGNOSTIC-FACTORS; LONG-TERM AB Multiple myeloma (MM) is a B cell neoplasm of the bone marrow with a complex array of clinical manifestations including anemia, bone lesions, hypercalcemia, renal dysfunction, and compromised immune function. It accounts for 10%-15% of all hematologic malignancies, and 20% of deaths related to cancers of the blood and bone marrow. The diagnosis of MM is based on the presence of neoplastic plasma cells in the bone marrow or other extramedullary sites, along with evidence of disease-related organ dysfunction. Although the disease remains incurable, significant advances in both basic and translational research have enhanced understanding of disease pathogenesis and guided the development of new and more effective therapies. These agents include the immunomodulatory drugs thalidomide and lenalidomide, the proteasome inhibitor bortezomib, and other therapeutics that are currently being evaluated. This review highlights important historical landmarks in the field of MM, examines the pathogenesis and clinical manifestations of the disease, and outlines principles of both diagnosis and treatment of MM. C1 [Laubach, Jacob; Richardson, Paul; Anderson, Kenneth] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Laubach, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jacobp_laubach@dfci.harvard.edu NR 98 TC 52 Z9 55 U1 3 U2 15 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0562-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2011 VL 62 BP 249 EP 264 DI 10.1146/annurev-med-070209-175325 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BTS32 UT WOS:000287956900018 PM 21090965 ER PT S AU Higgins, MJ Stearns, V AF Higgins, Michaela J. Stearns, Vered BE Caskey, CT TI Pharmacogenetics of Endocrine Therapy for Breast Cancer SO ANNUAL REVIEW OF MEDICINE, VOL 62, 2011 SE Annual Review of Medicine LA English DT Review; Book Chapter DE tamoxifen; CYP2D6; pharmacogenomics ID METABOLITE PLASMA-CONCENTRATIONS; REUPTAKE INHIBITOR PAROXETINE; RECEIVING ADJUVANT TAMOXIFEN; CYP2D6 GENOTYPE; GENETIC POLYMORPHISMS; POSTMENOPAUSAL WOMEN; HOT FLASHES; SURVIVAL; ASSOCIATION; RECURRENCE AB The selective estrogen receptor modulator tamoxifen has been used for more than three decades for the treatment, and more recently prevention, of breast cancer in women of all ages. The conversion of tamoxifen to active metabolites involves several cytochrome P450 (CYP) enzymes. CYP2D6 is the key enzyme responsible for the conversion of N-desmethyl tamoxifen to endoxifen. Single nucleotide polymorphisms in the CYP2D6 gene are not uncommon, and some alleles code for enzymes with reduced, null, or increased activity. Multiple studies suggest that women who carry one or two variant CYP2D6 alleles that encode enzymes with null or reduced activity may have an inferior breast cancer outcome when treated with tamoxifen in the adjuvant setting compared to women carrying two alleles encoding an enzyme with normal activity. Unfortunately, the data are not uniformly concordant, and definitive evidence that would change routine clinical practice is not yet available. CYP2D6 activity can also be reduced by concomitant use of drugs that inhibit the enzyme, including antidepressants used for psychiatric conditions or to relieve hot flashes, and these should be avoided in tamoxifen users whenever possible. Emerging data suggest that host factors may also predict interpatient variability in response to aromatase inhibitors. C1 [Higgins, Michaela J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Stearns, Vered] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. RP Higgins, MJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM mjhiggins@partners.org; vstearn1@jhmi.edu NR 57 TC 33 Z9 33 U1 0 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0562-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2011 VL 62 BP 281 EP 293 DI 10.1146/annurev-med-070909-182545 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BTS32 UT WOS:000287956900020 PM 21226615 ER PT S AU Eatock, RA Songer, JE AF Eatock, Ruth Anne Songer, Jocelyn E. BE Hyman, SE Jessell, TM Shatz, CJ Stevens, CF Zoghbi, HY TI Vestibular Hair Cells and Afferents: Two Channels for Head Motion Signals SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 34 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE mechanoelectrical transduction; adaptation; low-voltage-activated K channels; type I hair cells; calyx terminals; spike regularity ID MOUSE INNER-EAR; PERIPHERAL INNERVATION PATTERNS; TURTLE POSTERIOR CRISTA; SEMICIRCULAR CANAL AFFERENTS; EFFERENT-MEDIATED RESPONSES; APPLIED GALVANIC CURRENTS; AUDITORY-NERVE FIBERS; SQUIRREL-MONKEY; MECHANOELECTRICAL TRANSDUCTION; HIGH-FREQUENCY AB Vestibular epithelia of the inner ear detect head motions over a wide range of amplitudes and frequencies. In mammals, afferent nerve fibers from central and peripheral zones of vestibular epithelia form distinct populations with different response dynamics and spike timing. Central-zone afferents are large, fast conduits for phasic signals encoded in irregular spike trains. The finer afferents from peripheral zones conduct more slowly and encode more tonic, linear signals in highly regular spike trains. The hair cells are also of two types, I and II, but the two types do not correspond directly to the two afferent populations. Zonal differences in afferent response dynamics may arise at multiple stages, including mechanoelectrical transduction, voltage-gated channels in hair cells and afferents, afferent transmission at calyceal and bouton synapses, and spike generation in regular and irregular afferents. In contrast, zonal differences in spike timing may depend more simply on the selective expression of low-voltage-activated ion channels by irregular afferents. C1 [Eatock, Ruth Anne; Songer, Jocelyn E.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Dept Neurobiol,Eaton Peabody, Boston, MA 02114 USA. RP Eatock, RA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Dept Neurobiol,Eaton Peabody, Boston, MA 02114 USA. EM eatock@meei.harvard.edu; jocelyn_songer@meei.harvard.edu RI Eatock, Ruth/F-6404-2013; OI Eatock, Ruth Anne/0000-0001-7547-2051 FU NIDCD NIH HHS [R01 DC02290, R01 DC002290] NR 176 TC 62 Z9 62 U1 4 U2 21 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2434-6 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2011 VL 34 BP 501 EP 534 DI 10.1146/annurev-neuro-061010-113710 PG 34 WC Neurosciences SC Neurosciences & Neurology GA BWE70 UT WOS:000293772100021 PM 21469959 ER PT S AU Brown, EN Purdon, PL Van Dort, CJ AF Brown, Emery N. Purdon, Patrick L. Van Dort, Christa J. BE Hyman, SE Jessell, TM Shatz, CJ Stevens, CF Zoghbi, HY TI General Anesthesia and Altered States of Arousal: A Systems Neuroscience Analysis SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 34 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE dexmedetomidine; droperidol; ketamine; opioids; propofol ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; VENTROLATERAL PREOPTIC NUCLEUS; INDUCED RESPIRATORY DEPRESSION; CENTRAL-NERVOUS-SYSTEM; PROPOFOL ANESTHESIA; HEALTHY-VOLUNTEERS; HYPNOTIC RESPONSE; LOCUS-COERULEUS; AGONIST DEXMEDETOMIDINE AB Placing a patient in a state of general anesthesia is crucial for safely and humanely performing most surgical and many nonsurgical procedures. How anesthetic drugs create the state of general anesthesia is considered a major mystery of modern medicine. Unconsciousness, induced by altered arousal and/or cognition, is perhaps the most fascinating behavioral state of general anesthesia. We perform a systems neuroscience analysis of the altered arousal states induced by five classes of intravenous anesthetics by relating their behavioral and physiological features to the molecular targets and neural circuits at which these drugs are purported to act. The altered states of arousal are sedation-unconsciousness, sedation-analgesia, dissociative anesthesia, pharmacologic non-REM sleep, and neuroleptic anesthesia. Each altered arousal state results from the anesthetic drugs acting at multiple targets in the central nervous system. Our analysis shows that general anesthesia is less mysterious than currently believed. C1 [Brown, Emery N.; Purdon, Patrick L.; Van Dort, Christa J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Brown, Emery N.; Purdon, Patrick L.; Van Dort, Christa J.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Brown, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM enb@neurostat.mit.edu; patrickp@nmr.mgh.harvard.edu; vandortc@mit.edu FU NHLBI NIH HHS [HL07901, T32 HL007901]; NIH HHS [DP1 OD003646, DP1 OD003646-05, DP1OD003646, DP2 OD006454, DP2OD006454]; NINDS NIH HHS [K25 NS057580, NS057580] NR 181 TC 95 Z9 101 U1 1 U2 26 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2434-6 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2011 VL 34 BP 601 EP 628 DI 10.1146/annurev-neuro-060909-153200 PG 28 WC Neurosciences SC Neurosciences & Neurology GA BWE70 UT WOS:000293772100024 PM 21513454 ER PT S AU Anderson, KC Carrasco, RD AF Anderson, Kenneth C. Carrasco, Ruben D. BE Abbas, AK Galli, SJ Howley, PM TI Pathogenesis of Myeloma SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 6 SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE multiple myeloma; MGUS; plasma cell development; myeloma cancer stem cell; bone marrow microenvironment; myeloma oncogenomics ID NF-KAPPA-B; HUMAN MULTIPLE-MYELOMA; BONE-MARROW MICROENVIRONMENT; MEDIATED DRUG-RESISTANCE; PLASMA-CELL DIFFERENTIATION; CYCLIN-D DYSREGULATION; CANCER STEM-CELLS; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; GROWTH-FACTOR AB Multiple myeloma (MM) is a neoplasm of post germinal center, terminally differentiated B cells. It is characterized by a multifocal proliferation of clonal, long-lived plasma cells within the bone marrow (BM) and associated skeletal destruction, serum monoclonal gammopathy, immune suppression, and end-organ sequelae. MM is preceded by an age-progressive premalignant condition termed monoclonal gammopathy of undetermined significance. Unlike the genomes of most hematological malignancies, and similar to those of solid-tissue neoplasms, MM genomes are typified by numerous structural and numerical chromosomal aberrations as well as mutations in a number of oncogenes and tumor-suppressor genes, some of which have been linked to disease pathogenesis and clinical behavior. Recent studies have also defined the importance of interactions between the MM cells and their BM microenvironment, dysregulation in signaling pathways and in a specialized subpopulation of cells within the tumor (termed myeloma cancer stem cells) for tumor cell growth and survival, and the development of resistance to therapy. C1 [Anderson, Kenneth C.; Carrasco, Ruben D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ruben_carrasco@dfci.harvard.edu NR 145 TC 103 Z9 105 U1 6 U2 20 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1553-4006 BN 978-0-8243-4306-4 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech Dis. PY 2011 VL 6 BP 249 EP 274 DI 10.1146/annurev-pathol-011110-130249 PG 26 WC Pathology SC Pathology GA BUD40 UT WOS:000288922800011 PM 21261519 ER PT S AU Dixon, JA Spinale, FG AF Dixon, Jennifer A. Spinale, Francis G. BE Julius, D Clapham, DE TI Myocardial Remodeling: Cellular and Extracellular Events and Targets SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 73 SE Annual Review of Physiology LA English DT Review; Book Chapter DE matrix metalloproteinases; large-animal models; myocardial infarction ID COLONY-STIMULATING FACTOR; MESENCHYMAL STEM-CELLS; MATRIX-METALLOPROTEINASE INHIBITION; LEFT-VENTRICULAR FUNCTION; ENDOTHELIAL PROGENITOR CELLS; BONE-MARROW-CELLS; ENHANCES COLLATERAL PERFUSION; CARDIOVASCULAR RISK-FACTORS; CARDIAC FIBROBLAST FUNCTION; RANDOMIZED CONTROLLED-TRIAL AB The focus of this review is on translational studies utilizing large-animal models and clinical studies that provide fundamental insight into cellular and extracellular pathways contributing to post myocardial infarction (MI) left ventricle (LV) remodeling. Specifically, both large-animal and clinical studies have examined the potential role of endogenous and exogenous stem cells to alter the course of LV remodeling. Interestingly, there have been alterations in LV remodeling with stem cell treatment despite a lack of long-term cell engraftment. The translation of the full potential of stem cell treatments to clinical studies has yet to be realized. The modulation of proteolytic pathways that contribute to the post-MI remodeling process has also been examined. On the basis of recent large-animal studies, there appears to be a relationship between stem cell treatment post-MI and the modification of proteolytic pathways, generating the hypothesis that stem cells leave an echo effect that moderates LV remodeling. C1 [Dixon, Jennifer A.; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Dixon, Jennifer A.; Spinale, Francis G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Dixon, JA (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [R01 HL059165-12, R01 HL057952-12, HL059165, R01 HL057952, HL057952, R01 HL059165] NR 136 TC 24 Z9 24 U1 0 U2 8 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4278 BN 978-0-8243-0373-0 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2011 VL 73 BP 47 EP 68 DI 10.1146/annurev-physiol-012110-142230 PG 22 WC Physiology SC Physiology GA BUD92 UT WOS:000288968800003 PM 21314431 ER PT S AU Hand, SC Menze, MA Toner, M Boswell, L Moore, D AF Hand, Steven C. Menze, Michael A. Toner, Mehmet Boswell, Leaf Moore, Daniel BE Julius, D Clapham, DE TI LEA Proteins During Water Stress: Not Just for Plants Anymore SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 73 SE Annual Review of Physiology LA English DT Review; Book Chapter DE desiccation tolerance; anhydrobiosis; osmolytes; trehalose; intrinsically disordered proteins ID EMBRYOGENESIS ABUNDANT PROTEIN; SHOCK/ALPHA-CRYSTALLIN PROTEIN; MOLECULAR-CHAPERONE ACTIVITY; HEAT-SHOCK PROTEINS; DESICCATION TOLERANCE; IN-VITRO; ARTEMIA-FRANCISCANA; SACCHAROMYCES-CEREVISIAE; TARDIGRADE CUTICLE; HYDRATION CHANGES AB Late embryogenesis abundant (LEA) proteins are extremely hydrophilic proteins that were first identified in land plants. Intracellular accumulation is tightly correlated with acquisition of desiccation tolerance, and data support their capacity to stabilize other proteins and membranes during drying, especially in the presence of sugars like trehalose. Exciting reports now show that LEA proteins are not restricted to plants; multiple forms are expressed in desiccation-tolerant animals from at least four phyla. We evaluate here the expression, subcellular localization, biochemical properties, and potential functions of LEA proteins in animal species during water stress. LEA proteins are intrinsically unstructured in aqueous solution, but surprisingly, many assume their native conformation during drying. They are targeted to multiple cellular locations, including mitochondria, and evidence supports that LEA proteins stabilize vitrified sugar glasses thought to be important in the dried state. More in vivo experimentation will be necessary to fully unravel the multiple functional properties of these macromolecules (luring water stress. C1 [Hand, Steven C.; Menze, Michael A.; Boswell, Leaf; Moore, Daniel] Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, Baton Rouge, LA 70803 USA. [Toner, Mehmet] Harvard Univ, Ctr Engn Med & Surg Serv, Shriners Hosp Children, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Hand, SC (reprint author), Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, Baton Rouge, LA 70803 USA. EM shand@LSU.edu OI Menze, Michael/0000-0003-1072-5462 FU NIDDK NIH HHS [2R01DK046270-14A1] NR 105 TC 102 Z9 107 U1 14 U2 77 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4278 BN 978-0-8243-0373-0 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2011 VL 73 BP 115 EP 134 DI 10.1146/annurev-physiol-012110-142203 PG 20 WC Physiology SC Physiology GA BUD92 UT WOS:000288968800006 PM 21034219 ER PT J AU Koh, Y Haim, H Engelman, A AF Koh, Yasuhiro Haim, Hillel Engelman, Alan TI Identification and Characterization of Persistent Intracellular Human Immunodeficiency Virus Type 1 Integrase Strand Transfer Inhibitor Activity SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID REVERSE-TRANSCRIPTASE INHIBITORS; HIV-1 INTEGRASE; IN-VITRO; SELECTIVE-INHIBITION; HUMAN MACROPHAGES; REPLICATION; INFECTION; POTENT; DNA; PHARMACOKINETICS AB Pharmacokinetic and pharmacodynamic considerations significantly impact infectious disease treatment options. One aspect of pharmacodynamics is the postantibiotic effect, classically defined as delayed bacterial growth after antibiotic removal. The same principle can apply to antiviral drugs. For example, significant delays in human immunodeficiency virus type 1 (HIV-1) replication can be observed after nucleoside/nucleotide reverse transcriptase inhibitor (N/NtRTI) removal from culture medium, because these prodrugs must be anabolized into active, phosphorylated forms once internalized into cells. A relatively new class of anti-HIV-1 drugs is the integrase strand transfer inhibitors (INSTIs), and the INSTIs raltegravir (RAL) and elvitegravir (EVG) were tested here alongside positive N/NtRTI controls tenofovir disoproxil fumarate (TDF) and azidothymidine (AZT), as well as the nonnucleoside reverse transcriptase inhibitor negative control nevirapine (NVP), to assess potential postantiviral effects. Transformed and primary CD4-positive cells pretreated with INSTIs significantly resisted subsequent challenge by HIV-1, revealing the following hierarchy of persistent intracellular drug strength: TDF > EVG similar to AZT > RAL > NVP. A modified time-of-addition assay was moreover developed to assess residual drug activity levels. Approximately 0.8% of RAL and 2% of initial EVG and TDF 1-h pulse drug levels persisted during the acute phase of HIV-1 infection. EVG furthermore displayed significant virucidal activity. Although there is no reason to suspect obligate intracellular modification, this study nevertheless defines significant intracellular persistence of prototype INSTIs. Ongoing second-generation formulations should therefore consider the potential for significant postantiviral effects among this drug class. Combined intracellular persistence and virucidal activities suggest potential pre-exposure prophylaxis applications for EVG. C1 [Engelman, Alan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,CLS 1010, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu FU Merck Co., Inc. [LKR59419]; U.S. NIH [AI052014]; Mitsubishi Pharma Foundation; Japanese Association for Infectious Diseases; Japanese Society of Chemotherapy; Harvard University Center for AIDS Research; NIH, NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NCCAM [P30AI060354] FX This work was supported by Merck & Co., Inc. Investigator Initiated Program LKR59419 (A.E.), U.S. NIH grant AI052014 (A.E.), the Mitsubishi Pharma Foundation (Y.K.), the Japanese Association for Infectious Diseases (Y.K.), the Japanese Society of Chemotherapy (Y.K.), and the Harvard University Center for AIDS Research, an NIH-funded program (P30AI060354) that is supported by the following NIH institutes and centers: NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, and NCCAM. NR 48 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2011 VL 55 IS 1 BP 42 EP 49 DI 10.1128/AAC.01064-10 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 698FB UT WOS:000285577400003 PM 21060108 ER PT J AU Kim, HB Park, CH Gavin, M Jacoby, GA Hooper, DC AF Kim, Hong Bin Park, Chi Hye Gavin, Mariah Jacoby, George A. Hooper, David C. TI Cold Shock Induces qnrA Expression in Shewanella algae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MEDIATED QUINOLONE RESISTANCE; GLOBAL TRANSCRIPTOME ANALYSIS; PENTAPEPTIDE REPEAT PROTEINS; ONEIDENSIS MR-1; PLASMID; DNA; DETERMINANTS; ADAPTATION; GENES AB Plasmid-carried quinolone resistance genes, like qnrA, are widespread in Enterobacteriaceae. To gain insight into its little-understood native functions, we studied the effect of environmental conditions on chromosomal qnrA expression in Shewanella algae. Among conditions of DNA damage, oxidative and osmotic stress, starvation, heat, and cold, only cold shock increased gene expression, as measured by quantitative reverse transcription-PCR (qRT-PCR). Induction was graded and occurred during growth arrest, suggesting that qnrA may contribute to the adaptation of Shewanella to low temperatures. C1 [Kim, Hong Bin; Park, Chi Hye; Gavin, Mariah; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kim, Hong Bin] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea. [Kim, Hong Bin] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Jacoby, George A.] Lahey Clin Fdn, Burlington, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org RI Kim, Hong Bin/J-5452-2012 OI Kim, Hong Bin/0000-0001-6262-372X FU National Institutes of Health [R01AI057576, R01AI043312, R01AI057576-06]; U.S. Public Health Service FX This work was supported in part by grants R01AI057576 (to D.C.H.), R01AI043312 (to G.A.J.), and R01AI057576-06 (to D.C.H. and G.A.J.) from the National Institutes of Health, U.S. Public Health Service. NR 27 TC 10 Z9 10 U1 2 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2011 VL 55 IS 1 BP 414 EP 416 DI 10.1128/AAC.00991-10 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 698FB UT WOS:000285577400058 PM 21078945 ER PT J AU Anderson, RM Colman, RJ AF Anderson, Rozalyn M. Colman, Ricki J. TI Prospects and Perspectives in Primate Aging Research SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Editorial Material AB As improvements in standard of living and advances in medicine have resulted in greater life expectancy, the relative proportion of elderly has continued to increase in human populations across the globe. The primary goal of aging research is to gain a better understanding of the series of events that lead to increased frailty and disease vulnerability with age. The direct study of human aging is an active area of research; however, the opportunity to conduct mechanistic studies and gain insights into the underlying biology is limited. In this special forum issue of Antioxidant & Redox Signaling, we present a selection of articles and reviews that illustrate some of the recent advances in primate aging research. The overarching goal of this work is to underscore the potential for mechanistic discovery that is presented by nonhuman primate models, and to promote studies that validate novel approaches and techniques in nonhuman primates before their adaptation for human health care. Antioxid. Redox Signal. 14, 203-205. C1 [Anderson, Rozalyn M.] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Anderson, Rozalyn M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Anderson, Rozalyn M.; Colman, Ricki J.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA. RP Anderson, RM (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terrace, Madison, WI 53705 USA. EM rmanderson5@wisc.edu FU NIA NIH HHS [R01 AG037000, R01 AG040178] NR 8 TC 3 Z9 3 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN PY 2011 VL 14 IS 2 BP 203 EP 205 DI 10.1089/ars.2010.3227 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 695RR UT WOS:000285390800003 PM 20712396 ER PT S AU Kim, SS Subramanya, S Peer, D Shimaoka, M Shankar, P AF Kim, Sang-Soo Subramanya, Sandesh Peer, Dan Shimaoka, Motomu Shankar, Premlata BE VanRij, RP TI Antibody-Mediated Delivery of siRNAs for Anti-HIV Therapy SO ANTIVIRAL RNAI: CONCEPTS, METHODS, AND APPLICATIONS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE RNA interference; Small interfering RNA; Targeted delivery; Cationic peptide; Liposome; scFvCD7; Integrin; LFA-1 (lymphocyte function-associated antigen-1); I-tsNPs (integrin-targeted stabilized nanoparticles); HIV ID SMALL INTERFERING RNAS; MICE; BLOOD; CELLS AB RNA interference (RNAi) is a potent and specific gene silencing mechanism that utilizes small double-stranded RNA intermediates (small interfering RNAs or siRNAs) to target homologous mRNA sequences for degradation. The therapeutic potential of RNAi for HIV infection has been demonstrated in many studies. However, successful clinical application of RNAi is contingent on developing practical strategies to deliver siRNA to the desired target cells and tissues. Recently, there has been significant progress towards developing reagents that selectively deliver exogenous siRNA to immune cells that are targeted by HIV or involved in viral pathogenesis, such as T cells, macrophages, and dendritic cells. Here, we describe details of two antibody-based strategies for systemic delivery of siRNA either specifically to T cells via the CD7 receptor or to multiple immune cell types via LFA-1, present on all leukocytes. C1 [Kim, Sang-Soo; Subramanya, Sandesh; Shankar, Premlata] Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Ctr Excellence Infect Dis,Paul L Foster Sch Med, El Paso, TX USA. [Peer, Dan] Tel Aviv Univ, Ctr Nanosci & Nanotechnol, Dept Cell Res & Immunol, George S Wise Fac Life Sci,Lab Nanomed, IL-69978 Tel Aviv, Israel. [Shimaoka, Motomu] Harvard Univ, Program Cellular & Mol Med, Sch Med, Childrens Hosp Boston,Immune Dis Inst, Boston, MA USA. RP Kim, SS (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Ctr Excellence Infect Dis,Paul L Foster Sch Med, El Paso, TX USA. RI Peer, Dan/A-1785-2011 OI Peer, Dan/0000-0001-8238-0673 NR 16 TC 11 Z9 13 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-036-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 721 BP 339 EP 353 DI 10.1007/978-1-61779-037-9_21 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Medicine, Research & Experimental; Virology SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Virology GA BUD37 UT WOS:000288921500021 PM 21431696 ER PT J AU Levison, JH Orrell, C Losina, E Lu, ZG Freedberg, KA Wood, R AF Levison, Julie H. Orrell, Catherine Losina, Elena Lu, Zhigang Freedberg, Kenneth A. Wood, Robin TI Early outcomes and the virological effect of delayed treatment switching to second-line therapy in an antiretroviral roll-out programme in South Africa SO ANTIVIRAL THERAPY LA English DT Article ID RESOURCE-LIMITED SETTINGS; SUB-SAHARAN AFRICA; DRUG-RESISTANCE; 1-INFECTED PATIENTS; TREATMENT SERVICE; INCOME COUNTRIES; CLINICAL-TRIALS; EARLY MORTALITY; FAILURE; REGIMEN AB Background: More patients in resource-limited settings are starting second-line antiretroviral treatment (ART) following first-line ART failure. We aimed to describe predictors of lack of virological suppression in HIV-infected patients on second-line ART in a roll-out programme in South Africa. Methods: A retrospective analysis was performed on an adult HIV treatment cohort who started second-line ART (lopinavir/ritonavir, didanosine and zidovudine) after virological failure of first-line ART (two consecutive HIV RNA>1,000 copies/ml). Predictors of week 24 lack of suppression (HIV RNA>400 copies/ml) on second-line ART were determined by bivariate analysis where missing equals failure. A multivariable model that adjusted for gender, age and time to ART switch was used. We tested these findings in sensitivity analyses defining lack of suppression at week 24 as HIV RNA>1,000 and >5,000 copies/ml. Results: Of 6,339 patients on ART, 202 started second-line ART. At week 24, an estimated 41% (95% CI 34-47) did not achieve virological suppression. Female sex (adjusted OR 2.25, 95% CI 1.03-4.88) and time to ART switch (adjusted OR 1.07, 95% CI 1.01-1.14 for each additional month) increased the risk of lack of virological suppression. Age, CD4(+) T-cell count and HIV RNA at second-line ART initiation did not predict this outcome. In multivariate models, these findings were insensitive to the definition of lack of virological suppression. Conclusions: A substantial number of HIV-infected patients do not achieve virological suppression by week 24 of second-line ART. Women and patients with delayed start of second-line ART after first-line ART failure were at an increased risk of lack of virological suppression. C1 [Levison, Julie H.; Losina, Elena; Lu, Zhigang; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Levison, Julie H.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Orrell, Catherine; Wood, Robin] Univ Cape Town, Dept Med, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Lu, Zhigang; Freedberg, Kenneth A.] Harvard Univ, Harvard Ctr AIDS Res, Boston, MA 02115 USA. RP Levison, JH (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jlevison@partners.org RI Wood, Robin/G-8509-2011; OI Orrell, Catherine/0000-0003-1134-7475 FU US National Institute of Allergy and Infectious Diseases (NIAID) [T32 AI007433, RO1 AI58072, K24 A1062476]; Harvard Center for AIDS Research [P30-AI060354] FX Author contributions include formulation of the research question (JHL, KAF, EL, CO and RW), design of the analytic plan (JHL, KAF, EL and RW), data collection (CO and RW) and preparation (JHL) and crucial editing (JHL, KAF, EL, ZL, CO and RW) of the manuscript. The authors gratefully acknowledge the dedicated staff of the Hannan Crusaid ART Clinic and the Desmond Tutu HIV Centre. This study was financially supported by the US National Institute of Allergy and Infectious Diseases (NIAID T32 AI007433, RO1 AI58072 and K24 A1062476) and by the Harvard Center for AIDS Research (P30-AI060354). NR 47 TC 21 Z9 21 U1 2 U2 6 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 6 BP 853 EP 861 DI 10.3851/IMP1819 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 830LC UT WOS:000295657500008 PM 21900717 ER PT J AU Lundgren, K Brownell, H Cayer-Meade, C Milione, J Kearns, K AF Lundgren, Kristine Brownell, Hiram Cayer-Meade, Carol Milione, Janet Kearns, Kevin TI Treating metaphor interpretation deficits subsequent to right hemisphere brain damage: Preliminary results SO APHASIOLOGY LA English DT Article DE Right hemisphere disorder; Stroke; Treatment; Metaphor; Cognitive-linguistic deficits ID NORMALLY AGING ADULTS; VERBAL WORKING-MEMORY; TIME-SERIES ANALYSIS; SENTENCE COMPREHENSION; NEURAL MECHANISMS; WORD MEANINGS; APPRECIATION; LANGUAGE; REQUESTS; APHASIA AB Aims: This investigation sought to determine whether a structured intervention focused on improving use of semantic associations could improve patients' ability to provide oral interpretations of metaphors following right hemisphere damage (RHD). Methods Procedures: Principles of single participant experimental design provided the basis for the study. Five patients received either 10 or 20 baseline assessments of oral metaphor interpretation and, as a control, assessments of line orientation skill. They then received approximately 10 one-hour sessions of structured intervention to improve oral metaphor interpretation followed by post-training assessments and a 3-month follow up. Outcomes Results: Patients' performances revealed evidence of good response to training as shown by patients' ability to reach criterion on all intervention tasks and by their significant improvement on oral metaphor interpretation. There was relatively little improvement on the line orientation task. Conclusions: The results of this study support the clinical usefulness of this new approach to treating communication deficits associated with RHD due to stroke, even years post-onset. There are, however, questions that remain unanswered. For example, additional data will be needed to gauge how a patient's severity of impairment relates to the potential for improvement, to chart the durability and scope of improvement associated with the training, and to determine the type of visuospatial ability needed for using this type of pictorial material. C1 [Lundgren, Kristine] Univ N Carolina, Greensboro, NC 27402 USA. [Lundgren, Kristine; Brownell, Hiram; Cayer-Meade, Carol; Milione, Janet] VA Boston Healthcare Syst, W Roxbury, MA USA. [Lundgren, Kristine; Brownell, Hiram; Cayer-Meade, Carol; Milione, Janet] Boston Univ, Sch Med, Boston, MA 02215 USA. [Brownell, Hiram] Boston Coll, Chestnut Hill, MA 02167 USA. [Kearns, Kevin] SUNY Coll Fredonia, Fredonia, NY 14063 USA. RP Lundgren, K (reprint author), Univ N Carolina, 323 Ferguson Bldg, Greensboro, NC 27402 USA. EM k_lundgr@uncg.edu FU NIH:NIDCD [R21 DC007165, P30 DC05432, RO1 DC0520702]; Research Service of the Boston VA Healthcare System FX This work was supported by NIH:NIDCD grants R21 DC007165, P30 DC05432, and RO1 DC0520702 as well as the Research Service of the Boston VA Healthcare System. We wish to acknowledge Douglas Katz MD and T. Joy DePiero MD at Braintree Rehabilitation Hospital, Carol Abbott MS, CCC-SLP at New England Rehabilitation Hospital, and William Milberg PhD at the VA Boston Healthcare System for referring these patients, and Marissa Fond, Soma Roy, Michelle Nichols, Jacque Spitzer, Kate Caddick, and Andy Stringfellow for their contributions to this project. We thank the anonymous reviewers for their many useful comments that improved the paper substantially, and finally the participants and their families for their time and willingness to participate. NR 67 TC 13 Z9 13 U1 3 U2 10 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PY 2011 VL 25 IS 4 BP 456 EP 474 AR PII 927857091 DI 10.1080/02687038.2010.500809 PG 19 WC Clinical Neurology SC Neurosciences & Neurology GA 733LB UT WOS:000288263100003 PM 22837588 ER PT J AU Jensen, JD Fujita, M Dellavalle, RP AF Jensen, J. Daniel Fujita, Mayumi Dellavalle, Robert P. TI Validation of Psoriasis Clinical Severity and Outcome Measures Searching for a Gold Standard SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID PHYSICIANS GLOBAL ASSESSMENT; SELF-ADMINISTERED PSORIASIS; INVOLVED SURFACE-AREA; MINOLTA CHROMA METER; MACHINE VISION; INDEX; ERYTHEMA; DISEASE; EYE C1 [Jensen, J. Daniel; Fujita, Mayumi; Dellavalle, Robert P.] Univ Colorado Denver, Sch Med, Dept Dermatol, Aurora, CO USA. [Dellavalle, Robert P.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Dellavalle, Robert P.] Colorado Sch Publ Hlth, Aurora, CO USA. RP Dellavalle, RP (reprint author), Dept Vet Affairs Med Ctr, Dermatol Serv, 1055 Clermont St,POB 165, Denver, CO 80220 USA. EM robert.dellavalle@ucdenver.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X NR 22 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 2011 VL 147 IS 1 BP 95 EP 98 DI 10.1001/archdermatol.2010.242 PG 4 WC Dermatology SC Dermatology GA 706OZ UT WOS:000286229000023 PM 20855674 ER PT J AU Ojha, RP Offutt-Powell, TN Evans, EL Singh, KP AF Ojha, Rohit P. Offutt-Powell, Tabatha N. Evans, Eva L. Singh, Karan P. TI Correlation Coefficients in Ecologic Studies of Environment and Cancer SO ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH LA English DT Article DE aggregate; cancer; ecologic; environment; epidemiology; statistical measures ID EPIDEMIOLOGY AB The objective of this study was to determine the proportion of ecologic studies published during a 20-year period regarding environmental exposures and cancer in which correlation coefficients or coefficients of determination were used as a measure of association. The authors performed a descriptive analysis of published literature by conducting a systematic review of PubMed to identify eligible ecologic studies published between 1991 and 2010. The reported measure of association was extracted for all eligible studies. During the 20-year study period, 35/105 (33%, 95% confidence limits [CL]: 25%, 43%) ecologic studies used correlation coefficients or coefficients of determination as a measure of association. These results indicate that the use of correlation coefficients and coefficients of determination as measures of association in ecologic studies of environmental exposures and cancer is relatively common, despite extensive literature discouraging their interpretation as valid measures of association. C1 [Ojha, Rohit P.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Ojha, Rohit P.; Evans, Eva L.] Univ N Texas, Hlth Sci Ctr, Dept Epidemiol, Ft Worth, TX USA. [Offutt-Powell, Tabatha N.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Singh, Karan P.] Univ N Texas, Hlth Sci Ctr, Dept Biostat, Ft Worth, TX USA. RP Ojha, RP (reprint author), Dana Farber Canc Inst, Div Populat Sci, 450 Brookline Ave,SM 271, Boston, MA 02115 USA. EM rohit_ojha@dfci.harvard.edu OI Ojha, Rohit/0000-0003-0595-8990 NR 16 TC 0 Z9 0 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1933-8244 EI 2154-4700 J9 ARCH ENVIRON OCCUP H JI Arch. Environ. Occup. Health PY 2011 VL 66 IS 4 BP 241 EP 244 DI 10.1080/19338244.2010.539641 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 299VG UT WOS:000330423200009 PM 22014198 ER PT J AU Elman, I Zubieta, JK Borsook, D AF Elman, Igor Zubieta, Jon-Kar Borsook, David TI The Missing P in Psychiatric Training Why It Is Important to Teach Pain to Psychiatrists SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; BORDERLINE PERSONALITY-DISORDER; CHRONIC BACK-PAIN; CHRONIC NONMALIGNANT PAIN; PLASMA BETA-ENDORPHIN; AFFECTIVE DIMENSIONS; GENERAL-POPULATION; NUCLEUS-ACCUMBENS; DOPAMINE NEURONS; DECISION-MAKING AB Context: Pain problems are exceedingly prevalent among psychiatric patients. Moreover, clinical impressions and neurobiological research suggest that physical and psychological aspects of pain are closely related entities. Nonetheless, remarkably few pain-related themes are currently included in psychiatric residency training. Objectives: To provide clinical and scientific rationale for psychiatric-training enrichment with basic tenets of pain medicine and to raise the awareness and sensitivity of physicians, scientists, and educators to this important yet unmet clinical and public health need. Results: We present 3 lines of translational research evidence, extracted from a comprehensive literature review, in support of our objectives. First, the neuroanatomical and functional overlap between pain and emotion/reward/motivation brain circuitry suggests integration and mutual modulation of these systems. Second, psychiatric disorders are commonly associated with alterations in pain processing, whereas chronic pain may impair emotional and neurocognitive functioning. Third, given its stressful nature, pain may serve as a functional probe for unraveling pathophysiological mechanisms inherent in psychiatric morbidity. Conclusions: Pain training in psychiatry will contribute to deeper and more sophisticated insight into both pain syndromes and general psychiatric morbidity regardless of patients' pain status. Furthermore, it will ease the artificial boundaries separating psychiatric and medical formulations of brain disorders, thus fostering cross-fertilizing interactions among specialists in various disciplines entrusted with the care of patients experiencing pain. C1 [Elman, Igor] McLean Hosp, Clin Psychopathol Lab, Boston, MA USA. [Borsook, David] McLean Hosp, Dept Psychiat, PAIN Grp, Boston, MA USA. [Borsook, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Borsook, David] Harvard Univ, Sch Med, Boston, MA USA. [Zubieta, Jon-Kar] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Zubieta, Jon-Kar] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Zubieta, Jon-Kar] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. RP Borsook, D (reprint author), McLean Hosp, Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM dborsook@partners.org FU NCCIH NIH HHS [R01 AT 001415, R01 AT001415]; NIDA NIH HHS [DA017959, R01 DA016423, R01 DA017959, R01 DA022520, R01DA016423, R01DA022520]; NIMH NIH HHS [R01 MH086858, R01 MH086858-01, R01 MH086858-02]; NINDS NIH HHS [K24 NS064050, K24NS064050] NR 133 TC 54 Z9 54 U1 3 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2011 VL 68 IS 1 BP 12 EP 20 DI 10.1001/archgenpsychiatry.2010.174 PG 9 WC Psychiatry SC Psychiatry GA 702WY UT WOS:000285927800007 PM 21199962 ER PT J AU Baker, LD Cross, DJ Minoshima, S Belongia, D Watson, S Craft, S AF Baker, Laura D. Cross, Donna J. Minoshima, Satoshi Belongia, Dana Watson, Stennis Craft, Suzanne TI Insulin Resistance and Alzheimer-like Reductions in Regional Cerebral Glucose Metabolism for Cognitively Normal Adults With Prediabetes or Early Type 2 Diabetes SO ARCHIVES OF NEUROLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN ACTIVATION; BLOOD-FLOW; DISEASE; RISK; HYPERINSULINEMIA; INFORMATION; IMPAIRMENT; MELLITUS; IMAGES AB Background: Insulin resistance is a causal factor in prediabetes (PD) and type 2 diabetes (T2D) and increases the risk of developing Alzheimer disease (AD). Reductions in cerebral glucose metabolic rate (CMRglu) as measured by fludeoxyglucose F 18-positron emission tomography (FDG-PET) in parietotemporal, frontal, and cingulate cortices are associated with increased AD risk and can be observed years before dementia onset. Objectives: To examine whether greater homeostasis model assessment insulin resistance (HOMA-IR) is associated with reduced resting CMRglu in areas vulnerable in AD in cognitively normal adults with newly diagnosed PD or T2D(PD/T2D), and to determine whether adults with PD/T2D have abnormal patterns of CMRglu during a memory encoding task. Design: Randomized crossover design of resting and activation FDG-PET. Setting: University imaging center and Veterans Affairs clinical research unit. Participants: Twenty-three older adults (mean [SEM] age, 74.4 [1.4] years) with no prior diagnosis of diabetes but who met American Diabetes Association glycemic criteria for PD (n=11) or diabetes (n=12) based on fasting or 2-hour oral glucose tolerance test (OGTT) glucose values and 6 adults (mean [SEM] age, 74.3 [2.8] years) with normal fasting glucose values and glucose tolerance. No participant met Petersen criteria for mild cognitive impairment. Interventions: Fasting participants underwent resting and cognitive activation FDG-PET imaging on separate days. Following a 30-minute transmission scan, subjects received an intravenous injection of 5 mCi of FDG, and the emission scan commenced 40 minutes after injection. In the activation condition, a 35-minute memory encoding task was initiated at the time of tracer injection. Subjects were instructed to remember a repeating list of 20 words randomly presented in series through earphones. Delayed free recall was assessed once the emission scan was complete. Main Outcome Measures: The HOMA-IR value was calculated using fasting glucose and insulin values obtained during OGTT screening and then correlated with CMRglu values obtained during the resting scan. Resting CMRglu values were also subtracted from CMRglu values obtained during the memory encoding activation scan to examine task-related patterns of CMRglu. Results: Greater insulin resistance was associated with an AD-like pattern of reduced CMRglu in frontal, parietotemporal, and cingulate regions in adults with PD/T2D. The relationship between CMRglu and HOMA-IR was independen to fage, 2-hour OGTT glucose concentration, or apolipoprotein E epsilon 4 allele carriage. During the memory encoding task, healthy adults showed activation in right anterior and inferior prefrontal cortices, right inferior temporal cortex, and medial and posterior cingulate regions. Adults with PD/T2D showed a qualitatively different pattern during the memory encoding task, characterized by more diffuse and extensive activation, and recalled fewer items on the delayed memory test. Conclusions: Insulin resistance may be a marker of AD risk that is associated with reduced CMRglu and subtle cognitive impairments at the earliest stage of disease, even before the onset of mild cognitive impairment. C1 [Baker, Laura D.; Belongia, Dana; Watson, Stennis; Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Baker, Laura D.; Belongia, Dana; Watson, Stennis; Craft, Suzanne] Univ Washington, Sch Med, Ctr Geriatr Res Educ & Clin, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Cross, Donna J.; Minoshima, Satoshi] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. RP Baker, LD (reprint author), Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Box 356560,VAPSHCS A-182-GRECC, Seattle, WA 98195 USA. EM ldbaker@uw.edu FU National Institute of Diabetes [RO1 DK061606]; Digestive and Kidney Diseases; Department of Veterans Affairs FX This study was supported by grant RO1 DK061606 from the National Institute of Diabetes and Digestive and Kidney Diseases (Dr Craft) and by the Department of Veterans Affairs. NR 34 TC 186 Z9 192 U1 2 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2011 VL 68 IS 1 BP 51 EP 57 DI 10.1001/archneurol.2010.225 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 704MO UT WOS:000286057300007 PM 20837822 ER PT J AU Schneider, LS Insel, PS Weiner, MW AF Schneider, Lon S. Insel, Philip S. Weiner, Michael W. CA Alzheimers Dis Neuroimaging TI Treatment With Cholinesterase Inhibitors and Memantine of Patients in the Alzheimer's Disease Neuroimaging Initiative SO ARCHIVES OF NEUROLOGY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; PLACEBO-CONTROLLED TRIAL; CLINICAL-TRIALS; DOUBLE-BLIND; MODERATE; DIAGNOSIS; DONEPEZIL; EFFICACY; SCALE AB Objectives: To assess the clinical characteristics and course of patients with mild cognitive impairment (MCI) and mild Alzheimer disease (AD) treated with cholinesterase inhibitors (ChEIs) and memantine hydrochloride. Design: Cohort study. Setting: The 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants: Outpatients with MCI and AD in ADNI. Main Outcome Measures: The AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and Functional Activities Questionnaire (FAQ). Results: A total of 177 (44.0%) of 402 MCI patients and 159 (84.6%) of 188 mild-AD patients were treated with ChEIs and 11.4% of MCI patients and 45.7% of AD patients with memantine at entry. Mild-cognitive-impairment patients who received ChEIs with or without memantine were more impaired, showed greater decline in scores, and progressed to dementia sooner than patients who did not receive ChEIs. Alzheimer-disease patients who received ChEIs and memantine took them longer, were more functionally impaired, and showed greater decline on the MMSE and CDR (but not on the ADAS-cog or FAQ) than those who received ChEIs only. Conclusions: Academic physicians frequently prescribe ChEIs and memantine earlier than indicated in the US Food and Drug Administration-approved labeling to patients who are relatively more severely impaired or who are rapidly progressing toward cognitive impairment. The use of these medications in ADNI is associated with clinical decline and may affect the interpretation of clinical trial outcomes. C1 [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Behav Sci & Neurol, Los Angeles, CA 90033 USA. [Schneider, Lon S.] Leonard Davis Sch Gerontol, Los Angeles, CA USA. [Insel, Philip S.; Weiner, Michael W.] Univ Calif San Francisco, Sch Med, Ctr Imaging Neurodegenerat Dis, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Schneider, LS (reprint author), Univ So Calif, Keck Sch Med, Dept Psychiat, 1510 San Pablo St,HCC 600, Los Angeles, CA 90033 USA. EM lschneid@usc.edu RI Scharre, Douglas/E-4030-2011 FU Alzheimer's Association; AstraZeneca Pharmaceuticals; Baxter International Inc; Elan Pharmaceuticals; Forest Laboratories Inc; Johnson & Johnson Consumer Companies Inc; Eli Lilly and Company; Myriad Pharmaceuticals Inc; Novartis Pharmaceuticals Corporation; Pfizer Incorporated; Takeda Pharmaceutical Company Ltd; Wyeth Pharmaceuticals; Abbott Laboratories; AC Immune SA; Allergan Inc; Allon Therapeutics; Alzheimer's Drug Discovery Foundation; Bristol-Myers Squibb; ExonHit Therapeutics; GlaxoSmithKline plc; Ipsen Group; H. Lundbeck A/S, Myriad Pharmaceuticals Inc; MedAvante Inc; Medivation Inc; Merck Co Inc; Merz Pharmaceuticals GmbH; F. Hoffman-La Roche Ltd; Sanofi-aventis LLC; Servier Laboratories; Schering-Plough Corporation; Schwabe Pharmaceuticals; Teva Pharmaceutical Industries Ltd; Toyama Pharmaceutical Co Ltd; Transition Therapeutics Inc; Voyager Pharmaceuticals Corp; l'Alliance Medicale et Scientifique; Alzheimer's Disease Neuroimaging Initiative; Avid Pharmaceuticals Inc; Banner Pharmacaps Inc Alzheimer's Institute; Bayer Health-Care; Elan Corporation plc/Wyeth Pharmaceuticals Alzheimer's Immunotherapy North American Advisory Board; Beijing Institute of Geriatrics; Centre Hospitalier Regional Universitaire-Hopital Roger Salengro; Clinical Trials on Alzheimer's Disease; Colloquium Paris; Foundation for the National Institutes of Health; GE Healthcare Japan; Geneva University Hospitals; Innogenetics NV; Institut Catala de Neurociencias Aplicades; Ipsen; Johns Hopkins University; Korean Neurological Association; Michael J. Fox Foundation for Parkinson's Research; Montreal Neurological Institute and Hospital at McGill University; Mount Sinai Medical Center; National Multiple Sclerosis Society; Neuroscience Early Stage Research Training; NeuroVigil Inc; New York University; Pfizer Inc Global Research and Development; Research Association for Biotechnology; Rotman Research Institute of Baycrest; Siemens AG; Society of Photo-Optical Instrumentation Engineers; Tel-Aviv University Medical School; Telemedicine & Advanced Technology Research Center; University of Pittsburgh; Wien Center for Alzheimer's Disease and Memory Disorders; University of Califonia Davis; United States Social Security Administration; Wenner-Grem Foundation; Washington University in St Louis; United States Department of Veterans Affairs Central Office; University of New Mexico School of Medicine; University of Paris; Avid Radiopharmaceuticals Inc; National Institutes of Health [U01AG024904, P41 RR023953, R01AG10897, P01AG19724, P50AG23501, R24 RR021992, R01 NS031966, P01AG012435, P50AG05142]; United States Department of Defense [DAMD17-01-0764]; Veterans Administration [MIRECC VISN 21]; University of Southern California Alzheimer's Disease Research Center FX Dr Schneider is an editor for the Cochrane Dementia and Cognitive Improvement Group, which oversees systematic reviews of medications for cognitive impairment and dementia; has received a grant from the Alzheimer's Association for a registry for dementia and cognitive impairment trials and grant or research support from AstraZeneca Pharmaceuticals, Baxter International Inc, Elan Pharmaceuticals, Forest Laboratories Inc, Johnson & Johnson Consumer Companies Inc, Eli Lilly and Company, Myriad Pharmaceuticals Inc, Novartis Pharmaceuticals Corporation, Pfizer Incorporated, Takeda Pharmaceutical Company Ltd, and Wyeth Pharmaceuticals; has served as a consultant for or received consulting fees from Abbott Laboratories, AC Immune SA, Allergan Inc, Allon Therapeutics, Alzheimer's Drug Discovery Foundation, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly and Company, ExonHit Therapeutics, Forest Laboratories Inc, GlaxoSmithKline plc, Ipsen Group, Johnson & Johnson Consumer Companies Inc, H. Lundbeck A/S, Myriad Pharmaceuticals Inc, MedAvante Inc, Medivation Inc, Merck & Co Inc, Merz Pharmaceuticals GmbH, Novartis Pharmaceuticals Corporation, F. Hoffman-La Roche Ltd, Sanofi-aventis LLC, Servier Laboratories, Schering-Plough Corporation, Schwabe Pharmaceuticals, Teva Pharmaceutical Industries Ltd, Toyama Pharmaceutical Co Ltd, Transition Therapeutics Inc, Voyager Pharmaceuticals Corp, and Wyeth Pharmaceuticals. Dr Weiner serves on scientific advisory boards for Aegis Therapies, Allergan Inc, Araclon Biotech, Avid Radiopharmaceuticals Inc, the Banner Pharmacaps Inc Alzheimer's Institute Alzheimer's Prevention Initiative; Bayer Schering Pharma AG, Biogen Idec, Bristol-Myers Squibb, CoMentis Inc, the Elan Corporation plc/Wyeth Pharmaceuticals Alzheimer's Immunotherapy Program, Eli Lilly and Company, Eisai Inc, Forest Laboratories Inc, Genentech Inc, Institut Catala de Neurociencias Aplicades, Neurochem Inc, Lippincott Williams & Wilkins, McKinsey & Company, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Pfizer Inc, and the United States Department of Veterans Affairs Central Office Gulf War Veterans' Illnesses Advisory Committee; has received funding for traval from l'Alliance Medicale et Scientifique, Alzheimer's Association, Alzheimer's Disease Neuroimaging Initiative, AstraZeneca Pharmaceuticals, Avid Pharmaceuticals Inc, the Banner Pharmacaps Inc Alzheimer's Institute, Bayer Health-Care, Elan Corporation plc/Wyeth Pharmaceuticals Alzheimer's Immunotherapy Program North American Advisory Board, Beijing Institute of Geriatrics, Centre Hospitalier Regional Universitaire-Hopital Roger Salengro, Clinical Trials on Alzheimer's Disease, Colloquium Paris, Eli Lilly and Company, Forest Laboratories Inc, Foundation for the National Institutes of Health, GE Healthcare Japan, Geneva University Hospitals, Innogenetics NV, Institut Catala de Neurociencias Aplicades, Ipsen, The Johns Hopkins University, Korean Neurological Association, The Michael J.; Fox Foundation for Parkinson's Research, Montreal Neurological Institute and Hospital at McGill University, Mount Sinai Medical Center, National Multiple Sclerosis Society, Neuroscience Early Stage Research Training, NeuroVigil Inc, New York University, Pfizer Inc Global Research and Development, Research Association for Biotechnology, Rotman Research Institute of Baycrest, Siemens AG, Society of Photo-Optical Instrumentation Engineers, Tel-Aviv University Medical School, Telemedicine & Advanced Technology Research Center, University of Pittsburgh, Wen Center for Alzheimer's Disease and Memory Disorders, University of Califonia Davis, United States Social Security Administration, Wenner-Grem Foundation, Washington University in St Louis, United States Department of Veterans Affairs Central Office, University of New Mexico School of Medicine, and University of Paris and from Kenes International and Nestle SA to attend conferences not funded by industry; serves on the editorial board of Alzheimer's & Dementia: The Journal of the Alzheimer's Association; has received honoraria from American Academy of Neurology, BOLT International, GE Healthcare Japan, Institut Catala de Neurociencias Aplicades, Ipsen, The Johns Hopkins University, NeuroVigil Inc, the Rotman Research Institute, and the Research Institute for Biotechnology; serves as a consultant for Araclon Biotech, AstraZeneca Pharmaceuticals, Bayer Healthcare, Bayer Schering Pharma AG, Biogen Idec, CoMentis Inc, Daiichi Sankyo Co Ltd, Elan Corporation plc, Eli Lilly and Company, ExonHit Therapeutics SA, Forest Laboratories Inc, Medivation Inc/Pfizer Inc, Ipsen, Neurochem International Limited (now Bellus Health International Limited), Novartis Pharmaceuticals Corporation, Pfizer Inc Global Research and Development, Servier Laboratories, Synarc Inc, and TauRx Therapeutics LTD; receives research support from Merck & Co Inc, Avid Radiopharmaceuticals Inc, the National Institutes of Health (as a private investigator: U01AG024904, P41 RR023953, and R01AG10897; and as a coinvestigator: P01AG19724, P50AG23501, R24 RR021992, R01 NS031966, and P01AG012435), the United States Department of Defense (as a private investigator: DAMD17-01-0764), and the Veterans Administration (as a core private investigator: MIRECC VISN 21); and holds stock in Synarc Inc and Elan Corporation plc.; The Foundation for the National Institutes of Health (http://www.fnih.org) coordinates the private sector participation of the $60 million ADNI public/private partnership begun by the National Institute on Aging and supported by the National Institutes of Health. To date, more than $27 million has been provided to the FNIH by Abbott Laboratotries, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation plc, Genentech Inc, GE HealthCare, GlaxoSmithKline plc, Innogenetics, Johnson & Johnson Consumer Companies Inc, Eli Lilly and Company, Merck & Co Inc, Novartis AG, Pfizer Inc, F. Hoffmann-La Roche Ltd, Schering-Plough Corporation, Synarc Inc, and Wyeth Pharmaceuticals, as well as nonprofit partners the Alzheimer's Association and the Alzheimer's Drug Discovery Foundation. This research was also supported by National Institutes of Health grant P50AG05142 in conjunction with the University of Southern California Alzheimer's Disease Research Center. Additional Information: The Alzheimer's Disease Neuroimaging Initiative: Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI, NIA U01 AG024904) database (www.loni.ucla.edu/ADNI). As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete list of investigators in ADNI is listed at: http://adni.loni.ucla.edu/about/who-we-are/principal-investigators/. The primary goal of ADNI has been to test whether serial magnetic resonance imaging, positron emission tomography, other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of MCI and early AD. Determination of sensitive and specific markers of very early AD progression is intended to aid researchers and clinicians to develop new treatments and monitor their effectiveness, as well as to lessen the time and cost of clinical trials. NR 24 TC 60 Z9 64 U1 2 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 2011 VL 68 IS 1 BP 58 EP 66 DI 10.1001/archneurol.2010.343 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 704MO UT WOS:000286057300008 PM 21220675 ER PT J AU Oliveira, L Cade, F Dohlman, C AF Oliveira, Lauro Cade, Fabiano Dohlman, Claes TI Keratoprosthesis in the fight against corneal blindness in developing countries SO ARQUIVOS BRASILEIROS DE OFTALMOLOGIA LA English DT Editorial Material ID BOSTON KERATOPROSTHESIS C1 [Oliveira, Lauro; Cade, Fabiano] Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil. [Dohlman, Claes] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Oliveira, L (reprint author), Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil. NR 17 TC 1 Z9 1 U1 0 U2 1 PU CONSEL BRASIL OFTALMOLOGIA PI SAO PAULO PA ALAMEDA SANTOS 1343, 11 ANDAR CJ 1110, CERQUEIRA CESAR, SAO PAULO, SP 00000, BRAZIL SN 0004-2749 J9 ARQ BRAS OFTALMOL JI Arq. Bras. Oftalmol. PD JAN-FEB PY 2011 VL 74 IS 1 BP 5 EP 6 PG 2 WC Ophthalmology SC Ophthalmology GA 777JV UT WOS:000291612700001 PM 21670898 ER PT J AU Bonaca, MP Morrow, DA Braunwald, E Cannon, CP Jiang, ST Breher, S Sabatine, MS Kempf, T Wallentin, L Wollert, KC AF Bonaca, Marc P. Morrow, David A. Braunwald, Eugene Cannon, Christopher P. Jiang, Songtao Breher, Stephanie Sabatine, Marc S. Kempf, Tibor Wallentin, Lars Wollert, Kai C. TI Growth Differentiation Factor-15 and Risk of Recurrent Events in Patients Stabilized After Acute Coronary Syndrome Observations From PROVE IT-TIMI 22 SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE acute coronary syndromes; cholesterol-lowering drugs; coronary artery disease; cytokines; heart failure; outcomes; unstable angina ID C-REACTIVE PROTEIN; CHRONIC HEART-FAILURE; CARDIOVASCULAR DYSFUNCTION; INHIBITORY CYTOKINE-1; MYOCARDIAL-INFARCTION; BETA SUPERFAMILY; STRATIFICATION; MARKER; RECLASSIFICATION; BIOMARKERS AB Objective-To investigate growth differentiation factor (GDF)-15 at hospital discharge for assessment of the risk of death, recurrent myocardial infarction (MI), and congestive heart failure, and to determination of whether these risks can be modified by statins. Methods and Results-GDF-15 is a transforming growth factor-beta-related cytokine induced in response to tissue injury. GDF-15 concentration is associated with all-cause mortality in patients with acute coronary syndrome (ACS). We measured GDF-15 in 3501 patients after ACS, treated with moderate or intensive statin therapy in PROVE IT-TIMI 22. By using established cutoff points, GDF-15 (< 1200, 1200-1800, and > 1800 ng/L) was associated with 2-year risk of death or MI (5.7%, 8.1%, and 15.1%, respectively; P < 0.001), death (P < 0.001), MI (P < 0.001), and congestive heart failure (P < 0.001). After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, smoking, MI, qualifying event, renal function, B-type natriuretic peptide, and high-sensitivity C-reactive protein, GDF-15 was associated with the risk of death or MI (adjusted hazard ratio per ln increase GDF-15, 2.1 [95% CI, 1.6 to 2.9]; P < 0.001), death (P < 0.001), MI (P < 0.001), and congestive heart failure (P < 0.001). There was no significant interaction between GDF-15 and intensive statin therapy for the risk of death or MI (P = 0.24 for the interaction). Conclusion-GDF-15 is associated with recurrent events after ACS, independent of clinical predictors, B-type natriuretic peptide, and high-sensitivity C-reactive protein. This finding supports GDF-15 as a prognostic marker in ACS and investigation of other therapies that modify this risk. (Arterioscler Thromb Vasc Biol. 2011;31:203-210.) C1 [Bonaca, Marc P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Jiang, Songtao] Harvard Clin Res Inst, Boston, MA USA. [Breher, Stephanie; Kempf, Tibor; Wollert, Kai C.] Hannover Med Sch, Div Mol & Translat Cardiol, Dept Cardiol & Angiol, D-3000 Hannover, Germany. [Wallentin, Lars] Univ Hosp, Uppsala Clin Res Ctr, Uppsala, Sweden. RP Bonaca, MP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM mbonaca@partners.org; wollert.kai@mh-hannover.de FU German Ministry of Education and Research (BMBF, BioChancePlus) FX This study was supported by the German Ministry of Education and Research (BMBF, BioChancePlus) (Dr Wollert). NR 29 TC 48 Z9 49 U1 0 U2 4 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 JAN PY 2011 VL 31 IS 1 BP 203 EP 210 DI 10.1161/ATVBAHA.110.213512 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 695AG UT WOS:000285342400031 PM 20966402 ER PT J AU Morita, Y Ismail, DM Elkon, KB Chu, CQ AF Morita, Yoshiaki Ismail, Doaa M. Elkon, Keith B. Chu, Cong-Qiu TI Dichotomous Response to Transforming Growth Factor beta After T Cell Receptor Activation by Naive CD4+ T Cells From DBA/1 Mice Enhanced Retinoic Acid Receptor-Related Orphan Nuclear Receptor gamma t Expression yet Reduced FoxP3 Expression SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; IFN-GAMMA; TGF-BETA; DEFICIENT MICE; CYTOKINE MILIEU; DIFFERENTIATION; T(H)17; INTERLEUKIN-17; SUSCEPTIBILITY; INFLAMMATION AB Objective. To investigate the molecular mechanism for biased interleukin-17 (IL-17) production by DBA/1 CD4+ T cells upon T cell receptor (TCR) and transforming growth factor beta (TGF beta) stimulation. Methods. Purified naive CD4+ T cells were stimulated with anti-CD3/CD28 under Th1, Th2, Th17, and induced T regulatory (iTreg) cell conditions. Cytokine production was assayed by intracellular staining and enzyme-linked immunosorbent assay. Expression of transcription factors was determined by reverse transcription-polymerase chain reaction, flow cytometry, and immunoblotting techniques. Results. Naive CD4+ T cells from DBA/1 mice produced more IL-17 under Th17 cell polarizing conditions as compared with those from C57BL/6 or BALB/c mice. Further investigation revealed no difference among the strains in terms of CD4+ T cell survival, upstream TCR signaling, or CD69 expression or in the phosphorylation of STAT-3 and expression of suppressor of cytokine signaling 3 that positively or negatively regulate IL-17 cell production. However, DBA/1 CD4+ T cells expressed increased levels of retinoic acid-related orphan receptor gamma t (ROR gamma t). Furthermore, under iTreg cell polarizing conditions, DBA/1 CD4+ T cells showed a strikingly reduced level of FoxP3 expression. When interferon-gamma and IL-4 were blocked, FoxP3 expression increased but remained lower in DBA/1 CD4+ T cells following exposure to TGF beta as compared with C57BL/6 CD4+ T cells. Moreover, DBA/1 CD4+ T cells showed reduced phosphorylation of Smad2 and Smad3 under both Th17 and iTreg cell polarizing conditions. Conclusion. These results indicate that naive CD4+ T cells from DBA/1 mice have a dichotomous response to TGF beta: enhanced ROR gamma t, yet reduced FoxP3, up-regulation. This observation may help to elucidate the branch point of TGF beta signaling that leads to skewed Th17, but reduced iTreg, cell differentiation. C1 [Chu, Cong-Qiu] Oregon Hlth & Sci Univ, Div Arthrit & Rheumat Dis, Portland, OR 97239 USA. [Chu, Cong-Qiu] Portland VA Med Ctr, Portland, OR USA. [Morita, Yoshiaki; Ismail, Doaa M.; Elkon, Keith B.; Chu, Cong-Qiu] Univ Washington, Seattle, WA 98195 USA. RP Chu, CQ (reprint author), Oregon Hlth & Sci Univ, Div Arthrit & Rheumat Dis, 3181 SW Sam Jackson Pk Rd,OP09, Portland, OR 97239 USA. EM chuc@ohsu.edu FU NIH [AR-055254]; Herndon and Esther Maury Fund; Bristol-Myers Squibb FX Supported by the NIH (grant AR-055254 to Dr. Chu) and the Herndon and Esther Maury Fund. Dr. Chu has received speaking fees or honoraria from Bristol-Myers Squibb (less than $10,000). NR 29 TC 5 Z9 5 U1 0 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-US JI Arthritis Rheum. PD JAN PY 2011 VL 63 IS 1 BP 118 EP 126 DI 10.1002/art.27759 PG 9 WC Rheumatology SC Rheumatology GA 702ZJ UT WOS:000285934100014 PM 20862680 ER PT J AU Saag, KG Yazdany, J Alexander, C Caplan, L Coblyn, J Desai, SP Harrington, T Liu, JN McNiff, K Newman, E Olson, R AF Saag, Kenneth G. Yazdany, Jinoos Alexander, Christopher Caplan, Liron Coblyn, Jonathan Desai, Sonali Parekh Harrington, Timothy, Jr. Liu, Jigna McNiff, Kristen Newman, Eric Olson, Richard CA Amer Coll Rheumatology Quality Mea TI Defining Quality of Care in Rheumatology: The American College of Rheumatology White Paper on Quality Measurement SO ARTHRITIS CARE & RESEARCH LA English DT Article ID ELECTRONIC MEDICAL-RECORD; CONTROLLED-TRIAL; SYSTEM LEVELS; ARTHRITIS; IMPROVEMENT; DISEASES; PERSPECTIVE; MANAGEMENT; VACCINATION; POPULATION C1 [Saag, Kenneth G.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35233 USA. [Yazdany, Jinoos] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. [Coblyn, Jonathan; Desai, Sonali Parekh] Brigham & Womens Hosp, Boston, MA 02115 USA. [Harrington, Timothy, Jr.] Univ Wisconsin, Madison, WI 53706 USA. [McNiff, Kristen] Amer Coll Rheumatol, Atlanta, GA 30329 USA. [Newman, Eric] Geisinger Med Ctr, Danville, PA 17822 USA. [Olson, Richard] Rockford Orthoped Associates, Rockford, IL USA. RP Saag, KG (reprint author), Univ Alabama, Div Clin Immunol & Rheumatol, 510 20th St S,Fac Off Tower 820, Birmingham, AL 35233 USA. EM ksaag@uab.edu FU Lilly; Merck; Aventis; NicOx; Genentech; Pfizer; Amgen; Novartis; Corrona; Takeda; BMS; Abbott FX Dr. Saag has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Lilly, Merck, Aventis, NicOx, Genentech, and Pfizer, and (more than $10,000 each) from Amgen and Novartis. Dr. Harrington has received consultant fees, speaking fees, and/or honoraria (more than $10,000) from Corrona, and owns stock and/or holds stock options in Murray Electronics. Dr. Olson has received speaking fees (less than $10,000 each) from Lilly, Novartis, Takeda, BMS, and Abbott. NR 42 TC 18 Z9 18 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JAN PY 2011 VL 63 IS 1 BP 2 EP 9 DI 10.1002/acr.20369 PG 8 WC Rheumatology SC Rheumatology GA 703AA UT WOS:000285935800002 PM 20945349 ER PT J AU Dahlgren, M Khosroshahi, A Stone, JH AF Dahlgren, Mollie Khosroshahi, Arezou Stone, John H. TI A 22-Year-Old Woman With Severe Headaches, Vomiting, and Tonic-Clonic Seizures SO ARTHRITIS CARE & RESEARCH LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; POSTERIOR REVERSIBLE ENCEPHALOPATHY; ACUTE INTERMITTENT PORPHYRIA; HYPERTENSIVE ENCEPHALOPATHY; LEUKOENCEPHALOPATHY SYNDROME; ANTIPHOSPHOLIPID ANTIBODIES; DIAGNOSIS; LESIONS; CT; MANIFESTATIONS C1 [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM jhstone@partners.org NR 34 TC 1 Z9 1 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JAN PY 2011 VL 63 IS 1 BP 165 EP 171 DI 10.1002/acr.20249 PG 7 WC Rheumatology SC Rheumatology GA 703AA UT WOS:000285935800021 PM 20506341 ER PT J AU Katiyar, SK Raman, C AF Katiyar, Santosh K. Raman, Chander TI Green tea: a new option for the prevention or control of osteoarthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Editorial Material ID NITRIC-OXIDE SYNTHASE; HUMAN CHONDROCYTES; POLYPHENOLS; EXPRESSION; REPAIR; MICE AB IL-1 beta is a major cytokine driving the inflammatory processes leading to the pathophysiology of osteoarthritis and other inflammatory diseases. Blockade of IL-1 beta activity using substances such as the naturally occurring IL-1 receptor antagonist or anti-IL-1 beta monoclonal antibody are currently being used or tested as therapy. However, such treatments are ineffective in osteoarthritis. In a recent study, epigallocatechin-3-gallate, a green tea polyphenol, was found to be effective in reducing IL-1 beta-induced inflammatory cytokines, TNF alpha, IL-6, granulocyte-macrophage colony-stimulating factor and several chemokines from human chondrocytes. The use of green tea polyphenols may be beneficial as a therapeutic addition to biologics that control IL-1 beta activity by increasing effectiveness and/or reducing dosage. C1 [Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Raman, Chander] Univ Alabama, Div Clin Immunol & Rheumatol, Dept Med, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCCIH NIH HHS [5R01AT2536, R01 AT002536]; NCI NIH HHS [R21 CA140832, 1R01CA140197, CA140832, R01 CA140197]; NIAID NIH HHS [1R01AI1076562, R01 AI076562] NR 10 TC 7 Z9 7 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2011 VL 13 IS 4 AR 121 DI 10.1186/ar3428 PG 2 WC Rheumatology SC Rheumatology GA 849UG UT WOS:000297150200035 PM 21861859 ER PT J AU Hong, EK Pearlman, J Salatin, B Wang, HW Liu, HY Cooper, RA Hargroder, T AF Hong, Eun-Kyoung Pearlman, Jon Salatin, Benjamin Wang, Hongwu Liu, Hsin-Yi Cooper, Rory A. Hargroder, Todd TI Design and Development of a Lightweight, Durable, Adjustable Composite Backrest Mounting SO ASSISTIVE TECHNOLOGY LA English DT Article DE adjustment; ANSI/RESNA wheelchair testing; backrest; design; focus group; wheelchair ID SPINAL-CORD-INJURY; WHEELCHAIR PROPULSION; SHOULDER PAIN; USERS AB Rigid backrest systems for wheelchairs provide a stable and comfortable base of support to help users maintain good posture while propelling and sitting static. Unfortunately, these backrest systems lack the adjustability necessary to allow users to comfortably perform some tasks, such as dressing; consequently, many users retain their sling-style backrests. We developed a lightweight, durable, adjustable composite (LWDAC) backrest mounting system to address these shortcomings and performed engineering and human subjects testing to evaluate the feasibility of the device. The LWDAC prototype passed the static engineering evaluation, as well as nearly all of the fatigue testing prior to failure of the device. Clinicians (n = 9) and users (n = 8) who evaluated the device in a focus group forum had an overall positive response. The participants agreed the backrest mounting can be operated with one hand and felt comfortable when participants were seated. Wheelchair users were interested in purchasing the backrest, and clinicians indicated they would recommend the LDWAC. C1 [Hong, Eun-Kyoung; Pearlman, Jon; Salatin, Benjamin; Wang, Hongwu; Liu, Hsin-Yi; Cooper, Rory A.] Dept Vet Affairs, Human Engn Res Labs, Pittsburgh, PA USA. [Hong, Eun-Kyoung; Pearlman, Jon; Salatin, Benjamin; Wang, Hongwu; Liu, Hsin-Yi; Cooper, Rory A.] Univ Pittsburgh, CAF Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Hargroder, Todd] Accessible Designs Inc, San Antonio, TX USA. RP Cooper, RA (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151R1 H, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI Wang, Hongwu/J-6133-2013; OI Wang, Hongwu/0000-0002-6567-9144; Pearlman, Jon/0000-0003-0830-9136 NR 24 TC 1 Z9 1 U1 0 U2 4 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 EI 1949-3614 J9 ASSIST TECHNOL JI Assist. Technol. PY 2011 VL 23 IS 1 BP 24 EP 35 DI 10.1080/10400435.2010.541405 PG 12 WC Rehabilitation SC Rehabilitation GA 880SP UT WOS:000299427800003 ER PT J AU Cooper, RA Teodorski, EE Sporner, ML Collins, DM AF Cooper, Rory A. Teodorski, Emily E. Sporner, Michelle L. Collins, Diane M. TI Manual Wheelchair Propulsion Over Cross-Sloped Surfaces: A Literature Review SO ASSISTIVE TECHNOLOGY LA English DT Review DE accessibility; manual wheelchair; manual wheelchair propulsion ID USERS; REHABILITATION; BIOMECHANICS; DESIGN AB Manual wheelchair propulsion may be facilitated or impeded depending upon the surface and the environment. One barrier may be the cross-slope of pathways. The purpose of this systematic literature review was to determine the quality of the evidence on the effects of cross-slopes on manual wheelchair propulsion. The goal was to identify and to understand the optimal design for cross-slopes that have the least negative impact for wheelchair users. Fifty-two articles were reviewed by 15 expert reviewers. Six were identified to be relevant to propulsion over cross-slopes. Most studies agree that traversing a cross-slope in a manual wheelchair is more difficult than propelling on a level surface. However, agreement has not been reached as to the percentage increase in effort or the optimal degree of cross-slopes that should be used as an acceptable standard. There is a paucity of research investigating the impact of cross-slopes on wheelchair mobility and community participation. C1 [Cooper, Rory A.; Teodorski, Emily E.; Sporner, Michelle L.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Pittsburgh, PA 15206 USA. [Cooper, Rory A.; Teodorski, Emily E.; Sporner, Michelle L.; Collins, Diane M.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, 7180 Highland Dr,Bldg 4,2nd Floor,151R1-H, Pittsburgh, PA 15206 USA. EM Rory.Cooper@va.gov NR 17 TC 5 Z9 5 U1 0 U2 4 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PY 2011 VL 23 IS 1 BP 42 EP 51 DI 10.1080/10400435.2010.541408 PG 10 WC Rehabilitation SC Rehabilitation GA 880SP UT WOS:000299427800005 ER PT J AU Grindle, GG Wang, HW Salatin, BA Vazquez, JJ Cooper, RA AF Grindle, Garrett G. Wang, Hongwu Salatin, Benjamin A. Vazquez, Juan J. Cooper, Rory A. TI Design and Development of the Personal Mobility and Manipulation Appliance SO ASSISTIVE TECHNOLOGY LA English DT Article DE control; manipulation; power wheelchair; robots ID WHEELCHAIR; PEOPLE AB For people with significant mobility impairments who also have both lower and upper limb disability, there are few technology solutions. The aim of this article is to describe the design and development of the Personal Mobility and Manipulation Appliance, a device that provides coordinated mobility and bimanual manipulation for people with both lower and upper limb impairment. The Personal Mobility and Manipulation Appliance is integrated from several commercial products and custom technologies, including two robotic arms mounted on a mobile robotic base. It has three primary operating modes: local user, remote user, and autonomous. It also has a cooperative control mode where two or more of the primary modes can be used simultaneously. The device was evaluated in a kitchen and was able to perform several complex tasks. Future work should focus on interface improvements and evaluations by end users. C1 Univ Pittsburgh, Dept Vet Affairs, Pittsburgh, PA USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Qual Technol Engn Res Ctr, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151R1-H, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI Wang, Hongwu/J-6133-2013 OI Wang, Hongwu/0000-0002-6567-9144 NR 46 TC 8 Z9 10 U1 1 U2 2 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PY 2011 VL 23 IS 2 BP 81 EP 92 DI 10.1080/10400435.2011.567374 PG 12 WC Rehabilitation SC Rehabilitation GA 880SR UT WOS:000299428000004 ER PT J AU Cooper, RA Ferretti, E Oyster, M Kelleher, A Cooper, R AF Cooper, Rory A. Ferretti, Eliana Oyster, Michelle Kelleher, Annmarie Cooper, Rosemarie TI The Relationship Between Wheelchair Mobility Patterns and Community Participation Among Individuals With Spinal Cord Injury SO ASSISTIVE TECHNOLOGY LA English DT Article DE activity; community participation; manual wheelchair; powered wheelchair; wheelchair ID POWER-ASSISTED WHEELCHAIR; LIFE SATISFACTION; HEALTH-STATUS; PUSHRIM; TETRAPLEGIA; IMPACT; USERS AB Participation is considered the most meaningful outcome of rehabilitation. The purpose of this study was to investigate whether there were correlations between wheelchair activity recorded with a data logger and community participation as measured by the Participation Survey/Mobility. Data from 16 participants were included in this study. Data collected during a two week period using a data logging device were analyzed to determine the mobility characteristics of participants. Among manual wheelchair users, significant positive correlations were found between average speed traveled and the community participation content areas of transportation (r(s) = .837, p = .019) and socialization (r(s) = .772, p = .042). In addition, for manual wheelchair users there was a trend toward a significant correlation between average speed traveled and total community participation score (r(s) = .714, p = .071). Among power wheelchair users, there was a trend toward a significant negative correlation between average speed traveled and the community participation content area of leisure activity (r(s) = -.635, p = .066). Understanding the relationship between wheelchair speed and community participation can be useful information to enable clinicians to recommend the most appropriate mobility devices designed to enhance community participation. C1 [Cooper, Rory A.; Kelleher, Annmarie; Cooper, Rosemarie] Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, Dept Rehabil Sci & Technol,Rehabil Res & Dev Serv, Pittsburgh, PA 15206 USA. [Ferretti, Eliana] Dept Vet Affairs, Human Engn Res Labs, Rehabil Res & Dev Serv, Pittsburgh, PA USA. [Oyster, Michelle] Univ Pittsburgh, Human Engn Res Labs, Rehabil Res & Dev Serv, Dept Vet Affairs, Pittsburgh, PA 15206 USA. [Oyster, Michelle] Univ Pittsburgh, Human Engn Res Labs, Rehabil Res & Dev Serv, Dept Phys Med & Rehabil, Pittsburgh, PA 15206 USA. RP Cooper, RA (reprint author), Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, Dept Rehabil Sci & Technol,Rehabil Res & Dev Serv, 7180 Highland Dr,151R1-B, Pittsburgh, PA 15206 USA. EM Rory.Cooper@va.gov NR 28 TC 4 Z9 4 U1 0 U2 8 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PY 2011 VL 23 IS 3 BP 177 EP 183 DI 10.1080/10400435.2011.588991 PG 7 WC Rehabilitation SC Rehabilitation GA 880SU UT WOS:000299428300005 ER PT J AU Jefferds, AN Pearlman, JL Wee, J Cooper, RA AF Jefferds, Alexandra N. Pearlman, Jon L. Wee, Joy Cooper, Rory A. TI International Mobility Technology Research: A Delphi Study to Identify Challenges and Compensatory Strategies SO ASSISTIVE TECHNOLOGY LA English DT Article DE cross-cultural; Delphi technique; evidence-based practice; international; translations; wheelchairs ID INFORMED-CONSENT; REHABILITATION RESEARCH; COLLABORATIVE RESEARCH; HEALTH; ISSUES; INDIA; IDENTIFICATION; TRANSLATION; RECRUITMENT; DISABILITY AB We sought to identify logistical and ethical challenges to performing wheelchair-related research in low-and middle-income countries and to generate a list of compensatory strategies to address these challenges. Thirteen individuals with experience in the field participated in an online Delphi study. The surveys asked participants to identify research challenges, suggest strategies to address the selected challenges, and critique each other's strategies. Participants identified challenges in the use of research techniques, compensation for participation that does not result coercion, oral and written translation materials, funding for research, collaboration with local professionals, and "respect for persons." Effective international mobility research requires time, cultural sensitivity, collaboration, and careful planning. An understanding of these requirements can allow researchers to anticipate and compensate for common pitfalls of their work, thus making the research more productive and beneficial to subjects. Future research is required to verify the general effectiveness of compensatory strategies. C1 [Jefferds, Alexandra N.; Pearlman, Jon L.; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Pearlman, Jon L.; Cooper, Rory A.] Univ Pittsburgh, Dept Vet Affairs, Pittsburgh, PA USA. [Wee, Joy] Queens Univ, Kingston, ON, Canada. RP Pearlman, JL (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 7180 Highland Dr,Bldg 4,2nd Floor,151R1-H, Pittsburgh, PA 15206 USA. EM jlp46@pitt.edu OI Pearlman, Jon/0000-0003-0830-9136 NR 54 TC 1 Z9 1 U1 3 U2 5 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PY 2011 VL 23 IS 4 BP 232 EP 242 DI 10.1080/10400435.2011.614677 PG 11 WC Rehabilitation SC Rehabilitation GA 882PK UT WOS:000299576000006 PM 22256672 ER PT J AU Evans, KK Cohen, MA Tambouret, R Horowitz, T Kreindel, E Wolfe, JM AF Evans, Karla K. Cohen, Michael A. Tambouret, Rosemary Horowitz, Todd Kreindel, Erica Wolfe, Jeremy M. TI Does visual expertise improve visual recognition memory? SO ATTENTION PERCEPTION & PSYCHOPHYSICS LA English DT Article DE Visual recognition memory; Expertise; Medical images; Medical experts; Real world scenes; Objects ID LONG-TERM-MEMORY; PICTURES; PERCEPTION; LAYMEN; CHESS AB In general, humans have impressive recognition memory for previously viewed pictures. Many people spend years becoming experts in highly specialized image sets. For example, cytologists are experts at searching micrographs filled with potentially cancerous cells and radiologists are expert at searching mammograms for indications of cancer. Do these experts develop robust visual long-term memory for their domain of expertise? If so, is this expertise specific to the trained image class, or do such experts possess generally superior visual memory? We tested recognition memory of cytologists, radiologists, and controls with no medical experience for three visual stimulus classes: isolated objects, scenes, and mammograms or micrographs. Experts were better than control observers at recognizing images from their domain, but their memory for those images was not particularly good (D' similar to 1.0) and was much worse than memory for objects or scenes (D' > 2.0). Furthermore, experts were not better at recognizing scenes or isolated objects than control observers. C1 [Evans, Karla K.; Horowitz, Todd; Wolfe, Jeremy M.] Harvard Univ, Sch Med, Visual Attent Lab, Cambridge, MA 02139 USA. [Evans, Karla K.; Horowitz, Todd; Kreindel, Erica; Wolfe, Jeremy M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tambouret, Rosemary] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Evans, KK (reprint author), Harvard Univ, Sch Med, Visual Attent Lab, 64 Sidney St,Suite 170, Cambridge, MA 02139 USA. EM kevans@search.bwh.harvard.edu RI Wolfe, Jeremy/C-1621-2012; Horowitz, Todd/J-3376-2013; Wolfe, Jeremy/A-9248-2016 OI Wolfe, Jeremy/0000-0002-6475-1984; Wolfe, Jeremy/0000-0002-6475-1984 FU NRSA [F32EY019819-01]; NIH-NEI [EY017001] FX This research was funded by a NRSA F32EY019819-01 grant to Karla K. Evans and NIH-NEI EY017001 to Jeremy M. Wolfe. NR 19 TC 13 Z9 13 U1 3 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1943-3921 J9 ATTEN PERCEPT PSYCHO JI Atten. Percept. Psychophys. PD JAN PY 2011 VL 73 IS 1 BP 30 EP 35 DI 10.3758/s13414-010-0022-5 PG 6 WC Psychology; Psychology, Experimental SC Psychology GA 720BE UT WOS:000287254400005 PM 21258906 ER PT J AU Lee, J Nadol, JB Eddington, DK AF Lee, Joonhan Nadol, Joseph B., Jr. Eddington, Donald K. TI Factors Associated with Incomplete Insertion of Electrodes in Cochlear Implant Surgery: A Histopathologic Study SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Cochlear implant; Causes of incomplete electrode insertion; Histopathology of the human temporal bone ID SPIRAL GANGLION-CELLS; TEMPORAL BONE; WORD RECOGNITION; TRAUMA; RECONSTRUCTION; OTOSCLEROSIS; POSITION; DEPTH AB Objectives: Atraumatic and complete insertion of the electrode array is a stated objective of cochlear implant surgery. However, it is known that obstructions within the cochlea such as new bone formation, cochlear otosclerosis, temporal bone fracture, and cochlear anomalies may limit the depth of insertion of the electrode array. In addition, even among patients without obvious clinical or radiographic indicators of obstruction, incomplete insertion may occur. The current study is a histopathologic evaluation of possible sources of resistance to insertion of the electrode array using the temporal bone collection of the Massachusetts Eye and Ear Infirmary. Methods: Forty temporal bones from patients who in life had undergone cochlear implantation were evaluated. Temporal bones were removed at autopsy and fixed and prepared for histologic study by standard techniques. Specimens were then serially sectioned and reconstructed by 2-dimensional methods. Two electrode metrics were determined for each bone: the inserted length (IL: the distance measured from the cochleostomy site to the apical tip of the electrode) and the active electrode length (AEL: the distance between the most basal and most apical electrodes on the electrode array). The ratio of these two metrics (IL/AEL) was used to split the temporal bones into two groups: those with incomplete insertion (n = 27, IL/AEL < 1.0) and those with complete insertion (n = 13, IL/AEL 6 1.0). Seven possible histopathologic indicators of resistance to insertion of the electrode due to contact with the basilar membrane, osseous spiral lamina and/or spiral ligament were evaluated by analysis of serial sections from the temporal bones along the course of the electrode tracks. Results: Obvious obstruction by abnormal intracochlear bone or soft tissue accounted for only 6 (22%) of the 27 partial insertions. Of the remaining 21 bones with incomplete insertions and 13 bones with complete insertions, dissection of the spiral ligament to the lateral cochlear wall was the only histopathologic indicator of insertion resistance identified with significantly higher frequency in the partial-insertion bones than in the complete-insertion bones (p = 0.003). An observed trend for the percentage of complete insertions to decrease with the number of times the electrode penetrated the basilar membrane did not reach significance. In the bones without an obvious obstruction, the most frequently observed indicator of insertion resistance was dissection of the spiral ligament (with no contact of the lateral cochlear wall) identified in 67% (14/21) of partial-insertion bones and in 92% (12/13) of complete-insertion bones. Conclusion: These results are consistent with the view that (1) electrode contact with cochlear structures resulting in observable trauma to the basilar membrane, osseous spiral lamina and/or spiral ligament does not necessarily impact the likelihood of complete insertion of the electrode array and (2) once contact trauma to the spiral ligament reaches the point of dissection to the cochlear wall, the likelihood of incomplete insertion increases dramatically. Copyright (C) 2010 S. Karger AG, Basel C1 [Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Lee, Joonhan; Nadol, Joseph B., Jr.; Eddington, Donald K.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lee, Joonhan; Nadol, Joseph B., Jr.; Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Nadol, Joseph B., Jr.; Eddington, Donald K.] MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Lee, Joonhan] Chosun Univ, Coll Med, Dept Otolaryngol Head & Neck Surg, Kwangju, South Korea. RP Eddington, DK (reprint author), Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, 243 Charles St, Boston, MA 02114 USA. EM don_eddington@meei.harvard.edu FU NIDCD NIH HHS [R01DC000152, R01 DC000152] NR 23 TC 9 Z9 11 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2011 VL 16 IS 2 BP 69 EP 81 DI 10.1159/000316445 PG 13 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 633QK UT WOS:000280518800001 PM 20571258 ER PT J AU Lee, J Eddington, DK Nadol, JB AF Lee, Joonhan Eddington, Donald K. Nadol, Joseph B. TI The Histopathology of Revision Cochlear Implantation SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Electrode track; Histopathology; Revision cochlear implantation ID FIBROUS TISSUE; REIMPLANTATION; SURGERY; PERFORMANCE; FAILURES; RECONSTRUCTION; CHILDREN; BONE AB The current study evaluates histopathologic changes in the temporal bones of 4 human subjects who underwent revision cochlear implantation. Specimens were removed at autopsy, fixed and prepared for histological study by standard techniques. Specimens were serially sectioned, reconstructed by two-dimensional methods, and the tracks of the initial and revision cochlear-implant electrodes identified. The tracks were of three types: a 'common track' (shared by the reimplantation electrode and initial electrode), 'two tracks' (where the reimplantation electrode was in a different track than that of the initial electrode) and 'one track' (where the reimplantation electrode extended beyond the initial electrode, forming a single track). Associated histopathologic findings (new bone formation, fibrosis or inflammatory cells, and cochlear fluid) were evaluated for the three types of tracks. In all 4 subjects, the insertion depth of the revision cochlear implant was deeper than that of the initial cochlear implant. The primary track of the initial implantation did not interfere with insertion of a revision cochlear implant, and the trajectory of the revision electrode did not always follow the primary track. In cochlear segments with a common track or two tracks, the mean (across-subject) percent area of the extraelectrode cochlear duct filled with abnormal (new bone or fibrotic) tissue (43.2%) was significantly greater than the mean percent area occupied by fluid (13.4%; t = 3.12, d.f. = 19.9, p = 0.003). Copyright (C) 2010 S. Karger AG, Basel C1 [Eddington, Donald K.] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Lee, Joonhan; Eddington, Donald K.; Nadol, Joseph B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Lee, Joonhan; Eddington, Donald K.; Nadol, Joseph B.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Eddington, Donald K.; Nadol, Joseph B.] MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. [Lee, Joonhan] Chosun Univ, Coll Med, Dept Otolaryngol Head & Neck Surg, Kwangju, South Korea. RP Eddington, DK (reprint author), Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, 243 Charles St, Boston, MA 02114 USA. EM don_eddington@meei.harvard.edu FU NIDCD NIH HHS [R01 DC000152] NR 25 TC 6 Z9 8 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2011 VL 16 IS 5 BP 336 EP 346 DI 10.1159/000322307 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 806SV UT WOS:000293832800006 PM 21196725 ER PT J AU Cashman, EC Bresnihan, M Timon, C AF Cashman, E. C. Bresnihan, M. Timon, C. TI Patients' quality of life post thyroidectomy SO B-ENT LA English DT Article DE Thyroidectomy; surgery; quality of life; hyperthyroidism AB Patients' quality of life post thyroidectomy. Introduction: This study was designed to evaluate health related quality of life post thyroidectomy for hyperthyroidism with respect to clinical benefit and patient satisfaction. This is one of the first such studies in the literature evaluating quality of life post thyroidectomy for hyperthyroidism. Methods: A total of sixty-three patients who underwent thyroidectomy for hyperthyroidism over a four and a half year period were included in the study. All surgery was preformed by a single surgeon. Results: Sixty-three patients were contacted on average 26 months post thyroidectomy (range 4-51 months). The main indication for surgery in our series was failure to respond to medical therapy representing 92% (58/63) of cases. The main cause of hyperthyroidism was Grave's disease which represented 8.1% (51/63) of cases, toxic multinodular goitre accounted for 14% (9/63) of cases and 5% (3/63) of patients had a toxic adenoma. Ninety-five percent (60/63) underwent total thyroidectomy and 5% (3/63) underwent partial thyroidectomy. Eighty-one percent of patients were female (51/63) and 19% (12/63) were male. The median age of patients was 43 yrs (range 18-73 yrs). HRQL was significantly improved in physical, mental and social dimensions in the majority of patients. Conclusion: This study evaluates quality of life in a standardized analogue fashion, with significant improvement reported in all quality of life measures and we conclude that thyroidectomy remains an excellent treatment option for patients with hyperthyroidism. C1 [Cashman, E. C.] Royal Victoria Eye & Ear Hosp, Dublin 2, Ireland. [Bresnihan, M.; Timon, C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cashman, EC (reprint author), Harvard Univ, Sch Med, Dana Faber Canc Inst, Cambridge, MA 02138 USA. EM emmacashman@gmail.com NR 9 TC 0 Z9 1 U1 1 U2 3 PU ROYAL BELGIAN SOC EAR, NOSE, THROAT, HEAD & NECK SURGERY PI LEUVEN PA PO BOX 1248, LEUVEN, 00000, BELGIUM SN 0001-6497 J9 B-ENT JI B-ENT PY 2011 VL 7 IS 4 BP 261 EP 265 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 880IO UT WOS:000299401000005 PM 22338238 ER PT J AU Roberts, DS Faquin, WC Deschler, DG AF Roberts, D. S. Faquin, W. C. Deschler, D. G. TI Temporal bone giant cell tumour: report of a second primary giant cell tumour of the temporal bone and infratemporal fossa SO B-ENT LA English DT Article DE Giant cell tumour; temporal bone; infratemporal fossa ID SKULL AB Temporal bone giant cell tumour: report of a second primary giant cell tumour of the temporal bone and infratemporal fossa. Objective: To report a second primary giant cell tumour (GCT) of the temporal bone and infratemporal fossa. Methodology: Medical records were analyzed in the context of the available literature. Results: A 30 year-old male developed a temporal bone GCT with infratemporal fossa extension 12 years after undergoing successful surgical treatment of a GCT of the femur. These tumours were histologically distinct, suggesting the development of a second primary GCT rather than metastatic disease. This case differs from prior reported cases by surgical approach. Complete removal was achieved but required resection of the zygomatic arch and dissection of all upper facial nerve branches. The patient is disease free after 3 years with acceptable functional and cosmetic results. Conclusion: Complete resection of GCTs of the temporal bone and infratemporal fossa is advocated. Surgical techniques that allow for visualization of the facial nerve and increase surgical access can enhance overall clinical success. C1 [Roberts, D. S.; Deschler, D. G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. [Faquin, W. C.] Massachusetts Eye & Ear Infirm, Dept Pathol, Boston, MA 02114 USA. [Faquin, W. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roberts, DS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Daniel_Roberts@meei.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU ROYAL BELGIAN SOC EAR, NOSE, THROAT, HEAD & NECK SURGERY PI LEUVEN PA PO BOX 1248, LEUVEN, 00000, BELGIUM SN 0001-6497 J9 B-ENT JI B-ENT PY 2011 VL 7 IS 4 BP 301 EP 303 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 880IO UT WOS:000299401000013 PM 22338246 ER PT S AU Szmulewicz, DJ Waterston, JA MacDougall, HG Mossman, S Chancellor, AM McLean, CA Merchant, S Patrikios, P Halmagyi, GM Storey, E AF Szmulewicz, David J. Waterston, John A. MacDougall, Hamish G. Mossman, Stuart Chancellor, Andrew M. McLean, Catriona A. Merchant, Saumil Patrikios, Peter Halmagyi, G. Michael Storey, Elsdon BE Rucker, J Zee, DS TI Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of the clinical features and video-oculographic diagnosis SO BASIC AND CLINICAL OCULAR MOTOR AND VESTIBULAR RESEARCH SE Annals of the New York Academy of Sciences LA English DT Review CT Symposium on Basic and Clinical Ocular Motor and Vestibular Research CY MAR 25-27, 2011 CL Buenos Aires, ARGENTINA SP Univ Hosp Cleveland, Evenor Armington Fund, Fdn FAPS, Fdn Interacoust DE cerebellar ataxia; bilateral vestibular loss; MRI; cerebellar atrophy; neuronopathy ID MACHADO-JOSEPH-DISEASE; BILATERAL VESTIBULOPATHY; POLYNEUROPATHY; ENCEPHALOPATHY; ABNORMALITIES; DEGENERATION; FAMILIES; REFLEX; SIGN; EYE AB The association of bilateral vestibulopathy with cerebellar ataxia was first reported in 1991 and delineated as a distinct syndrome with a characteristic and measurable clinical sign-an absent visually enhanced vestibulo-ocular reflex-in 2004. We reviewed 27 patients with this syndrome and show that a non-length-dependent sensory deficit with absent sensory nerve action potentials is an integral component of this syndrome, which we now call "cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome" (CANVAS). All patients had brain MRI and 22/27 had evidence of cerebellar atrophy involving anterior and dorsal vermis, as well as the hemispheric crus I. Brain and temporal bone pathology in one patient showed marked loss of Purkinje cells and of vestibular, trigeminal, and facial ganglion cells, but not of spiral ganglion cells. There are two sets of sibling pairs, suggesting CANVAS is a late-onset recessive disorder. The characteristic clinical sign-the visual vestibulo-ocular reflex deficit can be demonstrated and measured clinically using video-oculography. C1 [Szmulewicz, David J.] Alfred Hosp, Dept Neurosci, Melbourne, Vic 3004, Australia. [Waterston, John A.; Storey, Elsdon] Monash Univ, Dept Neurosci, Melbourne, Vic 3004, Australia. [MacDougall, Hamish G.] Univ Sydney, Veslibular Res Lab, Sch Psychol, Sydney, NSW 2006, Australia. [Mossman, Stuart] Capital Coast Hlth, Dept Neurol, Wellington, New Zealand. [Chancellor, Andrew M.] Tauranga Hosp, Dept Med, Wellington, New Zealand. [McLean, Catriona A.] Alfred Hosp, Dept Anat Pathol, Melbourne, Vic 3004, Australia. [Merchant, Saumil] Massachusetts Eye & Ear Infirm, Dept Otopathol, Boston, MA 02114 USA. [Patrikios, Peter] Royal Brisbane & Womens Hosp, Dept Neurol, Brisbane, Qld, Australia. [Halmagyi, G. Michael] Royal Prince Alfred Hosp, Dept Neurol, Sydney, NSW, Australia. RP Szmulewicz, DJ (reprint author), Alfred Hosp, Dept Neurosci, Commercial Rd, Melbourne, Vic 3004, Australia. EM dsz@me.com RI Storey, Elsdon/A-9889-2013 NR 41 TC 28 Z9 28 U1 0 U2 7 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-843-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1233 BP 139 EP 147 DI 10.1111/j.1749-6632.2011.06158.x PG 9 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BXY20 UT WOS:000297604800018 PM 21950986 ER PT S AU Wray, SH Dalmau, J Chen, A King, S Leigh, RJ AF Wray, Shirley H. Dalmau, Josep Chen, Athena King, Susan Leigh, R. John BE Rucker, J Zee, DS TI Paraneoplastic disorders of eye movements SO BASIC AND CLINICAL OCULAR MOTOR AND VESTIBULAR RESEARCH SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Symposium on Basic and Clinical Ocular Motor and Vestibular Research CY MAR 25-27, 2011 CL Buenos Aires, ARGENTINA SP Univ Hosp Cleveland, Evenor Armington Fund, Fdn FAPS, Fdn Interacoust DE upbeat nystagmus; oscillopsia; pancreatic endocrine; neoplasm ID OPSOCLONUS-MYOCLONUS SYNDROME; DOWNBEAT NYSTAGMUS; VERTICAL NYSTAGMUS; GRAVITY DEPENDENCE; CLINICAL ANALYSIS; OCULAR DRIFT; ENCEPHALITIS AB Paraneoplastic syndromes affecting the brainstem and cerebellum are reported to cause a variety of abnormalities of eye movements. Recent studies have begun to account for the mechanisms underlying several syndromes, characterized by opsoclonus, slow, or dysmetric saccades, as well as downbeat nystagmus. We provide evidence that upbeat nysiagmus in a female patient with pancreatic cancer reflected a cerebellar-induced imbalance of otolithic pathways: she showed marked retropulsion, and her nystagmus was dependent on head position, being absent when supine, and suppressed with convergence. In addition to anti-Hu antibodies, we demonstrated antibodies to a novel neuronal cell surface antigen. Taken with other recent studies, our findings suggest that paraneoplastic syndromes arise due to antibodies against surface neuronal antigens, including receptors and channels. Abnormal eye movements in paraneoplastic syndromes offer insights into the pathogenesis of these disorders and the opportunity to test potential therapies, such as new drugs with effects on neuronal channels. C1 [Wray, Shirley H.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Dalmau, Josep] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Chen, Athena; King, Susan; Leigh, R. John] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Chen, Athena; King, Susan; Leigh, R. John] Vet Affairs Med Ctr, Neurol Serv, Cleveland, OH USA. [Chen, Athena; King, Susan; Leigh, R. John] Vet Affairs Med Ctr, Daroff DellOsso Lab, Cleveland, OH USA. RP Wray, SH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, WACC 705, Boston, MA 02114 USA. EM wray@helix.mgh.harvard.edu OI Dalmau, Josep/0000-0001-5856-2813 FU NIH [EY06717, RO1CA89054, 1RC1NS068204-01]; Department of Veterans Affairs; Evenor Armington Fund; McKnight Neuroscience of Brain Disorders award FX This work was supported by NIH Grant EY06717, the Department of Veterans Affairs, and the Evenor Armington Fund (to Dr. Leigh); and NIH Grants RO1CA89054, 1RC1NS068204-01, and a McKnight Neuroscience of Brain Disorders award (to Dr. Dalmau). NR 22 TC 3 Z9 3 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-843-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1233 BP 279 EP 284 DI 10.1111/j.1749-6632.2011.06113.x PG 6 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BXY20 UT WOS:000297604800037 PM 21951005 ER PT S AU Chan, HHL AF Chan, Henry H. L. BE Allemann, IB Goldberg, DJ TI Special Considerations for Darker-Skinned Patients SO BASICS IN DERMATOLOGICAL LASER APPLICATIONS SE Current Problems in Dermatology LA English DT Article; Book Chapter ID INTENSE PULSED-LIGHT; ND-YAG LASER; CHINESE PATIENTS; CUTANEOUS PHOTODAMAGE; MELASMA; ASIANS; SCALE AB Today, lasers are being used to treat an increasing number of medical and aesthetic challenges with great success. However, the effects of laser treatments upon darker-skinned patients differ from those on Caucasians in several aspects; this makes their use not without risk. First of all, skin of color has a greater epidermal melanin content than Caucasian skin, and this increase in epidermal pigmentation acts as a competing chromophore. Furthermore, with epidermal melanin acting as a competing chromophore, the light dosage that reaches the actual target is reduced, and higher fluence is necessary to produce a desirable effect. Although effective cooling and longer wavelengths with decreased melanin absorption have been used, the treatment of patients with Fitzpatrick skin types >IV remains associated with a significant risk of side effects. Thus, careful selection of laser and light source parameters in conjunction with skin cooling are important in obtaining desirable clinical outcomes in ethnic skin. Copyright (C) 2011 S. Karger AG, Basel C1 [Chan, Henry H. L.] Univ Hong Kong, Div Dermatol, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Chan, HHL (reprint author), 13th Floor,Club Lusitano 16 Ice House St, Hong Kong, Hong Kong, Peoples R China. EM hhlchan@hkucc.hku.hk NR 25 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1421-5721 BN 978-3-8055-9788-3 J9 CURR PROBL DERMATOL JI Curr.Probl.Dermatol. PY 2011 VL 42 BP 153 EP 159 PG 7 WC Dermatology SC Dermatology GA BXA71 UT WOS:000295549600016 PM 21865808 ER PT S AU Zucker, NL Herzog, D Moskovich, A Merwin, R Lin, T AF Zucker, Nancy L. Herzog, David Moskovich, Ashley Merwin, Rhonda Lin, Tammy BE Adan, RAH Kaye, WH TI Incorporating Dispositional Traits into the Treatment of Anorexia Nervosa SO BEHAVIORAL NEUROBIOLOGY OF EATING DISORDERS SE Current Topics in Behavioral Neurosciences LA English DT Article; Book Chapter DE Anorexia nervosa; Attention; Eating disorders; Perfectionism; Reinforcment; Temperament; Treatment ID DIALECTICAL BEHAVIOR-THERAPY; BORDERLINE PERSONALITY-DISORDER; DUAL PROCESS MODEL; NEGATIVE PERFECTIONISM; SELF-VERIFICATION; EFFORTFUL CONTROL; EATING-DISORDERS; PSYCHOLOGICAL DISTRESS; UNIVERSITY-STUDENTS; SUICIDE IDEATION AB We provide a general framework to guide the development of interventions that aim to address persistent features in eating disorders that may preclude effective treatment. Using perfectionism as an exemplar, we draw from research in cognitive neuroscience regarding attention and reinforcement learning, from learning theory and social psychology regarding vicarious learning and implications for the role modeling of significant others, and from clinical psychology on the importance of verbal narratives as barriers that may influence expectations and shape reinforcement schedules. C1 [Zucker, Nancy L.; Merwin, Rhonda] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Herzog, David] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Herzog, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Zucker, NL (reprint author), Duke Univ, Med Ctr, Durham, NC 27706 USA. EM Zucke001@mc.duke.edu FU NIMH NIH HHS [RC1 MH088678] NR 94 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-642-15130-9 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2011 VL 6 BP 289 EP 314 DI 10.1007/7854_2010_92 D2 10.1007/978-3-642-15131-6 PG 26 WC Behavioral Sciences; Neurosciences; Psychology SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA BTF77 UT WOS:000286843100017 PM 21243482 ER PT J AU Butler, PM McNamara, P Durso, R AF Butler, Paul M. McNamara, Patrick Durso, Raymon TI Side of onset in Parkinson's disease and alterations in religiosity: Novel behavioral phenotypes SO BEHAVIOURAL NEUROLOGY LA English DT Article DE Religiosity; Parkinson's disease; brain laterality; aesthetics; dopamine; frontal lobes ID TEMPORAL-LOBE EPILEPSY; INTERICTAL BEHAVIOR; COGNITIVE DECLINE; SPIRITUALITY; HEALTH; SELF; SCHIZOPHRENIA; RELIGIOUSNESS; DYSFUNCTION; ACTIVATION AB Behavioral neurologists have long been interested in changes in religiosity following circumscribed brain lesions. Advances in neuroimaging and cognitive experimental techniques have been added to these classical lesion-correlational approaches in attempt to understand changes in religiosity due to brain damage. In this paper we assess processing dynamics of religious cognition in patients with Parkinson's disease (PD). We administered a four-condition story-based priming procedure, and then covertly probed for changes in religious belief. Story-based priming emphasized mortality salience, religious ritual, and beauty in nature (Aesthetic). In neurologically intact controls, religious belief-scores significantly increased following the Aesthetic prime condition. When comparing effects of right (RO) versus left onset (LO) in PI) patients, a double-dissociation in religious belief-scores emerged based on prime condition. RO patients exhibited a significant increase in belief following the Aesthetic prime condition and LO patients significantly increased belief in the religious ritual prime condition. Results covaried with executive function measures. This suggests lateral cerebral specialization for ritual-based (left frontal) versus aesthetic-based (right frontal) religious cognition. Patient-centered individualized treatment plans should take religiosity into consideration as a complex disease-associated phenomenon connected to other clinical variables and health outcomes. C1 [Butler, Paul M.; McNamara, Patrick; Durso, Raymon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Butler, Paul M.; McNamara, Patrick; Durso, Raymon] VA Boston Healthcare Syst, Dept Neurol, Boston, MA USA. RP Butler, PM (reprint author), Boston Univ, Sch Med, Dept Neurol, 72 E Concord St,Robinson Bldg,5th Floor,Room 528, Boston, MA 02118 USA. EM pmbutler@bu.edu FU Office of Research Development; Medical Research Service; Department of Veterans Affairs; National Institute of Deafness and other Communication Disorders (NIDCD) [5RO1DC007956-03] FX The authors report no conflicts of interest. This is based on work supported by the Office of Research Development, Medical Research Service, Department of Veterans Affairs and the National Institute of Deafness and other Communication Disorders (NIDCD) Grant No. 5RO1DC007956-03. NR 54 TC 8 Z9 8 U1 2 U2 18 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2011 VL 24 IS 2 BP 133 EP 141 DI 10.3233/BEN-2011-0282 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 792CZ UT WOS:000292719400003 PM 21606574 ER PT J AU Meier, TB Naing, L Thomas, LE Nair, VA Hillis, AE Prabhakaran, V AF Meier, Timothy B. Naing, Lin Thomas, Lisa E. Nair, Veena A. Hillis, Argye E. Prabhakaran, Vivek TI Validating age-related functional imaging changes in verbal working memory with acute stroke SO BEHAVIOURAL NEUROLOGY LA English DT Article DE Working memory; aging; lesion; stroke ID EVENT-RELATED FMRI; PREFRONTAL CORTEX; CORTICAL HYPOPERFUSION; HEMISPHERIC-ASYMMETRY; NEURAL ACTIVITY; FRONTAL-CORTEX; BRAIN ACTIVITY; AGING AFFECTS; OLDER ADULTS; NEUROANATOMY AB Functional imaging studies consistently find that older adults recruit bilateral brain regions in cognitive tasks that are strongly lateralized in younger adults, a characterization known as the Hemispheric Asymmetry Reduction in Older Adults model. While functional imaging displays what brain areas are active during tasks, it cannot demonstrate what brain regions are necessary for task performance. We used behavioral data from acute stroke patients to test the hypothesis that older adults need both hemispheres for a verbal working memory task that is predominantly left-lateralized in younger adults. Right-handed younger (age <= 50, n = 7) and older adults (age > 50, n = 21) with acute unilateral stroke, as well as younger (n = 6) and older (n = 13) transient ischemic attack (TIA) patients, performed a self-paced verbal item-recognition task. Older patients with stroke to either hemisphere had a higher frequency of deficits in the verbal working memory task compared to older TIA patients. Additionally, the deficits in older stroke patients were mainly in retrieval time while the deficits in younger stroke patients were mainly in accuracy. These data suggest that bihemispheric activity is necessary for older adults to successfully perform a verbal working memory task. C1 [Meier, Timothy B.] Univ Wisconsin, Neurosci Training Program, Wisconsin Inst Med Res 1310D, Madison, WI 53705 USA. [Naing, Lin; Prabhakaran, Vivek] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Thomas, Lisa E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thomas, Lisa E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nair, Veena A.; Prabhakaran, Vivek] Univ Wisconsin, Dept Radiol, Madison, WI 53705 USA. [Hillis, Argye E.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MA USA. RP Meier, TB (reprint author), Univ Wisconsin, Neurosci Training Program, Wisconsin Inst Med Res 1310D, 1111 Highland Ave, Madison, WI 53705 USA. EM tbmeier@wisc.edu FU National Center for Research Resources (NCRR) [UL1RR025011]; NIMH ARRA [RC1MH090912]; National Institutes of Health (NIH) [T32-GM007507]; [RO1DC05375]; [NS047691] FX Supported by grants UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources (NCRR), RO1DC05375, NS047691; RC1MH090912 NIMH ARRA Challenge Grant, and T32-GM007507 training grant, National Institutes of Health (NIH). NR 57 TC 2 Z9 2 U1 2 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2011 VL 24 IS 3 BP 187 EP 199 DI 10.3233/BEN-2011-0331 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 834NC UT WOS:000295967200002 PM 21876259 ER PT J AU Mendez, MF Fras, IA Kremen, SA Tsai, PH AF Mendez, Mario F. Fras, Ivan Andrew Kremen, Sarah A. Tsai, Po-Heng TI False reports from patients with frontotemporal dementia: Delusions or confabulations? SO BEHAVIOURAL NEUROLOGY LA English DT Article ID SCHIZOPHRENIA-LIKE PSYCHOSIS; STRATEGIC RETRIEVAL; LOBAR DEGENERATION; DISEASE; DYSFUNCTION; MEMORY; RECOGNITION; PREVALENCE; MECHANISMS; SYMPTOMS AB Patients with behavioral variant frontotemporal dementia (bvFTD) can make false statements consistent with delusions or confabulations. It is unclear whether bvFTD is primarily associated with either delusions or with confabulations and whether they can be explained by the pathophysiology of this disease. In order to clarify this, we retrospectively surveyed the records of 48 patients with bvFTD for the presence of any false reports and identified four patients. Their false reports included continued interaction with a favorite but dead relation, fictitious marriages with movie stars, and two who claimed that their partner was having an affair. When confronted with the falsity of their statements, the patients conveyed a lack of certainty regarding their external or internal source but persisted in the constancy of their reports. On functional neuroimaging, the patients had predominant frontal involvement. This report found that patients with bvFTD can have both fantastic, wish fulfilling confabulations and typical content-specific delusions. We propose that both phenomena result from known disturbances of ventromedial prefrontal cortex in bvFTD, including deficits in source monitoring and in activating an automatic "doubt tag" for false reports. C1 [Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF,Dept Neurol & Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Biobehav Sci, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit 691 116AF,Dept Neurol & Psychiat, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu NR 59 TC 6 Z9 6 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 J9 BEHAV NEUROL JI Behav. Neurol. PY 2011 VL 24 IS 3 BP 237 EP 244 DI 10.3233/BEN-2011-0335 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 834NC UT WOS:000295967200006 PM 21876263 ER PT J AU Mulley, AG Wennberg, JE AF Mulley, Albert G., Jr. Wennberg, John E. BE Gigerenzer, G Gray, JAM TI Reducing Unwarranted Variation in Clinical Practice by Supporting Clinicians and Patients in Decision Making SO BETTER DOCTORS, BETTER PATIENTS, BETTER DECISIONS: ENVISIONING HEALTH CARE 2020 SE Strungmann Forum Reports LA English DT Proceedings Paper CT Ernst-Strungmann Forum on Better Doctors, Better Patients, Better Decisions - Envisioning Health Care 2020 CY OCT 25-30, 2009 CL Frankfurt, GERMANY AB Variation in clinical practice in seemingly similar populations of patients has been described for more than seventy years. International collaboration to increase understanding of the sources of practice variation and respond constructively have spawned efforts to expand and better manage professional knowledge, and to elicit and accommodate the personal knowledge of patients about what matters most to them when they face medical decisions under conditions of uncertainty. The approach, which has come to be known as shared decision making, can move us toward assurance that patients receive the care they need and no less and the care they want and no more. The use of decision aids to support shared decision making can effectively address the limitations in statistical thinking among clinicians as well as patients and thereby help establish informed patient choice as a standard of practice and improve the quality of medical decision making and the efficiency of health care. C1 [Mulley, Albert G., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 1 U2 4 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA BN 978-0-26229-985-5 J9 STRUNGMANN FORUM REP PY 2011 BP 45 EP 52 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA BYT82 UT WOS:000300216300004 ER PT S AU Chervitz, SA Deutsch, EW Field, D Parkinson, H Quackenbush, J Rocca-Serra, P Sansone, SA Stoeckert, CJ Taylor, CF Taylor, R Ball, CA AF Chervitz, Stephen A. Deutsch, Eric W. Field, Dawn Parkinson, Helen Quackenbush, John Rocca-Serra, Phillipe Sansone, Susanna-Assunta Stoeckert, Christian J., Jr. Taylor, Chris F. Taylor, Ronald Ball, Catherine A. BE Mayer, B TI Data Standards for Omics Data: The Basis of Data Sharing and Reuse SO BIOINFORMATICS FOR OMICS DATA: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Data sharing; Data exchange; Data standards; MGED; MIAME; Ontology; Data format; Microarray; Proteomics; Metabolomics ID STANFORD MICROARRAY DATABASE; GENE-EXPRESSION; FUNCTIONAL GENOMICS; MINIMUM INFORMATION; REPORTING STANDARDS; PLANT METABOLOMICS; MASS-SPECTROMETRY; SYSTEMS BIOLOGY; PUBLIC DATABASE; LIFE SCIENCES AB To facilitate sharing of lilies data, many groups of scientists have been working to establish the relevant data standards. The main components of data sharing standards arc experiment description standards, data exchange standards, terminology standards, and experiment execution standards. Here we provide a survey of existing and emerging standards that are intended to assist the tree and open exchange of large-format data. C1 [Chervitz, Stephen A.] Affymetrix Inc, Santa Clara, CA USA. [Ball, Catherine A.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. [Deutsch, Eric W.] Inst Syst Biol, Seattle, WA USA. [Field, Dawn] NERC Ctr Ecol & Hydrol, Oxford, England. [Parkinson, Helen; Rocca-Serra, Phillipe; Sansone, Susanna-Assunta; Taylor, Chris F.] EMBL EBI, Cambridge, England. [Quackenbush, John] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Stoeckert, Christian J., Jr.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Stoeckert, Christian J., Jr.] Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA. [Taylor, Ronald] Pacific NW Natl Lab, Computat Biol & Bioinformat Grp, Richland, WA 99352 USA. RP Chervitz, SA (reprint author), Affymetrix Inc, Santa Clara, CA USA. OI Taylor, Christopher/0000-0002-9666-798X; Parkinson, Helen/0000-0003-3035-4195; Sansone, Susanna-Assunta/0000-0001-5306-5690; Taylor, Ronald/0000-0001-9777-9767 FU Biotechnology and Biological Sciences Research Council [BB/E025080/1, BB/I000771/1]; NLM NIH HHS [R01 LM008795] NR 74 TC 16 Z9 16 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-026-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 719 BP 31 EP 69 DI 10.1007/978-1-61779-027-0_2 D2 10.1007/978-1-61779-027-0 PG 39 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA BUD45 UT WOS:000288923900002 PM 21370078 ER PT J AU Tregellas, JR Tanabe, J Rojas, DC Shatti, S Olincy, A Johnson, L Martin, LF Soti, F Kem, WR Leonard, S Freedman, R AF Tregellas, Jason R. Tanabe, Jody Rojas, Donald C. Shatti, Shireen Olincy, Ann Johnson, Lynn Martin, Laura F. Soti, Ferenc Kem, William R. Leonard, Sherry Freedman, Robert TI Effects of an Alpha 7-Nicotinic Agonist on Default Network Activity in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE CHRNA7; default network; functional magnetic resonance imaging; nicotinic receptors; schizophrenia ID TASK-INDUCED DEACTIVATION; RECEPTOR SUBUNIT GENE; NICOTINIC RECEPTORS; RESTING-STATE; GTS-21; FMRI; PHARMACOKINETICS; ASSOCIATION; SMOKING; HEALTHY AB Background: 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXB-A) is a partial agonist at alpha 7 nicotinic acetylcholine receptors that has been evaluated clinically for treatment of schizophrenia. This study examined the effects of DMXB-A on default network activity as a biomarker for drug effects on pathologic brain function associated with schizophrenia. Methods: Placebo and two doses of DMXB-A were administered in a random, double-blind crossover design during a Phase 2 study of DMXB-A. Functional magnetic resonance imaging was performed on 16 nonsmoking patients with schizophrenia while they performed a simple eye movement task. Independent component analysis was used to identify the default network component. Default network changes were evaluated in the context of a polymorphism in CHRNA7, the alpha 7-nicotinic acetylcholine receptor subunit gene, which was previously found to be associated with schizophrenia. Results: Compared with placebo, both 150 and 75 mg twice daily DMXB-A altered default network activity, including a reduction in posterior cingulate, inferior parietal cortex, and medial frontal gyrus activity and an increase in precuneus activity. The most robust difference, posterior cingulate activity reduction, was affected by CHRNA7 genotype. Conclusions: The observed DMXB-A-related changes are consistent with improved default network function in schizophrenia. Pharmacogenetic analysis indicates mediation of the effect through the alpha 7-nicotinic receptor. These results further implicate nicotinic cholinergic dysfunction in the disease and suggest that default network activity may be a useful indicator of biological effects of novel therapeutic agents. C1 [Tregellas, Jason R.; Tanabe, Jody; Rojas, Donald C.; Shatti, Shireen; Olincy, Ann; Johnson, Lynn; Martin, Laura F.; Leonard, Sherry; Freedman, Robert] Denver VA Med Ctr, Dept Psychiat, Aurora, CO USA. [Tregellas, Jason R.; Tanabe, Jody; Rojas, Donald C.; Shatti, Shireen; Olincy, Ann; Johnson, Lynn; Martin, Laura F.; Leonard, Sherry; Freedman, Robert] Univ Colorado Denver, Aurora, CO USA. [Tanabe, Jody] Univ Colorado Denver, Dept Radiol, Aurora, CO USA. [Soti, Ferenc; Kem, William R.] Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL USA. RP Tregellas, JR (reprint author), Univ Colorado, Sch Med, 13001 E 17th Pl,MS F546, Aurora, CO 80045 USA. EM Jason.tregellas@ucdenver.edu RI Rojas, Don/F-4296-2012; Tregellas, Jason/J-3637-2015; OI Rojas, Don/0000-0001-6560-9616 FU VA Biomedical Laboratory and Clinical Science Research and Development Service; Mental Illness Research, Education and Clinical Centers of Veterans Integrated Service Networks [19]; National Institute of Mental Health [MH-061412, MH-086383]; National Association for Research in Schizophrenia and Affective Disorders; Dana Foundation; National Institute on Drug Abuse [DA-024104, DA-027748]; Institute for Children's Mental Disorders; Lundbeck FX Supported by the VA Biomedical Laboratory and Clinical Science Research and Development Service; the Mental Illness Research, Education and Clinical Centers of Veterans Integrated Service Networks 5 and 19; National Institute of Mental Health Grant Nos. MH-061412 and MH-086383; the National Association for Research in Schizophrenia and Affective Disorders; the Dana Foundation and National Institute on Drug Abuse Grant Nos. DA-024104 and DA-027748; and the Institute for Children's Mental Disorders. We thank Dietmar Cordes, Ph.D., for critical comments during manuscript preparation.; Drs. Leonard and Freedman have patents through the Department of Veterans Affairs on the CHRNA7 gene sequence. Drs. Kem and Soti have patents through the University of Florida on the manufacture and use of DMXB-A. Drs. Olincy and Johnson receive research support from Lundbeck. All other authors report no biomedical financial interests or potential conflicts of interest. NR 26 TC 59 Z9 59 U1 2 U2 5 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 JAN 1 PY 2011 VL 69 IS 1 BP 7 EP 11 DI 10.1016/j.biopsych.2010.07.004 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 702RH UT WOS:000285911300003 PM 20728875 ER PT J AU Boo, M Ballen, K Maiers, M AF Boo, Michael Ballen, Karen Maiers, Martin TI Cord Blood Unit Access and Selection: 2010 and Beyond: Best Practices and Emerging Trends in Cord Blood Unit Selection SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Cord blood; Regulation; Matching algorithm ID ACUTE-LEUKEMIA; TRANSPLANTATION OUTCOMES; BONE-MARROW; GRAFT; ADULTS; INTENSITY; CHILDREN; ENGRAFTMENT; DISEASE; IMPACT AB One-fifth, more than 1000, of all transplants facilitated in 2010 by the National Marrow Donor Program (NMDP) have employed 1 or 2 umbilical cord blood units as the graft source. As the use of umbilical cord blood for unrelated allogeneic hematopoietic cell transplantation increases, several issues emerge that require additional attention and refinement. The U. S. Food and Drug Administration is now far along in its implementation of regulatory controls for umbilical cord blood. After October 20, 2011, every unrelated-donor cord blood unit transplanted in the United States must be either licensed or covered under an FDA-accepted IND. It is incumbent upon transplant physicians to review and understand the implications of the FDA's new regulations. In addition, as more transplant programs adopt umbilical cord blood for transplantation, it is important to stay current with the best practices surrounding identification and selection of the best available units. Cell dose, HLA matching, location of mismatched loci, and the role of noninherited maternal alleles are all important considerations for unit selection. This complexity in selection of appropriate units raises issues about the desired inventory of umbilical cord blood units. How many units are needed to meet the needs of all patients who might benefit from cord blood transplantation? Newly developed simulation models are being utilized by NMDP to answer this question. Biol Blood Marrow Transplant 17: S46-S51 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Boo, Michael; Maiers, Martin] Natl Marrow Donor Program, Minneapolis, MN 55447 USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Boo, M (reprint author), Natl Marrow Donor Program, 3001 Broadway St NE, Minneapolis, MN 55447 USA. EM mboo@nmdp.org OI Maiers, Martin/0000-0002-0198-2064 NR 40 TC 8 Z9 8 U1 0 U2 1 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 JAN PY 2011 VL 17 IS 1 SU 1 BP S46 EP S51 DI 10.1016/j.bbmt.2010.11.010 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 794DZ UT WOS:000292877000011 PM 21195309 ER PT J AU MacMillan, ML Hughes, MR Agarwal, S Daley, GQ AF MacMillan, Margaret L. Hughes, Mark R. Agarwal, Suneet Daley, George Q. TI Cellular Therapy for Fanconi Anemia: The Past, Present, and Future SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; HUMAN FIBROBLASTS; APLASTIC-ANEMIA; DEFINED FACTORS; CYCLOPHOSPHAMIDE; DONORS; IRRADIATION; DISEASE AB Allogeneic hematopoietic cell transplantation (HCT) remains the only proven curative therapy for the hematologic manifestation of Fanconi anemia (FA). Over the past 2 decades, major advances have been made such that transplant outcomes have markedly improved. With the development of in vitro fertilization and preimplantation genetic diagnosis, HLA-matched sibling donor umbilical blood transplantation may be an option for more patients with FA. Recently, the use of pluripotent stem cells has been explored as a novel approach to model the hematopoietic developmental defects in FA, and to provide a potential source of autologous stem cells that can be genetically manipulated and used to generate corrected hematopoietic progenitors. Biol Blood Marrow Transplant 17: S109-S114 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [MacMillan, Margaret L.] Univ Minnesota, Dept Pediat, Div Pediat Hematol Oncol & Blood & Marrow Transpl, Blood & Marrow Transplant Program, Minneapolis, MN 55455 USA. [Hughes, Mark R.] Appl Genom Technol Ctr Michigan, Genesis Genet Inst, Detroit, MI USA. [Agarwal, Suneet; Daley, George Q.] Childrens Hosp Boston, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Stem Cell Transplantat Program,Div Pediat Hematol, Boston, MA USA. [Agarwal, Suneet; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Agarwal, Suneet; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA USA. RP MacMillan, ML (reprint author), Univ Minnesota, Dept Pediat, Div Pediat Hematol Oncol & Blood & Marrow Transpl, Blood & Marrow Transplant Program, MMC 484,420 Delaware St SE, Minneapolis, MN 55455 USA. EM macmi002@umn.edu FU Epizyme; iPierian; Solasia KK; MPM Capital, LLP FX Dr. Daley is a member of the scientific advisory boards and holds stock in or receives consulting fees from the following companies: Epizyme, iPierian, Solasia KK, and MPM Capital, LLP. The remaining authors have nothing to disclose. NR 46 TC 8 Z9 9 U1 0 U2 4 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 JAN PY 2011 VL 17 IS 1 SU 1 BP S109 EP S114 DI 10.1016/j.bbmt.2010.11.027 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 794DZ UT WOS:000292877000021 PM 21195298 ER PT J AU Jani, A AF Jani, Alkesh BE Edelstein, CL TI Biomarkers in Kidney Transplantation SO BIOMARKERS OF KIDNEY DISEASE LA English DT Article; Book Chapter ID RENAL-ALLOGRAFT REJECTION; POLYOMAVIRUS-ASSOCIATED NEPHROPATHY; PRETRANSPLANT SOLUBLE CD30; MOLECULE GENE-EXPRESSION; ACUTE CELLULAR REJECTION; DELAYED GRAFT FUNCTION; ACUTE TUBULAR-NECROSIS; GROWTH-FACTOR BETA(1); URINE FLOW-CYTOMETRY; MESSENGER-RNA C1 Denver Vet Affairs Med Ctr, Renal Sect, Denver, CO 80220 USA. RP Jani, A (reprint author), Denver Vet Affairs Med Ctr, Renal Sect, Denver, CO 80220 USA. NR 117 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-375673-2 PY 2011 BP 233 EP 290 DI 10.1016/B978-0-12-375672-5.10006-4 PG 58 WC Pharmacology & Pharmacy; Urology & Nephrology SC Pharmacology & Pharmacy; Urology & Nephrology GA BEU29 UT WOS:000318163200008 ER PT J AU Arthur, JM Budisavljevic, MN Janech, MG AF Arthur, John M. Budisavljevic, Milos N. Janech, Michael G. BE Edelstein, CL TI Biomarkers in Glomerular Disease SO BIOMARKERS OF KIDNEY DISEASE LA English DT Article; Book Chapter ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GELATINASE-ASSOCIATED LIPOCALIN; IDIOPATHIC MEMBRANOUS NEPHROPATHY; FIBROBLAST-SPECIFIC PROTEIN-1; ACETYL-BETA-GLUCOSAMINIDASE; SERUM IGA/C3 RATIO; NEPHROTIC SYNDROME; URINARY INTERLEUKIN-6; PROGNOSTIC MARKER; GROWTH-FACTOR C1 [Arthur, John M.; Budisavljevic, Milos N.; Janech, Michael G.] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Arthur, John M.; Budisavljevic, Milos N.; Janech, Michael G.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Arthur, JM (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. OI Janech, Michael/0000-0002-3202-4811 NR 53 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-375673-2 PY 2011 BP 367 EP 383 DI 10.1016/B978-0-12-375672-5.10010-6 PG 17 WC Pharmacology & Pharmacy; Urology & Nephrology SC Pharmacology & Pharmacy; Urology & Nephrology GA BEU29 UT WOS:000318163200012 ER PT S AU Hargreaves, R Becerra, L Borsook, D AF Hargreaves, Richard Becerra, Lino Borsook, David BE Braddock, M TI Imaging as a CNS Biomarker SO BIOMEDICAL IMAGING: THE CHEMISTRY OF LABELS, PROBES AND CONTRAST AGENTS SE RSC Drug Discovery Series LA English DT Article; Book Chapter ID MAGNETIC-RESONANCE-SPECTROSCOPY; MAJOR DEPRESSIVE DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; POSITRON-EMISSION-TOMOGRAPHY; DEFICIT-HYPERACTIVITY-DISORDER; INDEPENDENT COMPONENT ANALYSIS; TRIGEMINAL NEUROPATHIC PAIN; MULTIPLE SYSTEM ATROPHY; VOXEL-BASED MORPHOMETRY; RESTING-STATE NETWORKS C1 [Hargreaves, Richard] Merck & Co Inc, Discovery Neurosci Res, West Point, PA 19486 USA. [Becerra, Lino; Borsook, David] McLean Hosp, PAIN Grp, Massachusetts Gen Hosp, Belmont, MA 02478 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Childrens Hosp, Belmont, MA 02478 USA. RP Hargreaves, R (reprint author), Merck & Co Inc, Discovery Neurosci Res, West Point, PA 19486 USA. NR 189 TC 2 Z9 2 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2041-3203 BN 978-1-84973-014-3; 978-1-84973-291-8 J9 RSC DRUG DISCOV JI RSC Drug Discov. PY 2011 IS 15 BP 411 EP 440 D2 10.1039/9781849732918 PG 30 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BIE26 UT WOS:000327851900014 ER PT S AU Haun, JB Yoon, TJ Lee, H Weissleder, R AF Haun, Jered B. Yoon, Tae-Jong Lee, Hakho Weissleder, Ralph BE Hurst, SJ TI Molecular Detection of Biomarkers and Cells Using Magnetic Nanoparticles and Diagnostic Magnetic Resonance SO BIOMEDICAL NANOETECHNOLOGY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Magnetic nanoparticles; Molecular biosensing; Diagnostic magnetic resonance; Magnetic relaxation switches ID TERMINAL ALKYNES; CLICK CHEMISTRY; CANCER-CELLS; RELAXATION; NANOSENSORS; CYCLOADDITION; TELOMERASE; CALCIUM; SENSORS; SYSTEM AB The rapid and sensitive detection of molecular targets such as proteins, cells, and pathogens in biological specimens is a major focus of ongoing medical research, as it could promote early disease diagnoses and the development of tailored therapeutic strategies. Magnetic nanoparticles (MNP) are attractive candidates for molecular biosensing applications because most biological samples exhibit negligible magnetic susceptibility, and thus the background against which measurements are made is extremely low. Numerous magnetic detection methods exist, but sensing based on magnetic resonance effects has successfully been developed into a general detection platform termed diagnostic magnetic resonance (DMR). DMR technology encompasses numerous assay configurations and sensing principles, and to date magnetic nanoparticle biosensors have been designed to detect a wide range of targets including DNA/mRNA, proteins, enzymes, drugs, pathogens, and tumor cells with exquisite sensitivity. The core principle behind DMR is the use of MNP as proximity sensors that modulate the transverse relaxation time of neighboring water molecules. This signal can be quantified using MR imagers or NMR relaxometers, including miniaturized NMR detector chips that are capable of performing highly sensitive measurements on microliter sample volumes and in a multiplexed format. The speed, sensitivity, and simplicity of the DMR principle, coupled with further advances in NMR biosensor technology should provide a high-throughput, low-cost, and portable platform for large-scale parallel sensing in clinical and point-of-care settings. C1 [Haun, Jered B.; Yoon, Tae-Jong; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Dept Syst Biol, Ctr Syst Biol,Sch Med, Boston, MA USA. RP Haun, JB (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RI Petrosko, Sarah/A-3606-2013 NR 35 TC 11 Z9 11 U1 3 U2 15 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-051-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 726 BP 33 EP 49 DI 10.1007/978-1-61779-052-2_3 D2 10.1007/978-1-61779-052-2 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Engineering, Biomedical; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Engineering; Science & Technology - Other Topics GA BUL40 UT WOS:000289741000003 PM 21424441 ER PT J AU Haase, A Rigosi, E Trona, F Anfora, G Vallortigara, G Antolini, R Vinegoni, C AF Haase, Albrecht Rigosi, Elisa Trona, Federica Anfora, Gianfranco Vallortigara, Giorgio Antolini, Renzo Vinegoni, Claudio TI In-vivo two-photon imaging of the honey bee antennal lobe SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID APIS-MELLIFERA; ODOR REPRESENTATION; NEURONS; BRAIN; ATLAS; MICROSCOPY AB Due to the honey bee's importance as a simple neural model, there is a great need for new functional imaging modalities. Herein we report on the development and new finding of a combined two-photon microscope with a synchronized odor stimulus platform for in-vivo functional and morphological imaging of the honey bee's olfactory system focusing on its primary centers, the antennal lobes (ALs). Our imaging platform allows for simultaneously obtaining both morphological measurements of the AL's functional units, the glomeruli, and in-vivo calcium recording of their neural activities. By applying external odor stimuli to the bee's antennae, we were able to record the characteristic glomerular odor response maps. Compared to previous works where conventional fluorescenc microscopy was used, our approach has been demonstrated to offer all the advantages of multi-photon imaging, providing substantial enhancement in both spatial and temporal resolutions while minimizing photo-damages. In addition, compared to previous full-fiel microscopy calcium recordings, a four-fold improvement in the functional signal has been achieved. Finally, the multi-photon associated extended penetration depth allows for functional imaging of profound glomeruli. (C) 2010 Optical Society of America C1 [Haase, Albrecht; Antolini, Renzo; Vinegoni, Claudio] Univ Trent, Dept Phys, I-38050 Povo, TN, Italy. [Rigosi, Elisa; Trona, Federica; Anfora, Gianfranco] Fdn E Mach, IASMA Res & Innovat Ctr, I-38010 San Michele All Adige, Italy. [Rigosi, Elisa; Vallortigara, Giorgio] Univ Trent, Ctr Mind Brain Sci, I-38068 Rovereto, Italy. [Vinegoni, Claudio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Haase, A (reprint author), Univ Trent, Dept Phys, Via Sommar 14, I-38050 Povo, TN, Italy. EM albrecht.haase@unitn.it RI Haase, Albrecht/H-4248-2012; OI Haase, Albrecht/0000-0002-8324-0047; ANFORA, Gianfranco/0000-0003-2545-1409 FU Provincia Autonoma di Trento FX We wish to thank T. Franke, J. Rybak, and R. Menzel for helpful discussions. C.V. acknowledges funding from the Provincia Autonoma di Trento (project COMNFI). NR 24 TC 3 Z9 3 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD JAN 1 PY 2011 VL 2 IS 1 BP 131 EP 138 DI 10.1364/BOE.2.000131 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 886RT UT WOS:000299872300013 ER PT J AU LaLonde, JM Elban, MA Courter, JR Sugawara, A Soeta, T Madani, N Princiotto, AM Do Kwon, Y Kwong, PD Schon, A Freire, E Sodroski, J Smith, AB AF LaLonde, Judith M. Elban, Mark A. Courter, Joel R. Sugawara, Akihiro Soeta, Takahiro Madani, Navid Princiotto, Amy M. Do Kwon, Young Kwong, Peter D. Schoen, Arne Freire, Ernesto Sodroski, Joseph Smith, Amos B., III TI Design, synthesis and biological evaluation of small molecule inhibitors of CD4-gp120 binding based on virtual screening SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE HIV; gp120; CD4; Entry inhibitor; Virtual screening; Docking; Shape-based similarity ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; HIV-1 ENTRY; ACCURATE DOCKING; CD4; GP120; RECEPTOR; RETROVIRUS; VALIDATION; CORECEPTOR AB The low-molecular-weight compound JRC-II-191 inhibits infection of HIV-1 by blocking the binding of the HIV-1 envelope glycoprotein gp120 to the CD4 receptor and is therefore an important lead in the development of a potent viral entry inhibitor. Reported here is the use of two orthogonal screening methods, GOLD docking and ROCS shape-based similarity searching, to identify amine-building blocks that, when conjugated to the core scaffold, yield novel analogs that maintain similar affinity for gp120. Use of this computational approach to expand SAR produced analogs of equal inhibitory activity but with diverse capacity to enhance viral infection. The novel analogs provide additional lead scaffolds for the development of HIV-1 entry inhibitors that employ protein-ligand interactions in the vestibule of gp120 Phe 43 cavity. (C) 2010 Elsevier Ltd. All rights reserved. C1 [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Elban, Mark A.; Courter, Joel R.; Sugawara, Akihiro; Soeta, Takahiro; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Madani, Navid; Princiotto, Amy M.; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Do Kwon, Young; Kwong, Peter D.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP LaLonde, JM (reprint author), Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. EM jlalonde@brynmawr.edu RI Kwon, Young Do/A-6957-2010; SOETA, Takahiro/E-7060-2015; OI SOETA, Takahiro/0000-0001-9883-4772; Sugawara, Akihiro/0000-0003-1266-7497 FU NIH [GM 56550]; Japan Society for the Promotion of Science FX We thank Irwin Chaiken and Wayne Hendrickson and all the members of the PO1 Consortium Structure-Based Antagonism of HIV-1 Envelope Function in Cell Entry. Funding was provided by NIH GM 56550 to JL, EF, ABS, and JS. A. Sugawara thanks the Japan Society for the Promotion of Science for research fellowship support. JL thanks the Pittsburgh Supercomputing Center for an allocation for computing resources #MCB090108. NR 44 TC 38 Z9 40 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2011 VL 19 IS 1 BP 91 EP 101 DI 10.1016/j.bmc.2010.11.049 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 700GA UT WOS:000285724800009 PM 21169023 ER PT S AU Zhou, GL Xin, L Liu, DP AF Zhou, Guo Ling Xin, Li Liu, De Pei BE Williams, MC Maher, LJ TI Long-Range Chromatin Interactions in Cells SO BIOPHYSICS OF DNA- PROTEIN INTERACTIONS: FROM SINGLE MOLECULES TO BIOLOGICAL SYSTEMS SE Biological and Medical Physics Biomedical Engineering LA English DT Article; Book Chapter ID DOMAIN-MEDIATED DIMERIZATION; LOCUS-CONTROL REGION; TH2 CYTOKINE LOCUS; BETA-GLOBIN LOCUS; CHROMOSOME CONFORMATION; GENE-EXPRESSION; ACTIVE CHROMATIN; X-INACTIVATION; ERYTHROID-DIFFERENTIATION; REGULATORY ELEMENTS C1 [Zhou, Guo Ling] Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Massachusetts Gen Hosp,Dept Genet, Boston, MA 02114 USA. [Liu, De Pei] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China. [Liu, De Pei] Peking Union Med Coll, Beijing 100005, Peoples R China. RP Zhou, GL (reprint author), Harvard Univ, Sch Med, Ctr Computat & Integrat Biol, Massachusetts Gen Hosp,Dept Genet, 185 Cambridge St, Boston, MA 02114 USA. EM gzhou@ccib.mgh.harvard.edu NR 72 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1618-7210 BN 978-0-387-92807-4 J9 BIOL MED PHYS BIOMED JI Biol. Med. Phys. Biomed. Eng. PY 2011 BP 325 EP 339 DI 10.1007/978-0-387-92808-1_14 D2 10.1007/978-0-387-92808-1 PG 15 WC Biology; Biophysics; Engineering, Biomedical SC Life Sciences & Biomedicine - Other Topics; Biophysics; Engineering GA BRS06 UT WOS:000283519500014 ER PT J AU Abe, M Xie, WL Regan, MM King, IB Stampfer, MJ Kantoff, PW Oh, WK Chan, JM AF Abe, Miyako Xie, Wanling Regan, Meredith M. King, Irena B. Stampfer, Meir J. Kantoff, Philip W. Oh, William K. Chan, June M. TI Single-nucleotide polymorphisms within the antioxidant defence system and associations with aggressive prostate cancer SO BJU INTERNATIONAL LA English DT Article DE single nucleotide polymorphisms; superoxide dismutase; glutathione peroxidase; aggressive prostate cancer; plasma selenium ID MANGANESE SUPEROXIDE-DISMUTASE; MITOCHONDRIAL TARGETING SEQUENCE; BEAM RADIATION-THERAPY; STRESS-RELATED GENES; OXIDATIVE STRESS; SERUM SELENIUM; PLASMA SELENIUM; BREAST-CANCER; RADICAL PROSTATECTOMY; ALPHA-TOCOPHEROL AB Prior studies have identified potential interaction effects between antioxidant nutrients and germline gene variants with regards to prostate cancer risk. In particular, the rs4880 gene variant in SOD2 (or MnSOD) has been linked to several cancers, including prostate, and appears to interact with antioxidant status and cancer risk. We identified additional variants in SOD2 and SOD1 that may affect risk of prostate cancer, or interact with selenium status to affect prostate cancer risk. OBJECTIVE To study the effects of oxidative stress on prostate cancer development as the exact biological mechanisms behind the relationship remain uncertain. We previously reported a statistically significant interaction between circulating selenium levels, variants in the superoxide dismutase 2 gene (SOD2; rs4880), and risk of developing prostate cancer and presenting with aggressive prostate cancer. PATIENTS AND METHODS We genotyped men with localized/regional prostate cancer for 26 loci across eight genes that are central to cellular antioxidant defence: glutathione peroxidase (GPX1, GPX4), peroxisome proliferator-activated receptor gamma coactivator (PPARGC1A, PPARGC1B), SOD1, SOD2, and SOD3, and 'X-ray repair complementing defective repair in Chinese hamster cell 1' (XRCC1). Among 489 men, we examined the relationships between genotypes, circulating selenium levels, and risk of presenting with aggressive prostate cancer at diagnosis, as defined by stage, grade and prostate-specific antigen (PSA) level (213 aggressive cases). RESULTS Two variants in SOD2 were significantly associated with the risk of aggressive prostate cancer (rs17884057, odds ratio 0.83, 95% confidence interval 0.70-0.99; and rs4816407, 1.27, 1.02-1.57); men with A alleles at rs2842958 in SOD2 had lower plasma selenium levels (median 116 vs 121.8 mu g/L, P = 0.03); and the association between plasma selenium levels and risk of aggressive prostate cancer was modified by SOD1 (rs10432782) and SOD2 (rs2758330). CONCLUSION While this study was cross-sectional and these associations might be due to chance, further research is warranted on the potential important role of antioxidant defence in prostate cancer. C1 [Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA. [Chan, June M.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94158 USA. [Abe, Miyako; Kantoff, Philip W.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Xie, Wanling; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Regan, Meredith M.; Stampfer, Meir J.; Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA USA. [King, Irena B.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Stampfer, Meir J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Oh, William K.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. RP Chan, JM (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, MC 3110,Helen Diller Family Canc Res Bldg,1450 3r, San Francisco, CA 94158 USA. EM june.chan@ucsf.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU National Cancer Institute/National Institutes of Health [R01 CA106947]; National Institutes of Health/National Cancer Institute [2 P50 CA090381-06]; University of California San Francisco [2 P50 CA089520-06]; American Association for Cancer Research; California Department of Public Health Early Career Development Award; Prostate Cancer Foundation; Arthur and Linda Gelb Center FX National Cancer Institute/National Institutes of Health (R01 CA106947); Prostate Cancer Specialized Programs of Research Excellence (SPORE) grant from National Institutes of Health/National Cancer Institute to Dana-Farber Harvard Cancer Center (2 P50 CA090381-06) and University of California San Francisco (2 P50 CA089520-06); American Association for Cancer Research and the California Department of Public Health Early Career Development Award; Prostate Cancer Foundation; and The Arthur and Linda Gelb Center. These funding agencies provided financial support for this work but were not directly involved in the design of the study, collection of data, analysis, interpretation, decisions regarding publication, or writing of the manuscript. NR 56 TC 24 Z9 25 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 2011 VL 107 IS 1 BP 126 EP 134 DI 10.1111/j.1464-410X.2010.09344.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 696CB UT WOS:000285418400017 PM 20477822 ER PT J AU Buracchio, TJ Mattek, NC Dodge, HH Hayes, TL Pavel, M Howieson, DB Kaye, JA AF Buracchio, Teresa J. Mattek, Nora C. Dodge, Hiroko H. Hayes, Tamara L. Pavel, Misha Howieson, Diane B. Kaye, Jeffrey A. TI Executive function predicts risk of falls in older adults without balance impairment SO BMC GERIATRICS LA English DT Article AB Background: Executive dysfunction has previously been found to be a risk factor for falls. The aim of this study is to investigate the association between executive dysfunction and risk of falling and to determine if this association is independent of balance. Methods: Participants were 188 community-dwelling individuals aged 65 and older. All participants underwent baseline and annual evaluations with review of health history, standardized neurologic examination, neuropsychological testing, and qualitative and quantitative assessment of motor function. Falls were recorded prospectively using weekly online health forms. Results: During 13 months of follow-up, there were 65 of 188 participants (34.6%) who reported at least one fall. Univariate analysis showed that fallers were more likely to have lower baseline scores in executive function than non-fallers (p = 0.03). Among participants without balance impairment we found that higher executive function z-scores were associated with lower fall counts (p = 0.03) after adjustment for age, sex, health status and prior history of falls using negative binomial regression models. This relationship was not present among participants with poor balance. Conclusions: Lower scores on executive function tests are a risk factor for falls in participants with minimal balance impairment. However, this effect is attenuated in individuals with poor balance where physical or more direct motor systems factors may play a greater role in fall risk. C1 [Buracchio, Teresa J.; Mattek, Nora C.; Dodge, Hiroko H.; Howieson, Diane B.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Buracchio, Teresa J.; Kaye, Jeffrey A.] Portland VA Med Ctr, Neurol Serv, Portland, OR 97239 USA. [Mattek, Nora C.; Dodge, Hiroko H.; Hayes, Tamara L.; Pavel, Misha; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97239 USA. [Hayes, Tamara L.; Pavel, Misha] Oregon Hlth & Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA. RP Buracchio, TJ (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,CR 131, Portland, OR 97239 USA. EM buracchi@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU National Institutes of Health [P30AG024978, R01AG024059, P30 AG008017, K01 AG23014]; Intel Corporation FX The authors thank the research volunteers for their invaluable donation to research, and the research staff of the Living Laboratory and ISAAC studies for their assistance. The study was funded by grants from the National Institutes of Health: P30AG024978, R01AG024059, P30 AG008017, K01 AG23014 and the Intel Corporation. NR 48 TC 17 Z9 17 U1 3 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2318 J9 BMC GERIATR JI BMC Geriatr. PY 2011 VL 11 AR 74 DI 10.1186/1471-2318-11-74 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA V29EM UT WOS:000208731700074 PM 22070602 ER PT J AU Hung, WW Ross, JS Boockvar, KS Siu, AL AF Hung, William W. Ross, Joseph S. Boockvar, Kenneth S. Siu, Albert L. TI Recent trends in chronic disease, impairment and disability among older adults in the United States SO BMC GERIATRICS LA English DT Article DE chronic disease; impairment; disability; prevalence trends AB Background: To examine concurrent prevalence trends of chronic disease, impairment and disability among older adults. Methods: We analyzed the 1998, 2004 and 2008 waves of the Health and Retirement Study, a nationally representative survey of older adults in the United States, and included 31,568 community dwelling adults aged 65 and over. Measurements include: prevalence of chronic diseases including hypertension, heart disease, stroke, diabetes, cancer, chronic lung disease and arthritis; prevalence of impairments, including impairments of cognition, vision, hearing, mobility, and urinary incontinence; prevalence of disability, including activities of daily living (ADLs) and instrumental activities of daily living (IADLs). Results: The proportion of older adults reporting no chronic disease decreased from 13.1% (95% Confidence Interval [CI], 12.4%-13.8%) in 1998 to 7.8% (95% CI, 7.2%-8.4%) in 2008, whereas the proportion reporting 1 or more chronic diseases increased from 86.9% (95% CI, 86.2%-89.6%) in 1998 to 92.2% (95% CI, 91.6%-92.8%) in 2008. In addition, the proportion reporting 4 or more diseases increased from 11.7% (95% CI, 11.0%-12.4%) in 1998 to 17.4% (95% CI, 16.6%-18.2%) in 2008. The proportion of older adults reporting no impairments was 47.3% (95% CI, 46.3%48.4%) in 1998 and 44.4% (95% CI, 43.3%-45.5%) in 2008, whereas the proportion of respondents reporting 3 or more was 7.2% (95% CI, 6.7%-7.7%) in 1998 and 7.3% (95% CI, 6.8%-7.9%) in 2008. The proportion of older adults reporting any ADL or IADL disability was 26.3% (95% CI, 25.4%-27.2%) in 1998 and 25.4% (95% CI, 24.5%-26.3%) in 2008. Conclusions: Multiple chronic disease is increasingly prevalent among older U.S. adults, whereas the prevalence of impairment and disability, while substantial, remain stable. C1 [Hung, William W.; Boockvar, Kenneth S.; Siu, Albert L.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hung, William W.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, Bronx, NY USA. [Hung, William W.; Boockvar, Kenneth S.; Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Ross, Joseph S.] Yale Univ, Sch Med, Div Gen Internal Med, New Haven, CT USA. [Ross, Joseph S.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Hung, WW (reprint author), Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. EM william.hung@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU National Institute on Aging [K08 AG032886, U01AG009740]; American Federation of Aging Research through the Paul B. Beeson Career Development Award Program FX WH is a John A Hartford Foundation Center of Excellence Scholar and a New York Academy of Medicine Hoar Fellow. JR is currently supported by the National Institute on Aging (K08 AG032886) and by the American Federation of Aging Research through the Paul B. Beeson Career Development Award Program. The Health and Retirement Study is sponsored by the National Institute on Aging (grant number U01AG009740) and conducted by the Institute for Social Research at the University of Michigan. NR 45 TC 72 Z9 77 U1 1 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2318 J9 BMC GERIATR JI BMC Geriatr. PY 2011 VL 11 AR 47 DI 10.1186/1471-2318-11-47 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA V29EM UT WOS:000208731700047 PM 21851629 ER PT J AU Olson, JC Cuff, CF Lukomski, S Lukomska, E Canizales, Y Wu, B Crout, RJ Thomas, JG McNeil, DW Weyant, RJ Marazita, ML Paster, BJ Elliott, T AF Olson, Joan C. Cuff, Christopher F. Lukomski, Slawomir Lukomska, Ewa Canizales, Yeremi Wu, Bei Crout, Richard J. Thomas, John G. McNeil, Daniel W. Weyant, Robert J. Marazita, Mary L. Paster, Bruce J. Elliott, Thomas TI Use of 16S ribosomal RNA gene analyses to characterize the bacterial signature associated with poor oral health in West Virginia SO BMC ORAL HEALTH LA English DT Article AB Background: West Virginia has the worst oral health in the United States, but the reasons for this are unclear. This pilot study explored the etiology of this disparity using culture-independent analyses to identify bacterial species associated with oral disease. Methods: Bacteria in subgingival plaque samples from twelve participants in two independent West Virginia dental-related studies were characterized using 16S rRNA gene sequencing and Human Oral Microbe Identification Microarray (HOMIM) analysis. Unifrac analysis was used to characterize phylogenetic differences between bacterial communities obtained from plaque of participants with low or high oral disease, which was further evaluated using clustering and Principal Coordinate Analysis. Results: Statistically different bacterial signatures (P < 0.001) were identified in subgingival plaque of individuals with low or high oral disease in West Virginia based on 16S rRNA gene sequencing. Low disease contained a high frequency of Veillonella and Streptococcus, with a moderate number of Capnocytophaga. High disease exhibited substantially increased bacterial diversity and included a large proportion of Clostridiales cluster bacteria (Selenomonas, Eubacterium, Dialister). Phylogenetic trees constructed using 16S rRNA gene sequencing revealed that Clostridiales were repeated colonizers in plaque associated with high oral disease, providing evidence that the oral environment is somehow influencing the bacterial signature linked to disease. Conclusions: Culture-independent analyses identified an atypical bacterial signature associated with high oral disease in West Virginians and provided evidence that the oral environment influenced this signature. Both findings provide insight into the etiology of the oral disparity in West Virginia. C1 [Olson, Joan C.; Cuff, Christopher F.; Lukomski, Slawomir; Lukomska, Ewa; Elliott, Thomas] W Virginia Univ, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. [Lukomska, Ewa] NIOSH, Hlth Effects Lab Div, CDC, Morgantown, WV USA. [Canizales, Yeremi] W Virginia Univ, Sch Dent, Morgantown, WV 26506 USA. [Wu, Bei] Duke Univ, Med Ctr, Sch Nursing, Durham, NC USA. [Crout, Richard J.] W Virginia Univ, Sch Dent, Dept Periodontol, Morgantown, WV 26506 USA. [Thomas, John G.] W Virginia Univ, Dept Pathol, Morgantown, WV 26506 USA. [McNeil, Daniel W.] W Virginia Univ, Dept Clin Psychol, Morgantown, WV 26506 USA. [Weyant, Robert J.] Univ Pittsburgh, Sch Dent Med, Dept Dent Publ Hlth & Informat Management, Pittsburgh, PA USA. [Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. [Marazita, Mary L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Paster, Bruce J.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Olson, JC (reprint author), W Virginia Univ, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26506 USA. EM jolson@hsc.wvu.edu FU NIH [5P20RR016477]; West Virginia University Health Sciences Center; West Virginia University School of Dentistry; National Institute of Dental and Craniofacial Research (NIDCR) [R01-DE014899]; NIDCR [R21-DE016970] FX We thank Sara Owen, a WVU summer INBRE student, who helped with 16S rRNA gene analyses. Her efforts were supported by NIH grant 5P20RR016477 to the West Virginia IDeA Network for Biomedical Research Excellence. 16S rRNA gene analysis performed in this study was funded by the West Virginia University Health Sciences Center Internal Grants funding program, and the West Virginia University School of Dentistry. The COHRA study was supported by a grant from the National Institute of Dental and Craniofacial Research (NIDCR) (R01-DE014899; MLM, RJC, DWM, RJW). The Cognitive study was supported by a grant from the NIDCR (R21-DE016970; BW, RJC). NR 17 TC 16 Z9 18 U1 0 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6831 J9 BMC ORAL HEALTH JI BMC Oral Health PY 2011 VL 11 AR 7 DI 10.1186/1472-6831-11-7 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA V27EP UT WOS:000208596800007 PM 21362199 ER PT J AU Saito, AM Landrum, MB Neville, BA Ayanian, JZ Earle, CC AF Saito, Akiko M. Landrum, Mary Beth Neville, Bridget A. Ayanian, John Z. Earle, Craig C. TI The effect on survival of continuing chemotherapy to near death SO BMC PALLIATIVE CARE LA English DT Article AB Background: Overuse of anti-cancer therapy is an important quality-of-care issue. An aggressive approach to treatment can have negative effects on quality of life and cost, but its effect on survival is not well-defined. Methods: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 7,879 Medicare-enrolled patients aged 65 or older who died after having survived at least 3 months after diagnosis of advanced non-small cell lung cancer (NSCLC) between 1991 and 1999. We used Cox proportional hazards regression analysis, propensity scores, and instrumental variable analysis (IVA) to compare survival among patients who never received chemotherapy (n = 4,345), those who received standard chemotherapy but not within two weeks prior to death (n = 3,235), and those who were still receiving chemotherapy within 14 days of death (n = 299). Geographic variation in the application of chemotherapy was used as the instrument for IVA. Results: Receipt of chemotherapy was associated with a 2-month improvement in overall survival. However, based on three different statistical approaches, no additional survival benefit was evident from continuing chemotherapy within 14 days of death. Moreover, patients receiving chemotherapy near the end of life were much less likely to enter hospice (81% versus 51% with no chemotherapy and 52% with standard chemotherapy, P < 0.001), or were more likely to be admitted within only 3 days of death. Conclusions: Continuing chemotherapy for advanced NSCLC until very near death is associated with a decreased likelihood of receiving hospice care but not prolonged survival. Oncologists should strive to discontinue chemotherapy as death approaches and encourage patients to enroll in hospice for better end-of-life palliative care. C1 [Saito, Akiko M.] Nagoya Med Ctr, Clin Res Ctr, Lab Clin Epidemiol & Hlth Serv Res, Nagoya, Aichi, Japan. [Landrum, Mary Beth; Ayanian, John Z.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Neville, Bridget A.] Dana Farber Canc Inst, Div Populat Sci, Dept Med Oncol, Boston, MA 02115 USA. [Ayanian, John Z.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Earle, Craig C.] Canc Care Ontario, Hlth Serv Res Program, Toronto, ON, Canada. [Earle, Craig C.] Ontario Inst Canc Res, Toronto, ON, Canada. RP Earle, CC (reprint author), Canc Care Ontario, Hlth Serv Res Program, Toronto, ON, Canada. EM craig.earle@ices.on.ca FU National Cancer Institute [CA 91753-02] FX This research was supported by a grant CA 91753-02 from the National Cancer Institute. The sponsor had no direct influence on the design of the study, analysis of the data, and interpretation of the results, the decision to submit the manuscript for publication, and the writing of the manuscript. NR 45 TC 31 Z9 31 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-684X J9 BMC PALLIAT CARE JI BMC Palliat. Care PY 2011 VL 10 AR 14 DI 10.1186/1472-684X-10-14 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA V27NG UT WOS:000208619300014 PM 21936940 ER PT J AU Maru, DSR Schwarz, R Schwarz, D Andrews, J Panizales, MT Karelas, G Brady, JS Rogers, S AF Maru, Duncan Smith-Rohrberg Schwarz, Ryan Schwarz, Dan Andrews, Jason Panizales, Maria Theresa Karelas, Gregory Brady, Jesse Stark Rogers, Selwyn TI Implementing surgical services in a rural, resource-limited setting: a study protocol SO BMJ OPEN LA English DT Article AB Introduction: There are well-established protocols and procedures for the majority of common surgical diseases, yet surgical services remain largely inaccessible for much of the world's rural poor. Data on the process and outcome of surgical care expansion, however, are very limited, and the roll-out process of rural surgical implementation in particular has never been studied. Here, we propose the first implementation research study to assess the surgical scale-up process in the rural district of Achham, Nepal. Methods and analysis: Based primarily on the protocols of the WHO's Integrated Management for Emergency and Essential Surgical Care (IMEESC), this study's threefold implementation strategy will include: (1) the core IMEESC surgical care program, (2) community-based follow-up via health workers, and (3) hospital-based quality improvement programs. The implementation program will employ additional emergency and surgical care protocols developed collaboratively by physicians, nurses and the authors. This strategy will be referred to as IMEESC-Plus. This study will employ both qualitative and quantitative research methodologies to collect clinical data and information on the reception and utilisation of services. The first 18 months of the implementation process will be studied and divided into an initial phase (first 6 months) and a consolidation phase (subsequent 12 months). Discussion: This study aims to describe the logistics of the implementation process of IMEESC-Plus, and assess the quality of the resulting IMEESC-Plus services during the course of the implementation process. Using data generated from this study, larger, multi-site implementation studies can be planned that assess the scale-up of surgical services worldwide in resource-limited areas. C1 [Maru, Duncan Smith-Rohrberg; Schwarz, Ryan; Schwarz, Dan; Andrews, Jason; Karelas, Gregory; Brady, Jesse Stark] Nyaya Hlth, Bayalpata Hosp, Ridikot Vdc, Achham, Nepal. [Maru, Duncan Smith-Rohrberg] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Schwarz, Ryan] Yale Univ, Sch Med, New Haven, CT USA. [Schwarz, Dan] Brown Univ, Sch Med, Providence, RI 02912 USA. [Andrews, Jason] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Panizales, Maria Theresa; Rogers, Selwyn] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Panizales, Maria Theresa; Rogers, Selwyn] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Brady, Jesse Stark] Montana State Univ, Div Hlth Sci, Bozeman, MT 59717 USA. RP Brady, JS (reprint author), Nyaya Hlth, Bayalpata Hosp, Ridikot Vdc, Achham, Nepal. EM jesse@nyayahealth.org FU Global Health Equity fellowship program within the Department of Medicine at Brigham and Women's Hospital FX Duncan Maru is supported by the Global Health Equity fellowship program within the Department of Medicine at Brigham and Women's Hospital. NR 33 TC 2 Z9 2 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2011 VL 1 IS 1 AR e000166 DI 10.1136/bmjopen-2011-000166 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA V27UL UT WOS:000208638000063 PM 22021781 ER PT J AU Blashill, AJ AF Blashill, Aaron J. TI Gender roles, eating pathology, and body dissatisfaction in men: A meta-analysis SO BODY IMAGE LA English DT Review DE Body dissatisfaction; Muscle dissatisfaction; Eating pathology; Gender roles; Sexual orientation; Men ID SEXUAL ORIENTATION; SELF-ESTEEM; RISK-FACTOR; GAY MEN; STATISTICAL TESTS; MASCULINE NORMS; ROLE-CONFLICT; DISORDERS; WOMEN; IMAGE AB The current study reviewed relationships between gender roles and (a) eating pathology, (b) body dissatisfaction, and (c) muscle dissatisfaction among men via meta-analysis. Moderators of sexual orientation and type of gender role measure were also investigated. Results revealed the relationship between femininity and eating and body-related variables did not significantly differ from zero. Sexual orientation moderated the relationship between femininity and muscle dissatisfaction (i.e., femininity was negatively related to muscle dissatisfaction for heterosexual but not gay men). Masculinity was negatively associated with eating pathology and body dissatisfaction. Type of masculinity measure moderated the relationship between masculinity and body dissatisfaction (i.e., trait-based measures produced a negative association, multidimensional measures yielded nonsignificant relationships). Type of masculinity measure produced a cross-over interaction when examining muscle dissatisfaction (i.e., trait-based instruments yielded a negative association and multidimensional instruments revealed a positive relationship). Findings highlight the salience of masculinity in men's eating and body concerns. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Blashill, Aaron J.] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. [Blashill, Aaron J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Blashill, Aaron J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Blashill, AJ (reprint author), St Louis Univ, Dept Psychol, 221 N Grand Blvd,Shannon Hall, St Louis, MO 63103 USA. EM ablashill@partners.org NR 85 TC 39 Z9 40 U1 3 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1740-1445 J9 BODY IMAGE JI Body Image PD JAN PY 2011 VL 8 IS 1 BP 1 EP 11 DI 10.1016/j.bodyim.2010.09.002 PG 11 WC Psychology, Clinical; Psychiatry; Psychology, Multidisciplinary SC Psychology; Psychiatry GA 714GH UT WOS:000286795000001 PM 20952263 ER PT J AU Smith, MR Martin, TJ AF Smith, Matthew R. Martin, T. John TI Foreword: Skeletal Complications of Cancer SO BONE LA English DT Editorial Material C1 [Martin, T. John] Univ Melbourne, Dept Med, St Vincents Inst, Fitzroy, Vic 3065, Australia. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Dept Oncol, Boston, MA 02114 USA. RP Martin, TJ (reprint author), Univ Melbourne, Dept Med, St Vincents Inst, 9 Princes St, Fitzroy, Vic 3065, Australia. EM jmartin@svi.edu.au NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JAN 1 PY 2011 VL 48 IS 1 SI SI BP 5 EP 5 DI 10.1016/j.bone.2010.10.162 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 705IL UT WOS:000286122000001 PM 20950719 ER PT J AU Lee, RJ Saylor, PJ Smith, MR AF Lee, Richard J. Saylor, Philip J. Smith, Matthew R. TI Treatment and prevention of bone complications from prostate cancer SO BONE LA English DT Review DE Bisphosphonate; Denosumab; Metastasis; Osteoclast; Prostate cancer; RANKL; Toremifene; Zoledronic acid ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ORAL SODIUM CLODRONATE; ADVANCED MULTIPLE-MYELOMA; LONG-TERM EFFICACY; ZOLEDRONIC ACID; BREAST-CANCER; DOUBLE-BLIND; SKELETAL COMPLICATIONS AB Bone metastases and skeletal complications are major causes of morbidity in prostate cancer patients. Despite the osteoblastic appearance of bone metastases on imaging studies, patients have elevated serum and urinary markers of bone resorption, indicative of high osteoclast activity. Increased osteoclast activity is independently associated with higher risk of subsequent skeletal complications, disease progression, and death. Osteoclast-targeted therapies are therefore a rational approach to reduction of risk for disease-related skeletal complications, bone metastases, and treatment-related fractures. This review focuses on recent advances in osteoclast-targeted therapy in prostate cancer. Bisphosphonates have been extensively studied in men with prostate cancer. Zoledronic acid significantly decreased the risk of skeletal complications in men with castration-resistant prostate cancer and bone metastases, and it is FDA-approved for this indication. Denosumab is a human monoclonal antibody that binds and inactivates RANKL, a critical mediator of osteoclast differentiation, activation, and survival. Recent global phase 3 clinic trials demonstrated an emerging role for denosumab in the treatment of prostate cancer bone metastases and prevention of fractures associated with androgen deprivation therapy. (C) 2010 Elsevier Inc. All rights reserved. C1 [Lee, Richard J.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Dept Oncol, Boston, MA 02114 USA. RP Lee, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Dept Oncol, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM rjlee@partners.org FU NCI NIH HHS [K24 CA121990-05, K24 CA121990, K24 CA121990-01A1] NR 63 TC 45 Z9 46 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JAN 1 PY 2011 VL 48 IS 1 SI SI BP 88 EP 95 DI 10.1016/j.bone.2010.05.038 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 705IL UT WOS:000286122000012 PM 20621630 ER PT J AU Roodman, GD AF Roodman, G. David TI Osteoblast function in myeloma SO BONE LA English DT Review DE Multiple myeloma; Bone disease; Osteoclast; Osteoblast; Cancer ID NF-KAPPA-B; MULTIPLE-MYELOMA; BONE-DISEASE; IN-VIVO; PROTEASOME INHIBITOR; SERUM CONCENTRATIONS; BORTEZOMIB; DIFFERENTIATION; CELLS; ACTIVATION AB Multiple myeloma (MM) is the most frequent cancer to involve the skeleton and results in purely osteolytic lesions that rarely heal. MM bone disease is responsible for some of the most devastating complications of MM. The marrow microenvironment plays a key role in MM bone disease as well as in the initiation, expansion and chemoresistance of MM cells. How this microenvironment becomes so supportive of MM, and the contribution and interaction of the various components of the microenvironment to enhancing MM growth are only beginning to be understood. However, it is clear that suppression of osteoblast activity plays a key role in the bone destructive process as well as progression of the tumor burden in myeloma. The impairment of osteoblast activity in MM results primarily from blockade of osteogenic differentiation of mesenchymal progenitors to mature osteoblasts. MM patients have low to normal levels of bone formation markers, such as alkaline phosphatase and osteocalcin in the setting of increased bone resorption. In contrast, MM patients without bone lesions display balanced bone remodeling with increased osteoclastogenesis and normal or increased bone formation rates. Both soluble factors and cell-to-cell contact between MM cells and osteoblast progenitors are responsible for the suppression of osteoblast differentiation in MM. In this article, the mechanism responsible for osteoblast suppression will be reviewed, and the effects of novel bone anabolic agents on myeloma bone disease will be discussed. (C) 2010 Elsevier Inc. All rights reserved. C1 [Roodman, G. David] VA Pittsburgh Healthcare Syst, Res & Dev, Pittsburgh, PA 15240 USA. [Roodman, G. David] Univ Pittsburgh, Dept Med Hematol Oncol, Pittsburgh, PA USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, Res & Dev, R&D 151U,Room 2E113,Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu NR 65 TC 26 Z9 28 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JAN 1 PY 2011 VL 48 IS 1 SI SI BP 135 EP 140 DI 10.1016/j.bone.2010.06.016 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 705IL UT WOS:000286122000019 PM 20601285 ER PT J AU McFadden, JL Borckardt, JJ George, MS Beam, W AF McFadden, James L. Borckardt, Jeff J. George, Mark S. Beam, William TI Reducing procedural pain and discomfort associated with transcranial direct current stimulation SO BRAIN STIMULATION LA English DT Article DE anode; cathode; EMLA; pain reduction; transcranial direct current stimulation; tDCS ID HIERARCHICAL LINEAR-MODELS; HUMAN MOTOR CORTEX; DC STIMULATION; PERCEPTION AB Background Transcranial direct current stimulation (tDCS) appears to have modulatory effects on the excitability of cortical brain tissue. Though tDCS as presently applied causes no apparent harm to brain structure or function, a number of uncomfortable sensations can occur beneath the electrodes during stimulation, including tingling, pain, itching, and burning sensations. Therefore, we investigated the effect of topically applied Eutectic mixture of local anesthetics (EMLA) on tDCS-related discomfort. Methods Nine healthy adults received both anodal and cathodal 2.0 mA tDCS for 5 minutes over the prefrontal cortex with the skin pretreated for 20 minutes with either EMLA or placebo cream. Participants rated procedural discomfort six times across eight dimensions of sensation. Results On average, the mean sensation ratings for EMLA-associated tDCS stimulation were significantly lower than placebo-associated stimulation for every cutaneous sensation evaluated. Cathodal stimulation was associated with higher ratings of "sharpness" and intolerability than anodal stimulation. Conclusions Topical EMLA may reduce tDCS-related discomfort. (C) 2011 Elsevier Inc. All rights reserved. C1 [McFadden, James L.; Borckardt, Jeff J.; George, Mark S.; Beam, William] Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Borckardt, JJ (reprint author), MUSC Inst Psychiat, 67 President St,PH 518, Charleston, SC 29425 USA. EM borckard@musc.edu RI Westwood, Sam/P-7000-2015 FU Medical University of South Carolina College of Graduate Studies; National Institutes of Health (National Institute of Mental Health, National Institute on Drug Abuse, National Institutes), the Department of Defense and Veterans Administration; National Institutes of Health (National Institute of Neurological Disorders and Stroke, National Institute of Nursing Research); Robert Wood Johnson Foundation FX Mr McFadden was funded through a grant from the Medical University of South Carolina College of Graduate Studies Summer Health Professionals Research Program.; Dr George was funded through grants from the National Institutes of Health (National Institute of Mental Health, National Institute on Drug Abuse, National Institutes), the Department of Defense and Veterans Administration.; Dr Borckardt was funded through grants from the National Institutes of Health (National Institute of Neurological Disorders and Stroke, National Institute of Nursing Research) and the Robert Wood Johnson Foundation. NR 16 TC 17 Z9 18 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X J9 BRAIN STIMUL JI Brain Stimul. PD JAN PY 2011 VL 4 IS 1 BP 38 EP 42 DI 10.1016/j.brs.2010.05.002 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 719AZ UT WOS:000287172900005 PM 21255753 ER PT J AU Fuentes, G Scaltriti, M Baselga, J Verma, CS AF Fuentes, Gloria Scaltriti, Maurizio Baselga, Jose Verma, Chandra S. TI Synergy between trastuzumab and pertuzumab for human epidermal growth factor 2 (Her2) from colocalization: an in silico based mechanism SO BREAST CANCER RESEARCH LA English DT Article ID MOLECULAR-DYNAMICS; FACTOR RECEPTOR; ERBB RECEPTORS; BREAST-CANCER; HERCEPTIN; PROTEINS; COMPLEX; ACTIVATION; RESISTANCE; ENERGIES AB Introduction: Human epidermal growth factor 2 (Her2), a receptor tyrosine kinase, is overexpressed in breast cancers. It has been successfully targeted by small molecule kinase inhibitors and by antibodies. Recent clinical data show a synergistic response in patients when two antibodies, trastuzumab and pertuzumab, are given in combination. Methods: This unexpected effect is rationalized through computer models and molecular dynamic simulations by hypothesizing that the two antibodies can co-localize on the same molecule of the Her2 extracellular domain. Results: Simulations suggest that the clinical synergism observed for the two antibodies arises partly from enhanced affinity that originates in cooperative interactions between these two antibodies when they are co-localized on Her2 and "clamp" it; this may inhibit dimerization and possibly higher oligomerizations with neighboring receptors. In the presence of trastuzumab, the receptor becomes highly plastic, especially domains I to III, and this appears to promote increased association with pertuzumab. Further, the presence of pertuzumab evokes novel interactions between the receptor and trastuzumab. Indeed, splicing out of this region in silico results in a big reduction in the interactions of the antibody with the receptor. Conclusions: If validated, these findings will bring about a new direction in the design of antibodies whereby different epitopes on the same antibody may be targeted to lead to synergistic/cooperative inhibition and contribute to generate more potent therapeutics and to increase clinical efficacy. C1 [Fuentes, Gloria; Verma, Chandra S.] Bioinformat Inst A STAR, Singapore 38671, Singapore. [Scaltriti, Maurizio; Baselga, Jose] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Div Hematol & Oncol, Boston, MA 02114 USA. [Scaltriti, Maurizio; Baselga, Jose] Vall Hebron Univ Hosp, Vall Hebron Inst Oncol VHIO, Med Oncol Dept, Barcelona 08035, Spain. [Verma, Chandra S.] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore. [Verma, Chandra S.] Nanyang Technol Univ, Sch Biol Sci, Singapore 637551, Singapore. RP Fuentes, G (reprint author), Bioinformat Inst A STAR, 30 Biopolis St,07-01 Matrix, Singapore 38671, Singapore. EM gfuentes@bii.a-star.edu.sg; chandra@bii.a-star.edu.sg RI fuentes, gloria/A-5018-2010 OI fuentes, gloria/0000-0003-3676-9666 FU European Research Council [AdG09 250244] FX CSV is adjunct at DBS (NUS) and SBS (NTU); Grant from European Research Council (AdG09 250244) is acknowledged. NR 38 TC 21 Z9 21 U1 2 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2011 VL 13 IS 3 AR R54 DI 10.1186/bcr2888 PG 9 WC Oncology SC Oncology GA 832ID UT WOS:000295797100006 PM 21600050 ER PT J AU Martrat, G Maxwell, CA Tominaga, E Porta-de-la-Riva, M Bonifaci, N Gomez-Baldo, L Bogliolo, M Lazaro, C Blanco, I Brunet, J Aguilar, H Fernandez-Rodriguez, J Seal, S Renwick, A Rahman, N Kuhl, J Neveling, K Schindler, D Ramirez, MJ Castella, M Hernandez, G Easton, DF Peock, S Cook, M Oliver, CT Frost, D Platte, R Evans, DG Lalloo, F Eeles, R Izatt, L Chu, C Davidson, R Ong, KR Cook, J Douglas, F Hodgson, S Brewer, C Morrison, PJ Porteous, M Peterlongo, P Manoukian, S Peissel, B Zaffaroni, D Roversi, G Barile, M Viel, A Pasini, B Ottini, L Putignano, AL Savarese, A Bernard, L Radice, P Healey, S Spurdle, A Chen, XQ Beesley, J Rookus, MA Verhoef, S Tilanus-Linthorst, MA Vreeswijk, MP Asperen, CJ Bodmer, D Ausems, MGEM van Os, TA Blok, MJ Meijers-Heijboer, HEJ Hogervorst, FBL Goldgar, DE Buys, S John, EM Miron, A Southey, M Daly, MB Harbst, K Borg, A Rantala, J Barbany-Bustinza, G Ehrencrona, H Stenmark-Askmalm, M Kaufman, B Laitman, Y Milgrom, R Friedman, E Domchek, SM Nathanson, KL Rebbeck, TR Oskar, T Couch, FJ Wang, XS Fredericksen, Z Cuadras, D Moreno, V Pientka, FK Depping, R Caldes, T Osorio, A Benitez, J Bueren, J Heikkinen, T Nevanlinna, H Hamann, U Torres, D Caligo, MA Godwin, AK Imyanitov, EN Janavicius, R Sinilnikova, OM Stoppa-Lyonnet, D Mazoyer, S Verny-Pierre, C Castera, L de Pauw, A Bignon, YJ Uhrhammer, N Peyrat, JP Vennin, P Ferrer, SF Collonge-Rame, MA Mortemousque, I McGuffog, L Chenevix-Trench, G Pereira-Smith, OM Antoniou, AC Ceron, J Tominaga, K Surralles, J Pujana, MA AF Martrat, Griselda Maxwell, Christopher A. Tominaga, Emiko Porta-de-la-Riva, Montserrat Bonifaci, Nuria Gomez-Baldo, Laia Bogliolo, Massimo Lazaro, Conxi Blanco, Ignacio Brunet, Joan Aguilar, Helena Fernandez-Rodriguez, Juana Seal, Sheila Renwick, Anthony Rahman, Nazneen Kuehl, Julia Neveling, Kornelia Schindler, Detlev Ramirez, Maria J. Castella, Maria Hernandez, Gonzalo Easton, Douglas F. Peock, Susan Cook, Margaret Oliver, Clare T. Frost, Debra Platte, Radka Evans, D. Gareth Lalloo, Fiona Eeles, Rosalind Izatt, Louise Chu, Carol Davidson, Rosemarie Ong, Kai-Ren Cook, Jackie Douglas, Fiona Hodgson, Shirley Brewer, Carole Morrison, Patrick J. Porteous, Mary Peterlongo, Paolo Manoukian, Siranoush Peissel, Bernard Zaffaroni, Daniela Roversi, Gaia Barile, Monica Viel, Alessandra Pasini, Barbara Ottini, Laura Putignano, Anna Laura Savarese, Antonella Bernard, Loris Radice, Paolo Healey, Sue Spurdle, Amanda Chen, Xiaoqing Beesley, Jonathan Rookus, Matti A. Verhoef, Senno Tilanus-Linthorst, Madeleine A. Vreeswijk, Maaike P. Asperen, Christi J. Bodmer, Danielle Ausems, Margreet G. E. M. van Os, Theo A. Blok, Marinus J. Meijers-Heijboer, Hanne E. J. Hogervorst, Frans B. L. Goldgar, David E. Buys, Saundra John, Esther M. Miron, Alexander Southey, Melissa Daly, Mary B. Harbst, Katja Borg, Ake Rantala, Johanna Barbany-Bustinza, Gisela Ehrencrona, Hans Stenmark-Askmalm, Marie Kaufman, Bella Laitman, Yael Milgrom, Roni Friedman, Eitan Domchek, Susan M. Nathanson, Katherine L. Rebbeck, Timothy R. Johannsson, Oskar Thor Couch, Fergus J. Wang, Xianshu Fredericksen, Zachary Cuadras, Daniel Moreno, Vctor Pientka, Friederike K. Depping, Reinhard Caldes, Trinidad Osorio, Ana Benitez, Javier Bueren, Juan Heikkinen, Tuomas Nevanlinna, Heli Hamann, Ute Torres, Diana Caligo, Maria Adelaide Godwin, Andrew K. Imyanitov, Evgeny N. Janavicius, Ramunas Sinilnikova, Olga M. Stoppa-Lyonnet, Dominique Mazoyer, Sylvie Verny-Pierre, Carole Castera, Laurent de Pauw, Antoine Bignon, Yves-Jean Uhrhammer, Nancy Peyrat, Jean-Philippe Vennin, Philippe Ferrer, Sandra Fert Collonge-Rame, Marie-Agnes Mortemousque, Isabelle McGuffog, Lesley Chenevix-Trench, Georgia Pereira-Smith, Olivia M. Antoniou, Antonis C. Ceron, Julian Tominaga, Kaoru Surralles, Jordi Angel Pujana, Miguel CA EMBRACE kConFab HEBON BCFR SWE-BRCA GEMO Study Collaborators TI Exploring the link between MORF4L1 and risk of breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID BRCA2 MUTATION CARRIERS; FANCONI-ANEMIA; SUSCEPTIBILITY GENE; HOMOLOGOUS RECOMBINATION; CAENORHABDITIS-ELEGANS; CHROMODOMAIN PROTEIN; PANCREATIC-CANCER; HELICASE BRIP1; GERM-CELLS; C-ELEGANS AB Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P(trend) = 0.45 and 0.05, P(2df) = 0.51 and 0.14, respectively; and rs10519219, P(trend) = 0.92 and 0.72, P(2df) = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers. C1 [Martrat, Griselda; Maxwell, Christopher A.; Bonifaci, Nuria; Gomez-Baldo, Laia; Moreno, Vctor; Ceron, Julian; Angel Pujana, Miguel] IDIBELL, Catalan Inst Oncol, Biomed Res Ctr Network Epidemiol & Publ Hlth CIBE, Lhospitalet Llobregat 08908, Spain. [Martrat, Griselda; Maxwell, Christopher A.; Gomez-Baldo, Laia; Aguilar, Helena; Angel Pujana, Miguel] Bellvitge Inst Biomed Res IDIBELL, Catalan Inst Oncol, Translat Res Lab, Lhospitalet Llobregat 08908, Spain. [Tominaga, Emiko; Pereira-Smith, Olivia M.; Tominaga, Kaoru] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. 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[Peterlongo, Paolo; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] IFOM Fdn Ist FIRC Oncol Mol, Dept Prevent & Predict Med, I-20139 Milan, Italy. [Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Roversi, Gaia] Fdn IRCCS INT, Dept Prevent & Predict Med, Unit Med Genet, I-20133 Milan, Italy. [Barile, Monica] Ist Europeo Oncol IEO, Div Canc Prevent & Genet, I-20141 Milan, Italy. [Viel, Alessandra] IRCCS, Ctr Riferimento Oncol CRO, Div Expt Oncol 1, I-33081 Aviano, Italy. [Pasini, Barbara] Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy. [Ottini, Laura] Univ Roma La Sapienza, Dept Mol Med, I-00161 Rome, Italy. [Ottini, Laura] Univ Florence, Dept Clin Physiopathol, Unit Med Genet, I-50139 Florence, Italy. [Putignano, Anna Laura] Fiorgen Fdn Pharmacogen, I-50019 Sesto Fiorentino, Italy. [Savarese, Antonella] Regina Elena Inst Canc Res, Div Med Oncol, I-00144 Rome, Italy. [Bernard, Loris] IEO, Dept Expt Oncol, I-20141 Milan, Italy. [Healey, Sue; Spurdle, Amanda; Chen, Xiaoqing; Beesley, Jonathan; Chenevix-Trench, Georgia] Queensland Inst Med Res, Div Genet & Populat Hlth, Brisbane, Qld 4029, Australia. [kConFab] Peter MacCallum Canc Ctr, Kathleen Cuningham Fdn Consortium Res Familial Br, Melbourne, Vic 8006, Australia. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, NL-1066 CX Amsterdam, Netherlands. [Verhoef, Senno; Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, NL-1066 CX Amsterdam, Netherlands. [Tilanus-Linthorst, Madeleine A.] Erasmus MC Daniel den Hoed Canc Ctr, Family Canc Clin, Dept Surg Oncol, NL-3075 AE Rotterdam, Netherlands. [Vreeswijk, Maaike P.; Asperen, Christi J.] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, NL-2333 ZA Leiden, Netherlands. [Bodmer, Danielle] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6520 GA Nijmegen, Netherlands. [Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, Netherlands. [van Os, Theo A.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Blok, Marinus J.] Univ Hosp Maastricht, Dept Clin Genet, NL-6229 HX Maastricht, Netherlands. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, NL-1007 MB Amsterdam, Netherlands. [HEBON] Netherlands Canc Inst, Dept Epidemiol, Hereditary Breast & Ovarian Canc Grp, NL-1066 CX Amsterdam, Netherlands. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84132 USA. [Buys, Saundra] Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA 94538 USA. [Miron, Alexander] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02210 USA. [Miron, Alexander] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02210 USA. [Southey, Melissa] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt MEGA, Melbourne, Vic 3010, Australia. [Daly, Mary B.] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. [BCFR] Univ Utah, Sch Med, Dept Dermatol, Breast Canc Family Registry, Salt Lake City, UT 84132 USA. Lund Univ, Dept Oncol, Swedish Breast Canc Study, S-22185 Lund, Sweden. [Harbst, Katja; Borg, Ake; SWE-BRCA] Skane Univ Hosp, S-22185 Lund, Sweden. [Rantala, Johanna; Barbany-Bustinza, Gisela] Karolinska Univ Hosp, Dept Clin Genet, S-17176 Stockholm, Sweden. [Ehrencrona, Hans] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, S-75185 Uppsala, Sweden. [Stenmark-Askmalm, Marie] Halsouniv Univ Sjukhuset, Univ Hosp, Dept Oncol, S-58185 Linkoping, Sweden. [Laitman, Yael; Milgrom, Roni; Friedman, Eitan] Chaim Sheba Med Ctr, Inst Oncol, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel. [Friedman, Eitan] Tel Aviv Univ, Sackler Fac Med, IL-69978 Ramat Aviv, Israel. [Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Nathanson, Katherine L.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Johannsson, Oskar Thor] 20A Landspitali LSH Hringbraut, Dept Oncol, IS-101 Reykjavik, Iceland. [Johannsson, Oskar Thor] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Couch, Fergus J.; Fredericksen, Zachary] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Cuadras, Daniel] IDIBELL, Stat Assessment Serv, Lhospitalet Llobregat 08908, Spain. [Pientka, Friederike K.; Depping, Reinhard] Univ Lubeck, Ctr Struct & Cell Biol Med, Dept Physiol, D-23538 Lubeck, Germany. [Caldes, Trinidad] Hosp Clin San Carlos, Med Oncol Branch, Madrid 28040, Spain. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Madrid 28029, Spain. [Osorio, Ana; Benitez, Javier] CIBERER, Madrid 28029, Spain. [Bueren, Juan] Ctr Invest Energet Medioambientales & Tecnol CIEM, Div Hematopoiesis & Gene Therapy, Madrid 28040, Spain. [Bueren, Juan] CIBERER, Madrid 28040, Spain. [Heikkinen, Tuomas; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Mol Genet Breast Canc, D-69120 Heidelberg, Germany. [Torres, Diana] Pontificia Univ Javeriana, Inst Genet Humana, Bogota, Colombia. [Caligo, Maria Adelaide] Univ Hosp Pisa, Sect Genet Oncol, I-56127 Pisa, Italy. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA. [Imyanitov, Evgeny N.] NN Petrov Oncol Res Inst, Mol Oncol Lab, St Petersburg 197758, Russia. [Janavicius, Ramunas] Vilnius Univ Hosp, Santariskiu Clin, Dept Mol & Regenerat Med, Hematol Oncol & Transfus Med Ctr, LT-08661 Vilnius, Lithuania. [GEMO Study Collaborators] Ctr Hosp Univ Lyon, Canc Genet Network Grp Genet & Canc, Unite Mixte Genet Constitut Canc Frequents, Ctr Leon Berard,Federat Natl Ctr Lutte Canc, F-6008 Lyon, France. [Sinilnikova, Olga M.; Mazoyer, Sylvie; Verny-Pierre, Carole] Univ Lyon 1, CNRS UMR5286, INSERM U1052, Canc Res Ctr Lyon, F-69373 Lyon, France. [Stoppa-Lyonnet, Dominique; Castera, Laurent; de Pauw, Antoine] Inst Curie, Serv Genet Oncol, F-75248 Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, Unite INSERM U830, F-75248 Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, F-75006 Paris, France. [Bignon, Yves-Jean; Uhrhammer, Nancy] Univ Clermont Ferrand, Dept Oncogenet, Ctr Jean Perrin, F-63011 Clermont Ferrand, France. [Peyrat, Jean-Philippe] Ctr Oscar Lambret, Lab Oncol Mol Humaine, F-59020 Lille, France. [Ferrer, Sandra Fert] Hotel Dieu Ctr Hosp, Lab Genet Chromosom, F-73011 Chambery, France. [Collonge-Rame, Marie-Agnes] CHU Besancon, Serv Genet Histol Biol Dev & Reprod, F-25000 Besancon, France. [Mortemousque, Isabelle] CHU Bretonneau, Serv Genet, F-37000 Tours, France. RP Ceron, J (reprint author), IDIBELL, Catalan Inst Oncol, Biomed Res Ctr Network Epidemiol & Publ Hlth CIBE, Gran Via 199, Lhospitalet Llobregat 08908, Spain. EM jceron@idibell.cat; ktominaga@hotmail.com; Jordi.Surralles@uab.cat; mapujana@iconcologia.net RI manoukian, siranoush/E-7132-2017; Maxwell, Christopher/B-3044-2011; Radice, Paolo/O-3119-2013; Blanco, Ignacio/D-2565-2013; Rahman, Nazneen/B-8890-2012; Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014; Ehrencrona, Hans/M-5619-2014; pujana, Miguel Angel/N-3127-2014; Bueren, Juan/L-6112-2014; Castella, Maria/J-8304-2015; Bodmer, D./L-4207-2015; Neveling, K./L-4544-2015; Spurdle, Amanda/A-4978-2011; Peissel, Bernard/E-8187-2017; Rahman, Nazneen/D-2802-2013; OI manoukian, siranoush/0000-0002-6034-7562; Maxwell, Christopher/0000-0002-0860-4031; Blanco, Ignacio/0000-0002-7414-7481; Osorio, Ana/0000-0001-8124-3984; Ehrencrona, Hans/0000-0002-5589-3622; pujana, Miguel Angel/0000-0003-3222-4044; Bueren, Juan/0000-0002-3228-7013; Spurdle, Amanda/0000-0003-1337-7897; Bogliolo, Massimo/0000-0001-8240-7784; PUTIGNANO, Anna Laura/0000-0001-9434-1612; Brunet, Joan/0000-0003-1945-3512; Nevanlinna, Heli/0000-0002-0916-2976; Moreno, Victor/0000-0002-2818-5487; Evans, Gareth/0000-0002-8482-5784; Peissel, Bernard/0000-0001-9233-3571; Nathanson, Katherine/0000-0002-6740-0901; Surralles, Jordi/0000-0002-4041-7519; Rahman, Nazneen/0000-0003-4376-0440; Cuadras, Daniel/0000-0001-8780-1764; FERNANDEZ RODRIGUEZ, JUANA/0000-0002-7760-5804; Eeles, Rosalind/0000-0002-3698-6241; Janavicius, Ramunas/0000-0002-3773-8485 FU Cancer Research - UK FX The authors thank Dr Andre Nussenzweig, Dr Laura Tusell and Dr Anton Gartner for providing Atm-deficient MEFs, anti-TRF2 and anti-RAD-51/RPA-1 antibodies, respectively. They also wish to thank all study participants, clinicians and centers for their valuable contribution, and the CGEMS initiative for making their genome-wide association study results available. The CIMBA data management is supported by Cancer Research - UK. Funding support is further detailed in Additional file 14. NR 69 TC 8 Z9 9 U1 2 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2011 VL 13 IS 2 AR R40 DI 10.1186/bcr2862 PG 14 WC Oncology SC Oncology GA 791VI UT WOS:000292694600029 PM 21466675 ER PT J AU Regan, MM Price, KN Giobbie-Hurder, A Thurlimann, B Gelber, RD AF Regan, Meredith M. Price, Karen N. Giobbie-Hurder, Anita Thuerlimann, Beat Gelber, Richard D. CA Int Breast Canc Study Grp BIG 1-98 Collaborative Grp TI Interpreting Breast International Group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer SO BREAST CANCER RESEARCH LA English DT Review ID AROMATASE INHIBITORS; PREDICTIVE-VALUE; BIG-1-98 TRIAL; ANASTROZOLE; METAANALYSIS; SURVIVAL; ARNO-95 AB The Breast International Group (BIG) 1-98 study is a four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one followed by 3 years of the other for postmenopausal women with endocrine-responsive early invasive breast cancer. From 1998 to 2003, BIG 1-98 enrolled 8,010 women. The enhanced design of the trial enabled two complementary analyses of efficacy and safety. Collection of tumor specimens further enabled treatment comparisons based on tumor biology. Reports of BIG 1-98 should be interpreted in relation to each individual patient as she weighs the costs and benefits of available treatments. ClinicalTrials.gov ID: NCT00004205. C1 [Regan, Meredith M.; Price, Karen N.; Giobbie-Hurder, Anita; Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG, Ctr Stat, Boston, MA 02215 USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA 02215 USA. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, CH-9007 St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res SAKK, CH-3008 Bern, Switzerland. RP Regan, MM (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG, Ctr Stat, 450 Brookline Ave, Boston, MA 02215 USA. EM mregan@jimmy.harvard.edu RI Munzone, Elisabetta/G-8848-2011; friedlander, michael/G-3490-2013; Cheuk, Robyn/H-1944-2013; Wardley, ANdrew/N-8135-2015; Wyld, David/B-8893-2015; Gonzalez Larriba, Jose Luis/G-6177-2016; OI friedlander, michael/0000-0002-6488-0604; Cheuk, Robyn/0000-0001-9516-5526; Wardley, ANdrew/0000-0002-9639-0888; Wyld, David/0000-0001-9523-4333; Gonzalez Larriba, Jose Luis/0000-0003-2631-0309; Segelov, Eva/0000-0002-4410-6144 FU Novartis (Basel, Switzerland); US National Cancer Institute [CA-75362]; Novartis; Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK); Susan G. Komen for the Cure [KG080081] FX Novartis (Basel, Switzerland), as the sponsor of the BIG 1-98 trial, contributed funds to the IBCSG to conduct the trial and retrospective tissue collection. Some of these funds were used to partially finance the IBCSG Statistical Center (MMR, AG-H, KNP, and RDG) and participating centers (BT). BT owns stock in Novartis.; The IBCSG Statistical Center is partially supported by US National Cancer Institute grant CA-75362. The BIG 1-98 trial is financed by Novartis and is coordinated by the IBCSG. Support for the IBCSG was provided from the Swedish Cancer Society, The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). Translational research was partially funded by Susan G. Komen for the Cure Promise Grant KG080081. NR 32 TC 23 Z9 23 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2011 VL 13 IS 3 AR 209 DI 10.1186/bcr2837 PG 16 WC Oncology SC Oncology GA 832ID UT WOS:000295797100028 PM 21635709 ER PT J AU Vachon, CM Sasano, H Ghosh, K Brandt, KR Watson, DA Reynolds, C Lingle, WL Goss, PE Li, R Aiyar, SE Scott, CG Pankratz, VS Santen, RJ Ingle, JN AF Vachon, Celine M. Sasano, Hironobu Ghosh, Karthik Brandt, Kathleen R. Watson, David A. Reynolds, Carol Lingle, Wilma L. Goss, Paul E. Li, Rong Aiyar, Sarah E. Scott, Christopher G. Pankratz, V. Shane Santen, Richard J. Ingle, James N. TI Aromatase immunoreactivity is increased in mammographically dense regions of the breast SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Aromatase; Breast density; Dense area ID POSTMENOPAUSAL WOMEN; ESTROGEN SULFOTRANSFERASE; PROLIFERATIVE ACTIVITY; ADIPOSE FIBROBLASTS; STEROID SULFATASE; ESTRADIOL LEVELS; HORMONE-THERAPY; STROMAL CELLS; RISK-FACTORS; EXPRESSION AB Mammographic breast density (MBD) is one of the strongest risk factors for breast cancer. Unfortunately, the biologic basis underlying this association is unknown. This study compared aromatase expression or immunoreactivity (IR) in core biopsies from mammographically dense versus non-dense regions of the breast to examine whether estrogen synthesis in the breast is associated with MBD and one possible mechanism through which MBD may influence breast cancer. Eligible participants were 40+ years, had a screening mammogram with visible MBD and no prior cancer or current endocrine therapy. Mammograms were used to identify dense and non-dense regions and ultrasound-guided core biopsies were performed to obtain tissue from these regions. Immunostaining for aromatase employed the streptavidin-biotin amplification method and #677 mouse monoclonal antibody. Aromatase IR was scored in terms of extent and intensity of staining for each cell type (stroma, epithelium, adipocytes) on histologic sections. A modified histological H-score provided quantitation of aromatase IR in each cell type and overall. Repeated measure analyses evaluated average differences (beta(H)) in H-score in dense versus non-dense tissue within and across cell types. Forty-nine women with mean age 50 years (range: 40-82), participated. Aromatase IR was increased in dense (vs. non-dense) tissue in both the stroma (beta(H) = 0.58) and epithelium (beta(H) = 0.12) (P < 0.01). Adipocytes from non-dense tissue, however, had a greater IR compared to those from dense tissue (beta(H) = -0.24, P < 0.01). An overall H-score which integrated results from all cell types demonstrated that aromatase IR was twice as great for dense (mean H-score = 0.90, SD = 0.53) versus non-dense (mean H-score = 0.45, SD = 0.39) breast tissue (beta(H) = 0.45; P < 0.001). Overall, aromatase IR was greater for mammographically dense versus non-dense tissue and may partly explain how MBD influences breast cancer. C1 [Vachon, Celine M.; Ghosh, Karthik; Brandt, Kathleen R.; Watson, David A.; Reynolds, Carol; Lingle, Wilma L.; Scott, Christopher G.; Pankratz, V. Shane; Ingle, James N.] Mayo Clin, Rochester, MN 55905 USA. [Sasano, Hironobu] Tohoku Univ, Sch Med, Sendai, Tohoku, Japan. [Goss, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Aiyar, Sarah E.; Santen, Richard J.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Li, Rong] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Vachon, CM (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM vachon.celine@mayo.edu OI Scott, Christopher/0000-0003-1340-0647 FU Mayo Clinic Breast SPORE [NIH CA116201]; NIH [K12 RR24151]; Friends for an Earlier Breast Cancer Test FX We thank the participants in this study, who provided samples for investigations of the determinants of breast density. This study was financially supported by the Mayo Clinic Breast SPORE, NIH CA116201; NIH K12 RR24151 for the KL2 Clinical and Translational Science Award-Mentored Career Development Program; and Friends for an Earlier Breast Cancer Test. NR 38 TC 21 Z9 22 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2011 VL 125 IS 1 BP 243 EP 252 DI 10.1007/s10549-010-0944-6 PG 10 WC Oncology SC Oncology GA 689UV UT WOS:000284956400029 PM 20526739 ER PT J AU Conrad, C Miller, DL Kaiser, C Jauch, KW Niess, H Huss, R AF Conrad, Claudius Miller, Diane L. Kaiser, Christina Jauch, Karl-Walter Niess, Hanno Huss, Ralf TI Spindle Cell Metaplastic Breast Carcinoma with Leiomyoid Differentiation: A Case Report SO BREAST CARE LA English DT Article DE Carcinoma; Leiomyoid; Metaplasia; Phylloides; Spindle Cell ID SONOGRAPHIC FINDINGS; FIBROMATOSIS; TUMORS AB Background: Metaplastic carcinoma of the breast is a rare but distinct entity within the group of undifferentiated invasive carcinomas. This entity accounts for less than 0.5% of all breast cancers and contains elements of epithelial (ductal), mesenchymal, and intermediate forms of differentiation. Of these metaplastic carcinomas, there have been reports of chondroid, squamous, osseous, and spindle differentiation. Case Report: We describe the clinical course of a 52-year-old female patient with an unusual histopathology of a spindle cell carcinoma of the breast, discuss the literature, and recommend an approach to diagnosis and treatment. The patient initially presented to an outside hospital with a rapidly growing breast mass that was originally diagnosed as a malignant phylloides tumor. She presented 11 months after the primary treatment with a local subcutaneous relapse. She later developed a local relapse of her metaplastic carcinoma in the chest wall. Extensive histopathological analysis lead to the diagnosis of a spindle cell metaplastic breast carcinoma with leiomyoid differentiation, which has not been described previously. Conclusions: Overlap in morphology can lead to a misinterpretation or underdiagnosis of metaplastic carcinomas. However, the prognosis is similar to more common types of breast adenocarcinoma. C1 [Conrad, Claudius] Massachusetts Gen Hosp, Dept Surg, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Miller, Diane L.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Kaiser, Christina; Huss, Ralf] Univ Munich, Inst Pathol, D-80539 Munich, Germany. [Jauch, Karl-Walter] Univ Munich, Dept Surg, D-80539 Munich, Germany. [Niess, Hanno] Univ Munich Grosshadern, Dept Surg, Munich, Germany. [Huss, Ralf] Roche Diagnost GmbH, Penzberg, Germany. RP Conrad, C (reprint author), Harvard Univ, Sch Med, 55 Fruit St,GRB-425, Boston, MA 02114 USA. EM cconrad1@partners.org NR 16 TC 2 Z9 3 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-3791 J9 BREAST CARE JI Breast Care PY 2011 VL 6 IS 3 BP 230 EP 233 DI 10.1159/000329330 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 786JF UT WOS:000292301600010 ER PT J AU Reisner, AT Xu, D Ryan, KL Convertino, VA Rickards, CA Mukkamala, R AF Reisner, A. T. Xu, D. Ryan, K. L. Convertino, V. A. Rickards, C. A. Mukkamala, R. TI Monitoring non-invasive cardiac output and stroke volume during experimental human hypovolaemia and resuscitation SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE arterial pressure, measurement; blood, loss; cardiovascular system, responses; equipment, finapres; monitoring, cardiopulmonary ID BODY NEGATIVE-PRESSURE; WAVE-FORM ANALYSIS; IMPEDANCE CARDIOGRAPHY; PULSE PRESSURE; MODEL; SHOCK; HYPOTENSION; VALIDATION; TOLERANCE; DYNAMICS AB Background. Multiple methods for non-invasive measurement of cardiac output (CO) and stroke volume (SV) exist. Their comparative capabilities are not clearly established. Methods. Healthy human subjects (n=21) underwent central hypovolaemia through progressive lower body negative pressure (LBNP) until the onset of presyncope, followed by termination of LBNP, to simulate complete resuscitation. Measurement methods were electrical bioimpedance (EBI) of the thorax and three measurements of CO and SV derived from the arterial blood pressure (ABP) waveform: the Modelflow (MF) method, the long-time interval (LTI) method, and pulse pressure (PP). We computed areas under receiver-operating characteristic curves (ROC AUCs) for the investigational metrics, to determine how well they discriminated between every combination of LBNP levels. Results. LTI and EBI yielded similar reductions in SV during progressive hypovolaemia and resuscitation (correlation coefficient 0.83) with ROC AUCs for distinguishing major LBNP (-60 mm Hg) vs resuscitation (0 mm Hg) of 0.98 and 0.99, respectively. MF yielded very similar reductions and ROC AUCs during progressive hypovolaemia, but after resuscitation, MF-CO did not return to baseline, yielding lower ROC AUCs (Delta ROC AUC range, -0.18 to -0.26, P < 0.01). PP declined during hypovolaemia but tended to be an inferior indicator of specific LBNP levels, and PP did not recover during resuscitation, yielding lower ROC curves (P < 0.01). Conclusions. LTI, EBI, and MF were able to track progressive hypovolaemia. PP decreased during hypovolaemia but its magnitude of reduction underestimated reductions in SV. PP and MF were inferior for the identification of resuscitation. C1 [Reisner, A. T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Xu, D.; Mukkamala, R.] Michigan State Univ, Dept Elect & Comp Engn, E Lansing, MI 48824 USA. [Ryan, K. L.; Convertino, V. A.; Rickards, C. A.] USA, Inst Surg Res, Ft Sam Houston, TX 78234 USA. RP Reisner, AT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM areisner@partners.org RI Xu, Da/A-6423-2012 FU United States Army MRMC [W23RYX6023N603, 604]; NHLBI [HL-080568] FX This work was supported by the United States Army MRMC Grant W23RYX6023N603 and 604 and by NHLBI Grant HL-080568. NR 33 TC 29 Z9 29 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JAN PY 2011 VL 106 IS 1 BP 23 EP 30 DI 10.1093/bja/aeq295 PG 8 WC Anesthesiology SC Anesthesiology GA 692YX UT WOS:000285192900005 PM 21051492 ER PT J AU Celli, A Mackenzie, DS Crumrine, DS Tu, CL Hupe, M Bikle, DD Elias, PM Mauro, TM AF Celli, A. Mackenzie, D. S. Crumrine, D. S. Tu, C. L. Hupe, M. Bikle, D. D. Elias, P. M. Mauro, T. M. TI Endoplasmic reticulum Ca2+ depletion activates XBP1 and controls terminal differentiation in keratinocytes and epidermis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID CALCIUM GRADIENT; PERMEABILITY BARRIER; MESSENGER-RNA; ER STRESS; SARCO/ENDOPLASMIC RETICULUM; INVOLUCRIN EXPRESSION; TRANSCRIPTION FACTOR; DARIER-DISEASE; MICE; SKIN AB P>Background Endoplasmic reticulum (ER) Ca2+ depletion, previously shown to signal pathological stress responses, has more recently been found also to trigger homeostatic physiological processes such as differentiation. In keratinocytes and epidermis, terminal differentiation and barrier repair require physiological apoptosis and differentiation, as evidenced by protein synthesis, caspase 14 expression, lipid secretion and stratum corneum (SC) formation. Objectives To investigate the role of Ca2+ depletion-induced ER stress in keratinocyte differentiation and barrier repair in vivo and in cell culture. Methods The SERCA2 Ca2+ pump inhibitor thapsigargin (TG) was used to deplete ER calcium both in cultured keratinocytes and in mice. Levels of the ER stress factor XBP1, loricrin, caspase 14, lipid synthesis and intracellular Ca2+ were compared after both TG treatment and barrier abrogation. Results We showed that these components of terminal differentiation and barrier repair were signalled by physiological ER stress, via release of stratum granulosum (SG) ER Ca2+ stores. We first found that keratinocyte and epidermal ER Ca2+ depletion activated the ER-stress-induced transcription factor XBP1. Next, we demonstrated that external barrier perturbation resulted in both intracellular Ca2+ emptying and XBP1 activation. Finally, we showed that TG treatment of intact skin did not perturb the permeability barrier, yet stimulated and mimicked the physiological processes of barrier recovery. Conclusions This report is the first to quantify and localize ER Ca2+ loss after barrier perturbation and show that homeostatic processes that restore barrier function in vivo can be reproduced solely by releasing ER Ca2+, via induction of physiological ER stress. C1 [Celli, A.; Mackenzie, D. S.; Tu, C. L.; Hupe, M.; Bikle, D. D.; Mauro, T. M.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94121 USA. [Crumrine, D. S.; Hupe, M.; Elias, P. M.; Mauro, T. M.] San Francisco VA Med Ctr, Dept Dermatol, San Francisco, CA 94121 USA. RP Celli, A (reprint author), Univ Calif San Francisco, Dept Dermatol, 4150 Clement St, San Francisco, CA 94121 USA. EM celli.anna@gmail.com FU National Institutes of Health [AR051930, AR19098]; San Francisco Veterans' Affairs Medical Center FX This work was supported by National Institutes of Health grants AR051930 (T.M.) and AR19098 (P.E.) and the San Francisco Veterans' Affairs Medical Center. The authors wish to thank Debra Crumrine for expert technical assistance. NR 39 TC 19 Z9 19 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2011 VL 164 IS 1 BP 16 EP 25 DI 10.1111/j.1365-2133.2010.10046.x PG 10 WC Dermatology SC Dermatology GA 700NY UT WOS:000285752000005 PM 20846312 ER PT J AU Singh, AV Bandi, M Aujay, MA Kirk, CJ Hark, DE Raje, N Chauhan, D Anderson, KC AF Singh, Ajita V. Bandi, Madhavi Aujay, Monette A. Kirk, Christopher J. Hark, David E. Raje, Noopur Chauhan, Dharminder Anderson, Kenneth C. TI PR-924, a selective inhibitor of the immunoproteasome subunit LMP-7, blocks multiple myeloma cell growth both in vitro and in vivo SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE apoptosis; Multiple-Myeloma; Immunoproteasome ID UBIQUITIN-PROTEASOME PATHWAY; DRUG-RESISTANCE; BONE-MARROW; MM CELLS; PS-341; DEATH; APOPTOSIS; THERAPY; DISEASE; BORTEZOMIB AB P>PR-924 is an LMP-7-selective tripeptide epoxyketone proteasome inhibitor that covalently modifies proteasomal N-terminal threonine active sites. In the present study, we show that PR-924 inhibits growth and triggers apoptosis in multiple myeloma (MM) cell lines and primary patient MM cells, without significantly affecting normal peripheral blood mononuclear cells. PR-924-induced apoptosis in MM cells is associated with activation of caspase-3, caspase-8, caspase-9, BID, PARP and cytochrome-c release. In vivo administration of PR-924 inhibits tumour growth in human plasmacytoma xenografts. Results from SCID-hu model show a significant reduction in the shIL-6R levels in mice treated with PR-924 versus vehicle-control. PR-924 treatment was well tolerated as evidenced by the lack of weight loss. Importantly, treatment of tumour-bearing mice with PR-924, but not vehicle alone, prolonged survival. Our preclinical findings therefore validate immunoproteasome LMP-7 subunit as a novel therapeutic target in MM. C1 [Singh, Ajita V.; Bandi, Madhavi; Hark, David E.; Raje, Noopur; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Singh, Ajita V.; Bandi, Madhavi; Hark, David E.; Raje, Noopur; Chauhan, Dharminder; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. [Aujay, Monette A.; Kirk, Christopher J.] Onyx Pharmaceut Inc, San Francisco, CA USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Mayer Bldg Room 561,44 Binney St, Boston, MA 02115 USA. EM Dharminder_Chauhan@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU NIH [SPORE-P50100707, PO1-CA078378, RO1CA050947]; MRF funds FX Grant support: This investigation was supported by NIH grants SPORE-P50100707, PO1-CA078378, and RO1CA050947; and MRF funds. KCA is an ACS clinical research professor. NR 43 TC 55 Z9 57 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2011 VL 152 IS 2 BP 155 EP 163 DI 10.1111/j.1365-2141.2010.08491.x PG 9 WC Hematology SC Hematology GA 700OD UT WOS:000285752600003 PM 21114484 ER PT J AU Komers, R Oyama, TT Beard, DR Anderson, S AF Komers, R. Oyama, T. T. Beard, D. R. Anderson, S. TI Effects of systemic inhibition of Rho kinase on blood pressure and renal haemodynamics in diabetic rats SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE diabetic nephropathy; RhoA GTPase; Rho associated kinase; Y27632; fasudil; effective renal plasma flow; myosin light chain; ruboxistaurin ID RENIN-ANGIOTENSIN SYSTEM; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS; PKC-BETA INHIBITOR; PROTEIN-KINASE; SIGNALING PATHWAYS; MICROVASCULAR TONE; MYOSIN PHOSPHATASE; HYPERTENSIVE-RATS; RHOA/RHO-KINASE AB BACKGROUND AND PURPOSE The RhoA/Rho associated kinases (ROCK) pathway has been implicated in the pathophysiology of diabetic nephropathy (DN). Early stages of diabetes are associated with renal haemodynamic changes, contributing to later development of DN. However, the role of RhoA/ROCK, known regulators of vascular tone, in this process has not been studied. EXPERIMENTAL APPROACH Blood pressure (BP), glomerular filtration (GFR), effective renal plasma flow and filtration fraction (FF) in response to the ROCK inhibitors Y27632 (0.1 and 0.5 mg center dot kg-1) and fasudil (0.3 and 1.5 mg center dot kg-1) were examined in streptozotocin-diabetic rats and non-diabetic controls. KEY RESULTS Diabetic rats demonstrated baseline increases in GFR and FF. In contrast to similar decreases in BP in diabetic and control rats, renal vasodilator effects and a decrease in FF, following ROCK inhibition were observed only in diabetic rats. The vasodilator effects of Y27632 and a further decrease in FF, were also detected in diabetic rats pretreated with the angiotensin antagonist losartan. The effects of ROCK inhibitors in diabetic rats were modulated by prior protein kinase C (PKC)beta inhibition with ruboxistaurin, which abolished their effects on FF. Consistent with the renal vasodilator effects, the ROCK inhibitors reduced phosphorylation of myosin light chain in diabetic kidneys. CONCLUSIONS AND IMPLICATIONS The results indicate greater dependence of renal haemodynamics on RhoA/ROCK and beneficial haemodynamic effects of ROCK inhibitors in diabetes, which were additive to the effects of losartan. In this process, the RhoA/ROCK pathway operated downstream of or interacted with, PKC beta in some segments of the renal vascular tree. C1 [Komers, R.; Oyama, T. T.; Anderson, S.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. [Beard, D. R.; Anderson, S.] Portland VA Med Ctr, Portland, OR USA. RP Komers, R (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM komersr@ohsu.edu FU Juvenile Diabetes Research Foundation [1-2008-314] FX Ruboxistaurin was a generous gift from Eli Lilly and Co. Parts of these studies have been previously presented at the meetings of the European Diabetic Nephropathy Study Group, Hannover, Germany, 2008; and the American Society of Nephrology, San Diego, CA, USA, 2009. These studies were supported by the Juvenile Diabetes Research Foundation (R.K. 1-2008-314). NR 52 TC 16 Z9 19 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2011 VL 162 IS 1 BP 163 EP 174 DI 10.1111/j.1476-5381.2010.01031.x PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 690LN UT WOS:000285006400013 PM 20840471 ER PT J AU Becker, AE Fay, KE Agnew-Blais, J Khan, AN Striegel-Moore, RH Gilman, SE AF Becker, Anne E. Fay, Kristen E. Agnew-Blais, Jessica Khan, A. Nisha Striegel-Moore, Ruth H. Gilman, Stephen E. TI Social network media exposure and adolescent eating pathology in Fiji SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID BODY-IMAGE CONCERNS; PEER INFLUENCES; GIRLS; DISORDERS; HEALTH; ADAPTATION; DISSATISFACTION; QUESTIONNAIRE; TELEVISION; IMPAIRMENT AB Background Mass media exposure has been associated with an increased risk of eating pathology. It is unknown whether indirect media exposure - such as the proliferation of media exposure in an individual's social network - is also associated with eating disorders. Aims To test hypotheses that both individual (direct) and social network (indirect) mass media exposures were associated with eating pathology in Fiji. Method We assessed several kinds of mass media exposure, media influence, cultural orientation and eating pathology by self-report among adolescent female ethnic Fijians (n = 523). We fitted a series of multiple regression models of eating pathology, assessed by the Eating Disorder Examination Questionnaire (EDE-Q), in which mass media exposures, sociodemographic characteristics and body mass index were entered as predictors. Results Both direct and indirect mass media exposures were associated with eating pathology in unadjusted analyses, whereas in adjusted analyses only social network media exposure was associated with eating pathology. This result was similar when eating pathology was operationalised as either a continuous or a categorical dependent variable (e.g. odds ratio OR = 1.60, 95% 01 1.15-2.23 relating social network media exposure to upper-quartile EDE-Q scores). Subsequent analyses pointed to individual media influence as an important explanatory variable in this association. Conclusions Social network media exposure was associated with eating pathology in this Fijian study sample, independent of direct media exposure and other cultural exposures. Findings warrant further investigation of its health impact in other populations. C1 [Becker, Anne E.] Harvard Univ, Dept Global Hlth & Social Med, Sch Med, Boston, MA 02115 USA. [Becker, Anne E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fay, Kristen E.] Tufts Univ, Eliot Pearson Dept Appl Child Dev, Medford, MA 02155 USA. [Agnew-Blais, Jessica; Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Khan, A. Nisha] Minist Hlth, Suva, Fiji. [Striegel-Moore, Ruth H.] Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Becker, AE (reprint author), Harvard Univ, Dept Global Hlth & Social Med, Sch Med, 641 Huntington Ave, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu RI Agnew-Blais, Jessica/L-9236-2015; Gilman, Stephen/E-7632-2010 OI Agnew-Blais, Jessica/0000-0002-0755-6867; Gilman, Stephen/0000-0002-8331-6419 FU National Institute of Mental Health [K23 MH068575]; Harvard University; Radcliffe Institute FX A.E.B. received funding from the National Institute of Mental Health (K23 MH068575), Harvard University (a Harvard University Research Enabling Grant) and the Radcliffe Institute. NR 38 TC 20 Z9 22 U1 6 U2 34 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JAN PY 2011 VL 198 IS 1 BP 43 EP 50 DI 10.1192/bjp.bp.110.078675 PG 8 WC Psychiatry SC Psychiatry GA 713ZC UT WOS:000286775100010 PM 21200076 ER PT J AU Habibollahi, P Ghahremani, MH Azizi, E Ostad, SN AF Habibollahi, Peiman Ghahremani, Mohammad Hossein Azizi, Ebrahim Ostad, Seyed Nasser TI Multi Drug Resistance-1 (MDR1) Expression in Response to Chronic Diazinon Exposure: An In vitro Study on Caco-2 Cells SO BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article DE P-glycoprotein; Multi drug resistance 1; Caco-2; Diazinon ID P-GLYCOPROTEIN; PESTICIDE EXPOSURE; TRANSPORT; LLC-PK1; DIGOXIN; LEVEL AB To evaluate the effect of chronic exposure to diazinon in the gastrointestinal tract, Caco-2 cells were made resistant by growing in low concentrations of diazinon (0.02 mu M) that was gradually increased to 20 mu M within 4.5 months. Resistant cells showed significant higher growth in the presence of 15, 45 and 135 mu M of diazinon (96.08, 81.80 and 65.16% of control) compared to parent cells (79.71, 71.76 and 29.50% of control, respectively; p < 0.05). P-glycoprotein (P-gp) expression increased significantly in resistant cells (P-gp to beta-actin ratio 0.586 for parent and 1.255 for resistant cells, respectively; p < 0.05) without any alteration in MDR-1 mRNA level (p > 0.05). C1 [Habibollahi, Peiman; Ghahremani, Mohammad Hossein; Azizi, Ebrahim; Ostad, Seyed Nasser] Univ Tehran Med Sci, Fac Pharm, Dept Pharmacol & Toxicol, Tehran, Iran. [Habibollahi, Peiman] Massachusetts Gen Hosp, Dept Radiol, Ctr Translat Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Habibollahi, Peiman; Ghahremani, Mohammad Hossein] Univ Tehran Med Sci, Sch Adv Med Technol, Dept Mol Med, Tehran, Iran. RP Ostad, SN (reprint author), Univ Tehran Med Sci, Fac Pharm, Dept Pharmacol & Toxicol, Tehran, Iran. EM ostadnas@tums.ac.ir NR 19 TC 4 Z9 5 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0007-4861 J9 B ENVIRON CONTAM TOX JI Bull. Environ. Contam. Toxicol. PD JAN PY 2011 VL 86 IS 1 BP 105 EP 109 DI 10.1007/s00128-010-0158-y PG 5 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 703RV UT WOS:000285999900018 PM 21127835 ER PT J AU Beard, C Stason, WB Wang, QA Manola, J Dean-Clower, E Dusek, JA DeCristofaro, S Webster, A Doherty-Gilman, AM Rosenthal, DS Benson, H AF Beard, Clair Stason, William B. Wang, Qian Manola, Judith Dean-Clower, Elizabeth Dusek, Jeffery A. DeCristofaro, Susan Webster, Ann Doherty-Gilman, Anne M. Rosenthal, David S. Benson, Herbert TI Effects of Complementary Therapies on Clinical Outcomes in Patients Being Treated With Radiation Therapy for Prostate Cancer SO CANCER LA English DT Article DE anxiety; clinical trials; energy medicine; mind-body medicine; prostate cancer; radiation therapy; Reiki; relaxation response therapy ID QUALITY-OF-LIFE; ALTERNATIVE MEDICINE USE; RELAXATION RESPONSE; MEN; TRIAL; RADIOTHERAPY; PREVALENCE; REIKI AB BACKGROUND. This pilot randomized controlled trial (RCT) examined the clinical effects of 2 complementary (CAM) therapies, relaxation response therapy (RRT) and Reiki therapy, in men being treated with external beam radiotherapy (EBRx) for prostate cancer. METHODS. Study participants were randomly assigned to weekly RRT, Reiki therapy twice weekly, or wait-list control. Well-validated instruments measured anxiety (STAI), depression (CES-D), and quality of life in cancer patients (FACT-G) at randomization and 3 subsequent time points. RESULTS. Fifty-four men were randomized, and 16 of 18 (89%) of RRT and 15 of 18 (83%) of Reiki patients completed the intervention protocol. No statistically significant difference was found between the RRT, Reiki, and control groups on total scores for the STAI, CES-D, or FACT-G instruments at any time point. However, at the end of the intervention, significant improvement was found on the emotional well-being subscale of the FACT-G quality of life scale in the RRT group compared with the Reiki and control groups (P = .01). In participants who were classified as "anxious" at baseline, statistically significant improvement occurred in the RRT group (P = .02), and a positive trend was found in the Reiki group (P = .10). CONCLUSIONS. This pilot study documented the feasibility of conducting a RCT of CAM therapies in men undergoing EBRx for prostate cancer. Relaxation response therapy improved emotional well being and eased anxiety in participants. Reiki therapy also had a positive effect in anxious patients. A larger study to verify and better define the benefits of these therapies in men with prostate cancer is warranted. Cancer 2011;117:96-102. (C) 2010 American Cancer Society. C1 [Beard, Clair] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Stason, William B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wang, Qian; Manola, Judith] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Dean-Clower, Elizabeth; DeCristofaro, Susan; Doherty-Gilman, Anne M.] Dana Farber Canc Inst, Leonard P Zakim Ctr Integrat Therapies, Boston, MA 02115 USA. [Dusek, Jeffery A.; Webster, Ann; Rosenthal, David S.; Benson, Herbert] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. RP Beard, C (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM cbeard@partners.org OI Dusek, Jeffery/0000-0001-9581-0564 FU Advanced Medical Research Foundation, Boston, Massachusetts FX Research support for this study was provided by the Advanced Medical Research Foundation, Boston, Massachusetts. NR 33 TC 15 Z9 15 U1 1 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2011 VL 117 IS 1 BP 96 EP 102 DI 10.1002/cncr.25291 PG 7 WC Oncology SC Oncology GA 695KF UT WOS:000285368300014 PM 20803609 ER PT J AU Wierda, WG Kipps, TJ Keating, MJ Brown, JR Gribben, JG Browning, M Rassenti, LZ Greaves, AW Neuberg, D O'Brien, SM AF Wierda, William G. Kipps, Thomas J. Keating, Michael J. Brown, Jennifer R. Gribben, John G. Browning, Mary Rassenti, Laura Z. Greaves, Andrew W. Neuberg, Donna O'Brien, Susan M. CA CLL Res Consortium TI Self-Administered, Subcutaneous Alemtuzumab to Treat Residual Disease in Patients With Chronic Lymphocytic Leukemia SO CANCER LA English DT Article DE chronic lymphocytic leukemia; alemtuzumab; minimal residual disease; monoclonal antibody ID STUDY-GROUP GCLLSG; PHASE-III TRIAL; 1ST REMISSION; FLUDARABINE; THERAPY; CONSOLIDATION; CLL; CAMPATH-1H; SURVIVAL; SAFETY AB BACKGROUND: Alemtuzumab is highly effective at treating chronic lymphocytic leukemia (CLL) in bone marrow, which is the usual site of residual disease after fludarabine-based treatment. Eliminating residual disease potentially is associated with longer remission and overall survival. The authors of this report evaluated the ability of subcutaneous alemtuzumab to treat residual disease. METHODS: Patients in partial remission (PR), nodular PR (nPR), or complete remission (CR) who had disease in bone marrow established by 2-color flow cytometry analysis were enrolled and received alemtuzumab 30 mg subcutaneously 3 times weekly for 4 weeks, and patients had the option to self-administer alemtuzumab. Responders were patients in PR who converted to an nPR or a CR, patients in nPR who converted to a CR, and patients in CR who had no evidence of disease on 2-color flow cytometry analysis after treatment. RESULTS: There were 31 patients enrolled, of whom 29 were evaluable, and there were 23 responders (4 of 4 patients who achieved a CR, 8 of 9 patients who achieved an nPR, and 11 of 16 patients who achieved a PR. Non-responders had significantly lower plasma alemtuzumab levels at the end of treatment. Furthermore, higher plasma alemtuzumab levels at the end of treatment were correlated with a longer response duration. Compared with the results from an historic group that received intravenous alemtuzumab for residual disease, there was a trend toward a higher response rate but a shorter response duration with subcutaneous alemtuzumab. CONCLUSIONS: The current results demonstrated that self-administered, subcutaneous alemtuzumab was safe and active for residual disease and that plasma alemtuzumab levels and real-time minimal residual disease evaluation are important endpoints to monitor in future alemtuzumab consolidation trials. Cancer 2011;117:116-24. (C) 2010 American Cancer Society. C1 [O'Brien, Susan M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Unit 428, Houston, TX 77030 USA. [Kipps, Thomas J.; Rassenti, Laura Z.; Greaves, Andrew W.] Univ Calif San Diego, Moores Univ Calif San Diego Canc Ctr, Dept Hematol Oncol, San Diego, CA 92103 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA. [Gribben, John G.] Barts & London Queen Marys Sch Med & Dent, Ctr Med Oncol, Dept Haematol, London, England. [Browning, Mary] Genzyme Oncol, Cambridge, MA USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP O'Brien, SM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Unit 428, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM sobrien@mdanderson.org FU Bayer Healthcare; CLL Research Consortium FX This clinical trial and correlative laboratory studies were supported by Bayer Healthcare. W. G. Wierda is a Leukemia and Lymphoma Society Clinical Scholar. This study was conducted with the infrastructure and support of the CLL Research Consortium. NR 19 TC 12 Z9 12 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2011 VL 117 IS 1 BP 116 EP 124 DI 10.1002/cncr.25379 PG 9 WC Oncology SC Oncology GA 695KF UT WOS:000285368300017 PM 20806349 ER PT J AU Freedman, RA Virgo, KS He, YL Pavluck, AL Winer, EP Ward, EM Keating, NL AF Freedman, Rachel A. Virgo, Katherine S. He, Yulei Pavluck, Alexandre L. Winer, Eric P. Ward, Elizabeth M. Keating, Nancy L. TI The Association of Race/Ethnicity, Insurance Status, and Socioeconomic Factors With Breast Cancer Care SO CANCER LA English DT Article DE breast cancer; race; insurance; socioeconomic status; disparity ID WHITE AMERICAN PATIENTS; AFRICAN-AMERICAN; DATA-BASE; ADJUVANT CHEMOTHERAPY; UNITED-STATES; OLDER WOMEN; DISPARITIES; SURVIVAL; THERAPY; OPPORTUNITIES AB BACKGROUND: Few data are available on how race/ethnicity, insurance, and socioeconomic status (SES) interrelate to influence breast cancer treatment. The authors examined care for a national cohort of breast cancer patients to assess whether insurance and SES were associated with racial/ethnic differences in care. METHODS: The authors used multivariate logistic regression to assess the probability of definitive locoregional therapy, hormone receptor testing, and adjuvant systemic therapy among 662,117 white, black, and Hispanic women diagnosed with invasive breast cancer during 1998-2005 at National Cancer Data Base hospitals. In additional models, the authors included insurance and area-level SES to determine whether these variables were associated with observed racial/ethnic disparities. RESULTS: Most women were white (86%), 10% were black, and 4% were Hispanic. Most had private insurance (51%) or Medicare (41%). Among eligible patients, 80.0% (stage I/II) had definitive locoregional therapy, 98.5% (stage I-IV) had hormone receptor testing, and 53.1% and 50.2% (stage I-III) received adjuvant hormonal therapy and chemotherapy, respectively. After adjustment, black (vs white) women had less definitive locoregional therapy (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.88-0.94), hormonal therapy (OR, 0.90; 95% CI, 0.87-0.93), and chemotherapy (OR, 0.87; 95% CI, 0.84-0.91). Hispanic (vs white) women were also less likely to receive hormonal therapy. Hormone receptor testing did not differ by race/ethnicity. Racial disparities persisted despite adjusting for insurance and SES. CONCLUSIONS: The modest association between black (vs white) race and guideline-recommended breast cancer care was insensitive to adjustment for insurance and area-level SES. Further study is required to better understand disparities and to ensure receipt of care. Cancer 2011;117:180-9. (C) 2010 American Cancer Society. C1 [Freedman, Rachel A.; Winer, Eric P.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Virgo, Katherine S.; Pavluck, Alexandre L.; Ward, Elizabeth M.] Amer Canc Soc, Surveillance & Hlth Policy Res Dept, Atlanta, GA 30329 USA. [He, Yulei; Keating, Nancy L.] Harvard Univ, Dept Hlth Care Policy, Sch Med, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM rafreedman@partners.org FU Susan G. Komen for the Cure FX Research support was provided by Susan G. Komen for the Cure. NR 38 TC 61 Z9 61 U1 2 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2011 VL 117 IS 1 BP 180 EP 189 DI 10.1002/cncr.25542 PG 10 WC Oncology SC Oncology GA 695KF UT WOS:000285368300024 PM 20939011 ER PT J AU Cheuk, DKL Billups, CA Martin, MG Roland, CR Ribeiro, RC Krasin, MJ Rodriguez-Galindo, C AF Cheuk, Daniel Ka Leung Billups, Catherine A. Martin, Michael G. Roland, Cynthia R. Ribeiro, Raul C. Krasin, Matthew J. Rodriguez-Galindo, Carlos TI Prognostic Factors and Long-Term Outcomes of Childhood Nasopharyngeal Carcinoma SO CANCER LA English DT Article DE children; cumulative incidence; long-term effects; nasopharyngeal carcinoma ID INTENSITY-MODULATED RADIOTHERAPY; YOUNG-PATIENTS; SINGLE-INSTITUTION; CHILDREN; CHEMOTHERAPY; ADOLESCENCE; EXPERIENCE; CANCER; CHEMORADIOTHERAPY; AMIFOSTINE AB BACKGROUND: The authors studied the survival and long-term morbidities of children with nasopharyngeal carcinoma (NPC). METHODS: This was a retrospective review of children with NPC who were treated at St. Jude Children's Research Hospital between 1961 and 2004. Prognostic factors and long term effects of therapy were analyzed. RESULTS: Fifty-nine patients (median age, 14.1 years) were identified. Most were male (66.1%) and black (54.2%) and had lymphoepitheloma (93.2%). Thirty-five patients had stage IV disease (59.3%), 20 patients had stage III disease (33.9%), and 4 patients had stage II disease (6.8%). All patients received radiotherapy (RT) to the primary tumor, and most received cervical RT (98.3%) and chemotherapy (88.1%). The 15-year survival and event-free survival (EFS) rates were 67.2% +/- 7.5% and 63.5% +/- 7.8%, respectively. Five patients (8.5%) developed subsequent malignancies 8.6 to 27 years after NPC diagnosis. EFS was improved in patients who were diagnosed after 1980 (74.8% +/- 10% vs 45.5% +/- 10.1%; P = .031), in patients who had stage III disease compared with patients who had stage IV disease (79.3% +/- 9.6% vs 56.2% +/- 11.8%; P = .049), in patients who received cisplatin (81% +/- 10.7% vs 45.8% +/- 9.7%; P =.013), and in patients who received >= 50 grays of RT (71.4% +/- 9.3% vs 43.8% +/- 11.6%; P=.048). White patients had higher distant failure rates than back patients (41.7% +/- 10.4% vs 15.6 +/- 6.5%; P = .045). The 15-year cumulative incidence (Cl) of any morbidity was 83.7% +/- 5.4%, the CI of sensorineural hearing loss was 52.9% +/- 6.7%, the Cl of primary hypothyroidism was 42.7% +/- 6.6%, and the Cl of growth hormone deficiency (GHD) was 14.1% +/- 4.7%. Dose-response relations were observed between the RT dose and primary hypothyroidism and GHD. CONCLUSIONS: The outcome of children with NPC improved over the past 4 decades with the use of cisplatin-based chemotherapy and higher RT doses. However, many survivors had long-term treatment-related morbidities. Cancer 2011;117:197-206. (C) 2070 American Cancer Society C1 [Cheuk, Daniel Ka Leung; Martin, Michael G.; Roland, Cynthia R.; Ribeiro, Raul C.; Rodriguez-Galindo, Carlos] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Billups, Catherine A.] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA. [Krasin, Matthew J.] St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. RP Rodriguez-Galindo, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM carlos_rodriguez-galindo@dfci.harvard.edu OI Cheuk, Daniel/0000-0001-9553-3528 FU American Lebanese Associated Charities [P30-CA23099, CA21765] FX Supported by Grants P30-CA23099 and CA21765 and by the American Lebanese Associated Charities. NR 43 TC 22 Z9 26 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 1 PY 2011 VL 117 IS 1 BP 197 EP 206 DI 10.1002/cncr.25376 PG 10 WC Oncology SC Oncology GA 695KF UT WOS:000285368300026 PM 20737561 ER PT J AU Ramakrishnan, V Kushwaha, D Koay, DC Reddy, H Mao, Y Zhou, LF Ng, K Zinn, P Carter, B Chen, CC AF Ramakrishnan, Valya Kushwaha, Deepa Koay, Debbie C. Reddy, Hasini Mao, Ying Zhou, Liangfu Ng, Kimberly Zinn, Pascal Carter, Bob Chen, Clark C. TI Post-transcriptional regulation of O-6-methylguanine-DNA methyltransferase MGMT in glioblastomas SO CANCER BIOMARKERS LA English DT Article DE Glioblastoma; TCGA; MGMT; methylation; therapeutic resistance; microRNA ID PROMOTER METHYLATION; IMMUNOHISTOCHEMICAL EXPRESSION; ADJUVANT TEMOZOLOMIDE; ANAPLASTIC GLIOMAS; ALKYLATING-AGENTS; REPAIR; RADIOTHERAPY; DNA; CONCOMITANT; MECHANISMS AB Background: The DNA repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT) confers therapeutic resistance to DNA alkylating agents, including temozolomide. It is largely believed that MGMT promoter methylation is associated with down regulation of MGMT transcription and corresponding protein expression, thereby predisposing tumor cells to the toxic effect of temozolomide. Here we rigorously examined this underlying assumption. Methods: We examined the correlation between MGMT promoter methylation, transcription, and protein expression using The Cancer Genome Atlas (TCGA) glioblastoma database as well as an independent collection of glioblastoma specimens. Results: In both analyses, we found that MGMT promoter methylation status correlates well with low MGMT mRNA levels (p = 0.04). On the other hand, glioblastomas with unmethylated MGMT promoters exhibited a wide range of MGMT mRNA expression. Intriguingly, the MGMT mRNA levels correlated poorly with MGMT protein levels by Western blotting (R-2 = 0.04, p = 0.34) or by ImmunoHistoChemical (IHC) stain quantitation (R-2 = 0.02, p = 0.50). To exclude the possibility that the poor correlation was due to substandard specimens, we determined the mRNA and protein levels of Colony Stimulating Factor 1 (CSF1), a gene previously shown to exhibit excellent mRNA/protein correlation. In contrast to MGMT, the mRNA level of CSF1 correlated well with the protein level (R-2 = 0.47, p = 0.001). Importantly, long-term passaged glioblastoma cell lines with comparable MGMT transcript levels differed in MGMT protein levels, suggesting mechanisms of post-transcriptional regulation. Accordingly, the correlation between MGMT promoter methylation and MGMT protein expression was poor (p = 0.27). In silico analysis predicted potential binding sites for several miRNA within the 3'UTR of MGMT, suggesting a mechanism for the post-transcriptional of MGMT. Conclusion: Our results suggest mechanisms such as miRNA mediated regulation for post-transcriptional regulation of MGMT. Identification of these mechanisms should enhance the value of MGMT based prognostic or predictive biomarker strategies. C1 [Ramakrishnan, Valya; Carter, Bob; Chen, Clark C.] Univ Calif San Diego, Div Neurosurg, Ctr Theoret & Appl Neurooncol, Moores Canc Ctr, La Jolla, CA 92093 USA. [Kushwaha, Deepa; Koay, Debbie C.; Ng, Kimberly] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Reddy, Hasini] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Mao, Ying; Zhou, Liangfu] Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200433, Peoples R China. [Zinn, Pascal] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. RP Chen, CC (reprint author), Univ Calif San Diego, Div Neurosurg, Ctr Theoret & Appl Neurooncol, Moores Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM clarkchen@ucsd.edu RI Chen, Clark/C-8714-2013; RAMAKRISHNAN, VALYA/L-6415-2016 OI Chen, Clark/0000-0001-6258-9277; NR 36 TC 19 Z9 19 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2011 VL 10 IS 3-4 BP 185 EP 193 DI 10.3233/CBM-2012-0245 PG 9 WC Oncology SC Oncology GA 957JK UT WOS:000305157500008 PM 22674304 ER PT J AU Cole, K Tabernero, M Anderson, KS AF Cole, Kimberly Tabernero, Maria Anderson, Karen S. TI Biologic characteristics of premalignant breast disease SO CANCER BIOMARKERS LA English DT Article DE Breast cancer; benign breast disease; biomarkers ID CARCINOMA-IN-SITU; ATYPICAL DUCTAL HYPERPLASIA; EPITHELIAL-MESENCHYMAL TRANSITION; COMPARATIVE GENOMIC HYBRIDIZATION; PLEOMORPHIC LOBULAR CARCINOMA; GENE-EXPRESSION SIGNATURE; SOUTHWEST-ONCOLOGY-GROUP; TERM-FOLLOW-UP; ESTROGEN-RECEPTOR; CANCER-CELLS AB Breast cancer is the second leading cause of cancer death in women in the United States. While mammography and breast magnetic resonance imaging (MRI) improve detection of early disease, there remains an unmet need for biomarkers for risk stratification, early detection, prediction, and disease prognosis. A number of early breast lesions, from atypical hyperplasias to carcinomas in situ, are associated with an increased risk of developing subsequent invasive breast carcinoma. The recent development of genomic, epigenomic, and proteomic tools for tissue biomarker detection, including array CGH, RNA expression microarrays, and proteomic arrays have identified a number of potential biomarkers that both identify patients at increased risk, as well as provided insights into the pathology of early breast cancer development. This chapter focuses on the detection and application of tissue and serum biomarkers for the identification and risk stratification of early breast cancer lesions. C1 [Anderson, Karen S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Cole, Kimberly] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Tabernero, Maria] Hosp Univ Salamanca, Lab Unidad Invest, Salamanca, Spain. RP Anderson, KS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, HIM 416,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM kanderson@partners.org RI 2011, Secribsal/D-9425-2012 FU NCI/Early Detection Research Network [5U01CA117374] FX This work is reproduced in part with permission from a review by Tabernero, Lv, and Anderson in Cancer Biomarkers, 2010. This work was supported in part by grants from the NCI/Early Detection Research Network (K.S.A.; 5U01CA117374). NR 202 TC 3 Z9 3 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2011 VL 9 IS 1-6 BP 177 EP 192 DI 10.3233/CBM-2011-0187 PG 16 WC Oncology SC Oncology GA 856ZB UT WOS:000297682300011 PM 22112476 ER PT J AU Park, BJ Chiosea, SI Grandis, JR AF Park, Brian J. Chiosea, Simion I. Grandis, Jennifer R. TI Molecular changes in the multistage pathogenesis of head and neck cancer SO CANCER BIOMARKERS LA English DT Article DE Head and neck cancer; molecular pathogenesis; squamous cell carcinoma; leukoplakia; premalignant; human papilloma virus ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; ORAL EPITHELIAL DYSPLASIA; COMPARATIVE GENOMIC HYBRIDIZATION; LYMPH-NODE METASTASIS; TYROSINE KINASE INHIBITOR; PHASE-II MULTICENTER; PREMALIGNANT LESIONS; LICHEN-PLANUS; MICROSATELLITE INSTABILITY AB Head and neck squamous cell carcinomas (SCCHN) arise in the mucosa of the upper aerodigestive tract at multiple anatomic sites. While tobacco and alcohol exposure remain the primary risk factors for this malignancy, infection with the human papilloma virus is emerging as a major contributing factor to cancers that arise primarily in the oropharynx. Despite therapeutic advances, survival has remained relatively unchanged over the past few decades. Increased understand of the cellular and molecular biology of these cancers will improve our understanding of this malignancy and facilitate the development of more effective therapeutic strategies. Alterations that have been studied to date include genetic and epigenetic changes. While the epidermal growth factor receptor (EGFR) is the only established molecular therapeutic target, other proteins and pathways are under active investigation to determine their contribution to SCCHN carcinogenesis and progression. C1 [Park, Brian J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Grandis, Jennifer R.] Univ Pittsburgh, Dept Otolaryngol, Inst Canc, Pittsburgh, PA 15260 USA. [Chiosea, Simion I.] Univ Pittsburgh, Dept Pathol, Inst Canc, Pittsburgh, PA USA. [Grandis, Jennifer R.] Univ Pittsburgh, Dept Pharmacol, Inst Canc, Pittsburgh, PA 15261 USA. RP Grandis, JR (reprint author), 200 Lothrop St,Eye & Ear Inst Bldg,Suite 500, Pittsburgh, PA 15213 USA. EM grandisjr@upmc.edu FU NIH [T32 CA060397, P50 CA097190]; American Cancer Society FX The authors of this work were supported by NIH grants T32 CA060397 and P50 CA097190 (to JRG) as well as an American Cancer Society Clinical Research Professorship (to JRG). NR 101 TC 4 Z9 4 U1 1 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2011 VL 9 IS 1-6 BP 325 EP 339 DI 10.3233/CBM-2011-0163 PG 15 WC Oncology SC Oncology GA 856ZB UT WOS:000297682300018 ER PT J AU Boffetta, P Jayaprakash, V Yang, P Asomaning, K Muscat, JE Schwartz, AG Zhang, ZF Le Marchand, L Cote, ML Stoddard, SM Morgenstern, H Hung, RJ Christiani, DC AF Boffetta, Paolo Jayaprakash, Vijayvel Yang, Ping Asomaning, Kofi Muscat, Joshua E. Schwartz, Ann G. Zhang, Zuo-Feng Le Marchand, Loic Cote, Michele L. Stoddard, Shawn M. Morgenstern, Hal Hung, Rayjean J. Christiani, David C. TI Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO) SO CANCER CAUSES & CONTROL LA English DT Article DE Lung cancer; Bronchioloalveolar carcinoma; Tobacco smoking ID K-RAS MUTATIONS; CIGARETTE-SMOKING; CELL-CARCINOMA; EPIDEMIOLOGY; ADENOCARCINOMA AB The International Lung Cancer Consortium (ILCCO) was established in 2004, based on the collaboration of research groups leading large molecular epidemiology studies of lung cancer that are ongoing or have been recently completed. This framework offered the opportunity to investigate the role of tobacco smoking in the development of bronchioloalveolar carcinoma (BAC), a rare form of lung cancer. Our pooled data comprised seven case-control studies from the United States, with detailed information on tobacco smoking and histology, which contributed 799 cases of BAC and 15,859 controls. We estimated the odds ratio of BAC for tobacco smoking, using never smokers as a referent category, after adjustment for age, sex, race, and study center. The odds ratio of BAC for ever smoking was 2.47 (95% confidence interval [CI] 2.08, 2.93); the risk increased linearly with duration, amount, and cumulative cigarette smoking and persisted long after smoking cessation. The proportion of BAC cases attributable to smoking was 0.47 (95% CI 0.39, 0.54). This analysis provides a precise estimate of the risk of BAC for tobacco smoking. C1 [Boffetta, Paolo] Int Prevent Res Inst, F-69006 Lyon, France. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Jayaprakash, Vijayvel] Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. [Yang, Ping; Stoddard, Shawn M.] Mayo Clin, Div Epidemiol, Rochester, MN USA. [Yang, Ping; Stoddard, Shawn M.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Asomaning, Kofi; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Muscat, Joshua E.] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA. [Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Zhang, Zuo-Feng] UCLA Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Le Marchand, Loic] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Morgenstern, Hal] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Hung, Rayjean J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Boffetta, P (reprint author), Int Prevent Res Inst, 95 Cours Lafayette, F-69006 Lyon, France. EM paolo.boffetta@i-pri.org RI Hung, Rayjean/A-7439-2013 FU NIH [R01CA60691, R01CA87895, N01PC35145, P30CA22453, R01CA074386, R01CA092824, P20CA090578, R01DA11386, R01CA90833, R01CA55874, CA 77118, CA 80127, CA 84354, CA-32617, CA-68384, CA-29580, CA-17613] FX The original studies were supported by the following grants: WSU1 and WSU2 studies: NIH R01CA60691, R01CA87895, N01PC35145, and P30CA22453; HU study: NIH R01CA074386, R01CA092824, and P20CA090578; UCLA study: NIH R01DA11386 and R01CA90833; UH study: NIH R01CA55874; Mayo study: NIH-CA 77118, NIH-CA 80127, and NIH-CA 84354; AHF study: NIH CA-32617, CA-68384, CA-29580, and CA-17613. NR 35 TC 7 Z9 7 U1 0 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 JAN PY 2011 VL 22 IS 1 BP 73 EP 79 DI 10.1007/s10552-010-9676-5 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 695HH UT WOS:000285360700008 PM 21072579 ER PT J AU Chan, JM Weinberg, V Magbanua, MJ Sosa, E Simko, J Shinohara, K Federman, S Mattie, M Hughes-Fulford, M Haqq, C Carroll, PR AF Chan, June M. Weinberg, Vivian Magbanua, Mark J. Sosa, Eduardo Simko, Jeffry Shinohara, Katsuto Federman, Scot Mattie, Mike Hughes-Fulford, Millie Haqq, Christopher Carroll, Peter R. TI Nutritional supplements, COX-2 and IGF-1 expression in men on active surveillance for prostate cancer SO CANCER CAUSES & CONTROL LA English DT Article DE Prostate cancer; Active surveillance; Fish oil; Lycopene; Randomized clinical trial ID FOOD FREQUENCY QUESTIONNAIRE; GROWTH-FACTOR SYSTEM; MARINE FATTY-ACIDS; LIFE-STYLE CHANGES; GENE-EXPRESSION; LYCOPENE SUPPLEMENTATION; ARACHIDONIC-ACID; DOUBLE-BLIND; FACTOR-I; RISK AB Nutritional factors are associated with reduced risk of prostate cancer progression, yet mechanisms remain unclear. We examined the effects of lycopene and fish oil supplements versus placebo on the normal prostate microenvironment, among men pursuing active surveillance for low-burden prostate cancer. We hypothesized that lycopene or fish oil supplements would down-regulate insulin-like growth factor-1 (IGF-1) and cyclooxygenase 2 (COX-2) gene expression, respectively, reflecting putative proliferation (IGF-1) and inflammatory (COX-2) pathways relevant to carcinogenesis. We conducted a 3-month randomized, double-blinded, clinical trial comparing prostate tissue gene expression profiles (assessed by qRT-PCR) among men with favorable-risk prostate cancer receiving either 30 mg/day lycopene, 3 g/day fish oil (including 1,098 mg eicosapentaenoic and 549 mg docosahexaenoic fatty acids) or placebo. Among 69 men (22 assigned to lycopene, 21 to fish, and 26 to placebo), there was no difference in the change from baseline to the 3 months in IGF-1 expression level between the placebo and lycopene arms (p = 0.93) nor in COX-2 expression between the placebo and fish arms (p = 0.99). Compared to placebo, 3-month intervention with lycopene or fish oil did not significantly change IGF-1 and COX-2 gene expression in the normal prostate microenvironment in men with low-burden prostate cancer. Further analysis of global gene expression profiles may shed light on the bioactivity and relevance of these nutrients in prostate cancer. C1 [Chan, June M.; Simko, Jeffry; Shinohara, Katsuto; Hughes-Fulford, Millie; Haqq, Christopher; Carroll, Peter R.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94158 USA. [Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA. [Chan, June M.; Magbanua, Mark J.; Sosa, Eduardo; Simko, Jeffry; Federman, Scot; Mattie, Mike; Carroll, Peter R.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA. [Weinberg, Vivian] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr Biostat C, San Francisco, CA 94158 USA. [Simko, Jeffry] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94158 USA. [Hughes-Fulford, Millie] San Francisco VA Med Ctr, San Francisco, CA USA. RP Chan, JM (reprint author), Univ Calif San Francisco, Dept Urol, MC 3110,1450 3rd St,POB 589001, San Francisco, CA 94158 USA. EM june.chan@ucsf.edu FU NCI NIH HHS [R01 CA101042, R01CA101042] NR 46 TC 21 Z9 22 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2011 VL 22 IS 1 BP 141 EP 150 DI 10.1007/s10552-010-9684-5 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 695HH UT WOS:000285360700016 PM 21103921 ER PT S AU Poulaki, V AF Poulaki, V. BE Cree, IA TI Angiogenesis Assays SO CANCER CELL CULTURE: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Angiogenesis; Endothelial cells; Co-culture; Fibroblasts; Matrigel; Retinopathy; Chorioallantoic membrane ID GROWTH; MOUSE; NEOVASCULARIZATION; RETINOPATHY; MEMBRANE; INVITRO; CELLS AB The angiogenic process is central in the pathogenesis of various diseases. The in vitro and in vivo monitoring of the neovascular process is essential for the development and evaluation of angiogenesis inhibitors or stimulators. Since no single method exists that can assess angiogenesis in a robust, reliable, and reproducible fashion, researchers often use a combination of assays to circumvent this problem. The experimental details of the most commonly in vitro, ex vivo, and in vivo assays are presented here. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, Boston, MA 02467 USA. RP Poulaki, V (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, Boston, MA 02467 USA. NR 25 TC 2 Z9 2 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-079-9 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 731 BP 345 EP 358 DI 10.1007/978-1-61779-080-5_28 D2 10.1007/978-1-61779-080-5 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BUV40 UT WOS:000290454900028 PM 21516420 ER PT J AU Wang, WL Conley, A Reynoso, D Nolden, L Lazar, AJ George, S Trent, JC AF Wang, Wei-Lien Conley, Anthony Reynoso, David Nolden, Laura Lazar, Alexander J. George, Suzanne Trent, Jonathan C. TI Mechanisms of resistance to imatinib and sunitinib in gastrointestinal stromal tumor SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE GIST; Mutated KIT; Imatinib-resistant disease; Gene mutations ID PROGRESSION-FREE SURVIVAL; SECONDARY KIT MUTATIONS; OF-FUNCTION MUTATIONS; BONE-SARCOMA-GROUP; EORTC-SOFT-TISSUE; C-KIT; TYROSINE KINASE; PHASE-II; ACQUIRED-RESISTANCE; THERAPEUTIC TARGET AB Gastrointestinal stromal tumor (GIST), the most common mesenchymal neoplasm of the GI tract and one of the most common sarcomas, is dependent on the expression of the mutated KIT or platelet-derived growth factor receptor in most cases. Imatinib mesylate potently abrogates the effects of KIT signaling by directly binding into the ATP-binding pocket of the kinase. It is becoming increasingly apparent that the binding affinity of imatinib for the receptor is dependent on the type and location of mutation. Within KIT, patients whose tumor has an exon 9 mutation are treated by many clinicians with higher doses of imatinib than those patients with mutations within exon 11. Additionally, there are over 400 unique mutations within exon 11 that may have distinctly different binding affinity for imatinib as well as other kinases. Secondary KIT mutations generally occur at a codon where imatinib binds resulting in KIT reactivation and resistance. Sunitinib malate, a second-generation KIT inhibitor is active in imatinib-resistant disease and is FDA-approved for use in this setting. In this review, we describe the biology of the genes and gene mutations responsible for GIST and discuss known and potential clinical implications. C1 [Conley, Anthony; Reynoso, David; Nolden, Laura; Trent, Jonathan C.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. [Wang, Wei-Lien; Lazar, Alexander J.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [George, Suzanne] Dana Farber Canc Inst, Ctr Soft Tissue & Bone Oncol, Boston, MA 02115 USA. RP Trent, JC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. EM jtrent@mdanderson.org RI Lazar, Alexander/A-3416-2008 OI Lazar, Alexander/0000-0002-6395-4499 FU Novartis FX Logistical support during submission of this article was provided by Springer Healthcare LLC. This support was funded by Novartis. NR 81 TC 30 Z9 33 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2011 VL 67 SU 1 SI SI BP 15 EP 24 DI 10.1007/s00280-010-1513-8 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 705GG UT WOS:000286116300004 ER PT J AU Haggerty, TJ Dunn, IS Rose, LB Newton, EE Martin, S Riley, JL Kurnick, JT AF Haggerty, Timothy J. Dunn, Ian S. Rose, Lenora B. Newton, Estelle E. Martin, Sunil Riley, James L. Kurnick, James T. TI Topoisomerase inhibitors modulate expression of melanocytic antigens and enhance T cell recognition of tumor cells SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Topoisomerase inhibitors; Immunotherapy; Melanoma; Melan-A/MART-1 ID DOWN-MODULATION; BETA-LAPACHONE; BREAST-CANCER; DNA-ADDUCTS; MELANOMA; THERAPY; CHEMOTHERAPY; ANTHRACYCLINES; TRANSCRIPTION; LYMPHOCYTES AB While there are many obstacles to immune destruction of autologous tumors, there is mounting evidence that tumor antigen recognition does occur. Unfortunately, immune recognition rarely controls clinically significant tumors. Even the most effective immune response will fail if tumors fail to express target antigens. Importantly, reduced tumor antigen expression often results from changes in gene regulation rather than irrevocable loss of genetic information. Such perturbations are often reversible by specific compounds or biological mediators, prompting a search for agents with improved antigen-enhancing properties. Some recent findings have suggested that certain conventional chemotherapeutic agents may have beneficial properties for cancer treatment beyond their direct cytotoxicities against tumor cells. Accordingly, we screened an important subset of these agents, topoisomerase inhibitors, for their effects on antigen levels in tumor cells. Our analyses demonstrate upregulation of antigen expression in a variety of melanoma cell lines and gliomas in response to nanomolar levels of certain specific topoisomerase inhibitors. To demonstrate the ability of CD8+ T cells to recognize tumors, we assayed cytokine secretion in T cells transfected with T cell receptors directed against Melan-A/MART-1 antigen. Three days of daunorubicin treatment resulted in enhanced antigen expression by tumor cells, in turn inducing co-cultured antigen-specific T cells to secrete Interleukin-2 and Interferon-gamma. These results demonstrate that specific topoisomerase inhibitors can augment melanoma antigen production, suggesting that a combination of chemotherapy and immunotherapy may be of potential value in the treatment of otherwise insensitive cancers. C1 [Haggerty, Timothy J.; Kurnick, James T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Haggerty, Timothy J.; Dunn, Ian S.; Rose, Lenora B.; Newton, Estelle E.; Kurnick, James T.] CytoCure LLC, Beverly, MA 01915 USA. [Martin, Sunil; Riley, James L.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Haggerty, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. EM thaggerty@cytocure.com RI Martin, Sunil /C-9300-2011; OI Riley, James/0000-0002-1057-576X FU NIH [R43-CA86153, R43-CA96271, R43-CA94700, R43-CA128309]; International Cancer Research Scholarship FX We thank Carl June for advice in use of the lentiviral T cell receptor system and helpful commentary on the manuscript. We also acknowledge Pedro Romero for provision of tetramers and assistance in improving the manuscript. This work was supported in part by grants from the NIH: R43-CA86153, R43-CA96271, R43-CA94700, R43-CA128309 and from the International Cancer Research Scholarship. NR 64 TC 7 Z9 7 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JAN PY 2011 VL 60 IS 1 BP 133 EP 144 DI 10.1007/s00262-010-0926-x PG 12 WC Oncology; Immunology SC Oncology; Immunology GA 712JF UT WOS:000286662100012 PM 21052994 ER PT J AU Issa, JPJ Garber, JE AF Issa, Jean-Pierre J. Garber, Judy E. TI Time to Think Outside the (Genetic) Box SO CANCER PREVENTION RESEARCH LA English DT Article ID BREAST-CANCER; PROMOTER METHYLATION; DNA METHYLATION; LYNCH SYNDROME; COLORECTAL-CANCER; RISK; INDIVIDUALS; PATHOLOGY; CARRIERS; BRCA1 AB Many patients develop cancers that have clinical features of inherited syndromes (e. g., young age of onset and unique pathology) but lack mutations in the genes characteristic of the disease. In this issue of the journal, Wong et al. report that somatic epigenetic inactivation could explain some such cases in the setting of BRCA1-associated breast cancer. Here, we discuss the implications of this work in terms of the etiology, risk, and potential prevention of cancer. Cancer Prev Res; 4(1); 6-8. (C) 2011 AACR. C1 [Issa, Jean-Pierre J.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Issa, JPJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd,Box 428, Houston, TX 77030 USA. EM jpissa@mdanderson.org; judy_garber@dfci.harvard.edu NR 27 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 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2011 VL 4 IS 1 BP 6 EP 8 DI 10.1158/1940-6207.CAPR-10-0348 PG 3 WC Oncology SC Oncology GA 702BS UT WOS:000285870200002 PM 21205738 ER PT J AU Dinh, TA Rosner, BI Atwood, JC Boland, CR Syngal, S Vasen, HFA Gruber, SB Burt, RW AF Dinh, Tuan A. Rosner, Benjamin I. Atwood, James C. Boland, C. Richard Syngal, Sapna Vasen, Hans F. A. Gruber, Stephen B. Burt, Randall W. TI Health Benefits and Cost-Effectiveness of Primary Genetic Screening for Lynch Syndrome in the General Population SO CANCER PREVENTION RESEARCH LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; DNA-MISMATCH-REPAIR; POLICY STATEMENT UPDATE; MSH6 GERMLINE MUTATIONS; ADJUSTED LIFE-YEAR; FAMILY-HISTORY; ENDOMETRIAL CARCINOMA; GYNECOLOGIC CANCERS; TESTING STRATEGIES; PREVENTIVE-SERVICES AB In current clinical practice, genetic testing to detect Lynch syndrome mutations ideally begins with diagnostic testing of an individual affected with cancer before offering predictive testing to at-risk relatives. An alternative strategy that warrants exploration involves screening unaffected individuals via demographic and family histories, and offering genetic testing to those individuals whose risks for carrying a mutation exceed a selected threshold. Whether this approach would improve health outcomes in a manner that is cost-effective relative to current standards of care has yet to be demonstrated. To do so, we developed a simulation framework that integrated models of colorectal and endometrial cancers with a 5-generation family history model to predict health and economic outcomes of 20 primary screening strategies (at a wide range of compliance levels) aimed at detecting individuals with mismatch repair gene mutations and their at-risk relatives. These strategies were characterized by (i) different screening ages for starting risk assessment and (ii) different risk thresholds above which to implement genetic testing. For each strategy, 100,000 simulated individuals, representative of the U. S. population, were followed from the age of 20, and the outcomes were compared with current practice. Findings indicated that risk assessment starting at ages 25, 30, or 35, followed by genetic testing of those with mutation risks exceeding 5%, reduced colorectal and endometrial cancer incidence in mutation carriers by approximately 12.4% and 8.8%, respectively. For a population of 100,000 individuals containing 392 mutation carriers, this strategy increased quality-adjusted life-years (QALY) by approximately 135 with an average cost-effectiveness ratio of $26,000 per QALY. The cost-effectiveness of screening for mismatch repair gene mutations is comparable to that of accepted cancer screening activities in the general population such as colorectal cancer screening, cervical cancer screening, and breast cancer screening. These results suggest that primary screening of individuals for mismatch repair gene mutations, starting with risk assessment between the ages of 25 and 35, followed by genetic testing of those whose risk exceeds 5%, is a strategy that could improve health outcomes in a cost-effective manner relative to current practice. Cancer Prev Res; 4(1): 9-22. (C) 2010 AACR. C1 [Gruber, Stephen B.] Univ Michigan, Div Mol Med & Genet, Ann Arbor, MI 48109 USA. [Dinh, Tuan A.; Rosner, Benjamin I.; Atwood, James C.] Archimedes Inc, San Francisco, CA USA. [Boland, C. Richard] Baylor Univ, Med Ctr, Sammons Canc Ctr, GI Canc Res Lab, Dallas, TX USA. [Syngal, Sapna] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Vasen, Hans F. A.] Leiden Univ, Med Ctr, Dept Gastroenterol & Hepatol, Leiden, Netherlands. [Burt, Randall W.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. RP Gruber, SB (reprint author), Univ Michigan, Div Mol Med & Genet, 1524 BSRB,109 Zina Pitcher, Ann Arbor, MI 48109 USA. EM sgruber@med.umich.edu FU Myriad Genetic Laboratories, Inc. FX This study was carried out by Archimedes, Inc., and its academic collaborators under grant support from Myriad Genetic Laboratories, Inc. NR 81 TC 74 Z9 74 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JAN PY 2011 VL 4 IS 1 BP 9 EP 22 DI 10.1158/1940-6207.CAPR-10-0262 PG 14 WC Oncology SC Oncology GA 702BS UT WOS:000285870200003 PM 21088223 ER PT J AU di Tomaso, E Snuderl, M Kamoun, WS Duda, DG Auluck, PK Fazlollahi, L Andronesi, OC Frosch, MP Wen, PY Plotkin, SR Hedley-Whyte, ET Sorensen, AG Batchelor, TT Jain, RK AF di Tomaso, Emmanuelle Snuderl, Matija Kamoun, Walid S. Duda, Dan G. Auluck, Pavan K. Fazlollahi, Ladan Andronesi, Ovidiu C. Frosch, Matthew P. Wen, Patrick Y. Plotkin, Scott R. Hedley-Whyte, E. Tessa Sorensen, A. Gregory Batchelor, Tracy T. Jain, Rakesh K. TI Glioblastoma Recurrence after Cediranib Therapy in Patients: Lack of "Rebound" Revascularization as Mode of Escape SO CANCER RESEARCH LA English DT Article ID HIGH-GRADE GLIOMA; TUMOR ANGIOGENESIS; BRAIN-TUMORS; VEGF; GROWTH; INVASION; HYPOXIA; ANGIOPOIETINS; BEVACIZUMAB; RECRUITMENT AB Recurrent glioblastomas (rGBM) invariably relapse after initial response to anti-VEGF therapy. There are 2 prevailing hypotheses on how these tumors escape antiangiogenic therapy: switch to VEGF-independent angiogenic pathways and vessel co-option. However, direct evidence in rGBM patients is lacking. Thus, we compared molecular, cellular, and vascular parameters in autopsy tissues from 5 rGBM patients who had been treated with the pan-VEGF receptor tyrosine kinase inhibitor cediranib versus 7 patients who received no therapy or chemoradiation but no antiangiogenic agents. After cediranib treatment, endothelial proliferation and glomeruloid vessels were decreased, and vessel diameters and perimeters were reduced to levels comparable to the unaffected contralateral brain hemisphere. In addition, tumor endothelial cells expressed molecular markers specific to the blood-brain barrier, indicative of a lack of revascularization despite the discontinuation of therapy. Surprisingly, in cediranib-treated GBM, cellular density in the central area of the tumor was lower than in control cases and gradually decreased toward the infiltrating edge, indicative of a change in growth pattern of rGBMs after cediranib treatment, unlike that after chemoradiation. Finally, cediranib-treated GBMs showed high levels of PDGF-C (platelet-derived growth factor C) and c-Met expression and infiltration by myeloid cells, which may potentially contribute to resistance to anti-VEGF therapy. In summary, we show that rGBMs switch their growth pattern after anti-VEGF therapy-characterized by lower tumor cellularity in the central area, decreased pseudopalisading necrosis, and blood vessels with normal molecular expression and morphology-without a second wave of angiogenesis. Cancer Res; 71(1); 19-28. (C) 2011 AACR. C1 [Jain, Rakesh K.] Massachusetts Gen Hosp, Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. [Snuderl, Matija; Auluck, Pavan K.; Fazlollahi, Ladan; Frosch, Matthew P.; Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. [Andronesi, Ovidiu C.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Andronesi, Ovidiu C.; Sorensen, A. Gregory] MIT, Boston, MA USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Plotkin, Scott R.; Batchelor, Tracy T.] Harvard Univ, Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Sch Med,Dept Neurol, Boston, MA USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Steele Lab, Dept Radiat Oncol, COX 734,100 Blossom St, Boston, MA 02114 USA. EM Jain@steele.mgh.harvard.edu RI leng, xianwei/F-9073-2011; OI Snuderl, Matija/0000-0003-0752-0917 FU NIH [P01-CA80124, R01-CA115767, R21-CA117079, K24-CA125440, R01-CA129371, P41-RR014075, M01-RR-01066]; Harvard Clinical and Translational Science Center GCRC; National Foundation for Cancer Research; Montesi Family Research Fund; NIH (Federal Share/NCI Proton Beam Program Income) FX This study was partially supported by grants from NIH (P01-CA80124, R01-CA115767, R21-CA117079, K24-CA125440, R01-CA129371, P41-RR014075, M01-RR-01066, and Federal Share/NCI Proton Beam Program Income) and from Harvard Clinical and Translational Science Center GCRC, National Foundation for Cancer Research, and the Montesi Family Research Fund. NR 30 TC 88 Z9 89 U1 0 U2 8 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 JAN PY 2011 VL 71 IS 1 BP 19 EP 28 DI 10.1158/0008-5472.CAN-10-2602 PG 10 WC Oncology SC Oncology GA 701NW UT WOS:000285826800004 PM 21199795 ER PT J AU Bagci-Onder, T Wakimoto, H Anderegg, M Cameron, C Shah, K AF Bagci-Onder, Tugba Wakimoto, Hiroaki Anderegg, Maarten Cameron, Cody Shah, Khalid TI A Dual PI3K/mTOR Inhibitor, PI-103, Cooperates with Stem Cell-Delivered TRAIL in Experimental Glioma Models SO CANCER RESEARCH LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE INHIBITION; IN-VIVO; INDUCED APOPTOSIS; S-TRAIL; PYRIDINYLFURANOPYRIMIDINE INHIBITOR; MALIGNANT GLIOMAS; TUMOR-REGRESSION; GLIOBLASTOMA; EFFICACY; THERAPY AB The resistance of glioma cells to a number of antitumor agents and the highly invasive nature of glioma cells that escape the primary tumor mass are key impediments to the eradication of tumors in glioma patients. In this study, we evaluated the therapeutic efficacy of a novel PI3-kinase/mTOR inhibitor, PI-103, in established glioma lines and primary CD133(+) glioma-initiating cells and explored the potential of combining PI-103 with stem cell-delivered secretable tumor necrosis factor apoptosis-inducing ligand (S-TRAIL) both in vitro and in orthotopic mouse models of gliomas. We show that PI-103 inhibits proliferation and invasion, causes G(0)-G(1) arrest in cell cycle, and results in significant attenuation of orthotopic tumor growth in vivo. Establishing cocultures of neural stem cells (NSC) and glioma cells, we show that PI-103 augments the response of glioma cells to stem cell-delivered S-TRAIL. Using bimodal optical imaging, we show that when different regimens of systemic PI-103 delivery are combined with NSC-derived S-TRAIL, a significant reduction in tumor volumes is observed compared with PI-103 treatment alone. To our knowledge, this is the first study that reveals the antitumor effect of PI-103 in intracranial gliomas. Our findings offer a preclinical rationale for application of mechanism-based systemically delivered antiproliferative agents and novel stem cell-based proapoptotic therapies to improve treatment of malignant gliomas. Cancer Res; 71(1); 154-63. (C) 2010 AACR. C1 [Bagci-Onder, Tugba; Anderegg, Maarten; Cameron, Cody; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA USA. [Bagci-Onder, Tugba; Anderegg, Maarten; Cameron, Cody; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Wakimoto, Hiroaki] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM kshah@helix.mgh.harvard.edu FU American Cancer Society; Alliance for Cancer Gene Therapy FX This work was supported by American Cancer Society (K. Shah) and Alliance for Cancer Gene Therapy (K. Shah). NR 38 TC 50 Z9 51 U1 0 U2 10 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 JAN PY 2011 VL 71 IS 1 BP 154 EP 163 DI 10.1158/0008-5472.CAN-10-1601 PG 10 WC Oncology SC Oncology GA 701NW UT WOS:000285826800018 PM 21084267 ER PT J AU Singh, T Vaid, M Katiyar, N Sharma, S Katiyar, SK AF Singh, Tripti Vaid, Mudit Katiyar, Nandan Sharma, Samriti Katiyar, Santosh K. TI Berberine, an isoquinoline alkaloid, inhibits melanoma cancer cell migration by reducing the expressions of cyclooxygenase-2, prostaglandin E-2 and prostaglandin E-2 receptors SO CARCINOGENESIS LA English DT Article ID GRAPE SEED PROANTHOCYANIDINS; MOUSE SKIN; INFLAMMATORY RESPONSES; CUTANEOUS MELANOMA; GUANYLATE-CYCLASE; CARCINOMA-CELLS; NITRIC-OXIDE; LUNG-CANCER; APOPTOSIS; ARREST AB Melanoma is the leading cause of death from skin disease due, in large part, to its propensity to metastasize. We have examined the effect of berberine, an isoquinoline alkaloid, on human melanoma cancer cell migration and the molecular mechanisms underlying these effects using melanoma cell lines, A375 and Hs294. Using an in vitro cell migration assay, we show that over expression of cyclooxygenase (COX)-2, its metabolite prostaglandin E-2 (PGE(2)) and PGE(2) receptors promote the migration of cells. We found that treatment of A375 and Hs294 cells with berberine resulted in concentration-dependent inhibition of migration of these cells, which was associated with a reduction in the levels of COX-2, PGE(2) and PGE(2) receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, or transient transfection of cells with COX-2 small interfering RNA, also inhibited cell migration. Treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an inducer of COX-2 or PGE(2), enhanced cell migration, whereas berberine inhibited TPA- or PGE(2)-promoted cell migration. Berberine reduced the basal levels as well as PGE(2)-stimulated expression levels of EP2 and EP4. Treatment of the cells with the EP4 agonist stimulated cell migration and berberine blocked EP4 agonist-induced cell migration activity. Moreover, berberine inhibited the activation of nuclear factor-kappa B (NE-kappa B), an upstream regulator of COX-2, in A375 cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NE-kappa B, inhibited cell migration. Together, these results indicate for the first time that berberine inhibits melanoma cell migration, an essential step in invasion and metastasis, by inhibition of COX-2, PGE(2) and PGE(2) receptors. C1 [Singh, Tripti; Vaid, Mudit; Katiyar, Nandan; Sharma, Samriti; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Katiyar, Santosh K.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU Veterans Administration FX Veterans Administration Merit Review Award to S.K.K. NR 29 TC 72 Z9 76 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2011 VL 32 IS 1 BP 86 EP 92 DI 10.1093/carcin/bgq215 PG 7 WC Oncology SC Oncology GA 707RF UT WOS:000286303000014 PM 20974686 ER PT J AU Milo-Cotter, O Cotter-Davison, B Lombardi, C Sun, HR Bettari, L Bugatti, S Rund, M Metra, M Kaluski, E Kobrin, I Frey, A Rainisio, M McMurray, JJV Teerlink, JR Cotter-Davison, G AF Milo-Cotter, Olga Cotter-Davison, Beth Lombardi, Carlo Sun, Hengrui Bettari, Luca Bugatti, Silvia Rund, Michele Metra, Marco Kaluski, Edo Kobrin, Isaac Frey, Aline Rainisio, Maurizio McMurray, John J. V. Teerlink, John R. Cotter-Davison, Gad TI Neurohormonal Activation in Acute Heart Failure: Results from VERITAS SO CARDIOLOGY LA English DT Article DE Heart failure; Inflammation; Prognosis ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; NATRIURETIC PEPTIDE; MYOCARDIAL-INFARCTION; PROGNOSTIC VALUE; CYTOKINES; TROPONIN; TRIAL; INTERLEUKIN-6; ENDOTHELIN-1 AB Objectives: Recent heart failure studies have suggested that inflammatory and immune system activation are associated with increased levels of cytokines, chemokines and inflammatory proteins during acutely decompensated heart failure. The objectives of this substudy were to evaluate the role of neurohormonal and inflammatory activation in the pathogenesis and outcome of acute heart failure (AHF) and the correlation between biomarker levels and clinical outcomes. Methods: Serum levels of B-type natriuretic peptide-32 (BNP-32), endothelin-1 (ET-1), norepinephrine, troponins I and T, C-reactive protein (CRP), von Willebrand factor, plasminogen activator inhibitor-1, interleukin-6 (IL-6) and tissue plasminogen activator (TPA) were measured at baseline, 24 and 48 h and 7 and 30 days in 112 patients with AHF recruited to the Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure Study neurohormonal substudy. Results: On univariable analysis, CRP, BNP and ET-1 were predictive of worsening heart failure by day 30; when considered together, only CRP and BNP were significantly associated with this outcome. On adjustment for age, baseline blood pressure, serum sodium and serum creatinine, only age and BNP remained significant. CRP, IL-6 and TPA levels were significantly correlated with 180-day mortality on univariable analysis. Conclusion: Circulating markers of inflammation may be useful in gauging prognosis in patients with AHF. Copyright (C) 2011 S. Karger AG, Basel C1 [Milo-Cotter, Olga; Cotter-Davison, Beth; Sun, Hengrui; Rund, Michele; Cotter-Davison, Gad] Momentum Res Inc, Durham, NC 27707 USA. [Kaluski, Edo] Univ Med & Dent New Jersey, Cardiac Catheterizat Labs, Dept Cardiol, Newark, NJ 07103 USA. [Teerlink, John R.] Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Lombardi, Carlo; Bettari, Luca; Bugatti, Silvia; Metra, Marco] Univ Brescia, Brescia, Italy. [Rainisio, Maurizio] AbaNovus Srl, San Remo, Italy. [Kobrin, Isaac; Frey, Aline] Actel Pharmaceut, Allschwil, Switzerland. [McMurray, John J. V.] Univ Glasgow, Glasgow, Lanark, Scotland. RP Milo-Cotter, O (reprint author), Momentum Res Inc, 3100 Tower Blvd,Suite 802, Durham, NC 27707 USA. EM olgacotter@momentum-research.com RI Teerlink, John/D-2986-2012; lombardi, carlo /O-2130-2013; OI lombardi, carlo /0000-0002-7120-5877; Davison, Beth/0000-0003-2374-6449; Metra, Marco/0000-0001-6691-8568; mcmurray, john/0000-0002-6317-3975; Kaluski, Edo/0000-0002-1400-3988 FU Actelion Pharmaceuticals Ltd., Allschwil, Switzerland; Momentum Research Inc., Durham, N.C., USA; Actelion FX The conduct of this substudy was supported by Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. Analysis and manuscript preparation were supported by Momentum Research Inc., Durham, N.C., USA.; Drs. Milo-Cotter, Cotter-Davison and Sun are employees of Momentum Research Inc., which has provided consulting and trial management services to Novacardia, Merck, Nile Therapeutics, Bioheart, Celladon, Corthera and Novartis. Drs. Kobrin and Frey are employees of Actelion. Dr. Rainisio was an employee of Actelion at the time the study was conducted. Drs. McMurray and Teerlink received research grants from Actelion, the sponsor of the study. NR 33 TC 21 Z9 21 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2011 VL 119 IS 2 BP 96 EP 105 DI 10.1159/000330409 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 824KR UT WOS:000295201300006 PM 21912122 ER PT J AU Durst, R Lotan, C AF Durst, Ronen Lotan, Chaim TI The Potential for Clinical Use of Cannabinoids in Treatment of Cardiovascular Diseases SO CARDIOVASCULAR THERAPEUTICS LA English DT Review DE Arrhythmia; Cannabinoids; Cardiomyopathy; Ischemic heart disease; preconditioning ID ISCHEMIA-REPERFUSION INJURY; REGIONAL HEMODYNAMIC-RESPONSES; ENDOGENOUS CANNABINOIDS; MYOCARDIAL-ISCHEMIA; MESENTERIC VASODILATION; ENDOCANNABINOID SYSTEM; INDUCED HYPOTENSION; CORONARY-OCCLUSION; BRAIN CONSTITUENT; HEART RESISTANCE AB P>Cannabinoids, the constituents of the marijuana plant and their analogs, have not only neurobehavioral but also cardiovascular effects. Great advances in the last couple of decades have led to better understanding of the physiological effects of the cannabinoids and of their role in various cardiovascular pathologies. The potential therapeutic use of cannabinoids in various cardiac diseases, such as ischemic injury, heart failure, and cardiac arrhythmias, has been studied in animal models. The purpose of this article is to review the physiological cardiovascular properties of cannabinoids and to summarize the knowledge related to their potential therapeutic use. C1 [Durst, Ronen] Hadassah Hebrew Univ, Div Cardiol, Med Ctr, Jerusalem, Israel. [Lotan, Chaim] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Durst, R (reprint author), Hadassah Hebrew Univ, Div Cardiol, Med Ctr, Jerusalem, Israel. EM rdurst@partners.org NR 67 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5914 J9 CARDIOVASC THER JI Cardiovasc. Ther. PY 2011 VL 29 IS 1 BP 17 EP 22 DI 10.1111/j.1755-5922.2010.00233.x PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 706NQ UT WOS:000286225500003 PM 20946323 ER PT J AU Basile, JN AF Basile, Jan N. TI The role of vasodilating beta-blockers in controlling arterial hypertension as a means of reducing cardiovascular and stroke risk SO CARDIOVASCULAR THERAPY AND PREVENTION LA Russian DT Review DE beta-blockers; efficacy; hypertension; nebivolol; tolerability; vasodilating beta-blockers ID RANDOMIZED CONTROLLED-TRIAL; BLOOD-PRESSURE; 1ST-LINE THERAPY; HEART-FAILURE; NITRIC-OXIDE; NEBIVOLOL; METOPROLOL; ATENOLOL; CARVEDILOL; PREVENTION AB beta-blockers have played a key role in the management of hypertension-related cardiovascular disease for decades, and continue to be recommended as a mainstay of therapy in national guidelines statements. Recent data have shown less optimal reductions in total mortality, CVD mortality, and CVD events with beta-blockers compared with renin-angiotensin system-blocking agents or calcium channel blockers. The beta-blocker class, however, spans a wide range of agents, and the growing concern about the risk-benefit profile of beta-blockers should not be generalized to later-generation vasodilating beta-blockers such as carvedilol and nebivolol. A growing database from hypertension studies confirms the clinical efficacy and safety of vasodilating beta-blockers, and outcome studies indicate that these agents can play an important role in global CVD reduction in patients with hypertensive or ischemic heart failure. C1 [Basile, Jan N.] Med Univ S Carolina, Coll Med, Seinsheimer Cardiovasc Hlth Program, Charleston, SC 29425 USA. [Basile, Jan N.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Basile, JN (reprint author), Med Univ S Carolina, Coll Med, Seinsheimer Cardiovasc Hlth Program, Charleston, SC 29425 USA. NR 39 TC 0 Z9 0 U1 0 U2 0 PU SILICEA-POLIGRAF PI MOSCOW PA KASHIRSKOJE SH 24 A/JA 509, MOSCOW, 115478, RUSSIA SN 1728-8800 J9 CARDIOVASC THER PREV JI Cardiovasc. Ther. Prevent. PY 2011 VL 10 IS 3 BP 97 EP 102 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 751EP UT WOS:000289600600017 ER PT J AU Bakris, GL Basile, JN Giles, TD Taylor, AA AF Bakris, G. L. Basile, J. N. Giles, T. D. Taylor, A. A. TI The role of nitric oxide in improving endothelial function andcardiovascular health: focus on nebivolor SO CARDIOVASCULAR THERAPY AND PREVENTION LA Russian DT Review DE beta-blockers; endothelial function; hypertension; nebivolol; nitric oxide; vasodilating beta-blockers ID DEPENDENT VASCULAR RELAXATION; VASODILATING BETA-BLOCKERS; CENTRAL AORTIC PRESSURE; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; ERECTILE DYSFUNCTION; INSULIN-RESISTANCE; RANDOMIZED-TRIAL; HEART-FAILURE AB Although beta-blockers have been endorsed by guidelines committees for the treatment of patients with hypertension, particularly those with significant CVD and high CVD risk, there are concerns about conventional beta-blockers related to poorer clinical outcomes compared with other classes of antihypertensive agents, as well as deleterious effects on quality of life and lipid and carbohydrate metabolism. beta-blockers comprise a heterogeneous group of antihypertensive agents, including nonselective agents, cardioselective, nonvasodilating agents, and vasodilating agents that either combine beta-nonselectivity with beta-blockade or possess cardioselectivity without beta-blockade. The pharmacologic, mechanistic, and hemodynamic differences between conventional, nonvasodilating beta-blockers and vasodilating beta-blockers are discussed in this review, with a focus on the cardioselective vasodilating beta-blocker nebivolol. These differences may have important clinical implications, particularly in the treatment of complicated hypertension, such as that associated with patients with diabetes or cardiometabolic syndrome, elderly patients, and African American patients, suggesting that mechanism of action may be an important consideration when choosing a beta-blocker. C1 [Bakris, G. L.] Univ Chicago, Med Ctr, Dept Med, Hypertens Dis Unit, Chicago, IL 60637 USA. [Basile, J. N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Coll Med, Charleston, SC USA. [Giles, T. D.] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. [Taylor, A. A.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Taylor, A. A.] Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. [Taylor, A. A.] Baylor Coll Med, Dept Mol Physiol, Houston, TX 77030 USA. RP Bakris, GL (reprint author), Univ Chicago, Med Ctr, Dept Med, Hypertens Dis Unit, Chicago, IL 60637 USA. NR 41 TC 0 Z9 0 U1 0 U2 1 PU SILICEA-POLIGRAF PI MOSCOW PA KASHIRSKOJE SH 24 A/JA 509, MOSCOW, 115478, RUSSIA SN 1728-8800 J9 CARDIOVASC THER PREV JI Cardiovasc. Ther. Prevent. PY 2011 VL 10 IS 2 BP 116 EP 121 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 770HL UT WOS:000291077500020 ER PT J AU Parisotto, TM King, WF Duque, C Mattos-Graner, RO Steiner-Oliveira, C Nobre-dos-Santos, M Smith, DJ AF Parisotto, T. M. King, W. F. Duque, C. Mattos-Graner, R. O. Steiner-Oliveira, C. Nobre-dos-Santos, M. Smith, D. J. TI Immunological and Microbiologic Changes during Caries Development in Young Children SO CARIES RESEARCH LA English DT Article DE Caries increment; Children; Immunology; Longitudinal study; Microbiology ID MUTANS STREPTOCOCCAL GLUCOSYLTRANSFERASE; GLUCAN-BINDING PROTEIN; EARLY-CHILDHOOD CARIES; IMMUNOGLOBULIN-A RESPONSES; DENTAL-CARIES; SECRETORY IMMUNITY; BRAZILIAN CHILDREN; PEPTIDE CONSTRUCTS; ORAL COLONIZATION; SUGAR EXPOSURE AB We explored the association between caries development, colonization with caries-associated microflora, and immunity as children begin the transition to mixed dentition. Forty children received dental examinations at 3-4 years of age, repeated a year later. Children were grouped into caries-free (n = 23; CF) and caries-active (n = 17; CA >= 3 new lesions on follow-up). Salivary IgA and IgA antibody to Streptococcus mutans virulence epitopes were measured by Luminex assay. Mutans streptococci (MS), lactobacilli and total microorganisms were enumerated on selective media from plaque samples. There was no significant difference in baseline levels of MS or lactobacilli between CF and CA groups. However, both MS and lactobacilli levels were higher at follow-up in the CA group. Furthermore, children with detectable lactobacilli at baseline had significantly higher caries risk. Salivary IgA concentrations increased significantly in both groups during the study. Both CF and CA groups also displayed significant increases in salivary IgA antibody levels to glucosyltransferase, glucan-binding protein (Gbp) and antigen I/II salivary binding region. CF antibody levels to seven peptides associated with domains of biological importance increased at follow-up, in contrast to increases to only three peptides in CA saliva samples. Multivariate modeling showed that a lower baseline level of salivary IgA anti-GbpB was associated with higher caries risk. These data indicate that MS and lactobacilli are associated with caries in this population, that the secretory immune system is undergoing significant maturation during this period, and that the breadth of mucosal IgA response to epitopes of S. mutans virulence components may influence the degree to which these cariogenic microorganisms can cause disease. Copyright (C) 2011 S. Karger AG, Basel C1 [Parisotto, T. M.; Duque, C.; Mattos-Graner, R. O.; Steiner-Oliveira, C.; Nobre-dos-Santos, M.] Univ Estadual Campinas, Piracicaba Dent Sch, Piracicaba, Brazil. [King, W. F.; Smith, D. J.] Forsyth Inst, Boston, MA USA. RP Nobre-dos-Santos, M (reprint author), Av Limeira 901, BR-13414903 Piracicaba, SP, Brazil. EM nobre@fop.unicamp.br RI Mattos-Graner, Renata/C-9410-2012; Duque, Cristiane/G-9505-2012; Steiner-Oliveira, Carolina/C-9899-2013; Parisotto, Thais/B-3574-2015 OI Mattos-Graner, Renata/0000-0001-8309-8135; Steiner-Oliveira, Carolina/0000-0002-0680-2253; FU FAPESP [2008/09510-3]; CNPq [480401/2008-0]; DE [04733] FX We thank the Secretary of Education and Health of Itatiba-SP/Brazil for collaborating with this research, as well as all the children who took part in this study. We also thank FAPESP (2008/09510-3), CNPq (480401/2008-0) and DE (04733) for financial support. NR 72 TC 14 Z9 15 U1 2 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PY 2011 VL 45 IS 4 BP 377 EP 385 DI 10.1159/000330230 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 809IT UT WOS:000294046500007 PM 21822016 ER PT J AU Cruz-Gonzalez, I Jneid, H Sanchez-Ledesma, M Cubeddu, RJ Martin-Moreiras, J Rengifo-Moreno, P Diaz, TA Kiernan, TJ Inglessis-Azuaje, I Maree, AO Sanchez, PL Palacios, IF AF Cruz-Gonzalez, Ignacio Jneid, Hani Sanchez-Ledesma, Maria Cubeddu, Roberto J. Martin-Moreiras, Javier Rengifo-Moreno, Pablo Diaz, Tullio A. Kiernan, Thomas J. Inglessis-Azuaje, Ignacio Maree, Andrew O. Sanchez, Pedro L. Palacios, Igor F. TI Difference in Outcome Among Women and Men After Percutaneous Mitral Valvuloplasty SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE VALV; valvular heart disease; mitral stenosis; mitral valvuloplasty ID VALVULAR HEART-DISEASE; BALLOON VALVOTOMY; IMMEDIATE; VARIABLES; STENOSIS; VALVE AB Objective: To analyze the differences in anatomical, clinical and echocardiographic characteristics of women and men undergoing PMV and to evaluate the relationship between sex, PMV success, and immediate and long-term clinical outcome. Background: Rheumatic mitral stenosis (MS) is predominantly a disease of middle-aged women. Percutaneous mitral valvuloplasty (PMV) has become the standard of care for suitable patients. However little is known about the relationship between sex, PMV success, and procedural outcome. Methods and results: We evaluated measures of procedural success and clinical outcome in consecutive patients (839 women and 176 men) who underwent PMV. Despite a lower baseline echocardiographic score (7.47 +/- 2.15 vs. 8.02 +/- 2.18, P = 0.002), women were less likely to achieve PMV success (69% vs. 83%, adjusted OR 0.44, 95% CI 0.27-0.74, P 5 0.002), and had a smaller post-procedural MV area (1.86 +/- 0.7 vs. 2.07 +/- 0.7 cm(2), P < 0.001). Overall procedural and in-hospital complication rates did not differ significantly between women and men. However, women were significantly more likely to develop severe MR immediately post PMV (adjusted OR 2.41, 95% CI 1.0-5.83, P = 0.05) and to undergo MV surgery (adjusted HR 1.54, 95% CI 1.03-2.3, P = 0.037) after a median follow-up of 3.1 years. Conclusions: Compared to men, women with rheumatic MS who undergo PMV are less likely to have a successful outcome and more likely to require MV surgery on long-term follow-up despite more favorable baseline MV anatomy. (C) 2010 Wiley-Liss, Inc. C1 [Cruz-Gonzalez, Ignacio; Jneid, Hani; Sanchez-Ledesma, Maria; Cubeddu, Roberto J.; Rengifo-Moreno, Pablo; Kiernan, Thomas J.; Inglessis-Azuaje, Ignacio; Maree, Andrew O.; Palacios, Igor F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Cruz-Gonzalez, Ignacio; Sanchez-Ledesma, Maria; Martin-Moreiras, Javier] Univ Hosp Salamanca, Div Cardiol, Salamanca, Spain. [Diaz, Tullio A.] St Elizabeths Med Ctr, Boston, MA USA. [Sanchez, Pedro L.] Univ Hosp Gregorio Maranon, Div Cardiol, Madrid, Spain. RP Cruz-Gonzalez, I (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM cruzgonzalez.ignacio@gmail.com RI 2011, Secribsal/D-9425-2012; OI Sanchez, Pedro L/0000-0002-4288-345X FU Spanish Society of Cardiology; Medtronic Iberia S.A.; University Hospital of Salamanca; Cardiovascular network RECAVA; Instituto Carlos III; Spanish Ministry of Health and Science FX Grant sponsors: Spanish Society of Cardiology (Hemodynamic section and Post-fellowship research grant 2007), Medtronic Iberia S.A., University Hospital of Salamanca, Cardiovascular network RECAVA, Instituto Carlos III, Spanish Ministry of Health and Science. NR 16 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JAN 1 PY 2011 VL 77 IS 1 BP 115 EP 120 DI 10.1002/ccd.22721 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 700UO UT WOS:000285770000027 PM 21053355 ER PT J AU Garcia, S Rider, JE Moritz, TE Pierpont, G Goldman, S Larsen, GC Shunk, K Littooy, F Santilli, S Rapp, J Reda, DJ Ward, HB McFalls, EO AF Garcia, Santiago Rider, James E. Moritz, Thomas E. Pierpont, Gordon Goldman, Steven Larsen, Greg C. Shunk, Kendrick Littooy, Fred Santilli, Steven Rapp, Joseph Reda, Domenic J. Ward, Herbert B. McFalls, Edward O. TI Preoperative Coronary Artery Revascularization and Long-Term Outcomes Following Abdominal Aortic Vascular Surgery in Patients with Abnormal Myocardial Perfusion Scans: A Subgroup Analysis of the Coronary Artery Revascularization Prophylaxis Trial SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE percutaneous coronary intervention; peripheral vascular disease; diagnostic cardiac catheterization ID PERIOPERATIVE CARDIOVASCULAR EVALUATION; HIGH-RISK PATIENTS; CARDIAC RISK; NONCARDIAC SURGERY; CARP TRIAL; INFARCTION; INDEX; DISEASE AB Background: Abdominal aortic operations have the highest perioperative cardiac risk. To test the impact of preoperative coronary artery revascularization (PR) in this high-risk subset, a post hoc analysis was performed in patients undergoing aortic surgery within the Coronary Artery Revascularization Prophylaxis (CARP) trial. Methods: The study cohort was a subset of 109 CARP patients with myocardial ischemia on nuclear imaging randomized to a strategy of PR (N = 52) or no PR (N = 57) before their scheduled abdominal aortic vascular operation. The clinical indications for vascular surgery were an expanding aneurysm (N = 62) or severe claudication (N = 47). The composite end-point of death and nonfatal myocardial infarction (MI) was determined by an intention-to-treat analysis following randomization. Results: The median time (Interquartiles) from randomization to vascular surgery was 56 (40, 81) days in patients assigned to PR and 19 (10, 43) days in patients assigned to no PR (P < 0.001). At 2.7 years following randomization, the probability of remaining free of death and nonfatal MI was 0.65 with PR and 0.55 with no PR [unadjusted P = 0.08, odds ratio 5 1.67, 95% confidence interval (0.93, 2.99)]. Using a Cox proportional hazard model, predictors of the composite of death and nonfatal MI (odds ratio; 95% confidence interval) were no PR (1.90; 1.06-3.43; P = 0.03) and anterior ischemia on preoperative imaging (1.79; 0.99-3.23; P = 0.07). Conclusions: In patients with an abnormal cardiac imaging before abdominal aortic vascular surgery, PR was associated with a reduced risk of death and nonfatal MI while anterior ischemia was an identifier of poor outcome independent of the revascularization status. (C) 2010 Wiley-Liss, Inc. C1 [Garcia, Santiago; Rider, James E.; Pierpont, Gordon; Santilli, Steven; Ward, Herbert B.; McFalls, Edward O.] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Garcia, Santiago; Rider, James E.; Pierpont, Gordon; McFalls, Edward O.] Univ Minnesota, Dept Med, Div Cardiol, Minneapolis, MN 55455 USA. [Moritz, Thomas E.; Reda, Domenic J.] VA Cooperat Studies Program, Hines, IL USA. [Goldman, Steven] So Arizona VA Hlth Care Syst, Tucson, AZ USA. [Goldman, Steven] Univ Arizona, Sarver Heart Ctr, Tucson, AZ USA. [Larsen, Greg C.] Portland VA Med Ctr, Div Cardiol, Portland, OR USA. [Santilli, Steven] Univ Minnesota, Dept Surg, Div Vasc Surg, Minneapolis, MN 55455 USA. [Ward, Herbert B.] Univ Minnesota, Dept Surg, Div Cardiovasc & Thorac Surg, Minneapolis, MN 55455 USA. [Shunk, Kendrick; Rapp, Joseph] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shunk, Kendrick; Rapp, Joseph] San Francisco VA Med Ctr, San Francisco, CA USA. [Littooy, Fred] Edward Hines VA Med Ctr, Div Peripheral Vasc Surg, Hines, IL USA. RP McFalls, EO (reprint author), VA Med Ctr, Div Cardiol, 111C,1 Vet Dr, Minneapolis, MN 55417 USA. EM mcfal00l@umn.edu FU Department of Veterans Affairs Office of Research and Development FX Grant sponsor: Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development NR 19 TC 9 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JAN 1 PY 2011 VL 77 IS 1 BP 134 EP 141 DI 10.1002/ccd.22699 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 700UO UT WOS:000285770000032 PM 20602474 ER PT J AU D'Orazio, J Fisher, DE AF D'Orazio, John Fisher, David E. TI Central role for cAMP signaling in pigmentation and UV resistance SO CELL CYCLE LA English DT Editorial Material ID MELANOCORTIN-1 RECEPTOR; MELANOMA; MELANOCYTES; STRATEGY; DAMAGE; MC1R C1 [Fisher, David E.] Univ Kentucky, Dept Pediat Oncol, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Univ Kentucky, Dept Pediat Oncol, Boston, MA USA. EM dfisher3@partners.org NR 11 TC 9 Z9 9 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2011 VL 10 IS 1 BP 8 EP 9 DI 10.4161/cc.10.1.14292 PG 2 WC Cell Biology SC Cell Biology GA 701RV UT WOS:000285841300005 PM 21200135 ER PT J AU Stegh, AH DePinho, RA AF Stegh, Alexander H. DePinho, Ronald A. TI Beyond effector caspase inhibition Bcl2L12 neutralizes p53 signaling in Glioblastoma SO CELL CYCLE LA English DT Article DE Bcl2L12; p53; glioblastoma multiforme (GBM); The Cancer Genome Atlas (TCGA) Project ID TUMOR-SUPPRESSOR; CELL-DEATH; IN-VIVO; APOPTOSIS; MDM2; ACTIVATION; GLIOMA; AUTOPHAGY; PROTEIN; GENE AB Malignant gliomas are the most common and lethal primary central nervous system cancer. Glioblastoma mutliforme (GBM), the most aggressive of these neoplasms, are generally lethal within two years of diagnosis due in part to the intense apoptosis resistance of its cancer cells, hence poor therapeutic response to conventional and targeted therapies. Twenty years of research has uncovered key genetic events involved in disease initiation and progression, foremost the Tp53 tumor suppressor that is mutated or deleted in 35% of GBM. The prime importance of p53 signaling for gliomapathogenesis is further evidenced by epistatic genetic events targeting additional pathway components including deletion of p14Arf (CDKN2A) and amplification of the p53-degrading ubiquitin ligases MDM2 and MDM4. Recent studies have identified and validated Bcl2-Like 12 (Bcl2L12) as a potent glioma oncoprotein with multiple strategic points in apoptosis regulatory networks, i.e. effector caspases and the p53 tumor suppressor. Bcl2L12 resides in both the cytoplasm and nucleus. In the cytoplasm, Bcl2L12 functions to inhibit caspases 3 and 7, in the nucleus, Bcl2L12 forms a complex with p53, modestly reduces p53 protein stability and prevents its binding to selected target gene promoters (e. g. p21, DR5, Noxa and PUMA), thereby inhibiting p53-directed transcriptomic changes upon DNA damage. Proteomic and multidimensional oncogenomic analyses confirmed a Bcl2L12-p53 signaling axis in GBM, as Bcl2L12 exhibited predominant genomic amplification, elevated mRNA and protein levels in GBM tumors with uncompromised p53 function. On the cell biological level, Bcl2L12 exerts robust inhibition of p53-dependent senescence and apoptosis processes in glioma cells. These multi-leveled studies establish Bcl2L12 as an important oncoprotein acting at the intersection of nuclear p53 and cytoplasmic caspase signaling and point to pharmacological disruption of the Bcl2L12: p53 complex as a promising novel therapeutic strategy for the enhanced treatment of GBM. C1 [Stegh, Alexander H.] Northwestern Univ, Ken & Ruth Davee Dept Neurol, Robert H Lurie Comprehens Canc Ctr, Brain Tumor Inst,Ctr Genet Med, Chicago, IL 60611 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci,Dept Med Oncol,Dept Med, Boston, MA 02115 USA. RP Stegh, AH (reprint author), Northwestern Univ, Ken & Ruth Davee Dept Neurol, Robert H Lurie Comprehens Canc Ctr, Brain Tumor Inst,Ctr Genet Med, Chicago, IL 60611 USA. EM a-stegh@northwestern.edu; ron_depinho@dfci.harvard.edu FU NIH [5R00CA129172-04, 5P01CA95616]; Ben and Catherine Ivy Foundation; Goldhirsh Foundation; Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science FX A. H. S. was supported by NIH grant 5R00CA129172-04, a Zell and a Sidney Kimmel Scholar award. Grant support to R. A. D. derives from the Ben and Catherine Ivy Foundation, the Goldhirsh Foundation and NIH grant 5P01CA95616. R. A. D. is an American Cancer Society Research Professor and supported by the Robert A. and Renee E. Belfer Foundation Institute for Innovative Cancer Science. The results reviewed here are in part based upon data generated by The Cancer Genome Atlas pilot project established by the NCI and NHGRI. Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at cancergenome.nih.gov. NR 57 TC 36 Z9 37 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2011 VL 10 IS 1 BP 33 EP 38 DI 10.4161/cc.10.1.14365 PG 6 WC Cell Biology SC Cell Biology GA 701RV UT WOS:000285841300018 PM 21200141 ER PT S AU Adamala, K Luisi, PL AF Adamala, Katarzyna Luisi, Pier Luigi BE Kubiak, JZ TI Experimental Systems to Explore Life Origin: Perspectives for Understanding Primitive Mechanisms of Cell Division SO CELL CYCLE IN DEVELOPMENT SE Results and Problems in Cell Differentiation LA English DT Article; Book Chapter ID MURCHISON CARBONACEOUS CHONDRITE; FATTY-ACID VESICLES; MONOCARBOXYLIC ACIDS; EVOLUTION; GROWTH; ENCAPSULATION; COMPARTMENTS; COMPETITION; COMPONENTS; LIPOSOMES AB Compartmentalization is a necessary element for the development of any cell cycle and the origin of speciation. Changes in shape and size of compartments might have been the first manifestation of development of so-called cell cycles. Cell growth and division, processes guided by biological reactions in modern cells, might have originated as purely physicochemical processes. Modern cells use enzymes to initiate and control all stages of cell cycle. Protocells, in the absence of advanced enzymatic machinery, might have needed to rely on physical properties of the membrane. As the division processes could not have been controlled by the cell's metabolism, the first protocells probably did not undergo regular cell cycles as we know it in cells of today. More likely, the division of protocells was triggered either by some inorganic catalyzing factor, such as porous surface, or protocells divided when the encapsulated contents reached some critical concentration. C1 [Adamala, Katarzyna] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Luisi, Pier Luigi] Univ Roma Tre, Dipartimento Biol, I-00146 Rome, Italy. RP Adamala, K (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM kate@protobiology.org OI Adamala, Kate/0000-0003-1066-7207 NR 29 TC 2 Z9 2 U1 2 U2 9 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-1844 BN 978-3-642-19064-3 J9 RESULTS PROBL CELL D JI Results Probl. Cell Differ. PY 2011 VL 53 BP 1 EP 9 DI 10.1007/978-3-642-19065-0_1 D2 10.1007/978-3-642-19065-0 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BVP45 UT WOS:000292219600001 PM 21630138 ER PT J AU Fang, PA Margolis, HC Conway, JF Simmer, JP Dickinson, GH Beniash, E AF Fang, Ping-An Margolis, Henry C. Conway, James F. Simmer, James P. Dickinson, Gary H. Beniash, Elia TI Cryogenic Transmission Electron Microscopy Study of Amelogenin Self-Assembly at Different pH SO CELLS TISSUES ORGANS LA English DT Article DE Cryogenic transmission electron microscopy; Amelogenin; Self-assembly; Nanospheres; pH ID DYNAMIC LIGHT-SCATTERING; IN-VITRO; RECOMBINANT AMELOGENIN; ENAMEL MATRIX; NANOSPHERES; TEMPERATURE; PROTEINS AB Cryogenic transmission electron microscopy (cryo-EM) was used to explore the self-assembly of recombinant murine amelogenin (rM179) in vitro. Our cryo-EM data showed that amelogenin self-assembly is a strongly pH-dependent process. At pH 4.4 the main fraction of the protein exists in a monomeric form, although some peculiar structures consisting of chains of monomers were also observed. At pH 5.8 large nanospheres comprising ring-like structures similar to 50 nm in diameter were the most abundant particle class. Similarly, at pH 8.0 amelogenins self-assembled into ring-like oligomers of different sizes, which subsequently assembled into nanospheres 15-20 nm in diameter. Furthermore, at pH 7.2, which is close to a physiological pH, branched chains of nanospheres were observed. Our results show that amelogenin assembly is a multistep hierarchical process and provides new insight into the control of enamel mineralization. Copyright (C) 2011 S. Karger AG, Basel C1 [Beniash, Elia] Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial Regenerat, Dept Oral Biol, Pittsburgh, PA 15261 USA. [Conway, James F.] Univ Pittsburgh, Dept Biol Struct, Pittsburgh, PA 15261 USA. [Margolis, Henry C.] Forsyth Inst, Dept Biomineralizat, Cambridge, MA USA. [Simmer, James P.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Beniash, E (reprint author), Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial Regenerat, Dept Oral Biol, 589 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM ebeniash@pitt.edu RI Fang, PINGAN/A-2461-2009; OI Dickinson, Gary/0000-0003-1073-1483 FU NIH [R01DE016376, R01DE016703]; Commonwealth of Pennsylvania grant [SAP 4100031302] FX Support for this work was provided by NIH grants R01DE016376 (H.C.M.) and R01DE016703 (E.B.), and by the Commonwealth of Pennsylvania grant SAP 4100031302 (J.F.C.). NR 26 TC 7 Z9 8 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2011 VL 194 IS 2-4 BP 166 EP 170 DI 10.1159/000324250 PG 5 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 806VH UT WOS:000293842500015 PM 21597263 ER PT J AU Le Norcy, E Kwak, SY Wiedemann-Bidlack, FB Beniash, E Yamakoshi, Y Simmer, JP Margolis, HC AF Le Norcy, E. Kwak, S. -Y. Wiedemann-Bidlack, F. B. Beniash, E. Yamakoshi, Y. Simmer, J. P. Margolis, H. C. TI Potential Role of the Amelogenin N-Terminus in the Regulation of Calcium Phosphate Formation in vitro SO CELLS TISSUES ORGANS LA English DT Article DE Amelogenin; Calcium phosphates; Enamel; LRAP; Mineralization ID DEVELOPING DENTAL ENAMEL; HYDROXYAPATITE CRYSTALS; AMORPHOUS PRECURSOR; MATRIX PROTEINS; C-TERMINUS; LRAP; PHOSPHORYLATION; AMELOBLASTIN; ORIENTATION; DEFECTS AB N-terminal and C-terminal (CT) domains of amelogenin have been shown to be essential for proper enamel formation. Recent studies have also suggested that although the C-terminus plays an apparent role in protein-mineral interactions, other amelogenin structural domains are involved. The objective was to explore the role of the amelogenin N-terminus in the regulation of calcium phosphate formation in vitro. Spontaneous mineralization studies were carried out using the phosphorylated (+P) and nonphosphorylated (-P) N-terminus of the leucine-rich amelogenin peptide (LRAP) that lacks the hydrophilic CT domain. Mineralization progress was monitored via changes in solution pH. Mineral phases formed were characterized using TEM, selected area electron diffraction, and FT-IR. In controls, amorphous calcium phosphate was initially formed and subsequently transformed to randomly oriented hydroxyapatite (HA) plate-like crystals. In contrast to the control, LRAP(+ P)-CT stabilized ACP formation for >1 day, while LRAP(-P)-CT accelerated the transformation of ACP to HA but had little effect on crystal shape or orientation. In conclusion, the N-terminal domain found in LRAP, as in amelogenins, appears to have the capacity to interact with forming calcium phosphate mineral phases. Results suggest that the N-terminal domain of amelogenin may play a direct role in early stages of enamel formation. Copyright (C) 2011 S. Karger AG, Basel C1 [Le Norcy, E.; Kwak, S. -Y.; Wiedemann-Bidlack, F. B.; Margolis, H. C.] Forsyth Inst, Dept Biomineralizat, Cambridge, MA 02142 USA. [Beniash, E.] Univ Pittsburgh, Dept Oral Biol, Pittsburgh, PA USA. [Yamakoshi, Y.; Simmer, J. P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, 245 1st St, Cambridge, MA 02142 USA. EM hmargolis@forsyth.org FU NIDCR [R01-DE016376] FX This work was supported by NIDCR grant R01-DE016376 (H.C.M.). NR 30 TC 10 Z9 10 U1 1 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2011 VL 194 IS 2-4 BP 188 EP 193 DI 10.1159/000324827 PG 6 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 806VH UT WOS:000293842500019 PM 21576914 ER PT J AU Simmer, JP Hu, YY Richardson, AS Bartlett, JD Hu, JCC AF Simmer, James P. Hu, Yuanyuan Richardson, Amelia S. Bartlett, John D. Hu, Jan C. -C. TI Why Does Enamel in Klk4-Null Mice Break above the Dentino-Enamel Junction? SO CELLS TISSUES ORGANS LA English DT Article DE Amelogenesis; Proteases; Teeth; Ameloblasts; Scanning electron microscopy; lacZ histostaining ID HYPOMATURATION AMELOGENESIS-IMPERFECTA; MOUSE INCISORS; EXPRESSION; MMP-20; AMELOBLASTIN; MUTATION; CLEAVAGE; DEFECTS; GENES; EMSP1 AB Background: The enamel layer of kallikrein 4 (Klk4)-null mice has a normal thickness and a decussating pattern of enamel rods, but it contains residual enamel proteins, is less highly mineralized, and fractures in its deepest part just above the dentino-enamel junction (DEJ). The plane of fracture is puzzling because the deepest enamel is deposited earliest and, through the action of the secretory stage enamel protease (Mmp20), is the most mature part of the enamel layer at the time of the onset of Klk4 expression. Objectives: To characterize the planes of fracture in Mmp20- and Klk4 -null mice and to localize Klk4 expression in developing teeth. Methods: Klk4- and Mmp20 -null mice were sacrificed at 7 weeks and their mandibular incisors were characterized by scanning electron microscopy. Klk4(+/lacZ) mice were mated with Klk4(+/lacZ) mice. Offspring were genotyped by polymerase chain reaction. Klk(4+/+), Klk4(+/lacZ), and Klk4(lacZ/lacZ) (null) littermates on postnatal days 5, 8, 11, and 14 were processed for beta-galactosidase histochemistry. Results: The enamel layer fractures at the DEJ in Mmp20 -null mice, and fractures occur in enamel above the DEJ in Klk4 -null mice. Klk4 is not expressed by secretory-stage ameloblasts, murine odontoblasts beneath the secretory stage, or maturation-stage ameloblasts. Klk4 is specifically expressed by transition and maturation-stage ameloblasts. Conclusions: The breakage of enamel near the DEJ in Klk4-null mice is not due to a failure of odontoblasts to express Klk4, but it relates to a progressive hypomineralization of enamel with depth. Copyright (C) 2011 S. Karger AG, Basel C1 [Simmer, James P.] Univ Michigan, Dent Res Lab, Dept Biol & Mat Sci, Sch Dent, Ann Arbor, MI 48108 USA. [Bartlett, John D.] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA USA. RP Simmer, JP (reprint author), Univ Michigan, Dent Res Lab, Dept Biol & Mat Sci, Sch Dent, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA. EM jsimmer@umich.edu FU National Institutes of Health [DE019775, DE016276] FX This research were supported by National Institutes of Health grants DE019775 (J.P.S.) and DE016276 (J.D.B.). NR 25 TC 17 Z9 17 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2011 VL 194 IS 2-4 BP 211 EP 215 DI 10.1159/000324260 PG 5 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 806VH UT WOS:000293842500023 PM 21546759 ER PT J AU Bartlett, JD Yamakoshi, Y Simmer, JP Nanci, A Smith, CE AF Bartlett, John D. Yamakoshi, Yasuo Simmer, James P. Nanci, Antonio Smith, Charles E. TI MMP20 Cleaves E-Cadherin and Influences Ameloblast Development SO CELLS TISSUES ORGANS LA English DT Article DE Matrix metalloproteinases; Adhesion; Cell junctions ID HYPOMATURATION AMELOGENESIS IMPERFECTA; NULL MOUSE ENAMEL; RAT INCISOR; P-CADHERIN; EXPRESSION; CELLS; ADHERENS; MMP-20; MATRIX-METALLOPROTEINASE-9; MORPHOGENESIS AB Dental enamel development occurs in stages as observed by the changing morphology of the ameloblasts that are responsible for enamel formation. During the secretory stage of development, proteins including MMP20 are secreted into the enamel matrix. MMP20 is required for proper enamel formation as mutation of the Mmp20 gene causes autosomal recessive amelogenesis imperfecta. Here, we examined in detail the morphology of the Mmp20-null ameloblast cell layer. Intriguingly, we found that the Mmp20-null mouse secretory stage ameloblasts retract their Tomes' processes as if preparing to enter the maturation stage but later reextend their Tomes' processes as if resuming the secretory stage. We also demonstrated that MMP20 cleaves epithelial cadherin, i.e. E-cadherin. Cadherins are transmembrane proteins with extracellular domains that provide adhesive contacts between neighboring cells. Their intracellular domains bind to the cell cytoskeleton through catenins, including beta-catenin. When specific MMPs cleave the cadherin extracellular domain, beta-catenin is released and may locate to the cell nucleus as a transcription factor. Therefore, MMP20 may influence ameloblast developmental progression through hydrolysis of cadherin extracellular domains with associated release of transcription factor(s). Copyright (C) 2011 S. Karger AG, Basel C1 [Bartlett, John D.] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02142 USA. [Bartlett, John D.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Cambridge, MA 02138 USA. [Yamakoshi, Yasuo; Simmer, James P.; Smith, Charles E.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Nanci, Antonio] Univ Montreal, Fac Med Dent, Montreal, PQ H3C 3J7, Canada. [Smith, Charles E.] McGill Univ, Dept Anat & Cell Biol, Facil Elect Microscopy Res, Montreal, PQ, Canada. [Smith, Charles E.] McGill Univ, Fac Dent, Montreal, PQ, Canada. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, 245 1st St, Cambridge, MA 02142 USA. EM jbartlett@forsyth.org FU NIDCR [DE016276, DE019775]; CIHR FX This work was funded by NIDCR grants DE016276 (J.D.B.) and DE019775 (J.P.S.) and by the CIHR (A.N.). NR 29 TC 8 Z9 8 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2011 VL 194 IS 2-4 BP 222 EP 226 DI 10.1159/000324205 PG 5 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 806VH UT WOS:000293842500025 PM 21525715 ER PT J AU Saless, N Litscher, SJ Houlihan, MJ Han, IK Wilson, D Demant, P Blank, RD AF Saless, Neema Litscher, Suzanne J. Houlihan, Meghan J. Han, In Kyu Wilson, Derek Demant, Peter Blank, Robert D. TI Comprehensive Skeletal Phenotyping and Linkage Mapping in an Intercross of Recombinant Congenic Mouse Strains HcB-8 and HcB-23 SO CELLS TISSUES ORGANS LA English DT Article DE Biomechanics; Bone modeling; Quantitative trait loci; Linkage; Pleiotropy; Principal components ID TRAITS; BONE; STRENGTH; POWER; GENE; MICE AB Bone biomechanical performance is a complex trait or, more properly, an ensemble of complex traits. Biomechanical performance incorporates flexibility under loading, yield and failure load, and energy to failure; all are important measures of bone function. To date, the vast majority of work has focused on yield and failure load and its surrogate, bone mineral density. We performed a reciprocal intercross of the mouse strains HcB-8 and HcB-23 to map and ultimately identify genes that contribute to differences in biomechanical performance. Mechanical testing was performed by 3-point bending of the femora. We measured femoral diaphysis cross-sectional anatomy from photographs of the fracture surfaces. We used beam equations to calculate material level mechanical properties. We performed a principal component (PC) analysis of normalized whole bone phenotypes (17 input traits). We measured distances separating mandibular landmarks from calibrated digital photographs and performed linkage analysis. Experiment-wide alpha = 0.05 significance thresholds were established by permutation testing. Three quantitative trait loci (QTLs) identified in these studies illustrate the advantages of with LOD scores as large as 17.5, encompassing size, cross-sectional ellipticity, stiffness, yield and failure load, and bone mineral density. This locus was linked to 3 of the PCs but unlinked to any of the tissue level phenotypes. From this pattern, we infer that the QTL operates by modulating the proliferative response to mechanical loading. On this basis, we successfully predicted that this locus also affects the length of a specific region of the mandible. A pleiotropic locus on chromosome 10 with LOD scores displays opposite effects on failure load and toughness with LOD scores of 4.5 and 5.5, respectively, so that the allele that increases failure load decreases toughness. A chromosome 19 QTL for PC2 with an LOD score of 4.8 was not detected with either the whole bone or tissue level phenotypes. We conclude that first, comprehensive, system-oriented phenotyping provides much information that could not be obtained by focusing on bone mineral density alone. Second, mechanical performance includes inherent trade-offs between strength and brittleness. Third, considering the aggregate phenotypic data allows prediction of novel QTLs. Copyright (C) 2011 S. Karger AG, Basel C1 [Saless, Neema; Litscher, Suzanne J.; Houlihan, Meghan J.; Han, In Kyu; Wilson, Derek; Blank, Robert D.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Saless, Neema; Litscher, Suzanne J.; Houlihan, Meghan J.; Han, In Kyu; Blank, Robert D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Wilson, Derek] Ft Valley State Univ, Ft Valley, GA USA. [Demant, Peter] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Blank, RD (reprint author), Univ Wisconsin, Dept Med, 4142 MFCB 5148,1685 Highland Ave, Madison, WI 53705 USA. EM rdb@medicine.wisc.edu OI Blank, Robert Daniel/0000-0003-2950-1944 FU Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs; NIH [R01 AR054753] FX This material is based on work supported by the Office of Research and Development, Biomedical Laboratory R&D Service, Department of Veterans Affairs (R.D.B.), and this work was performed in part at the Geriatrics Research, Education, and Clinical Center of the William S. Middleton Memorial Veterans Hospital. This is Madison GRECC manuscript 10-23. This study was also supported by NIH R01 AR054753 (R.D.B.). NR 14 TC 9 Z9 9 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2011 VL 194 IS 2-4 BP 244 EP 248 DI 10.1159/000324774 PG 5 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 806VH UT WOS:000293842500029 PM 21625064 ER PT J AU Vilardaga, JP Romero, G Friedman, PA Gardella, TJ AF Vilardaga, Jean-Pierre Romero, Guillermo Friedman, Peter A. Gardella, Thomas J. TI Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE G protein-coupled receptor; Parathyroid hormone; Cyclic AMP; G proteins; Internalization; Signaling selectivity; Signaling endosomes ID PROTEIN-COUPLED-RECEPTORS; PTH-RELATED PROTEIN; REGULATED KINASE ACTIVATION; ACTING PTH(1-28) ANALOG; BETA-ARRESTIN; PTH/PTHRP RECEPTOR; METAPHYSEAL CHONDRODYSPLASIA; BLOMSTRAND-CHONDRODYSPLASIA; FUNCTIONAL SELECTIVITY; PHOSPHORYLATION SITES AB The parathyroid hormone (PTH) receptor type 1 (PTHR), a G protein-coupled receptor (GPCR), transmits signals to two hormone systems-PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine-to regulate different biological processes. PTHR responds to these hormonal stimuli by activating heterotrimeric G proteins, such as G(S) that stimulates cAMP production. It was thought that the PTHR, as for all other GPCRs, is only active and signals through G proteins on the cell membrane, and internalizes into a cell to be desensitized and eventually degraded or recycled. Recent studies with cultured cell and animal models reveal a new pathway that involves sustained cAMP signaling from intracellular domains. Not only do these studies challenge the paradigm that cAMP production triggered by activated GPCRs originates exclusively at the cell membrane but they also advance a comprehensive model to account for the functional differences between PTH and PTHrP acting through the same receptor. C1 [Vilardaga, Jean-Pierre; Romero, Guillermo; Friedman, Peter A.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, Pittsburgh, PA 15261 USA. [Vilardaga, Jean-Pierre; Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre; Gardella, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. RP Vilardaga, JP (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Lab GPCR Biol, E1357 Thomas E Starzl Biochem Sci Tower,200 Lothr, Pittsburgh, PA 15261 USA. EM jpv@pitt.edu FU National Institutes of Health [DK087688, DK69998, DK11794] FX Original work described was supported by the National Institutes of Health grants DK087688 (J.-P.V.), DK69998 (P.A.F.), and DK11794 (T.J.G.). NR 125 TC 52 Z9 55 U1 0 U2 10 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JAN PY 2011 VL 68 IS 1 BP 1 EP 13 DI 10.1007/s00018-010-0465-9 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 701AL UT WOS:000285786600001 PM 20703892 ER PT J AU Alessandrini, A De Haseth, S Fray, M Miyajima, M Colvin, RB Williams, WW Cosimi, AB Benichou, G AF Alessandrini, Alessandro De Haseth, Stephanie Fray, Michael Miyajima, Masahiro Colvin, Robert B. Williams, Winfred W. Cosimi, A. Benedict Benichou, Gilles TI Dendritic cell maturation occurs through the inhibition of GSK-3 beta SO CELLULAR IMMUNOLOGY LA English DT Article DE Dendritic cells; GSK-3beta; DC maturation ID GLYCOGEN-SYNTHASE KINASE-3; COLONY-STIMULATING FACTOR; N-TERMINAL KINASE; SIGNAL-TRANSDUCTION; ALLOGRAFT SURVIVAL; INTACT-CELLS; BETA-CATENIN; ACTIVATION; DIFFERENTIATION; INSULIN AB Dendritic cell (DC) maturation results in changes in antigen processing and presentation, governing the fate of adaptive immunity. Understanding the intracellular signaling pathways governing DC maturation is therefore critical. In this study, we observed that the kinase, GSK-3 beta, is present in its active form in resting immature DCs isolated from the spleen and bone marrow of mice. Induction of DC maturation using GM-CSF, IL-4 and TNF-alpha resulted in GSK-3 beta inhibition, as reflected by increased phosphorylation of Serine 9 on the kinase, and concomitant stabilization of its substrate, beta-catenin. Treatment of immature DCs with a GSK-3 beta inhibitor increased cell surface expression of CD80, CD86 and CD40 on DCs, enhancing their ability to present antigen and activating IL-2 secretion by T cells. GSK-30 inhibition also parallels dendritic cell maturation in vivo. Our results show that GSK-33 signaling controls DC maturation and suggest that this kinase could be manipulated to modulate adaptive immunity. (C) 2011 Elsevier Inc. All rights reserved. C1 [Alessandrini, Alessandro; De Haseth, Stephanie; Fray, Michael; Miyajima, Masahiro; Cosimi, A. Benedict; Benichou, Gilles] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Unit,Dept Surg, Boston, MA 02114 USA. [Colvin, Robert B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Williams, Winfred W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Boston, MA 02114 USA. RP Alessandrini, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Unit,Dept Surg, 55 Fruit St,Thier 807, Boston, MA 02114 USA. EM aalessandrini@partners.org FU Surgical Research Council; NIH [5PO1 HL18646, U19 DK080652, KO2AI53103, R01 HD050484] FX This work was supported by a Surgical Research Council Junior Faculty Award to A.A. by grants from the NIH (5PO1 HL18646 and U19 DK080652) to A.B.C; by grants from the NIH (KO2AI53103 and R01 HD050484) to G.B. NR 34 TC 4 Z9 5 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PY 2011 VL 270 IS 2 BP 114 EP 125 DI 10.1016/j.cellimm.2011.04.007 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 812UV UT WOS:000294319300003 PM 21601837 ER PT J AU Sukumaran, B Mastronunzio, JE Narasimhan, S Fankhauser, S Uchil, PD Levy, R Graham, M Colpitts, TM Lesser, CF Fikrig, E AF Sukumaran, Bindu Mastronunzio, Juliana E. Narasimhan, Sukanya Fankhauser, Sarah Uchil, Pradeep D. Levy, Roie Graham, Morven Colpitts, Tonya Michelle Lesser, Cammie F. Fikrig, Erol TI Anaplasma phagocytophilum AptA modulates Erk1/2 signalling SO CELLULAR MICROBIOLOGY LA English DT Article ID HUMAN GRANULOCYTIC EHRLICHIOSIS; YEAST SACCHAROMYCES-CEREVISIAE; INTERMEDIATE-FILAMENTS; EVASION MECHANISMS; VIRULENCE PROTEINS; ENDOTHELIAL-CELLS; HUMAN NEUTROPHILS; GENE-EXPRESSION; HOST-CELLS; MAP KINASE AB P>Anaplasma phagocytophilum causes human granulocytic anaplasmosis, one of the most common tick-borne diseases in North America. This unusual obligate intracellular pathogen selectively persists within polymorphonuclear leucocytes. In this study, using the yeast surrogate model we identified an A. phagocytophilum virulence protein, AptA (A. phagocytophilum toxin A), that activates mammalian Erk1/2 mitogen-activated protein kinase. This activation is important for A. phagocytophilum survival within human neutrophils. AptA interacts with the intermediate filament protein vimentin, which is essential for A. phagocytophilum-induced Erk1/2 activation and infection. A. phagocytophilum infection reorganizes vimentin around the bacterial inclusion, thereby contributing to intracellular survival. These observations reveal a major role for the bacterial protein, AptA, and the host protein, vimentin, in the activation of Erk1/2 during A. phagocytophilum infection. C1 [Sukumaran, Bindu; Mastronunzio, Juliana E.; Narasimhan, Sukanya; Colpitts, Tonya Michelle; Fikrig, Erol] Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT 06510 USA. [Uchil, Pradeep D.] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06510 USA. [Graham, Morven] Yale Univ, Sch Med, Ctr Cellular & Mol Imaging, New Haven, CT 06510 USA. [Fankhauser, Sarah; Levy, Roie; Lesser, Cammie F.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med Microbiol & Mol Med, Cambridge, MA 02139 USA. [Fankhauser, Sarah; Levy, Roie; Lesser, Cammie F.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. RP Fikrig, E (reprint author), Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT 06510 USA. EM erol.fikrig@yale.edu OI Colpitts, Tonya/0000-0003-3915-1554 FU NIH [R01 AI41440, R01 AI064285, R03 AI080993-01A1] FX We thank Drs Munderloh and Michael Herron, University of Minnesota for providing us with fluorescently labelled A. phagocytophilum, Yasuko Rikihisa (Ohio State University) for providing the HZ strain of A. phagocytophilum. This work was supported by grants from NIH to E. F. (R01 AI41440), C. F. L. (R01 AI064285) and B. S. (R03 AI080993-01A1). NR 66 TC 21 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JAN PY 2011 VL 13 IS 1 BP 47 EP 61 DI 10.1111/j.1462-5822.2010.01516.x PG 15 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 700PM UT WOS:000285756400005 PM 20716207 ER PT J AU Reimold, FR Heneghan, JF Stewart, AK Zelikovic, I Vandorpe, DH Shmukler, BE Alper, SL AF Reimold, Fabian R. Heneghan, John F. Stewart, Andrew K. Zelikovic, Israel Vandorpe, David H. Shmukler, Boris E. Alper, Seth L. TI Pendrin Function and Regulation in Xenopus Oocytes SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE Iodide; Bromide; Chloride; Formate; Xenopus oocyte; Methanethiosulfonate; Phorbol ester; Protein kinase C delta ID AE2 ANION-EXCHANGER; PROTEIN-KINASE-C; NH2-TERMINAL CYTOPLASMIC DOMAIN; NONSYNDROMIC HEARING-LOSS; INTRACELLULAR PH; INTERCALATED CELLS; SYNDROME GENE; PKC-DELTA; WILD-TYPE; TRANSPORT AB SLC26A4/PDS mutations cause Pendred Syndrome and non-syndromic deafness. but some aspects of function and regulation of the SLC26A4 polypeptide gene product, pendrin, remain controversial or incompletely understood. We have therefore extended the functional analysis of wildtype and mutant pendrin in Xenopus oocytes, with studies of isotopic flux, electrophysiology, and protein localization. Pendrin mediated electroneutral, pH-insensitive, DIDS-insensitive anion exchange, with extracellular K((1/2)) (in mM) of 1.9 (Cl(-)), 1.8 (I(-)), and 0.9 (Br(-)). The unusual phenotype of Pendred Syndrome mutation E303Q (loss-of-function with normal surface expression) prompted systematic mutagenesis at position 303. Only mutant E303K exhibited loss-of-function unrescued by forced overexpression. Mutant E303C was insensitive to charge modification by methanethiosulfonates. The corresponding mutants SLC26A2 E336Q, SLC26A3 E293Q, and SLC26A6 E298Q exhibited similar loss-of-function phenotypes, with wildtype surface expression also documented for SLC26A2 E336Q. The strong inhibition of wildtype SLC26A2, SLC26A3, and SLC26A6 by phorbol ester contrasts with its modest inhibition of pendrin. Phorbol ester inhibition of SLC26A2, SLC26A3, and SLC26A6 was blocked by coexpressed kinase-dead PKC delta but was without effect on pendrin. Mutation of SLC26A2 serine residues conserved in PKC delta -sensitive SLC26 proteins but absent from pendrin failed to reduce PKCd sensitivity of SLC26A2 (190). Copyright (C) 2011 S. Karger AG, Basel C1 [Reimold, Fabian R.; Heneghan, John F.; Stewart, Andrew K.; Vandorpe, David H.; Shmukler, Boris E.; Alper, Seth L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Renal Div, Boston, MA 02215 USA. [Reimold, Fabian R.; Heneghan, John F.; Stewart, Andrew K.; Vandorpe, David H.; Shmukler, Boris E.; Alper, Seth L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Mol & Vasc Med Unit, Boston, MA 02215 USA. [Reimold, Fabian R.; Heneghan, John F.; Stewart, Andrew K.; Vandorpe, David H.; Shmukler, Boris E.; Alper, Seth L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zelikovic, Israel] Technion Israel Inst Technol, Fac Med, Lab Dev Nephrol, Dept Physiol & Biophys, Haifa, Israel. [Zelikovic, Israel] Technion Israel Inst Technol, Rappaport Family Inst Res Med Sci, IL-31096 Haifa, Israel. [Zelikovic, Israel] Rambam Med Ctr, Div Pediat Nephrol, Haifa, Israel. RP Alper, SL (reprint author), Beth Israel Deaconess Med Ctr RN 380F, 99 Brookline Ave, Boston, MA 02215 USA. EM salper@bidmc.harvard.edu FU NIH [R01 DK43495, HL077765, DK07094, DK07477, DK007199]; US-Israel Binational Science Foundation; Harvard Digestive Diseases Center [DK34854]; Robert-Bosch-Stiftung FX This work was supported by NIH grants R01 DK43495 and HL077765 (SLA), by a grant from the US-Israel Binational Science Foundation (SLA and IZ) and by the Harvard Digestive Diseases Center DK34854 (SLA and AKS). FRR was supported by a postdoctoral fellowship from the Robert-Bosch-Stiftung. JFH was supported by NIH T32 postdoctoral fellowship grants DK07094, DK07477, and DK007199. NR 74 TC 16 Z9 16 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2011 VL 28 IS 3 BP 435 EP 450 DI 10.1159/000335106 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 861IA UT WOS:000298011400006 PM 22116357 ER PT J AU Wagner, CA Mohebbi, N Uhlig, U Giebisch, GH Breton, S Brown, D Geibel, JP AF Wagner, Carsten A. Mohebbi, Nilufar Uhlig, Ulrike Giebisch, Gerhard H. Breton, Sylvie Brown, Dennis Geibel, John P. TI Angiotensin II Stimulates H+-ATPase Activity in Intercalated Cells from Isolated Mouse Connecting Tubules and Cortical Collecting Ducts SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE Pendrin; Bicarbonate secretion; Chloride absorption ID PROXIMAL CONVOLUTED TUBULE; URINARY ACIDIFICATION; METABOLIC-ACIDOSIS; INTRACELLULAR PH; RAT-KIDNEY; RECEPTOR SUBTYPES; LUMINAL MEMBRANE; CONCANAMYCIN-A; TURTLE-BLADDER; V-ATPASES AB Intercalated cells in the collecting duct system express V-type H+-ATPases which participate in acid extrusion, bicarbonate secretion, and chloride absorption depending on the specific subtype. The activity of H+-ATPases is regulated by acid-base status and several hormones, including angiotensin II and aldosterone. Angiotensin II stimulates chloride absorption mediated by pendrin in type B intercalated cells and this process is energized by the activity of H+-ATPases. Moreover, angiotensin II stimulates bicarbonate secretion by the connecting tubule (CNT) and early cortical collecting duct (CCD). In the present study we examined the effect of angiotensin II (10 nM) on H+-ATPase activity and localization in isolated mouse connecting tubules and cortical collecting ducts. Angiotensin II stimulated Na+-independent intracellular pH recovery about 2-3 fold, and this was abolished by the specific H+-ATPase inhibitor concanamycin. The effect of angiotensin II was mediated through type 1 angiotensin II receptors (AT(1)-receptors) because it could be blocked by saralasin. Stimulation of H+-ATPase activity required an intact microtubular network - it was completely inhibited by colchicine. Immunocytochemistry of isolated CNT/CCDs incubated in vitro with angiotensin II suggests enhanced membrane associated staining of H+-ATPases in pendrin expressing intercalated cells. In summary, angiotensin II stimulates H+-ATPases in CNT/CCD intercalated cells, and may contribute to the regulation of chloride absorption and bicarbonate secretion in this nephron segment. Copyright (C) 2011 S. Karger AG, Basel C1 [Wagner, Carsten A.; Mohebbi, Nilufar] Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland. [Wagner, Carsten A.; Mohebbi, Nilufar] Univ Zurich, Zurich Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. [Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Massachusetts Gen Hosp Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Breton, Sylvie; Brown, Dennis] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Breton, Sylvie; Brown, Dennis] Harvard Univ, Sch Med, Boston, MA USA. [Wagner, Carsten A.; Uhlig, Ulrike; Giebisch, Gerhard H.; Geibel, John P.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. [Uhlig, Ulrike; Geibel, John P.] Yale Univ, Dept Surg, Sch Med, New Haven, CT 06520 USA. RP Wagner, CA (reprint author), Univ Zurich, Inst Physiol, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM Wagnerca@access.uzh.ch FU NIH [HD40793, DK42956, DK-17433]; Swiss National Science Foundation [3100-068318, 31003A-122217] FX This study was supported by NIH grants HD40793 to S. Breton, DK42956 to D. Brown, and DK-17433 to J.P. Geibel and the Swiss National Science Foundation (3100-068318 and 31003A-122217) to C.A. Wagner. C.A. Wagner was a Feodor Lynen fellow of the Humboldt foundation, Germany. NR 58 TC 18 Z9 18 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2011 VL 28 IS 3 BP 513 EP 520 DI 10.1159/000335112 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 861IA UT WOS:000298011400014 PM 22116365 ER PT J AU Ahmad, A Khundmiri, SJ Pribble, F Merchant, ML Ameen, M Klein, JB Levi, M Lederer, ED AF Ahmad, Aamir Khundmiri, Syed J. Pribble, Francesca Merchant, Michael L. Ameen, Mohammed Klein, Jon B. Levi, Moshe Lederer, Eleanor D. TI Role of Vacuolar ATPase in the Trafficking of Renal Type IIa Sodium-phosphate Cotransporter SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE NpT2a; Opossum Kidney (OK) cells; Lysosomal degradation; PTH; Low Pi medium; Brefeldin A ID NA/P-I COTRANSPORTER; PARATHYROID-HORMONE; H+-ATPASE; PROXIMAL TUBULES; EPITHELIAL-CELLS; KIDNEY-CELLS; K ATPASE; V-ATPASE; EXPRESSION; PROTEIN AB Background/Aims: Total body phosphate homeostasis is regulated by expression of type IIa sodium phosphate cotransporter (NpT2a) in the apical membrane (BBM) of renal proximal tubule cells. NpT2a expression is regulated by dietary phosphate and PTH but the mechanisms for trafficking of the protein are unknown. Based on 2D gel electrophoresis and mass spectroscopy data that changes in dietary phosphate stimulated changes in BBM expression of vacuolar H(+)-ATPase, we hypothesized that vacuolar H(+)-ATPase plays a significant role in regulation of NpT2a in opossum kidney (OK) cells, a model for renal proximal tubule transport. Methods: Role of vacuolar H(+)-ATPase was studied in opossum kidney (OK) cells by examining the effect of inhibition of vacuolar H(+)-ATPase on Pi uptake and NpT2a expression. Results: Pretreatment of OK cells with bafilomycin A 1 and concanamycin A, inhibitors of vacuolar H(+)-ATPases, blocked high phosphate-and PTH-induced degradation of NpT2a, but had no effect on high phosphate or PTH induced inhibition of sodium-dependent phosphate transport. Exposure of the cells to bafilomycin A 1 significantly decreased phosphate transport and apical membrane expression of NpT2a. Treatment with brefeldin A, an inhibitor of Golgi transport, decreased phosphate transport and apical membrane expression of NpT2a while treatment of cells with both brefeldin A and bafilomycin A 1 had no additive effect. Conclusion: We conclude that vacuolar H(+)-ATPase plays a significant role in exocytosis of NpT2a into the apical membrane and in degradation of NpT2a but has no role in endocytosis. Copyright (C) 2011 S. Karger AG, Basel C1 [Lederer, Eleanor D.] Univ Louisville, Kidney Dis Program, Dept Med, Louisville, KY 40202 USA. [Khundmiri, Syed J.; Lederer, Eleanor D.] Univ Louisville, Dept Physiol, Louisville, KY 40202 USA. [Klein, Jon B.; Lederer, Eleanor D.] Louisville Vet Affairs Hosp, Louisville, KY USA. [Levi, Moshe] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Levi, Moshe] Univ Colorado, Hlth Sci Ctr, Dept Physiol, Denver, CO 80262 USA. [Levi, Moshe] Denver Vet Affairs Hosp, Denver, CO USA. [Levi, Moshe] Univ Colorado, Hlth Sci Ctr, Dept Biophys, Denver, CO USA. RP Lederer, ED (reprint author), Univ Louisville, Kidney Dis Program, Dept Med, Baxter Res Bldg,102 570 S Preston St, Louisville, KY 40202 USA. EM e.lederer@louisville.edu RI Klein, Jon/B-9833-2013; Merchant, Michael/F-7109-2013; OI Levi, Moshe/0000-0002-6225-946X; Ahmad, Aamir/0000-0003-1784-5723 FU Veteran Affairs; NIH [1 R01 DK066029]; American Heart Association [0435153N, 0120318B] FX "The opinions expressed in this manuscript do not reflect the opinions of the Department of Veteran Affairs". The authors thank Nina Lesousky for expert technical assistance. The work was supported by Veteran Affairs Merit Review grant (EDL and JBK), NIH 1 R01 DK066029 to ML, and Scientist Development Grant from American Heart Association (National, 0435153N) and American Heart Association, Ohio Valley Affiliate, postdoctoral fellowship grant (0120318B) to SJK. NR 29 TC 6 Z9 6 U1 0 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PY 2011 VL 27 IS 6 BP 703 EP 714 DI 10.1159/000330079 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 779CX UT WOS:000291756800009 PM 21691088 ER PT J AU Vannini, P O'Brien, J O'Keefe, K Pihlajamaki, M LaViolette, P Sperling, RA AF Vannini, P. O'Brien, J. O'Keefe, K. Pihlajamaeki, M. LaViolette, P. Sperling, R. A. TI What Goes Down Must Come Up: Role of the Posteromedial Cortices in Encoding and Retrieval SO CEREBRAL CORTEX LA English DT Article DE cued recall; default mode network; episodic memory; fMRI; posterior cingulate ID EVENT-RELATED FMRI; COMPLEMENTARY-LEARNING-SYSTEMS; MILD COGNITIVE IMPAIRMENT; POSTERIOR PARIETAL CORTEX; EPISODIC MEMORY RETRIEVAL; ALZHEIMERS-DISEASE; DEFAULT-MODE; RECOGNITION MEMORY; FUNCTIONAL MRI; RESTING-STATE AB The hypothesis that the neural network supporting successful episodic memory retrieval overlaps with the regions involved in episodic encoding has garnered much interest; however, the role of the posteromedial regions remains to be fully elucidated. Functional magnetic resonance imaging (fMRI) studies during successful encoding typically demonstrate deactivation of posteromedial cortices, whereas successful retrieval of previously encoded information has been associated with activation of these regions. Here, we performed an event-related fMRI experiment during an associative face-name encoding and retrieval task to investigate the topography and functional relationship of the brain regions involved in successful memory processes. A conjunction analysis of novel encoding and subsequent successful retrieval of names revealed an anatomical overlap in bilateral posteromedial cortices. In this region, a significant negative correlation was found: Greater deactivation during encoding was related to greater activation during successful retrieval. In contrast, the hippocampus and prefrontal cortex demonstrated positive activation during both encoding and retrieval. Our results provide further evidence that posteromedial regions constitute critical nodes in the large-scale cortical network subserving episodic memory. These results are discussed in relation to the default mode hypothesis, the involvement of posteromedial cortices in successful memory formation and retention, as well as potential implications for aging and neurodegenerative disease. C1 [Vannini, P.; LaViolette, P.; Sperling, R. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Vannini, P.; LaViolette, P.; Sperling, R. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. [Vannini, P.; LaViolette, P.; Sperling, R. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. [Vannini, P.; O'Brien, J.; O'Keefe, K.; Pihlajamaeki, M.; Sperling, R. A.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol,Med Sch, Boston, MA 02115 USA. [Vannini, P.] Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, SE-14186 Stockholm, Sweden. RP Vannini, P (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, 149 13th St,Suite 2691, Boston, MA 02129 USA. EM patrizia@nmr.mgh.harvard.edu FU Karolinska Institutet foundations [Fobi0794]; Swedish Research Council; Royal Science Academy in Sweden; European Union [FP7-PEOPLE-2007-4-1-IOF]; National Institutes of Health [R01 AG027435, P01AG036694]; Alzheimer's Association FX Karolinska Institutet foundations (Fobi0794) to P.V.; Swedish Research Council to P.V.; Royal Science Academy in Sweden to P.V.; Marie Curie Fellowship (FP7-PEOPLE-2007-4-1-IOF) from the European Union to P.V. National Institutes of Health (R01 AG027435, P01AG036694 to R.A.S.); Alzheimer's Association to R.A.S. NR 97 TC 48 Z9 50 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2011 VL 21 IS 1 BP 22 EP 34 DI 10.1093/cercor/bhq051 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 692ZZ UT WOS:000285195700003 PM 20363808 ER PT J AU Yue, XM Cassidy, BS Devaney, KJ Holt, DJ Tootell, RBH AF Yue, Xiaomin Cassidy, Brittany S. Devaney, Kathryn J. Holt, Daphne J. Tootell, Roger B. H. TI Lower-Level Stimulus Features Strongly Influence Responses in the Fusiform Face Area SO CEREBRAL CORTEX LA English DT Article DE CMF; contrast gain; face recognition; FFA; V1 ID HUMAN VISUAL-CORTEX; LATERAL OCCIPITAL COMPLEX; INFERIOR TEMPORAL CORTEX; OBJECT RECOGNITION; STRIATE CORTEX; FUNCTIONAL MRI; CONTRAST DISCRIMINATION; SPATIAL-FREQUENCY; CORTICAL REGION; MACAQUE MONKEY AB An intriguing region of human visual cortex (the fusiform face area; FFA) responds selectively to faces as a general higher-order stimulus category. However, the potential role of lower-order stimulus properties in FFA remains incompletely understood. To clarify those lower-level influences, we measured FFA responses to independent variation in 4 lower-level stimulus dimensions using standardized face stimuli and functional Magnetic Resonance Imaging (fMRI). These dimensions were size, position, contrast, and rotation in depth (viewpoint). We found that FFA responses were strongly influenced by variations in each of these image dimensions; that is, FFA responses were not "invariant" to any of them. Moreover, all FFA response functions were highly correlated with V1 responses (r = 0.95-0.99). As in V1, FFA responses could be accurately modeled as a combination of responses to 1) local contrast plus 2) the cortical magnification factor. In some measurements (e.g., face size or a combinations of multiple cues), the lower-level variations dominated the range of FFA responses. Manipulation of lower-level stimulus parameters could even change the category preference of FFA from "face selective" to "object selective." Altogether, these results emphasize that a significant portion of the FFA response reflects lower-level visual responses. C1 [Yue, Xiaomin; Cassidy, Brittany S.; Devaney, Kathryn J.; Holt, Daphne J.; Tootell, Roger B. H.] Harvard Univ, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Dept Radiol,Med Sch, Charlestown, MA 02129 USA. RP Yue, XM (reprint author), Harvard Univ, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Dept Radiol,Med Sch, 149 13th St, Charlestown, MA 02129 USA. EM xiaomin@nmr.mgh.harvard.edu FU National Institutes of Health [EY017081, MH076054]; National Alliance for Research on Schizophrenia and Depression (NARSAD); Sidney J. Bear Trust; Martinos Center for Biomedical Imaging, National Center for Research Resources (NCRR) [P41RR14075] FX National Institutes of Health (EY017081 to R.B.H.T., MH076054 to D.J.H.); the National Alliance for Research on Schizophrenia and Depression (NARSAD) (R.B.H.T., D.J.H.); the Sidney J. Bear Trust (D.J.H.); Martinos Center for Biomedical Imaging, National Center for Research Resources (NCRR) (P41RR14075). NR 92 TC 51 Z9 51 U1 2 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2011 VL 21 IS 1 BP 35 EP 47 DI 10.1093/cercor/bhq050 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 692ZZ UT WOS:000285195700004 PM 20375074 ER PT J AU Takahashi, E Dai, GP Rosen, GD Wang, RP Ohki, K Folkerth, RD Galaburda, AM Wedeen, VJ Grant, PE AF Takahashi, Emi Dai, Guangping Rosen, Glenn D. Wang, Ruopeng Ohki, Kenichi Folkerth, Rebecca D. Galaburda, Albert M. Wedeen, Van J. Grant, P. Ellen TI Developing Neocortex Organization and Connectivity in Cats Revealed by Direct Correlation of Diffusion Tractography and Histology SO CEREBRAL CORTEX LA English DT Article DE cat; cortical plate; development; diffusion spectrum imaging; ubplate; tractography ID DEVELOPING MOUSE-BRAIN; PRIMARY VISUAL-CORTEX; HUMAN FETAL CEREBRUM; MAGNETIC-RESONANCE; WHITE-MATTER; ANATOMICAL CHARACTERIZATION; POSTNATAL-DEVELOPMENT; LAMINAR ORGANIZATION; TENSOR MRI; ANISOTROPY AB The immature cortex (cortical plate [CP]) and underlying subplate (SP), a transient cell layer just below the CP, play critical roles in the formation of intracerebral connections. The purpose of this study was to examine the diffusion characteristics of the developing cortex and subcortical structures and compare to histology. We obtained high-resolution diffusion spectrum images of postnatal day (P) 0 (newborn), P35 (pediatric), and P100 (adult) cat brains, performed tractography analysis, and correlated with histological findings. Tractography revealed radial organization and radial afferent/efferent tracts not only in the CP but also in external SP at P0. Radial organization persisted only in the cortex but decreased at P35 and P100. Radial organization correlated with radial cellular organization, with highest cellular density at P0 (Cresyl Violet staining). At P0, the internal SP contained abundant corticocortical and projection tractography pathways, crossing at wide angles in areas with no myelination by Luxol Fast Blue staining. At P35 and P100, increased directional coherence of white matter was observed, with fewer local tracts, but more long association pathways. These results suggest that diffusion tractography can differentially characterize internal and external SP zones and their transition into mature cortical pathways. C1 [Takahashi, Emi; Grant, P. Ellen] Harvard Univ, Childrens Hosp Boston, Dept Med, Div Newborn Med,Med Sch, Boston, MA 02115 USA. [Takahashi, Emi; Grant, P. Ellen] Fetal Neonatal Imaging & Dev Sci Ctr, Boston, MA 02115 USA. [Takahashi, Emi; Dai, Guangping; Wang, Ruopeng; Wedeen, Van J.; Grant, P. Ellen] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02119 USA. [Rosen, Glenn D.; Galaburda, Albert M.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA. [Ohki, Kenichi] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Ohki, Kenichi] Kyushu Univ, Grad Sch Med Sci, Dept Mol Physiol, Higashi Ku, Fukuoka 8128582, Japan. [Folkerth, Rebecca D.] Harvard Univ, Childrens Hosp Boston, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Grant, P. Ellen] Harvard Univ, Childrens Hosp Boston, Dept Radiol, Sch Med, Boston, MA 02115 USA. RP Takahashi, E (reprint author), Harvard Univ, Childrens Hosp Boston, Dept Med, Div Newborn Med,Med Sch, Boston, MA 02115 USA. EM emi@nmr.mgh.harvard.edu OI Rosen, Glenn/0000-0001-8281-5446 FU NIH [RO1 MH 64044]; National Science Foundation [PHY 0855161, PHY 0855453]; Ellison Medical Foundation [208556] FX NIH (RO1 MH 64044); National Science Foundation (PHY 0855161, PHY 0855453), and the Ellison Medical Foundation (208556). NR 69 TC 30 Z9 30 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2011 VL 21 IS 1 BP 200 EP 211 DI 10.1093/cercor/bhq084 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 692ZZ UT WOS:000285195700019 PM 20494968 ER PT J AU Venketasubramanian, N Rother, J Bhatt, DL Pasquet, B Mas, JL Alberts, MJ Hill, MD Aichner, F Steg, PG AF Venketasubramanian, Narayanaswamy Roether, Joachim Bhatt, Deepak L. Pasquet, Blandine Mas, Jean-Louis Alberts, Mark J. Hill, Michael D. Aichner, Franz Steg, P. Gabriel CA REACH Investigators TI Two-Year Vascular Event Rates in Patients with Symptomatic Cerebrovascular Disease: The REACH Registry SO CEREBROVASCULAR DISEASES LA English DT Article DE Atherothrombosis; Cerebrovascular disease; Epidemiology; Risk factors; Stroke ID TRANSIENT ISCHEMIC ATTACK; RANDOMIZED CONTROLLED-TRIAL; ARTERIAL ORIGIN ESPRIT; RECURRENT STROKE; CEREBRAL-ISCHEMIA; ASPIRIN; RISK; CLOPIDOGREL; PREVENTION; ATHEROTHROMBOSIS AB Background and Purpose: Few practice-based studies have reported vascular outcome events among patients with cerebrovascular disease (CeVD). We describe 2-year vascular outcomes among symptomatic CeVD patients from the REduction of Atherothrombosis for Continued Health (REACH) Registry. Methods: Vascular events (stroke; myocardial infarction, MI; cardiovascular death, CV death; hospitalization) were studied among symptomatic CeVD patients from a prospective cohort of stable outpatients with established atherothrombosis or >= 3 atherothrombotic risk factors. Results: Of the 69,055 patients in REACH, 18,992 (28%) had symptomatic CeVD, of which outcome data were available for 18,189 patients. At 2 years, the frequency of non-fatal stroke was 5.93% (95% CI 5.22-6.64), non-fatal MI 2.21% (95% CI 1.65-2.76), CV death 4.45% (95% CI 3.66-5.22), combined vascular endpoint 11.48% (95% CI 10.46-12.49), and all deaths 7.39% (95% CI 6.34-8.42). The frequency of stroke, MI, CV death, or hospitalization for atherothrombotic events was 21.05% (95% CI 20.05-22.03). Event rates were lowest among patients with CeVD alone and highest among patients with CeVD, coronary artery disease, and peripheral artery disease. Other predictors of the primary outcome were increasing age, history of diabetes, current smoking, asymptomatic carotid stenosis, and carotid plaque. Outcomes were similar across geographical regions. Conclusions: Symptomatic CeVD patients encounter high vascular event rates despite treatment. Recurrent nonfatal stroke is more common than nonfatal MI. Copyright (C) 2011 S. Karger AG, Basel C1 [Venketasubramanian, Narayanaswamy] Natl Univ Singapore, Natl Univ Hlth Syst, Div Neurol, Singapore 119228, Singapore. [Roether, Joachim] Asklepios Klin Altona, Dept Neurol, Hamburg, Germany. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Pasquet, Blandine] Hop Xavier Bichat, APHP, INSERM, CIE 801,Dept Epidemiol, Paris, France. [Mas, Jean-Louis] Paris Descartes Univ, INSERM U894, Hop St Anne, Dept Neurol, Paris, France. [Steg, P. Gabriel] Univ Paris 07, INSERM U698, Paris, France. [Steg, P. Gabriel] Hop Bichat Claude Bernard, AP HP, F-75877 Paris, France. [Hill, Michael D.] Univ Calgary, Foothills Hosp, Dept Clin Neurosci, Calgary, AB, Canada. [Aichner, Franz] Acad Teaching Hosp Wagner Jauregg, Linz, Austria. RP Venketasubramanian, N (reprint author), Natl Univ Singapore, Natl Univ Hlth Syst, Div Neurol, 1E Kent Ridge Rd, Singapore 119228, Singapore. EM ramani_nv@nuhs.edu.sg OI Hill, Michael/0000-0002-6269-1543 FU Sanofi-Aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); Astra Zeneca; Eisai; Ethicon; Heartscape; Medicines Company; Servier; Boehringer-Ingelheim; Schering-Plough; Genentech; Pfizer; PDL Biopharm; Hoffmann-La Roche Canada Ltd; Bayer Canada FX The REACH Registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan).; N.V. - Research grant: Sanofi-Aventis.; D.L.B. - Institutional research grants: Astra Zeneca, Bristol-Myers Squibb, Eisai, Ethicon, Heartscape, Sanofi-Aventis, The Medicines Company.; J.-L.M. - Consulting fees: Sanofi-Aventis, Servier, Bristol-Myers Squibb; lecture fees: Sanofi-Aventis, Bristol-Myers Squibb, Boehringer-Ingelheim.; M.J.A. - Research grants, honoraria, consulting fees: Sanofi-Aventis, Bristol-Myers Squibb, Astra-Zeneca, Schering-Plough, Genentech, Boehringer-Ingelheim; honoraria and consulting fees: The Medicines Company, Pfizer, PDL Biopharm; consulting: Eli Lilly, Merck, GlaxoSmithKline, Biosite, Cardax.; M.D.H. - Advisory boards: Sanofi-Aventis Canada, Vernalis Group Ltd; member: Reach Registry Canadian Steering Committee and the Global Stroke Subcommittee; research grants: Hoffmann-La Roche Canada Ltd, Bayer Canada.; P.G.S. - Research Grant: Sanofi-Aventis; Speakers bureau: Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Nycomed, Sanofi-Aventis, Servier, The Medicines Company; Consulting/advisory board: Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Endotis, GlaxoSmithKline, Medtronic, MSD, Nycomed, Sanofi-Aventis, Servier, The Medicines Company. NR 21 TC 17 Z9 18 U1 5 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2011 VL 32 IS 3 BP 254 EP 260 DI 10.1159/000328650 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 883NU UT WOS:000299641800009 PM 21876353 ER PT J AU Seebeck, FP Ricardo, A Szostak, JW AF Seebeck, Florian P. Ricardo, Alonso Szostak, Jack W. TI Artificial lantipeptides from in vitro translations SO CHEMICAL COMMUNICATIONS LA English DT Article ID DEHYDROALANINE-CONTAINING PEPTIDES; LANTIBIOTIC NISIN; AMINO-ACIDS; LIPID-II; BIOSYNTHESIS; SYNTHETASE; CONVERSION; MECHANISM; PROTEINS; ANALOGS AB We have devised a protocol for enzyme-free insertion of dehydroalanine, dehydrobutyrine and thioether crosslinks into translated peptides. In vitro translation using 4-selenalysine and 4-selenoisoleucine as substitutes for lysine and isoleucine yields peptides that can be converted to polycyclic structures using mild chemistry in water. This methodology presents a gateway for exploring the potential of artificial lantipeptides as scaffolds for drug development. C1 [Seebeck, Florian P.; Ricardo, Alonso; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Seebeck, Florian P.; Ricardo, Alonso; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Simches Res Ctr, Boston, MA 02114 USA. [Seebeck, Florian P.] Max Planck Inst Mol Physiol, Dept Phys Biochem, D-44139 Dortmund, Germany. [Ricardo, Alonso] Ra Pharmaceut Inc, Boston, MA USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU National Institutes of Health [GM 074505-02] FX We would like to thank M. C. T. Hartman, and B. Seelig for insightful advice. J.W.S. is an Investigator of the Howard Hughes Medical Institute and F. P. S was supported by the National Institutes of Health (GM 074505-02). J.W.S. is a co-founder and A. R. an employee of Ra Pharmaceuticals and therefore declare competing financial interests. NR 27 TC 22 Z9 23 U1 1 U2 10 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2011 VL 47 IS 21 BP 6141 EP 6143 DI 10.1039/c0cc05663d PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 764KI UT WOS:000290628000061 PM 21528125 ER PT B AU Spagnolli, E Zapol, WM AF Spagnolli, Ester Zapol, Warren M. BE Mozzarelli, A Bettati, S TI The Role of Reactive Oxygen and Nitrogen Species in Ischemia/Reperfusion Injury SO CHEMISTRY AND BIOCHEMISTRY OF OXYGEN THERAPEUTICS: FROM TRANSFUSION TO ARTIFICIAL BLOOD LA English DT Article; Book Chapter ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE SYNTHASE; ACUTE MYOCARDIAL-INFARCTION; SOLUBLE GUANYLYL CYCLASE; ISOLATED RAT-HEART; INHALED NO; FREE-RADICALS; OXIDATIVE STRESS; S-NITROSYLATION; MECHANISMS C1 [Spagnolli, Ester; Zapol, Warren M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02163 USA. RP Spagnolli, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02163 USA. NR 72 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-119-97543-4; 978-0-470-68668-3 PY 2011 BP 63 EP 77 D2 10.1002/9781119975427 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA5XQ UT WOS:000337054800006 ER PT B AU Mirzakhani, H Nozari, A AF Mirzakhani, Hooman Nozari, Ala BE Mozzarelli, A Bettati, S TI Ischemia SO CHEMISTRY AND BIOCHEMISTRY OF OXYGEN THERAPEUTICS: FROM TRANSFUSION TO ARTIFICIAL BLOOD LA English DT Article; Book Chapter ID POSTISCHEMIC TISSUE-INJURY; COMPLETE CEREBRAL-ISCHEMIA; SICKLE-CELL-DISEASE; METHYL-D-ASPARTATE; CARDIAC-ARREST; NITRIC-OXIDE; INTRACELLULAR CALCIUM; NEUROLOGIC RECOVERY; ARTERY OCCLUSION; OXYGEN-THERAPY C1 [Mirzakhani, Hooman; Nozari, Ala] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02163 USA. RP Mirzakhani, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02163 USA. NR 85 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-119-97543-4; 978-0-470-68668-3 PY 2011 BP 145 EP 158 D2 10.1002/9781119975427 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA5XQ UT WOS:000337054800011 ER PT B AU Moskowitz, A Chan, YFY Singhal, AB AF Moskowitz, Ari Chan, Yu-Feng Yvonne Singhal, Aneesh B. BE Mozzarelli, A Bettati, S TI Normobaric and Hyperbaric Oxygen Therapy for Ischemic Stroke and Other Neurological Conditions SO CHEMISTRY AND BIOCHEMISTRY OF OXYGEN THERAPEUTICS: FROM TRANSFUSION TO ARTIFICIAL BLOOD LA English DT Article; Book Chapter ID FOCAL CEREBRAL-ISCHEMIA; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; FLUID-PERCUSSION INJURY; TRAUMATIC BRAIN-INJURY; RAT MODEL; ARTERY OCCLUSION; INFARCT VOLUME; EMBOLIC STROKE; UP-REGULATION; BLOOD-FLOW C1 [Moskowitz, Ari; Chan, Yu-Feng Yvonne] Mt Sinai Med Ctr, Dept Emergency Med, New York, NY 10029 USA. [Singhal, Aneesh B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Moskowitz, A (reprint author), Mt Sinai Med Ctr, Dept Emergency Med, New York, NY 10029 USA. NR 107 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-119-97543-4; 978-0-470-68668-3 PY 2011 BP 159 EP 177 D2 10.1002/9781119975427 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA5XQ UT WOS:000337054800012 ER PT J AU Prabhu, SP Ng, S Vajapeyam, S Kieran, MW Pollack, IF Geyer, R Haas-Kogan, D Boyett, JM Kun, L Poussaint, TY AF Prabhu, Sanjay P. Ng, Sarah Vajapeyam, Sridhar Kieran, Mark W. Pollack, Ian F. Geyer, Russell Haas-Kogan, Daphne Boyett, James M. Kun, Larry Poussaint, Tina Young TI DTI assessment of the brainstem white matter tracts in pediatric BSG before and after therapy SO CHILDS NERVOUS SYSTEM LA English DT Article DE MRI; Diffusion tensor imaging; Brainstem glioma; Pediatrics ID HIGH-GRADE GLIOMAS; DIFFUSION; TUMORS; INVOLVEMENT; PATTERNS; TRACKING; CHILDREN AB To assess changes in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in brainstem gliomas (BSG) in children and to observe the temporal evolution of changes in the white matter tracts following therapy using diffusion tensor imaging (DTI) analysis. Serial ADC and FA measurements were obtained in three patients with newly diagnosed BSG on two approved treatment protocols. Values were compared with a set of normative ADC, FA, and eigenvalues of age-matched children of the corticospinal, transverse pontine and medial lemniscal tracts. Fiber tracking of the tracts coursing through the brainstem was performed using standard diffusion tractography analysis. We found increased ADC values within tumor at baseline compared to age-matched controls, with subsequent drop following treatment and subsequent increase with recurrence. Correspondingly, FA values were reduced at presentation, but transiently recovered during the phase of tumor response to treatment, and finally decreased significantly during tumor progression. These changes were concordant with the tractography analysis of white matter tracts in the brainstem. Based on these results, we suggest that initial changes in ADC and FA values reflects tract infiltration by tumor, but not complete disruption, whereas tumor progression results in complete loss of anisotropy possibly due to tract disruption. Serial changes in ADC and FA values and tractography data in pediatric BSG suggest initial tumor infiltration, with transient improvement on treatment and subsequent loss of tract anisotropy during tumor progression. This technique may have potential use in assessing response to treatment regimens for pediatric BSG. C1 [Prabhu, Sanjay P.; Ng, Sarah; Vajapeyam, Sridhar; Poussaint, Tina Young] Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp Boston, Boston, MA 02115 USA. [Kieran, Mark W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pollack, Ian F.] Childrens Hosp Pittsburgh, Dept Neurosurg, Pittsburgh, PA 15213 USA. [Geyer, Russell] Seattle Childrens Hosp, Dept Hematol Oncol, Seattle, WA 98105 USA. [Haas-Kogan, Daphne] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. [Boyett, James M.] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA. [Kun, Larry] St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. RP Prabhu, SP (reprint author), Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp Boston, 300 Longwood Ave, Boston, MA 02115 USA. EM sanjay.prabhu@childrens.harvard.edu FU National Institute of Health (NIH) [U01 CA81457]; Pediatric Brain Tumor Consortium Foundation; Pediatric Brain Tumor Foundation of the United States; American Lebanese-Syrian Associated Charities FX The authors acknowledge the support of the National Institute of Health (NIH) [U01 CA81457], the Pediatric Brain Tumor Consortium Foundation, the Pediatric Brain Tumor Foundation of the United States, and the American Lebanese-Syrian Associated Charities. NR 19 TC 18 Z9 19 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0256-7040 J9 CHILD NERV SYST JI Childs Nerv. Syst. PD JAN PY 2011 VL 27 IS 1 BP 11 EP 18 DI 10.1007/s00381-010-1323-7 PG 8 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 701AO UT WOS:000285786900004 PM 21052693 ER PT J AU Hui, KKKS Sporko, TN Vangel, MG Li, M Fang, JL Lao, LX AF Hui, Kathleen K. K. S. Sporko, Tara N. Vangel, Mark G. Li, Ming Fang, Jiliang Lao, Lixing TI Perception of Deqi by Chinese and American acupuncturists: a pilot survey SO CHINESE MEDICINE LA English DT Article AB Background: In acupuncture, deqi is the sensory experience related to clinical efficacy. As the first study taking into account cultural differences on deqi sensation, this pilot survey aims to corroborate the acupuncturists' general experience in clinical practice with functional magnetic resonance imaging (fMRI) findings. Methods: Questionnaires were distributed to acupuncturists of TCM (traditional Chinese medicine) hospitals and acupuncturists attending workshops and seminars in the United States and China. Questions covered clinical significance of deqi, patient attitude and the nature of some pain-related sensations elicited by manual needling. Results: 47 out of a total of 86 acupuncturists agreed that dull pain was deqi and over half regarded it beneficial, while sharp pain was non-deqi and harmful instead. The patients' attitude toward deqi sensation showed a difference between US and China. There was no other dimension showing a difference. Conclusion: Results of this pilot survey indicate that the acupuncturists' perception is consistent with our previous fMRI findings. Results showed almost complete agreement that dull pain is considered deqi and beneficial to treatment, while sharp pain is not deqi and harmful. Particularly, dull pain was deqi and was beneficial to treatment whereas sharp pain was not. Patients in China liked the deqi experience whereas those in the US did not. C1 [Hui, Kathleen K. K. S.; Sporko, Tara N.; Vangel, Mark G.; Li, Ming; Fang, Jiliang] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Hui, Kathleen K. K. S.; Sporko, Tara N.; Vangel, Mark G.; Li, Ming; Fang, Jiliang] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Fang, Jiliang] China Acad Chinese Med Sci, Guang AnMen Hosp, Dept Radiol, Beijing 100053, Peoples R China. [Lao, Lixing] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21207 USA. RP Sporko, TN (reprint author), Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. EM tsporko@nmr.mgh.harvard.edu RI Lao, Lixing/I-7979-2013; OI Lao, Lixing/0000-0003-0198-9714 FU NIH/National Center for Complementary and Alternative Medicine [1-P01-002048-01, 2-P01-002048-06]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery Institute (MIND); Brain Project Grant [NS 34189] FX The work was supported by the NIH/National Center for Complementary and Alternative Medicine (1-P01-002048-01) (2-P01-002048-06), National Center for Research Resources (P41RR14075), Mental Illness and Neuroscience Discovery Institute (MIND) and Brain Project Grant (NS 34189). NR 28 TC 19 Z9 25 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-8546 J9 CHIN MED-UK JI Chin. Med. PY 2011 VL 6 AR UNSP 2 DI 10.1186/1749-8546-6-2 PG 5 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA V29AU UT WOS:000208722100002 PM 21251312 ER PT J AU Eckman, MH Singer, DE Rosand, J Greenberg, SM AF Eckman, Mark H. Singer, Daniel E. Rosand, Jonathan Greenberg, Steven M. TI Moving the Tipping Point The Decision to Anticoagulate Patients With Atrial Fibrillation SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE anticoagulants; atrial fibrillation; health services research; stroke prevention; decision analysis ID CLINICAL CLASSIFICATION SCHEMES; LOBAR INTRACEREBRAL HEMORRHAGE; WARFARIN-ASSOCIATED HEMORRHAGE; STROKE RISK STRATIFICATION; ANTITHROMBOTIC THERAPY; INTRACRANIAL HEMORRHAGE; CEREBRAL-HEMORRHAGE; ORAL ANTICOAGULANTS; AMYLOID ANGIOPATHY; RANDOMIZED-TRIALS AB Background-The rate of ischemic stroke associated with traditional risk factors for patients with atrial fibrillation has declined over the past 2 decades. Furthermore, new and potentially safer anticoagulants are on the horizon. Thus, the balance between risk factors for stroke and benefit of anticoagulation may be shifting. Methods and Results-The Markov state transition decision model was used to analyze the CHADS(2) score, above which anticoagulation is preferred, first using the stroke rate predicted for the CHADS(2) derivation cohort, and then using the stroke rate from the more contemporary AnTicoagulation and Risk Factors In Atrial Fibrillation cohort for any CHADS(2) score. The base case was a 69-year-old man with atrial fibrillation. Interventions included oral anticoagulant therapy with warfarin or a hypothetical "new and safer" anticoagulant (based on dabigatran), no antithrombotic therapy, or aspirin. Warfarin is preferred above a stroke rate of 1.7% per year, whereas aspirin is preferred at lower rates of stroke. Anticoagulation with warfarin is preferred even for a score of 0 using the higher rates of the older CHADS(2) derivation cohort. Using more contemporary and lower estimates of stroke risk raises the threshold for use of warfarin to a CHADS(2) score >= 2. However, anticoagulation with a "new, safer" agent, modeled on the results of the Randomized Evaluation of Long-Term Anticoagulation Therapy trial of dabigatran, leads to a lowering of the threshold for anticoagulation to a stroke rate of 0.9% per year. Conclusions-Use of a more contemporary estimate of stroke risk shifts the "tipping point," such that anticoagulation is preferred at a higher CHADS(2) score, reducing the number of patients for whom anticoagulation is recommended. The introduction of "new, safer" agents, however, would shift the tipping point in the opposite direction. (Circ Cardiovasc Qual Outcomes. 2011;4:14-21.) C1 [Eckman, Mark H.] Univ Cincinnati, Med Ctr, Div Gen Internal Med, Cincinnati, OH 45267 USA. [Eckman, Mark H.] Univ Cincinnati, Ctr Clin Effectiveness, Cincinnati, OH USA. [Rosand, Jonathan; Greenberg, Steven M.] Massachusetts Gen Hosp, Dept Neurol, Res Grp, Boston, MA 02114 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Eckman, MH (reprint author), Univ Cincinnati, Med Ctr, Div Gen Internal Med, POB 670535, Cincinnati, OH 45267 USA. EM mark.eckman@uc.edu FU National Center for Research Resources; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Library of Medicine; Massachusetts General Hospital; National Institutes of Neurological Disorders and Stroke; Gilead Sciences, Inc.; Daiichi Sankyo Inc. FX Dr Eckman was supported by The National Center for Research Resources, The National Institute of Diabetes and Digestive and Kidney Diseases, The National Heart, Lung, and Blood Institute, and the National Library of Medicine. Dr Singer was supported by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital, and The National Heart, Lung, and Blood Institute. Dr Rosand was supported by National Institutes of Neurological Disorders and Stroke. The funding sources listed had no role in the design or implementation of the study or in the decision to seek publication.; Dr Eckman has consulted for Savient Pharmaceuticals and has received research support from Gilead Sciences, Inc. Dr Singer has consulted for Boehringer Ingelheim, Daiichi Sankyo, Inc, Bayer Healthcare, Johnson & Johnson, Inc, Merck and Co, and Sanofi Aventis, Inc, and has received research support from Daiichi Sankyo Inc. NR 53 TC 102 Z9 103 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 EI 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2011 VL 4 IS 1 BP 14 EP 21 DI 10.1161/CIRCOUTCOMES.110.958108 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 707TS UT WOS:000286311700006 PM 21139092 ER PT J AU Joynt, KE Jha, AK AF Joynt, Karen E. Jha, Ashish K. TI Who Has Higher Readmission Rates for Heart Failure, and Why? Implications for Efforts to Improve Care Using Financial Incentives SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE heart failure; quality of care; outcomes research; readmissions ID PAY-FOR-PERFORMANCE; QUALITY-OF-CARE; ADMINISTRATIVE DATA; MYOCARDIAL-INFARCTION; HOSPITAL READMISSION; SOCIOECONOMIC-STATUS; ELDERLY-PATIENTS; OUTCOMES; ASSOCIATION; REFORM AB Background-Reducing readmissions for heart failure is an important goal for policymakers. Current national policies financially penalize hospitals with high readmission rates, which may have unintended consequences if these institutions are resource-poor, either financially or clinically. Methods and Results-We analyzed national claims data for Medicare patients with heart failure discharged from US hospitals in 2006 to 2007. We used multivariable models to examine hospital characteristics, 30-day all-cause readmission rates, and likelihood of performing in the worst quartile of readmission rates nationally. Among 905 764 discharges in our sample, patients discharged from public hospitals (27.9%) had higher readmission rates than nonprofit hospitals (25.7%, P<0.001), as did patients discharged from hospitals in counties with low median income (29.4%) compared with counties with high median income (25.7%, P<0.001). Patients discharged from hospitals without cardiac services (27.2%) had higher readmission rates than those from hospitals with full cardiac services (25.1%, P<0.001); patients discharged from hospitals in the lowest quartile of nurse staffing (28.5%) had higher readmission rates than those from hospitals in the highest quartile (25.4%, P<0.001). Patients discharged from small hospitals (28.4%) had higher readmission rates than those discharged from large hospitals (25.2%, P<0.001). These same characteristics identified hospitals that were likely to perform in the worst quartile nationally. Conclusions-Given that many poor-performing hospitals also have fewer resources, they may suffer disproportionately from financial penalties for high readmission rates. As we seek to improve care for patients with heart failure, we should ensure that penalties for poor performance do not worsen disparities in quality of care. (Circ Cardiovasc Qual Outcomes. 2011;4:53-59.) C1 [Joynt, Karen E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. [Joynt, Karen E.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA. RP Joynt, KE (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM kjoynt@partners.org FU NIH [T32HL007604-24]; Brigham and Women's Hospital, Division of Cardiovascular Medicine FX Dr Joynt was supported by NIH Training Grant T32HL007604-24, Brigham and Women's Hospital, Division of Cardiovascular Medicine. NR 33 TC 85 Z9 86 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2011 VL 4 IS 1 BP 53 EP 59 DI 10.1161/CIRCOUTCOMES.110.950964 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 707TS UT WOS:000286311700011 PM 21156879 ER PT J AU Funkhouser, E Houston, TK Levine, DA Richman, J Allison, JJ Kiefe, CI AF Funkhouser, Ellen Houston, Thomas K. Levine, Deborah A. Richman, Joshua Allison, Jeroan J. Kiefe, Catarina I. TI Physician and Patient Influences on Provider Performance beta-Blockers in Postmyocardial Infarction Management in the MI-Plus Study SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE myocardial infarction; beta-blockers; provider performance ID ACUTE MYOCARDIAL-INFARCTION; TRANSIENT ISCHEMIC ATTACK; HEALTH-CARE; SECONDARY PREVENTION; CLINICAL-EXPERIENCE; RANDOMIZED TRIAL; ELDERLY-PATIENTS; KIDNEY-DISEASE; QUALITY; GUIDELINES AB Background-Efforts to improve the quality of care for patients with cardiovascular disease frequently target the decrease of physician-level performance variability. We assessed how variability in providing beta-blockers to ambulatory postmyocardial infarction (MI) patients was influenced by physician and patient level characteristics. Methods and Results-beta-Blocker prescription and patient characteristics were abstracted from charts of post-MI patients treated by 133 primary care physicians between 2003 and 2007 and linked to physician and practice characteristics. Associations of beta-blocker prescription with physician-and patient-level characteristics were examined using mixed-effects models, with physician-level effects as random. Mean physician-specific predicted probabilities and the intraclass correlations, which assessed the proportion of variance explainable at the physician level, were estimated. Of 1901 patients without major contraindication, 69.1% (range across physicians, 20% to 100%) were prescribed beta-blockers. Prescription varied with comorbidity from 78.3% in patients with chronic kidney disease to 54.7% for patients with stroke. Although physician characteristics such as older physician age, group practice, and rural location were each positively associated with beta-blocker prescription, physician factors accounted for only 5% to 8% of the variance in beta-blocker prescription; the preponderance of the variance, 92% to 95%, was at the patient level. The mean physician-specific probability of beta-blocker prescription (95% confidence interval) in the fully adjusted model was 63% (61% to 65%). Conclusions-beta-Blocker prescription rates were surprisingly low. The contribution of physician factors to overall variability in beta-blocker prescription, however, was limited. Increasing evidence-based use of beta-blockers may not be accomplished by focusing mostly on differential performance across physicians. (Circ Cardiovasc Qual Outcomes. 2011;4:99-106.) C1 [Funkhouser, Ellen; Richman, Joshua] Birmingham VA Med Ctr, VA Res Enhancement Award Program, Birmingham, AL USA. [Funkhouser, Ellen; Levine, Deborah A.; Richman, Joshua] Univ Alabama, Sch Med, Dept Med, Birmingham, AL USA. [Funkhouser, Ellen; Richman, Joshua] Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. [Houston, Thomas K.; Allison, Jeroan J.; Kiefe, Catarina I.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. [Levine, Deborah A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Levine, Deborah A.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Levine, Deborah A.] Univ Michigan, VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. RP Funkhouser, E (reprint author), UAB, SOM, Div Prevent Med, 1717 11th Ave S,611 MT, Birmingham, AL 35205 USA. EM emfunk@uab.edu RI Houston, Thomas/F-2469-2013 FU Centers for Medicare and Medicaid Services, Department of Health Human Services [500-02-AL02]; National Heart, Lung, and Blood Institute [R01 HL70786]; VA Health Services Research and Development [SDR 03-090-1] FX We greatly appreciate the contributions of the Division of Continuing Medical Education at the University of Alabama at Birmingham and Periyakaruppan Krishnamoorthy, whose expertise in computer programming and website development facilitated the completion of this project. The analyses on which this publication is based were performed under Contract No. 500-02-AL02, entitled "Utilization and Quality Control Peer Review Organization for the State (Commonwealth) of Alabama," sponsored by the Centers for Medicare and Medicaid Services, Department of Health & Human Services.; This project was funded in part by grant NR 39 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2011 VL 4 IS 1 BP 99 EP 106 DI 10.1161/CIRCOUTCOMES.110.942318 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 707TS UT WOS:000286311700017 PM 21139090 ER PT J AU Alexander, KP Wang, TY Li, SA Lytle, BL Slattery, LE Calhoun, S Poteat, J Roe, MT Rumsfeld, JS Cannon, CP Peterson, ED AF Alexander, Karen P. Wang, Tracy Y. Li, Shuang Lytle, Barbara L. Slattery, Lara E. Calhoun, Sarah Poteat, Jennifer Roe, Matthew T. Rumsfeld, John S. Cannon, Christopher P. Peterson, Eric D. TI Randomized Trial of Targeted Performance Feedback to Facilitate Quality Improvement in Acute Myocardial Infarction Care SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE randomized controlled trials; quality improvement; acute myocardial infarction ID ACUTE CORONARY SYNDROMES; OF-CARE; OUTCOMES; INTERVENTION; ASSOCIATION; GUIDELINES; LESSONS; SURGERY AB Background-Efforts to improve quality of care for patients with acute myocardial infarction (AMI) are a national priority. To date, there have been few studies that have prospectively evaluated hospital quality improvement (QI) interventions. Methods and Results-Using hospitals in the National Cardiovascular Data Registry (NCDR) ACTION Registry-GWTG, a cluster randomized trial of the effectiveness of targeted performance feedback to facilitate process improvement for AMI care will be conducted. ACTION Registry-GWTG hospitals with a minimum of 50 AMI patients per 2 quarters are eligible for randomization. The control arm receives standard performance feedback reports, and the intervention arm receives standard performance feedback reports in addition to a supplemental report on the "top 3" centrally identified, hospital-specific performance gaps. The primary outcome will be improvement in a composite of all metrics, and the secondary outcome will be improvement in the targeted metrics. At study inception in January 2009, 149 sites were randomized: 76 to the intervention arm, and 73 to the control arm. Intervention and control sites were well balanced in terms of baseline performance, center characteristics, and AMI volume (approximate to 70 patients per quarter). The intervention phase will continue for 5 feedback cycles, each containing 2 quarters of data feedback over 18 months. A final trial outcome report will follow. Conclusions-This randomized trial will evaluate a novel hospital-level QI intervention of targeted performance feedback for AMI, thereby demonstrating the effective use of national registries for QI and furthering our understanding of effective QI methods. C1 [Alexander, Karen P.; Wang, Tracy Y.; Li, Shuang; Lytle, Barbara L.; Calhoun, Sarah; Poteat, Jennifer; Roe, Matthew T.; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. [Alexander, Karen P.; Wang, Tracy Y.; Roe, Matthew T.; Peterson, Eric D.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Slattery, Lara E.] Amer Coll Cardiol, Washington, DC USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Alexander, KP (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Box 3411, Durham, NC 27710 USA. EM karen.alexander@duke.edu FU Agency for Healthcare Research and Quality [U18HS010548]; Society of Chest Pain Centers; Society of Hospital Medicine; American College of Emergency Physicians; Bristol-Myers Squibb/Sanofi Pharmaceuticals; Bristol Myers Squibb; Daiichi Pharmaceuticals; Heartscape Technologies; Johnson Johnson; Lilly; Sanofi-Aventis; Schering Plough Corporation; Medicines Company; Eli Lilly Co; Acumetrics; AstraZeneca; GlaxoSmithKline; Intekrin Therapeutis; Merck; Takeda; Bristol-Myers Squibb/Sanofi; Novartis; Alnylam; American College of Cardiology; Society of Thoracic Surgeons; American Heart Association FX This project was supported by grant number U18HS010548 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors, and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. The ACTION Registry-GWTG is an initiative of the American College of Cardiology Foundation and the American Heart Association, with partnering support from Society of Chest Pain Centers, The Society of Hospital Medicine, and The American College of Emergency Physicians. The registry is sponsored by Bristol-Myers Squibb/Sanofi Pharmaceuticals.; Dr Wang received research grants from Bristol Myers Squibb, Daiichi Pharmaceuticals, Heartscape Technologies, Johnson & Johnson, Lilly, Sanofi-Aventis, Schering Plough Corporation, and The Medicines Company; education activities or lectures include Heartscape Technologies. Dr Roe received research grants from Bristol Myers Squibb, Eli Lilly & Co, Sanofi-Aventis, and Schering-Plough Corporation; consulting includes AstraZeneca, Bristol Myers Squibb, Eli Lilly & Company, Glaxo SmithKline, Merck & Co, Novartis Pharmaceutical Company, Sanofi-Aventis, and Schering-Plough Corporation. Dr Rumsfeld is Chief Science Officer for the National Cardiovascular Data Registry (NCDR). Dr Cannon received research grants from Acumetrics, AstraZeneca, GlaxoSmithKline, Intekrin Therapeutis, Merck, and Takeda; advisory board (but funds donated to charity) includes Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam; honorarium for development of independent educational symposia includes Pfizer and AstraZeneca; clinical advisor and equity in Automedics Medical Systems. Dr Peterson received research grants from the American College of Cardiology, Bristol Myers Squibb, Eli Lilly & Company, Johnson & Johnson, Merck & Co, Sanofi-Aventis, Schering-Plough Corporation, the Society of Thoracic Surgeons, and the American Heart Association; consulting includes Bristol Myers Squibb, Merck & Co, and Tethysbio, Astra Zeneca. NR 23 TC 4 Z9 4 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD JAN PY 2011 VL 4 IS 1 BP 129 EP 135 DI 10.1161/CIRCOUTCOMES.110.958470 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 707TS UT WOS:000286311700021 PM 21245461 ER PT J AU Komajda, M Carson, PE Hetzel, S McKelvie, R McMurray, J Ptaszynska, A Zile, MR DeMets, D Massie, BM AF Komajda, Michel Carson, Peter E. Hetzel, Scott McKelvie, Robert McMurray, John Ptaszynska, Agata Zile, Michael R. DeMets, David Massie, Barry M. TI Factors Associated With Outcome in Heart Failure With Preserved Ejection Fraction Findings From the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-PRESERVE) SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; preserved ejection fraction; outcome; prognosis evaluation ID OBSTRUCTIVE PULMONARY-DISEASE; CONVERTING ENZYME-INHIBITORS; SYSTOLIC FUNCTION; MYOCARDIAL-INFARCTION; CONTROLLED-TRIAL; RISK-FACTOR; MORTALITY; DYSFUNCTION; PREDICTION; HOSPITALIZATIONS AB Background-The determinants of prognosis in patients with heart failure and preserved ejection fraction (HF-PEF) are poorly documented. Methods and Results-We evaluated data from 4128 patients in the I-PRESERVE trial (Irbesartan in Heart Failure with Preserved Ejection Fraction Study). Multivariable Cox regression models were developed using 58 baseline demographic, clinical, and biological variables to model the primary outcome of all-cause mortality or cardiovascular hospitalization (1505 events), all-cause mortality (881 events), and HF death or hospitalization (716 events). Log N-terminal pro-B-type natriuretic peptide, age, diabetes mellitus, and previous hospitalization for HF were the most powerful factors associated with the primary outcome and with the HF composite. For all-cause mortality, log N-terminal pro-B-type natriuretic peptide, age, diabetes mellitus, and left ventricular EF were the strongest independent factors. Other independent factors associated with poor outcome included quality of life, a history of chronic obstructive lung disease, log neutrophil count, heart rate, and estimated glomerular filtration rate. The models accurately stratified the actual 3-year rate of outcomes from 8.1% to 59.9% (primary outcome) 2.7% to 36.5% (all-cause mortality), and 2.1% to 38.9% (HF composite) for the lowest to highest septiles of predicted risks. Conclusions-In a large sample of elderly patients with HF and preserved EF enrolled in I-Preserve, simple clinical, demographic, and biological variables were associated with outcome and identified subgroups at very high and very low risk of events. C1 [Komajda, Michel] Univ Paris 06, Pitie Salpetriere Hosp, Paris, France. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Carson, Peter E.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Hetzel, Scott; DeMets, David] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [McKelvie, Robert] McMaster Univ, Hamilton, ON, Canada. [McMurray, John] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Ptaszynska, Agata] Bristol Myers Squibb Co, Princeton, NJ USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Zile, Michael R.] Vet Affairs Med Ctr, RHJ Dept, Charleston, SC 29403 USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Komajda, M (reprint author), CHU Pitie Salpetriere, Inst Cardiol, 47-83 Blvd Hop, F-75013 Paris, France. EM michel.komajda@psl.aphp.fr FU Bristol-Myers-Squibb; SanofiAventis FX Drs Komajda, Carson, McKelvie, Zile, and Massie received consulting fees from Bristol-Myers-Squibb as Executive Committee Members of the I-PRESERVE trial. Dr McMurray received support from Bristol-Myers-Squibb to Glasgow University. Scott Hetzel and Dr DeMets are employed by the Statistical Data Analysis Center at the University of Wisconsin-Madison, which conducted statistical analysis for the study supported by Bristol-Myers-Squibb and SanofiAventis. Dr Ptaszynska is an employee of and has an equity interest in Bristol-Myers-Squibb. NR 40 TC 94 Z9 94 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2011 VL 4 IS 1 BP 27 EP U73 DI 10.1161/CIRCHEARTFAILURE.109.932996 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 707UC UT WOS:000286312900009 PM 21068341 ER PT J AU Stewart, GC Lopez-Molina, J Gottumukkala, RVSRK Rosner, GF Anello, MS Hecht, JL Winters, GL Padera, RF Baughman, KL Lipes, MA AF Stewart, Garrick C. Lopez-Molina, Javier Gottumukkala, Raju V. S. R. K. Rosner, Gregg F. Anello, Mary S. Hecht, Jonathan L. Winters, Gayle L. Padera, Robert F. Baughman, Kenneth L. Lipes, Myra A. TI Myocardial Parvovirus B19 Persistence Lack of Association With Clinicopathologic Phenotype in Adults With Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; viruses; biopsy; cardiomyopathy; myocarditis ID LEFT-VENTRICULAR DYSFUNCTION; POLYMERASE-CHAIN-REACTION; DILATED CARDIOMYOPATHY; B19-ASSOCIATED MYOCARDITIS; ENDOMYOCARDIAL BIOPSIES; CARDIOTROPIC VIRUSES; HIGH PREVALENCE; VIRAL GENOMES; INFECTION; DISEASE AB Background-Multiple viruses have been isolated from the heart, but their significance remains controversial. We sought to determine the prevalence of cardiotropic viruses in endomyocardial biopsy (EMB) samples from adult patients with heart failure (HF) and to define the clinicopathologic profile of patients exhibiting viral positivity. Methods and Results-EMB from 100 patients (median ejection fraction, 30%; interquartile range [IQR], 20% to 45%) presenting for cardiomyopathy evaluation (median symptom duration, 5 months; IQR, 1 to 13 months) were analyzed by polymerase chain reaction for adenovirus, cytomegalovirus, enteroviruses, Epstein-Barr virus, and parvovirus B19. Each isolate was sequenced, and viral load was determined. Parvovirus B19 was the only virus detected in EMB samples (12% of subjects). No patient had antiparvovirus IgM antibodies, but all had IgG antibodies, suggesting viral persistence. The clinical presentation of parvovirus-positive patients was markedly heterogeneous with both acute and chronic HF, variable ventricular function, and ischemic cardiomyopathy. No patient met Dallas histopathologic criteria for active or borderline myocarditis. Two patients with a positive cardiac MRI and presumed "parvomyocarditis" had similar viral loads to autopsy controls without heart disease. The oldest parvovirus-positive patients were positive for genotype 2, suggesting lifelong persistence in the myocardium. Conclusions-Parvovirus B19 was the only virus isolated from EMB samples in this series of adult patients with HF from the United States. Positivity was associated with a wide array of clinical presentations and HF phenotypes. Our studies do not support a causative role for parvovirus B19 persistence in HF and, therefore, advocate against the use of antiviral therapy for these patients. (Circ Heart Fail. 2011;4:71-78.) C1 [Lopez-Molina, Javier; Gottumukkala, Raju V. S. R. K.; Lipes, Myra A.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Hecht, Jonathan L.] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Stewart, Garrick C.; Anello, Mary S.; Baughman, Kenneth L.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Winters, Gayle L.; Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Gottumukkala, Raju V. S. R. K.; Rosner, Gregg F.; Lipes, Myra A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Lipes, MA (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr, 1 Joslin Pl,Room 373, Boston, MA 02215 USA. EM myra.lipes@joslin.harvard.edu FU National Institutes of Health [R01 HL077554, 5P30 DK036836-24]; Harvard/MIT Health Sciences and Technology; Beth Israel Deaconess Medical Center; Pfizer Inc; Merck Co FX This work was supported by National Institutes of Health grant R01 HL077554 (to Dr Lipes) and 5P30 DK036836-24 (to the Joslin Diabetes Center). Additional support came from the Clinical Investigator Training Program at Harvard/MIT Health Sciences and Technology and Beth Israel Deaconess Medical Center in collaboration with Pfizer Inc and Merck & Co (to Dr Stewart). NR 35 TC 23 Z9 24 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD JAN PY 2011 VL 4 IS 1 BP 71 EP 78 DI 10.1161/CIRCHEARTFAILURE.110.958249 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 707UC UT WOS:000286312900015 PM 21097605 ER PT J AU Oklu, R Hesketh, R Wicky, S Metcalfe, JC AF Oeklue, Rahmi Hesketh, Robin Wicky, Stephan Metcalfe, James C. TI Localization of Latent Transforming Growth Factor-beta Binding Protein-1 in Human Coronary Atherosclerotic Plaques SO CIRCULATION JOURNAL LA English DT Article DE Atherosclerosis; Coronary heart disease; Genes; Immunohistochemistry; Molecular biology ID SMOOTH-MUSCLE-CELLS; AMERICAN-HEART-ASSOCIATION; TGF-BETA; EXTRACELLULAR-MATRIX; VASCULAR-LESIONS; EXPRESSION; RECEPTOR; COMPLEX; GROWTH-FACTOR-BETA-1; FACTOR-BETA-1 AB Background: Transforming growth factor-beta (TGF beta) and its receptors have been detected by immunohistochemistry in the normal vessel wall and in atherosclerotic lesions of human coronary arteries. However, TGF beta is normally secreted as an inactive complex associated with a latent TGF beta-binding protein (LTBP). Therefore, detection of TGF beta antigen only in the arterial wall does not imply the activated form of the growth factor. Methods and Results: In situ hybridization and immunohistochemistry demonstrated LTBP1 mRNA and protein expression throughout the media and intima of early coronary artery lesions, with the highest levels of protein at the luminal surface. In advanced lesions, LTBP1 mRNA and protein were detected mainly in regions of high cell density, such as the fibrous cap. Conclusions: Assays of the TGF beta signalling pathway will be required to determine the activity associated with TGF beta antigen in the vessel wall. (Circ J 2011; 75: 196-200) C1 [Oeklue, Rahmi; Wicky, Stephan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02155 USA. [Hesketh, Robin; Metcalfe, James C.] Univ Cambridge, Dept Biochem, Sect Cardiovasc Biol, Cambridge CB2 1QW, England. RP Oklu, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02155 USA. EM roklu@partners.org FU British Heart Foundation; Ali Y. Koc, Koc Holding, Istanbul, Turkey FX This work was supported by a Program Grant from the British Heart Foundation to J.C.M. R.O. is the recipient of a Koc scholarship from Ali Y. Koc, Koc Holding, Istanbul, Turkey. We thank the surgeons at Papworth Hospital for their cooperation. NR 30 TC 5 Z9 5 U1 0 U2 4 PU JAPANESE CIRCULATION SOC PI KYOTO PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO, 606-8305, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD JAN PY 2011 VL 75 IS 1 BP 196 EP 200 DI 10.1253/circj.CJ-10-0334 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 701JN UT WOS:000285814300032 PM 21071877 ER PT J AU Mallone, R Mannering, SI Brooks-Worrell, BM Durinovic-Bello, I Cilio, CM Wong, FS Schloot, NC AF Mallone, R. Mannering, S. I. Brooks-Worrell, B. M. Durinovic-Bello, I. Cilio, C. M. Wong, F. S. Schloot, N. C. CA Immunology Diabet Soc T Cell Works TI Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Review DE ELISPOT; freezing; shipping; T cell; tetramer ID LEPTIN RECEPTOR MUTATION; WHOLE-BLOOD; AUTOIMMUNE ENCEPHALOMYELITIS; LYMPHOCYTE IMMUNOPHENOTYPE; ACETYLCHOLINE-RECEPTOR; CYTOKINE PRODUCTION; ELISPOT DETECTION; OXIDATIVE STRESS; CLINICAL-TRIALS; FLOW-CYTOMETRY AB P>Autoimmune T cell responses directed against insulin-producing beta cells are central to the pathogenesis of type 1 diabetes (T1D). Detection of such responses is therefore critical to provide novel biomarkers for T1D 'immune staging' and to understand the mechanisms underlying the disease. While different T cell assays are being developed for these purposes, it is important to optimize and standardize methods for processing human blood samples for these assays. To this end, we review data relevant to critical parameters in peripheral blood mononuclear cell (PBMC) isolation, (cryo)preservation, distribution and usage for detecting antigen-specific T cell responses. Based on these data, we propose recommendations on processing blood samples for T cell assays and identify gaps in knowledge that need to be addressed. These recommendations may be relevant not only for the analysis of T cell responses in autoimmune disease, but also in cancer and infectious disease, particularly in the context of clinical trials. C1 [Mallone, R.] Hop St Vincent de Paul, DeAR Lab Avenir, INSERM, U986, F-75674 Paris 14, France. [Mannering, S. I.] Univ Melbourne, St Vincents Inst Med Res, Dept Med, St Vincents Hosp, Fitzroy, Vic 3065, Australia. [Brooks-Worrell, B. M.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Washington, DC USA. [Durinovic-Bello, I.] Benaroya Res Inst, Seattle, WA USA. [Cilio, C. M.] Lund Univ, Dept Clin Sci, Cellular Autoimmun Unit, Malmo, Sweden. [Wong, F. S.] Cardiff Univ, Ctr Endocrine & Diabet Sci, Cardiff, S Glam, Wales. [Schloot, N. C.] Univ Dusseldorf, Inst Clin Diabetol, German Diabet Ctr, Leibniz Inst Diabet Res,Dept Metab Dis,Univ Hosp, Dusseldorf, Germany. RP Mallone, R (reprint author), Hop St Vincent de Paul, DeAR Lab Avenir, INSERM, U986, 82 Ave Denfert Rochereau, F-75674 Paris 14, France. EM roberto.mallone@inserm.fr RI Mallone, Roberto/H-4430-2013 FU Juvenile Diabetes Research Foundation (JDRF) [5-2009-413] FX The T-Cell Workshop Committee of the Immunology of Diabetes Society is supported generously by the Juvenile Diabetes Research Foundation (JDRF grant no. 5-2009-413). We wish to thank L. C. Harrison, T. Delovitch, G. T. Nepom and B. O. Roep for critical review of the manuscript. NR 72 TC 80 Z9 82 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2011 VL 163 IS 1 BP 33 EP 49 DI 10.1111/j.1365-2249.2010.04272.x PG 17 WC Immunology SC Immunology GA 688LW UT WOS:000284851800005 PM 20939860 ER PT J AU Pickel, H Reich, O Young, RH AF Pickel, H. Reich, O. Young, R. H. TI Kiwisch von Rotterau - a pioneer of European obstetrics, gynecology and gynecopathology SO CLINICAL AND EXPERIMENTAL OBSTETRICS & GYNECOLOGY LA English DT Editorial Material C1 [Pickel, H.; Reich, O.] Med Univ Graz, Dept Obstet & Gynecol, A-8036 Graz, Austria. [Young, R. H.] Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Reich, O (reprint author), Med Univ Graz, Dept Obstet & Gynecol, Auenbruggerpl 14, A-8036 Graz, Austria. EM olaf.reich@meduni-graz.at NR 13 TC 0 Z9 0 U1 0 U2 0 PU I R O G CANADA, INC PI MONTREAL PA 4900 COTE ST-LUC, APT#212, MONTREAL, QUEBEC H3W 2H3, CANADA SN 0390-6663 J9 CLIN EXP OBSTET GYN JI Clin. Exp. Obstet. Gynecol. PY 2011 VL 38 IS 4 BP 338 EP 341 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 860LA UT WOS:000297948600011 PM 22268270 ER PT J AU Bi, XC Liu, JM Zheng, XG Xian, ZY Feng, ZW Lou, YX Zhong, WD Wu, CL AF Bi, Xue-cheng Liu, Jiu-Min Zheng, Xiang-guang Xian, Zhi-Yong Feng, Zi-Wei Lou, Yao-Xiong Zhong, Wei-de Wu, Chin-lee TI Over-expression of extracellular matrix metalloproteinase inducer in prostate cancer is associated with high risk of prostate-specific antigen relapse after radical prostatectomy SO CLINICAL AND INVESTIGATIVE MEDICINE LA English DT Article ID TUMOR-CELL INVASION; HEPATOCELLULAR-CARCINOMA; EMMPRIN; CD147; PROGNOSIS; MMP-2; ANGIOGENESIS; GROWTH; PROGRESSION; INHIBITION AB Purpose: The prognostic efficiency of clinical grading and staging in patients with confined or moderately differentiated prostate cancer (PCa) has been markedly improved, which underscores the importance of new prognostic markers. Extracellular matrix metalloproteinase inducer (EMMPRIN) has been demonstrated to be involved in cancerangiogenesis, metastasis and invasion. EMMPRIN expression was evaluated by measuring mRNA and protein levels in a large cohort of patients with PCa following prostatectomy and the findings were compared with clinico-pathological parameters, including prostate-specific antigen (PSA) relapse time. Methods: EMMPRIN mRNA levels in 20 pairs of normal and cancerous prostate tissues were determined by quantitative real-time PCR. Protein expression in paraffin-embedded specimens of prostates gathered from 300 patients with PCa was detected by immunohistochemistry using a monoclonal antibody against EMMPRIN. The associations of EMMPRIN protein expression with the clinico-pathological parameters and PSA relapse-free time after radical prostatectomy were subsequently assessed. Results: Both EMMPRIN mRNA and protein levels were higher in PCa tissue, compared with adjacent normal tissue. In addition, the positive expression rates of EMMPRIN in PCa tissues were significantly associated with preoperative PSA levels (p=0.008), AJCC stage (p=0.006) and Gleason Score (p<0.001), Risk classification (p<0.001), lymph node status post-surgery (p<0.001) and surgical margin status (p<0.001) were also determined. Multivariate analysis, using the Cox proportional hazards model, revealed that positive EMMPRIN expression was an independent prognostic factor for an increased risk of PSA relapse. Conclusion: Over-expression of EMMPRIN correlated with the aggressiveness of PCa, and the PSA relapse-free time, and may be a novel and useful biomarker for follow-up and treatment decisions for PCa. C1 [Zhong, Wei-de] Guangzhou First Municipal Peoples Hosp, Guangzhou Med Coll, Dept Urol, Guangzhou 510180, Guangdong, Peoples R China. [Bi, Xue-cheng; Liu, Jiu-Min; Zheng, Xiang-guang; Xian, Zhi-Yong; Feng, Zi-Wei; Lou, Yao-Xiong] Guangdong Acad Med Sci, Guangdong Gen Hosp, Dept Urol, Guangzhou 510180, Guangdong, Peoples R China. [Zhong, Wei-de] Guangzhou Med Coll, Urol Key Lab Guangdong Prov, Guangzhou 510230, Guangdong, Peoples R China. [Zhong, Wei-de] So Med Univ, Guangdong Prov Inst Nephrol, Guangzhou 510515, Guangdong, Peoples R China. [Wu, Chin-lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Zhong, WD (reprint author), Guangdong Gen Hosp, Municipal Peoples Hosp 1, Guangzhou Med Coll, Guangzhou 510180, Guangdong, Peoples R China. EM zhongwd2009@liven.cn FU National Natural Science Foundation of China [30872960, 81170699]; Guangzhou Municipal Science and Technology Key Project [11C23150711]; Bureau of Health in Guangzhou Municipality [201102A212015]; Guangdong Key Laboratory of Urology [2010A060801016] FX This work was supported by grants from National Natural Science Foundation of China (30872960, 81170699), Guangzhou Municipal Science and Technology Key Project (11C23150711), Key Projects of Bureau of Health in Guangzhou Municipality (201102A212015) and Projects of Guangdong Key Laboratory of Urology (2010A060801016). NR 35 TC 7 Z9 9 U1 0 U2 2 PU CANADIAN SOC CLINICAL INVESTIGATION PI OTTAWA PA CSCI HEAD OFFICE, 774 ECHO DRIVE, OTTAWA, ON K1S 5N8, CANADA SN 0147-958X J9 CLIN INVEST MED JI Clin. Invest. Med. PY 2011 VL 34 IS 6 BP E358 EP E365 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 857OG UT WOS:000297727400009 PM 22129926 ER PT J AU Morrow, DA Cook, NR AF Morrow, David A. Cook, Nancy R. TI Determining Decision Limits for New Biomarkers: Clinical and Statistical Considerations SO CLINICAL CHEMISTRY LA English DT Editorial Material ID OPERATING CHARACTERISTIC CURVE; PREDICTIVE ABILITY; ROC CURVE; RECLASSIFICATION; MEDICINE; MARKER; AREA; RISK C1 [Morrow, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. [Cook, Nancy R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 14 TC 5 Z9 5 U1 1 U2 3 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 JAN PY 2011 VL 57 IS 1 BP 1 EP 3 DI 10.1373/clinchem.2010.155879 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 699TQ UT WOS:000285686100001 PM 21078839 ER PT J AU Galbiati, S Brisci, A Lalatta, F Seia, M Makrigiorgos, GM Ferrari, M Cremonesi, L AF Galbiati, Silvia Brisci, Angela Lalatta, Faustina Seia, Manuela Makrigiorgos, G. Mike Ferrari, Maurizio Cremonesi, Laura TI Full COLD-PCR Protocol for Noninvasive Prenatal Diagnosis of Genetic Diseases SO CLINICAL CHEMISTRY LA English DT Letter C1 [Galbiati, Silvia; Brisci, Angela; Ferrari, Maurizio; Cremonesi, Laura] Ist Sci San Raffaele, Genom Unit Diag Human Pathol, Ctr Genom & Bioinformat, I-20132 Milan, Italy. [Seia, Manuela] Politecn Milan, Osped Maggiore, Fdn IRCCS Ca Granda, Med Genet Lab, I-20133 Milan, Italy. [Lalatta, Faustina] Politecn Milan, Osped Maggiore, Fdn IRCCS Ca Granda, UO Dipartimentale Genet Med, I-20133 Milan, Italy. [Makrigiorgos, G. Mike] Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Ferrari, Maurizio] Univ Vita Salute San Raffaele, Milan, Italy. [Ferrari, Maurizio] Diagnost & Ric San Raffaele SpA, Milan, Italy. RP Cremonesi, L (reprint author), Ist Sci San Raffaele, Genom Unit Diag Human Pathol, Ctr Genom & Bioinformat, Via Olgettina 60, I-20132 Milan, Italy. EM cremonesi.laura@hsr.it OI Galbiati, Silvia/0000-0003-1642-8506 FU NCI NIH HHS [R21 CA138280, R21 CA138280-02] NR 5 TC 25 Z9 30 U1 1 U2 7 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 JAN PY 2011 VL 57 IS 1 BP 136 EP 138 DI 10.1373/clinchem.2010.155671 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 699TQ UT WOS:000285686100023 PM 20974797 ER PT J AU Liang, YM Hasturk, H Elliot, J Noronha, A Liu, XP Wetzler, LM Massari, P Kantarci, A Winter, HS Farraye, FA Ganley-Leal, LM AF Liang, YanMei Hasturk, Hatice Elliot, Jennifer Noronha, Ansu Liu, Xiuping Wetzler, Lee M. Massari, Paola Kantarci, Alpdogan Winter, Harland S. Farraye, Francis A. Ganley-Leal, Lisa M. TI Toll-like receptor 2 induces mucosal homing receptor expression and IgA production by human B cells SO CLINICAL IMMUNOLOGY LA English DT Article DE Adjuvants; B cells; Toll-like receptor 2; Human; Mucosal immunity ID MENINGOCOCCAL PORIN PORB; CYTOKINE PRODUCTION; DISEASE PATIENTS; SECRETING CELLS; VACCINES; TLR2; INTUSSUSCEPTION; REQUIRES; IMMUNITY; GUT AB There is a need for developing vaccines that elicit mucosal immunity. Although oral or nasal vaccination methods would be ideal, current strategies have yielded mixed success. Toll-like receptor 2 (TLR2) ligands are effective adjuvants and are currently used in the Hoemophilus influenzae type B vaccine. Induction of humoral immunity in the mucosa is critical for effective vaccination; thus, we sought to determine the effects of TLR2 ligands on human mucosal B cell differentiation. We demonstrate that TLR2 ligands induce CCR9 and CCR10 expression by circulating B cells and increased chemotaxis to cognate chemokines CCL25 and CCL28 suggesting that TLR2 induces B cell homing to the gastrointestinal tract. TLR2 stimulation of B cells also induced J chain and IgA production demonstrating the induction of mucosal-like antibody secreting cells. These observations suggest that vaccines containing TLR2-ligands as adjuvants could induce mucosal B cell immunity even when delivered in a non-mucosal manner. (C) 2010 Elsevier Inc. All rights reserved. C1 [Liang, YanMei; Elliot, Jennifer; Liu, Xiuping; Wetzler, Lee M.; Massari, Paola; Ganley-Leal, Lisa M.] Boston Univ, Sch Med, Infect Dis Sect, Dept Med,Boston Med Ctr, Boston, MA 02118 USA. [Hasturk, Hatice; Kantarci, Alpdogan] Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. [Noronha, Ansu; Farraye, Francis A.] Boston Med Ctr, Gastroenterol Sect, Boston, MA 02118 USA. [Winter, Harland S.] MassGen Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA USA. RP Ganley-Leal, LM (reprint author), Boston Univ, Sch Med, Infect Dis Sect, Dept Med,Boston Med Ctr, 650 Albany St,Room 630, Boston, MA 02118 USA. EM lisa.ganleyleal@bmc.org OI Farraye, Francis/0000-0001-6371-2441; Massari, Paola/0000-0003-3106-0711 FU The Broad Foundation FX We would like to thank the volunteers who participated in this study. The authors appreciate the efforts of Jeremy Hetzel and Jennifer Coukos for clinical coordination, Marie Washek and Lauren Drake in collecting the pediatric samples, and Matthew Rarick for technical advice. This work was supported by Broad Medical Research Program of The Broad Foundation (L. M. G.-L.). This work was supported in part by philanthrophy provided by Martin Schlaff and Jim Brooks to Harland S. Winter, MD. NR 30 TC 16 Z9 16 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JAN PY 2011 VL 138 IS 1 BP 33 EP 40 DI 10.1016/j.clim.2010.09.003 PG 8 WC Immunology SC Immunology GA 713DA UT WOS:000286714000006 PM 20947433 ER PT J AU Granato, R Marin, C Gil, JN Chuang, SK Dodson, TB Suzuki, M Coelho, PG AF Granato, Rodrigo Marin, Charles Gil, Jose N. Chuang, Sung-Kiang Dodson, Thomas B. Suzuki, Marcelo Coelho, Paulo G. TI Thin Bioactive Ceramic-Coated Alumina-Blasted/Acid-Etched Implant Surface Enhances Biomechanical Fixation of Implants: An Experimental Study in Dogs SO CLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH LA English DT Article DE bioactive ceramic; cozating; dog; implant; in vivo; surface ID PLASMA-SPRAYED HYDROXYAPATITE; IN-VIVO; ENDOSSEOUS IMPLANTS; TITANIUM SURFACE; BONE; RABBIT AB Background: Thin bioceramic coatings have been regarded as potential substitutes for plasma-sprayed hydroxyapatite coatings. Purpose: This study tested the hypothesis that a thin bioactive ceramic coating deposition on an alumina-blasted/acid-etched (AB/AE) surface would positively affect the biomechanical fixation and bone-to-implant contact (BIC) of plateau root form implants. Materials and Methods: Implants of two different lengths (i.e., 4.5 x 11 mm long, n = 36) and 4.5 x 6 mm (short, n = 36) and two different surfaces, that is, control (AB/AE) and test (AB/AE + 300 - 500 nm bioactive ceramic coating), were placed in the proximal tibiae of six beagle dogs. The implants were retrieved for analyses 2 and 4 weeks after placement. The implants in bone specimens were subjected to torque loads until a 10% drop of the maximum torque was recorded. The specimens were evaluated under optical microscopy for bone morphology and percent BIC. Statistical analysis was performed by a generalized linear mixed effects analysis of variance model and statistical significance set at p < 0.05. Results: Significantly higher torque-to-interface fracture levels for test surface groups of both lengths when compared to control surfaces were observed. No significant difference in BIC was observed between test and control implants of equal length. Histomorphological analysis showed higher degrees of bone organization between the plateaus of test implant surfaces at both implantation times. Conclusion: Because the presence of a thin bioactive ceramic coating on the surface did not affect BIC, but positively affected implant biomechanical fixation, the hypothesis was partially validated. C1 [Granato, Rodrigo; Gil, Jose N.] Univ Fed Santa Catarina, Sch Dent, Florianopolis, SC, Brazil. [Marin, Charles] Pontificia Univ Catolica Rio Grande do Sul, Sch Dent, Dept Oral & Maxillofacial Surg, Porto Alegre, RS, Brazil. [Chuang, Sung-Kiang; Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang; Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Suzuki, Marcelo] Tufts Univ, Sch Dent Med, Dept Prosthodont, Boston, MA 02111 USA. [Coelho, Paulo G.] NYU, Sch Dent, Dept Biomat & Biomimet, New York, NY USA. RP Coelho, PG (reprint author), 345 24th St,Room 804S, New York, NY 10010 USA. EM pgcoelho@nyu.edu RI Marin, Charles/I-1821-2012; Granato, Rodrigo/A-5372-2013 FU Bicon LLC, Department of Oral and Maxillofacial Surgery at Federal University of Santa Catarina; Center for Applied Clinical Investigation, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital FX This study was partially funded by Bicon LLC, Department of Oral and Maxillofacial Surgery at Federal University of Santa Catarina, and the Center for Applied Clinical Investigation, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital (S.-K.C. and T.B.D.). NR 30 TC 17 Z9 17 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1523-0899 J9 CLIN IMPLANT DENT R JI Clin. Implant Dent. Relat. Res. PY 2011 VL 13 IS 2 BP 87 EP 94 DI 10.1111/j.1708-8208.2009.00186.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 754ZL UT WOS:000289896300001 PM 19681928 ER PT J AU Marty, FM Petschnigg, EM Hammond, SP Ready, JE Ho, VT Soiffer, RJ Magee, C Milner, DA Antin, JH Baden, LR AF Marty, Francisco M. Petschnigg, Eva M. Hammond, Sarah P. Ready, John E. Ho, Vincent T. Soiffer, Robert J. Magee, Colm Milner, Danny A. Antin, Joseph H. Baden, Lindsey R. TI Invasive Fungal Disease after Remote Inoculation in Transplant Recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CUTANEOUS ASPERGILLOSIS; CLADOPHIALOPHORA-BANTIANA; INFECTION AB We describe 3 cases of invasive fungal disease in the setting of transplantation-associated immunosuppression, developing months to years after clinically resolved penetrating soft-tissue injuries with wood fragments. Invasive fungal disease resulting from remote inoculation is a distinct syndrome in immunocompromised patients presenting with soft-tissue abnormalities in areas of prior trauma. C1 [Marty, Francisco M.; Petschnigg, Eva M.; Hammond, Sarah P.; Baden, Lindsey R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Ready, John E.] Brigham & Womens Hosp, Div Orthoped Surg, Boston, MA 02115 USA. [Ho, Vincent T.; Soiffer, Robert J.; Antin, Joseph H.] Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. [Magee, Colm] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. [Milner, Danny A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Marty, Francisco M.; Hammond, Sarah P.; Ho, Vincent T.; Soiffer, Robert J.; Antin, Joseph H.; Baden, Lindsey R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Marty, Francisco M.; Hammond, Sarah P.; Ready, John E.; Ho, Vincent T.; Soiffer, Robert J.; Milner, Danny A.; Antin, Joseph H.; Baden, Lindsey R.] Harvard Univ, Sch Med, Boston, MA USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A4, Boston, MA 02115 USA. EM fmarty@partners.org NR 11 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2011 VL 52 IS 1 DI 10.1093/cid/ciq040 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 706JI UT WOS:000286214200027 PM 21148507 ER PT J AU Ciesielski, KT Rowland, LM Harris, RJ Kerwin, AA Reeve, A Knight, JE AF Ciesielski, Kristina T. Rowland, Laura M. Harris, Richard J. Kerwin, Audra A. Reeve, Alya Knight, Jeanne E. TI Increased anterior brain activation to correct responses on high-conflict Stroop task in obsessive-compulsive disorder SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Obsessive-compulsive disorder (OCD); Event-related potentials (ERPs); Inhibition; A high-conflict Stroop task; Prefrontal cortex; Cingulate gyrus; Adaptive mechanism ID MEDIAL FRONTAL-CORTEX; ERROR-RELATED NEGATIVITY; WORKING-MEMORY TASK; CINGULATE CORTEX; COGNITIVE CONTROL; FUNCTIONAL-ANATOMY; LOBE DYSFUNCTION; ATTENTION; PERFORMANCE; INHIBITION AB Objective: An abnormally increased activation in anterior brain networks, accompanied by normal task performance, has been reported in studies on biological mechanisms of obsessive-compulsive disorder (OCD). We test a hypothesis, that this phenomenon, deemed specific to OCD, will be compromised by a very difficult task, which may lead to reduced cortical information processing and erroneous performance, as found in other disorders such as schizophrenia. Methods: We designed a new variant of high-conflict Stroop-word-color interference task (Stroop-WCIT) with each incongruent (INC) trial preceded by multiple congruent trials. Event-related potentials (ERPs) were acquired from subjects with OCD and case-matched healthy controls (C). We analyzed ERPs elicited by correct responses to conflict-related INC trials. Results: Our hypothesis found no support. Although the anterior ERPs N200, a negative component within 140-300 ms latency window, was significantly abnormally increased in OCD subjects, their performance accuracy remained normal. Conclusions: Current findings suggest an enhanced adaptive top-down control in OCD mediated by the prefrontal lateral and dorsal anterior cingulate networks. Significance: Further studies are warranted to test the hypothesis that increased activity within the anterior network for top-down inhibitory control in OCD may be a part of an adaptive compensatory neural mechanism. Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 [Ciesielski, Kristina T.] Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ciesielski, Kristina T.; Rowland, Laura M.; Harris, Richard J.; Kerwin, Audra A.; Knight, Jeanne E.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Reeve, Alya] Univ New Mexico, Hlth Sci Ctr, Dept Psychiat, Albuquerque, NM 87131 USA. RP Ciesielski, KT (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM ktc@nmr.mgh.harvard.edu NR 83 TC 12 Z9 13 U1 0 U2 10 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 JAN PY 2011 VL 122 IS 1 BP 107 EP 113 DI 10.1016/j.clinph.2010.05.027 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 695XS UT WOS:000285406600017 PM 20580602 ER PT J AU Gordon, SN Fitzpatrick, PJ Hilsabeck, RC AF Gordon, Shalanda N. Fitzpatrick, Pamela J. Hilsabeck, Robin C. TI No Effect of PTSD and Other Psychiatric Disorders on Cognitive Functioning in Veterans With Mild TBI SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Mild traumatic brain injury; mTBI; Post-traumatic stress disorder; PTSD; Cognitive functioning ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; HEAD-INJURY; POSTCONCUSSIVE SYMPTOMS; VIETNAM VETERANS; PROCESSING SPEED; TEST-PERFORMANCE; IRAQ-WAR; ATTENTION; SEQUELAE AB There has been speculation that post-traumatic stress disorder (PTSD) superimposed on mild traumatic brain injury (mTBI) may have synergistic, negative effects on cognitive functioning. The purpose of this study was to investigate differences in processing speed, executive functioning, and memory of 82 veterans with mTBI and PTSD, mTBI, and another psychiatric condition, or mTBI alone. It was hypothesized that there would be no group differences in cognitive performances. Participants completed the Trail Making Test, Stroop, Rey Complex Figure, and California Verbal Learning Test-2. There were no significant group differences on any cognitive measure. Findings suggest that PTSD and other psychiatric disorders do not necessarily have a negative exacerbating effect on processing speed, executive functioning, or memory in veterans with mTBI. C1 [Hilsabeck, Robin C.] S Texas Vet Hlth Care Syst, Psychol Serv 116B, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.] Univ Calif San Diego, San Diego, CA 92103 USA. [Gordon, Shalanda N.] Cent Texas Vet Hlth Care Syst, Temple, TX USA. RP Hilsabeck, RC (reprint author), S Texas Vet Hlth Care Syst, Psychol Serv 116B, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Hilsabeck@uthscsa.edu RI Schueter, nicos/A-3625-2014 NR 52 TC 15 Z9 15 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2011 VL 25 IS 3 BP 337 EP 347 AR PII 934025482 DI 10.1080/13854046.2010.550634 PG 11 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 751RU UT WOS:000289636100001 PM 21360415 ER PT J AU Pella, RD Fallows, RR Hilsabeck, RC AF Pella, Russell D. Fallows, Robert R. Hilsabeck, Robin C. TI Casebook of clinical neuropsychology. SO CLINICAL NEUROPSYCHOLOGIST LA English DT Book Review C1 [Pella, Russell D.; Fallows, Robert R.; Hilsabeck, Robin C.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Pella, RD (reprint author), S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM rpella1@lsu.edu NR 1 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 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2011 VL 25 IS 5 BP 843 EP 845 DI 10.1080/13854046.2011.586597 PG 3 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 882JE UT WOS:000299559000010 ER PT J AU Hilsabeck, RC Gordon, SN Hietpas-Wilson, T Zartman, AL AF Hilsabeck, Robin C. Gordon, Shalanda N. Hietpas-Wilson, Tammy Zartman, Andrea L. TI Use of Trial 1 of the Test of Memory Malingering (TOMM) as a Screening Measure of Effort: Suggested Discontinuation Rules SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Malingering; Effort; Discontinuation rules; Test of Memory Malingering; TOMM; Cognitive disorders ID BASE RATES; CLINICAL NEUROPSYCHOLOGY; INSUFFICIENT EFFORT; RESPONSE BIAS; UNITED-STATES; PERFORMANCE; NAN AB Trial 1 of the Test of Memory Malingering (TOMM) has been suggested as a screening tool, with several possible cut-off scores proposed. The purpose of the present study was to replicate the utility of previously suggested cut-off scores and to characterize neuropsychological profiles of persons who "pass'' the TOMM but obtain Trial 1 scores <45 and of persons with cognitive disorders. A total of 229 veterans were administered the TOMM as part of a neuropsychological evaluation. Trial 1 scores >= 41 and <= 25 showed good utility as discontinuation scores for adequate and poor effort, respectively, beyond which administration of additional trials were unnecessary. Findings suggest better Trial 1 performance is significantly related to better speeded mental flexibility and memory. C1 [Hilsabeck, Robin C.; Gordon, Shalanda N.; Hietpas-Wilson, Tammy; Zartman, Andrea L.] S Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Gordon, Shalanda N.] Cent Texas Vet Hlth Care Syst, Psychol Serv, Austin, TX USA. [Zartman, Andrea L.] Vet Affairs N Texas Hlth Care Syst, Psychol Serv, Dallas, TX USA. RP Hilsabeck, RC (reprint author), S Texas Vet Hlth Care Syst, Psychol Serv 116B, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM Hilsabeck@uthscsa.edu NR 26 TC 9 Z9 9 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2011 VL 25 IS 7 BP 1228 EP 1238 DI 10.1080/13854046.2011.589409 PG 11 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 882JJ UT WOS:000299559600009 PM 21846261 ER PT J AU Goudreau, KA AF Goudreau, Kelly A. TI LACE, APRN Consensus ... and WIIFM (What's in It for Me)? SO CLINICAL NURSE SPECIALIST LA English DT Editorial Material C1 Portland VA Med Ctr, Portland, OR 97239 USA. RP Goudreau, KA (reprint author), Portland VA Med Ctr, P2EDUC,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kagoudreau@hotmail.com NR 1 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD JAN-FEB PY 2011 VL 25 IS 1 BP 5 EP 7 DI 10.1097/NUR.0b013e3182036221 PG 3 WC Nursing SC Nursing GA 691NF UT WOS:000285087300002 PM 21139459 ER PT J AU Bedair, H Ting, N Jacovides, C Saxena, A Moric, M Parvizi, J Della Valle, CJ AF Bedair, Hany Ting, Nicholas Jacovides, Christina Saxena, Arjun Moric, Mario Parvizi, Javad Della Valle, Craig J. TI The Mark Coventry Award Diagnosis of Early Postoperative TKA Infection Using Synovial Fluid Analysis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the Knee-Society CY MAR, 2010 CL New Orleans, LA SP Knee Soc ID TOTAL KNEE ARTHROPLASTY; REVISION TOTAL HIP; BLOOD-CELL COUNTS; QUALITY-OF-LIFE; PROSTHESES; RATES AB Background Synovial fluid white blood cell count is useful for diagnosing periprosthetic infections but the utility of this test in the early postoperative period remains unknown as hemarthrosis and postoperative inflammation may render standard cutoff values inaccurate. Questions/purposes We evaluated the diagnostic performance of four common laboratory tests, the synovial white blood cell count, differential, C-reactive protein, and erythrocyte sedimentation rate to detect infection in the first 6 weeks after primary TKA. Methods We reviewed 11,964 primary TKAs and identified 146 that had a knee aspiration within 6 weeks of surgery. Infection was diagnosed in 19 of the 146 knees by positive cultures or gross purulence. We compared demographic information, time from surgery, and the laboratory test values between infected and noninfected knees to determine if any could identify infection early postoperatively. Receiver operating characteristic curves were constructed to determine optimal cutoff values for each of the test parameters. Results Synovial white blood cell count (92,600 versus 4200 cells/mu L), percentage of polymorphonuclear cells (89.6% versus 76.9%), and C-reactive protein (171 versus 88 mg/L) were higher in the infected group. The optimal synovial white blood cell cutoff was 27,800 cells/mu L (sensitivity, 84%; specificity, 99%; positive predictive value, 94%; negative predictive value, 98%) for diagnosing infection. The optimal cutoff for the differential was 89% polymorphonuclear cells and for C-reactive protein 95 mg/L. Conclusions With a cutoff of 27,800 cells/mu L, synovial white blood cell count predicted infection within 6 weeks after primary TKA with a positive predicted value of 94% and a negative predictive value of 98%. The use of standard cutoff values for this parameter (similar to 3000 cells/mu L) would have led to unnecessary reoperations. C1 [Bedair, Hany] Ctr Adult Joint Reconstruct, Newton, MA 02462 USA. [Bedair, Hany] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Bedair, Hany] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ting, Nicholas; Della Valle, Craig J.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [Moric, Mario] Rush Univ, Med Ctr, Dept Anesthesia, Chicago, IL 60612 USA. [Jacovides, Christina; Saxena, Arjun; Parvizi, Javad] Thomas Jefferson Univ, Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP Bedair, H (reprint author), Ctr Adult Joint Reconstruct, 2014 Washington St, Newton, MA 02462 USA. EM hbedair@gmail.com OI Moric, Mario/0000-0003-2844-8168 NR 28 TC 73 Z9 75 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2011 VL 469 IS 1 BP 34 EP 40 DI 10.1007/s11999-010-1433-2 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 716AX UT WOS:000286938400007 PM 20585914 ER PT J AU Bedair, H Berli, M Gezer, S Jacobs, JJ Della Valle, CJ AF Bedair, Hany Berli, Martin Gezer, Sefer Jacobs, Joshua J. Della Valle, Craig J. TI Hematologic Genetic Testing in High-risk Patients Before Knee Arthroplasty A Pilot Study SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the Knee-Society CY MAR, 2010 CL New Orleans, LA SP Knee Soc ID TOTAL HIP-ARTHROPLASTY; FACTOR-V-LEIDEN; VENOUS THROMBOSIS; THROMBOEMBOLIC DISEASE; PULMONARY-EMBOLISM; HEALTHY POPULATION; PROTHROMBIN GENE; THROMBOPHILIA; PREVALENCE; PLASMA AB Background Patients with a personal or familial history of thromboembolism are considered at higher risk for thromboembolic disease after knee arthroplasty. While it remains unclear why some patients develop deep vein thrombosis (DVT) or pulmonary embolism (PE) despite similar operative procedures and the same prophylactic regimen, we presume one explanation would be genetic predisposition. Questions/purposes We determined the frequency of 12 factors including antithrombin III activity, prothrombin gene mutations, and the presence of phospholipid antibodies in a high-risk patient cohort and compared those findings with the known prevalence in the population at large. Patients and Methods Patients identified preoperatively as having a personal or familial history of DVT and/or PE were referred for hemostatic serum and genetic tests, including % antithrombin III activity (ATIII), protein C and protein S activities, APC resistance, Factor V gene (Leiden) mutations, prothrombin gene mutations, lupus anticoagulant antibody presence, cardiolipin antibody presence, phosphatidyl antibody presence, beta 2-glycoprotein antibody presence, and serum homocysteine and lipoprotein(a) levels The frequencies of varying abnormalities were identified and compared to the prevalence reported in the literature. Results Forty-three of 1944 patients undergoing knee arthroplasty had a history of DVT or PE. Sixteen of 43 (37%) patients had an abnormality and eight of these (19%) had two or more abnormalities. The frequency of nine of the 12 tests appeared to be greater in this cohort than in the population at large. Conclusions Patients with a personal or familial history of DVT or PE appear to have a high frequency of hereditary prothrombotic abnormalities. Preoperative evaluation by a hematologist may be warranted in patients with a personal or familial history of DVT or PE as the postoperative anticoagulation protocols may be altered and identification of these abnormalities may affect a patient's risk for other disease states. C1 [Bedair, Hany] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Bedair, Hany] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bedair, Hany] Ctr Joint Reconstruct, Newton, MA 02462 USA. [Berli, Martin; Jacobs, Joshua J.; Della Valle, Craig J.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. [Gezer, Sefer] Rush Univ, Med Ctr, Dept Hematol, Chicago, IL 60612 USA. RP Bedair, H (reprint author), Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. EM hbedair@gmail.com OI Jacobs, Joshua/0000-0003-3902-7334 NR 22 TC 1 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2011 VL 469 IS 1 BP 131 EP 137 DI 10.1007/s11999-010-1514-2 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 716AX UT WOS:000286938400020 PM 20824408 ER PT J AU Nakano, V Silva, ADE Merino, VRC Wexler, HM Avila-Campos, MJ AF Nakano, Viviane do Nascimento e Silva, Amanda Castillo Merino, Victor Rafael Wexler, Hannah M. Avila-Campos, Mario Julio TI Antimicrobial resistance and prevalence of resistance genes in intestinal Bacteroidales strains SO CLINICS LA English DT Article DE Bacteroides spp.; Parabacteroides distasonis; beta-lactamase activity; Antimicrobial resistance; Resistance genes ID IN-VITRO ACTIVITY; ANAEROBIC-BACTERIA; CARBAPENEM RESISTANCE; INSERTION-SEQUENCE; MULTICENTER SURVEY; CLINICAL ISOLATE; FRAGILIS GROUP; SUSCEPTIBILITY; DETERMINANTS; INFECTIONS AB OBJECTIVE: This study examined the antimicrobial resistance profile and the prevalence of resistance genes in Bacteroides spp. and Parabacteroides distasonis strains isolated from children's intestinal microbiota. METHODS: The susceptibility of these bacteria to 10 antimicrobials was determined using an agar dilution method. beta-lactamase activity was assessed by hydrolysis of the chromogenic cephalosporin of 114 Bacteriodales strains isolated from the fecal samples of 39 children, and the presence of resistance genes was tested using a PCR assay. RESULTS: All strains were susceptible to imipenem and metronidazole. The following resistance rates were observed: amoxicillin (93%), amoxicillin/clavulanic acid (47.3%), ampicillin (96.4%), cephalexin (99%), cefoxitin (23%), penicillin (99%), clindamycin (34.2%) and tetracycline (53.5%). beta-lactamase production was verified in 92% of the evaluated strains. The presence of the cfiA, cepA, ermF, tetQ and nim genes was observed in 62.3%, 76.3%, 27%, 79.8% and 7.8% of the strains, respectively. CONCLUSIONS: Our results indicate an increase in the resistance to several antibiotics in intestinal Bacteroides spp. and Parabacteroides distasonis and demonstrate that these microorganisms harbor antimicrobial resistance genes that may be transferred to other susceptible intestinal strains. C1 [Nakano, Viviane; do Nascimento e Silva, Amanda; Castillo Merino, Victor Rafael; Avila-Campos, Mario Julio] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Anaerobe Lab, Sao Paulo, Brazil. [Wexler, Hannah M.] Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. [Wexler, Hannah M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Nakano, V (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Anaerobe Lab, Sao Paulo, Brazil. EM vivinkn@usp.br RI Nakano, Viviane/D-7955-2012; Avila-Campos, Mario/D-7727-2012 OI Avila-Campos, Mario/0000-0002-2378-7251 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [08/57330-4, 09/03792-0] FX The authors thank Mrs. Zulmira Alves de Souza for her technical support. This study was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP Grant 08/57330-4 and 09/03792-0). NR 31 TC 17 Z9 17 U1 2 U2 10 PU HOSPITAL CLINICAS, UNIV SAO PAULO PI SAO PAULO PA FAC MEDICINA, UNIV SAO PAULO, SAO PAULO, SP 00000, BRAZIL SN 1807-5932 J9 CLINICS JI Clinics PY 2011 VL 66 IS 4 BP 543 EP 547 DI 10.1590/S1807-59322011000400004 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 773MT UT WOS:000291312100004 PM 21655744 ER PT J AU Azeka, E Fregni, F Auler, JOC AF Azeka, Estela Fregni, Felipe Costa Auler Junior, Jose Otavio TI The past, present and future of clinical research SO CLINICS LA English DT Editorial Material C1 [Azeka, Estela] Univ Sao Paulo, Fac Med, Hosp Clin,Inst Coracao InCor, Unit Pediat Cardiol & Adult Congenital Heart Dis, BR-05508 Sao Paulo, Brazil. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Lab Neuromodulat, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Ctr Clin Res Learning, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Costa Auler Junior, Jose Otavio] Univ Sao Paulo, Fac Med, Discipline Anesthesiol, Dept Surg, BR-05508 Sao Paulo, Brazil. RP Azeka, E (reprint author), Univ Sao Paulo, Fac Med, Hosp Clin,Inst Coracao InCor, Unit Pediat Cardiol & Adult Congenital Heart Dis, BR-05508 Sao Paulo, Brazil. EM fregni.felipe@mgh.harvard.edu RI Auler Junior, Jose Otavio Costa/C-4492-2017 OI Auler Junior, Jose Otavio Costa/0000-0002-3919-1743 NR 12 TC 4 Z9 5 U1 0 U2 1 PU HOSPITAL CLINICAS, UNIV SAO PAULO PI SAO PAULO PA FAC MEDICINA, UNIV SAO PAULO, SAO PAULO, SP 00000, BRAZIL SN 1807-5932 J9 CLINICS JI Clinics PY 2011 VL 66 IS 6 BP 931 EP 932 DI 10.1590/S1807-59322011000600001 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 801AY UT WOS:000293410000001 PM 21808853 ER PT J AU Ferreira, JC Bensenor, FEM Rocha, MJJ Salge, JM Harris, RS Malhotra, A Kairalla, RA Kacmarek, RM Carvalho, CRR AF Ferreira, Juliana C. Bensenor, Fabio E. M. Rocha, Marcelo J. J. Salge, Joao M. Harris, R. Scott Malhotra, Atul Kairalla, Ronaldo A. Kacmarek, Robert M. Carvalho, Carlos R. R. TI A sigmoidal fit for pressure-volume curves of idiopathic pulmonary fibrosis patients on mechanical ventilation: clinical implications SO CLINICS LA English DT Article DE Lung mechanics; Lung volume measurements; Respiration artificial; Respiratory mechanics; Respiratory physiology ID RESPIRATORY-DISTRESS-SYNDROME; INTERSTITIAL PNEUMONIA; GENERAL-ANESTHESIA; ACUTE EXACERBATION; SMALL AIRWAYS; LUNG; FAILURE; MODEL; RECRUITMENT; ALVEOLITIS AB OBJECTIVE: Respiratory pressure-volume curves fitted to exponential equations have been used to assess disease severity and prognosis in spontaneously breathing patients with idiopathic pulmonary fibrosis. Sigmoidal equations have been used to fit pressure-volume curves for mechanically ventilated patients but not for idiopathic pulmonary fibrosis patients. We compared a sigmoidal model and an exponential model to fit pressure-volume curves from mechanically ventilated patients with idiopathic pulmonary fibrosis. METHODS: Six idiopathic pulmonary fibrosis patients and five controls underwent inflation pressure-volume curves using the constant-flow technique during general anesthesia prior to open lung biopsy or thymectomy. We identified the lower and upper inflection points and fit the curves with an exponential equation, V = A-B.e(-k.P), and a sigmoid equation, V = a+b/(1+e(-(P-c)/d)). RESULTS: The mean lower inflection point for idiopathic pulmonary fibrosis patients was significantly higher (10.5 +/- 5.7 cm H(2)O) than that of controls (3.6 +/- 2.4 cm H(2)O). The sigmoidal equation fit the pressure-volume curves of the fibrotic and control patients well, but the exponential equation fit the data well only when points below 50% of the inspiratory capacity were excluded. CONCLUSION: The elevated lower inflection point and the sigmoidal shape of the pressure-volume curves suggest that respiratory system compliance is decreased close to end-expiratory lung volume in idiopathic pulmonary fibrosis patients under general anesthesia and mechanical ventilation. The sigmoidal fit was superior to the exponential fit for inflation pressure-volume curves of anesthetized patients with idiopathic pulmonary fibrosis and could be useful for guiding mechanical ventilation during general anesthesia in this condition. C1 [Ferreira, Juliana C.; Rocha, Marcelo J. J.; Salge, Joao M.; Kairalla, Ronaldo A.; Carvalho, Carlos R. R.] Univ Sao Paulo, Fac Med, Div Pneumol, Inst Coracao InCor, Sao Paulo, Brazil. [Ferreira, Juliana C.; Harris, R. Scott; Kacmarek, Robert M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Bensenor, Fabio E. M.] Univ Sao Paulo, Dept Anestesia, Sao Paulo, Brazil. [Malhotra, Atul] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ferreira, JC (reprint author), Univ Sao Paulo, Fac Med, Div Pneumol, Inst Coracao InCor, Sao Paulo, Brazil. EM julianacarvalhoferreira@gmail.com RI Carvalho, Carlos/H-2161-2011; Kairalla, Ronaldo/D-5736-2014; Ferreira, Juliana/F-3455-2011; Salge, Joao/B-5157-2015 OI Kairalla, Ronaldo/0000-0001-7194-0479; Ferreira, Juliana/0000-0001-6548-1384; Salge, Joao/0000-0001-5121-0129 FU NHLBI NIH HHS [P01 HL095491, R01 HL085188, K24 HL093218, R01 HL086717, R01 HL090897] NR 40 TC 5 Z9 5 U1 1 U2 4 PU HOSPITAL CLINICAS, UNIV SAO PAULO PI SAO PAULO PA FAC MEDICINA, UNIV SAO PAULO, SAO PAULO, SP 00000, BRAZIL SN 1807-5932 J9 CLINICS JI Clinics PY 2011 VL 66 IS 7 BP 1157 EP 1163 DI 10.1590/S1807-59322011000700006 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 814GQ UT WOS:000294436800006 PM 21876967 ER PT J AU Kasckow, J Felmet, K Zisook, S AF Kasckow, John Felmet, Kandi Zisook, Sidney TI Managing Suicide Risk in Patients with Schizophrenia SO CNS DRUGS LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PSYCHIATRIC-INPATIENTS; DOUBLE-BLIND; SCHIZOAFFECTIVE DISORDER; DEPRESSIVE SYMPTOMS; CLOZAPINE TREATMENT; ANTIPSYCHOTIC MEDICATION; RESISTANT SCHIZOPHRENIA; PSYCHOLOGICAL AUTOPSY; COMPLETED SUICIDE AB The management of suicide risk in patients with schizophrenia poses many challenges for clinicians. Compared with the general population, these patients have an 8.5-fold greater risk of suicide. This article reviews the literature dealing with the treatment of at-risk patients with schizophrenia. An integrated psychosocial and pharmacological approach to managing this population of patients is recommended. Although there is at least modest evidence suggesting that antipsychotic medications protect against suicidal risk, the evidence appears to be most favourable for second-generation anti-psychotics, particularly clozapine, which is the only medication approved by the US FDA for preventing suicide in patients with schizophrenia. In addition, treating depressive symptoms in patients with schizophrenia is an important component of suicide risk reduction. While selective serotonin receptor inhibitors (SSRIs) ameliorate depressive symptoms in patients with schizophrenia, they also appear to attenuate suicidal thoughts. Further research is needed to more effectively personalize the treatment of suicidal thoughts and behaviours and the prevention of suicide in patients with schizophrenia. C1 [Kasckow, John; Felmet, Kandi] VA Pittsburgh Hlth Care Syst, MIRECC, Pittsburgh, PA 15206 USA. [Kasckow, John; Felmet, Kandi] VA Pittsburgh Hlth Care Syst, Behav Hlth Serv, Pittsburgh, PA 15206 USA. [Kasckow, John] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. [Zisook, Sidney] VA San Diego Hlth Care Syst, San Diego, CA USA. [Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Kasckow, J (reprint author), VA Pittsburgh Hlth Care Syst, MIRECC, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM kasckowjw@upmc.edu FU VISN 4 CPPF; American Foundation for Suicide Prevention; VISN 4 and VISN 22 MIRECC; University of California, San Diego Center for Community; Aspect Medical and PamLab; Forest; AstraZeneca; Bristol Meyers Squibb; Pfizer; Johnson Johnson; Solvay; Eli Lilly; [MH6398] FX Supported by MH6398 (SZ, JK), a VISN 4 CPPF grant (JK) and a grant from the American Foundation for Suicide Prevention (JK), the VISN 4 and VISN 22 MIRECC and the University of California, San Diego Center for Community-Based Research in Older People with Psychoses. The contents do not represent the views of the Department of Veterans Affairs of the US government.; Sidney Zisook, MD, has received research support from Aspect Medical and PamLab and speaker's honoraria from Forest Pharmaceuticals, Inc. and GlaxoSmithKline. John Kasckow, MD, PhD, has received grant support as well as honoraria for speaking and consultation from Forest, AstraZeneca, Bristol Meyers Squibb, Pfizer, Johnson & Johnson, Solvay and Eli Lilly. Ms Felmet has no conflicts of interest to declare. NR 134 TC 31 Z9 33 U1 4 U2 13 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2011 VL 25 IS 2 BP 129 EP 143 DI 10.2165/11586450-000000000-00000 PG 15 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 724DS UT WOS:000287556900003 PM 21254789 ER PT J AU Matthews, AM Wilson, VB Mitchell, SH AF Matthews, Annette M. Wilson, Vanessa B. Mitchell, Suzanne H. TI The Role of Antipsychotics in Smoking and Smoking Cessation SO CNS DRUGS LA English DT Review ID NICOTINE REPLACEMENT THERAPY; PLACEBO-CONTROLLED TRIAL; CHRONIC-SCHIZOPHRENIA; CIGARETTE-SMOKING; SUBSTANCE-ABUSE; DOUBLE-BLIND; COCAINE DEPENDENCE; REDUCES SMOKING; CLOZAPINE; SMOKERS AB Persons with severe and persistent mental illnesses, e.g. schizophrenia spectrum disorders and bipolar disorder, smoke at a much higher rate than the general population. Treatment options for schizophrenia spectrum disorders and bipolar disorder often include the first-generation (typical) and second-generation (atypical) antipsychotics, which have been shown to be effective in treating both psychotic and mood symptoms. This article reviews studies examining the relationship between antipsychotic medication and cigarette smoking. These studies suggest that in persons with schizophrenia and schizoaffective disorder, typical antipsychotics may increase basal smoking and decrease people's ability to stop smoking, whereas atypical antipsychotics decrease basal smoking and promote smoking cessation. However, we found that the data available were generally of moderate quality and from small studies, and that there were conflicting findings. The review also critically assesses a number of potential mechanisms for this effect: the use of smoking as a form of self-medication for the side effects of antipsychotics, the effect of antipsychotics on smoking-related cues and the effect of antipsychotics on the appreciation of the economic cost of smoking behaviour. Gaps in the research are noted and recommendations for further study are included. More study of this important issue is needed to clarify the effect of antipsychotics on smoking behaviours. C1 [Matthews, Annette M.] Portland VA Med Ctr, Res & Dev Serv, Portland, OR USA. [Matthews, Annette M.] Portland VA Med Ctr, Behav Hlth & Neurosci Div, Portland, OR USA. [Matthews, Annette M.; Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Wilson, Vanessa B.; Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Matthews, AM (reprint author), Portland VA Med Ctr P3 MHDC, 3710 SW US Vet Hosp Rd,POB 1035, Portland, OR 97207 USA. EM Annette.Matthews@va.gov OI Mitchell, Suzanne/0000-0002-0225-7200 FU Veterans Affairs Career Developmant Award; National Institutes of Health [DA0145543, DA024195] FX This work was done as part of a Veterans Affairs Career Developmant Award (A.M. Matthews) and National Institutes of Health grants DA0145543 and DA024195 (S.H. Mitchell). The funding sources did not influence the content of the text. The authors report no conflicts of interest. The authors would like to thank Andrew Hamilton and Sharon Medley for help obtaining the reviewed material. NR 69 TC 15 Z9 15 U1 1 U2 14 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1172-7047 EI 1179-1934 J9 CNS DRUGS JI CNS Drugs PY 2011 VL 25 IS 4 BP 299 EP 315 PG 17 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 750GT UT WOS:000289535300003 PM 21425883 ER PT J AU Vorobeychik, Y Gordin, V Mao, JR Chen, L AF Vorobeychik, Yakov Gordin, Vitaly Mao, Jianren Chen, Lucy TI Combination Therapy for Neuropathic Pain A Review of Current Evidence SO CNS DRUGS LA English DT Review ID CONCENTRATION CAPSAICIN PATCH; SPINOTHALAMIC TRACT NEURONS; PLACEBO-CONTROLLED TRIAL; POSTHERPETIC NEURALGIA; DOUBLE-BLIND; CANCER PAIN; DIABETIC-NEUROPATHY; DORSAL HORN; SPINAL-CORD; PHARMACOLOGICAL MANAGEMENT AB Neuropathic pain is a debilitating chronic condition that remains very difficult to treat. Recently, a number of clinical studies have compared the effectiveness of combination drug therapy with monotherapy for neuropathic pain treatment. In this article, we summarize up-to-date clinical studies of combination therapy for the treatment of both cancer- and non-cancer-related neuropathic pain. Despite a relatively small number of clinical studies on this topic, several positive indications have emerged. First, clinical studies using gabapentin (five positive trials) and pregabalin (five positive trials and one negative trial) in combination with an opioid, cyclo-oxygenase-2 inhibitor or antidepressant have shown positive responses greater than the respective monotherapies for pain related to diabetic neuropathy and postherpetic neuropathy. Second, high-concentration (8%) topical capsaicin and a 5% lidocaine patch seem to be effective add-on therapies (a modality of combination therapy) for various neuropathic pain conditions. Third, combination therapy for cancer-related neuropathic pain has yielded only limited success based on a number of small-scale clinical studies. While there are benefits of using combination therapy for neuropathic pain treatment, including better pain relief and reduced adverse effects, more clinical studies are required in order to (i) make head-to-head comparisons between combination and single-drug therapies, (ii) identify symptom-specific combination therapies for distinctive clinical neuropathic pain conditions, (iii) explore combination therapies that include non-drug modalities such as physical therapy, psychological coping and biofeedback to facilitate functional restoration and (iv) develop new and objective evaluation tools for clinical outcome assessment. C1 [Mao, Jianren; Chen, Lucy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. [Vorobeychik, Yakov; Gordin, Vitaly] Penn State Coll Med, Penn State Milton S Hershey Med Ctr, Dept Anesthesiol, Hershey, PA 17033 USA. RP Chen, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, 15 Parkman St, Boston, MA 02114 USA. EM llchen@partners.org FU National Institutes of Health (NIH) [R01DE18214, R01DE18538, P20DA26002] FX This study was supported by National Institutes of Health (NIH) grants R01DE18214, R01DE18538 and P20DA26002 (to Dr Mao). Dr Vorobeychik has been a speaker bureau member for Eli Lilly and Forest Pharmaceuticals. The remaining authors have no conflicts of interest that are directly relevant to the content of this review. NR 78 TC 43 Z9 46 U1 0 U2 12 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2011 VL 25 IS 12 BP 1023 EP 1034 PG 12 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 871CA UT WOS:000298714000003 PM 22133325 ER PT J AU Sampaio, AS Fagerness, J Crane, J Leboyer, M Delorme, R Pauls, DL Stewart, SE AF Sampaio, Aline S. Fagerness, Jesen Crane, Jacquelyn Leboyer, Marion Delorme, Richard Pauls, David L. Stewart, S. Evelyn TI Association Between Polymorphisms in GRIK2 Gene and Obsessive-Compulsive Disorder: A Family-Based Study SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Genes; Glutamate receptors; Kainate; Obsessive-compulsive disorder ID RECEPTOR SUBUNIT; TRANSPORTER GENE; GLUTAMATE; OCD; SCHIZOPHRENIA; TRANSMISSION; HAPLOTYPE; CHILDREN; DISEASE; GLUR6 AB Several studies support a genetic influence on obsessive-compulsive disorder (OCD) etiology. The role of glutamate as an important neurotransmitter affecting OCD pathophysiology has been supported by neuroimaging, animal model, medication, and initial candidate gene studies. Genes involved in glutamatergic pathways, such as the glutamate receptor, ionotropic, kainate 2 (GRIK2), have been associated with OCD in previous studies. This study examines GRIK2 as a candidate gene for OCD susceptibility in a family-based approach. Probands had full DSM-IV diagnostic criteria for OCD. Forty-seven OCD probands and their parents were recruited from tertiary care OCD specialty clinics from France and USA. Genotypes of single nucleotide polymorphism (SNP) markers and related haplotypes were analyzed using Haploview and FBAT software. The polymorphism at rs1556995 (P = 0.0027; permuted P-value = 0.03) was significantly associated with the presence of OCD. Also, the two marker haplotype rs1556995/rs1417182, was significantly associated with OCD (P = 0.0019, permuted P-value = 0.01). This study supports previously reported findings of association between proximal GRIK2 SNPs and OCD in a comprehensive evaluation of the gene. Further study with independent samples and larger sample sizes is required. C1 [Fagerness, Jesen; Crane, Jacquelyn; Pauls, David L.; Stewart, S. Evelyn] Harvard Univ, Massachusetts Gen Hosp, PNGU, Boston, MA 02114 USA. [Sampaio, Aline S.] Univ Sao Paulo Med Sch, Dept Psychiat, Sao Paulo, Brazil. [Sampaio, Aline S.] Univ Sao Paulo Med Sch, Inst Psychiat, Sao Paulo, Brazil. [Leboyer, Marion; Delorme, Richard] Fac Med, INSERM U 513, F-94010 Creteil, France. [Leboyer, Marion] Hop Henri Mondor & Albert Chenevier, AP HP, Psychiat Serv, Creteil, France. [Delorme, Richard] Hop Robert Debre, AP HP, Serv Psychopathol Enfant & Adolescent, F-75019 Paris, France. RP Stewart, SE (reprint author), Harvard Univ, Massachusetts Gen Hosp, PNGU, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM stewart@pngu.mgh.harvard.edu RI SAMPAIO, ALINE/M-1229-2013; OI SAMPAIO, ALINE/0000-0001-5568-6167; Stewart, S. Evelyn/0000-0002-0994-6383 FU McIngvale Foundation; OC Foundation; ADAA; CAPES-Brazil FX The authors would like to acknowledge Ariane Machado Lima and Andrew Kirby who provided helpful technical assistance. This study was supported in part by the McIngvale Foundation (S.E.E, D.L.P), the OC Foundation (S.E.S), the ADAA (S.E.S), and the CAPES-Brazil (A.S.S.). NR 39 TC 19 Z9 21 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2011 VL 17 IS 3 BP 141 EP 147 DI 10.1111/j.1755-5949.2009.00130.x PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 761LE UT WOS:000290398500001 PM 20370803 ER PT J AU Rougemont-Bucking, A Linnman, C Zeffiro, TA Zeidan, MA Lebron-Milad, K Rodriguez-Romaguera, J Rauch, SL Pitman, RK Milad, MR AF Rougemont-Buecking, Ansgar Linnman, Clas Zeffiro, Thomas A. Zeidan, Mohamed A. Lebron-Milad, Kelimer Rodriguez-Romaguera, Jose Rauch, Scott L. Pitman, Roger K. Milad, Mohammed R. TI Altered Processing of Contextual Information during Fear Extinction in PTSD: An fMRI Study SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE Amygdala; Contextual signaling; dACC; Fear extinction; fMRI; Hippocampus; vmPFC ID POSTTRAUMATIC-STRESS-DISORDER; ANTERIOR CINGULATE CORTEX; VENTROMEDIAL PREFRONTAL CORTEX; ANXIETY DISORDERS; CONDITIONED FEAR; BASOLATERAL AMYGDALA; DECISION-MAKING; MEMORY; HIPPOCAMPAL; MODULATION AB Medial prefrontal cortical areas have been hypothesized to underlie altered contextual processing in posttraumatic stress disorder (PTSD). We investigated brain signaling of contextual information in this disorder. Eighteen PTSD subjects and 16 healthy trauma-exposed subjects underwent a two-day fear conditioning and extinction paradigm. On day 1, within visual context A, a conditioned stimulus (CS) was followed 60% of the time by an electric shock (conditioning). The conditioned response was then extinguished (extinction learning) in context B. On day 2, recall of the extinction memory was tested in context B. Skin conductance response (SCR) and functional magnetic resonance imaging (fMRI) data were collected during context presentations. There were no SCR group differences in any context presentation. Concerning fMRI data, during late conditioning, when context A signaled danger, PTSD subjects showed dorsal anterior cingulate cortical (dACC) hyperactivation. During early extinction, when context B had not yet fully acquired signal value for safety, PTSD subjects still showed dACC hyperactivation. During late extinction, when context B had come to signal safety, they showed ventromedial prefrontal cortex (vmPFC) hypoactivation. During early extinction recall, when context B signaled safety, they showed both vmPFC hypoactivation and dACC hyperactivation. These findings suggest that PTSD subjects show alterations in the processing of contextual information related to danger and safety. This impairment is manifest even prior to a physiologically-measured, cue-elicited fear response, and characterized by hypoactivation in vmPFC and hyperactivation in dACC. C1 [Rougemont-Buecking, Ansgar; Linnman, Clas; Zeffiro, Thomas A.; Zeidan, Mohamed A.; Lebron-Milad, Kelimer; Rodriguez-Romaguera, Jose; Rauch, Scott L.; Pitman, Roger K.; Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Rougemont-Buecking, Ansgar; Linnman, Clas; Zeffiro, Thomas A.; Zeidan, Mohamed A.; Lebron-Milad, Kelimer; Rodriguez-Romaguera, Jose; Rauch, Scott L.; Pitman, Roger K.; Milad, Mohammed R.] Harvard Univ, Sch Med, Charlestown, MA USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. RP Rougemont-Bucking, A (reprint author), Serv Psychiat Communautaire, Rue St Martin 7, CH-1003 Lausanne, Switzerland. EM ansgar.rougemont-buecking@chuv.ch OI Linnman, Clas/0000-0001-8449-894X FU National Institute of Mental Health [1R21MH072156-1]; NARSAD; Centre Hospitalier Universitaire Vaudois; University of Lausanne, Switzerland; Societe Academique Vaudoise, Lausanne, Switzerland; Sweden-America foundation; Latin American Network for the Training and Exchange of Researchers in Neuroscience (LANTERN); Multicultural Affairs Office from Massachusetts General Hospital FX This study was funded by a grant from the National Institute of Mental Health (1R21MH072156-1) to Scott L. Rauch and a Young Investigator Award from NARSAD to Mohammed R. Milad. Ansgar Rougemont-Bucking received funding from the Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland, as well as a grant from the Societe Academique Vaudoise, Lausanne, Switzerland. Clas Linnman received funding from the Sweden-America foundation. Jose Rodriguez-Romaguera received funding from the Latin American Network for the Training and Exchange of Researchers in Neuroscience (LANTERN) and the Summer Research Training Program (SRTP) from the Multicultural Affairs Office from Massachusetts General Hospital. The authors wish to thank Jacques Besson for institutional support to the first author, as well as Scott P. Orr and Gregory J. Quirk for helpful discussion on data interpretation. NR 46 TC 82 Z9 84 U1 2 U2 27 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2011 VL 17 IS 4 BP 227 EP 236 DI 10.1111/j.1755-5949.2010.00152.x PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 791VL UT WOS:000292695000004 PM 20406268 ER PT J AU Simone, MJ Tan, ZS AF Simone, Mark J. Tan, Zaldy S. TI The Role of Inflammation in the Pathogenesis of Delirium and Dementia in Older Adults: A Review SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Alzheimer's disease; Delirium; Dementia; Inflammation ID NECROSIS-FACTOR-ALPHA; C-REACTIVE PROTEIN; INTERLEUKIN-1 RECEPTOR ANTAGONIST; BRAIN-BARRIER PERMEABILITY; AMYLOID PRECURSOR PROTEIN; WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; ELDERLY-PATIENTS; SYSTEMIC INFLAMMATION; GENE POLYMORPHISMS AB Aims: To review recent evidence that suggests inflammation plays a similar role in the pathogenesis of delirium and dementia. Methods: We performed a literature search of original research and review articles in PubMed using the keywords: delirium, dementia, and inflammation. We summarized the evidence linking inflammation to the pathogenesis of delirium and dementia. Discussion: Delirium and dementia share similarities in clinical and pathogenic features, leading to the speculation that instead of being distinct clinical entities, the two age-related conditions may be linked by a common pathogenic mechanism. Inflammatory markers have been shown to be elevated in both delirium and dementia, thereby implicating inflammation as a possible mediating factor in their genesis. There is evidence in both basic science and clinical research literature that elevated cytokines play a crucial role in the development of cognitive dysfunction observed in both dementia and delirium. Conclusion: Mounting evidence supports the role of inflammation in the development of both dementia and delirium. Further studies are needed to elucidate the mechanisms underlying these relationships. C1 [Simone, Mark J.] Mt Auburn Hosp, Div Gerontol, Cambridge, MA 02138 USA. [Simone, Mark J.; Tan, Zaldy S.] Harvard Univ, Sch Med, Boston, MA USA. [Tan, Zaldy S.] Brigham & Womens Hosp, GRECC, VA Boston Healthcare Syst, Div Aging, Boston, MA 02115 USA. RP Simone, MJ (reprint author), Mt Auburn Hosp, Div Gerontol, 300 Mt Auburn St,Suite 517, Cambridge, MA 02138 USA. EM msimone@mah.harvard.edu FU Health Resources and Services Administration FX Both authors contributed equally to the concept and design of this paper, the literature search, review of the material, drafting, revising, and final approval of the paper. The authors report no sources of funding for this project or additional individuals who have contributed to this paper. Dr. Tan is the recipient of a Geriatric Academic Career Award from the Health Resources and Services Administration. Dr. Simone reports receiving an honorarium for developing an online educational module for the Fenway Community Health Center. NR 73 TC 25 Z9 26 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PY 2011 VL 17 IS 5 BP 506 EP 513 DI 10.1111/j.1755-5949.2010.00173.x PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 824CM UT WOS:000295178700020 PM 20553303 ER PT J AU Singh, JA Wells, GA Christensen, R Ghogomu, ET Maxwell, L MacDonald, JK Filippini, G Skoetz, N Francis, D Lopes, LC Guyatt, GH Schmitt, J La Mantia, L Weberschock, T Roos, JF Siebert, H Hershan, S Lunn, MPT Tugwell, P Buchbinder, R AF Singh, J. A. Wells, G. A. Christensen, R. Ghogomu, Tanjong E. Maxwell, L. MacDonald, J. K. Filippini, G. Skoetz, N. Francis, D. Lopes, L. C. Guyatt, G. H. Schmitt, J. La Mantia, L. Weberschock, T. Roos, J. F. Siebert, H. Hershan, S. Lunn, M. P. T. Tugwell, P. Buchbinder, R. TI Adverse effects of biologics: a network meta-analysis and Cochrane overview SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID ACTIVE RHEUMATOID-ARTHRITIS; PLACEBO-CONTROLLED TRIAL; NECROSIS-FACTOR-ALPHA; RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; INTERLEUKIN-1 RECEPTOR ANTAGONIST; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; PATIENT-REPORTED OUTCOMES; RECEIVING CONCOMITANT METHOTREXATE AB Background Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates. Objectives To compare the adverse effects of tumor necrosis factor blocker (etanercept, adalimumab, infliximab, golimumab, certolizumab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS). Methods Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework. Main results We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95% CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95% CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95% CI 1.06 to 1.64; NNTH = 37, 95% CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706) compared to control. The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95% CI 1.59 to 7.79; NNTH = 17, 95% CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95% CI 1.43 to 2.91; NNTH = 12, 95% CI 8 to 28). Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events. Authors' conclusions Overall, in the short term biologics were associated with significantly higher rates of total adverse events, withdrawals due to adverse events and TB reactivation. Some biologics had a statistically higher association with certain adverse outcomes compared to control, but there was no consistency across the outcomes so caution is needed in interpreting these results. There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short-and longer-term safety of biologics. C1 [Singh, J. A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL 35294 USA. [Wells, G. A.] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Christensen, R.] Copenhagen Univ Hosp, Parker Inst, Musculoskeletal Stat Unit MSU, Copenhagen, Denmark. [Christensen, R.] Univ So Denmark, Inst Sports Sci & Clin Biomech, Fac Hlth Sci, Odense, Denmark. [Ghogomu, Tanjong E.; Maxwell, L.] Univ Ottawa, Inst Populat Hlth, Ctr Global Hlth, Ottawa, ON, Canada. [MacDonald, J. K.] Robarts Res Inst, London, ON N6A 5C1, Canada. [Filippini, G.] Fdn IRCCS, Neuroepidemiol Unit, Ist Neurol Carlo Besta, Milan, Italy. [Skoetz, N.] Univ Hosp Cologne, Cochrane Haematol Malignancies Grp, Dept Internal Med 1, Cologne, Germany. [Lopes, L. C.] Univ Sorocaba, Sci Pharmaceut Program, Sao Paulo, Sorocaba, Brazil. [Francis, D.] Univ W Indies, Epidemiol Res Unit, Kingston 7, Jamaica. [Guyatt, G. H.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Schmitt, J.] Univ Hosp Carl Gustav Carus, Dept Dermatol, Dresden, Germany. [La Mantia, L.] IRCCS Santa Maria Nascente Fdn Don Gnocchi, Unit Neurol, Multiple Sclerosis Ctr, Milan, Italy. [Weberschock, T.] JW Goethe Univ Hosp, Ctr Dermatol, Frankfurt, Germany. [Weberschock, T.] Goethe Univ Frankfurt, Inst Gen Practice, Frankfurt, Germany. [Roos, J. F.; Hershan, S.; Buchbinder, R.] Monash Univ, Monash Dept Clin Epidemiol, Cabrini Hosp, Dept Epidemiol & Prevent Med, Malvern, Australia. [Siebert, H.] Univ Hosp Cologne, Cochrane Haematol Malignancies Grp, Cologne, Germany. [Lunn, M. P. T.] Natl Hosp Neurol & Neurosurg, Dept Neurol, London WC1N 3BG, England. [Tugwell, P.] Univ Ottawa, Fac Med, Ctr Global Hlth, Inst Populat Hlth, Ottawa, ON, Canada. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Dept Med, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com RI Buchbinder, Rachelle/G-2952-2011; Fittipaldo, Andrea/A-5991-2013 FU AMGEN; Allergan; Takeda; Savient; URL Pharma; Novartis; Bristol-Myers Squibb; Abbott; UCB; Astellas Pharma; Axellus; Cambridge Nutritional Foods; Centocor; DSM Nutritional Products; Hypo-Safe; MSD; MundiPharma; NorPharma; Pharmavie; Pfizer; Roche; Sanofi-Aventis; Scandinavian Clinical Nutrition; Lotte and John Hecht Foundation; Astra Zeneca; Up-To-Date; Eli Lilly Canada; Bristol Myers; Chiltern International; Wyeth; Institute of Population Health, University of Ottawa, Canada; Oak Foundations; Canadian Institutes of Health Research, Canada; National Institutes of Health Research, UK FX JS: speaker honoraria from Abbott; research grants from AMGEN, Allergan, Takeda, Savient; consultant fee from Savient, URL Pharma, Novartis; GW: research grant and consultant fee from Bristol-Myers Squibb; consultant fees from Abbott, Amgen, UCB; Data Safety Monitoring for Novartis.; RC: has received consulting fees, honoraria, research or institutional support, educational grants, equipment, services or expenses from: Abbott, Astellas Pharma, Axellus, Bristol-Myers Squibb, Cambridge Nutritional Foods, Centocor, DSM Nutritional Products, Hypo-Safe, MSD, MundiPharma, NorPharma, Pharmavie, Pfizer, Roche, Sanofi-Aventis, Scandinavian Clinical Nutrition.; Guyatt: in the last 5 years, Dr Guyatt has received grant funding from Pfizer, Lotte and John Hecht Foundation, Bristol-Myers-Squibb, and Astra Zeneca. Dr Guyatt has also received consultation fee from Up-To-Date and Eli Lilly Canada. To our knowledge, none of these are conflicted with the subject matter of this submission.; PT: grants/honoraria from Bristol Myers, Chiltern International, and UCB; Schmitt: research grant from Wyeth.; Institute of Population Health, University of Ottawa, Canada.; Logistic support; The Parker Institute: Musculoskeletal Statistics Unit, Copenhagen University Hospital, Denmark.; The Oak Foundations provide support to the Parker Institute; Canadian Institutes of Health Research, Knowledge Synthesis Grant, Canada.; Funding for logistics, organization and administrative support; National Institutes of Health Research, Cochrane Review Incentive Scheme 2009, UK.; Funding for administrative support NR 281 TC 164 Z9 166 U1 3 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2011 IS 2 AR CD008794 DI 10.1002/14651858.CD008794.pub2 PG 60 WC Medicine, General & Internal SC General & Internal Medicine GA 738CJ UT WOS:000288616600032 ER PT J AU Rapuano, BE MacDonald, DE AF Rapuano, Bruce E. MacDonald, Daniel E. TI Surface oxide net charge of a titanium alloy Modulation of fibronectin-activated attachment and spreading of osteogenic cells SO COLLOIDS AND SURFACES B-BIOINTERFACES LA English DT Article DE Cell attachment; Coatings; Fibronnectin; Metal oxides; Surface charge ID HUMAN-PLASMA FIBRONECTIN; ATOMIC-FORCE MICROSCOPY; CONFORMATIONAL-CHANGES; IN-VITRO; PROTEIN ADSORPTION; BONE SIALOPROTEIN; THIN-FILMS; ADHESION; DIFFERENTIATION; FLUORESCENCE AB In the current study we have altered the surface oxide properties of a Ti6A14V alloy using heat treatment or radiofrequency glow discharge (RFGD) in order to evaluate the relationship between the physico chemical and biological properties of the alloys surface oxide The effects of surface pretreatments on the attachment of cells from two osteogenic cell lines (MG63 and MC3T3) and a mesenchymal stem cell line (C3H10T1/2) to fibronectin adsorbed to the alloy were measured Both heat and RFGD pretreatments produced a several fold increase in the number of cells that attached to fibronectin adsorbed to the alloy at a range of coating concentrations (0001-10 nM FN) for each cell line tested An antibody (HFN7 1) directed against the central integrin binding domain of fibronectin produced a 65-70% inhibition of cell attachment to fibronectin-coated disks indicating that cell attachment to the metal discs was dependent on fibronectin binding to cell integrin receptors Both treatments also accelerated the cell spreading response manifested by extensive flattening and an increase in mean cellular area The treatment induced increases in the cell attachment activity of adsorbed fibronectin were correlated with previously demonstrated increases in Ti6A14V oxide negative net surface charge at physiological pH produced by both heat and RFGD pretreatments Since neither treatment increased the adsorption mass of fibronectin these findings suggest that negatively charged surface oxide functional groups in Ti6A14V can modulate fibronectin's integrin receptor activity by altering the adsorbed protein's conformation Our results further suggest that negatively charged functional groups in the surface oxide can play a prominent role in the osseointegration of metallic implant materials Published by Elsevier B V C1 [Rapuano, Bruce E.; MacDonald, Daniel E.] Cornell Univ, Weill Med Coll, Hosp Special Surg, New York, NY 10021 USA. [MacDonald, Daniel E.] Gen Med Res James J Peters VA Med Ctr, Bronx, NY 10468 USA. [MacDonald, Daniel E.] Columbia Univ, Langmuir Ctr Colloids & Interfaces, New York, NY 10027 USA. RP MacDonald, DE (reprint author), Cornell Univ, Weill Med Coll, Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. FU NIH [RO1 DE017695]; National Center for Research Resources NIH [C06-RR12538-01] FX The project described was supported by Grant Number NIH RO1 DE017695 (Awarded to DEM) The sponsor did not have any role in the study design the collection analysis and interpretation of data the writing of the report or the decision to submit the paper for publication This material is also the result of work supported with resources and the use of facilities at the James J Peters VA Medical Center Bronx New York This investigation was also conducted at the HSS research facility constructed with support of Grant C06-RR12538-01 from the National Center for Research Resources NIH We would like to acknowledge Dr Stephen Doty and Tony Labisserie for help with scanning electron microscopy Special thanks goes to Christine Marsh and Kyle Hackshaw for their assistance with the cell culture experiments NR 74 TC 26 Z9 26 U1 1 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0927-7765 J9 COLLOID SURFACE B JI Colloid Surf. B-Biointerfaces PD JAN 1 PY 2011 VL 82 IS 1 BP 95 EP 103 DI 10.1016/j.colsurfb.2010.08.023 PG 9 WC Biophysics; Chemistry, Physical; Materials Science, Biomaterials SC Biophysics; Chemistry; Materials Science GA 673YH UT WOS:000283699600014 PM 20884181 ER PT J AU MacDonald, DE Rapuano, BE Schniepp, HC AF MacDonald, Daniel E. Rapuano, Bruce E. Schniepp, Hannes C. TI Surface oxide net charge of a titanium alloy Comparison between effects of treatment with heat or radiofrequency plasma glow discharge SO COLLOIDS AND SURFACES B-BIOINTERFACES LA English DT Article DE Titanium alloy; Oxides; Surface treatments; Net surface charge; Wettability ID ATOMIC-FORCE MICROSCOPY; OSTEOBLAST-LIKE CELLS; PHOTOELECTRON-SPECTROSCOPY; PHYSIOLOGICAL SOLUTION; THIN-FILMS; ADSORPTION; BEHAVIOR; BIOMATERIAL; FIBRONECTIN; ROUGHNESS AB In the current study we have compared the effects of heat and radiofrequency plasma glow discharge (RFGD) treatment of a Ti6Al4V alloy on the physico chemical properties of the alloys surface oxide Titanium alloy (Ti6Al4V) disks were passivated alone heated to 600 C or RFGD plasma treated in pure oxygen RFGD treatment did not alter the roughness topography elemental composition or thickness of the alloys surface oxide layer In contrast heat treatment altered oxide topography by creating a pattern of oxide elevations approximately 50-100 nm in diameter These nanostructures exhibited a three fold increase in roughness compared to untreated surfaces when RMS roughness was calculated after applying a spatial high-pass filter with a 200 nm cutoff wavelength Heat treatment also produced a surface enrichment in aluminum and vanadium oxides Both RFGD and heat treatment produced similar increases in oxide wettability Atomic force microscopy (AFM) measurements of metal surface oxide net charge signified by a long-range force of attraction to or repulsion from a (negatively charged) silicon nitride AFM probe were also obtained for all three experimental groups Force measurements showed that the RFGD treated Ti6Al4V samples demonstrated a higher net positive surface charge at pH values below 6 and a higher net negative surface charge at physiological pH (pH values between 7 and 8) compared to control and heat treated samples These findings suggest that RFGD treatment of metallic implant materials can be used to study the role of negatively charged surface oxide functional groups in protein bioactivity osteogenic cell behavior and osseointegration independently of oxide topography Published by Elsevier B V C1 [MacDonald, Daniel E.; Rapuano, Bruce E.] Cornell Univ, Weill Med Coll, Hosp Special Surg, New York, NY 10021 USA. [MacDonald, Daniel E.] Gen Med Res James Peters VA Med Ctr, Bronx, NY 10468 USA. [MacDonald, Daniel E.] Columbia Univ, Langmuir Ctr Colloids & Interfaces, New York, NY 10027 USA. [Schniepp, Hannes C.] Coll William & Mary, Dept Appl Sci, Williamsburg, VA 23185 USA. RP MacDonald, DE (reprint author), Cornell Univ, Weill Med Coll, Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. RI Schniepp, Hannes/B-8368-2008 OI Schniepp, Hannes/0000-0003-4645-9469 FU NIH [RO1 DE017695]; National Center for Research Resources NIH [C06-RR12538-01] FX The project described was supported by Grant number NIH RO1 DE017695 (Awarded to DEM) The sponsor did not have any role in the study design the collection analysis and interpretation of data the writing of the report or the decision to submit the paper for publication This material is also the result of work supported with resources and the use of facilities at the James J Peters VA Medical Center Bronx New York This investigation was also conducted at the HSS research facility constructed with support of Grant C06-RR12538-01 from the National Center for Research Resources NIH We would like to acknowledge Michael Stranick of Colgate Palmolive Inc for assistance with the ESCA measurements Special thanks goes to Ryan Jeong and Dana McCloskey for their help in preparing and treating the alloy disks NR 62 TC 18 Z9 19 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0927-7765 J9 COLLOID SURFACE B JI Colloid Surf. B-Biointerfaces PD JAN 1 PY 2011 VL 82 IS 1 BP 173 EP 181 DI 10.1016/j.colsurfb.2010.08.031 PG 9 WC Biophysics; Chemistry, Physical; Materials Science, Biomaterials SC Biophysics; Chemistry; Materials Science GA 673YH UT WOS:000283699600025 PM 20880672 ER PT J AU Chan, SY Loscalzo, J AF Chan, Stephen Y. Loscalzo, Joseph TI Pulmonary Vascular Disease Related to Hemodynamic Stress in the Pulmonary Circulation SO COMPREHENSIVE PHYSIOLOGY LA English DT Article AB Hemodynamic stress in the pulmonary vessel is directly linked to the development of vascular remodeling and dysfunction, ultimately leading to pulmonary hypertension. Recently, some advances have been made in our molecular understanding of the exogenous upstream stimuli that initiate hemodynamic pertubations as well as the downstream vasoactive effectors that control these responses. However, much still remains unknown regarding how these complex signaling pathways connect in order to result in these characteristic pathophysiological changes. This chapter will describe our current understanding of and needed areas of research into the clinical, physiological, and molecular changes associated with pressure/volume overload in the pulmonary circulation. (C) 2011 American Physiological Society. Compr Physiol 1:123-139, 2011. C1 [Chan, Stephen Y.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Cardiol, Boston, MA USA. [Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. RP Loscalzo, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. EM jloscalzo@partners.org FU NIH-T32 Cardiovascular Training grant [5T32HL007208-30]; AHA Founders Affiliate Postdoctoral grant [0825906D]; NIH [HL 61795, NO1 HV 28178, PO1 81587] FX This work was supported by the NIH-T32 Cardiovascular Training grant 5T32HL007208-30 (Massachusetts General Hospital), AHA Founders Affiliate Postdoctoral grant 0825906D (S.Y.C.), and the NIH grants HL 61795, NO1 HV 28178, and PO1 81587 (J.L.). The authors thank Stephanie Tribuna for expert administrative assistance. NR 202 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2040-4603 J9 COMPR PHYSIOL JI Compr. Physiol. PD JAN PY 2011 VL 1 IS 1 BP 123 EP 139 DI 10.1002/cphy.c090004 PG 17 WC Physiology SC Physiology GA V27SJ UT WOS:000208632600006 PM 23737167 ER PT J AU Gottlieb, JD Mueser, KT Rosenberg, SD Xie, HY Wofe, RS AF Gottlieb, Jennifer D. Mueser, Kim T. Rosenberg, Stanley D. Xie, Haiyi Wofe, Rosemarie S. TI Psychotic depression, posttraumatic stress disorder, and engagement in cognitive-behavioral therapy within an outpatient sample of adults with serious mental illness SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID NONPSYCHOTIC MAJOR DEPRESSION; CHILDHOOD SEXUAL-ABUSE; NATIONAL COMORBIDITY SURVEY; DSM-IV; TRAUMA; PREVALENCE; FEATURES; SCHIZOPHRENIA; EXPOSURE; HISTORY AB Depression with psychotic features afflicts a substantial number of people and has been characterized by significantly greater impairment, higher levels of dysfunctional beliefs, and poorer response to psychopharmacologic and psychosocial interventions than nonpsychotic depression. Those with psychotic depression also experience a host of co-occurring disorders, including posttraumatic stress disorder (PTSD), which is not surprising given the established relationships between trauma exposure and increased rates of psychosis and between PTSD and major depression. To date, there has been very limited research on the psychosocial treatment of psychotic depression; and even less is known about those who also suffer from PTSD. The purpose of this study was to better understand the rates and clinical correlates of psychotic depression in those with PTSD. Clinical and symptom characteristics of 20 individuals with psychotic depression and 46 with nonpsychotic depression, all with PTSD, were compared before receiving cognitive-behavioral therapy for PTSD treatment or treatment as usual. Patients with psychotic depression exhibited significantly higher levels of depression and anxiety, a weaker perceived therapeutic alliance with their case managers, more exposure to traumatic events, and more negative beliefs related to their traumatic experiences, as well as increased levels of maladaptive cognitions about themselves and the world, compared with participants without psychosis. Implications for cognitive-behavioral therapy treatment aimed at dysfunctional thinking for this population are discussed. (C) 2011 Elsevier Inc. All rights reserved. C1 [Gottlieb, Jennifer D.; Mueser, Kim T.; Rosenberg, Stanley D.; Xie, Haiyi; Wofe, Rosemarie S.] Dartmouth Psychiat Res Ctr, Concord, NH 03301 USA. [Gottlieb, Jennifer D.; Mueser, Kim T.; Rosenberg, Stanley D.; Wofe, Rosemarie S.] Dartmouth Med Sch, Dept Psychiat, Concord, NH 03301 USA. [Mueser, Kim T.; Xie, Haiyi] Dartmouth Med Sch, Dept Community, Concord, NH 03301 USA. [Mueser, Kim T.; Xie, Haiyi] Dartmouth Med Sch, Dept Family Med, Concord, NH 03301 USA. [Gottlieb, Jennifer D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Gottlieb, JD (reprint author), Dartmouth Psychiat Res Ctr, Concord, NH 03301 USA. EM jennifer.gottlieb@dartmouth.edu FU NIMH NIH HHS [R01 MH064662-03, R01 MH064662] NR 66 TC 6 Z9 6 U1 1 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 2011 VL 52 IS 1 BP 41 EP 49 DI 10.1016/j.comppsych.2010.04.012 PG 9 WC Psychiatry SC Psychiatry GA 709BL UT WOS:000286410100006 PM 21220064 ER PT J AU Willi, R Pfab, F Zilker, T Buters, J Schalock, P Huss-Marp, J Todorova, A Ring, J Darsow, U AF Willi, Robert Pfab, Florian Zilker, Thomas Buters, Jeroen Schalock, Peter Huss-Marp, Johannes Todorova, Antonia Ring, Johannes Darsow, Ulf TI Danger from the workplace: allergic contact dermatitis from the first exposure to isothiazolinones SO CONTACT DERMATITIS LA English DT Editorial Material DE allergy; contact dermatitis; isothiazolinones ID INDUCTION; BIOCIDE C1 [Darsow, Ulf] Tech Univ Munich, Klin & Poliklin Dermatol & Allergol Biederstein, Dept Dermatol & Allergy Biederstein, D-80802 Munich, Germany. [Pfab, Florian; Buters, Jeroen; Huss-Marp, Johannes; Ring, Johannes; Darsow, Ulf] Tech Univ Munich, Div Environm Dermatol, D-80802 Munich, Germany. [Pfab, Florian; Buters, Jeroen; Huss-Marp, Johannes; Ring, Johannes; Darsow, Ulf] Tech Univ Munich, Allergy Helmholtz Ctr Munich TUM, D-80802 Munich, Germany. [Pfab, Florian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Martinos Ctr Biomed Imaging, Boston, MA 02774 USA. [Zilker, Thomas] Tech Univ Munich, Dept Toxicol, D-80802 Munich, Germany. [Schalock, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02774 USA. RP Darsow, U (reprint author), Tech Univ Munich, Klin & Poliklin Dermatol & Allergol Biederstein, Dept Dermatol & Allergy Biederstein, Biedersteiner Str 29, D-80802 Munich, Germany. EM ulf.darsow@lrz.tum.de RI Buters, Jeroen/G-5070-2011; OI Schalock, Peter/0000-0001-8953-4639 NR 7 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-1873 EI 1600-0536 J9 CONTACT DERMATITIS JI Contact Dermatitis PY 2011 VL 64 IS 6 BP 361 EP 362 DI 10.1111/j.1600-0536.2011.01905.x PG 2 WC Allergy; Dermatology SC Allergy; Dermatology GA 762PM UT WOS:000290491900012 PM 21564130 ER PT J AU Gros, DF Strachan, M Ruggiero, KJ Knapp, RG Frueh, BC Egede, LE Lejuez, CW Tuerk, PW Acierno, R AF Gros, Daniel F. Strachan, Martha Ruggiero, Kenneth J. Knapp, Rebecca G. Frueh, B. Christopher Egede, Leonard E. Lejuez, C. W. Tuerk, Peter W. Acierno, Ron TI Innovative service delivery for secondary prevention of PTSD in at-risk OIF-OEF service men and women SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE PTSD; Depression; Exposure therapy; Telehealth; OEF/OIF ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY PERSONNEL; EXPOSURE THERAPY; COMBAT VETERANS; HEALTH PROBLEMS; PRIMARY-CARE; US VETERANS; TELEPSYCHIATRY; AFGHANISTAN; SYMPTOMS AB Service personnel involved in Operation Enduring Freedom/Operation Iraqi Freedom are at high risk for trauma-related physical injury and emotional problems, including posttraumatic stress disorder (PTSD) and major depression. Although evidence-based psychotherapies are increasingly available and effective in treating symptoms of PTSD, a large number of service personnel are reluctant to seek mental health treatments due to both perceived stigma associated with these treatments and geographically-based barriers to care at specialized treatment facilities. The present investigation evaluates an innovation in service delivery designed to address these concerns. Specifically, we are comparing exposure-based therapy for PTSD delivered via traditional, in-person settings to the same exposure-based treatment delivered via telehealth technology. The proposed project is a prospective, randomized repeated measures design with two treatment groups (telehealth and in-person) assessed at pre-treatment, mid-treatment, post-treatment and 3- and 12-month follow-up points. Outcome measures ascertain longer-term effects of the treatments on three domains: clinical, process, and economic. Non-inferiority and superiority analyses will be conducted to determine symptom changes between pre-treatment, post-treatment, and follow-up time points between the two treatment conditions. The study will determine whether an exposure therapy for PTSD delivered via telehealth is at least as successful as the same exposure-based therapy delivered in-person in treating the symptoms of PTSD in both subthreshold and fully diagnosed cases. Published by Elsevier Inc. C1 [Gros, Daniel F.] Ralph H Johnson VAMC, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.; Strachan, Martha; Ruggiero, Kenneth J.; Knapp, Rebecca G.; Egede, Leonard E.; Tuerk, Peter W.; Acierno, Ron] Med Univ S Carolina, Charleston, SC 29425 USA. [Frueh, B. Christopher] Univ Hawaii, Hilo, HI 96720 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Lejuez, C. W.] Univ Maryland, Ctr Addict Personal & Emot Res, College Pk, MD 20742 USA. RP Gros, DF (reprint author), Ralph H Johnson VAMC, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU Department of Defense [W81XWH-07-FTSD-IIRA]; Ralph H. Johnson VAMC Research Enhancement Award [REA08-261]; Center for Disease Prevention and Health Interventions for Diverse Populations FX This research is supported by the Department of Defense Grant W81XWH-07-FTSD-IIRA (PI: Acierno). Several authors are also core and affiliate members of the Ralph H. Johnson VAMC Research Enhancement Award Program (REA08-261; PI: Egede), the Center for Disease Prevention and Health Interventions for Diverse Populations. NR 44 TC 21 Z9 21 U1 5 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2011 VL 32 IS 1 BP 122 EP 128 DI 10.1016/j.cct.2010.10.003 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 710YI UT WOS:000286552500017 PM 20951235 ER PT B AU Shemansky, WJ Goldstein, G AF Shemansky, Wendy J. Goldstein, Gerald BE Goldstein, G Incagnoli, TM Puente, AE TI Behavioral toxicological disorders SO CONTEMPORARY NEUROBEHAVIORAL SYNDROMES LA English DT Article; Book Chapter ID SICK-BUILDING SYNDROME; MULTIPLE CHEMICAL-SENSITIVITY; PRENATAL METHYLMERCURY EXPOSURE; DEPLETED URANIUM EXPOSURE; RISK-ASSESSMENT; GENERAL-POPULATION; MERCURY EXPOSURE; FISH CONSUMPTION; METHYL MERCURY; PCB EXPOSURE C1 [Shemansky, Wendy J.] VA Med Ctr, Pittsburgh, PA USA. [Goldstein, Gerald] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Shemansky, WJ (reprint author), VA Med Ctr, Pittsburgh, PA USA. NR 102 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 978-0-20382-965-3 PY 2011 BP 195 EP 218 PG 24 WC Psychology, Biological; Psychiatry SC Psychology; Psychiatry GA BUM37 UT WOS:000289774000010 ER PT J AU Colby, K Bhat, P Novais, G Jakobiec, FA AF Colby, Kathryn Bhat, Pooja Novais, Gustavo Jakobiec, Frederick A. TI Recurrent Primary Acquired Melanosis With Atypia Involving a Clear Corneal Phacoemulsification Wound SO CORNEA LA English DT Article DE primary acquired melanosis (PAM) with atypia; Bowman layer; corneal incision; conjunctival melanoma; phacoemulsification; cataract surgery ID CONJUNCTIVAL MELANOMA; RISK AB Purpose: To report a case of corneal primary acquired melanosis (PAM) with atypia after cataract surgery. Methods: Retrospective case report with literature review. Results: Excision of an elevated pigmented conjunctival lesion was performed at the time of cataract extraction by clear corneal phacoemulsification by an outside surgeon. Histopathologic examination revealed PAM with atypia. Three months after the initial surgery, recurrent melanosis involving the peripheral corneal epithelium was noted, with extension of pigment into the corneal stroma through the paracentesis site. Excision of the involved corneal epithelium and the adjacent conjunctiva was performed, and microscopically recurrent PAM with atypia was confirmed. Adjuvant cryotherapy was applied at the time of surgery, and topical mitomycin C was given postoperatively. Repeat biopsies revealed no remaining malignancy, and the intrastromal pigment has disappeared during 18 months of follow-up. Conclusion: We present this case to illustrate the importance of complete evaluation and treatment of potentially atypical melanocytic conjunctival lesions before proceeding with elective intraocular surgery. C1 [Colby, Kathryn] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Comea Serv,Dept Ophthalmol, Boston, MA 02114 USA. [Bhat, Pooja; Jakobiec, Frederick A.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, David Cogan Lab Ophthalm Pathol,Dept Ophthalmol, Boston, MA 02114 USA. [Novais, Gustavo] Univ Fed Sao Paulo, Dept Ophthalmol, UNIFESP EPM, Sao Paulo, Brazil. RP Colby, K (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Comea Serv,Dept Ophthalmol, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JAN PY 2011 VL 30 IS 1 BP 114 EP 116 DI 10.1097/ICO.0b013e3181e2efb8 PG 3 WC Ophthalmology SC Ophthalmology GA 691MY UT WOS:000285086400023 PM 20847655 ER PT J AU Stoodley, CJ Stein, JF AF Stoodley, Catherine J. Stein, John F. TI The cerebellum and dyslexia SO CORTEX LA English DT Editorial Material ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EXERCISE-BASED TREATMENT; COGNITIVE-AFFECTIVE SYNDROME; IMPLICIT LEARNING DEFICIT; REACTION-TIME-TASK; DEVELOPMENTAL DYSLEXIA; READING DIFFICULTIES; EYE-MOVEMENTS; FUNCTIONAL LOCALIZATION; SPEECH-PERCEPTION C1 [Stoodley, Catherine J.] Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Grp, Boston, MA 02114 USA. [Stoodley, Catherine J.] Harvard Univ, Sch Med, Boston, MA USA. [Stein, John F.] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 2JD, England. RP Stoodley, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Grp, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM cstoodley@partners.org RI Stoodley, Catherine/P-2081-2016 OI Stoodley, Catherine/0000-0003-2629-0213 NR 223 TC 30 Z9 30 U1 4 U2 22 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 EI 1973-8102 J9 CORTEX JI Cortex PD JAN PY 2011 VL 47 IS 1 BP 101 EP 116 DI 10.1016/j.cortex.2009.10.005 PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 710XY UT WOS:000286551500010 PM 20060110 ER PT J AU Branski, LK Herndon, DN Byrd, JF Kinsky, MP Lee, JO Fagan, SP Jeschke, MG AF Branski, Ludwik K. Herndon, David N. Byrd, Jaron F. Kinsky, Michael P. Lee, Jong O. Fagan, Shawn P. Jeschke, Marc G. TI Transpulmonary thermodilution for hemodynamic measurements in severely burned children SO CRITICAL CARE LA English DT Article ID CRITICALLY-ILL PATIENTS; INTRATHORACIC BLOOD-VOLUME; DYSFUNCTION PELOD SCORE; MAJOR THERMAL-INJURY; CARDIAC-OUTPUT; PULMONARY-ARTERY; FLUID-MANAGEMENT; LUNG WATER; TRAUMA; RESUSCITATION AB Introduction: Monitoring of hemodynamic and volumetric parameters after severe burns is of critical importance. Pulmonary artery catheters, however, have been associated with many risks. Our aim was to show the feasibility of continuous monitoring with minimally invasive transpulmonary thermodilution (TPTD) in severely burned pediatric patients. Methods: This prospective cohort study was conducted in patients with severe burns over 40% of the total body surface area (TBSA) who were admitted to the hospital within 96 hours after sustaining the injury. TPTD measurements were performed using the PiCCO system (Pulsion Medical Systems, Munich, Germany). Cardiac Index (CI), Intrathoracic Blood Volume Index (ITBVI) (Stewart-Hamilton equation), Extravascular Lung Water Index (EVLWI) and Systemic Vascular Resistance Index (SVRI) measurements were recorded twice daily. Statistical analysis was performed using one-way repeated measures analysis of variance with the post hoc Bonferroni test for intra-and intergroup comparisons. Results: Seventy-nine patients with a mean age (+/- SD) of 9 +/- 5 years and a mean TBSA burn (+/- SD) of 64% +/- 20% were studied. CI significantly increased compared to level at admission and was highest 3 weeks postburn. ITBVI increased significantly starting at 8 days postburn. SVRI continuously decreased early in the perioperative burn period. EVLWI increased significantly starting at 9 days postburn. Young children (0 to 5 years old) had a significantly increased EVLWI and decreased ITBVI compared to older children (12 to 18 years old). EVLWI was significantly higher in patients who did not survive burn injury. Conclusions: Continuous PiCCO measurements were performed for the first time in a large cohort of severely burned pediatric patients. The results suggest that hyperdynamic circulation begins within the first week after burn injury and continues throughout the entire intensive care unit stay. C1 [Jeschke, Marc G.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Ross Tilley Burn Ctr, Toronto, ON M4N 3M5, Canada. [Jeschke, Marc G.] Univ Toronto, Dept Surg, Div Plast Surg, Toronto, ON M4N 3M5, Canada. [Branski, Ludwik K.; Herndon, David N.; Byrd, Jaron F.; Kinsky, Michael P.; Lee, Jong O.] Shriners Hosp Children, Galveston, TX 77550 USA. [Branski, Ludwik K.; Herndon, David N.; Byrd, Jaron F.; Lee, Jong O.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA. [Kinsky, Michael P.] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA. [Fagan, Shawn P.] Shriners Hosp Children, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. [Fagan, Shawn P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jeschke, MG (reprint author), Univ Toronto, Sunnybrook Hlth Sci Ctr, Ross Tilley Burn Ctr, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM marc.jeschke@sunnybrook.ca FU National Institutes of Health (NIH) [T32-GM08256, P50 GM60338]; Special Shared Facility; Clinical Research and Computer Research Support Shriners Hospitals for Children [8480]; Spectrometry Core Shriners Hospitals for Children [8490]; American Surgical Association Foundation; NIH National Center for Research Resources [M01 RR-00073]; Shriners Hospitals for Children Research [8505] FX The authors thank David Chinkes for assistance with statistical analysis and Eileen Figueroa and Steve Schuenke for their help in the preparation of this manuscript. We also thank the entire clinical nursing staff for their great assistance in the conduction of this study. LKB thanks Dr. Robert E Barrow, PhD, for years of outstanding teaching, many hours of stimulating scientific discussion and multiple critical revisions of this manuscript. This work was supported by postdoctoral training in trauma and burns National Institutes of Health (NIH) grant T32-GM08256, assessment of anabolic agents/exercise in children NIH grant P50 GM60338, Special Shared Facility: Clinical Research and Computer Research Support Shriners Hospitals for Children grant 8480, Mass Spectrometry Core Shriners Hospitals for Children grant 8490, the American Surgical Association Foundation. It was supported in part by grant M01 RR-00073 from the NIH National Center for Research Resources. LKB is supported by a Shriners Hospitals for Children Research Fellowship (8505). NR 43 TC 14 Z9 15 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2011 VL 15 IS 2 AR R118 DI 10.1186/cc10147 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 789HJ UT WOS:000292506000042 PM 21507260 ER PT J AU Derwall, M Francis, RCE Kida, K Bougaki, M Crimi, E Adrie, C Zapol, WM Ichinose, F AF Derwall, Matthias Francis, Roland C. E. Kida, Kotaro Bougaki, Masahiko Crimi, Ettore Adrie, Christophe Zapol, Warren M. Ichinose, Fumito TI Administration of hydrogen sulfide via extracorporeal membrane lung ventilation in sheep with partial cardiopulmonary bypass perfusion: a proof of concept study on metabolic and vasomotor effects SO CRITICAL CARE LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; ANIMATION-LIKE STATE; CARDIAC-ARREST; HYPOXIA; MICE; HYPOTHERMIA; RESPONSES; VASODILATION; INHALATION; MECHANISM AB Introduction: Although inhalation of 80 parts per million (ppm) of hydrogen sulfide (H(2)S) reduces metabolism in mice, doses higher than 200 ppm of H(2)S were required to depress metabolism in rats. We therefore hypothesized that higher concentrations of H(2)S are required to reduce metabolism in larger mammals and humans. To avoid the potential pulmonary toxicity of H(2)S inhalation at high concentrations, we investigated whether administering H(2)S via ventilation of an extracorporeal membrane lung (ECML) would provide means to manipulate the metabolic rate in sheep. Methods: A partial venoarterial cardiopulmonary bypass was established in anesthetized, ventilated (fraction of inspired oxygen = 0.5) sheep. The ECML was alternately ventilated with air or air containing 100, 200, or 300 ppm H(2)S for intervals of 1 hour. Metabolic rate was estimated on the basis of total CO(2) production ((V) over dot CO(2)) and O(2) consumption ((V) over dot O(2)). Continuous hemodynamic monitoring was performed via indwelling femoral and pulmonary artery catheters. Results: (V) over dot CO(2), (V) over dot O(2), and cardiac output ranged within normal physiological limits when the ECML was ventilated with air and did not change after administration of up to 300 ppm H(2)S. Administration of 100, 200 and 300 ppm H(2)S increased pulmonary vascular resistance by 46, 52 and 141 dyn.s/cm(5), respectively (all P <= 0.05 for air vs. 100, 200 and 300 ppm H(2)S, respectively), and mean pulmonary artery pressure by 4 mmHg (P <= 0.05), 3 mmHg (n.s.) and 11 mmHg (P <= 0.05), respectively, without changing pulmonary capillary wedge pressure or cardiac output. Exposure to 300 ppm H2S decreased systemic vascular resistance from 1,561 +/- 553 to 870 +/- 138 dyn.s/cm(5) (P <= 0.05) and mean arterial pressure from 121 +/- 15 mmHg to 66 +/- 11 mmHg (P <= 0.05). In addition, exposure to 300 ppm H(2)S impaired arterial oxygenation (P(a)O(2) 114 +/- 36 mmHg with air vs. 83 +/- 23 mmHg with H(2)S; P <= 0.05). Conclusions: Administration of up to 300 ppm H(2)S via ventilation of an extracorporeal membrane lung does not reduce (V) over dot CO(2) and (V) over dot O(2), but causes dose-dependent pulmonary vasoconstriction and systemic vasodilation. These results suggest that administration of high concentrations of H(2)S in venoarterial cardiopulmonary bypass circulation does not reduce metabolism in anesthetized sheep but confers systemic and pulmonary vasomotor effects. C1 [Derwall, Matthias; Francis, Roland C. E.; Kida, Kotaro; Bougaki, Masahiko; Crimi, Ettore; Adrie, Christophe; Zapol, Warren M.; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Derwall, Matthias; Francis, Roland C. E.; Kida, Kotaro; Bougaki, Masahiko; Crimi, Ettore; Adrie, Christophe; Zapol, Warren M.; Ichinose, Fumito] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Derwall, Matthias] Rhein Westfal TH Aachen, Dept Anesthesia, Fac Med, D-52074 Aachen, Germany. RP Derwall, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, 55 Fruit St, Boston, MA 02114 USA. EM mderwall@partners.org FU German Research Foundation (Deutsche Forschungsgemeinschaft) [DE 1685/1-1]; RCF [FR 2555/3-1]; WMZ; National Institutes of Health [R01 HL101930]; Arthur Sachs Scholarship Fund FX This work was supported by fellowship grants from the German Research Foundation (Deutsche Forschungsgemeinschaft) to MD (DE 1685/1-1) and RCF (FR 2555/3-1), by laboratory funds of WMZ and National Institutes of Health grant R01 HL101930 to FI. CA was supported by the Arthur Sachs Scholarship Fund. We are indebted to Dr. Kenneth D. Bloch from the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, for advice and assistance in the design of the study and in the editing of the manuscript. NR 41 TC 17 Z9 18 U1 2 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2011 VL 15 IS 1 AR R51 DI 10.1186/cc10016 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 742RJ UT WOS:000288961900051 PM 21299857 ER PT J AU Peacock, WF Varon, J Baumann, BM Borczuk, P Cannon, CM Chandra, A Cline, DM Diercks, D Hiestand, B Hsu, A Jois-Bilowich, P Kaminski, B Levy, P Nowak, RM Schrock, JW AF Peacock, W. Frank Varon, Joseph Baumann, Brigitte M. Borczuk, Pierre Cannon, Chad M. Chandra, Abhinav Cline, David M. Diercks, Deborah Hiestand, Brian Hsu, A. Jois-Bilowich, Preeti Kaminski, Brian Levy, Philip Nowak, Richard M. Schrock, Jon W. TI CLUE: a randomized comparative effectiveness trial of IV nicardipine versus labetalol use in the emergency department SO CRITICAL CARE LA English DT Article ID POSTOPERATIVE HYPERTENSION; MANAGEMENT; PATTERNS AB Introduction: Our purpose was to compare the safety and efficacy of food and drug administration (FDA) recommended dosing of IV nicardipine versus IV labetalol for the management of acute hypertension. Methods: Multicenter randomized clinical trial. Eligible patients had 2 systolic blood pressure (SBP) measures = 180 mmHg and no contraindications to nicardipine or labetalol. Before randomization, the physician specified a target SBP +/- 20 mmHg (the target range: TR). The primary endpoint was the percent of subjects meeting TR during the initial 30 minutes of treatment. Results: Of 226 randomized patients, 110 received nicardipine and 116 labetalol. End organ damage preceded treatment in 143 (63.3%); 71 nicardipine and 72 labetalol patients. Median initial SBP was 212.5 (IQR 197, 230) and 212 mmHg (IQR 200,225) for nicardipine and labetalol patients (P = 0.68), respectively. Within 30 minutes, nicardipine patients more often reached TR than labetalol (91.7 vs. 82.5%, P = 0.039). Of 6 BP measures (taken every 5 minutes) during the study period, nicardipine patients had higher rates of five and six instances within TR than labetalol (47.3% vs. 32.8%, P = 0.026). Rescue medication need did not differ between nicardipine and labetalol (15.5 vs. 22.4%, P = 0.183). Labetalol patients had slower heart rates at all time points (P < 0.01). Multivariable modeling showed nicardipine patients were more likely in TR than labetalol patients at 30 minutes (OR 2.73, P = 0.028; C stat for model = 0.72) Conclusions: Patients treated with nicardipine are more likely to reach the physician-specified SBP target range within 30 minutes than those treated with labetalol. C1 [Peacock, W. Frank] Cleveland Clin, Dept Emergency Med, Cleveland, OH 44195 USA. [Varon, Joseph] Univ Texas Hlth Sci Ctr Houston, Galveston, TX 77555 USA. [Varon, Joseph] Univ Texas Med Branch Galveston, Galveston, TX 77555 USA. [Baumann, Brigitte M.] Cooper Univ Hosp, Div Clin Res, Camden, NJ 08103 USA. [Borczuk, Pierre] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Cannon, Chad M.] Univ Kansas Hosp, Dept Emergency Med, Kansas City, KS 66103 USA. [Chandra, Abhinav] Duke Univ, Med Ctr, Div Emergency Med, Durham, NC 27710 USA. [Cline, David M.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA. [Diercks, Deborah] Univ Calif, Davis Med Ctr, Sacramento, CA 95817 USA. [Hiestand, Brian] Ohio State Univ, Columbus, OH 43210 USA. [Jois-Bilowich, Preeti] Univ Florida, Coll Med, Dept Emergency Med, Gainesville, FL 32610 USA. [Kaminski, Brian] Toledo Hosp, Toledo, OH 43606 USA. [Levy, Philip] Wayne State Univ, Sch Med, Dept Emergency Med, Detroit, MI 48201 USA. [Levy, Philip] Wayne State Univ, Cardiovasc Res Inst, Detroit, MI 48201 USA. [Nowak, Richard M.] Wayne State Univ, Sch Med, Henry Ford Hosp, Dept Emergency Med, Detroit, MI 48202 USA. [Schrock, Jon W.] Case Western Reserve Univ, Sch Med, MetroHlth Med Ctr, Dept Emergency Med, Cleveland, OH 44109 USA. RP Peacock, WF (reprint author), Cleveland Clin, Dept Emergency Med, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM peacocw@ccf.org FU EKR FX EKR Grant support was provided for Peacock, Varon and Baumann. There is a competing interest with The Medicine's Company involving Peacock, Varon, Baumann, Chandra and Hiestand. Co-authors Barczuk, Cannon, Cline, Diercks, Jois-Bilowich, Hsu, Kaminski, Levy, Nowak and Schrock has "no competing interest" to disclose. Chandra also has a competing interest with EKR. Hiestand has received Grant support from The Medicines Company and he has competing interest with Medtronic Inc., Biosite Inc., Inovise Medical Inc., Heartscape International, Nanosphere Inc., and Mitsubishi Medicine. NR 10 TC 14 Z9 14 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2011 VL 15 IS 3 AR R157 DI 10.1186/cc10289 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 832JB UT WOS:000295799700039 PM 21707983 ER PT J AU Rempell, JS Noble, VE AF Rempell, Joshua S. Noble, Vicki E. TI Using lung ultrasound to differentiate patients in acute dyspnea in the prehospital emergency setting SO CRITICAL CARE LA English DT Editorial Material ID ALVEOLAR-INTERSTITIAL SYNDROME; NATRIURETIC PEPTIDE; HEART-FAILURE; SIGN AB The diagnosis and treatment of dyspnea in the emergency department and in the prehospital setting is a challenge faced by the emergency physician and other prehospital care providers. While the use of lung ultrasound as a diagnostic tool in dyspneic patients has been well researched, there has been limited evaluation of its use in the prehospital setting. In the previous issue of Critical Care, Prosen and colleagues study the accuracy of lung ultrasound compared with both N-terminal pro-brain natriuretic peptide and the clinical examination for differentiating between acute decompensated congestive heart failure and chronic obstructive pulmonary disease exacerbations for patients in the prehospital setting. Their article adds to the growing body of evidence demonstrating the diagnostic efficacy of lung ultrasound in differentiating between these two disease processes in the acutely dyspneic patient. C1 [Rempell, Joshua S.; Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Rempell, JS (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM jrempell@partners.org NR 10 TC 4 Z9 4 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2011 VL 15 IS 3 AR 161 DI 10.1186/cc10226 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 832JB UT WOS:000295799700048 PM 21635703 ER PT J AU Ehlenbach, WJ Curtis, JR AF Ehlenbach, William J. Curtis, J. Randall TI The meaning of do-not-resuscitation orders: A need for clarity SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE cardiopulmonary resuscitation; do-not-resuscitate; advance care planning; end-of-life; ethics ID DECISION-MAKING; IMPACT C1 [Ehlenbach, William J.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Ehlenbach, William J.; Curtis, J. Randall] Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Ehlenbach, WJ (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. NR 14 TC 3 Z9 3 U1 1 U2 4 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 JAN PY 2011 VL 39 IS 1 BP 193 EP 194 DI 10.1097/CCM.0b013e318202e7d4 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 698FQ UT WOS:000285579600032 PM 21178531 ER PT B AU McIntyre, LK Langdale, LA AF McIntyre, Lisa K. Langdale, Lorrie A. BE Bland, KI Sarr, MG Buchler, MW Csendes, A Garden, OJ Wong, J TI Pulmonary Embolism SO CRITICAL CARE SURGERY: HANDBOOKS IN GENERAL SURGERY LA English DT Article; Book Chapter ID D-DIMER; VENOUS THROMBOEMBOLISM; CLINICAL-MODEL; PROBABILITY; CT C1 [McIntyre, Lisa K.] Univ Washington, Harborview Med Ctr, Dept Gen Surg, Seattle, WA 98104 USA. [Langdale, Lorrie A.] Univ Washington, Dept Surg, Seattle, WA 98104 USA. [Langdale, Lorrie A.] VA Puget Sound Hlth Care, Seattle, WA USA. RP McIntyre, LK (reprint author), Univ Washington, Harborview Med Ctr, Dept Gen Surg, 325 9th Ave, Seattle, WA 98104 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND BN 978-1-84996-377-0 PY 2011 BP 157 EP 171 DI 10.1007/978-1-84996-378-7_10 D2 10.1007/978-1-84996-378-7 PG 15 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA BRS18 UT WOS:000283523400010 ER PT J AU Gonzalez, R Ballester, I Lopez-Posadas, R Suarez, MD Zarzuelo, A Martinez-Augustin, O De Medina, F AF Gonzalez, R. Ballester, I. Lopez-Posadas, R. Suarez, M. D. Zarzuelo, A. Martinez-Augustin, O. De Medina, F. Sanchez TI Effects of Flavonoids and other Polyphenols on Inflammation SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review DE asthma; inflammatory bowel disease; arthritis; pharmacokinetics; atherosclerosis; mechanism of action ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE SYNTHASE; HUMAN ENDOTHELIAL-CELLS; HUMAN UMBILICAL VEIN; GREEN TEA POLYPHENOL; ADHESION MOLECULE EXPRESSION; LENS EPITHELIAL-CELLS; ACID-INDUCED COLITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AB Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-B signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others. C1 [Gonzalez, R.; Lopez-Posadas, R.; De Medina, F. Sanchez] Univ Granada, Sch Pharm, CIBERehd, Dept Pharmacol, Granada 18071, Spain. [Ballester, I.] Massachusetts Gen Hosp, Gastrointestinal Unit GRJ716, Boston, MA 02114 USA. RP De Medina, F (reprint author), Univ Granada, Sch Pharm, CIBERehd, Dept Pharmacol, Campus Cartuja S-N, Granada 18071, Spain. EM fsanchez@ugr.es RI Zarzuelo, Antonio/L-2840-2014; Lorente, M Dolores/N-1313-2014; Suarez Ortega, Maria Dolores/H-1240-2015; Martinez Augustin, Olga/K-6720-2014 OI Suarez Ortega, Maria Dolores/0000-0003-3197-2518; Martinez Augustin, Olga/0000-0001-8291-3468 FU Ministry of Science and Innovation [AGL2008-04332, SAF2008-01432]; CIBERehd; Instituto de Salud Carlos III; Ministry of Education and Science, Spain; European Regional Development Fund [BFU2007-30688-E/BFI]; Fundacion Ramon Areces FX This study was supported by grants of the Ministry of Science and Innovation (AGL2008-04332 and SAF2008-01432) and the CIBERehd. RG is funded by the CIBERehd. RLP and IB are funded by the Ministry of Science and Innovation. The CIBERehd is funded by the Instituto de Salud Carlos III. The group is member of the Network for Cooperative Research on Membrane Transport Proteins (REIT), co-funded by the Ministry of Education and Science, Spain and the European Regional Development Fund (Grant (BFU2007-30688-E/BFI). The authors also acknowledge the support of the Fundacion Ramon Areces. NR 458 TC 173 Z9 179 U1 11 U2 103 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2011 VL 51 IS 4 BP 331 EP 362 AR PII 935267685 DI 10.1080/10408390903584094 PG 32 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 742OJ UT WOS:000288953600003 PM 21432698 ER PT J AU Fletcher, AL Calder, A Hince, MN Boyd, RL Chidgey, AP AF Fletcher, Anne L. Calder, Adrienne Hince, Melanie N. Boyd, Richard L. Chidgey, Ann P. TI The Contribution of Thymic Stromal Abnormalities to Autoimmune Disease SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE thymus; thymic stromal cells; autoimmunity; Aire; negative selection ID REGULATORY T-CELLS; NEW-ZEALAND MICE; CANDIDIASIS-ECTODERMAL DYSTROPHY; BONE-MARROW-TRANSPLANTATION; ORGAN-SPECIFIC AUTOIMMUNITY; 22Q11.2 DELETION SYNDROME; AIRE DEFICIENT MICE; EPITHELIAL-CELLS; MYASTHENIA-GRAVIS; IMMUNE-SYSTEM AB In essence, normal thymus function involves the production of a broad repertoire of alpha beta T cells capable of responding to foreign antigens with low risk of autoreactivity. Thymic epithelial cells are an essential component of the thymic stromal microenvironment, promoting the growth and export of self-tolerant thymocytes. Autoimmune disease, resulting from a loss of self-tolerance, is clinically and genetically complex, and accordingly has many potential etiological origins. However, it is commonly linked to defects in the thymic epithelial microenvironment. The study of autoimmune-linked thymic stromal dysfunction has indisputably advanced our understanding of T cell tolerance; notably, a field-wide paradigm shift occurred when autoimmune regulator (Aire) was found to drive expression of a multitude of peripheral tissue-restricted antigens in medullary thymic epithelial cells. Many other associations with polygenically controlled autoimmune diseases have been reported but are more difficult to definitively dissect. Paradoxically, immunodeficiency and age-related immunosenescence are also linked with increased autoimmunity. Here we discuss the theoretical basis and the evidence gathered thus far to support these associations. C1 [Fletcher, Anne L.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Fletcher, Anne L.; Calder, Adrienne; Hince, Melanie N.; Boyd, Richard L.; Chidgey, Ann P.] Monash Univ, Monash Immunol & Stem Cell Labs, Melbourne, Vic 3004, Australia. RP Fletcher, AL (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM AnneL_Fletcher@dfci.harvard.edu RI Fletcher, Anne/A-1590-2011 NR 143 TC 12 Z9 12 U1 0 U2 3 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2011 VL 31 IS 3 BP 171 EP 187 PG 17 WC Immunology SC Immunology GA 782KA UT WOS:000292006000001 PM 21740349 ER PT J AU Hatoum, HT Lin, SJ Guo, A Lipton, A Smith, MR AF Hatoum, Hind T. Lin, Swu-Jane Guo, Amy Lipton, Allan Smith, Matthew R. TI Zoledronic acid therapy impacts risk and frequency of skeletal complications and follow-up duration in prostate cancer patients with bone metastasis SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE Bone metastasis; Prostate; Prostatic neoplasms; Skeletal complication; Zoledronic acid ID BISPHOSPHONATE TREATMENT; SOLID TUMORS; LUNG-CANCER; PREVENTION; MANAGEMENT; COST AB To evaluate the effects of timing and length of zoledronic acid (ZA) treatment on outcomes for patients with prostate cancer in clinical practice. Patients with prostate cancer and first bone metastasis diagnosed from January 2003 to October 2006 were included. Patients were considered 'untreated' if no ZA was given, 'early ZA-treated' if ZA was initiated before skeletal complication (SC) occurrence or 'late ZA-treated' if one or more SC was documented before or at ZA initiation. Patients were classified with short (90 days), medium (91-180 days) or long (> 180 days) treatment persistence. Assessments included follow-up duration (FUP) and risk of developing one or more SC. Among eligible patients, 847 were untreated, 243 were early ZA-treated and 218 were late ZA-treated. For untreated versus early ZA-treated groups, median FUP was 263 versus 357 days (p < 0.0001), respectively, and time to first SC was 199 versus 273 days (p < 0.0001), respectively. ZA treatment was associated with significantly longer FUP and lower SC risk. The early ZA-treated group had significantly longer FUP versus the late ZA-treated group (median days, 357 vs. 299.5); the late ZA-treated group experienced significantly higher SC risk vs. the early ZA-treated group (odds ratio, 1.51). Compared with the long-persistence group, FUP was 56% and 40% shorter in the short and medium groups, respectively (p < 0.0001). Treatment with and early initiation of ZA for patients with prostate cancer and bone metastasis significantly prolonged time to and reduced risk of developing SC, while extending FUP. C1 [Hatoum, Hind T.; Lin, Swu-Jane] Hind T Hatoum & Co, Chicago, IL 60647 USA. [Hatoum, Hind T.; Lin, Swu-Jane] Univ Illinois, Chicago, IL USA. [Guo, Amy] Novartis Pharmaceut, E Hanover, NJ USA. [Lipton, Allan] Milton S Hershey Med Ctr, Hershey, PA USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hatoum, HT (reprint author), Hind T Hatoum & Co, 1758 N Wilmot Ave, Chicago, IL 60647 USA. EM HTHatoum@sbcglobal.net FU Novartis Pharmaceuticals; Novartis FX The study was supported by Novartis Pharmaceuticals.; H.T.H. has disclosed that she is a paid consultant to Novartis, the marketer of zoledronic acid. S.-J.L. has disclosed that she is a consultant to Hind T. Hatoum & Company. M. R. S. and A. L. have disclosed that they act in an advisory capacity with Novartis. In addition, A. L. has disclosed that he has received laboratory research funding and provided expert testimony for Novartis. A. G. has disclosed that she is an employee of Novartis. The authors had full control of the findings and results presented, without any oversight or interference from the sponsor of the work. NR 26 TC 8 Z9 8 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD JAN PY 2011 VL 27 IS 1 BP 55 EP 62 DI 10.1185/03007995.2010.535511 PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 696BF UT WOS:000285416200005 PM 21083514 ER PT J AU Khosroshahi, A Stone, JH AF Khosroshahi, Arezou Stone, John H. TI A clinical overview of IgG4-related systemic disease SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE autoimmune pancreatitis; IgG4; IgG4-related systemic disease ID COMPLICATING AUTOIMMUNE PANCREATITIS; IDIOPATHIC RETROPERITONEAL FIBROSIS; CHRONIC SCLEROSING SIALADENITIS; IGG4-POSITIVE PLASMA-CELLS; DISTINCT CLINICOPATHOLOGICAL ENTITY; OF-THE-LITERATURE; SERUM IGG4; INFLAMMATORY PSEUDOTUMOR; FIBROINFLAMMATORY DISEASE; DIAGNOSTIC-CRITERIA AB Purpose of review To summarize the existing knowledge of various clinical presentations of IgG4-related systemic disease (IgG4-RSD) and to review the evolving list of organs affected by IgG4-RSD. Recent findings The term IgG4-RSD encompasses a variety of clinical entities once regarded as being entirely separate diseases. The list of organs associated with this condition is growing steadily. Tissue biopsies reveal striking histopathological similarity, regardless of which organ is involved, although subtle differences across organs exist. Diffuse lymphoplasmacytic infiltrates, presence of abundant IgG4-positive plasma cells and extensive fibrosis are the hallmark pathology findings. Tumorous swelling, eosinophilia, and obliterative phlebitis are other frequently observed features. Polyclonal elevations of serum IgG4 are found in most but not all patients. Summary IgG4-RSD is an underrecognized condition about which knowledge is now growing rapidly. Yet there remain many unknowns with regard to its cause, pathogenesis, various clinical presentations, approach to treatment, disease monitoring, and long-term outcomes. A wide variety of organs can be involved in IgG4-RSD. Clinicians should be aware of this entity and consider the diagnosis in the appropriate settings. C1 [Khosroshahi, Arezou; Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Khosroshahi, A (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM akhosroshahi@partners.org NR 86 TC 131 Z9 147 U1 5 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2011 VL 23 IS 1 BP 57 EP 66 DI 10.1097/BOR.0b013e3283418057 PG 10 WC Rheumatology SC Rheumatology GA 688RC UT WOS:000284868700010 PM 21124086 ER PT J AU Khosroshahi, A Stone, JH AF Khosroshahi, Arezou Stone, John H. TI Treatment approaches to IgG4-related systemic disease SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE autoimmune pancreatitis; B-cell depletion; IgG4; IgG4-related systemic disease; rituximab ID IMMUNOGLOBULIN G4-ASSOCIATED CHOLANGITIS; LONG-TERM PROGNOSIS; AUTOIMMUNE PANCREATITIS; CORTICOSTEROID-TREATMENT; LYMPHOPLASMACYTIC AORTITIS; RITUXIMAB THERAPY; STEROID-THERAPY; RELAPSE; BORTEZOMIB; REMISSION AB Purpose of review IgG4-related systemic disease (IgG4-RSD) is a systemic fibroinflammatory condition that can affect any organ system. Prompt recognition and management of this disease process are necessary to prevent sclerosis and permanent organ damage. Here, we review the advances in treatment approaches to IgG4-RSD. Recent findings Most information regarding treatment is derived from retrospective case series of patients with autoimmune pancreatitis (AIP), and follow-up periods have generally been short. A variety of IgG4-RSD presentations respond rapidly to glucocorticoid treatment. Glucocorticoids have become a standard therapy for AIP, but the indications requiring treatment as well as the appropriate starting dose and duration of therapy remain controversial. The importance of maintenance of glucocorticoids following remission induction is debatable. As our knowledge grows regarding other organ manifestations of IgG4-RSD with longer follow-ups, the necessity of steroid-sparing agents to manage frequent relapses becomes clear. Summary The natural history and long-term prognosis of IgG4-RSD are not well understood. Large prospective studies and randomized controlled trials of patients with wide spectrum manifestations of IgG4-RSD are required to support better approaches to treatment. C1 [Khosroshahi, Arezou; Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Khosroshahi, A (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM akhosroshahi@partners.org NR 29 TC 94 Z9 104 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2011 VL 23 IS 1 BP 67 EP 71 DI 10.1097/BOR.0b013e328341a240 PG 5 WC Rheumatology SC Rheumatology GA 688RC UT WOS:000284868700011 PM 21124087 ER PT J AU Khosroshahi, A Stone, JH AF Khosroshahi, Arezou Stone, John H. TI IgG4-related systemic disease: the age of discovery SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Editorial Material ID CHRONIC SCLEROSING SIALADENITIS; LYMPHOPLASMACYTIC AORTITIS; RETROPERITONEAL FIBROSIS; LYMPHADENOPATHY; FIBROSCLEROSIS C1 [Khosroshahi, Arezou; Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Khosroshahi, A (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM akhosroshahi@partners.org NR 17 TC 13 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2011 VL 23 IS 1 BP 72 EP 73 DI 10.1097/BOR.0b013e328341a229 PG 2 WC Rheumatology SC Rheumatology GA 688RC UT WOS:000284868700012 PM 21124088 ER PT J AU Stone, JR AF Stone, James R. TI Aortitis, periaortitis, and retroperitoneal fibrosis, as manifestations of IgG4-related systemic disease SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE arteritis; inflammatory aneurysm; inflammatory aortopathy; pancreatitis; periaortitis; plasma cells; vasculitis ID AUTOIMMUNE PANCREATITIS; SCLEROSING DISEASE; LYMPHOPLASMACYTIC AORTITIS; ANEURYSM; IGG4; SIALADENITIS; INVOLVEMENT AB Purpose of review In last few years, there have been significant advances in our understanding of a newly recognized condition known as IgG4-related systemic disease. This review will focus on IgG4-related systemic disease as a cause of thoracic aortitis, inflammatory abdominal aortic aneurysm or periaortitis, and retroperitoneal fibrosis. Recent findings A significant fraction of thoracic lymphoplasmacytic aortitis cases, about 40% of inflammatory abdominal aortic aneurysms/abdominal periaortitis cases, and a portion of retroperitoneal fibrosis cases are all caused by IgG4-related systemic disease. Assessing pathologic specimens for the fraction of plasma cells that express IgG4 is useful in identifying patients with this disorder. Recently reported data may indicate IgG4-related aortic disease to be more common than widely realized. Summary IgG4-related systemic disease is a newly recognized disorder that may manifest as thoracic aortitis, inflammatory abdominal aortic aneurysm or retroperitoneal fibrosis. IgG4-related systemic disease should be considered in any patient found to have aortitis or periaortitis. Further studies into diagnostic criteria, disease prevalence, prognosis, therapeutic interventions, and differentiating possible localized hypersensitivity reactions from systemic disease are areas of active investigation. Criteria are presented for the pathologic diagnosis of IgG4-related aortitis. C1 [Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stone, James R.] Harvard Univ, Sch Med, Boston, MA USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,Room 8236,185 Cambridge St CPZN, Boston, MA 02114 USA. EM jrstone@partners.org FU Massachusetts General Hospital FX This work was supported by Massachusetts General Hospital. NR 47 TC 110 Z9 117 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2011 VL 23 IS 1 BP 88 EP 94 DI 10.1097/BOR.0b013e3283412f7c PG 7 WC Rheumatology SC Rheumatology GA 688RC UT WOS:000284868700015 PM 21037477 ER PT J AU Geyer, JT Deshpande, V AF Geyer, Julia T. Deshpande, Vikram TI IgG4-associated sialadenitis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE chronic sclerosing sialadenitis; IgG4; IgG4-related systemic disease; Mikulicz disease; orbital pseudotumor; sialadenitis ID CHRONIC SCLEROSING SIALADENITIS; IGG4-RELATED AUTOIMMUNE-DISEASE; KUTTNER TUMOR; SUBMANDIBULAR-GLAND; SALIVARY-GLAND; SJOGRENS-SYNDROME; PANCREATITIS; LYMPHOMA AB Purpose of review An enlarged salivary gland or lacrimal gland raises a wide differential diagnosis that includes both benign inflammatory conditions and malignant disorders. This review aims to address the numerous controversies that have arisen regarding inflammatory diseases of the salivary gland over the past two centuries and more specifically address the relevance of IgG4 in this setting. Recent findings A significant percentage of cases previously classified as Mikulicz disease, Kuttner tumor, and orbital pseudotumor (idiopathic orbital inflammation) show elevated numbers of IgG4-positive plasma cells, and some of these cases also show elevated levels of serum IgG4. These data support the evolving concept of IgG4-associated sialadenitis/dacroadenitis. The disease presents with enlargement of one of more salivary gland(s) and/or lacrimal gland(s). Histologically this disease is characterized by a dense polyclonal lymphoplasmacytic infiltrate, and is frequently associated with germinal centers, fibrosis and obliterative phlebitis. IgG4-bearing plasma cells are virtually always present, as is an elevated ratio of IgG4 to IgG containing plasma cells. Summary IgG4-related sialadenitis belongs to the IgG4-related systemic disease spectrum and shows a swift response to immunosuppression. C1 [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Geyer, Julia T.] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. RP Geyer, JT (reprint author), Massachusetts Gen Hosp, Pathol Dept Warren 2, 55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 46 TC 44 Z9 52 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 EI 1531-6963 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD JAN PY 2011 VL 23 IS 1 BP 95 EP 101 DI 10.1097/BOR.0b013e3283413011 PG 7 WC Rheumatology SC Rheumatology GA 688RC UT WOS:000284868700016 PM 21124091 ER PT S AU Jang, JW Ng, AK AF Jang, Joanne W. Ng, Andrea K. BE Lu, JJ Brady, LW TI Non-Hodgkin's Lymphoma SO DECISION MAKING IN RADIATION ONCOLOGY, VOL 2 SE Medical Radiology-Radiation Oncology LA English DT Article; Book Chapter C1 [Jang, Joanne W.; Ng, Andrea K.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Ng, Andrea K.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ng, AK (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1,L2, Boston, MA 02115 USA. EM jwjang@partners.org; ANG@lroc.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0942-5373 BN 978-3-642-16333-3 J9 MED RADIOL RADIAT ON PY 2011 BP 747 EP 770 DI 10.1007/978-3-642-16333-3_8 D2 10.1007/978-3-642-16333-3 PG 24 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BGW78 UT WOS:000324405100009 ER PT J AU Marshall, GA Olson, LE Frey, MT Maye, J Becker, JA Rentz, DM Sperling, RA Johnson, KA AF Marshall, Gad A. Olson, Lauren E. Frey, Meghan T. Maye, Jacqueline Becker, J. Alex Rentz, Dorene M. Sperling, Reisa A. Johnson, Keith A. CA Alzheimer's Dis Neuroimaging Initi TI Instrumental Activities of Daily Living Impairment Is Associated with Increased Amyloid Burden SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Alzheimer's disease; Amyloid; Instrumental activities of daily living; Mild cognitive impairment; Pittsburgh compound B; Positron emission tomography ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH COMPOUND-B; ALZHEIMERS-DISEASE; FUNCTIONAL CONNECTIVITY; OLDER-ADULTS; DEMENTIA; DEPOSITION; PET; POPULATION; COMMUNITY AB Background/Aims: Instrumental activities of daily living (IADL) impairment in Alzheimer's disease has been associated with global amyloid deposition in postmortem studies. We sought to determine whether IADL impairment is associated with increased cortical Pittsburgh Compound B (PiB) retention. Methods: Fifty-five subjects (19 normal older controls, NC, and 36 with mild cognitive impairment, MCI) underwent clinical assessments and dynamic PiB positron emission tomography imaging. Results: A linear multiple regression model showed that greater IADL impairment was associated with greater global PiB retention in all subjects (R(2) = 0.40; unstandardized partial regression coefficient, beta = 5.8; p = 0.0002) and in MCI subjects only (R(2) = 0.28; beta = 6.1; p = 0.003), but not in NC subjects only. Conclusion: These results suggest that daily functional impairment is related to greater amyloid burden in MCI. Copyright (C) 2011 S. Karger AG, Basel C1 [Marshall, Gad A.; Olson, Lauren E.; Frey, Meghan T.; Rentz, Dorene M.; Sperling, Reisa A.; Johnson, Keith A.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA 02115 USA. [Marshall, Gad A.; Olson, Lauren E.; Rentz, Dorene M.; Sperling, Reisa A.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Maye, Jacqueline; Johnson, Keith A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Marshall, GA (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, 221 Longwood Ave,BL 104H, Boston, MA 02115 USA. EM gamarshall@partners.org RI Scharre, Douglas/E-4030-2011 FU Rosalinde and Arthur Gilbert Foundation [R01 AG027435S, 1K23AG033634]; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; ADNI National Institutes of Health [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; National Institutes of Health [P30 AG010129, K01 AG030514]; Dana Foundation FX This study was supported by R01 AG027435S, 1K23AG033634, the Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), and the ADNI National Institutes of Health grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc., F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by National Institutes of Health grants P30 AG010129 and K01 AG030514, and the Dana Foundation. NR 37 TC 16 Z9 16 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2011 VL 31 IS 6 BP 443 EP 450 DI 10.1159/000329543 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 806TO UT WOS:000293835800008 PM 21778725 ER PT J AU Ibrahimi, OA Avram, MM Hanke, CW Kilmer, SL Anderson, RR AF Ibrahimi, Omar A. Avram, Mathew M. Hanke, C. William Kilmer, Suzanne L. Anderson, R. Rox TI Laser hair removal SO DERMATOLOGIC THERAPY LA English DT Review DE laser hair removal; photoepilation; selective photothermolysis ID MODE RUBY-LASER; DIODE-LASER; ISOTRETINOIN THERAPY; ALEXANDRITE LASER; SELECTIVE PHOTOTHERMOLYSIS; RANDOMIZED-TRIAL; HUMAN-SKIN; FOLLOW-UP; HIRSUTISM; COMBINATION AB The extended theory of selective photothermolysis enables the laser surgeon to target and destroy hair follicles, thereby leading to hair removal. Today, laser hair removal (LHR) is the most commonly requested cosmetic procedure in the world and is routinely performed by dermatologists, other physicians, and non-physician personnel with variable efficacy. The ideal candidate for LHR is fair skinned with dark terminal hair; however, LHR can today be successfully performed in all skin types. Knowledge of hair follicle anatomy and physiology, proper patient selection and preoperative preparation, principles of laser safety, familiarity with the various laser/light devices, and a thorough understanding of laser-tissue interactions are vital to optimizing treatment efficacy while minimizing complications and side effects. C1 [Ibrahimi, Omar A.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95816 USA. [Ibrahimi, Omar A.; Kilmer, Suzanne L.] Laser & Skin Surg Ctr No Calif, Sacramento, CA USA. [Avram, Mathew M.; Anderson, R. Rox] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hanke, C. William] Laser & Skin Surg Ctr Indiana, Carmel, IN USA. RP Ibrahimi, OA (reprint author), Univ Calif Davis, Dept Dermatol, 3301 C St,Suite 1400, Sacramento, CA 95816 USA. EM omar.ibrahimi@gmail.com NR 57 TC 38 Z9 40 U1 1 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD JAN-FEB PY 2011 VL 24 IS 1 BP 94 EP 107 DI 10.1111/j.1529-8019.2010.01382.x PG 14 WC Dermatology SC Dermatology GA 713WV UT WOS:000286769000009 PM 21276162 ER PT J AU Fett, N Liu, RH AF Fett, Nicole Liu, Rosemarie H. TI Multicentric Reticulohistiocytosis with Dermatomyositis-Like Features: A More Common Disease Presentation than Previously Thought SO DERMATOLOGY LA English DT Review DE Multicentric reticulohistiocytosis; Dermatomyositis ID INTERSTITIAL LUNG-DISEASE; AMYOPATHIC DERMATOMYOSITIS; THERAPY; METHOTREXATE; CYCLOPHOSPHAMIDE; COMBINATION; INFLIXIMAB; INHIBITOR; LESIONS AB Multicentric reticulohistiocytosis (MRH) is a rare form of non-Langerhans histiocytosis that presents with erosive arthritis and skin nodules. Approximately 25% of patients with MRH have an associated malignancy. Dermatomyositis is an inflammatory autoimmune condition that has also been associated with malignancy. To date, 7 cases of MRH have been reported to present with cutaneous features of dermatomyositis. We describe an eighth patient with MRH who presented with dermatomyositis-like features (V-neck erythema, shawl sign, Gottron's papules and periungual erythema), who developed metastatic breast cancer 1 year after diagnosis. We hypothesized that clinical overlap between MRH and dermatomyositis was not as uncommon as review of the literature suggested. Careful review of the physical exam findings and photographs of the 234 papers reporting MRH revealed 27 cases of MRH with dermatomyositis-like features. Of these 27 cases, 7 (26%) were associated with a malignancy. Skin biopsies of the cutaneous features mimicking dermatomyositis revealed pathologic features of MRH. This is a descriptive analysis of published case reports. Based on a review of published case reports, MRH presenting with dermatomyositis-like features is likely fairly common. Histological examination of skin biopsies allows for disease differentiation. Differentiating MRH from dermatomyositis is important for management decisions and comorbidity screening. Copyright (C) 2011 S. Karger AG, Basel C1 [Fett, Nicole] Univ Penn, Sch Med, Perelman Ctr Adv Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Fett, Nicole] Univ Penn, Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Liu, Rosemarie H.] Univ Wisconsin, Madison Hosp & Clin, Madison, WI USA. RP Fett, N (reprint author), Univ Penn, Sch Med, Perelman Ctr Adv Med, Dept Dermatol, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM nicole.fett@uphs.upenn.edu NR 42 TC 7 Z9 8 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 2011 VL 222 IS 2 BP 102 EP 108 DI 10.1159/000323254 PG 7 WC Dermatology SC Dermatology GA 757NM UT WOS:000290094200002 PM 21252485 ER PT J AU Mosimann, C Kaufman, CK Li, PL Pugach, EK Tamplin, OJ Zon, LI AF Mosimann, Christian Kaufman, Charles K. Li, Pulin Pugach, Emily K. Tamplin, Owen J. Zon, Leonard I. TI Ubiquitous transgene expression and Cre-based recombination driven by the ubiquitin promoter in zebrafish SO DEVELOPMENT LA English DT Article DE Transgenesis; ubiquitin promoter; creER; loxP; Zebrafish ID IN-VIVO; MOSAIC ANALYSIS; GENE-FUNCTION; MICE; TRANSPLANTATION; GENERATION; VECTORS; EMBRYOS; STRAIN; TOOLS AB Molecular genetics approaches in zebrafish research are hampered by the lack of a ubiquitous transgene driver element that is active at all developmental stages. Here, we report the isolation and characterization of the zebrafish ubiquitin (ubi) promoter, which drives constitutive transgene expression during all developmental stages and analyzed adult organs. Notably, ubi expresses in all blood cell lineages, and we demonstrate the application of ubi-driven fluorophore transgenics in hematopoietic transplantation experiments to assess true multilineage potential of engrafted cells. We further generated transgenic zebrafish that express ubiquitous 4-hydroxytamoxifen-controlled Cre recombinase activity from a ubi:cre(ERt2) transgene, as well as ubi:loxP-EGFP-loxP-mCherry (ubi:Switch) transgenics and show their use as a constitutive fluorescent lineage tracing reagent. The ubi promoter and the transgenic lines presented here thus provide a broad resource and important advancement for transgenic applications in zebrafish. C1 [Mosimann, Christian; Li, Pulin; Pugach, Emily K.; Tamplin, Owen J.; Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Mosimann, Christian; Li, Pulin; Pugach, Emily K.; Tamplin, Owen J.; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Mosimann, Christian; Li, Pulin; Pugach, Emily K.; Tamplin, Owen J.; Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Childrens Hosp Boston,Div Hematol Oncol, Boston, MA 02115 USA. [Kaufman, Charles K.; Zon, Leonard I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zon, LI (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu RI Tamplin, Owen/C-1617-2014 OI Tamplin, Owen/0000-0001-9146-4860 FU EMBO; HFSP; National Institutes of Health [5T32CA09172-34, 5PO1HL32262-28]; Heart and Stroke Foundation of Canada; Canadian Institutes of Health Research FX We thank A. Chen and K. Lawson for technical assistance, C. Lawrence and I. Adatto for fish husbandry, and Drs S. Lacadie and K. Kathrein for insightful discussion and critical comments. C.M. received support through an EMBO long-term fellowship and a HFSP long-term fellowship. C.K.K. is supported by NIH grant 5T32CA09172-34. O.J.T. is funded by fellowships from the Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research. This study was supported by National Institutes of Health grant 5PO1HL32262-28. L.I.Z. is an HHMI investigator. Deposited in PMC for release after 6 months. NR 31 TC 97 Z9 97 U1 3 U2 28 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 JAN 1 PY 2011 VL 138 IS 1 BP 169 EP 177 DI 10.1242/dev.059345 PG 9 WC Developmental Biology SC Developmental Biology GA 690YO UT WOS:000285046500018 PM 21138979 ER PT J AU Da'as, S Teh, EM Dobson, JT Nasrallah, GK McBride, ER Wang, H Neuberg, DS Marshall, JS Lin, TJ Berman, JN AF Da'as, Sahar Teh, Evelyn M. Dobson, J. Tristan Nasrallah, Gheyath K. McBride, Eileen R. Wang, Hao Neuberg, Donna S. Marshall, Jean S. Lin, Tong-Jun Berman, Jason N. TI Zebrafish mast cells possess an Fc epsilon RI-like receptor and participate in innate and adaptive immune responses SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article DE Zebrafish; Mast cells; Ketotifen; Aeromonas salmonicida; Anaphylaxis; Toll-like receptor ID TOLL-LIKE-RECEPTOR; CELLS/EOSINOPHILIC GRANULE CELLS; IMMUNOGLOBULIN-E; TELEOSTEAN FISH; RODLET CELLS; DANIO-RERIO; STAINING PROPERTIES; EXPRESSION ANALYSIS; ALLERGIC DISEASES; IGE RECEPTOR AB We previously identified a zebrafish mast cell (MC) lineage and now aim to determine if these cells function analogously in innate and adaptive immunity like their mammalian counterparts. Intraperitoneal (IP) injection of compound 48/80 or live Aeromonas salmonicida resulted in significant MC degranulation evident histologically and by increased plasma tryptase compared with saline-injected controls (p = 0.0006, 0.005, respectively). Pre-treatment with ketotifen abrogated these responses (p = 0.0004, 0.005, respectively). Cross-reactivity was observed in zebrafish to anti-human high-affinity IgE receptor gamma (FceRI gamma) and IgE heavy chain-directed antibodies. Whole mount in situ hybridization on 7-day embryos demonstrated co-localization of cpa5, a MC-specific marker, with myd88, a toll-like receptor adaptor, and zebrafish Fc epsilon RI subunit homologs. Zebrafish injected IP with matched dinitrophenyl-sensitized mouse (anti-DNP) IgE and DNP-BSA or trinitrophenyl-sensitized mouse (anti-TNP) IgE and TNP-BSA demonstrated increased plasma tryptase compared with mismatched controls (p = 0.03, 0.010, respectively). These results confirm functional conservation and validate the zebrafish model as an in vivo screening tool for novel MC modulating agents. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Berman, Jason N.] Dalhousie Univ, IWK Hlth Ctr, Dept Pediat, Div Pediat Hematol Oncol, Halifax, NS B3K 6R8, Canada. [Dobson, J. Tristan; Nasrallah, Gheyath K.; Marshall, Jean S.; Lin, Tong-Jun; Berman, Jason N.] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS B3K 6R8, Canada. [Wang, Hao] Canc Care Nova Scotia, Halifax, NS B3H 2Y9, Canada. [Neuberg, Donna S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Berman, JN (reprint author), Dalhousie Univ, IWK Hlth Ctr, Dept Pediat, Div Pediat Hematol Oncol, POB 9700,5850-5980 Univ Ave, Halifax, NS B3K 6R8, Canada. EM jason.berman@iwk.nshealth.ca FU Dalhousie Clinical Scholar; CIHR-NSHRF FX We would like to thank Chris Hall and Phil Crosier for providing myd88::GFP embryos, Jeffrey Yoder for providing fcer1g and fcer1gl cDNA clones and critical review of the manuscript. We would like to thank David Traver for critical review of the manuscript. We would like to thank Graham Dellaire for assistance with reviewing gene conservation including assisting with generating phylogenetic trees. Western blots were conducted in the laboratory of Rafael Garduno. We would like to thank Jocelyn Jaques for administrative assistance. J.N.B. is supported by Dalhousie Clinical Scholar and CIHR-NSHRF Regional Partnership Awards. NR 51 TC 23 Z9 24 U1 2 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PD JAN PY 2011 VL 35 IS 1 BP 125 EP 134 DI 10.1016/j.dci.2010.09.001 PG 10 WC Immunology; Zoology SC Immunology; Zoology GA 690RW UT WOS:000285024400015 PM 20849876 ER PT J AU Renstrom, F Shungin, D Johansson, I Florez, JC Hallmans, G Hu, FB Franks, PW AF Renstrom, Frida Shungin, Dmitry Johansson, Ingegerd Florez, Jose C. Hallmans, Goran Hu, Frank B. Franks, Paul W. CA MAGIC Investigators TI Genetic Predisposition to Long-Term Nondiabetic Deteriorations in Glucose Homeostasis Ten-Year Follow-Up of the GLACIER Study SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES RISK; IMPAIRED FASTING GLUCOSE; MELATONIN-RECEPTOR; NORTHERN SWEDEN; POPULATION; VARIANTS; INSULIN; POLYMORPHISM; MELLITUS AB OBJECTIVE-To assess whether recently discovered genetic loci associated with hyperglycemia also predict long-term changes in glycemic traits. RESEARCH DESIGN AND METHODS-Sixteen fasting glucose-raising loci were genotyped in middle-aged adults from the Gene x Lifestyle interactions And Complex traits Involved in Elevated disease Risk (GLACIER) Study, a population-based prospective cohort study from northern Sweden. Genotypes were tested for association with baseline fasting and 2-h postchallenge glycemia (N = 16,330), and for changes in these glycemic traits during a 10-year follow-up period (N = 4,059). RESULTS-Cross-sectional directionally consistent replication with fasting glucose concentrations was achieved for 12 of 16 variants; 10 variants were also associated with impaired fasting glucose (IFG) and 7 were independently associated with 2-h postchallenge glucose concentrations. In prospective analyses, the effect alleles at four loci (GCK rs4607517, ADRA2A rs10885122, DGKB-TMEM195 rs2191349, and G6PC2 rs560887) were nominally associated with worsening fasting glucose concentrations during 10-years of follow-up. MTNR1B rs10830963, which was predictive of elevated fasting glucose concentrations in cross-sectional analyses, was associated with a protective effect on postchallenge glucose concentrations during follow-up; however, this was only when baseline fasting and 2-h glucoses were adjusted for. An additive effect of multiple risk alleles on glycemic traits was observed: a weighted genetic risk score (80th vs. 20th centiles) was associated with a 0.16 mmol/l (P = 2.4 x 10(-6)) greater elevation in fasting glucose and a 64% (95% CI: 33-201%) higher risk of developing IFG during 10 years of follow-up. CONCLUSIONS-Our findings imply that genetic profiling might facilitate the early detection of persons who are genetically susceptible to deteriorating glucose control; studies of incident type 2 diabetes and discrete cardiovascular end points will help establish whether the magnitude of these changes is clinically relevant. Diabetes 60:345-354, 2011 C1 [Renstrom, Frida; Shungin, Dmitry; Franks, Paul W.] Umea Univ Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. [Renstrom, Frida; Hu, Frank B.; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Shungin, Dmitry; Johansson, Ingegerd] Umea Univ Hosp, Dept Odontol, S-90185 Umea, Sweden. [MAGIC Investigators] Wellcome Trust Sanger Inst, Metab Dis Grp, Hinxton CB10 1SA, Cambs, England. [Florez, Jose C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hallmans, Goran] Umea Univ Hosp, Sect Nutr Res, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden. [Franks, Paul W.] Lund Univ, Dept Clin Sci, Skane Univ Hosp, Malmo, Sweden. RP Franks, PW (reprint author), Umea Univ Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. EM paul.franks@med.lu.se OI Shungin, Dmitry/0000-0001-7900-5856; Franks, Paul/0000-0002-0520-7604 FU Novo Nordisk; Swedish Heart-Lung Foundation; Swedish Diabetes Association; Pahlssons Foundation; Swedish Research Council; Umea Medical Research Foundation; Heart Foundation of Northern Sweden FX The GLACIER Study was funded by project grants from Novo Nordisk, the Swedish Heart-Lung Foundation, the Swedish Diabetes Association, the Pahlssons Foundation, the Swedish Research Council, the Umea Medical Research Foundation, and The Heart Foundation of Northern Sweden (all to P.W.F.). F.R. was supported by a postdoctoral stipend from the Swedish Heart-Lung Foundation. NR 40 TC 31 Z9 31 U1 1 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 JAN PY 2011 VL 60 IS 1 BP 345 EP 354 DI 10.2337/db10-0933 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703YG UT WOS:000286017300042 PM 20870969 ER PT J AU de Miguel-Yanes, JM Shrader, P Pencina, MJ Fox, CS Manning, AK Grant, RW Dupuis, J Florez, JC D'Agostino, RB Cupples, LA Meigs, JB AF de Miguel-Yanes, Jose M. Shrader, Peter Pencina, Michael J. Fox, Caroline S. Manning, Alisa K. Grant, Richard W. Dupuis, Josee Florez, Jose C. D'Agostino, Ralph B., Sr. Cupples, L. Adrienne Meigs, James B. CA MAGIC Investigators DIAGRAM Investigators TI Genetic Risk Reclassification for Type 2 Diabetes by Age Below or Above 50 Years Using 40 Type 2 Diabetes Risk Single Nucleotide Polymorphisms SO DIABETES CARE LA English DT Article ID ASSOCIATION ANALYSIS; SUSCEPTIBILITY LOCI; VARIANTS; MELLITUS AB OBJECTIVE- To test if knowledge of type 2 diabetes genetic variants improves disease prediction. RESEARCH DESIGN AND METHODS- We tested 40 single nucleotide polymorphisms (SNPs) associated with diabetes in 3,471 Framingham Offspring Study subjects followed over 34 years using pooled logistic regression models stratified by age (<50 years, diabetes cases = 144; or >= 50 years, diabetes cases = 302). Models included clinical risk factors and a 40-SNP weighted genetic risk score. RESULTS- In people <50 years of age, the clinical risk factors model C-statistic was 0.908; the 40-SNP score increased it to 0.911 (P = 0.3; net reclassification improvement (NRI): 10.2%, P = 0.001). In people >= 50 years of age, the C-statistics without and with the score were 0.883 and 0.884 (P = 0.2; NRI: 0.4%). The risk per risk allele was higher in people <50 than >= 50 years of age (24 vs. 11%; P value for age interaction = 0.02). CONCLUSIONS- Knowledge of common genetic variation appropriately reclassifies younger people for type 2 diabetes risk beyond clinical risk factors but not older people. C1 [de Miguel-Yanes, Jose M.; Shrader, Peter; Grant, Richard W.; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [de Miguel-Yanes, Jose M.; Fox, Caroline S.; Grant, Richard W.; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [de Miguel-Yanes, Jose M.] Hosp Gen Univ Gregorio Maranon, Dept Med Interna, Madrid, Spain. [Pencina, Michael J.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Fox, Caroline S.; Dupuis, Josee; D'Agostino, Ralph B., Sr.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA. [Manning, Alisa K.; Dupuis, Josee; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jmeigs@partners.org OI Griffin, Simon/0000-0002-2157-4797; Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603; Grant, Richard/0000-0002-6164-8025 FU National Heart, Lung, and Blood Institute [N01-HC- 25195]; National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK078616, K24 DK080140, K23 DK65978, R21 DK084527]; "Instituto de Salud Carlos III", Madrid, Spain [2009/90071]; National Institutes of Health National Center for Research Resources [1S10RR163736-01A1] FX This study was supported by the by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC- 25195), the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01 DK078616 and K24 DK080140 (to J.B.M.), NIDDK Research Career Award K23 DK65978 (to J.C.F.), NIDDK Grant R21 DK084527 (to R.W.G.), "Bolsa de Ampliacion de Estudios" from the "Instituto de Salud Carlos III", Madrid, Spain (2009/90071) (to J.M.D.M.Y.), and the Boston University Linux Cluster for Genetic Analysis (LinGA) funded by the National Institutes of Health National Center for Research Resources Shared Instrumentation Grant (1S10RR163736-01A1). NR 15 TC 90 Z9 91 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2011 VL 34 IS 1 BP 121 EP 125 DI 10.2337/dc10-1265 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710FT UT WOS:000286497000025 PM 20889853 ER PT J AU Moon, HS Chamberland, JP Diakopoulos, KN Fiorenza, CG Ziemke, F Schneider, B Mantzoros, CS AF Moon, Hyun-Seuk Chamberland, John P. Diakopoulos, Kalliope N. Fiorenza, Christina G. Ziemke, Florencia Schneider, Benjamin Mantzoros, Christos S. TI Leptin and Amylin Act in an Additive Manner to Activate Overlapping Signaling Pathways in Peripheral Tissues In vitro and ex vivo studies in humans SO DIABETES CARE LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; WEIGHT-LOSS; OB/OB MICE; EXPRESSION; OBESITY; NEUROENDOCRINE; RESISTANCE; INSULIN; CANCER; ALPHA AB OBJECTIVE- Amylin interacts with leptin to alter metabolism. We evaluated, for the first time, amylin- and/or leptin-activated signaling pathways in human peripheral tissues (hPTs). RESEARCH DESIGN AND METHODS- Leptin and amylin signaling studies were performed in vitro in human primary adipocytes (hPAs) and human peripheral blood mononuclear cells (hPBMCs) and ex vivo in human adipose tissue (hAT) from male versus female subjects, obese versus lean subjects, and subjects with subcutaneous versus omental adipose tissue. RESULTS- The long form of leptin receptor was expressed in human tissues and cells studied in ex vivo and in vitro, respectively. Leptin and amylin alone and in combination activate signal transducer and activator of transcription 3 (STAT3), AMP-activated protein kinase, Akt, and extracellular signal-regulated kinase signaling pathways in hAT ex vivo and hPAs and hPBMCs in vitro; all phosphorylation events were saturable at leptin and amylin concentrations of similar to 50 and similar to 20 ng/ml, respectively. The effects of leptin and amylin on STAT3 phosphorylation in hPAs and hPBMCs in vitro were totally abolished under endoplasmic reticulum stress and/or in the presence of a STAT3 inhibitor. Results similar to those in the in vitro studies were observed in hAT studied ex vivo. CONCLUSIONS- Leptin and amylin activate overlapping intracellular signaling pathways in humans and have additive, but not synergistic, effects in signaling pathways studied in hPTs in vitro and ex vivo. C1 [Moon, Hyun-Seuk; Chamberland, John P.; Diakopoulos, Kalliope N.; Fiorenza, Christina G.; Ziemke, Florencia; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Schneider, Benjamin] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Minimally Invas Surg, Boston, MA USA. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. EM cmantzor@bidmc.harvard.edu RI Moon, Hyun-Seuk/G-8576-2015; OI Moon, Hyun-Seuk/0000-0002-5216-2090; Chamberland, John/0000-0002-7862-1371; Diakopoulos, Kalliope/0000-0002-9236-0489 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK58785, DK79929, DK81913]; Beth Israel Deaconess Medical Center; [AG032030] FX Funding was received from the National Institute of Diabetes and Digestive and Kidney Diseases grants DK58785, DK79929, and DK81913 and AG032030. The Mantzoros Laboratory is also supported by a discretionary grant from Beth Israel Deaconess Medical Center. NR 29 TC 43 Z9 43 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2011 VL 34 IS 1 BP 132 EP 138 DI 10.2337/dc10-0518 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710FT UT WOS:000286497000028 PM 20870968 ER PT J AU Funnell, MM Brown, TL Childs, BP Haas, LB Hosey, GM Jensen, B Maryniuk, M Peyrot, M Piette, JD Reader, D Siminerio, LM Weinger, K Weiss, MA AF Funnell, Martha M. Brown, Tammy L. Childs, Belinda P. Haas, Linda B. Hosey, Gwen M. Jensen, Brian Maryniuk, Melinda Peyrot, Mark Piette, John D. Reader, Diane Siminerio, Linda M. Weinger, Katie Weiss, Michael A. TI National Standards for Diabetes Self-Management Education SO DIABETES CARE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; CHRONIC DISEASE MANAGEMENT; IMPROVE GLYCEMIC CONTROL; PRIMARY-CARE PATIENTS; HEALTH-CARE; COMMUNITY-HEALTH; COMPLICATIONS TRIAL; PATIENT EDUCATION; AFRICAN-AMERICAN; CHRONIC ILLNESS C1 [Funnell, Martha M.] Univ Michigan, Dept Med Educ, Diabet Res & Training Ctr, Ann Arbor, MI 48109 USA. [Brown, Tammy L.] Indian Hlth Serv, Albuquerque, NM USA. [Childs, Belinda P.] MidAmer Diabet Associates, Wichita, KS USA. [Haas, Linda B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Hosey, Gwen M.] Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Jensen, Brian] Lakeshore Apothacare, Two Rivers, WI USA. [Maryniuk, Melinda; Weinger, Katie] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Peyrot, Mark] Loyola Coll, Baltimore, MD 21210 USA. [Piette, John D.] VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. [Piette, John D.] Univ Michigan, Dept Internal Med, Diabet Res & Training Ctr, Ann Arbor, MI 48109 USA. [Reader, Diane] Int Diabet Ctr, Minneapolis, MN USA. [Siminerio, Linda M.] Univ Pittsburgh, Med Ctr, Inst Diabet, Pittsburgh, PA USA. [Weiss, Michael A.] Patient Centered Solut, Pittsburgh, PA USA. RP Funnell, MM (reprint author), Univ Michigan, Dept Med Educ, Diabet Res & Training Ctr, Ann Arbor, MI 48109 USA. EM mfunnell@umich.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [NIH5P60 DK20572, 1 R18 0K062323] FX Work on this article was supported in part by grant nos. NIH5P60 DK20572 and 1 R18 0K062323 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. NR 164 TC 59 Z9 63 U1 3 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2011 VL 34 SU 1 BP S89 EP S96 DI 10.2337/dc11-S089 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710FU UT WOS:000286497100008 PM 21193633 ER PT J AU Grant, RW Pabon-Nau, L Ross, KM Youatt, EJ Pandiscio, JC Park, ER AF Grant, Richard W. Pabon-Nau, Lina Ross, Kaile M. Youatt, Emily J. Pandiscio, Jennifer C. Park, Elyse R. TI Diabetes Oral Medication Initiation and Intensification Patient Views Compared With Current Treatment Guidelines SO DIABETES EDUCATOR LA English DT Article ID PSYCHOLOGICAL INSULIN-RESISTANCE; EUROPEAN-ASSOCIATION; CONSENSUS STATEMENT; CLINICAL INERTIA; THERAPY; MANAGEMENT; ADHERENCE; HYPERGLYCEMIA; POPULATION; ADJUSTMENT AB Purpose The purpose of this study was to compare patient perceptions about medication management with principles underlying American Diabetes Association (ADA) published treatment algorithms. Methods Six focus groups (4 English and 2 Spanish) were conducted with 50 patients with type 2 diabetes. Patients were asked about their prior experiences with initiating and changing oral medicines. They were also shown a medication plan for a hypothetical patient depicting future potential changes to achieve glycemic control. Coded responses were mapped to 3 concepts implicit in the ADA recommended treatment algorithm: (1) prescribing medicines to achieve A1c goal is beneficial, (2) medical regimens are generally intensified, and (3) intensification should be timely. Results Patient perceptions contrasted markedly with the treatment algorithm: (1) most patients had negative perceptions of medication initiation, viewing this event as evidence of personal failure and an increased burden; (2) patients equated medication intensification with increased risk for diabetes-related complications (rather than a step to reduce future risk) and viewed de-escalation as a primary goal; and (3) no patients expressed concerns about delays in medication intensification. Patients responded very favorably to an individualized medication plan depicting future potential changes. Conclusions Patients in this study described a conceptual model for medication therapy that contrasted in critical ways from the principles of current treatment guidelines. Underscoring the key role of patient-provider communication, the results suggest that effective counseling should also include an informed discussion of future medication intensification. C1 [Grant, Richard W.; Pabon-Nau, Lina; Pandiscio, Jennifer C.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Ross, Kaile M.; Youatt, Emily J.; Pandiscio, Jennifer C.; Park, Elyse R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Grant, Richard W.; Pabon-Nau, Lina; Park, Elyse R.] Harvard Univ, Sch Med, Boston, MA USA. RP Grant, RW (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50-9 Staniford St, Boston, MA 02114 USA. EM rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK [R03 DK080183, K23067452] FX This study was funded by NIDDK R03 DK080183 and by NIDDK K23067452. The authors have no conflicts of interest to disclose. NR 29 TC 20 Z9 20 U1 3 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD JAN-FEB PY 2011 VL 37 IS 1 BP 78 EP 84 DI 10.1177/0145721710388427 PG 7 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 715LC UT WOS:000286885000006 PM 21115980 ER PT J AU Tomas, E Wood, JA Stanojevic, V Habener, JF AF Tomas, E. Wood, J. A. Stanojevic, V. Habener, J. F. TI Glucagon-like peptide-1(9-36)amide metabolite inhibits weight gain and attenuates diabetes and hepatic steatosis in diet-induced obese mice SO DIABETES OBESITY & METABOLISM LA English DT Article DE animal pharmacology; antidiabetic drug; antiobesity drug; diabetes mellitus; energy expenditure; energy regulation; GLP-1; insulin resistance; metabolic syndrome ID HIGH-FAT DIET; INSULIN-RESISTANCE; PEPTIDE-1 RECEPTOR; NEUTRAL ENDOPEPTIDASE-24.11; TISSUE DISTRIBUTION; INCRETIN RECEPTORS; ENERGY-EXPENDITURE; GLUCOSE-PRODUCTION; OXIDATIVE STRESS; MOUSE MODEL AB Aims: The metabolic syndrome, a disease arising from the world-wide epidemic of obesity, is manifested as severe insulin resistance, hyperlipidaemia, hepatic steatosis and diabetes. Previously we reported that GLP-1(9-36)amide, derived from the gluco-incretin hormone, glucagon-like peptide-1 (GLP-1), suppresses gluconeogenesis in isolated hepatocytes. The aims of this study were to determine the effects of GLP-1(9-36) amide in diet-induced obese mice that model the development of the metabolic syndrome. Methods: Mice rendered obese by feeding a very high fat diet were administered GLP-1(9-36) amide via subcutaneous osmopumps for 8 weeks. Body weight, energy intake, plasma insulin and glucose levels (insulin-resistance), and hepatic steatosis were assessed. Results: Eight-week infusions of GLP-1(9-36) amide inhibited weight gain, increased energy intake, prevented the development of fasting hyperinsulinaemia and hyperglycaemia, and curtailed the accumulation of liver triglycerides. The peptide had no effects in mice fed a normal chow diet. Notably, energy intake in the obese mice receiving GLP-1(9-36) amide was 20% greater than obese mice receiving vehicle control. Conclusions: GLP-1(9-36) amide exerts insulin-like actions in the presence of insulin resistance and prevents the development of metabolic syndrome. Curtailment of weight gain in the face of increased caloric intake suggests that GLP-1(9-36) amide increases energy expenditure. These findings suggest the possibility of the use of GLP-1(9-36) amide, or a peptide mimetic derived there from, for the treatment of obesity, insulin resistance and the metabolic syndrome. C1 [Tomas, E.; Wood, J. A.; Stanojevic, V.; Habener, J. F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St Wellman 306,Thier 306, Boston, MA 02114 USA. EM Jhabener@partners.org NR 44 TC 19 Z9 21 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD JAN PY 2011 VL 13 IS 1 BP 26 EP 33 DI 10.1111/j.1463-1326.2010.01316.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 686LQ UT WOS:000284698200004 PM 21114600 ER PT J AU Wade, AN Fedyna, S Mehta, NN St Clair, C Ginwala, N Krishna, RK Qasim, AN Braunstein, S Iqbal, N Schutta, MH Reilly, MP AF Wade, Alisha N. Fedyna, Sean Mehta, Nehal N. St Clair, Caitlin Ginwala, Naeema Krishna, Rama K. Qasim, Atif N. Braunstein, Seth Iqbal, Nayyar Schutta, Mark H. Reilly, Muredach P. TI Type 2 diabetes does not attenuate racial differences in coronary calcification SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Race; Coronary artery calcification; Atherosclerosis; Type 2 diabetes ID CARDIOVASCULAR RISK-FACTORS; ELECTRON-BEAM TOMOGRAPHY; ARTERY CALCIFICATION; COMPUTED-TOMOGRAPHY; ATHEROSCLEROSIS MESA; ETHNIC-DIFFERENCES; ASYMPTOMATIC SUBJECTS; HEART-DISEASE; CALCIUM; PREVALENCE AB Aims: Coronary artery calcification (CAC) is a strong predictor of atherosclerotic cardiovascular disease (CVD). Whites appear to have a higher prevalence of CAC than African-Americans (AAs), but it is unknown if type 2 diabetes, a major cardiovascular risk factor, attenuates this difference. We investigated the relationship of race and CAC in a sample of patients with type 2 diabetes without clinical CVD. Methods: Multivariable analyses of self-reported ethnicity and CAC scores, stratified by gender, in 861 subjects [32% AA, 66.9% male] with type 2 diabetes. Results: AA race was associated with lower CAC scores in age-adjusted models in males [Tobit ratio for AAs vs. Whites 0.14 (95% CI 0.08-0.24, p < 0.001)] and females [Tobit ratio 0.26 (95% CI 0.09-0.77, p = 0.015)]. This persisted in men after adjustment for traditional, metabolic and inflammatory risk factors, but adjustment for plasma triglycerides [0.48 (95% CI 0.15-1.49, p = 0.201)] and HOMA-IR [0.28 (95% CI 0.08-1.03, p = 0.055)] partially attenuated the association in women. Conclusions: Relative to African-Americans, White race is a strong predictor of CAC, even in the presence of type 2 diabetes. The relationship in women appears less robust possibly due to gender differences in metabolic risk factors. (C) 2010 Published by Elsevier Ireland Ltd. C1 [Reilly, Muredach P.] Univ Penn, Med Ctr, Cardiovasc Inst, Sch Med, Philadelphia, PA 19104 USA. [Wade, Alisha N.; Fedyna, Sean; Braunstein, Seth; Schutta, Mark H.; Reilly, Muredach P.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Reilly, Muredach P.] Univ Penn, Sch Med, Dept Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Reilly, Muredach P.] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Ginwala, Naeema] SUNY Upstate Med Univ, Syracuse, NY USA. [Krishna, Rama K.] Penn Hosp, Philadelphia, PA 19104 USA. [Iqbal, Nayyar] Philadelphia Vet Affairs Med Ctr, Dept Med, Div Endocrinol, Philadelphia, PA 19104 USA. [Wade, Alisha N.] Univ Witwatersrand, Fac Hlth Sci, Div Endocrinol & Metab, Johannesburg, South Africa. RP Reilly, MP (reprint author), Univ Penn, Med Ctr, Cardiovasc Inst, Sch Med, 609 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM muredach@mail.med.upenn.edu FU National Center for Research Resources (NCRR) [UL1RR024134]; Diabetes and Endocrine Research Center [P20-DK 019525]; National Institutes of Health [RO1-DK071224, P50 HL-083799-SCCOR] FX This work was supported by a Clinical and Translational Science Award (UL1RR024134) from the National Center for Research Resources (NCRR) and a Diabetes and Endocrine Research Center (P20-DK 019525) award, both to the University of Pennsylvania. M. P. R. is also supported by RO1-DK071224 and P50 HL-083799-SCCOR from the National Institutes of Health. NR 28 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD JAN PY 2011 VL 91 IS 1 BP 101 EP 107 DI 10.1016/j.diabres.2010.07.004 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 698XS UT WOS:000285629100024 PM 21067835 ER PT J AU Prisciandaro, JJ Gebregziabher, M Grubaugh, AL Gilbert, GE Echols, C Egede, LE AF Prisciandaro, James J. Gebregziabher, Mulugeta Grubaugh, Anouk L. Gilbert, Gregory E. Echols, Carrae Egede, Leonard E. TI Impact of Psychiatric Comorbidity on Mortality in Veterans with Type 2 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID COMMON MENTAL-DISORDERS; GLYCEMIC CONTROL; ALL-CAUSE; DEPRESSION; PREVALENCE; MORBIDITY; MELLITUS; ILLNESS; ADULTS AB Background: Particular psychiatric disorders, such as depression, have a significant and negative effect on diabetes outcomes. However, we know very little about the impact of other psychiatric disorders, and of the effect of multiple psychiatric comorbidities, on the clinical course of diabetes. As such, the present study examined the impact of a wide range of psychiatric comorbidities on all-cause mortality in individuals with type 2 diabetes. Methods: Retrospective follow-up was conducted of 15,065 veterans with type 2 diabetes enrolled in hospital care between 1997 and 2006. Clinical diagnoses from patient records were used to construct four psychiatric disorder scales: internalizing (i.e., depression and anxiety); externalizing (i.e., alcohol and drug abuse); psychotic; and bipolar. Longitudinal relationships were examined between these scales and mortality using Cox regression. Results: Only externalizing disorders were significantly associated with mortality: hazard ratio = 1.22 (95% confidence interval = 1.02-1.47). In other words, each additional diagnosed externalizing disorder increased an individual's chance of dying over the follow-up period by 22%. This association remained significant when demographics and medical comorbidities were statistically controlled, but was rendered nonsignificant when medication adherence was introduced to the regression model. Conclusions: The results provide evidence that among individuals with diabetes, alcohol and drug abuse/dependence have a significant impact on mortality. This increased risk of mortality may have been due to the association between psychiatric disorders and adherence to antidiabetes medications observed in the present study. Individuals with co-occurring diabetes and alcohol or drug abuse should be targeted for intensive interventions given their acute increased risk of mortality. C1 [Prisciandaro, James J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta] Med Univ S Carolina, Div Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Gebregziabher, Mulugeta; Grubaugh, Anouk L.; Gilbert, Gregory E.; Echols, Carrae; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. RP Prisciandaro, JJ (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, 67 President St,POB 250861, Charleston, SC 29425 USA. EM priscian@musc.edu RI Gilbert, Gregory/C-7735-2016; OI Gilbert, Gregory/0000-0003-0879-5496; Gebregziabher, Mulugeta/0000-0002-4826-481X FU VA Health Services Research and Development Program [REA 08-261, IIR-04-421-3, IIR 07-139-3, IIR-06-219-2, MHI 08-105-2]; National Institutes of Health [RO1DK081121-01A1, T35DK007431]; Centers for Disease Control and Prevention [U58DP001015]; Department of Defense [PT073980] FX L.E.E. is funded on multiple grants from the VA Health Services Research and Development Program (REA 08-261, IIR-04-421-3, IIR 07-139-3, IIR-06-219-2, and MHI 08-105-2), the National Institutes of Health (RO1DK081121-01A1 and T35DK007431), the Centers for Disease Control and Prevention (U58DP001015), and the Department of Defense (PT073980). NR 26 TC 9 Z9 9 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JAN PY 2011 VL 13 IS 1 BP 73 EP 78 DI 10.1089/dia.2010.0092 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 697WH UT WOS:000285550000011 PM 21175275 ER PT J AU Borg, R Kuenen, JC Carstensen, B Zheng, H Nathan, DM Heine, RJ Nerup, J Borch-Johnsen, K Witte, DR AF Borg, R. Kuenen, J. C. Carstensen, B. Zheng, H. Nathan, D. M. Heine, R. J. Nerup, J. Borch-Johnsen, K. Witte, D. R. CA ADAG Study Grp TI HbA(1c) and mean blood glucose show stronger associations with cardiovascular disease risk factors than do postprandial glycaemia or glucose variability in persons with diabetes: the A1C-Derived Average Glucose (ADAG) study SO DIABETOLOGIA LA English DT Article DE ADAG study; CVD risk; Glucose monitoring; Glucose variability; HbA(1c); Postprandial glycaemia; z score ID HYPERGLYCEMIA AB Increased glucose excursions and postprandial hyperglycaemia have been suggested as unique risk factors for cardiovascular disease (CVD) and mortality in patients with diabetes mellitus. Much of the evidence is based on a single 2 h glucose value after oral glucose tolerance testing in epidemiological studies. We examined the association between various indices of glycaemia measured during everyday activities and metabolic CVD risk factors in the A1C-Derived Average Glucose (ADAG) study. Participants (268 with type 1 diabetes, 159 with type 2 diabetes) completed 16 weeks of intensive continuous glucose monitoring (CGM) and self-monitoring of blood glucose (SMBG). From these data, common indices of postprandial glycaemia, overall hyperglycaemia, glucose variability and HbA(1c) were derived. The associations between glycaemic indices and known CVD risk factors (lipids, high-sensitivity C-reactive protein and blood pressure) were explored in linear regression models. For both diabetes types, the overall strongest associations with CVD risk factors were seen for the measures of average glycaemia (mean blood glucose and HbA(1c)). Associations between self-monitored postprandial and fasting glucose and CVD risk factors were weaker, but significant. Measurements of blood glucose variability showed non-significant associations. Overall, calculations based on CGM were not more informative than those based on frequent SMBG. Mean glycaemia and HbA(1c) show consistent and stronger associations with CVD risk factors than fasting glucose or postprandial glucose levels or measures of glucose variability in patients with diabetes. C1 [Borg, R.; Carstensen, B.; Nerup, J.; Borch-Johnsen, K.; Witte, D. R.] Steno Diabet Ctr AS, DK-2820 Gentofte, Denmark. [Kuenen, J. C.; Heine, R. J.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Zheng, H.; Nathan, D. M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Zheng, H.; Nathan, D. M.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Zheng, H.; Nathan, D. M.] Harvard Univ, Sch Med, Boston, MA USA. [Heine, R. J.] Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Borg, R (reprint author), Steno Diabet Ctr AS, Niels Steensens Vej 2-4, DK-2820 Gentofte, Denmark. EM RBrg@steno.dk RI Witte, Daniel/C-1722-2008 OI Witte, Daniel/0000-0002-0769-2922 FU ADA; EASD; Abbott Diabetes Care; Bayer Healthcare; GlaxoSmithKline; sanofi-aventis Netherlands; Merck; Lifescan and Medtronic Minimed; Sehested Hansen Foundation; Steno Diabetes Center; Danish Diabetes Association FX The ADAG study was supported by research grants from the ADA and EASD. Financial support was provided by Abbott Diabetes Care, Bayer Healthcare, GlaxoSmithKline, sanofi-aventis Netherlands, Merck, Lifescan and Medtronic Minimed, and supplies and equipment were provided by Medtronic Minimed, Lifescan and Hemocue. The assessment of CVD risk factor analyses was supported by research grants from the Sehested Hansen Foundation, Steno Diabetes Center and the Danish Diabetes Association. NR 10 TC 31 Z9 33 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2011 VL 54 IS 1 BP 69 EP 72 DI 10.1007/s00125-010-1918-2 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 688ZQ UT WOS:000284896900012 PM 20886203 ER PT J AU Jafar-Mohammadi, B Groves, CJ Gjesing, AP Herrera, BM Winckler, W Stringham, HM Morris, AP Lauritzen, T Doney, ASF Morris, AD Weedon, MN Swift, AJ Kuusisto, J Laakso, M Altshuler, D Hattersley, AT Collins, FS Boehnke, M Hansen, T Pedersen, O Palmer, CNA Frayling, TM Gloyn, AL McCarthy, MI AF Jafar-Mohammadi, B. Groves, C. J. Gjesing, A. P. Herrera, B. M. Winckler, W. Stringham, H. M. Morris, A. P. Lauritzen, T. Doney, A. S. F. Morris, A. D. Weedon, M. N. Swift, A. J. Kuusisto, J. Laakso, M. Altshuler, D. Hattersley, A. T. Collins, F. S. Boehnke, M. Hansen, T. Pedersen, O. Palmer, C. N. A. Frayling, T. M. Gloyn, A. L. McCarthy, M. I. CA DIAGRAM Consortium TI A role for coding functional variants in HNF4A in type 2 diabetes susceptibility SO DIABETOLOGIA LA English DT Article DE HNF4A; Low-frequency variants; T130I; Type 2 diabetes; V255M ID GENOME-WIDE ASSOCIATION; NUCLEAR FACTOR 4-ALPHA; CHROMOSOME 20Q; FACTOR-4-ALPHA GENE; COMMON VARIANTS; T130I MUTATION; UK POPULATION; LOCI; RISK; REPLICATION AB Aims/hypothesis Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4 alpha (HNF-4A), account for similar to 5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, minor allele frequency [MAF] similar to 0.1%; T130I, MAF similar to 3.0%)-known to influence downstream HNF-4A target gene expression-are of interest, but previous type 2 diabetes association reports were inconclusive. We aimed to evaluate the contribution of these variants to type 2 diabetes susceptibility through large-scale association analysis. Methods We genotyped both variants in at least 5,745 cases and 14,756 population controls from the UK and Denmark. We also undertook an expanded association analysis that included previously reported and novel genotype data obtained in Danish, Finnish, Canadian and Swedish samples. A meta-analysis incorporating all published association studies of the T130I variant was subsequently carried out in a maximum sample size of 14,279 cases and 26,835 controls. Results We found no association between V255M and type 2 diabetes in either the initial (p = 0.28) or the expanded analysis (p = 0.44). However, T130I demonstrated a modest association with type 2 diabetes in the UK and Danish samples (additive per allele OR 1.17 [95% CI 1.08-1.28]; p = 1.5 x 10(-4)), which was strengthened in the meta-analysis (OR 1.20 [95% CI 1.10-1.30]; p = 2.1 x 10(-5)). Conclusions Our data are consistent with T130I as a low-frequency variant influencing type 2 diabetes risk, but are not conclusive when judged against stringent standards for genome-wide significance. This study exemplifies the difficulties encountered in association testing of low-frequency variants. C1 [Jafar-Mohammadi, B.; Groves, C. J.; Herrera, B. M.; Gloyn, A. L.; McCarthy, M. I.] Univ Oxford, Churchill Hosp, OCDEM, Oxford OX3 7LJ, England. [Jafar-Mohammadi, B.; Groves, C. J.; Gloyn, A. L.; McCarthy, M. I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Gjesing, A. P.; Hansen, T.; Pedersen, O.] Steno Diabet Ctr, Copenhagen, Denmark. [Gjesing, A. P.; Hansen, T.; Pedersen, O.] Hagedorn Res Inst, Copenhagen, Denmark. [Herrera, B. M.; Morris, A. P.; McCarthy, M. I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Winckler, W.; Altshuler, D.] Broad Inst Harvard, Cambridge, MA USA. [Winckler, W.; Altshuler, D.] MIT, Cambridge, MA 02139 USA. [Stringham, H. M.; Boehnke, M.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Lauritzen, T.] Univ Aarhus, Dept Gen Practice, Aarhus, Denmark. [Doney, A. S. F.; Morris, A. D.] Univ Dundee, Ninewells Hosp & Med Sch, Diabet Res Grp, Dundee DD1 9SY, Scotland. [Weedon, M. N.; Hattersley, A. T.; Frayling, T. M.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Weedon, M. N.; Hattersley, A. T.; Frayling, T. M.] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Swift, A. J.] NHGRI, NIH, Bethesda, MD 20892 USA. [Kuusisto, J.; Laakso, M.] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. [Kuusisto, J.; Laakso, M.] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Altshuler, D.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Altshuler, D.] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA. [Altshuler, D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, D.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Hansen, T.] Univ So Denmark, Fac Hlth Sci, Odense, Denmark. [Pedersen, O.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Pedersen, O.] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Palmer, C. N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland. RP McCarthy, MI (reprint author), Univ Oxford, Churchill Hosp, OCDEM, Old Rd, Oxford OX3 7LJ, England. EM mark.mccarthy@drl.ox.ac.uk RI Altshuler, David/A-4476-2009; Palmer, Colin/C-7053-2008; Boehm, Bernhard/F-8750-2015; Study, GoDARTS/K-9448-2016 OI Altshuler, David/0000-0002-7250-4107; Palmer, Colin/0000-0002-6415-6560; FU Medical Research Council (MRC) [G0000934, 81696]; Wellcome Trust [068545/Z/02, GR072960]; Oxford NIHR Biomedical Research Centre; Danish Agency for Science Technology and Innovation [271-06-0539]; National Health Services in the counties of Copenhagen, Aarhus, Ringkobing, Ribe and South Jutland; Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment; National Board of Health; Danish Medical Research Council; Aarhus University Research Foundation; Novo Nordisk Foundation; Novo Nordisk; Novo Nordisk Scandinavia; Astra Denmark; Pfizer Denmark; GlaxoSmithKline Pharma Denmark; Servier Denmark; HemoCue Denmark; US National Institutes of Health [DK062370, DK072193, HL084729, HG002651, U54 DA021519]; National Human Genome Research Institute [1 Z01 HG000024]; Academy of Finland; EVO [5263]; Sigrid Juselius Foundation; Finnish Diabetes Research Foundation; Folkhalsan Research Foundation; EC [BM4-CT95-0662]; Swedish Medical Research Council; JDF Wallenberg Foundation FX We acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council (MRC) grant G0000934 and the Wellcome Trust grant 068545/Z/02. We acknowledge Diabetes UK for funding the collection of the Warren 2 resource and would also like to thank G. Hitman, Barts and The London School of Medicine and Dentistry, UK, and M. Walker, Newcastle University, UK. We thank the staff and senior management of the UK Blood Services responsible for the UK Blood Services Collection. The UK Type 2 Diabetes Genetics Consortium collection was supported by the Wellcome Trust (Biomedical Collections Grant GR072960). B. Jafar-Mohammadi is a Diabetes UK Clinical Training Fellow. A. L. Gloyn is an MRC New Investigator (Grant Reference 81696). This work was part funded in Oxford by the Oxford NIHR Biomedical Research Centre Programme. The Danish studies were supported by the Danish Agency for Science Technology and Innovation (grant no. 271-06-0539). The ADDITION study was initiated by: K. Borch-Johnsen, Steno Diabetes Centre, Gentofte, Denmark (principal investigator), T. Lauritzen, University of Aarhus, Denmark (principal investigator) and A. Sandbaek, University of Aarhus, Aarhus, Denmark. The study was supported by the National Health Services in the counties of Copenhagen, Aarhus, Ringkobing, Ribe and South Jutland, together with the Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment, the diabetes fund of the National Board of Health, the Danish Medical Research Council, the Aarhus University Research Foundation and the Novo Nordisk Foundation. The study received unrestricted grants from Novo Nordisk, Novo Nordisk Scandinavia, Astra Denmark, Pfizer Denmark, GlaxoSmithKline Pharma Denmark, Servier Denmark and HemoCue Denmark. We acknowledge use of the FUSION genotyping data. Support for this study was provided by US National Institutes of Health grants (DK062370, DK072193, HL084729, HG002651 and U54 DA021519) as well as National Human Genome Research Institute intramural project number 1 Z01 HG000024. The METSIM study was supported by the Academy of Finland and the EVO grant (no. 5263). The Broad study would like to acknowledge the many clinical researchers involved with these sample collections. The Scandinavian collections are part of the Botnia Study, and are principally supported by the Sigrid Juselius Foundation, the Academy of Finland, the Finnish Diabetes Research Foundation, the Folkhalsan Research Foundation, EC (BM4-CT95-0662, GIFT), the Swedish Medical Research Council, the JDF Wallenberg Foundation, and the Novo Nordisk Foundation. We thank other members of the DIAGRAM consortium (see the ESM for a full listing) for sharing data. Funding sources for the DIAGRAM consortium are included in Voight et al. [8]. D. Altshuler is a Burroughs Wellcome Fund Clinical Scholar in Translational Research, which supported this work. NR 33 TC 14 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2011 VL 54 IS 1 BP 111 EP 119 DI 10.1007/s00125-010-1916-4 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 688ZQ UT WOS:000284896900018 PM 20878384 ER PT J AU Sadacca, LA Lamia, KA deLemos, AS Blum, B Weitz, CJ AF Sadacca, L. A. Lamia, K. A. deLemos, A. S. Blum, B. Weitz, C. J. TI An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice SO DIABETOLOGIA LA English DT Article DE Circadian clock; Glucose homeostasis; Insulin; Islets ID RHYTHM AB Loss of circadian clocks from all tissues causes defective glucose homeostasis as well as loss of feeding and activity rhythms. Little is known about peripheral tissue clocks, so we tested the hypothesis that an intrinsic circadian clock of the pancreas is important for glucose homeostasis. We monitored real-time bioluminescence of pancreas explants from circadian reporter mice and examined clock gene expression in beta cells by immunohistochemistry and in situ hybridisation. We generated mice selectively lacking the essential clock gene Bmal1 (also known as Arntl) in the pancreas and tested mutant mice and littermate controls for glucose and insulin tolerance, insulin production and behaviour. We examined islets isolated from mutants and littermate controls for glucose-stimulated insulin secretion and total insulin content. Pancreas explants exhibited robust circadian rhythms. Clock genes Bmal1 and Per1 were expressed in beta cells. Despite normal activity and feeding behaviour, mutant mice lacking clock function in the pancreas had severe glucose intolerance and defective insulin production; their isolated pancreatic islets had defective glucose-stimulated insulin secretion, but normal total insulin content. The mouse pancreas has an autonomous clock function and beta cells are very likely to be one of the pancreatic cell types possessing an intrinsic clock. The Bmal1 circadian clock gene is required in the pancreas, probably in beta cells, for normal insulin secretion and glucose homeostasis. Our results provide evidence for a previously unrecognised molecular regulator of pancreatic glucose-sensing and/or insulin secretion. C1 [Sadacca, L. A.; Lamia, K. A.; deLemos, A. S.; Weitz, C. J.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [deLemos, A. S.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Blum, B.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Weitz, CJ (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. EM cweitz@hms.harvard.edu FU NIH [R01 NS060860]; Life Sciences Research Foundation; Training Program in Sleep Circadian and Respiratory Neurobiology Pre-Doctoral Fellowship [T32 HL07901]; Research Training in Digestive Diseases Fellowship [T32 DK07191]; EMBO FX We thank D. Melton (Harvard University, Cambridge, MA, USA) for Pdx1-Cre mice, B. Lowell and D. Kong (Beth Israel Deaconess Medical Center, Boston, MA, USA) for advice and M. Liu (Department of Neurobiology, Harvard Medical School, Boston, MA, USA) for technical assistance. This work was supported by NIH grant R01 NS060860 (to C. J. Weitz), a Merck Fellowship of the Life Sciences Research Foundation (to K. A. Lamia), a Training Program in Sleep, Circadian and Respiratory Neurobiology Pre-Doctoral Fellowship T32 HL07901 (to L. A. Sadacca), and a Research Training in Digestive Diseases Fellowship T32 DK07191 (to A. S. deLemos). B. Blum is supported by an EMBO long-term postdoctoral fellowship. NR 10 TC 114 Z9 122 U1 3 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2011 VL 54 IS 1 BP 120 EP 124 DI 10.1007/s00125-010-1920-8 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 688ZQ UT WOS:000284896900019 PM 20890745 ER PT J AU Cotsapas, C Prokunina-Olsson, L Welch, C Saxena, R Weaver, C Usher, N Guiducci, C Bonakdar, S Turner, N LaCroix, B Hall, JL AF Cotsapas, C. Prokunina-Olsson, L. Welch, C. Saxena, R. Weaver, C. Usher, N. Guiducci, C. Bonakdar, S. Turner, N. LaCroix, B. Hall, J. L. TI Expression analysis of loci associated with type 2 diabetes in human tissues (vol 53, pg 2334, 2010) SO DIABETOLOGIA LA English DT Correction C1 [Welch, C.; Weaver, C.; Usher, N.; Turner, N.; LaCroix, B.; Hall, J. L.] Lillehei Heart Inst, Dept Med, Minneapolis, MN 55455 USA. [Prokunina-Olsson, L.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Cotsapas, C.; Saxena, R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Hall, J. L.] Univ Minnesota, Ctr Dev Biol, Minneapolis, MN USA. [Cotsapas, C.; Saxena, R.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Cotsapas, C.; Saxena, R.; Guiducci, C.; Bonakdar, S.] Broad Inst, Cambridge, MA USA. RP Hall, JL (reprint author), Lillehei Heart Inst, Dept Med, 4-280 NHH,312 Church St SE, Minneapolis, MN 55455 USA. EM jlhall@umn.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2011 VL 54 IS 1 BP 209 EP 209 DI 10.1007/s00125-010-1939-x PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 688ZQ UT WOS:000284896900031 ER PT J AU Akiba, Y Kaunitz, JD AF Akiba, Yasutada Kaunitz, Jonathan D. TI Duodenal Chemosensing and Mucosal Defenses SO DIGESTION LA English DT Article; Proceedings Paper CT 2010 IUPHAR Gastrointestinal Pharmacology Section Workshop on Gastrointestinal Nutrient Chemosensing and the Gut Brain Axis CY JUL 17-24, 2010 CL Copenhagen, DENMARK DE Acid sensor; Vanilloid receptor; Carbonic anhydrase; Luminal nutrient; G-protein-coupled receptors ID CALCIUM-SENSING RECEPTOR; GLUCAGON-LIKE PEPTIDE-2; PROTEIN-COUPLED RECEPTORS; BITTER TASTE RECEPTORS; GASTRIC-ACID-SECRETION; RAT SMALL-INTESTINE; GASTROINTESTINAL-TRACT; BICARBONATE SECRETION; ENTEROENDOCRINE CELLS; CARBONIC-ANHYDRASES AB The duodenal mucosa is exposed to endogenous and exogenous chemicals, including acid, CO2, bile acids and nutrients. Mucosal chemical sensors are necessary to exert physiological responses such as secretion, digestion, absorption, and motility. We propose a mucosal chemosensing system by which luminal chemicals are sensed via mucosal acid sensors and G-protein-coupled receptors. Luminal acid/CO2 sensing consists of ecto- and cytosolic carbonic anhydrases, epithelial ion transporters, and acid sensors expressed on the afferent nerves in the duodenum. Furthermore, a luminal L-glutamate signal is mediated via mucosal L-glutamate receptors, including metabotropic glutamate receptors and taste receptor 1 family heterodimers, with activation of afferent nerves and cyclooxygenase, whereas luminal Ca2+ is differently sensed via the calcium-sensing receptor in the duodenum. Recent studies also show the involvement of enteroendocrine G-protein-coupled receptors in bile acid and fatty acid sensing in the duodenum. These luminal chemosensors help activate mucosal defense mechanisms in order to maintain the mucosal integrity and physiological responses. Stimulation of luminal chemosensing in the duodenal mucosa may prevent mucosal injury, affect nutrient metabolism, and modulate sensory nerve activity. Copyright (C) 2011 S. Karger AG, Basel C1 Univ Calif Los Angeles, Sch Med, Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Akiba, Y (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yakiba@mednet.ucla.edu FU NIDDK NIH HHS [R01 DK054221, R01 DK54221] NR 71 TC 16 Z9 16 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 J9 DIGESTION JI Digestion PY 2011 VL 83 SU 1 BP 25 EP 31 DI 10.1159/000323401 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 734DD UT WOS:000288312500006 PM 21389725 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Effects of Environment and Lifestyle on Gastroesophageal Reflux Disease SO DIGESTIVE DISEASES LA English DT Article DE Barrett's esophagus; Erosive esophagitis; Esophageal adenocarcinoma; Geographic variation; Gastroesophageal reflux disease; Helicobacter pylori; Natural history; Obesity; Peptic stricture; Time trends ID LOWER ESOPHAGEAL SPHINCTER; BARRETTS-ESOPHAGUS; RISK-FACTORS; ACID REFLUX; UNITED-STATES; PEPTIC-ULCER; EPIDEMIOLOGIC TRENDS; HELICOBACTER-PYLORI; SYSTEMIC-SCLEROSIS; HIATAL-HERNIA AB Background: Gastroesophageal reflux disease (GERD) is comprised of a spectrum of related disorders, including hiatal hernia, reflux disease with its associated symptoms, erosive esophagitis, peptic stricture, Barrett's esophagus, and esophageal adenocarcinoma. Besides multiple pathophysiological associations among these disorders, they are also characterized by their comorbid occurrence in identical patients and by their similar epidemiologic behavior. The occurrence of GERD is shaped by marked temporal and geographic variations, suggesting the influence of environmental risk factors in the etiology of these diseases. Variations by Time, Geography, and Race: Between 1975 and 2005, the incidence of GERD and esophageal adenocarcinoma increased fivefold in most Western countries. The incidence of GERD also appears to be rising in the most developed countries of Asia. All severe forms of GERD, such as erosive esophagitis, peptic stricture, Barrett's metaplasia, and esophageal adenocarcinoma, are more common among whites than other ethnic groups. Affluence and Obesity as Risk Factors: Barrett's esophagus and esophageal adenocarcinoma tend to occur slightly more often in subjects with higher income. Overweight and obesity contribute to the development of hiatal hernia, increase intra-abdominal pressure, and promote gastroesophageal reflux. Weight gain increases reflux symptoms, whereas weight loss decreases such symptoms. Other risk factors, such as smoking, alcohol, dietary fat, or drugs, play only a minor role in shaping the epidemiologic patterns of GERD. Protection through Helicobacter pylori : On a population level, a high prevalence of H. pylori infection is likely to reduce levels of acid secretion and protect some carriers of the infection against reflux disease and its associated complications. Several studies have confirmed a lesser prevalence of H. pylori among subjects with than without GERD. Until recently, populations in Africa and Asia may have been protected against the development of GERD and esophageal adenocarcinoma by their higher prevalence of H. pylori infection. Conclusion: The study of environmental risk factors may provide an opportunity to better understand GERD and develop a means of its prevention. Copyright (C) 2011 S. Karger AG, Basel C1 [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 58 TC 19 Z9 19 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 2011 VL 29 IS 2 BP 229 EP 234 DI 10.1159/000323927 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 789FI UT WOS:000292499500015 PM 21734389 ER PT J AU Ananthakrishnan, AN McGinley, EL Binion, DG Saeian, K AF Ananthakrishnan, Ashwin N. McGinley, Emily L. Binion, David G. Saeian, Kia TI Fracture-Associated Hospitalizations in Patients with Inflammatory Bowel Disease SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Inflammatory bowel disease; Fractures; Osteoporosis; Nationwide Inpatient Sample; Crohn's disease; Ulcerative colitis ID POPULATION-BASED COHORT; BONE-MINERAL DENSITY; MANITOBA IBD COHORT; CROHNS-DISEASE; CORTICOSTEROID USE; VITAMIN-D; OSTEOPOROSIS; RISK; PREVALENCE AB Background Maintenance of bone health is an important concern in patients with inflammatory bowel disease (IBD). They may frequently have impaired bone density resulting in greater incidence of fractures. Aims To examine fracture-associated hospitalization costs in IBD patients from a nationwide representative sample, and to compare the risk factors for such fractures in IBD and non-IBD patients. Methods We identified discharges with IBD and coexisting codes for hip, vertebral or wrist fractures (IBD-Fr) from the Nationwide Inpatient Sample and compared them with IBD hospitalizations without codes for these fractures. A second analysis was performed using 2008 inpatient data from the Wisconsin Hospital Association (WHA) comparing characteristics of patients with IBD-Fr and non-IBD controls hospitalized for similar fractures. Results There were 1,653 discharges in the IBD-Fr group accounting for 10,461 days of hospital stay and US $46 million in total hospitalization charges. On multivariate analysis, age >65 years [odds ratio (OR) 28.8, 95% confidence interval (CI) 12.3-67.6] and female sex (OR 1.3, 95% CI 1.0-1.6) were associated with higher odds of hospitalization associated with fractures. We found no differences in age, gender, or race among IBD-Fr and non-IBD fracture controls. However, IBD-fractures were twice as likely to be associated with osteoporosis as non-IBD fractures (OR 2.19, 95% CI 1.10-4.33). Conclusions Older age, female sex, and osteoporosis were more commonly associated with hospitalization for fractures in IBD patients. Osteoporosis appears to be more common among IBD-Fr patients than non-IBD fracture controls. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [McGinley, Emily L.] Med Coll Wisconsin, Div Epidemiol, Milwaukee, WI 53226 USA. [Binion, David G.] Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Saeian, Kia] Med Coll Wisconsin, Div Gastroenterol & Hepatol, Milwaukee, WI 53226 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org NR 30 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2011 VL 56 IS 1 BP 176 EP 182 DI 10.1007/s10620-010-1433-9 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 703UD UT WOS:000286005900023 PM 20936351 ER PT J AU Bambara, JK Turner, AP Williams, RM Haselkorn, JK AF Bambara, Jennifer K. Turner, Aaron P. Williams, Rhonda M. Haselkorn, Jodie K. TI Perceived social support and depression among Veterans with multiple sclerosis SO DISABILITY AND REHABILITATION LA English DT Article DE Social support; depression; Veterans; multiple sclerosis ID QUALITY-OF-LIFE; MAJOR DEPRESSION; DISABILITY; ADJUSTMENT; COMORBIDITY; IMPAIRMENT; PREVALENCE; SEVERITY; SYMPTOMS; ILLNESS AB Purpose. To examine the association between perceived social support and self-reported depression among Veterans of the US Armed Forces ('Veterans') with multiple sclerosis (MS), and differences in this relationship between specific support subtypes (tangible, positive social interaction, emotional/informational and affective). Method. Participants were Veterans with MS (N = 451) receiving medical services through the Veterans Health Administration who completed mailed surveys. Hierarchical regression examined the extent to which global perceived social support concurrently predicted depression among a predominantly male sample of individuals with MS. Exploratory correlational analyses examined the relationship between specific subtypes of perceived social support and depression. Results. Greater global perceived social support was associated with less depression after controlling for sociodemographic and disease-related variables. In follow-up analyses examining specific subtypes of support, greater positive social interaction, greater emotional/informational support, and greater affective support were related to less depression. There was no relationship between perceived tangible support and depression. Conclusions. Interventions aimed at increasing positive social interactions, expressed affection and emotional/information support may be particularly helpful for individuals with MS and their caregivers. C1 [Bambara, Jennifer K.; Turner, Aaron P.; Williams, Rhonda M.; Haselkorn, Jodie K.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. [Bambara, Jennifer K.; Turner, Aaron P.; Williams, Rhonda M.; Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Heath Care Syst, Dept Rehabil Med, S-117 RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov OI Turner, Aaron/0000-0001-6897-8003 FU VA Rehabilitation Research and Development Service [B4972W] FX This material is based on work supported by a grant for the Department of Veterans Affairs VHA VISN 20 and by VA Rehabilitation Research and Development Service Career Development grant (B4972W). NR 54 TC 7 Z9 7 U1 3 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PY 2011 VL 33 IS 1 BP 1 EP 8 DI 10.3109/09638288.2010.481026 PG 8 WC Rehabilitation SC Rehabilitation GA 686KL UT WOS:000284695100001 PM 20812812 ER PT J AU Lehman, LA Woodbury, M Shechtman, O Wang, YC Pomeranz, J Gray, DB Velozo, CA AF Lehman, Leigh A. Woodbury, Michelle Shechtman, Orit Wang, Ying-Chih Pomeranz, Jamie Gray, David B. Velozo, Craig A. TI Development of an item bank for a computerised adaptive test of upper-extremity function SO DISABILITY AND REHABILITATION LA English DT Article DE ICF; ICF activity measure; upper-extremity; computer adaptive testing ID INFORMATION-SYSTEM PROMIS; OUTCOMES MEASUREMENT; MANUAL ABILITY; SHOULDER AB Purpose. The purpose of this study was to determine the psychometric characteristics of an upper-extremity item bank as a precursor to developing a computer adaptive patient reported outcome instrument. The Activity dimension of the World Health Organization's International Classification of Functioning, Disability and Health (ICF) provided the conceptual framework for the items. Method. Factor and Rasch analyses were used to evaluate the psychometric properties of the item bank, including: monotonicity, local independence, dimensionality, item difficulty hierarchy and match between sample ability and item difficulty. Results. Monotonicity of the rating scale was supported. Nine item pairs were locally dependent, and thus one item from each pair was removed from subsequent analyses. There was evidence for two unidimensional constructs; gross upper-extremity and fine hand. Both constructs showed good internal consistency and person separation. In general, the order of item difficulty within each construct replicated the hypothesised item difficulty order. The fine hand construct had a ceiling effect. Conclusions. The above study of our newly developed upper-extremity item bank empirically verified the intended item difficulty order, identified separate constructs (i.e. gross upper-extremity and fine hand) and provided insights into eliminating the ceiling effect of one of the constructs. These findings are critical precursors to the development of upper-extremity components of the ICF Activity Measure, an ICF-based, CAT located on the web at: www.icfmeasure.phhp.ufl.edu. C1 [Lehman, Leigh A.] Univ S Carolina Upstate, Dept Psychol, Spartanburg, SC 29303 USA. [Woodbury, Michelle] Ralph H Johnson Vet Affairs Med Ctr, Dept Occupat Therapy, Charleston, SC 29401 USA. [Woodbury, Michelle] Med Univ S Carolina, Dept Occupat Therapy, Charleston, SC 29403 USA. [Shechtman, Orit; Velozo, Craig A.] Univ Florida, Dept Occupat Therapy, Gainesville, FL 32601 USA. [Wang, Ying-Chih] Univ Wisconsin, Dept Occupat Sci & Technol, Milwaukee, WI 53201 USA. [Wang, Ying-Chih] Focus Therapeut Outcomes Inc, Knoxville, TN 37939 USA. [Pomeranz, Jamie] Univ Florida, Dept Behav Sci & Community Hlth, Gainesville, FL 32610 USA. [Gray, David B.] Washington Univ, Sch Med, Dept Neurol & Occupat Therapy, St Louis, MO 63108 USA. [Velozo, Craig A.] N Florida S Georgia Vet Affairs Syst Rehabil Outc, Lake City, FL 32025 USA. RP Lehman, LA (reprint author), Univ S Carolina Upstate, Dept Psychol, 800 Univ Way, Spartanburg, SC 29303 USA. EM llehman@uscupstate.edu FU Department of Education, National Institute of Disability Rehabilitation Research (NIDRR) [H133G000227] FX This study was funded by the Department of Education, National Institute of Disability Rehabilitation Research (NIDRR), project number H133G000227. NR 39 TC 5 Z9 5 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PY 2011 VL 33 IS 21-22 BP 2092 EP 2104 DI 10.3109/09638288.2011.560336 PG 13 WC Rehabilitation SC Rehabilitation GA 826GJ UT WOS:000295340600019 PM 21401332 ER PT J AU Bikle, DD Oda, Y Teichert, A AF Bikle, Daniel David Oda, Yuko Teichert, Arnaud TI The Vitamin D Receptor: A Tumor Suppressor in Skin SO DISCOVERY MEDICINE LA English DT Article AB Epidemiologic evidence supporting a major chemopreventive role for vitamin D in various malignancies is strong. Likewise the use of the active metabolite of vitamin D, 1,25(OH)(2)D-3, and its analogs to prevent and/or treat a wide variety of malignancies in animals is well established. The evidence has been less compelling for epidermal carcinogenesis perhaps because the same agent that produces vitamin D in the skin, UVB radiation (UVR), is also the same agent that results in most epidermal malignancies. However, recent studies indicate that the role of vitamin D and its receptor (VDR) in protecting against the development of epidermal tumors deserves a closer look. One such study found mice lacking the VDR were quite sensitive to epidermal tumor formation following the administration of the carcinogen DMBA. A more recent study showed that these mice were similarly more sensitive to tumor formation following UVR, results we have confirmed. The epidermis of the VDR null mouse is hyperproliferative with gross distortion of hair follicles, structures that may provide the origin for the tumors found in the skin following such treatment. Two interacting pathways critical for epidermal and hair follicle function, beta-catenin and hedgehog (Hh), result in epidermal tumors when they are activated abnormally. Thus, we considered the possibility that loss of VDR predisposes to epidermal tumor formation by activation of either or both beta-catenin and Hh signaling. We determined that all elements of the Hh signaling pathway are upregulated in the epidermis and utricles of the VDR null mouse, and that 1,25(OH)(2)D-3 suppresses the expression of these elements in normal mouse skin. In addition we observed that the transcriptional activity of beta-catenin was increased in keratinocytes lacking the VDR. These results lead us to the hypothesis that the VDR with its ligand 1,25(OH)(2)D-3 functions as a tumor suppressor with respect to epidermal tumor formation in response to UVR by regulating Hh and beta-catenin signaling. [Discovery Medicine 11(56):7-17, January 2011] C1 [Bikle, Daniel David] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Bikle, DD (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St, San Francisco, CA 94121 USA. EM daniel.bikle@ucsf.edu FU BLRD VA [I01 BX001066]; NIAMS NIH HHS [R01 AR050023] NR 61 TC 24 Z9 25 U1 1 U2 1 PU DISCOVERY MEDICINE PI TIMONIUM PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA SN 1539-6509 EI 1944-7930 J9 DISCOV MED JI Discov. Med. PD JAN PY 2011 VL 11 IS 56 BP 7 EP 17 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V27UW UT WOS:000208639100001 PM 21276406 ER PT J AU Yehuda, R AF Yehuda, Rachel TI Disease Markers: Molecular Biology of PTSD Introduction SO DISEASE MARKERS LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; HOLOCAUST SURVIVORS C1 James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY USA. EM Rachel.Yehuda@va.gov NR 4 TC 2 Z9 2 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2011 VL 30 IS 2-3 BP 61 EP 65 DI 10.3233/DMA-2011-0785 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 773YN UT WOS:000291348100001 PM 21508510 ER PT J AU Yehuda, R Koenen, KC Galea, S Flory, JD AF Yehuda, Rachel Koenen, Karestan C. Galea, Sandro Flory, Janine D. TI The role of genes in defining a molecular biology of PTSD SO DISEASE MARKERS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SEROTONIN TRANSPORTER GENOTYPE; GLUCOCORTICOID-RECEPTOR NUMBER; HURRICANE-EXPOSED ADULTS; DNA METHYLATION; MATERNAL-CARE; CHILDHOOD ABUSE; ENVIRONMENTAL-INFLUENCES; INDIVIDUAL-DIFFERENCES; TRAUMATIC EVENTS AB Because environmental exposure to trauma is the sine qua non for the development of Post Traumatic Stress Disorder (PTSD), the recent focus on genetic studies has been noteworthy. The main catalyst for such studies is the observation from epidemiological studies that not all trauma survivors develop this disorder. Furthermore, neuroendocrine findings suggest pre-existing hormonal alterations that confer risk for PTSD. This paper presents the rationale for examining genetic factors in PTSD and trauma exposure, but suggests that studies of genotype may only present a limited picture of the molecular biology of this disorder. We describe the type of information that can be obtained from candidate gene and genomic studies that incorporate environmental factors in the design (i.e., gene - environment interaction and gene-environment correlation studies) and studies that capitalize on the idea that environment modifies gene expression, via epigenetic or other molecular mechanisms. The examination of epigenetic mechanisms in tandem with gene expression will help refine models that explain how PTSD risk, pathophysiology, and recovery is mediated by the environment. Since inherited genetic variation may also influence the extent of epigenetic or gene expression changes resulting from the environment, such studies should optimally be followed up by studies of genotype. C1 [Yehuda, Rachel; Flory, Janine D.] James J Peters Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. [Yehuda, Rachel; Flory, Janine D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Koenen, Karestan C.] Harvard Ctr Developing Child, Cambridge, MA USA. [Galea, Sandro] Columbia Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. EM Rachel.Yehuda@va.gov NR 79 TC 22 Z9 24 U1 6 U2 18 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2011 VL 30 IS 2-3 BP 67 EP 76 DI 10.3233/DMA-2011-0794 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 773YN UT WOS:000291348100002 PM 21508511 ER PT J AU Amstadter, AB Nugent, NR Yang, BZ Miller, A Siburian, R Moorjani, P Haddad, S Basu, A Fagerness, J Saxe, G Smoller, JW Koenen, KC AF Amstadter, Ananda B. Nugent, Nicole R. Yang, Bao-Zhu Miller, Alisa Siburian, Richie Moorjani, Priya Haddad, Stephen Basu, Aditi Fagerness, Jesen Saxe, Glenn Smoller, Jordan W. Koenen, Karestan C. TI Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients SO DISEASE MARKERS LA English DT Article DE Posttraumatic stress disorder; CRHR1; hypothalamic-pituitary-adrenal axis; genetic; injury ID SUBSEQUENT PTSD SYMPTOMS; ADULT DEPRESSION; COMBAT VETERANS; TRAUMATIC EVENT; CORTISOL; CHILDREN; ASSOCIATION; POLYMORPHISMS; CHILDHOOD; RISK AB Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n = 103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth. C1 [Amstadter, Ananda B.] Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. [Nugent, Nicole R.] Brown Med Sch, Dept Psychiat, Providence, RI USA. [Nugent, Nicole R.] Rhode Isl Hosp, Providence, RI USA. [Yang, Bao-Zhu; Moorjani, Priya; Haddad, Stephen; Basu, Aditi; Fagerness, Jesen] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, New Haven, CT USA. [Miller, Alisa; Saxe, Glenn] Boston Childrens Hosp, Dept Psychiat, Boston, MA USA. [Siburian, Richie; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. [Siburian, Richie; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Koenen, Karestan C.] Harvard Ctr Developing Child, Cambridge, MA USA. [Saxe, Glenn; Smoller, Jordan W.] Harvard Univ, Sch Med, Boston, MA USA. RP Amstadter, AB (reprint author), Virginia Commonwealth Univ, Dept Psychiat, Virginia Inst Psychiat & Behav Genet, 800 E Leigh St,POB 980126, Richmond, VA 23298 USA. EM abamstadter@vcu.edu OI Saxe, Glenn/0000-0002-4756-1169 FU US-NICHD [HD055885]; US-NIMH [K01 MH087240, K08 MH070627]; US-NIDA [K01 DA024758]; Harvard School of Public Health; US-NIH [MH078928, MH063247, MH086309]; Robert Wood Johnson Foundation FX Dr. Amstadter is supported by US-NICHD HD055885. Dr. Nugent is supported by US-NIMH K01 MH087240. Dr. Yang is supported by US-NIDA K01 DA024758. Dr. Koenen is supported by US-NIMH K08 MH070627 and a Junior Faculty Sabbatical from the Harvard School of Public Health. This work was also supported by US-NIH grants MH078928, MH063247, MH086309 and the Robert Wood Johnson Foundation. NR 44 TC 48 Z9 49 U1 8 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2011 VL 30 IS 2-3 BP 89 EP 99 DI 10.3233/DMA-2011-0761 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 773YN UT WOS:000291348100004 PM 21508513 ER PT J AU Sarapas, C Cai, GQ Bierer, LM Golier, JA Galea, S Ising, M Rein, T Schmeidler, J Muller-Myhsok, B Uhr, M Holsboer, F Buxbaum, JD Yehuda, R AF Sarapas, Casey Cai, Guiqing Bierer, Linda M. Golier, Julia A. Galea, Sandro Ising, Marcus Rein, Theo Schmeidler, James Mueller-Myhsok, Bertram Uhr, Manfred Holsboer, Florian Buxbaum, Joseph D. Yehuda, Rachel TI Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks SO DISEASE MARKERS LA English DT Article DE Stress disorders; post-traumatic; gene expression; genotype; FKBP5 protein; human; cortisol; September 11 terrorist attacks; childhood trauma ID POSTTRAUMATIC-STRESS-DISORDER; SEPTEMBER-11 TERRORIST ATTACKS; NEW-YORK-CITY; PERIPHERAL-BLOOD; GLUCOCORTICOID-RECEPTOR; EXPRESSION PROFILES; TRAUMA EXPOSURE; IN-VIVO; FKBP5; POLYMORPHISMS AB We have previously reported the differential expression of 17 probe sets in survivors of the 9/11 attacks with current posttraumatic stress disorder (PTSD) compared to similarly exposed survivors with no lifetime PTSD. The current study presents an expanded analysis of these subjects, including genotype at FKBP5, a modulator of glucocorticoid receptor (GR) sensitivity. It includes data from additional subjects who developed PTSD following 9/11 but then recovered, distinguishing expression profiles associated with risk for developing PTSD, resilience, and symptom recovery. 40 Caucasians (20 with and 20 without PTSD, matched for exposure, age, and gender) were selected from a population-representative sample of persons exposed to the 9/11 attacks from which longitudinal data had been collected in four previous waves. Whole blood gene expression and cortisol levels were obtained and genome-wide gene expression was analyzed. 25 probe sets were differentially expressed in PTSD. Identified genes were generally involved in hypothalamic-pituitary-adrenal axis, signal transduction, or in brain and immune cell function. STAT5B, a direct inhibitor of GR, and nuclear factor I/A, both showed reduced expression in PTSD. Comparison of lifetime versus current PTSD identified overlapping genes with altered expression suggesting enduring markers, while some markers present only in current PTSD may reflect state measures. As a follow-up, direct comparisons of expression in current PTSD, lifetime-only PTSD, and control groups identified FKBP5 and MHC Class II as state markers, and also identified several trait markers. An analysis of indirect effects revealed that homozygosity for any of 4 PTSD risk-related polymorphisms at FKBP5 predicted FKBP5 expression, which mediated indirect effects of genotype on plasma cortisol and PTSD severity. C1 [Bierer, Linda M.; Golier, Julia A.; Schmeidler, James; Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY 10458 USA. [Sarapas, Casey] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. [Cai, Guiqing; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, Lab Mol Neuropsychiat, New York, NY USA. [Bierer, Linda M.; Golier, Julia A.; Schmeidler, James; Yehuda, Rachel] Mt Sinai Sch Med, Traumat Stress Studies Div, Bronx, NY USA. [Galea, Sandro] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Ising, Marcus; Rein, Theo; Mueller-Myhsok, Bertram; Uhr, Manfred; Holsboer, Florian] Max Planck Inst Psychiat, D-80804 Munich, Germany. RP Yehuda, R (reprint author), James J Peters Vet Affairs Med Ctr, 526 OOMH PTSD 116-A,130 W Kingsbridge Rd, Bronx, NY 10458 USA. EM rachel.yehuda@va.gov RI Muller-Myhsok, Bertram/A-3289-2013; OI Buxbaum, Joseph/0000-0001-8898-8313 NR 41 TC 52 Z9 52 U1 11 U2 21 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2011 VL 30 IS 2-3 BP 101 EP 110 DI 10.3233/DMA-2011-0764 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 773YN UT WOS:000291348100005 PM 21508514 ER PT J AU O'Donovan, A Sun, B Cole, S Rempel, H Lenoci, M Pulliam, L Neylan, T AF O'Donovan, Aoife Sun, Bing Cole, Steve Rempel, Hans Lenoci, Maryann Pulliam, Lynn Neylan, Thomas TI Transcriptional control of monocyte gene expression in post-traumatic stress disorder SO DISEASE MARKERS LA English DT Article ID NF-KAPPA-B; URINARY CORTISOL EXCRETION; PITUITARY-ADRENAL AXIS; LONG-TERM STRESS; HOLOCAUST SURVIVORS; DISEASE MORTALITY; SEX-DIFFERENCES; ACTH RESPONSE; PTSD SYMPTOMS; CATECHOLAMINES AB Post-traumatic stress disorder (PTSD) confers an increased risk for disorders with an inflammatory etiology. PTSD-related dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary adrenal (HPA) axis and associated alterations in inflammatory activity may contribute to this increased risk. However, little is known about convergent SNS, HPA and inflammatory signaling at the level of the immune cell transcriptome in PTSD. To explore such signaling, we examined the prevalence of specific transcription factor binding motifs in the promoter regions of differentially expressed genes in monocytes from individuals with PTSD and matched controls. Participants included 49 men (24 PTSD+ and 25 trauma-exposed controls) and 18 women (10 PTSD+ and 8 controls). Men with PTSD showed up-regulation of target genes for the NF-kappa B/Rel family of transcription factors, which convey inflammatory signals, up-regulation of target genes for CREB/ATF transcription factors, which convey adrenergic signals from the SNS, and down-regulation of target genes for the glucocorticoid receptor, which conveys glucocorticoid signals from the HPA axis. Women with PTSD also showed significant up-regulation of target genes for NF-kappa B and non-significant down-regulation of target genes for GR, but significant down-regulation of target genes for CREB/ATF. Altered transcriptional control of monocyte gene expression could contribute to exaggerated inflammatory activity in PTSD. C1 [O'Donovan, Aoife] Univ Calif San Francisco, Dept Psychiat, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [O'Donovan, Aoife; Sun, Bing; Rempel, Hans; Lenoci, Maryann; Pulliam, Lynn; Neylan, Thomas] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [O'Donovan, Aoife; Sun, Bing; Rempel, Hans; Lenoci, Maryann; Pulliam, Lynn; Neylan, Thomas] No Calif Inst Res & Educ, San Francisco, CA USA. [Sun, Bing; Pulliam, Lynn] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94121 USA. [Cole, Steve] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. RP O'Donovan, A (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. EM aoife.odonovan@ucsf.edu FU Department of Defense [W81XWH-05-2-0094]; Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration; National Institute for Mental Health (TCN) [R01 MH73978] FX We thank Cyrus Calosing for excellent technical assistance and Joshua D. Woolley, MD/PhD for comments on an earlier draft of this manuscript. This research was supported in part by grants from the Department of Defense (W81XWH-05-2-0094), the Mental Illness Research and Education Clinical Center (MIRECC) of the US Veterans Health Administration, and the National Institute for Mental Health (TCN: R01 MH73978). This material is the result of work supported with resources and the use of facilities at the Veterans Administration Medical Center, San Francisco California. NR 68 TC 47 Z9 47 U1 3 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2011 VL 30 IS 2-3 BP 123 EP 132 DI 10.3233/DMA-2011-0768 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 773YN UT WOS:000291348100007 PM 21508516 ER PT J AU Flory, JD Bierer, LM Yehuda, R AF Flory, Janine D. Bierer, Linda M. Yehuda, Rachel TI Maternal exposure to the holocaust and health complaints in offspring SO DISEASE MARKERS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CORONARY-HEART-DISEASE; ADULT LIFE; DEVELOPMENTAL ORIGINS; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASES; METABOLIC SYNDROME; LOW CORTISOL; RISK; PTSD AB Although the link between chronic stress and the development of cardiovascular and metabolic diseases of adulthood has been known for some time, there is growing recognition that early environmental influences may result in developmental programming via epigenetic mechanisms, thereby affecting the developmental trajectory of disease progression. Previous studies support the idea that offspring of Holocaust survivors may have been subjected to early developmental programming. We evaluated the relationship between parental exposure to the Holocaust and self-reported health ratings and disorders made by their adult offspring (i.e., second generation Holocaust survivors). A total of 137 subjects were evaluated. Regression analyses demonstrated that maternal but not paternal exposure to the Holocaust was related to poorer subjective impressions of emotional and physical health. This relationship was diminished when the offspring's own level of trait anxiety was considered. Offspring with maternal, but not paternal, Holocaust exposure also reported greater use of psychotropic and other medications, including medications for the treatment of hypertension and lipid disorders. The mechanism linking these health outcomes and maternal exposure deserves further investigation, including the possibility that fetal or early developmental programming is involved. C1 [Flory, Janine D.] CUNY, Queens Coll, Dept Psychol, Flushing, NY 11367 USA. [Flory, Janine D.] CUNY, Grad Ctr, Flushing, NY 11367 USA. [Flory, Janine D.; Bierer, Linda M.; Yehuda, Rachel] Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. [Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Flory, JD (reprint author), CUNY, Queens Coll, Dept Psychol, NSB E-318,65-30 Kissena Blvd, Flushing, NY 11367 USA. EM janine.flory@qc.cuny.edu FU NIMH [R01-MH-64675-01] FX This work was supported by NIMH grant R01-MH-64675-01 ("Biology of Risk and PTSD in Holocaust Survivor Offspring") to Rachel Yehuda. NR 47 TC 14 Z9 14 U1 3 U2 10 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2011 VL 30 IS 2-3 BP 133 EP 139 DI 10.3233/DMA-2011-0748 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 773YN UT WOS:000291348100008 PM 21508517 ER PT J AU Apidianakis, Y Rahme, LG AF Apidianakis, Yiorgos Rahme, Laurence G. TI Drosophila melanogaster as a model for human intestinal infection and pathology SO DISEASE MODELS & MECHANISMS LA English DT Review ID AUTOGRAPHA-CALIFORNICA NUCLEOPOLYHEDROVIRUS; MIDGUT EPITHELIAL-CELLS; CONTROLS SELF-RENEWAL; STEM-CELLS; BACTERIAL-INFECTION; POSTERIOR MIDGUT; IMMUNE-RESPONSE; HOST-DEFENSE; PEPTIDOGLYCAN RECOGNITION; METAGENOMICS ERA AB Recent findings concerning Drosophila melanogaster intestinal pathology suggest that this model is well suited for the study of intestinal stem cell physiology during aging, stress and infection. Despite the physiological divergence between vertebrates and insects, the modeling of human intestinal diseases is possible in Drosophila because of the high degree of conservation between Drosophila and mammals with respect to the signaling pathways that control intestinal development, regeneration and disease. Furthermore, the genetic amenability of Drosophila makes it an advantageous model species. The well-studied intestinal stem cell lineage, as well as the tools available for its manipulation in vivo, provide a promising framework that can be used to elucidate many aspects of human intestinal pathology. In this Perspective, we discuss recent advances in the study of Drosophila intestinal infection and pathology, and briefly review the parallels and differences between human and Drosophila intestinal regeneration and disease. C1 [Apidianakis, Yiorgos; Rahme, Laurence G.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02114 USA. RP Rahme, LG (reprint author), Massachusetts Gen Hosp, Dept Surg, 50 Blossom St,Their 340, Boston, MA 02114 USA. EM rahme@molbio.mgh.harvard.edu OI Apidianakis, Yiorgos/0000-0002-7465-3560 NR 100 TC 79 Z9 83 U1 2 U2 30 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD JAN PY 2011 VL 4 IS 1 BP 21 EP 30 DI 10.1242/dmm.003970 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 725WO UT WOS:000287677800006 PM 21183483 ER PT J AU Blackiston, D Adams, DS Lemire, JM Lobikin, M Levin, M AF Blackiston, Douglas Adams, Dany S. Lemire, Joan M. Lobikin, Maria Levin, Michael TI Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway SO DISEASE MODELS & MECHANISMS LA English DT Article ID LEFT-RIGHT ASYMMETRY; NEURAL CREST CELLS; CANCER STEM-CELLS; SODIUM-CHANNEL EXPRESSION; CENTRAL-NERVOUS-SYSTEM; HUMAN PROSTATE-CANCER; HUMAN-MELANOMA CELLS; VOLTAGE-GATED K+; XENOPUS-LAEVIS; IN-VIVO AB Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest's environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl). Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT). These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior. C1 [Blackiston, Douglas; Adams, Dany S.; Lemire, Joan M.; Lobikin, Maria; Levin, Michael] Tufts Univ, Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. [Blackiston, Douglas; Adams, Dany S.; Lemire, Joan M.; Lobikin, Maria; Levin, Michael] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Blackiston, Douglas] Forsyth Inst, Dept Regenerat & Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Tufts Univ, Ctr Regenerat & Dev Biol, 200 Boston Ave,Suite 4600, Medford, MA 02155 USA. EM michael.levin@tufts.edu FU NIH [GM078484]; NHTSA [DTNH22-06-G-00001]; DOD [W81XWH-10-2-0058]; Forsyth Institute [T32-DE-007327]; NIH/NIDCR [K22DE016633] FX We thank Punita Koustubhan and Amber Currier for Xenopus husbandry, and Dayong Qiu and Norman Lautsch for histology. We are grateful to the Drug Synthesis and Chemistry Branch, Developmental Therapeutics program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, for providing NSC-84093 compound, Daryl Davies and Miriam Fine for the GlyCl expression construct, John Mihic for useful discussions and for the overactive D97R mutant of human glyR alpha 1, Nancy Papalopulu for helpful comments on the manuscript, and Carole Labonne for Sox10 plasmid. M. Levin gratefully acknowledges the support of the NIH (grant GM078484), NHTSA (grant DTNH22-06-G-00001) and DOD (grant W81XWH-10-2-0058). D.B. was supported by Forsyth Institute's T32-DE-007327 training grant. D.S.A. was supported by the NIH/NIDCR (grant K22DE016633). NR 195 TC 49 Z9 50 U1 1 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 EI 1754-8411 J9 DIS MODEL MECH JI Dis. Model. Mech. PD JAN PY 2011 VL 4 IS 1 BP 67 EP 85 DI 10.1242/dmm.005561 PG 19 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 725WO UT WOS:000287677800010 PM 20959630 ER PT J AU Bordeianou, L Savitt, L Dursun, A AF Bordeianou, Liliana Savitt, Lieba Dursun, Abdulmetin TI Measurements of Pelvic Floor Dyssynergia: Which Test Result Matters? SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY MAY 14-19, 2010 CL Minneapolis, MN SP Amer Soc Colon & Rectal Surg DE Contractions of puborectalis; Pelvic floor dyssynergia; Obstructed defecation ID BIOFEEDBACK; CONSTIPATION; DEFECATION; ANISMUS AB PURPOSE: Failure to expel a 60-mL balloon on manometry and abnormal relaxation of anal sphincter on electromyographic testing are frequently used to diagnose pelvic floor dyssynergia. However, the relationship between these 2 test results and their relationship to defecography is poorly characterized. We aimed to describe this relationship and create a predictive model for pelvic floor dyssynergia on defecography. METHODS: From March 2008 to April 2010 consecutive patients with symptoms suggestive of functional constipation were evaluated at our Pelvic Floor Disorders Center 125 and the results of their workups were collected prospectively. Sixty-three patients with pelvic floor dyssynergia on defecography were compared with 60 patients without dyssynergia in terms of manometry pressures, electromyographic text results, and balloon expulsion testing results (chi(2), t tests). RESULTS: Of 125 patients meeting Rome II symptom criteria for constipation, 123 patients underwent defecography and, of these, 63 (51.2%) had evidence of pelvic floor dyssynergia. Patients with and without dyssynergia had a slight difference in mean resting pressures (62.8 mmHg vs 49.5 mmHg, P = .02) and no discernable differences in rectal sensitivity and compliance: first sensation (56.5 vs 62.5, P = .34) and maximum tolerated volume (164.2 vs 191.2, P = .09). It appeared that abnormalities in electromyographic relaxation and balloon expulsion occurred in the same patients: 84.1% of patients with abnormal electromyographic results also did not expel the balloon. However, the presence of these abnormalities, in isolation or together, did not predict the presence of dyssynergia on defecography. CONCLUSION: Normal electromyographic results or the ability to expel a 60-mL balloon does not exclude the presence of pelvic floor dyssynergia on defecography. It is unclear which of these 3 tests should be used to guide the recommendation for (and to then measure response to) biofeedback. C1 [Bordeianou, Liliana] Massachusetts Gen Hosp, Colon & Rectal Surg Program, Pelv Floor Disorders Serv, Div Gastrointestinal Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bordeianou, L (reprint author), Massachusetts Gen Hosp, Colon & Rectal Surg Program, Pelv Floor Disorders Serv, Div Gastrointestinal Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 20 TC 18 Z9 19 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD JAN PY 2011 VL 54 IS 1 BP 60 EP 65 DI 10.1007/DCR.0b013e3181fd2373 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 695NK UT WOS:000285377500011 PM 21160315 ER PT S AU Lin, CX Ke, YG Chhabra, R Sharma, J Liu, Y Yan, H AF Lin, Chenxiang Ke, Yonggang Chhabra, Rahul Sharma, Jaswinder Liu, Yan Yan, Hao BE Zuccheri, G Samori, B TI Synthesis and Characterization of Self-Assembled DNA Nanostructures SO DNA NANOTECHNOLOGY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE DNA nanotechnology; Self-assembly; Electrophoresis; Atomic force microscopy ID GOLD NANOPARTICLE ARRAYS; PROTEIN ARRAYS; NANOARCHITECTURES; DESIGN; NANOARRAYS; SURFACE AB The past decade witnessed the fast evolvement of structural DNA nanotechnology, which uses DNA as blueprint and building material to construct artificial nanostructures. Using branched DNA as the main building block (also known as a "tile") and cohesive single-stranded DNA (ssDNA) ends to designate the pairing strategy for tile-tile recognition, one can rationally design and assemble complicated nanoarchitextures from specifically designed DNA oligonucleotides. Objects in both two- and three-dimensions with a large variety of geometries and topologies have been built from DNA with excellent yield; this development enables the construction of DNA-based nanodevices and DNA-template directed organization of other molecular species. The construction of such nanoscale objects constitutes the basis of DNA nanotechnology. This chapter describes the protocol for the preparation of ssDNA as starting material, the self-assembly of DNA nanostructures, and some of the most commonly used methods to characterize the self-assembled DNA nanostructures. C1 [Lin, Chenxiang; Ke, Yonggang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lin, Chenxiang] Harvard Univ, Wyss Inst, Boston, MA 02115 USA. [Liu, Yan; Yan, Hao] Arizona State Univ, Dept Chem & Biochem, Biodesign Inst, Tempe, AZ USA. [Chhabra, Rahul] Univ Alberta, Natl Inst Nanotechnol, Edmonton, AB, Canada. [Sharma, Jaswinder] Los Alamos Natl Lab, Ctr Integrated Nanotechnol, Los Alamos, NM USA. RP Lin, CX (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Lin, Chenxiang/0000-0001-7041-1946 NR 31 TC 1 Z9 1 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-141-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 749 BP 1 EP 11 DI 10.1007/978-1-61779-142-0_1 D2 10.1007/978-1-61779-142-0 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BVR34 UT WOS:000292531200001 PM 21674361 ER PT J AU Huang, YY Sharma, SK Carroll, J Hamblin, MR AF Huang, Ying-Ying Sharma, Sulbha K. Carroll, James Hamblin, Michael R. TI BIPHASIC DOSE RESPONSE IN LOW LEVEL LIGHT THERAPY - AN UPDATE SO DOSE-RESPONSE LA English DT Article DE low level laser therapy; photobiomodulation; biphasic dose response; reactive oxygen species; nitric oxide; traumatic brain injury ID HELIUM-NEON LASER; HUMAN SKIN FIBROBLASTS; NF-KAPPA-B; NITRIC-OXIDE; CELLULAR-RESPONSES; IN-VITRO; IRRADIATION; RADIATION; FLUENCE; RATS AB Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments. C1 [Huang, Ying-Ying; Sharma, Sulbha K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Guilin, Guangxi, Peoples R China. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Carroll, James/0000-0002-9205-1061; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research [FA9950-04-1-0079] FX This work was supported by NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research (FA9950-04-1-0079). NR 50 TC 113 Z9 118 U1 4 U2 14 PU INT DOSE-RESPONSE SOC PI AMHERST PA UNIV MASSACHUSETTS SPH, MORRILL SCI CTR 1, N344, 639 N PLEASANT ST, AMHERST, MA 01003-9298 USA SN 1559-3258 J9 DOSE-RESPONSE JI Dose-Response PY 2011 VL 9 IS 4 BP 602 EP 618 DI 10.2203/dose-response.11-009.Hamblin PG 17 WC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology SC Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging; Toxicology GA 858NN UT WOS:000297806500009 PM 22461763 ER PT J AU Weingart, SN Seger, AC Feola, N Heffernan, J Schiff, G Isaac, T AF Weingart, Saul N. Seger, Andrew C. Feola, Nicholas Heffernan, James Schiff, Gordon Isaac, Thomas TI Electronic Drug Interaction Alerts in Ambulatory Care The Value and Acceptance of High-Value Alerts in US Medical Practices as Assessed by an Expert Clinical Panel SO DRUG SAFETY LA English DT Article ID PHYSICIAN ORDER ENTRY; VIEWS AB Background: Computerized physician order entry systems are known to improve patient safety in acute-care hospitals. However, as clinicians frequently override drug interaction and allergy alerts, their value in ambulatory care remains uncertain. Objective: The purpose of the study was to examine whether ambulatory care clinicians were more likely to accept drug-drug interaction alerts that an expert panel judged to be of high clinical value. Study Design: We convened an expert panel to examine drug-drug interaction alerts generated by 2872 clinicians in Massachusetts, Pennsylvania and New Jersey who used a common electronic prescribing system between 1 January 2006 and 30 September 2006. We selected 120 representative drug interaction alerts from the most commonly encountered class-class interactions. Measurements: The expert panel rated each alert based on the following categories: (i) strength of the scientific evidence; (ii) probability that the interaction would result in an adverse drug event (ADE); (iii) severity of typical and most serious ADEs; (iv) the likelihood that a clinician could act on the information; and (v) the overall value of the alert to the average primary care clinician. We then used multivariate regression techniques to examine the relationship between the alert acceptance rate and the expert panel's mean rating of each category. Results: The decision of clinicians to accept drug interaction alerts increased (relative to a baseline alert acceptance rate of 8.8%) by 2.7% (95% CI 0.4, 5.1) for interactions that panelists judged would result in an ADE, by 2.3% (95% CI 0.9, 3.7) when primary care providers (PCPs) lacked prior knowledge about the information presented in the alert, and by 3.3% (95% CI 0.9, 5.8) when the PCP could readily act on the information provided in the alert. Conclusion: The value of electronic drug interaction alerts is influenced heavily by clinicians' judgements about the clinical value of the alert. Expert judgement should be taken into account when developing electronic decision support. C1 [Weingart, Saul N.; Seger, Andrew C.; Isaac, Thomas] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02215 USA. [Weingart, Saul N.; Heffernan, James; Isaac, Thomas] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Seger, Andrew C.; Schiff, Gordon] Brigham & Womens Hosp, Ctr Excellence Patient Safety Res & Practice, Boston, MA 02115 USA. [Seger, Andrew C.; Feola, Nicholas] Massachusetts Coll Pharm & Allied Hlth Sci, Boston, MA USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 450 Brookline Ave, Boston, MA 02215 USA. EM saul_weingart@dfci.harvard.edu FU Physicians' Foundation for Health Systems Excellence FX This research was funded by a grant from the Physicians' Foundation for Health Systems Excellence. The authors acknowledge Daniela Brouillard for her invaluable assistance in completing this project. The authors have no conflicts of interest to declare that are directly relevant to the content of this study. NR 14 TC 16 Z9 16 U1 3 U2 7 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2011 VL 34 IS 7 BP 587 EP 593 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 787GC UT WOS:000292363600005 PM 21663334 ER PT J AU Connolly, KR Thase, ME AF Connolly, K. Ryan Thase, Michael E. TI If at First You Don't Succeed A Review of the Evidence for Antidepressant Augmentation, Combination and Switching Strategies SO DRUGS LA English DT Review ID MAJOR DEPRESSIVE DISORDER; TREATMENT-RESISTANT-DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; ASTERISK-D REPORT; TREATMENT-REFRACTORY DEPRESSION; MONOAMINE-OXIDASE INHIBITORS; VENLAFAXINE EXTENDED-RELEASE; FAILED MEDICATION TREATMENTS; DOUBLE-BLIND AB Major depressive disorder is a common and disabling illness that leads to significant reductions in quality of life and considerable cost to society. Despite numerous advances in the pharmacological treatment of depression, many patients remain ill despite initial treatment. Beyond first-line treatment, current guidelines recommend either augmentation or switching of the initial antidepressant. In this narrative review, we summarize the data from randomized controlled trials and meta-analyses in order to concisely discuss how the impact of current research can be translated into clinical practice and, ultimately, into lasting improvements in patient outcomes. The augmentation strategies reviewed are lithium, thyroid hormone, pindolol, psychostimulants and second-generation antipsychotics. The data on switching from first-line antidepressants to other antidepressants are also reviewed, and include switching within the same class, switching to other first-line antidepressant classes and switching to less commonly prescribed antidepressants. Finally, the strategy of antidepressant combinations is examined. Overall, the strength of evidence supporting a trial of augmentation or a switch to a new agent is very similar, with remission rates between 25% and 50% in both cases. Our review of the evidence suggests several conclusions. First, although it is true that adjunctive lithium and thyroid hormone have established efficacy, we can only be confident that this is true for use in combination with tricyclic antidepressants (TCAs), and the trials were done in less treatment-resistant patients than those who typically receive TCAs today. Of these two options, triiodothyronine augmentation seems to offer the best benefit/risk ratio for augmentation of modern antidepressants. After failure of a first-line selective serotonin reuptake inhibitor (SSRI), neither a switch within class nor a switch to a different class of antidepressant is unequivocally supported by the data, although switching from an SSRI to venlafaxine or mirtazapine may potentially offer greater benefits. Interestingly, switching from a newer antidepressant to a TCA after a poor response to the former is not supported by strong evidence. Of all strategies to augment response to new-generation antidepressants, quetiapine and aripiprazole are best supported by the evidence, although neither the cost effectiveness nor the longer-term benefit of these strategies has been established. The data to guide later steps in the treatment of resistant depression are sparse. Given the wide variety of options for the treatment of major depressive disorder, and the demonstrated importance of truly adequate treatment to the long-term outcomes of patients facing this illness, it is clear that further well conducted studies are needed. C1 [Connolly, K. Ryan; Thase, Michael E.] Univ Penn, Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP Connolly, KR (reprint author), Univ Penn, Sch Med, Philadelphia VA Med Ctr, MIRECC Rm 228B, Philadelphia, PA 19104 USA. EM Kevin.connolly2@va.gov FU Eli Lilly Company; GlaxoSmithKline; National Institute of Mental Health; Sepracor, Inc.; American Psychiatric Publishing, Inc.; Guilford Publications; Herald House; Oxford University Press; W.W. Norton Company; Philadelphia Veterans Affairs Medical Center's Mental Illness Research Education and Clinical Center (MIRECC) FX No sources of funding were used in the preparation of this article. Dr Thase has provided scientific consultation to Astra-Zeneca, Bristol-Myers Squibb Company, Eli Lilly & Company, Forest Pharmaceuticals, Inc., GlaxoSmithKline, MedAvante, Inc., Neuronetics, Inc., Novartis, Pfizer (formerly Wyeth-Ayerst Laboratories), Schering-Plough, Shire US Inc., Supernus Pharmaceuticals, Takeda and Transcept Pharmaceuticals. Dr Thase has been a member of the speakers' bureaus for AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly & Company and Pfizer (formerly Wyeth-Ayerst Laboratories). He receives grant funding from Eli Lilly & Company, GlaxoSmithKline, National Institute of Mental Health and Sepracor, Inc. Dr Thase has equity holdings in MedAvante, Inc. and receives royalty income from American Psychiatric Publishing, Inc., Guilford Publications, Herald House, Oxford University Press and W.W. Norton & Company. His wife is employed as the senior medical director for Advogent.; Dr Connolly would like to thank the Philadelphia Veterans Affairs Medical Center's Mental Illness Research Education and Clinical Center (MIRECC) for their support. Dr Connolly has no competing interests. NR 84 TC 102 Z9 106 U1 3 U2 19 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2011 VL 71 IS 1 BP 43 EP 64 DI 10.2165/11587620-000000000-00000 PG 22 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 710HU UT WOS:000286502700003 PM 21175239 ER PT J AU Saylor, PJ Keating, NL Freedland, SJ Smith, MR AF Saylor, Philip J. Keating, Nancy L. Freedland, Stephen J. Smith, Matthew R. TI Gonadotropin-Releasing Hormone Agonists and the Risks of Type 2 Diabetes and Cardiovascular Disease in Men with Prostrate Cancer SO DRUGS LA English DT Editorial Material ID ANDROGEN-DEPRIVATION THERAPY; ADVANCED PROSTATE-CANCER; RANDOMIZED CONTROLLED-TRIAL; PHASE-III; MYOCARDIAL-INFARCTION; SUPPRESSION THERAPY; ARTERIAL STIFFNESS; RADIATION-ONCOLOGY; BODY-COMPOSITION; RTOG 85-31 C1 [Saylor, Philip J.; Smith, Matthew R.] Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA. [Keating, Nancy L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gen Internal Med, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Freedland, Stephen J.] Durham VA Med Ctr, Durham, NC USA. [Freedland, Stephen J.] Duke Prostate Ctr, Div Urol Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Dept Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Dept Pathol, Durham, NC 27706 USA. RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Ctr Canc, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA. EM psaylor@partners.org FU NCI NIH HHS [5K24CA121990-02, K24 CA121990] NR 49 TC 5 Z9 5 U1 0 U2 1 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2011 VL 71 IS 3 BP 255 EP 261 DI 10.2165/11588930-000000000-00000 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 734CU UT WOS:000288311600001 PM 21319864 ER PT J AU Venkatesh, KK Swaminathan, S Andrews, JR Mayer, KH AF Venkatesh, Kartik K. Swaminathan, Soumya Andrews, Jason R. Mayer, Kenneth H. TI Tuberculosis and HIV Co-Infection Screening and Treatment Strategies SO DRUGS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; ISONIAZID PREVENTIVE THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; RECONSTITUTION INFLAMMATORY SYNDROME; SUB-SAHARAN AFRICA; RESOURCE-LIMITED SETTINGS; MULTIDRUG-RESISTANT TUBERCULOSIS; NEGATIVE PULMONARY TUBERCULOSIS; ACQUIRED RIFAMYCIN RESISTANCE; SPUTUM SMEAR MICROSCOPY AB Globally, tuberculosis (TB) and HIV interact in deadly synergy. The high burden of TB among HIV-infected individuals underlies the importance of TB diagnosis, treatment and prevention for clinicians involved in HIV care. Despite expanding access to antiretroviral therapy (ART) to treat HIV infection in resource-limited settings, many individuals in need of therapy initiate ART too late and have already developed clinically significant TB by the time they present for care. Many co-infected individuals are in need of concurrent ART and anti-TB therapy, which dramatically improves survival, but also raises several management challenges, including drug interactions, shared drug toxicities and TB immune reconstitution inflammatory syndrome (IRIS). Due to the survival benefits of promptly initiating ART among all HIV-infected individuals, including those with TB, it is recommended that co-infected individuals receive treatment for both diseases, regardless of CD4+ cell count. We review current screening and treatment strategies for TB and HIV co-infection. Recent findings and ongoing studies will assist clinicians in managing the prevention and treatment of TB and HIV co-infection, which remains a major global health challenge. C1 [Venkatesh, Kartik K.; Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Div Infect Dis, Dept Med,Alpert Med Sch, Providence, RI 02906 USA. [Venkatesh, Kartik K.; Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Dept Community Hlth, Alpert Med Sch, Providence, RI 02906 USA. [Swaminathan, Soumya] Indian Council Med Res, Dept Clin Res, TB Res Ctr, Chennai, Tamil Nadu, India. [Swaminathan, Soumya] UNDP UNICEF World Bank WHO Special Programme Res, Geneva, Switzerland. [Andrews, Jason R.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Infect Dis, Boston, MA USA. [Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. RP Mayer, KH (reprint author), Brown Univ, Miriam Hosp, Div Infect Dis, Dept Med,Alpert Med Sch, 164 Summit Ave, Providence, RI 02906 USA. EM Kenneth_Mayer@brown.edu FU Lifespan/Tufts/Brown Center for AIDS Research [P30 AI42853]; Brown/Tufts/Miriam Fogarty AIDS International Training and Research Program [D43TW000237]; NIMH Ruth Kirschstein National Research Service [F30 MH079738-01A2] FX This research has been facilitated by the infrastructure and resources provided by the Lifespan/Tufts/Brown Center for AIDS Research (grant# P30 AI42853, P.I. Charles Carpenter) and the Brown/Tufts/Miriam Fogarty AIDS International Training and Research Program (grant# D43TW000237, P.I. Kenneth Mayer). KK Venkatesh is supported by the NIMH Ruth Kirschstein National Research Service Award (NRSA) [grant # F30 MH079738-01A2]. NR 186 TC 12 Z9 13 U1 0 U2 5 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2011 VL 71 IS 9 BP 1133 EP 1152 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 797CH UT WOS:000293101200003 PM 21711060 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Arctic spectacles: The frozen north in visual culture, 1818-1875 SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PY 2011 VL 9 IS 4 BP 363 EP 365 DI 10.1080/17460654.2011.621329 PG 3 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 883OM UT WOS:000299643600008 ER PT J AU Means, TK Aballay, A AF Means, Terry K. Aballay, Alejandro TI Models to study ancient host-pathogen interactions: lessons from Crete SO EMBO REPORTS LA English DT Editorial Material ID INNATE IMMUNITY; CAENORHABDITIS-ELEGANS; GENES; INFECTION; SCREEN AB The Aegean Conferences' first International Conference on Model Hosts took place on the picturesque Greek island of Crete. This meeting was the first of its kind and gathered together international experts who are using a vast array of hosts as models of infection, including worms, insects, mice, fish, rats, humans, squids, pigs, monkeys, protozoa, amoebae and ticks. C1 [Means, Terry K.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Means, Terry K.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Means, Terry K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Aballay, Alejandro] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27706 USA. RP Means, TK (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. EM tmeans@partners.org; a.aballay@duke.edu FU NIAID NIH HHS [R01 AI084884]; NIGMS NIH HHS [R01 GM070977] NR 11 TC 2 Z9 2 U1 1 U2 4 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 JAN PY 2011 VL 12 IS 1 BP 5 EP 7 DI 10.1038/embor.2010.205 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 702RT UT WOS:000285913400004 PM 21164515 ER PT J AU Siegfried, KR AF Siegfried, K. R. BE Farrell, AP TI Molecular and Chromosomal Aspects of Sex Determination SO ENCYCLOPEDIA OF FISH PHYSIOLOGY: FROM GENOME TO ENVIRONMENT, VOLS 1-3 LA English DT Article; Book Chapter ID ORYZIAS-LATIPES; MEDAKA; FISH; DIFFERENTIATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Siegfried, KR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092323-9 PY 2011 BP 2025 EP 2031 PG 7 WC Fisheries; Zoology SC Fisheries; Zoology GA BFK29 UT WOS:000320225700246 ER PT J AU Beaser, RS Neighbours, JE Brown, J Ronk, KM Wolyniec, WW AF Beaser, Richard S. Neighbours, James E. Brown, Julie Ronk, Katie M. Wolyniec, Walter W. TI USAGE PATTERNS OF DEVICES DESIGNED TO SUPPORT DIABETES MANAGEMENT: AN EDUCATIONAL NEEDS ASSESSMENT SO ENDOCRINE PRACTICE LA English DT Article ID BLOOD-GLUCOSE; GLYCEMIC CONTROL; RECEIVING INSULIN AB Objective: To determine knowledge, competence, and attitudinal issues among diabetes specialists and primary care providers (PCPs) regarding the use of insulin delivery devices such as insulin pens and insulin pumps and the role of glucose monitoring devices and systems in the care of patients with diabetes. Methods: A quantitative survey tool was developed that contained 51 questions directed to diabetes specialists and 49 questions directed to PCPs. A 5-point, Likert-type scale or multipie-choice format was used. Data were collected from attendees at live symposia across the United States. Results were analyzed for frequency of response and significant relationships among the variables. Results: The survey was completed by 136 specialists and 418 PCPs. There were higher usage rates for insulin pens among specialists than PCPs, although there were higher usage rates among more experienced PCPs. Regarding glucose monitoring, most specialists and PCPs did not recommend "block checking," which has been commonly thought of as a reasonable compromise checking schedule for patients with type 2 diabetes not using insulin. PCPs who were more experienced and used outside educational resources, such as a certified diabetes educator, and specialists who saw more patients on a weekly basis were more likely to prescribe the use of continuous glucose monitoring. There was a general underuse of continuous glucose monitoring in eligible patients. Conclusions: These findings underscore the discordance between PCPs and specialists with regard to advanced knowledge and confidence required for the use of newer technologies for glucose monitoring and insulin replacement. We have identified important remedial opportunities for quality- and performance-based educational interventions. (Endocr Pract. 2011;17:51-57) C1 [Beaser, Richard S.; Neighbours, James E.; Brown, Julie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Ronk, Katie M.] Forward Hlth Grp Inc, Madison, WI USA. [Wolyniec, Walter W.] Confluent Healthcare Solut LLC, Ridgefield, CT USA. RP Beaser, RS (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Richard.Beaser@joslin.harvard.edu FU sanofi-aventis U.S., LLC FX Funding for this research was provided in the form of an educational grant from sanofi-aventis U.S., LLC. NR 9 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CLIN ENDOCRINOL PI JACKSONVILLE PA 1000 RIVERSIDE AVE, STE 205, JACKSONVILLE, FL 32204 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD JAN-FEB PY 2011 VL 17 IS 1 BP 51 EP 57 DI 10.4158/EP10160.OR PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746UH UT WOS:000289272700006 PM 20713339 ER PT J AU Muscogiuri, G Kamat, A Balas, B Giaccari, A DeFronzo, RA Musi, N Katz, MS AF Muscogiuri, Giovanna Kamat, Amrita Balas, Bogdan Giaccari, Andrea DeFronzo, Ralph A. Musi, Nicolas Katz, Michael S. TI beta-Adrenergic Responsive Induction of Insulin Resistance in Liver of Aging Rats SO ENDOCRINE RESEARCH LA English DT Article DE Glucose production; Catecholamines; beta-Adrenergic receptor ID ADENYLATE-CYCLASE; GLUCOSE-PRODUCTION; DIABETIC RATS; HUMAN TISSUES; AGE; GLYCOGENOLYSIS; EPINEPHRINE; EXPRESSION; RECEPTORS; STRESS AB Introduction. We previously demonstrated increases in beta-adrenergic receptor (beta-AR) density in rat liver, in association with increased beta-AR-mediated stimulation of glucose output in rat hepatocytes, during senescent aging. We therefore hypothesized that pharmacologic beta-adrenergic stimulation might induce insulin resistance and glucose output in liver of aging rats in vivo. Methods. In this study, pancreatic clamps were performed on young adult (4-month-old) and senescent (24-month-old) Fischer 344 male rats by infusing somatostatin (3 mu g/kg/min) at time 0 to inhibit insulin secretion, and then infusing insulin (1 mU/kg/min) to replace basal insulin concentrations. At time 0 rats also received either the beta-AR agonist isoproterenol (100 ng/kg/min) or saline (control). After 120 min the insulin infusion rate was increased to 4 mU/kg/min for an additional 120 min. Tritiated glucose was infused throughout the study to measure glucose turnover rates. Results and Conclusion. The results of the pancreatic clamp studies demonstrated that under saline control conditions hepatic glucose production (HGP) was suppressed during hyper-insulinemia in both young and old rats, with a trend toward reduced insulin sensitivity in the older animals. Isoproterenol infusion impaired insulin-induced suppression of HGP in both age groups. The results suggest that beta-AR stimulation by isoproterenol increases HGP and acutely induces hepatic insulin resistance in both young and old rats. A similar role for beta-adrenergic-mediated hepatic insulin resistance in aging humans would suggest a novel therapeutic target for the treatment or prevention of glucose dysregulation and diabetes developing with advancing age. C1 [Kamat, Amrita; Katz, Michael S.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Muscogiuri, Giovanna; Kamat, Amrita; Balas, Bogdan; DeFronzo, Ralph A.; Musi, Nicolas; Katz, Michael S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Kamat, Amrita; DeFronzo, Ralph A.; Musi, Nicolas] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Giaccari, Andrea] Catholic Univ, Rome & Don Gnocchi Fdn, Dept Endocrinol, Milan, Italy. [Katz, Michael S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. RP Kamat, A (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM kamat@uthscsa.edu RI Giaccari, Andrea/J-1889-2012 OI Giaccari, Andrea/0000-0002-7462-7792 FU Department of Veterans Affairs; American Heart Association; Kronos Longevity Research Institute FX This work was supported by a VISN 17 Award from the Department of Veterans Affairs (AK), a Grant-in-Aid American Heart Association Award (AK), and a research grant from the Kronos Longevity Research Institute (MSK). NR 35 TC 6 Z9 6 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 2011 VL 36 IS 2 BP 74 EP 82 DI 10.3109/07435800.2010.539993 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758KK UT WOS:000290163400004 PM 21438725 ER PT J AU Wu, SV Yuan, PQ Lai, J Wong, K Chen, MC Ohning, GV Tache, Y AF Wu, S. Vincent Yuan, Pu-Qing Lai, Jim Wong, Kelvin Chen, Monica C. Ohning, Gordon V. Tache, Yvette TI Activation of Type 1 CRH Receptor Isoforms Induces Serotonin Release from Human Carcinoid BON-1N Cells: An Enterochromaffin Cell Model SO ENDOCRINOLOGY LA English DT Article ID 7TH TRANSMEMBRANE DOMAIN; IRRITABLE-BOWEL-SYNDROME; FUNCTIONAL-CHARACTERIZATION; CRF1 RECEPTOR; IN-VITRO; VISCERAL HYPERSENSITIVITY; HORMONE-RECEPTOR; COLONIC FUNCTION; 5-HT3 RECEPTORS; CONSCIOUS RATS AB CRH and 5-hydroxytryptamine (5-HT) are expressed in human colonic enterochromaffin (EC) cells, but their interactions at the cellular level remain largely unknown. The mechanistic and functional relationship between CRH and 5-HT systems in EC cells was investigated in a human carcinoid cloned BON cell line (BON-1N), widely used as an in vitro model of EC cell function. First, we identified multiple CRH(1) splice variants, including CRH(1a), CRH(1c), CRH(1f), and a novel form lacking exon 4, designated here as CRH(1i), in the BON-1N cells. The expression of CRH(1i) was also confirmed inhumanbrain cortex, pituitary gland, and ileum. Immunocytochemistry and immunoblot analysis confirmed that BON-1N cells were CRH(1) and 5-HT positive. CRH, urocortin (Ucn)-1, and cortagine, a selective CRH(1) agonist, all increased intracellular cAMP, and this concentration-dependent response was inhibited by CRH(1)-selective antagonist NBI-35965. CRH and Ucn-1, but not Ucn-2, stimulated significant ERK1/2 phosphorylation. In transfected human embryonic kidney-293 cells, CRH1i isoforms produced a significant increase in pERK1/2 in response to CRH(1) agonists that was sensitive to NBI-35965. CRH and Ucn-1 stimulated 5-HT release that reached a maximal increase of 3.3- and 4-fold at 10(-8) M over the basal level, respectively. In addition, exposure to CRH for 24-h up-regulated tryptophan hydroxylase-1 mRNA levels in the BON-1N cells. These findings define the expression of EC cell-specific CRH(1) isoforms and activation of CRH(1)-dependent pathways leading to 5-HT release and synthesis; thus, providing functional evidence of a link exists between CRH and 5-HT systems, which have implications in stress-induced CRH(1) and 5-HT-mediated stimulation of lower intestinal function. (Endocrinology 152: 126-137, 2011) C1 [Wu, S. Vincent] Vet Affairs Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med, Los Angeles, CA 90073 USA. RP Wu, SV (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Bldg 115,Room 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM vwu@ucla.edu FU National Institutes of Health (NIH) [DK 57238]; NIH Center [DK 41301]; Hirshberg Foundation FX This work was supported by the National Institutes of Health (NIH) R01 Grant DK 57238; a Veterans Affairs (VA) Merit Review award and a VA Research Career Scientist award (Y.T.); the Peptidomics and Antibody Core from NIH Center Grant DK 41301 CURE: Digestive Diseases Research Center (to G.V.O.); and a Seed grant from Hirshberg Foundation (S.V.W.). NR 57 TC 17 Z9 17 U1 1 U2 6 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 JAN PY 2011 VL 152 IS 1 BP 126 EP 137 DI 10.1210/en.2010-0997 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 698DT UT WOS:000285573000014 PM 21123435 ER PT J AU Sonnenberg, A AF Sonnenberg, A. TI When to stop the search for an elusive source of gastrointestinal bleeding SO ENDOSCOPY LA English DT Article ID EPIDEMIOLOGY; DIAGNOSIS AB Background and study aims: This analysis investigates the clinical parameters that should drive decisions about when to continue or stop the search for an elusive source of gastrointestinal bleeding. Patients and methods: The number of endoscopies necessary to find a source of bleeding was estimated using the geometric distribution. A threshold analysis was used to develop a stop rule for the search for a site of bleeding. Bayes' formula served to estimate changes in the probability of achieving a diagnosis associated with a series of consecutive endoscopic tests. Results: With decreasing probability of diagnostic success associated with an individual endoscopic procedure, such as p = 50%, 33%, or 25%, the mean (standard deviation [SD]) number of procedures needed to find the source of bleeding increases to 2 (1.41), 3 (2.45), or 4 (3.46), respectively. The threshold analysis suggests that workup should be discontinued if the expected rise in diagnostic probability does not exceed the ratio of work-up cost to bleeding cost, that is, Delta p < work-up cost/bleeding cost. For instance, a 10-fold higher cost of bleeding than endoscopy would justify continued work-up if it can improve diagnostic probability by 10%. Bayesian analysis shows that after three negative tests the diagnostic probability drops below such a threshold. Conclusions: The analysis suggests the following basic rules. The search for a site of gastrointestinal bleeding will take on average 2 procedures with a range of 1-4. The search should be continued as long as the diagnostic probability is expected to rise by more than 10%, which is unlikely after three consecutive negative tests. C1 Portland VA Med Ctr, Portland, OR 97239 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 7 TC 3 Z9 3 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD JAN PY 2011 VL 43 IS 1 BP 4 EP 7 DI 10.1055/s-0030-1255847 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 706AY UT WOS:000286186700001 PM 21038292 ER PT S AU Hurwitz, M Machtinger, R Fennessy, F AF Hurwitz, Mark Machtinger, Ronit Fennessy, Fiona BE Ryan, TP TI Magnetic resonance-guided focused ultrasound surgery for treatment of painful osseous metastases SO ENERGY-BASED TREATMENT OF TISSUE AND ASSESSMENT VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Energy-Based Treatment of Tissue and Assessment VI CY JAN 23-24, 2011 CL San Francisco, CA SP SPIE DE Magnetic Resonance; Focused Ultrasound; MRgFUS; Image Guided Therapy; Bone Metastases ID PERCUTANEOUS RADIOFREQUENCY ABLATION; ADVANCED PROSTATE-CANCER; BONE METASTASES; RANDOMIZED-TRIAL; RADIATION-THERAPY; UTERINE LEIOMYOMAS; PALLIATION; TUMORS; RADIOTHERAPY; BISPHOSPHONATES AB Magnetic resonance guided focused ultrasound surgery (MRgFUS) is an emerging technology that can non-invasively heat and ablate targeted tissue utilizing ultrasound energy. Use of MR imaging for treatment guidance provides several key advantages over more widely used ultrasound guidance for focused ultrasound ablation. MR allows for precise targeting, detailed beam path visualization, real time non-invasive temperature measurement, and treatment feedback to ensure therapeutic goals are achieved. In the realm of oncology, management of painful bone metastases is a common and daunting clinical problem. The Insightec ExAblate System has been shown in phase I/II trials for treatment of bone metastases to have an excellent safety profile and high rates of pain response. An international multi-center phase III trial for patients with painful bone metastases or multiple myeloma who are not candidates for radiation therapy is currently open. Patients are randomized 3:1 to MRgFUS or sham treatment with crossover to study treatment allowed for sham failures. The primary study endpoint is assessment of pain control over 3 months following treatment. In addition safety, quality of life, cost effectiveness analysis, and patient perceived clinical benefit are also being assessed. Details of the MRgFUS system, technical and clinical therapeutic parameters, use of real time non-invasive MR thermometry, and examples of patient treatments with use of MRgFUS to treat bone metastases will be discussed. New directions in use of MRgFUS including an update on development of a new mobile applicator and integration of MRgFUS in multimodality oncologic care will also be presented. C1 [Hurwitz, Mark] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Hurwitz, M (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RI Emchi, Karma/Q-1952-2016 NR 39 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8438-3 J9 PROC SPIE PY 2011 VL 7901 AR 79010M DI 10.1117/12.876434 PG 9 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BXZ28 UT WOS:000297679200021 ER PT S AU Walsh, CJ Slocum, AH Gupta, R AF Walsh, Conor J. Slocum, Alexander H. Gupta, Rajiv BE Ryan, TP TI Preliminary Evaluation of Robotic Needle Distal Tip Repositioning SO ENERGY-BASED TREATMENT OF TISSUE AND ASSESSMENT VI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Energy-Based Treatment of Tissue and Assessment VI CY JAN 23-24, 2011 CL San Francisco, CA SP SPIE DE robot; steering; ablation; computed tomography; image-guided ID PERCUTANEOUS RADIOFREQUENCY ABLATION; TISSUE ABLATION; LUNG; LESIONS AB Advances in medical imaging now provide detailed images of solid tumors inside the body and miniaturized energy delivery systems enable tumor destruction through local heating powered by a thin electrode. We have developed a robot for accurately repositioning the distal tip of a medical instrument such an ablation probe to adjacent points within tissue. The position accuracy in ballistics gelatin was evaluated in a 2D experimental setup with a digital SLR camera that was fixed to a rig that also contained the gelatin. The robot was mounted to the rig in such a way that the stylet was deployed in a plane parallel the camera's lens. A grid paper attached to the back of the box containing the gelatin provided a stationary reference point for each of the pictures taken and also served as a coordinate system for making measurements. The measurement repeatability error was found by taking a stylet tip position measurement five times for two different pictures and found to be 0.26 mm. For a stylet with a radius of curvature of 31.5 mm and a diameter of 0.838 mm, the targeting accuracy was found to be 2.5 +/- 1.4 mm at points that were approximately 38 mm lateral from the cannula axis. C1 [Walsh, Conor J.; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Walsh, CJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM walshcj@mit.edu NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8438-3 J9 PROC SPIE PY 2011 VL 7901 AR 790108 DI 10.1117/12.876604 PG 9 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BXZ28 UT WOS:000297679200008 ER PT J AU Long, N Sumi, M Dung, D Thuan, T AF Long Ngo Sumi Mehta Dung Do Thuan Thach TI The Effects of Short-term Exposure on Hospital Admissions for Acute Lower Respiratory Infections in Young Children of Ho Chi Minh City, Viet Nam SO EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Conference of International-Society-of-Exposure-Science/International-Society-for-Envi ronmental-Epidemiology CY AUG 28-SEP 01, 2010 CL Seoul, SOUTH KOREA SP Int Soc Exposure Sci, Int Soc Environm Epidemiol C1 [Long Ngo] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. [Long Ngo; Sumi Mehta; Dung Do; Thuan Thach] Collaborat Working Grp Air Pollut Poverty & Hlth, Ho Chi Minh City, Vietnam. [Sumi Mehta] Hlth Effects Inst, Boston, MA USA. [Dung Do] Univ Pharm & Med, Ho Chi Minh City, Vietnam. [Thuan Thach] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2011 VL 22 IS 1 SU S BP S228 EP S229 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 695VN UT WOS:000285400800697 ER PT J AU Black, JC Whetstine, JR AF Black, Joshua C. Whetstine, Johnathan R. TI Chromatin landscape Methylation beyond transcription SO EPIGENETICS LA English DT Article DE chromatin; heterochromatin; euchromatin; lysine methylation; KMT; KDM; histone methyltransferase; histone demethylase; HP1; lamin; histone demethylases; histone; H3K9; H3K9me3 ID HETEROCHROMATIN PROTEIN-1 HP1; HISTONE LYSINE METHYLATION; BETA-GLOBIN LOCUS; MAMMALIAN-CELLS; DNA-REPLICATION; HUMAN GENOME; CANCER; CHROMOSOME; DEMETHYLASES; ORGANIZATION AB The nucleus is organized and compartmentalized into a highly ordered structure that contains DNA, RNA, chromosomal and histone proteins. The dynamics associated with these various components are responsible for making sure that the DNA is properly duplicated, genes are properly transcribed and the genome is stabilized. It is no surprise that alterations in these various components are directly associated with pathologies like cancer. This Point-of-View focuses on the role the chromatin modification landscape, especially histone 3 lysine 9 methylation (H3K9me) and heterochromatin proteins (HP1) play in regulating DNA-templated processes, with a particular focus on their role at non-genic regions and effects on chromatin structure. These observations will be further extended to the role that alterations in chromatin landscape will contribute to diseases. This Point-of-View emphasizes that alterations in histone modification landscapes are not only relevant to transcription but have broad range implications in chromatin structure, nuclear architecture, cell cycle, genome stability and disease progression. C1 [Whetstine, Johnathan R.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Dept Med, Sch Med, Charlestown, MA USA. RP Whetstine, JR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. EM jwhetstine@hms.harvard.edu RI Black, Joshua/Q-2484-2015 NR 59 TC 14 Z9 14 U1 0 U2 7 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD JAN PY 2011 VL 6 IS 1 BP 13 EP 19 DI 10.4161/epi.6.1.13331 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701OG UT WOS:000285828700003 ER PT J AU van Eeghen, AM Numis, AI Staley, BA Therrien, SE Thibert, RL Thiele, EA AF van Eeghen, Agnies M. Numis, Adam I. Staley, Brigid A. Therrien, Samuel E. Thibert, Ronald L. Thiele, Elizabeth A. TI Characterizing sleep disorders of adults with tuberous sclerosis complex: A questionnaire-based study and review SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy; Sleep; Tuberous sclerosis complex; Behavior ID RESTLESS LEGS SYNDROME; QUALITY-OF-LIFE; INTELLECTUAL DISABILITIES; DEFICIT DISORDERS; EPILEPSY; MELATONIN; CHILDREN; DISTURBANCE; PREVALENCE; LEVETIRACETAM AB An adult cohort with tuberous sclerosis complex was investigated for the prevalence of sleep disturbances and the relationship with seizure variables, medication, and psychological functioning. Information on 35 adults was gathered using four questionnaires: Epworth Sleepiness Scale (ESS), Sleep and Epilepsy Questionnaire (SEQ), Sleep Diagnosis List (SDL), and Adult Self-Report Scale (ASR). In addition, clinical, genetic and electrophysiological data were collected. Of 35 respondents, 25 had a history of epilepsy. A subjective sleep disorder was found in 31% of the cohort. Insomnia scores showed a significant positive correlation with obstructive sleep apnea syndrome and restless legs syndrome scores. Significant correlations were found between daytime sleepiness and scores on depression, antisocial behavior, and use of mental health medication. A subgroup using antiepileptic medication showed high correlations between daytime sleepiness, attention deficits, and anxiety scores. (c) 2010 Elsevier Inc. All rights reserved. C1 [van Eeghen, Agnies M.; Numis, Adam I.; Staley, Brigid A.; Therrien, Samuel E.; Thibert, Ronald L.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, 55 Fruit St,VBK 830, Boston, MA 02114 USA. EM ethiele@partners.org FU MGH Herscot Center for TSC; NIH/NINDS [P01 NS024279] FX This work is supported by the MGH Herscot Center for TSC, and NIH/NINDS P01 NS024279. We are grateful for the assistance with statistical analysis of Susana Camposano, M.D., and Elkan Halpern, PhD. NR 51 TC 8 Z9 8 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JAN PY 2011 VL 20 IS 1 BP 68 EP 74 DI 10.1016/j.yebeh.2010.10.023 PG 7 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 721DG UT WOS:000287331300014 PM 21130696 ER PT J AU Larson, PS Martin, AJ AF Larson, Paul S. Martin, Alastair J. BE Arle, JE Shils, JL TI Safety Concerns and Limitations SO ESSENTIAL NEUROMODULATION LA English DT Article; Book Chapter ID DEEP BRAIN-STIMULATION; SPINAL-CORD STIMULATION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; INITIAL-EXPERIENCE; PARKINSONS-DISEASE; CARDIAC-PACEMAKERS; PATIENT; MRI; ELECTRODES; DEVICES C1 [Larson, Paul S.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Larson, Paul S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Martin, Alastair J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Larson, PS (reprint author), Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. NR 39 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-381410-4 PY 2011 BP 397 EP 410 DI 10.1016/B978-0-12-381409-8.00018-8 PG 14 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA BGM07 UT WOS:000323483300035 ER PT J AU Azim, HA Santoro, L Pavlidis, N Gelber, S Kroman, N Azim, H Peccatori, FA AF Azim, Hatem A., Jr. Santoro, Luigi Pavlidis, Nicholas Gelber, Shari Kroman, Niels Azim, Hamdy Peccatori, Fedro A. TI Safety of pregnancy following breast cancer diagnosis: A meta-analysis of 14 studies SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Pregnancy after breast cancer; Safety; Counselling; Fertility; Healthy mother effect ID YOUNG-WOMEN; SURVIVAL; SUBSEQUENT; CARCINOMA; BIRTH; RISK; CHILDBEARING; STATISTICS; MASTECTOMY; FERTILITY AB Background: Due to the rising trend of delaying pregnancy to later in life, more women are diagnosed with breast cancer before completing their families. Therefore, enquiry into the feasibility and safety of pregnancy following breast cancer diagnosis is on the rise. Available evidence suggests that women with a history of breast cancer are frequently advised against future conception for fear that pregnancy could adversely affect their breast cancer outcome. Hence, we conducted a meta-analysis to understand the effect of pregnancy on overall survival of women with a history of breast cancer. Methods: Two of the authors independently performed a literature search up to September 2009 with no language restrictions. Eligible studies were published retrospective control-matched, population-based and hospital-based studies that have addressed the impact of pregnancy on the overall survival of women with history of breast cancer. Pooling of data was done using the random effect model. Unpublished statistics from three studies were obtained to perform further subgroup and sensitivity analyses. This included examining the effect of pregnancy according to age at diagnosis, healthy mother effect, type of study, nodal status and other parameters. Results: Fourteen studies were included in this meta-analysis (1244 cases and 18,145 controls). Women who got pregnant following breast cancer diagnosis had a 41% reduced risk of death compared to women who did not get pregnant [PRR: 0.59 (90% confidence interval (CI): 0.50-0.70)]. This difference was seen irrespective of the type of the study and particularly in women with history of node-negative disease. In a subgroup analysis, we compared the outcome of women with history of breast cancer who became pregnant to breast cancer patients who did not get pregnant and were known to be free of relapse. In this analysis, we did not find significant differences in survival between either group [PRR: 0.85; 95% CI: 0.53-1.35]. Conclusions: This study confirms that pregnancy in women with history of breast cancer is safe and does not compromise their overall survival. Hence, breast cancer survivors should not be denied the opportunity of future conception. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Peccatori, Fedro A.] European Inst Oncol, Dept Med, Div Hematol Oncol, I-20141 Milan, Italy. [Azim, Hatem A., Jr.] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Azim, Hatem A., Jr.] Cairo Univ, Dept Med Oncol, Natl Canc Inst, Cairo, Egypt. [Santoro, Luigi] European Inst Oncol, Div Epidemiol & Biostat, I-20141 Milan, Italy. [Pavlidis, Nicholas] Univ Ioannina, Dept Med Oncol, GR-45110 Ioannina, Greece. [Gelber, Shari] Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. [Kroman, Niels] Rigshosp, Dept Breast Surg, DK-2100 Copenhagen, Denmark. [Kroman, Niels] Rigshosp, Danish Breast Canc Cooperat Grp, DK-2100 Copenhagen, Denmark. [Azim, Hamdy] Cairo Univ Hosp, Dept Clin Oncol, Cairo, Egypt. RP Peccatori, FA (reprint author), European Inst Oncol, Dept Med, Div Hematol Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM fedro.peccatori@ieo.it NR 43 TC 75 Z9 77 U1 1 U2 13 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 JAN PY 2011 VL 47 IS 1 BP 74 EP 83 DI 10.1016/j.ejca.2010.09.007 PG 10 WC Oncology SC Oncology GA 713YZ UT WOS:000286774700008 PM 20943370 ER PT J AU Dimopoulos, MA San-Miguel, JF Anderson, KC AF Dimopoulos, Meletios A. San-Miguel, Jesus F. Anderson, Kenneth C. TI Emerging therapies for the treatment of relapsed or refractory multiple myeloma SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Review DE multiple myeloma; immunomodulatory drug; proteasome inhibitor; Akt inhibitor; histone deacetylase inhibitor ID HISTONE DEACETYLASE INHIBITORS; LENALIDOMIDE PLUS DEXAMETHASONE; T-CELL LYMPHOMA; SUBEROYLANILIDE HYDROXAMIC ACID; HIGH-DOSE CHEMOTHERAPY; PHASE-I; VAD CHEMOTHERAPY; CANCER-THERAPY; BORTEZOMIB; THALIDOMIDE AB Encouraging progress has been made in the treatment of patients with relapsed/refractory multiple myeloma (MM). The rapidly evolving understanding of key pathways responsible for tumor growth and survival has led to the development of novel agents (including immunomodulatory drugs, proteasome inhibitors, histone deacetylase inhibitors, and other targeted agents) with the potential to provide significant improvements in response and survival, and influence treatment guidelines. This review summarizes recent advances in understanding of the biology of relapsed/refractory MM and clinical trials with novel targeted agents that are currently under investigation for patients with this disease. C1 [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece. [San-Miguel, Jesus F.] Univ Hosp Salamanca, Salamanca, Spain. [Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dimopoulos, MA (reprint author), Univ Athens, Sch Med, Dept Clin Therapeut, Alexandra Hosp, 80 Vas Sofias, Athens 11528, Greece. EM mdimop@med.uoa.gr RI 2011, Secribsal/D-9425-2012; OI SAN MIGUEL, JESUS/0000-0002-9183-4857 NR 118 TC 36 Z9 38 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0902-4441 EI 1600-0609 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JAN PY 2011 VL 86 IS 1 BP 1 EP 15 DI 10.1111/j.1600-0609.2010.01542.x PG 15 WC Hematology SC Hematology GA 694ML UT WOS:000285302200001 PM 20942854 ER PT J AU Dimopoulos, MA Mateos, MV Richardson, PG Schlag, R Khuageva, NK Shpilberg, O Kropff, M Spicka, I Palumbo, A Wu, KL Esseltine, DL Liu, K Deraedt, W Cakana, A van de Velde, H San Miguel, JF AF Dimopoulos, Meletios A. Mateos, Maria-Victoria Richardson, Paul G. Schlag, Rudolf Khuageva, Nuriet K. Shpilberg, Ofer Kropff, Martin Spicka, Ivan Palumbo, Antonio Wu, Ka Lung Esseltine, Dixie-Lee Liu, Kevin Deraedt, William Cakana, Andrew van de Velde, Helgi San Miguel, Jesus F. TI Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE peripheral neuropathy; multiple myeloma; subanalysis; VISTA; phase 3; bortezomib ID THALIDOMIDE-DEXAMETHASONE; PLUS MELPHALAN; APEX TRIAL; INDUCTION; THERAPY; TRANSPLANTATION; MM AB Objectives: This subanalysis of the phase 3 VISTA trial aimed to assess the frequency, characteristics and reversibility of, and prognostic factors for, bortezomib-associated peripheral neuropathy (PN) in newly diagnosed patients with multiple myeloma ineligible for high-dose therapy who received bortezomib plus melphalan-prednisone. Methods: Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m2, days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, and days 1, 8, 22, 29, cycles 5-9; melphalan 9 mg/m2, days 1-4, cycles 1-9; and prednisone 60 mg/m2, days 1-4, cycles 1-9). Results: Overall, 47% of patients receiving VMP developed PN, including 19% grade 2 and 13% grade >= 3 (< 1% grade 4). The PN incidence was dose-related and reached a plateau at a cumulative bortezomib dose of approximately 45 mg/m2. Median time to PN onset was 2.3 months. Bortezomib-associated PN was reversible; 79% of events improved by at least one NCI CTCAE grade within a median of 1.9 months and 60% completely resolved within a median of 5.7 months, with reversibility similar in responding and non-responding patients. By multivariate analysis, baseline neuropathy was the only consistent risk factor for any PN [hazard ratio (HR) 1.785, P = 0.0065], grade >= 2 PN (HR 2.205, P = 0.0032), and grade >= 3 PN (HR 2.438, P = 0.023); age, pre-existing diabetes, International Staging System stage, obesity, and creatinine clearance did not affect the overall rate of PN. Conclusions: Rates of bortezomib-induced PN in the frontline setting were similar to those in relapsed patients and resolved in most cases. (Clinicaltrials.gov identifier: NCT00111319). C1 [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Athens 14565, Greece. [Mateos, Maria-Victoria; San Miguel, Jesus F.] IBMCC USAL CSIC, CIC, Hosp Univ Salamanca, Salamanca, Spain. [Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlag, Rudolf] Praxisklin Dr Schlag, Wurzburg, Germany. [Khuageva, Nuriet K.] SP Botkin Moscow City Clin Hosp, Moscow, Russia. [Shpilberg, Ofer] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, Martin] Univ Munster, Munster, Germany. [Spicka, Ivan] Univ Hosp, Prague, Czech Republic. [Palumbo, Antonio] Univ Turin, Turin, Italy. [Wu, Ka Lung] Belgian Hematol Soc, Myeloma Study Grp, Brussels, Belgium. [Esseltine, Dixie-Lee] Millennium Pharmaceut Inc, Cambridge, MA USA. [Liu, Kevin] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Deraedt, William; van de Velde, Helgi] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Cakana, Andrew] Johnson & Johnson Pharmaceut Res & Dev, High Wycombe, Bucks, England. RP Dimopoulos, MA (reprint author), Univ Athens, Sch Med, Athens 14565, Greece. EM mdimop@med.uoa.gr RI 2011, Secribsal/D-9425-2012; OI SAN MIGUEL, JESUS/0000-0002-9183-4857 FU Millennium Pharmaceuticals, Inc; Johnson & Johnson Pharmaceutical Research and Development L.L.C. FX The study was funded by Millennium Pharmaceuticals, Inc and Johnson & Johnson Pharmaceutical Research and Development L.L.C. NR 36 TC 43 Z9 46 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JAN PY 2011 VL 86 IS 1 BP 23 EP 31 DI 10.1111/j.1600-0609.2010.01533.x PG 9 WC Hematology SC Hematology GA 694ML UT WOS:000285302200003 PM 20874823 ER PT J AU Biswas, A Wilmanski, J Forsman, H Hrncir, T Hao, LM Tlaskalova-Hogenova, H Kobayashi, KS AF Biswas, Amlan Wilmanski, Jeanette Forsman, Huamei Hrncir, Tomas Hao, Liming Tlaskalova-Hogenova, Helena Kobayashi, Koichi S. TI Negative regulation of Toll-like receptor signaling plays an essential role in homeostasis of the intestine SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Caspase-1; Colitis; IL-10; IRAK-M; Microbiota ID INFLAMMATORY-BOWEL-DISEASE; INTERLEUKIN-1-BETA CONVERTING-ENZYME; KINASE IRAK FAMILY; T-CELLS; INTERLEUKIN-10-DEFICIENT MICE; CHRONIC ENTEROCOLITIS; BACTEROIDES-VULGATUS; COMMENSAL BACTERIA; ENTERIC BACTERIA; IMMUNE-RESPONSE AB A healthy intestinal tract is characterized by controlled homeostasis due to the balanced interaction between commensal bacteria and the host mucosal immune system. Human and animal model studies have supported the hypothesis that breakdown of this homeostasis may underlie the pathogenesis of inflammatory bowel diseases. However, it is not well understood how intestinal microflora stimulate the intestinal mucosal immune system and how such activation is regulated. Using a spontaneous, commensal bacteria-dependent colitis model in IL-10-deficient mice, we investigated the role of TLR and their negative regulation in intestinal homeostasis. In addition to IL-10(-/-)MyD88(-/-) mice, IL-10(-/-)TLR4(-/-) mice exhibited reduced colitis compared to IL-10(-/-) mice, indicating that TLR4 signaling plays an important role in inducing colitis. Interestingly, the expression of IRAK-M, a negative regulator of TLR signaling, is dependent on intestinal commensal flora, as IRAK-M expression was reduced in mice re-derived into a germ-free environment, and introduction of commensal bacteria into germ-free mice induced IRAK-M expression. IL-10(-/-)IRAK-M(-/-) mice exhibited exacerbated colitis with increased inflammatory cytokine gene expression. Therefore, this study indicates that intestinal microflora stimulate the colitogenic immune system through TLR and negative regulation of TLR signaling is essential in maintaining intestinal homeostasis. C1 [Biswas, Amlan; Wilmanski, Jeanette; Forsman, Huamei; Kobayashi, Koichi S.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Biswas, Amlan; Wilmanski, Jeanette; Forsman, Huamei; Kobayashi, Koichi S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Hrncir, Tomas; Tlaskalova-Hogenova, Helena] Acad Sci Czech Republic, Inst Microbiol, Dept Immunol & Gnotobiol, Prague, Czech Republic. [Hrncir, Tomas; Tlaskalova-Hogenova, Helena] Acad Sci Czech Republic, Inst Microbiol, Dept Immunol & Gnotobiol, Novy Hradek, Czech Republic. [Hao, Liming] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Tlaskalova-Hogenova, Helena] Charles Univ Prague, Inst Microbiol & Immunol, Fac Med 1, Prague, Czech Republic. RP Kobayashi, KS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dana 1420A,44 Binney St, Boston, MA 02115 USA. EM Koichi_Kobayashi@dfci.harvard.edu RI Hrncir, Tomas/H-6733-2014; Tlaskalova-Hogenova, Helena/J-8008-2014 FU NIH [R01DK074738, R03 TW 006833]; Czech Science Foundation [310/09/P182]; Cancer Research Institute; Claudia Adams Barr Award FX The authors thank Tanja Petnicki-Ocwieja, Torsten Meissner, Kyoung-Hee Lee for helpful discussions; Amelia Chen, Yuen-Joyce Liu, Amy Li for critical reading; and Norman Lautsch, Amelia Chen, Andrea Dearch for technical assistance. This work was supported by a grant from the NIH (R01DK074738, R03 TW 006833) to K. S. K. and by a grant from the Czech Science Foundation (310/09/P182) to T. H. K. S. K. is a recipient of the Investigator Award from the Cancer Research Institute and the Claudia Adams Barr Award. NR 54 TC 45 Z9 48 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2011 VL 41 IS 1 BP 182 EP 194 DI 10.1002/eji.201040479 PG 13 WC Immunology SC Immunology GA 702YY UT WOS:000285933000019 PM 21182089 ER PT J AU He, QH Wang, P Tian, N AF He, Quanhua Wang, Ping Tian, Ning TI Light-evoked synaptic activity of retinal ganglion and amacrine cells is regulated in developing mouse retina SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE GABAergic; glutamatergic; light deprivation; patch-clamp recording; synaptic current ID INNER PLEXIFORM LAYER; NMDA-RECEPTOR FUNCTION; D-ASPARTATE RECEPTORS; RAT RETINA; VISUAL EXPERIENCE; RABBIT RETINA; DEVELOPMENTAL EXPRESSION; PRESYNAPTIC INHIBITION; MAMMALIAN RETINA; DEPRIVED CATS AB Recent studies have shown a continued maturation of visual responsiveness and synaptic activity of retina after eye opening, including the size of receptive fields of retinal ganglion cells (RGCs), light-evoked synaptic output of RGCs, bipolar cell spontaneous synaptic inputs to RGCs, and the synaptic connections between RGCs and ON and OFF bipolar cells. Light deprivation retarded some of these age-dependent changes. However, many other functional and morphological features of RGCs are not sensitive to visual experience. To determine whether light-evoked synaptic responses of RGCs undergo developmental change, we directly examined the light-evoked synaptic inputs from ON and OFF synaptic pathways to RGCs in developing retinas, and found that both light-evoked excitatory and inhibitory synaptic currents decreased, but not increased, with age. We also examined the light-evoked synaptic inputs from ON and OFF synaptic pathways to amacrine cells in developing retinas and found that the light-evoked synaptic input of amacrine cells is also downregulated in developing mouse retina. Different from the developmental changes of RGC spontaneous synaptic activity, dark rearing has little effect on the developmental changes of light-evoked synaptic activity of both RGCs and amacrine cells. Therefore, we concluded that the synaptic mechanisms mediating spontaneous and light-evoked synaptic activity of RGCs and amacrine cells are likely to be different. C1 [Wang, Ping; Tian, Ning] Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA. [He, Quanhua] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [He, Quanhua] Harvard Univ, Sch Med, Boston, MA USA. RP Tian, N (reprint author), Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84132 USA. EM ning.tian@hsc.utah.edu FU NIH [R01EY012345, P30 EY000785]; Connecticut Lion; Eye Research Foundation FX This work was supported by NIH grants R01EY012345 and P30 EY000785, Research to Prevent Blindness (RPB) and Funds from the Connecticut Lion, Eye Research Foundation (N. Tian), Fight for Sight (Q. He). We wish to thank Ms Britta Ameel for grammar and editing assistance. NR 77 TC 15 Z9 15 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2011 VL 33 IS 1 BP 36 EP 48 DI 10.1111/j.1460-9568.2010.07484.x PG 13 WC Neurosciences SC Neurosciences & Neurology GA 702DZ UT WOS:000285876100004 PM 21091802 ER PT J AU Novakovic, V Sher, L Lapidus, KAB Mindes, J Golier, JA Yehuda, R AF Novakovic, Vladan Sher, Leo Lapidus, Kyle A. B. Mindes, Janet Golier, Julia A. Yehuda, Rachel TI Brain stimulation in posttraumatic stress disorder SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Review DE Brain stimulation; PTSD; ECT; TMS; depression; anxiety AB Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration. C1 [Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A. B.; Mindes, Janet; Golier, Julia A.; Yehuda, Rachel] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A. B.; Mindes, Janet; Golier, Julia A.; Yehuda, Rachel] James J Peters VA Med Ctr, Dept Psychiat, New York, NY 10468 USA. RP Novakovic, V (reprint author), James J Peters VA Med Ctr, Dept Psychiat, New York, NY 10468 USA. EM Vladan.Novakovic@va.gov NR 126 TC 7 Z9 7 U1 7 U2 21 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2011 VL 2 AR 5609 DI 10.3402/ejpt.v2i0.5609 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA V31EX UT WOS:000208868000002 ER PT J AU Oe, M Schnyder, U Schumacher, S Mueller-Pfeiffer, C Wilhelm, FH Martin-Soelch, C AF Oe, Misari Schnyder, Ulrich Schumacher, Sonja Mueller-Pfeiffer, Christoph Wilhelm, Frank H. Martin-Soelch, Chantal TI Lower Plasma DHEA Concentration in the Long-Term after Severe Accidental Injury SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Meeting Abstract C1 [Oe, Misari; Schnyder, Ulrich; Schumacher, Sonja; Mueller-Pfeiffer, Christoph; Martin-Soelch, Chantal] Univ Zurich Hosp, Zurich, Switzerland. [Mueller-Pfeiffer, Christoph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Wilhelm, Frank H.] Salzburg Univ, A-5020 Salzburg, Austria. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2011 VL 2 SU 1 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA V31EZ UT WOS:000208868200393 ER PT J AU Ruzek, JI Weingardt, K Kuhn, E Hoffman, JE AF Ruzek, Josef I. Weingardt, Ken Kuhn, Eric Hoffman, Julia E. TI Caring for Trauma Survivors in Large Health Care Systems: Towards Internet-Facilitated Treatment SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Meeting Abstract C1 [Ruzek, Josef I.; Kuhn, Eric] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Palo Alto, CA USA. [Weingardt, Ken] US Dept Vet Affairs, Vet Hlth Adm, Washington, DC USA. [Hoffman, Julia E.] Natl Ctr Telehlth & Technol, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2011 VL 2 SU 1 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA V31EZ UT WOS:000208868200011 ER PT J AU Al Jurdi, RK Gyulai, L Sajatovic, M Nguyen, CX AF Al Jurdi, R. K. Gyulai, L. Sajatovic, M. Nguyen, C. X. TI BIPOLAR DEPRESSION SYMPTOMS ACROSS THE LIFESPAN SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Al Jurdi, R. K.; Nguyen, C. X.] Michael E De Bakey VA Med Ctr, Houston, TX USA. [Al Jurdi, R. K.] Baylor Coll Med, Houston, TX 77030 USA. [Gyulai, L.] Univ Penn, Philadelphia, PA 19104 USA. [Sajatovic, M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. RI Sajatovic, Martha/I-8001-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2011 VL 26 SU 1 MA P01-189 PG 2 WC Psychiatry SC Psychiatry GA V27VS UT WOS:000208641300190 ER PT J AU Blum, K Stice, E Liu, Y Giordano, J Morse, S Bailey, JA Thompson, J Smolen, A Oscar-Berman, M Bowirrat, A Allen, C Manka, M Downs, BW Fonari, F Tan, J Damle, UJ Braverman, ER AF Blum, K. Stice, E. Liu, Y. Giordano, J. Morse, S. Bailey, J. A. Thompson, J. Smolen, A. Oscar-Berman, M. Bowirrat, A. Allen, C. Manka, M. Downs, B. W. Fonari, F. Tan, J. Damle, U. J. Braverman, E. R. TI GENETIC ADDICTION RISK SCORE ANALYSIS: HYPODOPAMINERGIC POLYMORPHIC RISK ALLELES IN POLYDRUG ADDICTED MALES AND MESO-LIMBIC DOPAMINERGIC AGONISTIC ACTIVATION BY NEUROADAPTAGEN AMINO-ACID THERAPY SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Blum, K.; Liu, Y.; Bailey, J. A.] Univ Florida, Dept Psychiat, Coll Med, McKnight Brain Inst, Gainesville, FL 32611 USA. [Blum, K.; Giordano, J.; Morse, S.] G&G Holist Addict Treatment Ctr, Dept Clin Rehabil, N Miami Beach, FL USA. [Blum, K.; Downs, B. W.] LifeGen Inc, Dept Nutrigen, San Diego, CA USA. [Blum, K.; Fonari, F.] Domin Diagnost, Kingston, RI USA. [Stice, E.] Oregon Res Inst, Eugene, OR 97403 USA. [Thompson, J.] Enhancement Solut & Technol, Orlando, FL USA. [Smolen, A.] Univ Colorado, Inst Behav Genet, Denver, CO 80202 USA. [Oscar-Berman, M.] Boston Univ, Dept Psychiat Anat & Neurobiol, Boston, MA 02215 USA. [Oscar-Berman, M.] Boston VA Healthcare Syst, Boston, MA USA. [Bowirrat, A.] Ziv Govt Med Ctr, Safed, Israel. [Allen, C.] Synapt Connect Res Inst, Charleston, SC USA. [Allen, C.] Welcome Home Vets, Charleston, SC USA. [Manka, M.] LifeStream Inc, Prescott, AZ USA. [Tan, J.] Chinese Acad Sci, Inst Automat, Med Image Proc Grp, Beijing, Peoples R China. [Damle, U. J.; Braverman, E. R.] PATH Fdn NY, New York, NY USA. [Braverman, E. R.] Weill Cornell Med Coll, Dept Neurosurg, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2011 VL 26 SU 1 MA P02-207 PG 1 WC Psychiatry SC Psychiatry GA V27VS UT WOS:000208641300798 ER PT J AU Gurrera, R Karel, M Azar, A Moye, J AF Gurrera, R. Karel, M. Azar, A. Moye, J. TI NEUROPSYCHOLOGICAL PERFORMANCE VARIABILITY IS ASSOCIATED WITH REDUCED TREATMENT CONSENT CAPACITY SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Gurrera, R.] VA Boston Healthcare Syst, Psychiat, Brockton, MA USA. [Karel, M.; Azar, A.; Moye, J.] VA Boston Healthcare Syst, Psychol, Brockton, MA USA. Harvard Univ, Sch Med, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2011 VL 26 SU 1 MA P02-240 PG 1 WC Psychiatry SC Psychiatry GA V27VS UT WOS:000208641300831 ER PT J AU Papakostas, G Shelton, R Zajecka, J Rickels, K Clain, A Baer, L Schoenfeld, D Nelson, E Barbee, J Lydiard, B Mischoulon, D Alpert, J Zisook, S Fava, M AF Papakostas, G. Shelton, R. Zajecka, J. Rickels, K. Clain, A. Baer, L. Schoenfeld, D. Nelson, E. Barbee, J. Lydiard, B. Mischoulon, D. Alpert, J. Zisook, S. Fava, M. TI L-METHYLFOLATE AUGMENTATION OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS) FOR MAJOR DEPRESSIVE DISORDER: RESULTS OF TWO RANDOMIZED, DOUBLE-BLIND TRIALS SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Papakostas, G.; Clain, A.; Baer, L.; Schoenfeld, D.; Mischoulon, D.; Alpert, J.; Fava, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Shelton, R.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Zajecka, J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Rickels, K.] Univ Penn, Philadelphia, PA 19104 USA. [Nelson, E.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. [Barbee, J.] Louisiana State Univ, Behav Sci Ctr, New Orleans, LA USA. [Lydiard, B.] SE Hlth Consultants, Charleston, SC USA. [Zisook, S.] Univ San Diego, VA Med Ctr, San Diego, CA 92110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2011 VL 26 SU 1 MA P01-588 PG 1 WC Psychiatry SC Psychiatry GA V27VS UT WOS:000208641300589 ER PT J AU Tapp, A Wood, AE Kennedy, A Sylvers, P AF Tapp, A. Wood, A. E. Kennedy, A. Sylvers, P. TI QUETIAPINE FOR THE TREATMENT OF COCAINE DEPENDENCE SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Tapp, A.; Wood, A. E.; Kennedy, A.; Sylvers, P.] VA Puget Sound Hlth Care Syst, Tacoma, WA USA. [Tapp, A.; Wood, A. E.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2011 VL 26 SU 1 MA P01-113 PG 1 WC Psychiatry SC Psychiatry GA V27VS UT WOS:000208641300114 ER PT J AU Karlo, C Leschka, S Goetti, RP Feuchtner, G Desbiolles, L Stolzmann, P Plass, A Falk, V Marincek, B Alkadhi, H Baumuller, S AF Karlo, Christoph Leschka, Sebastian Goetti, Robert Paul Feuchtner, Gudrun Desbiolles, Lotus Stolzmann, Paul Plass, Andre Falk, Volkmar Marincek, Borut Alkadhi, Hatem Baumueller, Stephan TI High-pitch dual-source CT angiography of the aortic valve-aortic root complex without ECG-synchronization SO EUROPEAN RADIOLOGY LA English DT Article DE Dual-source computed tomography; DSCT; High pitch; Radiation dose; Aortic valve ID MULTIDETECTOR ROW CT; ACUTE CHEST-PAIN; COMPUTED-TOMOGRAPHY; CORONARY-ANGIOGRAPHY; THORACIC AORTA; IMAGE QUALITY; REDUCTION; EXPOSURE AB To compare image quality and radiation dose of high-pitch computed tomography angiography(CTA) of the aortic valve-aortic root complex with and without prospective ECG-gating compared to a retrospectively ECG-gated standard-pitch acquisition. 120 patients(mean age 68 +/- 13 years) were examined using a 128-slice dual-source CT system using prospectively ECG-gated high-pitch(group A; n = 40), non-ECG-gated high-pitch(group B; n = 40) or retrospectively ECG-gated standard-pitch(C; n = 40) acquisition techniques. Image quality of the aortic root, valve and ascending aorta including the coronary ostia was assessed by two independent readers. Image noise was measured, radiation dose estimates were calculated. Interobserver agreement was good(kappa = 0.64-0.78). Image quality was diagnostic in 38/40 patients(group A), 37/40(B) and 38/40(C) with no significant difference in number of patients with diagnostic image quality among all groups (p = 0.56). Significantly more patients showed excellent image quality in group A compared to groups B and C(each, p < 0.01). Average image noise was significantly different between all groups(p < 0.05). Mean radiation dose estimates in groups A and B(each; 2.4 +/- 0.3 mSv) were significantly lower compared to group C(17.5 +/- 4.4 mSv; p < 0.01). High-pitch dual-source CTA provides diagnostic image quality of the aortic valve-aortic root complex even without ECG-gating at 86% less radiation dose when compared to a standard-pitch ECG-gated acquisition. C1 [Karlo, Christoph; Leschka, Sebastian; Goetti, Robert Paul; Feuchtner, Gudrun; Desbiolles, Lotus; Stolzmann, Paul; Marincek, Borut; Alkadhi, Hatem; Baumueller, Stephan] Univ Zurich Hosp, Inst Diagnost & Intervent Radiol, CH-8091 Zurich, Switzerland. [Plass, Andre; Falk, Volkmar] Univ Zurich Hosp, Cardiovasc Surg Clin, CH-8091 Zurich, Switzerland. [Alkadhi, Hatem] Massachusetts Gen Hosp, Cardiac MR PET CT Grp, Boston, MA 02114 USA. [Alkadhi, Hatem] Harvard Univ, Sch Med, Boston, MA USA. RP Karlo, C (reprint author), Univ Zurich Hosp, Inst Diagnost & Intervent Radiol, Ramistr 100, CH-8091 Zurich, Switzerland. EM christoph.karlo@usz.ch RI Goetti, Robert/I-8961-2012 NR 22 TC 39 Z9 45 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD JAN PY 2011 VL 21 IS 1 BP 205 EP 212 DI 10.1007/s00330-010-1907-3 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 689AO UT WOS:000284899700027 PM 20677006 ER PT J AU Cadranel, J Zalcman, G Sequist, L AF Cadranel, J. Zalcman, G. Sequist, L. TI Genetic profiling and epidermal growth factor receptor-directed therapy in nonsmall cell lung cancer SO EUROPEAN RESPIRATORY JOURNAL LA English DT Review DE Biomarker; epidermal growth factor receptor; epidermal growth factor receptor inhibitors; genetic profiling; mutational testing; nonsmall cell lung cancer ID PHASE-III TRIAL; PREVIOUSLY TREATED PATIENTS; TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; EGFR MUTATIONS; GEFITINIB SENSITIVITY; MOLECULAR PREDICTORS; 1ST-LINE THERAPY; COPY NUMBER; ACTIVATING MUTATIONS AB The principle of preferentially selecting patients most likely to benefit from therapy according to their genetic profile has led to substantial clinical benefit in some tumour types, and has potential to considerably refine treatment in advanced nonsmall cell lung cancer (NSCLC). Effective, reliable use of molecular biomarkers to inform clinical practice requires the standardisation of testing methods and careful assessment of biomarkers' predictive and prognostic value. Although a number of studies have shown that patients with activating mutations in exons 18-21 of the epidermal growth factor receptor (EGFR) gene respond particularly well to gefitinib and erlotinib, a prospective, randomised study was needed to differentiate between the prognostic and predictive value of EGFR mutations. From one such study, it appeared that mutational testing should become standard at diagnosis, at least for adenocarcinoma patients with a never or low smoking history, as clinical predictors are insufficient to optimise treatment. However, outstanding questions remain: what are the treatment options for patients with tumours resistant to erlotinib/gefitinib? What conclusions about treatment can we draw from EGFR copy number or KRAS mutation status? What role should anti-EGFR antibodies play in NSCLC treatment, and in which patients? This review considers current evidence linking biomarker profile to efficacy of EGFR-targeted therapy in NSCLC, and clinical implications of recent findings. C1 [Cadranel, J.] Univ Paris 06, Hop Tenon, AP HP, Serv Pneumol, F-75970 Paris, France. [Zalcman, G.] Univ Caen Basse Normandie, CHU Caen, Serv Pneumol, Caen, France. [Sequist, L.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Cadranel, J (reprint author), Univ Paris 06, Hop Tenon, AP HP, Serv Pneumol, 4 Rue Chine, F-75970 Paris, France. EM jacques.cadranel@tnn.aphp.fr RI ZALCMAN, Gerard/L-7809-2015; Mendez, Pedro /J-8955-2016 OI ZALCMAN, Gerard/0000-0002-0343-9575; Mendez, Pedro /0000-0001-6713-7907 FU Boehringer Ingelheim FX Boehringer Ingelheim provided financial support for the assistance of Ogilvy Healthworld Medical Education. NR 96 TC 19 Z9 19 U1 0 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 EI 1399-3003 J9 EUR RESPIR J JI Eur. Resp. J. PD JAN PY 2011 VL 37 IS 1 BP 183 EP 193 DI 10.1183/09031936.00179409 PG 11 WC Respiratory System SC Respiratory System GA 700OB UT WOS:000285752400027 PM 21030453 ER PT S AU Cooper, RA Cooper, R Srinivasa, S Xu, JJ Wang, HW Grindle, G Salatin, B Chung, CS Kelleher, A Vazquez, J AF Cooper, Rory A. Cooper, Rosemarie Srinivasa, Siddhartha Xu, Jijie Wang, Hongwu Grindle, Garrett Salatin, Ben Chung, Chengshiu Kelleher, Annmarie Vazquez, Juan BE Gelderblom, GJ Soede, M Adriaens, L Miesenberger, K TI Quality of Life Technology Robots (QoLTbots): Towards Providing Assistance in the Home and Community for People with Disabilities and Older Adults SO EVERYDAY TECHNOLOGY FOR INDEPENDENCE AND CARE SE Assistive Technology Research Series LA English DT Proceedings Paper CT 11th Bi-Annual AAATE Conference CY AUG 31-SEP 02, 2011 CL Maastricht, NETHERLANDS SP Assoc Advancement Assist Technol Europe DE Assistive robots; QolTbots; robot; rehabilitation; acceptance; design ID ASSISTIVE TECHNOLOGY; WHEELCHAIR; USERS AB There is increasing progress towards robotic devices that will provide beneficial assistance to people with disabilities and older adults in the home. In recent years, there has been a break from the traditional robotics approach of creating autonomous robotic systems and tele-operated robots, towards symbiotic robotic systems that work in partnership with and incorporate the strengths and capabilities of humans and robots working collaboratively, and in many cases intimately together. This has resulted in a new class of assistive robots termed Quality of Life Technology Robots or QoLTbots. This paper describes work on two QoLTbots with different structures, yet they share many core technologies. The ultimate goal of these QoLTbots is to create a framework and actual demonstration units (i.e., testbeds) to demonstrate the ability to assist people with disabilities and older adults in meaningful ways, and to study their acceptance of QoLTbots. C1 [Cooper, Rory A.; Cooper, Rosemarie; Xu, Jijie; Wang, Hongwu; Grindle, Garrett; Salatin, Ben; Chung, Chengshiu; Kelleher, Annmarie; Vazquez, Juan] US Dept Vet Affairs, Human Engn Res Labs, Rehabil Res & Dev Serv, Washington, DC USA. [Cooper, Rory A.; Cooper, Rosemarie; Xu, Jijie; Wang, Hongwu; Grindle, Garrett; Salatin, Ben; Chung, Chengshiu; Kelleher, Annmarie; Vazquez, Juan] Univ Pittsburgh, Dept Rehabil Sci & Technol, 5044 Forbes Tower, Pittsburgh, PA 15260 USA. [Srinivasa, Siddhartha] Intel Res Labs, Pittsburgh, PA USA. [Cooper, Rory A.; Cooper, Rosemarie; Srinivasa, Siddhartha; Xu, Jijie; Wang, Hongwu; Grindle, Garrett; Salatin, Ben; Chung, Chengshiu; Kelleher, Annmarie; Vazquez, Juan] Univ Pittsburgh, Qual Life Technol Ctr, Pittsburgh, PA 15260 USA. [Cooper, Rory A.; Cooper, Rosemarie; Srinivasa, Siddhartha; Xu, Jijie; Wang, Hongwu; Grindle, Garrett; Salatin, Ben; Chung, Chengshiu; Kelleher, Annmarie; Vazquez, Juan] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, 5044 Forbes Tower, Pittsburgh, PA 15260 USA. EM rcooper@pitt.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1383-813X BN 978-1-60750-814-4; 978-1-60750-813-7 J9 ASSIST TECHNOL RES S PY 2011 VL 29 BP 550 EP 556 DI 10.3233/978-1-60750-814-4-550 PG 7 WC Rehabilitation SC Rehabilitation GA BG9NW UT WOS:000393465400071 ER PT J AU Langevin, HM Wayne, PM MacPherson, H Schnyer, R Milley, RM Napadow, V Lao, LX Park, J Harris, RE Cohen, M Sherman, KJ Haramati, A Hammerschlag, R AF Langevin, Helene M. Wayne, Peter M. MacPherson, Hugh Schnyer, Rosa Milley, Ryan M. Napadow, Vitaly Lao, Lixing Park, Jongbae Harris, Richard E. Cohen, Misha Sherman, Karen J. Haramati, Aviad Hammerschlag, Richard TI Paradoxes in Acupuncture Research: Strategies for Moving Forward SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Review ID LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIAL; TRADITIONAL-CHINESE-MEDICINE; COMPLEX INTERVENTIONS; CLINICAL-TRIALS; CARDIOVASCULAR-RESPONSES; ALTERNATIVE MEDICINE; PLACEBO TREATMENTS; HEALING INTENTION; BLOOD-FLOW AB In November 2007, the Society for Acupuncture Research (SAR) held an international symposium to mark the 10th anniversary of the 1997 NIH Consensus Development Conference on Acupuncture. The symposium presentations revealed the considerable maturation of the field of acupuncture research, yet two provocative paradoxes emerged. First, a number of well-designed clinical trials have reported that true acupuncture is superior to usual care, but does not significantly outperform sham acupuncture, findings apparently at odds with traditional theories regarding acupuncture point specificity. Second, although many studies using animal and human experimental models have reported physiological effects that vary as a function of needling parameters (e. g., mode of stimulation) the extent to which these parameters influence therapeutic outcomes in clinical trials is unclear. This White Paper, collaboratively written by the SAR Board of Directors, identifies gaps in knowledge underlying the paradoxes and proposes strategies for their resolution through translational research. We recommend that acupuncture treatments should be studied (1) "top down" as multi-component " whole-system" interventions and (2) " bottom up" as mechanistic studies that focus on understanding how individual treatment components interact and translate into clinical and physiological outcomes. Such a strategy, incorporating considerations of efficacy, effectiveness and qualitative measures, will strengthen the evidence base for such complex interventions as acupuncture. C1 [Langevin, Helene M.] Univ Vermont, Dept Neurol, Burlington, VT 05405 USA. [Wayne, Peter M.] Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, Boston, MA 02215 USA. [MacPherson, Hugh] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Schnyer, Rosa] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Milley, Ryan M.; Hammerschlag, Richard] Oregon Coll Oriental Med, Dept Res, Portland, OR 97216 USA. [Napadow, Vitaly] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Lao, Lixing] Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21207 USA. [Park, Jongbae] Univ N Carolina, Chapel Hill, NC 27599 USA. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48106 USA. [Cohen, Misha] Chicken Soup Chinese Med, San Francisco, CA 94103 USA. [Sherman, Karen J.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Haramati, Aviad] Georgetown Univ, Med Ctr, Dept Phys & Biophys, Washington, DC 20057 USA. RP Langevin, HM (reprint author), Univ Vermont, Dept Neurol, Burlington, VT 05405 USA. EM helene.langevin@uvm.edu RI Harris, Richard/F-1307-2011; OI Cohen, Misha/0000-0001-6362-6148; MacPherson, Hugh/0000-0003-4255-4768; Lao, Lixing/0000-0003-0198-9714 NR 59 TC 73 Z9 75 U1 3 U2 32 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2011 AR 180805 DI 10.1155/2011/180805 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 799RE UT WOS:000293303000001 ER PT B AU Kim, JY Van Cott, EM Lewandrowski, KB AF Kim, Ji Yeon Van Cott, Elizabeth M. Lewandrowski, Kent B. BE Marchevsky, AM Wick, MR TI The Use of Decision Analysis Tools for the Selection of Clinical Laboratory Tests: Developing Diagnostic and Forecasting Models Using Laboratory Evidence SO EVIDENCE BASED PATHOLOGY AND LABORATORY MEDICINE LA English DT Article; Book Chapter DE Decision support; Medical order entry systems; Laboratory utilization; Evidence-based medicine ID ACUTE MYOCARDIAL-INFARCTION; BRAIN NATRIURETIC PEPTIDE; EVIDENCE-BASED MEDICINE; CLOSED MALPRACTICE CLAIMS; HIGH-SENSITIVITY TROPONIN; HOSPITALIZED-PATIENTS; EMERGENCY-DEPARTMENT; REGIONAL-VARIATIONS; HEALTH INFORMATION; COMPUTER-PROGRAMS C1 [Kim, Ji Yeon; Van Cott, Elizabeth M.; Lewandrowski, Kent B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lewandrowski, Kent B.] Harvard Univ, Gray Chem Massachusetts Gen Hosp 5 536, Sch Med, Boston, MA 02114 USA. [Kim, Ji Yeon; Van Cott, Elizabeth M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM Klewandrowski@partners.org NR 83 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1029-5 PY 2011 BP 305 EP 322 DI 10.1007/978-1-4419-1030-1_18 D2 10.1007/978-1-4419-1030-1 PG 18 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA BVX78 UT WOS:000293097100018 ER PT B AU Melanson, SEF Morrison, AP Bates, DW Tanasijevic, MJ AF Melanson, Stacy E. F. Morrison, Aileen P. Bates, David W. Tanasijevic, Milenko J. BE Marchevsky, AM Wick, MR TI Implementation and Benefits of Computerized Physician Order Entry and Evidence-Based Clinical Decision Support Systems SO EVIDENCE BASED PATHOLOGY AND LABORATORY MEDICINE LA English DT Article; Book Chapter DE Evidence-based clinical decision support systems; Computerized physician order entry; Evidence-based medicine; Clinical decision support systems ID RANDOMIZED CONTROLLED-TRIAL; DIAGNOSTIC-TESTS; LABORATORY TESTS; ALERTING SYSTEM; CRITICAL-VALUES; APPROPRIATENESS; ERRORS; INTERVENTION; NOTIFICATION; INPATIENTS C1 [Tanasijevic, Milenko J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tanasijevic, Milenko J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Melanson, Stacy E. F.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Healthcare Ctr Lab, Sch Med, Boston, MA 02115 USA. [Morrison, Aileen P.] Brigham & Womens Hosp, Dept Pathol, Div Clin Labs, Boston, MA 02115 USA. [Bates, David W.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Bates, David W.] Partners HealthCare Syst Inc, Clin & Qual Anal, Boston, MA USA. [Bates, David W.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Tanasijevic, MJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM mtanasijevic@partners.org NR 43 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1029-5 PY 2011 BP 323 EP 335 DI 10.1007/978-1-4419-1030-1_19 D2 10.1007/978-1-4419-1030-1 PG 13 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA BVX78 UT WOS:000293097100019 ER PT B AU Viser, AS Reinold, MM Rodenhi, KJ Gill, TJ AF Viser, Anne S. Reinold, Michael M. Rodenhi, Kyle J. Gill, Thomas J. BE Wilson, F Gormley, J Hussey, J TI The Shoulder Complex SO EXERCISE THERAPY IN THE MANAGEMENT OF MUSCULOSKELETAL DISORDERS LA English DT Article; Book Chapter ID PROFESSIONAL BASEBALL PITCHERS; ELECTROMYOGRAPHIC ANALYSIS; MUSCLE-ACTIVITY; REHABILITATION EXERCISES; GLENOHUMERAL JOINT; THROWING ATHLETE; IMPINGEMENT SYNDROME; CLINICAL-TRIAL; LITTLE-LEAGUE; EMG ANALYSIS C1 [Viser, Anne S.; Rodenhi, Kyle J.] Massachusetts Gen Hosp, Sports Phys Therapy, Boston, MA 02114 USA. [Reinold, Michael M.; Gill, Thomas J.] Boston Red Sox Baseball Club, Boston, MA USA. [Reinold, Michael M.] Massachusetts Gen Hosp, Dept Orthoped Surg, Div Sports Med, Rehabil Res & Educ, Boston, MA 02114 USA. [Gill, Thomas J.] Massachusetts Gen Hosp, Sports Med Serv, Boston, MA 02114 USA. [Gill, Thomas J.] Harvard Univ, Sch Med, Orthoped Surg, Boston, MA USA. RP Viser, AS (reprint author), Massachusetts Gen Hosp, Sports Phys Therapy, Boston, MA 02114 USA. NR 62 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-78862-2; 978-1-4051-6938-7 PY 2011 BP 94 EP 112 D2 10.1002/9781118788622 PG 19 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA BE2JH UT WOS:000369407100008 ER PT J AU Sims, RC Whitfield, KE Ayotte, BJ Gamaldo, AA Edwards, CL Allaire, JC AF Sims, Regina C. Whitfield, Keith E. Ayotte, Brian J. Gamaldo, Alyssa A. Edwards, Christopher L. Allaire, Jason C. TI SUBJECTIVE MEMORY IN OLDER AFRICAN AMERICANS SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID SELF-REPORTED MEMORY; WHITE COMMUNITY RESIDENTS; DEPRESSIVE SYMPTOMS; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; ELDERLY PERSONS; TEST-PERFORMANCE; COMPLAINTS; IMPAIRMENT; DEMENTIA AB The current analysis examined (a) if measures of psychological well-being predict subjective memory, and (b) if subjective memory is consistent with actual memory. Five hundred seventy-nine older African Americans from the Baltimore Study of Black Aging completed measures assessing subjective memory, depressive symptomatology, perceived stress, locus of control, and verbal and working memory. Higher levels of perceived stress and greater externalized locus of control predicted poorer subjective memory, but subjective memory did not predict objective verbal or working memory. Results suggest that subjective memory is influenced by aspects of psychological well-being but is unrelated to objective memory in older African Americans. C1 [Sims, Regina C.] Howard Univ, Dept Psychol, Washington, DC 20059 USA. [Whitfield, Keith E.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Ayotte, Brian J.] VA Boston Healthcare Syst, Boston, MA USA. [Gamaldo, Alyssa A.; Allaire, Jason C.] N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA. [Edwards, Christopher L.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. RP Sims, RC (reprint author), Howard Univ, Dept Psychol, 525 Bryant St NW,CB Powell Bldg, Washington, DC 20059 USA. EM regina.sims@howard.edu FU National Institute on Aging [R01 AG24108, AG024108-02S1, R01AG24108-S4, T32 AG00029] FX The Baltimore Study of Black Aging is supported by grants from the National Institute on Aging (R01 AG24108; Minority Supplement AG024108-02S1; R01AG24108-S4) to K. E. W. Additional support is provided to the first author by a grant from the National Institute on Aging (T32 AG00029). The authors would like to thank Alana Bennett, Otis Best, Haolan Cai, Andrea Darby, Janet Downing, and Jeannine Skinner for their assistance in the data collection and entry. NR 59 TC 6 Z9 6 U1 2 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PY 2011 VL 37 IS 2 BP 220 EP 240 DI 10.1080/0361073X.2011.555640 PG 21 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 736ZJ UT WOS:000288533700005 PM 21424958 ER PT J AU Goral, M Clark-Cotton, M Spiro, A AF Goral, Mira Clark-Cotton, Manuella Spiro, Avron, III TI THE CONTRIBUTION OF SET SWITCHING AND WORKING MEMORY TO SENTENCE PROCESSING IN OLDER ADULTS SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID INDIVIDUAL-DIFFERENCES; AGE-DIFFERENCES; LANGUAGE COMPREHENSION; GENDER-DIFFERENCES; INTERFERENCE; CAPACITY; PERFORMANCE; INHIBITION; SPEECH; YOUNG AB This study evaluates the involvement of switching skills and working-memory capacity in auditory sentence processing in older adults. The authors examined 241 healthy participants, aged 55 to 88 years, who completed four neuropsychological tasks and two sentence-processing tasks. In addition to age and the expected contribution of working memory, switching ability, as measured by the number of perseverative errors on the Wisconsin Card Sorting Test, emerged as a strong predictor of performance on both sentence-processing tasks. Individuals with both low working-memory spans and more perseverative errors achieved the lowest accuracy scores. These findings are consistent with compensatory accounts of successful performance in older age. C1 [Goral, Mira] CUNY, Dept Speech Language Hearing Sci, Lehman Coll, Bronx, NY 10468 USA. [Goral, Mira] CUNY, Grad Sch, Bronx, NY 10468 USA. [Goral, Mira] CUNY, Univ Ctr, Bronx, NY 10468 USA. [Goral, Mira] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Clark-Cotton, Manuella] Boston Univ, Sch Med, Dept Rheumatol, Boston, MA 02118 USA. [Spiro, Avron, III] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Boston, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Goral, M (reprint author), CUNY, Dept Speech Language Hearing Sci, Lehman Coll, 250 Bedford Pk Blvd, Bronx, NY 10468 USA. EM mira.goral@lehman.cuny.edu OI Spiro III, Avron/0000-0003-4080-8621 FU Clinical Science Research and Development Service, US Department of Veterans Affairs; National Institute on Aging [AG14345, AG 027532] FX This project was supported in part by the Clinical Science Research and Development Service, US Department of Veterans Affairs, by grants AG14345 (PI: Martin L. Albert) and AG 027532 (PI: Mira Goral) from the National Institute on Aging, and by Merit Reviews to Christopher Brady and Avron Spiro by the Clinical Science Research and Development Service, US Department of Veterans Affairs. The authors thank Christopher Brady, Rebecca Williams, Elaine Dibbs, Jordan Awerbach, Becky Brown, Jason Cohen, Josh Berger, and Keely Sayers for their contributions to this project. The authors also thank all the participants. The authors thank Jeffrey Elias and two anonymous reviewers for their comments on earlier versions of the manuscript. NR 61 TC 8 Z9 9 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PY 2011 VL 37 IS 5 BP 516 EP 538 DI 10.1080/0361073X.2011.619858 PG 23 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 855SE UT WOS:000297583900003 PM 22091580 ER PT J AU Bikle, DD AF Bikle, Daniel D. TI Vitamin D: an ancient hormone SO EXPERIMENTAL DERMATOLOGY LA English DT Editorial Material DE animals; calcium; evolution; exoskeleton; plankton; plants; vitamin D ID CALCIUM-SENSING RECEPTOR; CRUSTACEAN ORCHESTIA-CAVIMANA; HUMAN EPIDERMAL-KERATINOCYTES; BREAM SPARUS-AURATUS; CELL-CELL ADHESION; D-BINDING PROTEIN; NF-KAPPA-B; E-CADHERIN; EXTRACELLULAR CALCIUM; 1,25-DIHYDROXYVITAMIN D-3 AB Vitamin D has been produced by plants and animals almost from the time life began. The ability to transport and metabolize vitamin D to more active forms evolved as the structures of plants and animals became more complex, and the cells within these organisms took on more specialized functions. In higher-order animals, the vitamin D receptor (VDR) is found in nearly every cell, and the ability of the cell to produce the active hormone, 1,25(OH)(2)D, is also widely distributed. Furthermore, the physiological functions with which vitamin D signalling is now associated are as diverse as the tissues in which the VDR is located. Why is this, and is there a common theme? This viewpoint article argues that there is. All cells maintain a fairly constant and submicromolar concentration of free calcium. Calcium is an important regulator of many processes within the cell. The ebb and flow of calcium within cells is controlled by calcium pumps, antiporters and channels. Animals with calcified exo- or endoskeletons have an additional need for calcium, a need that changes during the life cycle of the organism. In this article, I make the case that vitamin D signalling evolved to enable the organism to effectively regulate calcium flux, storage and signalling and that such regulation is critical for the evolutionary process. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Bikle, DD (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. EM daniel.bikle@ucsf.edu FU BLRD VA [I01 BX001066]; NIAMS NIH HHS [R01 AR050023] NR 88 TC 49 Z9 50 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD JAN PY 2011 VL 20 IS 1 BP 7 EP 13 DI 10.1111/j.1600-0625.2010.01202.x PG 7 WC Dermatology SC Dermatology GA 695QY UT WOS:000285388900002 PM 21197695 ER PT J AU Dirice, E Kahraman, S Elpek, GO Aydin, C Balci, MK Omer, A Sanlioglu, S Sanlioglu, AD AF Dirice, Ercument Kahraman, Sevim Elpek, Gulsum Ozlem Aydin, Cigdem Balci, Mustafa Kemal Omer, Abdulkadir Sanlioglu, Salih Sanlioglu, Ahter Dilsad TI TRAIL and DcR1 Expressions Are Differentially Regulated in the Pancreatic Islets of STZ- versus CY-Applied NOD Mice SO EXPERIMENTAL DIABETES RESEARCH LA English DT Article ID APOPTOSIS-INDUCING LIGAND; DEATH RECEPTOR; CELL-DEATH; DIABETES-MELLITUS; DNA-DAMAGE; T-CELLS; STREPTOZOTOCIN; MOUSE; CYCLOPHOSPHAMIDE; KILLER/DR5 AB TNF-related apoptosis-inducing ligand (TRAIL) is an important component of the immune system. Although it is well acknowledged that it also has an important role in Type 1 Diabetes (T1D) development, this presumed role has not yet been clearly revealed. Streptozotocin (STZ) and Cyclophosphamide (CY) are frequently used agents for establishment or acceleration of T1D disease in experimental models, including the non-obese diabetic (NOD) mice. Although such disease models are very suitable for diabetes research, different expression patterns for various T1D-related molecules may be expected, depending on the action mechanism of the applied agent. We accelerated diabetes in female NOD mice using STZ or CY and analyzed the expression profiles of TRAIL ligand and receptors throughout disease development. TRAIL ligand expression followed a completely different pattern in STZ-versus CY-accelerated disease, displaying a prominent increase in the former, while appearing at reduced levels in the latter. Decoy receptor 1 (DcR1) expression also increased significantly in the pancreatic islets in STZ-induced disease. Specific increases observed in TRAIL ligand and DcR1 expressions may be part of a defensive strategy of the beta islets against the infiltrating leukocytes, while the immune-suppressive agent CY may partly hold down this defense, contributing further to diabetes development. C1 [Dirice, Ercument; Kahraman, Sevim; Aydin, Cigdem; Sanlioglu, Salih; Sanlioglu, Ahter Dilsad] Akdeniz Univ Hosp & Clin, Human Gene & Cell Therapy Ctr, TR-07058 Antalya, Turkey. [Dirice, Ercument] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Med, Boston, MA 02215 USA. [Kahraman, Sevim; Aydin, Cigdem; Sanlioglu, Salih; Sanlioglu, Ahter Dilsad] Akdeniz Univ, Fac Med, Dept Med Biol & Genet, TR-07058 Antalya, Turkey. [Elpek, Gulsum Ozlem] Akdeniz Univ, Fac Med, Dept Pathol, TR-07058 Antalya, Turkey. [Balci, Mustafa Kemal] Akdeniz Univ, Fac Med, Div Endocrinol & Metab Dis, TR-07058 Antalya, Turkey. [Omer, Abdulkadir] Univ Massachusetts, Dept Med, Div Endocrinol & Diabet, Worcester, MA 01545 USA. RP Sanlioglu, AD (reprint author), Akdeniz Univ Hosp & Clin, Human Gene & Cell Therapy Ctr, TR-07058 Antalya, Turkey. EM ahter@akdeniz.edu.tr RI BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Ahter/C-6504-2016; Sanlioglu, Salih/F-9305-2016; Dirice, Ercument/B-2825-2017; OI BALCI, Mustafa Kemal/0000-0002-6494-3249; Sanlioglu, Ahter/0000-0003-4504-0375; Kahraman, Sevim/0000-0002-2880-6589 FU Scientific and Technological Research Council of Turkey (TUBITAK); Akdeniz University Scientific Research Administration Division; [SBAG 107S374] FX This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK), by the project no. SBAG 107S374, and by Akdeniz University Scientific Research Administration Division. E. Dirice and S. Kahraman equally contributed to this paper. NR 29 TC 6 Z9 6 U1 0 U2 7 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-5214 J9 EXP DIABETES RES JI Exp. Diabetes Res. PY 2011 AR 625813 DI 10.1155/2011/625813 PG 11 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA 870PZ UT WOS:000298682700001 ER PT J AU McKiernan, SH Colman, RJ Lopez, M Beasley, TM Aiken, JM Anderson, RM Weindruch, R AF McKiernan, Susan H. Colman, Ricki J. Lopez, Marisol Beasley, T. Mark Aiken, Judd M. Anderson, Rozalyn M. Weindruch, Richard TI Caloric restriction delays aging-induced cellular phenotypes in rhesus monkey skeletal muscle SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Sarcopenia; Calorie restriction; Rhesus monkey ID DNA DELETION MUTATIONS; DIETARY RESTRICTION; PHYSICAL-ACTIVITY; CAUSAL ROLE; SARCOPENIA; ATROPHY; FIBERS; MASS; ABNORMALITIES; APOPTOSIS AB Sarcopenia is the age-related loss of skeletal muscle mass and function and is characterized by a reduction in muscle mass and fiber cross-sectional area, alterations in muscle fiber type and mitochondrial functional changes. In rhesus monkeys, calorie restriction (CR) without malnutrition improves survival and delays the onset of age-associated diseases and disorders including sarcopenia. We present a longitudinal study on the impact of CR on early stage sarcopenia in the upper leg of monkeys from similar to 16 years to similar to 22 years of age. Using dual-energy X-ray absorptiometry we show that CR delayed the development of maximum muscle mass and, unlike Control animals, muscle mass of the upper leg was preserved in CR animals during early phase sarcopenia. Histochemical analyses of vastus lateralis muscle biopsies revealed that CR opposed age-related changes in the proportion of Type II muscle fibers and fiber cross-sectional area. In contrast the number of muscle fibers with mitochondrial electron transport system enzyme abnormalities (ETS(ab)) was not significantly affected by CR. Laser capture microdissection of ETS(ab) fibers and subsequent PCR analysis of the mitochondria! DNA revealed large deletion mutations in fibers with abnormal mitochondrial enzyme activities. CR did not prevent stochastic mitochondrial deletion mutations in muscle fibers but CR may have contributed to the maintenance of affected fibers. (c) 2010 Elsevier Inc. All rights reserved. C1 [McKiernan, Susan H.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. [McKiernan, Susan H.; Colman, Ricki J.; Lopez, Marisol] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. [Lopez, Marisol; Aiken, Judd M.] Univ Wisconsin, Dept Comparat Biosci, Madison, WI 53706 USA. [Beasley, T. Mark] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Aiken, Judd M.] Univ Alberta, Dept Agr Food & Nutr Sci, Edmonton, AB T6G 2M8, Canada. [Anderson, Rozalyn M.; Weindruch, Richard] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Anderson, Rozalyn M.; Weindruch, Richard] Univ Wisconsin, William S Middleton Mem Vet Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. RP McKiernan, SH (reprint author), Univ Wisconsin, Dept Kinesiol, 2000 Observ Dr, Madison, WI 53706 USA. EM shmckier@wisc.edu FU NIH [P01 AG-11915, P51 RR000167]; Ellison Medical Foundation; Research Facilities Improvement Program [RR15459-01, RR020141-01] FX We acknowledge the efforts of the veterinary staff of the Wisconsin National Primate Research Center. This work was supported by NIH grants P01 AG-11915; P51 RR000167 and the Ellison Medical Foundation Senior Scholar Award (Judd Aiken). This research was conducted in part at a facility constructed with support from the Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. NR 37 TC 30 Z9 30 U1 0 U2 30 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JAN PY 2011 VL 46 IS 1 BP 23 EP 29 DI 10.1016/j.exger.2010.09.011 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 710UP UT WOS:000286542800004 PM 20883771 ER PT S AU Barnes, JL Glass, WF AF Barnes, Jeffrey L. Glass, William F., II BE Herrera, GA TI Renal Interstitial Fibrosis: A Critical Evaluation of the Origin of Myofibroblasts SO EXPERIMENTAL MODELS FOR RENAL DISEASES: PATHOGENESIS AND DIAGNOSIS SE Contributions to Nephrology LA English DT Article; Book Chapter ID TO-MESENCHYMAL TRANSITION; UNILATERAL URETERAL OBSTRUCTION; POLYCYSTIC KIDNEY-DISEASE; SPONTANEOUSLY HYPERTENSIVE-RATS; CHRONIC ALLOGRAFT-NEPHROPATHY; TUBULAR EPITHELIAL-CELLS; RENIN-ANGIOTENSIN SYSTEM; PROGRESSIVE TUBULOINTERSTITIAL FIBROSIS; MICE DEVELOP GLOMERULOSCLEROSIS; COLLAGEN-PRODUCING CELLS AB Interstitial fibrosis is a common feature of chronic kidney disease, regardless of the etiology of the primary renal syndrome. Moreover, interstitial fibrosis is the strongest morphologic predictor of clinical outcome and is most tightly linked to progression of disease, even though the primary disease may be of glomerular origin. Also, the presence of an interstitial component in chronic kidney disease often indicates an ominous outcome. The incidence of chronic kidney disease has reached epidemic proportions; thus, understanding the pathophysiology of interstitial renal disease is paramount for the development of new therapeutic approaches to slowing progression. Experimental models of renal fibrosis have been essential in determining the mechanisms and sequence of progression of fibrogenesis, including the roles of endothelium, infiltrating leukocytes and myofibroblasts; of profibrogenic cytokine and growth factor release; of tubular injury and atrophy; and of interstitial extracellular matrix accumulation. Over the last decade, considerable attention has been paid to the origin of the myofibroblast, the cell type most responsible for interstitial matrix accumulation. However, the origin(s) of myofibroblasts and how they gain access to the peritubular interstitium has become a matter of controversy and debate. Interstitial myofibroblasts have been proposed to originate from one or more of five sources: resident fibroblasts (pericytes), adventitial fibroblasts, circulating fibrocytes, tubular epithelial-mesenchymal transition (EMT) or endothelial/mesenchymal transition. To date, EMT has become the pre-eminent theory of the origin of myofibroblasts; however, a role for EMT in renal fibrosis is rigorously challenged by anecdotal and recent scientific evidence. This chapter will briefly discuss the experimental models used to explore interstitial renal disease in general and will then focus on the controversy related to the origin of myofibroblasts. Copyright (C) 2011 S. Karger AG, Basel C1 [Barnes, Jeffrey L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Barnes, Jeffrey L.] Audie Murphy Mem Vet Adm Hosp, Med Res Serv, S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Glass, William F., II] Nephrocor, Glen Allen, VA USA. [Glass, William F., II] Bostwick Labs Inc, Glen Allen, VA USA. RP Barnes, JL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM barnesj@uthscsa.edu FU NIDDK NIH HHS [R01 DK080106] NR 230 TC 41 Z9 48 U1 0 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 BN 978-3-8055-9537-7 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2011 VL 169 BP 73 EP 93 PG 21 WC Urology & Nephrology SC Urology & Nephrology GA BTP65 UT WOS:000287717700006 PM 21252512 ER PT J AU Krishnaswamy, A Lincoff, AM Cannon, CP AF Krishnaswamy, Amar Lincoff, A. Michael Cannon, Christopher P. TI Bleeding complications of unfractionated heparin SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE anticoagulation; AutoHep; bleeding classification; heparin ID ACUTE CORONARY SYNDROMES; PARTIAL THROMBOPLASTIN TIME; ST-SEGMENT ELEVATION; ACUTE MYOCARDIAL-INFARCTION; INTERNATIONAL RANDOMIZED-TRIAL; ACTIVE THROMBOEMBOLIC DISEASE; THROMBOLYTIC THERAPY; CLINICAL-OUTCOMES; TREATED PATIENTS; GUSTO-I AB Introduction: Unfractionated heparin is an anticoagulant used in the treatment of myocardial infarction, pulmonary embolism and other thrombotic disorders. However, with anticoagulation comes the risk of bleeding and adverse events. These risks increase with supratherapeutic dosing. Areas covered: In this review, we discuss the reasons for supratherapeutic dosing, and the incidence of adverse events and clinical consequences of the same, with a focus on heparin use in acute coronary syndromes. We also provide some opportunities for safer use of intravenous heparin. At the end of this article, the reader should have a better understanding of the proper use of heparin as well as the magnitude of bleeding and a respect for its consequences. Expert opinion: Heparin is an indispensable anticoagulant used in a number of clinical scenarios. Careful attention must be paid to dosing in order to minimize the risk of bleeding and related adverse events including death. The use of weight-based nomograms is paramount. Devices to automate testing and titration are currently under development. C1 [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Krishnaswamy, Amar; Lincoff, A. Michael] Cleveland Clin, Div Cardiovasc Med, Cleveland, OH 44115 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM CPCannon@partners.org FU AstraZeneca; Bristol-Myers Squibb; Genentech; Johnson Johnson; Kai Pharmaceuticals; Lilly; Medicines Company; Novartis; Pfizer; Roche; Sankyo; Sanofi-Aventis; Schering-Plough; Scios; Takeda Pharmaceuticals; Accumetrics; Bristol-Myers Squibb/Sanofi Partnership; Intekrin Therapeutics; Merck; Takeda FX A Krishnaswamy reports no financial conflicts of interest or relationships with industry. AM Lincoff has received research support from AstraZeneca, Bristol-Myers Squibb, Genentech, Johnson & Johnson, Kai Pharmaceuticals, Lilly, The Medicines Company, Novartis, Pfizer, Roche, Sankyo, Sanofi-Aventis, Schering-Plough, Scios, and Takeda Pharmaceuticals. CP Cannon receives Research grants/support from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, Intekrin Therapeutics, Merck, Novartis, Takeda, and is a Clinical Advisor and holds equity in Automedics Medical Systems. NR 38 TC 2 Z9 2 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD JAN PY 2011 VL 10 IS 1 BP 77 EP 84 DI 10.1517/14740338.2011.521150 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 695QW UT WOS:000285388700009 PM 20868290 ER PT J AU Mroz, P Hashmi, JT Huang, YY Lang, N Hamblin, MR AF Mroz, Pawel Hashmi, Javad T. Huang, Ying-Ying Lang, Norbert Hamblin, Michael R. TI Stimulation of anti-tumor immunity by photodynamic therapy SO EXPERT REVIEW OF CLINICAL IMMUNOLOGY LA English DT Review DE anti-tumor immunity; cancer vaccines; cytotoxic T-lymphocytes; damage-associated molecular patterns; dendritic cells; photodynamic therapy; Toll-like receptor agonists; tumor-associated antigens ID REGULATORY T-CELLS; VULVAL INTRAEPITHELIAL NEOPLASIA; TUMOR-INFILTRATING LYMPHOCYTES; TRANSCRIPTION FACTOR FOXP3; LOW-DOSE CYCLOPHOSPHAMIDE; HEAT-SHOCK PROTEINS; TOLL-LIKE RECEPTORS; C-TYPE LECTINS; SOLID TUMORS; DENDRITIC CELLS AB Photodynamic therapy (PDT) is a rapidly developing cancer treatment that utilizes the combination of nontoxic dyes and harmless visible light to destroy tumors by generating reactive oxygen species. PDT produces tumor-cell destruction in the context of acute inflammation that acts as a 'danger signal' to the innate immune system. Activation of the innate immune system increases the priming of tumor-specific T lymphocytes that have the ability to recognize and destroy distant tumor cells and, in addition, lead to the development of an immune memory that can combat recurrence of the cancer at a later point in time. PDT may be also successfully combined with immunomodulating strategies that are capable of overcoming or bypassing the escape mechanisms employed by the progressing tumor to evade immune attack. This article will cover the role of the immune response in PDT anti-tumor effectiveness. It will highlight the milestones in the development of PDT-mediated anti-tumor immunity and emphasize the combination strategies that may improve this therapy. C1 [Mroz, Pawel; Hashmi, Javad T.; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Mroz, Pawel; Hashmi, Javad T.; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Lang, Norbert] Univ Lausanne, Univ Geneva, Sch Pharmaceut Sci, CH-1211 Geneva, Switzerland. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU Partners Genzyme Translational Grant; Swiss Science Foundation [205320-122144, IZLSZ2 _123011, 310030-119938, K-32K1-116460]; NIH [R01AI050875]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research [FA9950-04-1-0079] FX Pawel Mroz was partly supported by Partners Genzyme Translational Grant. Norbert Lange was supported by the Swiss Science Foundation (Grants #205320-122144, #IZLSZ2 _123011, #310030-119938 and #K-32K1-116460). Michael R Hamblin was supported by NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research (FA9950-04-1-0079). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 159 TC 53 Z9 56 U1 5 U2 23 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1744-666X J9 EXPERT REV CLIN IMMU JI Expert Rev. Clin. Immunol. PD JAN PY 2011 VL 7 IS 1 BP 75 EP 91 DI 10.1586/ECI.10.81 PG 17 WC Immunology SC Immunology GA 749GJ UT WOS:000289451800015 PM 21162652 ER PT J AU Thompson, D Cullen, KW Reed, DB Konzelmann, K Smalling, AL AF Thompson, Debbe Cullen, Karen Weber Reed, Debra B. Konzelmann, Karen Smalling, Aggie Lara TI Formative Assessment in the Development of an Obesity Prevention Component for the Expanded Food and Nutrition Education Program in Texas SO FAMILY & COMMUNITY HEALTH LA English DT Article DE curriculum development; nutrition; obesity ID PHYSICAL-ACTIVITY; CHILDHOOD OBESITY; DIETARY-INTAKE; LOW-INCOME; PARENTS; OVERWEIGHT; CHILDREN; MOTHERS; VEGETABLES; FAMILIES AB This study conducted formative research (surveys, focus groups) to assess the nutrition education needs of clients in the Texas Expanded Food and Nutrition Education Program prior to curriculum revision. Participants were current Expanded Food and Nutrition Education Program participants in 3 Texas cities (Austin, Houston, San Antonio). Data were used to tailor the curriculum to the target population. This research provides evidence that members of the target audience can provide valuable insights into a particular topic. Formative work prior to intervention development should be conducted to identify key issues regarding a particular topic and to evaluate potential educational approaches. C1 [Thompson, Debbe; Cullen, Karen Weber; Konzelmann, Karen] Baylor Coll Med, USDA, ARS, Childrens Nutr Res Ctr,Dept Pediat, Houston, TX 77030 USA. [Reed, Debra B.] Texas Tech Univ, Coll Human Nutr Sci, Dept Nutr Hospitality & Retailing, Lubbock, TX 79409 USA. [Smalling, Aggie Lara] Vet Adm Hosp, Houston, TX USA. RP Thompson, D (reprint author), Baylor Coll Med, USDA, ARS, Childrens Nutr Res Ctr,Dept Pediat, 1100 Bates St, Houston, TX 77030 USA. EM dit@bcm.tmc.edu NR 25 TC 2 Z9 2 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-6379 J9 FAM COMMUNITY HEALTH JI Fam. Community Health PD JAN-MAR PY 2011 VL 34 IS 1 BP 61 EP 71 DI 10.1097/FCH.0b013e3181fdeb3f PG 11 WC Family Studies; Public, Environmental & Occupational Health SC Family Studies; Public, Environmental & Occupational Health GA 690XS UT WOS:000285044000008 PM 21135629 ER PT J AU Danzer, KM Ruf, WP Putcha, P Joyner, D Hashimoto, T Glabe, C Hyman, BT McLean, PJ AF Danzer, Karin M. Ruf, Wolfgang P. Putcha, Preeti Joyner, Daniel Hashimoto, Tadafumi Glabe, Charles Hyman, Bradley T. McLean, Pamela J. TI Heat-shock protein 70 modulates toxic extracellular alpha-synuclein oligomers and rescues trans-synaptic toxicity SO FASEB JOURNAL LA English DT Article DE Parkinson's disease; aggregation; microfluidic culture system; protein complementation ID PARKINSONS-DISEASE; INCLUSION FORMATION; MAMMALIAN-CELLS; STRESS-PROTEINS; LEWY BODIES; IN-VITRO; HSP70; RELEASE; PATHOLOGY; DROSOPHILA AB The paradoxical appearance of aggregated alpha-synuclein (alpha syn) in naive transplanted embryonic stem cells in Parkinson's disease (PD) brains has recently been reported, highlighting the possibility of neuron to neuron transmission of alpha syn in PD. Here, we demonstrate in a cellular model the presence of alpha syn oligomers in the extracellular space, their uptake by neurons, retrograde axonal transport to cell soma, and detrimental effects on neighboring cells. Moreover, we demonstrate that Hsp70 chaperones alpha syn in the extracellular space and reduces extracellular alpha syn oligomer formation and related toxicity. These novel findings provide evidence that extracellular alpha syn oligomers may represent a crucial player in the propagation of pathology in PD, with their modulation by Hsp70 representing a potential new target for therapeutic interventions.-Danzer, K. M., Ruf, W. P., Putcha, P., Joyner, D., Hashimoto, T., Glabe, C., Hyman, B. T., McLean, P. J. Heat-shock protein 70 modulates toxic extracellular alpha-synuclein oligomers and rescues trans-synaptic toxicity. FASEB J. 25, 326-336 (2011). www.fasebj.org C1 [Danzer, Karin M.; Ruf, Wolfgang P.; Putcha, Preeti; Joyner, Daniel; Hashimoto, Tadafumi; Hyman, Bradley T.; McLean, Pamela J.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis,Med Sch, Charlestown, MA 02129 USA. [Glabe, Charles] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. RP McLean, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis,Med Sch, 114 16th St, Charlestown, MA 02129 USA. EM pmclean@partners.org RI Hashimoto, Tadafumi/A-7723-2013 FU U.S. National Institutes of Health (NIH) [NS063963]; BioMEMS Resource Center [P41 EB002503]; Massachusetts General Hospital-Massachusetts Institute of Technology Udall Center for Excellence in Parkinson Disease Research [NIH NS038372] FX The authors thank Jon Edd and Daniel Irima for help and advice on the microfluid chamber production. This work was supported by the U.S. National Institutes of Health (NIH; NS063963 to P.J.M.), the BioMEMS Resource Center (P41 EB002503 to J.E. and D.I.), and the Massachusetts General Hospital-Massachusetts Institute of Technology Udall Center for Excellence in Parkinson Disease Research (NIH NS038372). NR 56 TC 120 Z9 120 U1 1 U2 28 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2011 VL 25 IS 1 BP 326 EP 336 DI 10.1096/fj.10-164624 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 702BL UT WOS:000285869500029 PM 20876215 ER PT J AU Borrero, S Abebe, K Dehlendorf, C Schwarz, EB Creinin, MD Nikolajski, C Ibrahim, S AF Borrero, Sonya Abebe, Kaleab Dehlendorf, Christine Schwarz, Eleanor Bimla Creinin, Mitchell D. Nikolajski, Cara Ibrahim, Said TI Racial variation in tubal sterilization rates: role of patient-level factors SO FERTILITY AND STERILITY LA English DT Article DE Tubal sterilization; disparities; knowledge and attitudes; race/ethnicity ID UNITED-STATES; CONTRACEPTIVE STERILIZATION; INSURANCE STATUS; REVERSAL; REPLACEMENT; DISPARITIES; KNOWLEDGE; REGRET; WOMEN AB Objective: To assess racial differences in attitudes and knowledge about sterilization. Design: Cross-sectional survey. Setting: Questionnaires were mailed to participants' home addresses. Patient(s): One hundred ninety-three women, aged 18-45, who had undergone tubal sterilization. Intervention(s): None. Main Outcome Measure(s): Attitudes and knowledge about tubal sterilization and awareness of contraceptive alternatives. Result(s): We received 193 completed surveys (64% response rate). African American (AA) woman were more likely to have a family member who had undergone tubal sterilization, to report that their mothers influenced their sterilization decisions, and to report that prior unintended pregnancy and desire to avoid insertion of a foreign object were very important factors in their decision to choose sterilization over other methods. Compared with white women, AA women more often thought that sterilization reversal could easily restore fertility (62% vs. 36%); that a woman's sterilization would reverse itself after 5 years (60% vs. 23%); and that a man cannot ejaculate after vasectomy (38% vs. 13%). Fewer AA women had ever heard of intrauterine contraception (90% vs. 98%). Racial differences in knowledge remained statistically significant after adjusting for socioeconomic confounders. Conclusion(s): Misinformation about sterilization and limited awareness of contraceptive alternatives among AA women may contribute to racial disparities in tubal sterilization rates. (Fertil Steril (R) 2011; 95: 17-22. (C)2011 by American Society for Reproductive Medicine.) C1 [Borrero, Sonya; Abebe, Kaleab; Schwarz, Eleanor Bimla; Nikolajski, Cara; Ibrahim, Said] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Borrero, Sonya; Abebe, Kaleab; Schwarz, Eleanor Bimla; Nikolajski, Cara; Ibrahim, Said] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. [Borrero, Sonya; Nikolajski, Cara; Ibrahim, Said] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Dehlendorf, Christine] Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. [Schwarz, Eleanor Bimla; Creinin, Mitchell D.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Creinin, Mitchell D.] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Borrero, S (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM borrerosp@upmc.edu RI Potter, Joseph/A-3122-2008; OI Abebe, Kaleab/0000-0002-3644-8419; Schwarz, Eleanor Bimla/0000-0002-9912-8236 FU National Center for Research Resources, National Institutes of Health (NIH) [KL2 RR024154]; NIH Roadmap for Medical Research FX This publication was made possible by Grant KL2 RR024154 from the National Center for Research Resources, a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. NR 24 TC 24 Z9 24 U1 0 U2 5 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 JAN PY 2011 VL 95 IS 1 BP 17 EP 22 DI 10.1016/j.fertnstert.2010.05.031 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 695ZL UT WOS:000285411600010 PM 20579640 ER PT J AU Eisenberg, DM Harris, ESJ Littlefield, BA Cao, SG Craycroft, JA Scholten, R Bayliss, P Fu, YL Wang, WQ Qiao, YJ Zhao, ZZ Chen, HBA Liu, Y Kaptchuk, T Hahn, WC Wang, XX Roberts, T Shamu, CE Clardy, J AF Eisenberg, David M. Harris, Eric S. J. Littlefield, Bruce A. Cao, Shugeng Craycroft, Jane A. Scholten, Robert Bayliss, Peter Fu, Yanling Wang, Wenquan Qiao, Yanjiang Zhao, Zhongzhen Chen, Hubiao Liu, Yong Kaptchuk, Ted Hahn, William C. Wang, Xiaoxing Roberts, Thomas Shamu, Caroline E. Clardy, Jon TI Developing a library of authenticated Traditional Chinese Medicinal (TCM) plants for systematic biological evaluation - Rationale, methods and preliminary results from a Sino-American collaboration SO FITOTERAPIA LA English DT Article DE Herbal medicine; Library; Traditional Chinese; Ethnomedicine ID BENIGN PROSTATIC HYPERPLASIA; DRUG DISCOVERY; UNITED-STATES; ECHINACEA-ANGUSTIFOLIA; RHINOVIRUS INFECTIONS; SEASONAL-VARIATIONS; HERBAL SUPPLEMENT; PANAX-NOTOGINSENG; GENETIC DIVERSITY; NATURAL-PRODUCTS AB While the popularity of and expenditures for herbal therapies (aka "ethnomedicines") have increased globally in recent years, their efficacy, safety, mechanisms of action, potential as novel therapeutic agents, cost-effectiveness, or lack thereof, remain poorly defined and controversial. Moreover, published clinical trials evaluating the efficacy of herbal therapies have rightfully been criticized, post hoc, for their lack of quality assurance and reproducibility of study materials, as well as a lack of demonstration of plausible mechanisms and dosing effects. In short, clinical botanical investigations have suffered from the lack of a cohesive research strategy which draws on the expertise of all relevant specialties. With this as background, US and Chinese co-investigators with expertise in Traditional Chinese Medicine (TCM), botany, chemistry and drug discovery, have jointly established a prototype library consisting of 202 authenticated medicinal plant and fungal species that collectively represent the therapeutic content of the majority of all commonly prescribed TCM herbal prescriptions. Currently housed at Harvard University, the library consists of duplicate or triplicate kilogram quantities of each authenticated and processed species, as well as "detanninized" extracts and sub-fractions of each mother extract. Each species has been collected at 2-3 sites, each separated geographically by hundreds of miles, with precise GPS documentation, and authenticated visually and chemically prior to testing for heavy metals and/or pesticides contamination. An explicit decision process has been developed whereby samples with the least contamination were selected to undergo ethanol extraction and HPLC sub-fractionation in preparation for high throughput screening across a broad array of biological targets including cancer biology targets. As envisioned, the subtractions in this artisan collection of authenticated medicinal plants will be tested for biological activity individually and in combinations (i.e., "complex mixtures") consistent with traditional ethnomedical practice. This manuscript summarizes the rationale, methods and preliminary "proof of principle" for the establishment of this prototype, authenticated medicinal plant library. It is hoped that these methods will foster scientific discoveries with therapeutic potential and enhance efforts to systematically evaluate commonly used herbal therapies worldwide. (C) 2010 Elsevier B.V. All rights reserved. C1 [Eisenberg, David M.; Harris, Eric S. J.; Littlefield, Bruce A.; Cao, Shugeng; Craycroft, Jane A.; Scholten, Robert; Kaptchuk, Ted; Clardy, Jon] Harvard Univ, Sch Med, Osher Res Ctr, Div Res & Educ Complementary & Integrat Med Thera, Boston, MA 02115 USA. [Harris, Eric S. J.; Littlefield, Bruce A.; Cao, Shugeng; Clardy, Jon] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Eisenberg, David M.; Kaptchuk, Ted] Beth Israel Deaconess Med Ctr, Div Gen Internal Med, Dept Med, Boston, MA 02215 USA. [Bayliss, Peter; Qiao, Yanjiang; Hahn, William C.; Wang, Xiaoxing; Roberts, Thomas] Dana Farber Canc Inst, Dept Canc Biol & Med Oncol, Boston, MA 02115 USA. [Bayliss, Peter] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Fu, Yanling] Beijing Univ Chinese Med, Int Cooperat Ctr, Beijing 100029, Peoples R China. [Wang, Wenquan; Liu, Yong] Beijing Univ Chinese Med, Sch Chinese Pharm, Beijing 100102, Peoples R China. [Zhao, Zhongzhen; Chen, Hubiao] Hong Kong Baptist Univ, Sch Chinese Med, Kowloon Tong, Hong Kong, Peoples R China. [Shamu, Caroline E.] Harvard Univ, Sch Med, ICCB Longwood Screening Facil, Boston, MA 02115 USA. [Shamu, Caroline E.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Eisenberg, DM (reprint author), Harvard Univ, Sch Med, Osher Res Ctr, Div Res & Educ Complementary & Integrat Med Thera, 77 Louis Pasteur Ave,Suite 1030, Boston, MA 02115 USA. EM David_Eisenberg@hms.harvard.edu OI Chen, Hubiao/0000-0003-0708-6073 FU National Institutes of Health National Cancer Institute [U19 CA128534]; National Center for Complementary and Alternative Medicine [AT03002 PIRC]; Bernard Osher Foundation; Hope Funds for Cancer Research FX This work was supported in part by grants from the National Institutes of Health National Cancer Institute (U19 CA128534), the National Center for Complementary and Alternative Medicine (AT03002 PIRC), the Bernard Osher Foundation, and Hope Funds for Cancer Research. NR 60 TC 22 Z9 22 U1 7 U2 31 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0367-326X J9 FITOTERAPIA JI Fitoterapia PD JAN PY 2011 VL 82 IS 1 SI SI BP 17 EP 33 DI 10.1016/j.fitote.2010.11.017 PG 17 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 724HS UT WOS:000287567300005 PM 21108995 ER PT J AU Curley, MD Garrett, LA Schorge, JO Foster, R Rueda, BR AF Curley, Michael D. Garrett, Leslie A. Schorge, John O. Foster, Rosemary Rueda, Bo R. TI Evidence for cancer stem cells contributing to the pathogenesis of ovarian cancer SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Ovary; Human; Cancer; Stem Cells; Xenograft; Transplantation; Review ID TUMOR-INITIATING CELLS; HEPATOCELLULAR-CARCINOMA CELLS; ACUTE MYELOID-LEUKEMIA; SIDE POPULATION CELLS; PLASMA-MEMBRANE PROTRUSIONS; BETA-CATENIN GENE; PANCREATIC-CANCER; BREAST-CANCER; HEMATOPOIETIC STEM; CD133 EXPRESSION AB Ovarian cancer represents the most lethal gynecologic malignancy, primarily due to a lack of early detection, which results in most patients being diagnosed at an advanced stage of disease. Though the ovarian surface epithelium is thought to provide the primary site of tumorigenesis, the exact etiology of the various tumor types associated with this disease remain undefined. Recent evidence suggests that ovarian tumors, like other solid tumors, contain distinct populations of cells that are responsible for tumor initiation, maintenance and growth. These specialized cells, termed cancer stem cells, display some of the hallmarks of normal stem cells and are thought to evade current chemotherapeutic strategies, resulting in an increased risk of recurrence. Here we review evidence for the existence of cancer stem cells in ovarian malignancies and their contribution to the pathology of this disease, critically evaluate the methods used for ovarian cancer stem cell definition and isolation, and discuss their clinical relevance. C1 [Curley, Michael D.; Garrett, Leslie A.; Foster, Rosemary; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. [Garrett, Leslie A.; Schorge, John O.; Rueda, Bo R.] Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. [Garrett, Leslie A.; Schorge, John O.; Foster, Rosemary; Rueda, Bo R.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, 55 Fruit St,THR 901, Boston, MA 02114 USA. EM brueda@partners.org FU Advanced Medical Research Foundation; Ovarian Cancer Research Fund; Ovarian Cancer Education and Awareness Network (O.C.E.A.N.); Vincent Memorial Research Funds; Harvard Stem Cell Institute; DFHCC Ovarian SPORE [5P50CA105009] FX Rosemary Foster and Bo R. Rueda contributed equally to this work. The preparation of this manuscript was funded in part by the Advanced Medical Research Foundation, Ovarian Cancer Research Fund, Ovarian Cancer Education and Awareness Network (O.C.E.A.N.), Vincent Memorial Research Funds, the Harvard Stem Cell Institute and the DFHCC Ovarian SPORE (5P50CA105009). The authors would also like to thank Dr. Kashmira Kulkarni and Dr. Jose Teixeira for their careful review of the manuscript. NR 210 TC 30 Z9 32 U1 2 U2 6 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JAN 1 PY 2011 VL 16 BP 368 EP 392 DI 10.2741/3693 PG 25 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 757MU UT WOS:000290091800023 PM 21196176 ER PT J AU Fletcher, AL Malhotra, D Acton, SE Lukacs-Kornek, V Bellemare-Pelletier, A Curry, M Armant, M Turley, SJ AF Fletcher, Anne L. Malhotra, Deepali Acton, Sophie E. Lukacs-Kornek, Veronika Bellemare-Pelletier, Angelique Curry, Mark Armant, Myriam Turley, Shannon J. TI Reproducible isolation of lymph node stromal cells reveals site-dependent differences in fibroblastic reticular cells SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE stromal cells; lymph node stromal cells; fibroblastic reticular cells; endothelial cells; tolerance; human lymph nodes; mouse lymph nodes AB Within lymph nodes, non-hematopoietic stromal cells organize and interact with leukocytes in an immunologically important manner. In addition to organizing T and B cell segregation and expressing lymphocyte survival factors, several recent studies have shown that lymph node stromal cells shape the naive T cell repertoire, expressing self-antigens which delete self-reactive T cells in a unique and non-redundant fashion. A fundamental role in peripheral tolerance, in addition to an otherwise extensive functional portfolio, necessitates closer study of lymph node stromal cell subsets using modern immunological techniques; however this has not routinely been possible in the field, due to difficulties reproducibly isolating these rare subsets. Techniques were therefore developed for successful ex vivo and in vitro manipulation and characterization of lymph node stroma. Here we discuss and validate these techniques in mice and humans, and apply them to address several unanswered questions regarding lymph node composition. We explored the steady-state stromal composition of lymph nodes isolated from mice and humans, and found that marginal reticular cells and lymphatic endothelial cells required lymphocytes for their normal maturation in mice. We also report alterations in the proportion and number of fibroblastic reticular cells (FRCs) between skin-draining and mesenteric lymph nodes. Similarly, transcriptional profiling of FRCs revealed changes in cytokine production from these sites. Together, these methods permit highly reproducible stromal cell isolation, sorting, and culture. C1 [Fletcher, Anne L.; Malhotra, Deepali; Acton, Sophie E.; Lukacs-Kornek, Veronika; Bellemare-Pelletier, Angelique; Turley, Shannon J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Malhotra, Deepali] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA. [Curry, Mark] Dana Farber Canc Inst, Flow Cytometry Core Facil, Boston, MA 02115 USA. [Armant, Myriam] Immune Dis Inst, Ctr Human Cell Therapy, Boston, MA USA. [Turley, Shannon J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Turley, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave, Boston, MA 02115 USA. EM shannon_turley@dfci.harvard.edu OI Acton, Sophie/0000-0003-2704-716X; Malhotra, Deepali/0000-0002-8215-7639 FU National Institutes of Health [DK074500, AI045757, R24 AI072073]; NHMRC Australia [546259] FX This work was supported by grants from the National Institutes of Health (DK074500, AI045757, to Shannon J. Turley, and R24 AI072073 to the Immunological Genome Project), and NHMRC Australia (Overseas Postdoctoral Training Fellowship 546259, to Anne L. Fletcher). The authors wish to thank members of the ImmGen consortium for technical help and discussions. NR 51 TC 59 Z9 61 U1 2 U2 4 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2011 VL 2 DI 10.3389/fimmu.2011.00035 PG 15 WC Immunology SC Immunology GA V40TR UT WOS:000209501400035 PM 22566825 ER PT J AU Keskin, DB Reinhold, B Lee, SY Zhang, GL Lank, S O'Connor, DH Berkowitz, RS Brusic, V Kim, SJ Reinherz, EL AF Keskin, Derin B. Reinhold, Bruce Lee, Sun Young Zhang, Guanglan Lank, Simon O'Connor, David H. Berkowitz, Ross S. Brusic, Vladimir Kim, Seung Jo Reinherz, Ellis L. TI Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE T cell epitopes; mass spectrometry; tumor antigens; human papilloma virus; El; GILT; CTL targets; T cell vaccines AB Persistent infection with high-risk human papilloma viruses (HPV) is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile, and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS3) to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A*02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS3 analysis of HLA-A*02 immunoprecipitates detected E7(11-19) peptide (YMLDLQPET) in seven of the nine tumor biopsies. The remaining two samples were E7(11-19) negative and lacked the HLA-A*02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A*02 alleles. Thus, the conserved E7(11-19) peptide is a dominant HLA-A*02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A*02:01 tumors lack expression of both E7(11-19) and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development. C1 [Keskin, Derin B.; Reinhold, Bruce; Zhang, Guanglan; Berkowitz, Ross S.; Brusic, Vladimir; Reinherz, Ellis L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Keskin, Derin B.; Reinhold, Bruce; Zhang, Guanglan; Berkowitz, Ross S.; Brusic, Vladimir; Reinherz, Ellis L.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Sun Young; Kim, Seung Jo] CHA Univ, Gynecol Canc Ctr, Songnam, South Korea. [Lank, Simon; O'Connor, David H.] Univ Wisconsin, Madison, WI USA. [Berkowitz, Ross S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, 77 Ave Louis Pasteur,HIM 418, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu OI o'connor, david/0000-0003-2139-470X FU NIH [UO1 AI090043, R24RR021745]; DFCI; Wisconsin Alumni research Foundation [MSN 100252] FX This work was supported by NIH grant UO1 AI090043, DFCI institutional funding for the Cancer Vaccine Center, NIH grant R24RR021745 and The Wisconsin Alumni research Foundation award MSN 100252. We gratefully acknowledge the pathological consultation of Dr. Christopher Crum, Director of Women's and Perinatal Pathology, Brigham and Women's Hospital. NR 61 TC 5 Z9 5 U1 0 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2011 VL 2 AR UNSP 75 DI 10.3389/fimmu.2011.00075 PG 26 WC Immunology SC Immunology GA V40TR UT WOS:000209501400075 PM 22566864 ER PT J AU Olsen, LR Zhang, GL Keskin, DB Reinherz, EL Brusic, V AF Olsen, Lars Ronn Zhang, Guang Lan Keskin, Derin B. Reinherz, Ellis L. Brusic, Vladimir TI Conservation analysis of dengue virus T-cell epitope-based vaccine candidates using peptide block entropy SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE antigenic diversity; epitope-based vaccines; immunoinformatics; polyvalent vaccines; reverse vaccinology; vaccine informatics AB Broad coverage of the pathogen population is particularly important when designing CD8+ T-cell epitope vaccines against viral pathogens. Traditional approaches are based on combinations of highly conserved T-cell epitopes. Peptide block entropy analysis is a novel approach for assembling sets of broadly covering antigens. Since T-cell epitopes are recognized as peptides rather than individual residues, this method is based on calculating the information content of blocks of peptides from a multiple sequence alignment of homologous proteins rather than using the information content of individual residues. The block entropy analysis provides broad coverage of variant antigens. We applied the block entropy analysis method to the proteomes of the four serotypes of dengue virus (DENV) and found 1,551 blocks of 9-mer peptides, which cover 99% of available sequences with five or fewer unique peptides. In contrast, the benchmark study by Khan et al. (2008) resulted in 165 conserved 9-mer peptides. Many of the conserved blocks are located consecutively in the proteins. Connecting these blocks resulted in 78 conserved regions. Of the 1551 blocks of 9-mer peptides 110 comprised predicted HLA binder sets. In total, 457 subunit peptides that encompass the diversity of all sequenced DENV strains of which 333 are T-cell epitope candidates. C1 [Olsen, Lars Ronn; Zhang, Guang Lan; Reinherz, Ellis L.; Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02118 USA. [Olsen, Lars Ronn] Tech Univ Denmark, Ctr Biol Sequence Anal, Dept Syst Biol, DK-2800 Lyngby, Denmark. [Keskin, Derin B.; Reinherz, Ellis L.; Brusic, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Keskin, Derin B.; Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02118 USA. RP Brusic, V (reprint author), Dana Farber Canc Inst, Canc Vaccine Ctr, Harvard Inst Med 401,77 Ave Louis Pasteur, Boston, MA 02118 USA. EM vladimir_brusic@dfci.harvard.edu OI Olsen, Lars Ronn/0000-0002-6725-7850 FU NIH [U01 AI 90043]; Otto Monsteds Foundation; Rudolph Als Foundation; Civil Engineer Frants Alling's Scholarship; Rebild National Park Society, Inc.; Inge and Jorgen Larsen's Memorial Scholarship; Mayor Niels Albrechtsen's Scholarship; Danish Society of Engineers Scholarship; Oticon Foundation FX This work was supported by NIH grant U01 AI 90043 (Guang Lan Zhang, Derin B. Keskin, Ellis L. Reinherz, and Vladimir Brusic). Lars Ronn Olsen was supported by a number of Danish student grants (Otto Monsteds Foundation; Rudolph Als Foundation; Civil Engineer Frants Alling's Scholarship; Julie Damm's; Rebild National Park Society, Inc.; Inge and Jorgen Larsen's Memorial Scholarship; Mayor Niels Albrechtsen's Scholarship; Danish Society of Engineers Scholarship; and Oticon Foundation). NR 50 TC 9 Z9 9 U1 1 U2 2 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2011 VL 2 AR UNSP 69 DI 10.3389/fimmu.2011.00069 PG 15 WC Immunology SC Immunology GA V40TR UT WOS:000209501400069 PM 22566858 ER PT J AU Reinherz, EL Acuto, O AF Reinherz, Ellis L. Acuto, Oreste TI Molecular T cell biology - basic and translational challenges in the twenty-first century SO FRONTIERS IN IMMUNOLOGY LA English DT Editorial Material C1 [Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. [Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Reinherz, Ellis L.] Harvard Univ, Harvard Fac Arts & Sci, Cambridge, MA 02138 USA. [Acuto, Oreste] Univ Oxford, Sir William Dunn Sch Pathol, Dept Pathol, T Cell Signalling Lab, Oxford OX1 3RE, England. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu; oreste.acuto@path.ox.ac.uk NR 59 TC 0 Z9 0 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2011 VL 2 DI 10.3389/fimmu.2011.00003 PG 5 WC Immunology SC Immunology GA V40TR UT WOS:000209501400003 ER PT J AU Rucci, F Poliani, PL Caraffi, S Paganini, T Fontana, E Giliani, S Alt, FW Notarangelo, LD AF Rucci, Francesca Poliani, Pietro Luigi Caraffi, Stefano Paganini, Tiziana Fontana, Elena Giliani, Silvia Alt, Frederick W. Notarangelo, Luigi Daniele TI Abnormalities of thymic stroma may contribute to immune dysregulation in murine models of leaky severe combined mmunodeficiency SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE severe combined immunodeficiency; recombination-activating gene 1; DNA ligase 4; thymic epithelial cells; thymus; dendritic cells; Aire; regulatory T cells AB Lymphostromal cross-talk in the thymus is essential to allow generation of a diversified repertoire of T lymphocytes and to prevent autoimmunity by self-reactive T cells. Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. We have studiedT cell development and thymic stroma architecture and maturation in two mouse models of leaky severe combined immune deficiency, carrying hypomorphic mutations in rag1 and lig4 genes. Defective T cell development was associated with abnormalities of thymic architecture that predominantly affect the thymic medulla, with reduction of the pool of mature medullary thymic epithelial cells (mTECs). While the ability of mTECs to express autoimmune regulator (Aire) is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens is severely reduced. Similarly, the ability of CD4(+) T cells to differentiate into Foxp3(+) natural regulatory T cells is preserved in rag1 and lig4 mutant mice, but their number is greatly reduced. These data indicate that hypomorphic defects in T cell development may cause defective lymphostromal cross-talk and impinge on thymic stromal cells maturation, and thus favor immune dysregulation. C1 [Rucci, Francesca; Caraffi, Stefano; Notarangelo, Luigi Daniele] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Rucci, Francesca; Caraffi, Stefano; Notarangelo, Luigi Daniele] Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Poliani, Pietro Luigi; Fontana, Elena] Univ Brescia, Dept Pathol, Brescia, Italy. [Paganini, Tiziana; Giliani, Silvia] Univ Brescia, Angelo Nocivelli Inst Mol Med, Brescia, Italy. [Paganini, Tiziana; Giliani, Silvia] Univ Brescia, Dept Pediat, Brescia, Italy. [Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. [Alt, Frederick W.] Harvard Univ, Sch Med, Boston, MA USA. RP Notarangelo, LD (reprint author), Childrens Hosp, Div Immunol, Karp Res Bldg,Room 9210,1 Blackfan Circle, Boston, MA 02115 USA. EM luigi.notarangelo@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU National Institutes of Health [P01 AI076210-01A1]; Manton Foundation; Fondazione "Angelo Nocivelli"; Fondazione CARIPLO FX We thank Mike Recher, Laura Patrizi, and Divij Matthew for animal care. This work was partially supported by the National Institutes of Health Grant P01 AI076210-01A1 (to Luigi Daniele Notarangelo and Frederick W. Alt), by the Manton Foundation (Luigi Daniel Notarangelo), by Fondazione "Angelo Nocivelli" (Silvia Giliani) and by Fondazione CARIPLO (Pietro Luigi Poliani). Frederick W. Alt is a Howard Hughes Investigator. NR 72 TC 7 Z9 7 U1 1 U2 2 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2011 VL 2 DI 10.3389/fimmu.2011.00015 PG 13 WC Immunology SC Immunology GA V40TR UT WOS:000209501400015 ER PT J AU Zhou, B Chen, Q Mallis, RJ Zhang, HM Liu, H Reinherz, EL Wang, JH AF Zhou, Bo Chen, Qiang Mallis, Robert J. Zhang, Hongmin Liu, Jin-huan Reinherz, Ellis L. Wang, Jia-huai TI A conserved hydrophobic patch on V beta domains revealed by TCR beta chain crystal structures: implications for pre-TCR dimerization SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE T cell receptor; beta chain; crystal structure; pre-TCR AB The alpha beta T cell receptor (TCR) is a multimeric complex whose beta chain plays a crucial role in thymocyte development as well as antigen recognition by mature T lymphocytes. We report here crystal structures of individual beta subunits, termed N15 beta (V beta 5.2D beta 2J beta 2.6C beta 2) and N30 beta (V beta 13D beta 1J beta 1.1C beta 2), derived from two alpha beta TCRs specific for the immunodominant vesicular stomatitis virus octapeptide (VSV-8) bound to the murine H-2K(b) MHC class I molecule. The crystal packing of the N15 beta structure reveals a homodimer formed through two V beta domains.The V beta/V beta module is topologically very similar to the V alpha/V beta module in the N15 alpha beta heterodimer. By contrast, in the N30 beta structure, the V beta domain's external hydrophobic CFG face is covered by the neighboring molecule's C beta domain. In conjunction with systematic investigation of previously published TCR single-subunit structures, we identified several conserved residues forming a concave hydrophobic patch at the center of the CFG outer face of the V beta and other V-type Ig-like domains. This hydrophobic patch is shielded from solvent exposure in the crystal packing, implying that it is unlikely to be thermodynamically stable if exposed on the thymocyte surface. Accordingly, we propose a dimeric pre-TCR model distinct from those suggested previously by others and discuss its functional and structural implications. C1 [Zhou, Bo; Chen, Qiang; Zhang, Hongmin; Liu, Jin-huan; Reinherz, Ellis L.; Wang, Jia-huai] Harvard Univ, Sch Med, Immunobiol Lab, Dana Farber Canc Inst, Boston, MA USA. [Zhou, Bo; Chen, Qiang; Zhang, Hongmin; Liu, Jin-huan; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Mallis, Robert J.; Wang, Jia-huai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhang, Hongmin] Univ Hong Kong, Dept Physiol, Hong Hom, Hong Kong, Peoples R China. [Wang, Jia-huai] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Wang, JH (reprint author), Dana Farber Canc Inst, 44 Binney St,SM 1030, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu RI Zhang, Hongmin/C-4503-2009 OI Chen, Qiang/0000-0002-2398-4482; Zhang, Hongmin/0000-0001-6357-4106 FU NIH FX This work has been supported by NIH grants to Ellis L. Reinherz and Jia-Huai Wang. We thank our colleagues for helpful discussion. We also thank Rob Meijers for valuable comments. NR 52 TC 10 Z9 10 U1 0 U2 0 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2011 VL 2 DI 10.3389/fimmu.2011.00005 PG 9 WC Immunology SC Immunology GA V40TR UT WOS:000209501400005 PM 22566796 ER PT J AU Smith, PM Garrett, WS AF Smith, Patrick M. Garrett, Wendy S. TI The gut microbiota and mucosal T cells SO FRONTIERS IN MICROBIOLOGY LA English DT Review DE gut microbiota; T cells; mucosal immunity AB It is intuitive that immune cells in the gut may require microbiota-derived cues for their differentiation. The proximity between host and microbe in the intestine would seemingly necessitate co-adaptation. However, it has been challenging to determine the members and features of the gut microbiota that influence immune system development and function. The recent identification of immunomodulatory members of the commensal microbiota is providing insight into the dependence of select, intestinal immune cell subsets on specific microbial species. In this review, we focus on the gut microbiota's influence on the development and function of mucosal T cells subsets, specifically intraepithelial lymphocytes and lamina propria CD4 T cells. C1 [Smith, Patrick M.; Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Smith, Patrick M.; Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Garrett, Wendy S.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Garrett, WS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave,SPH 1,9th Floor, Boston, MA 02115 USA. EM wgarrett@hsph.harvard.edu FU Burroughs Wellcome Fund; Cancer Research Institute; NIH [AIO78942, CA1544260] FX We thank members of the Garrett laboratory, Curtis Huttenhower and members of his laboratory, and members of MiRiBA (Broad Institute) for thoughtful discussions. We thank Carey Ann Gallini for assistance with manuscript preparation, and we thank our funding sources [Burroughs Wellcome Fund, Cancer Research Institute, and the NIH (AIO78942 and CA1544260)] for their support. NR 42 TC 24 Z9 25 U1 1 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 111 DI 10.3389/fmicb.2011.00111 PG 6 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500121 PM 21833339 ER PT J AU Kovesdi, E Gyorgy, AB Kwon, SKC Wingo, DL Kamnaksh, A Long, JB Kasper, CE Agoston, DV AF Kovesdi, Erzsebet Gyorgy, Andrea B. Kwon, Sook-Kyung C. Wingo, Daniel L. Kamnaksh, Alaa Long, Joseph B. Kasper, Christine E. Agoston, Denes V. TI The effect of enriched environment on the outcome of traumatic brain injury; a behavioral, proteomics, and histological study SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE neurogenesis; enriched environment; traumatic brain injury; memory; anxiety; hippocampus; histology; proteomics AB De novo hippocampal neurogenesis contributes to functional recovery following traumatic brain injury (TBI). Enriched environment (EEN) can improve the outcome of TBI by positively affecting neurogenesis. Blast induced traumatic brain injury (bTBI) characterized by memory impairment and increased anxiety levels, is a leading cause of chronic disability among soldiers. Using a rodent model of bTBI we asked: (a) whether long-term exposure to EEN after injury can ameliorate behavioral abnormalities and (b) what the effects of EEN are at the molecular and cellular levels and on de novo neurogenesis. We found that housing injured animals in EEN resulted in significantly improved spatial memory while animals in normal housing (NH) showed persistent memory impairment. VEGF and Tau protein but not Interleukin-6 (IL-6) levels were normalized in the dorsal hippocampus (DHC) of EEN rats while all three markers remained elevated in NH rats. Interestingly, after peaking at 6 weeks post-injury, anxiety returned to normal levels at 2 months independent of housing conditions. Housing animals in EEN had no significant effect on VEGF and Tau protein levels in the ventral hippocampus (VHC) and the amygdala (AD). We also found that EEN reduced IL-6 and IFN gamma levels in the VHC; these markers remained elevated following NH. We observed an increase in GFAP and DCX immunoreactivities in the VHC of NH animals at 2 months post-injury. Conversely, injured animals housed in EEN showed no increase in GFAP or DCX immunoreactivity in their VHC. In summary, long-term exposure of injured animals to EEN appears to play a positive role in the restoration of memory functions but not on anxiety, which returned to normal levels after a significant period of time. Cellular and molecular changes in response to EEN appear to be a part of neurogenesis-independent as well as dependent recovery processes triggered by bTBI. C1 [Kovesdi, Erzsebet; Kasper, Christine E.] US Dept Vet Affairs, Vet Affairs Cent Off, Washington, DC USA. [Gyorgy, Andrea B.; Kwon, Sook-Kyung C.; Wingo, Daniel L.; Kamnaksh, Alaa; Agoston, Denes V.] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Long, Joseph B.] Walter Reed Army Inst Res, Div Mil Casualty Res, Silver Spring, MD USA. RP Agoston, DV (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM vagoston@usuhs.edu FU VA grant [B5044R] FX We thank the Neurotrauma Team (WRAIR) for their technical help during the blast exposures; Dr. David Jacobowitz (USU) for his help in brain micropunch dissections; Ms. Cara Olsen (USU) for her help in statistical analysis; Drs. Neil Grunberg and John Wu (USU) for their input in designing and interpreting the behavioral experiments. The work was supported by VA grant # B5044R. NR 125 TC 45 Z9 45 U1 3 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2011 VL 5 AR 42 DI 10.3389/fnins.2011.00042 PG 12 WC Neurosciences SC Neurosciences & Neurology GA V36GI UT WOS:000209200600038 PM 21503146 ER PT J AU Laderas, TG Walter, NAR Mooney, M Vartanian, K Darakjian, P Buck, K Harrington, CA Belknap, J Hitzemann, R McWeeney, SK AF Laderas, Ted G. Walter, Nicole A. R. Mooney, Michael Vartanian, Kristina Darakjian, Priscila Buck, Kari Harrington, Christina A. Belknap, John Hitzemann, Robert McWeeney, Shannon K. TI Computational detection of alternative exon usage SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE alternative splicing; exon array AB Background: With the advent of the GeneChip Exon Arrays, it is now possible to extract "exon-level" expression estimates, allowing for detection of alternative splicing events, one of the primary mechanisms of transcript diversity. In the context of (1) a complex trait use case and (2) a human cerebellum vs. heart comparison on previously validated data, we present a transcript-based statistical model and validation framework to allow detection of alternative exon usage (AEU) between different groups. To illustrate the approach, we detect and confirm differences in exon usage in the two of the most widely studied mouse genetic models (the C57BL/6J and DBA/2J inbred strains) and in a human dataset. Results: We developed a computational framework that consists of probe level annotation mapping and statistical modeling to detect putative AEU events, as well as visualization and alignment with known splice events. We show a dramatic improvement (similar to 25 fold) in the ability to detect these events using the appropriate annotation and statistical model which is actually specified at the transcript level, as compared with the transcript cluster/gene-level annotation used on the array. An additional component of this workflow is a probe index that allows ranking AEU candidates for validation and can aid in identification of false positives due to single nucleotide polymorphisms. Discussion: Our work highlights the importance of concordance between the functional unit interrogated (e.g., gene, transcripts) and the entity (e.g., exon, probeset) within the statistical model. The framework we present is broadly applicable to other platforms (including RNAseq). C1 [Laderas, Ted G.; McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Oregon Clin Res & Translat Inst, Portland, OR 97239 USA. [Laderas, Ted G.; McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Laderas, Ted G.; Mooney, Michael; McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. [Walter, Nicole A. R.; Buck, Kari; Belknap, John; Hitzemann, Robert] Portland VA Med Ctr, Portland, OR USA. [Walter, Nicole A. R.; Darakjian, Priscila; Buck, Kari; Belknap, John; Hitzemann, Robert; McWeeney, Shannon K.] Portland Alcohol Res Ctr, Portland, OR USA. [Walter, Nicole A. R.; Buck, Kari; Belknap, John; Hitzemann, Robert] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Vartanian, Kristina; Harrington, Christina A.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [McWeeney, Shannon K.] Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. RP McWeeney, SK (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, Mail Code CR145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM mcweeney@ohsu.edu OI Laderas, Ted/0000-0002-6207-7068; Mooney, Michael/0000-0003-1372-8722; McWeeney, Shannon/0000-0001-8333-6607 FU US National Institutes of Health [AA010760, AA11034, AA13484, AA011114, DA05228, MH51372]; Department of Veterans Affairs Merit Awards; Affymetrix Fellowship; National Library of Medicine Biomedical Informatics Fellowship [LM007088] FX Supported by US National Institutes of Health grants AA010760, AA11034, AA13484, AA011114, DA05228, and MH51372, Department of Veterans Affairs Merit Awards, Affymetrix, and National Library of Medicine Biomedical Informatics Fellowships to M. Mooney (LM007088) and Ted Laderas. NR 20 TC 6 Z9 6 U1 0 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2011 VL 5 AR 69 DI 10.3389/fnins.2011.00069 PG 11 WC Neurosciences SC Neurosciences & Neurology GA V36GI UT WOS:000209200600065 PM 21625610 ER PT J AU Salomone, S Waeber, C AF Salomone, Salvatore Waeber, Christian TI Selectivity and specificity of sphingosine-1-phosphate receptor ligands: caveats and critical thinking in characterizing receptor-mediated effects SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE JTE-013; BML-241; CAY10444; VPC23019; antagonist AB Receptors for sphingosine-1-phosphate (S1P) have been identified only recently. Their medicinal chemistry is therefore still in its infancy, and few selective agonists or antagonists are available. Furthermore, the selectivity of S1P receptor agonists or antagonists is not well established. JTE-013 and BML-241 (also known as CAY10444), used extensively as specific S1P(2) and S1P(3) receptors antagonists respectively, are cases in point. When analyzing S1P-induced vasoconstriction in mouse basilar artery, we observed that JTE-013 inhibited not only the effect of S1P, but also the effect of U46619, endothelin-1 or high KCl; JTE-013 strongly inhibited responses to S1P in S1P(2) receptor knockout mice. Similarly, BML-241 has been shown to inhibit increases in intracellular Ca2+ concentration via P-2 receptor or alpha(1A)-adrenoceptor stimulation and alpha(1A)-adrenoceptor-mediated contraction of rat mesenteric artery, while it did not affect S1P(3)-mediated decrease of forskolin-induced cyclic AMP accumulation. Another putative S1P(1/3) receptor antagonist, VPC23019, does not inhibit S1P(3)-mediated vasoconstriction. With these examples in mind, we discuss caveats about relying on available pharmacological tools to characterize receptor subtypes. C1 [Salomone, Salvatore] Catania Univ, Dept Clin & Mol Biomed, Catania, Italy. [Waeber, Christian] Massachusetts Gen Hosp, Dept Radiol, Stroke & Neurovasc Lab Regulat, Charlestown, MA 02129 USA. RP Waeber, C (reprint author), Massachusetts Gen Hosp, CNY149 Room 6403,149 13th St, Charlestown, MA 02129 USA. EM waeber@helix.mgh.harvard.edu OI Salomone, Salvatore/0000-0001-5307-6103 NR 63 TC 32 Z9 32 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-9812 J9 FRONT PHARMACOL JI Front. Pharmacol. PY 2011 VL 2 AR UNSP 9 DI 10.3389/fphar.2011.00009 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V35XB UT WOS:000209177400010 PM 21687504 ER PT J AU Wu, SV Hui, HX AF Wu, Shuping Vincent Hui, Hongxiang TI Treat your bug right SO FRONTIERS IN PHYSIOLOGY LA English DT Editorial Material C1 [Wu, Shuping Vincent] VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Wu, Shuping Vincent; Hui, Hongxiang] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Excellence Pancreat Dis, Los Angeles, CA 90095 USA. [Hui, Hongxiang] Southern Med Univ, Guangzhou, Guangdong, Peoples R China. RP Wu, SV (reprint author), VA Greater Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM vwu@ucla.edu NR 6 TC 4 Z9 4 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PY 2011 VL 2 AR 9 DI 10.3389/fphys.2011.00009 PG 1 WC Physiology SC Physiology GA V35UD UT WOS:000209172600009 PM 21483729 ER PT J AU de Gelder, B Van den Stock, J AF de Gelder, Beatrice Van den Stock, Jan TI The bodily expressive action stimulus test (BEAST). Construction and validation of a stimulus basis for measuring perception of whole body expression of emotions SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE body expression; emotion; action; test validation AB Whole body expressions are among the main visual stimulus categories that are naturally associated with faces and the neuroscientific investigation of how body expressions are processed has entered the research agenda this last decade. Here we describe the stimulus set of whole body expressions termed bodily expressive action stimulus test (BEAST), and we provide validation data for use of these materials by the community of emotion researchers. The database was composed of 254 whole body expressions from 46 actors expressing 4 emotions (anger, fear, happiness, and sadness). In all pictures the face of the actor was blurred and participants were asked to categorize the emotions expressed in the stimuli in a four alternative-forced-choice task. The results show that all emotions are well recognized, with sadness being the easiest, followed by fear, whereas happiness was the most difficult. The BEAST appears a valuable addition to currently available tools for assessing recognition of affective signals. It can be used in explicit recognition tasks as well as in matching tasks and in implicit tasks, combined either with facial expressions, with affective prosody, or presented with affective pictures as context in healthy subjects as well as in clinical populations. C1 [de Gelder, Beatrice; Van den Stock, Jan] Tilburg Univ, Lab Cognit & Affect Neurosci, NL-5000 LE Tilburg, Netherlands. [de Gelder, Beatrice; Van den Stock, Jan] Katholieke Univ Leuven, Dept Neurosci, Brain & Emot Lab Leuven, Louvain, Belgium. [de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [de Gelder, Beatrice] Harvard Univ, Sch Med, Boston, MA USA. RP de Gelder, B (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Room 417,Bldg 36,First St, Boston, MA 02129 USA. EM degelder@nmr.mgh.harvard.edu RI Van den Stock, Jan/F-1906-2014 OI Van den Stock, Jan/0000-0001-5756-3195 NR 46 TC 35 Z9 35 U1 2 U2 10 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PY 2011 VL 2 AR 181 DI 10.3389/fpsyg.2011.00181 PG 6 WC Psychology, Multidisciplinary SC Psychology GA V31DG UT WOS:000208863700191 PM 21886632 ER PT J AU Kret, ME Pichon, S Grezes, J de Gelder, B AF Kret, Mariska Esther Pichon, Swann Grezes, Julie de Gelder, Beatrice TI Men fear other men most: gender specific brain activations in perceiving threat from dynamic faces and bodies - an fMRI study SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE fMRI; emotion; social threat; faces; bodies; gender differences; gender of actor AB Gender differences are an important factor regulating our daily interactions. Using functional magnetic resonance imaging we show that brain areas involved in processing social signals are activated differently by threatening signals send from male and female facial and bodily expressions and that their activation patterns are different for male and female observers. Male participants pay more attention to the female face as shown by increased amygdala activity. But a host of other areas show selective sensitivity for male observers attending to male threatening bodily expressions (extrastriate body area, superior temporal sulcus, fusiform gyrus, pre-supplementary motor area, and premotor cortex). This is the first study investigating gender differences in processing dynamic female and male facial and bodily expressions and it illustrates the importance of gender differences in affective communication. C1 [Kret, Mariska Esther] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [Pichon, Swann; Grezes, Julie] Ecole Normale Super, Dept Etud Cognit, INSERM, Lab Neurosci Cognit,U960, F-75231 Paris, France. [Pichon, Swann] Univ Geneva, Sch Med, Dept Neurosci, Lab Behav Neurol & Imaging Cognit, CH-1211 Geneva, Switzerland. [de Gelder, Beatrice] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP de Gelder, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Bldg 36,First St,Room 409, Charlestown, MA 02129 USA. EM degelder@nmr.mgh.harvard.edu RI Kret, Mariska/B-4798-2010; pichon, swann/M-2966-2014; Grezes, Julie/E-5060-2016 OI pichon, swann/0000-0001-5697-702X; NR 65 TC 25 Z9 26 U1 1 U2 11 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PY 2011 VL 2 AR 3 DI 10.3389/fpsyg.2011.00003 PG 11 WC Psychology, Multidisciplinary SC Psychology GA V31DG UT WOS:000208863700015 PM 21713131 ER PT J AU Samson, F Zeffiro, TA Toussaint, A Belin, P AF Samson, Fabienne Zeffiro, Thomas A. Toussaint, Alain Belin, Pascal TI Stimulus complexity and categorical effects in human auditory cortex: an Activation Likelihood Estimation meta-analysis SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE fMRI; category; time; frequency; hierarchy AB Investigations of the functional organization of human auditory cortex typically examine responses to different sound categories. An alternative approach is to characterize sounds with respect to their amount of variation in the time and frequency domains (i.e., spectral and temporal complexity). Although the vast majority of published studies examine contrasts between discrete sound categories, an alternative complexity-based taxonomy can be evaluated through meta-analysis. In a quantitative meta-analysis of 58 auditory neuroimaging studies, we examined the evidence supporting current models of functional specialization for auditory processing using grouping criteria based on either categories or spectro-temporal complexity. Consistent with current models, analyses based on typical sound categories revealed hierarchical auditory organization and left-lateralized responses to speech sounds, with high speech sensitivity in the left anterior superior temporal cortex. Classification of contrasts based on spectro-temporal complexity, on the other hand, revealed a striking within-hemisphere dissociation in which caudo-lateral temporal regions in auditory cortex showed greater sensitivity to spectral changes, while anterior superior temporal cortical areas were more sensitive to temporal variation, consistent with recent findings in animal models. The meta-analysis thus suggests that spectro-temporal acoustic complexity represents a useful alternative taxonomy to investigate the functional organization of human auditory cortex. C1 [Samson, Fabienne; Toussaint, Alain] Univ Montreal, Ctr Excellence Troubles Envahissants Dev, Montreal, PQ, Canada. [Samson, Fabienne; Toussaint, Alain] Univ Montreal, Dept Psychiat, Ctr Rech Fernand Seguin, Montreal, PQ H3C 3J7, Canada. [Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. [Belin, Pascal] Univ Glasgow, Inst Neurosci & Psychol, Glasgow, Lanark, Scotland. [Belin, Pascal] McGill Univ, Int Labs Brain Mus & Sound, Montreal, PQ, Canada. [Belin, Pascal] Univ Montreal, Montreal, PQ, Canada. RP Samson, F (reprint author), Hop Riviere des Prairies, Rech TN, 7070 Blvd Perras, Montreal, PQ H1E 1A4, Canada. EM samsonfabienne1@gmail.com RI Belin, Pascal/C-6247-2009 OI Belin, Pascal/0000-0002-7578-6365 NR 136 TC 8 Z9 9 U1 2 U2 5 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PY 2011 VL 2 AR 241 DI 10.3389/fpsyg.2010.00241 PG 23 WC Psychology, Multidisciplinary SC Psychology GA V31DG UT WOS:000208863700007 PM 21833294 ER PT J AU Park, EM Liu, BG Xia, XJ Zhu, F Jami, WB Hu, YL AF Park, Eunmi Liu, Bigang Xia, Xiaojun Zhu, Feng Jami, Willette-Brown Hu, Yinling TI Role of IKK alpha in skin squamous cell carcinomas SO FUTURE ONCOLOGY LA English DT Review DE carcinogenesis; EGFR; gene mutations; IKK alpha; keratinocyte differentiation and proliferation; squamous cell carcinoma; TGF beta ID NF-KAPPA-B; SEVERE LIVER DEGENERATION; GROWTH-FACTOR RECEPTOR; GAMMA-DEFICIENT MICE; HARVEY-RAS ONCOGENE; KINASE-ALPHA; TERMINAL DIFFERENTIATION; INCONTINENTIA PIGMENTI; TGF-BETA; HA-RAS AB Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are two major types of skin cancer derived from keratinocytes. SCC is a more aggressive type of cancer than BCC in humans. One significant difference between SCC and BCC is that SCC development is generally associated with cell dedifferentiation and morphological changes. When SCC is converted to spindle cell carcinoma, the latest stage of cancer, the tumor cells change to a fibroblastic cell morphology (epithelial-to-mesenchymal transition) and lose their differentiation markers. Recently, several laboratories have reported altered I kappa B kinase alpha (IKK alpha) protein localization, downregulated IKK alpha, and IKK alpha gene deletions and mutations in human SCCs of the skin, lung, esophagus, and neck and head. In addition, IKK alpha reduction promotes chemical carcinogen- and ultraviolet B-induced skin carcinogenesis, and IKK alpha deletion in keratinocytes causes spontaneous skin SCCs, but not BCCs, in mice. Thus, IKK alpha emerges as a bona fide skin tumor suppressor. In this article, we will discuss the role of IKK alpha in skin SCC development. C1 [Jami, Willette-Brown; Hu, Yinling] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. [Park, Eunmi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Liu, Bigang; Zhu, Feng] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78957 USA. [Xia, Xiaojun] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. RP Hu, YL (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21701 USA. EM huy2@mail.nih.gov FU National Cancer Institute [CA102510, CA117314, CA105345] FX National Cancer Institute grants CA102510 and CA117314 (to Yinling Hu), CA105345 (to Susan M Fischer), and the National Cancer Institute intramural budget supported the work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 79 TC 6 Z9 6 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD JAN PY 2011 VL 7 IS 1 BP 123 EP 134 DI 10.2217/FON.10.166 PG 12 WC Oncology SC Oncology GA 719BJ UT WOS:000287173900014 PM 21174543 ER PT S AU Vilardaga, JP AF Vilardaga, Jean-Pierre BE Giraldo, J Pin, JP TI Emerging Signalling Properties of the PTH Receptor SO G PROTEIN-COUPLED RECEPTORS: FROM STRUCTURE TO FUNCTION SE RSC Drug Discovery Series LA English DT Article; Book Chapter ID PARATHYROID-HORMONE RECEPTOR; PROTEIN-COUPLED-RECEPTOR; PEPTIDE RECEPTOR; LIVING CELLS; NONPEPTIDE ANTAGONISTS; TRANSMEMBRANE HELICES; QUANTITATIVE-ANALYSIS; MOLECULAR-BASIS; I RECEPTOR; KINASE-C C1 [Vilardaga, Jean-Pierre] Univ Pittsburgh, Sch Med, Lab GPCR Biol, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. [Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Vilardaga, JP (reprint author), Univ Pittsburgh, Sch Med, Lab GPCR Biol, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA. NR 66 TC 0 Z9 0 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 2041-3203 BN 978-1-84973-183-6; 978-1-84973-344-1 J9 RSC DRUG DISCOV JI RSC Drug Discov. PY 2011 IS 8 BP 217 EP 231 D2 10.1039/9781849733441 PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BIE27 UT WOS:000327871700012 ER PT J AU Segal, AD Orendurff, MS Czerniecki, JM Schoen, J Klute, GK AF Segal, Ava D. Orendurff, Michael S. Czerniecki, Joseph M. Schoen, Jason Klute, Glenn K. TI Comparison of transtibial amputee and non-amputee biomechanics during a common turning task SO GAIT & POSTURE LA English DT Article DE Transtibial amputee; Rotation; Torque; Transverse plane; Turning ID GROUND REACTION FORCES; PROSTHETIC FEET; WALKING; GAIT; DEGENERATION; KINETICS; PATH; PAIN AB The biomechanics of amputee turning gait has been minimally studied, in spite of its integral relationship with the more complex gait required for household or community ambulation. This study compares the biomechanics of unilateral transtibial amputees and non-amputees completing a common turning task. Full body gait analysis was completed for subjects walking at comparable self-selected speeds around a 1 m radius circular path. Peak internal and external rotation moments of the hip, knee and ankle, mediolateral ground reaction impulse (ML GRI), peak effective limb length, and stride length were compared across conditions (non-amputee, amputee prosthetic limb, amputee sound limb). Amputees showed decreased internal rotation moments at the prosthetic limb hip and knee compared to non-amputees, perhaps as a protective mechanism to minimize stress on the residual limb. There was also an increase in amputee sound limb hip external rotation moment in early stance compared to non-amputees, which may be a compensation for the decrease in prosthetic limb internal rotation moment during late stance of the prior step. ML GRI was decreased for the amputee inside limb compared to non-amputee, possibly to minimize the body's acceleration in the direction of the turn. Amputees also exhibited a shorter inside limb stride length compared to non-amputees. Both decreased ML GRI and stride length indicate a COM that is more centered over the base of support, which may minimize the risk of falling. Finally, a longer effective limb length was found for the amputee inside limb turning, possibly due to excessive trunk shift. Published by Elsevier By. C1 [Segal, Ava D.; Orendurff, Michael S.; Czerniecki, Joseph M.; Schoen, Jason; Klute, Glenn K.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Seattle, WA USA. [Segal, Ava D.; Klute, Glenn K.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Klute, Glenn K.] Univ Washington, Dept Mech & Elect Engn, Seattle, WA 98195 USA. [Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Klute, GK (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, 1660 S Columbian Way,MS-151, Seattle, WA USA. EM gklute@u.washington.edu FU Office of Rehabilitation R&D Service, Department of Veterans Affairs, VA Puget Sound Health Care System, Seattle, WA [A36111] FX Jane B. Shofer, MS completed the statistical analysis for the present manuscript. This material is based upon work supported by the Office of Rehabilitation R&D Service (Grant # A36111), Department of Veterans Affairs, VA Puget Sound Health Care System, Seattle, WA. NR 22 TC 17 Z9 19 U1 3 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD JAN PY 2011 VL 33 IS 1 BP 41 EP 47 DI 10.1016/j.gaitpost.2010.09.021 PG 7 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 724FI UT WOS:000287561100008 PM 20974535 ER PT J AU Kastrinos, F Steyerberg, EW Mercado, R Balmana, J Holter, S Gallinger, S Siegmund, KD Church, JM Jenkins, MA Lindor, NM Thibodeau, SN Burbidge, LA Wenstrup, RJ Syngal, S AF Kastrinos, Fay Steyerberg, Ewout W. Mercado, Rowena Balmana, Judith Holter, Spring Gallinger, Steven Siegmund, Kimberly D. Church, James M. Jenkins, Mark A. Lindor, Noralane M. Thibodeau, Stephen N. Burbidge, Lynn Anne Wenstrup, Richard J. Syngal, Sapna TI The PREMM1,2,6 Model Predicts Risk of MLH1, MSH2, and MSH6 Germline Mutations Based on Cancer History SO GASTROENTEROLOGY LA English DT Article DE Lynch Syndrome; Gene-Specific Risk Estimates; Prediction Model; Colon Cancer Family Registry ID NONPOLYPOSIS COLORECTAL-CANCER; POPULATION-BASED COHORT; MISMATCH-REPAIR GENES; LYNCH-SYNDROME; COLON-CANCER; BETHESDA GUIDELINES; CLINICAL-CRITERIA; CARRIERS; FAMILIES; HNPCC AB BACKGROUND & AIMS: We developed and validated a model to estimate the risks of mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6 based on personal and family history of cancer. METHODS: Data were analyzed from 4539 probands tested for mutations in MLH1, MSH2, and MSH6. A multivariable polytomous logistic regression model (PREMM1,2,6) was developed to predict the overall risk of MMR gene mutations and the risk of mutation in each of the 3 genes. The discriminative ability of the model was validated in 1827 population-based colorectal cancer (CRC) cases. RESULTS: Twelve percent of the original cohort carried pathogenic mutations (204 in MLH1, 250 in MSH2, and 71 in MSH6). The PREMM1,2,6 model incorporated the following factors from the probands and first-and second-degree relatives (odds ratio; 95% confidence intervals [CIs]): male sex (1.9; 1.5-2.4), a CRC (4.3; 3.3-5.6), multiple CRCs (13.7; 8.5-22), endometrial cancer (6.1; 4.6-8.2), and extracolonic cancers (3.3; 2.4-4.6). The areas under the receiver operating characteristic curves were 0.86 (95% CI, 0.82-0.91) for MLH1 mutation carriers, 0.87 (95% CI, 0.83-0.92) for MSH2, and 0.81 (95% CI, 0.69-0.93) for MSH6; in validation, they were 0.88 for the overall cohort (95% CI, 0.86-0.90) and the population-based cases (95% CI, 0.83-0.92). CONCLUSIONS: We developed the PREMM1,2,6 model, which incorporates information on cancer history from probands and their relatives to estimate an individual's risk of mutations in the MMR genes MLH1, MSH2, and MSH6. This Web-based decision making tool can be used to assess risk of hereditary CRC and guide clinical management. C1 [Kastrinos, Fay] Columbia Univ Med Ctr, New York, NY 10032 USA. [Kastrinos, Fay] Herbert Irving Comprehens Canc Ctr, Div Digest & Liver Dis, New York, NY USA. [Steyerberg, Ewout W.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Mercado, Rowena; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Balmana, Judith] Univ Autonoma Barcelona, Dept Med, Hosp Vall dHebron, Dept Med Oncol, E-08193 Barcelona, Spain. [Holter, Spring; Gallinger, Steven] Univ Toronto, Mt Sinai Hosp, Dr Zane Cohen Digest Dis Clin Res Ctr, Toronto, ON M5G 1X5, Canada. [Gallinger, Steven] Univ Toronto, Dept Surg, Univ Hlth Network, Toronto, ON, Canada. [Siegmund, Kimberly D.] USC Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Church, James M.] Cleveland Clin Fdn, Dept Colorectal Surg, Inst Digest Dis, Cleveland, OH 44195 USA. [Jenkins, Mark A.] Victorian Canc Registry, Canc Epidemiol Ctr, Carlton, Vic, Australia. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Burbidge, Lynn Anne; Wenstrup, Richard J.] Myriad Genet Labs Inc, Salt Lake City, UT USA. [Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. RP Kastrinos, F (reprint author), Columbia Univ Med Ctr, 630 W 168th St, New York, NY 10032 USA. EM fk18@columbia.edu RI Gallinger, Steven/E-4575-2013; Jenkins, Mark/P-7803-2015; OI Jenkins, Mark/0000-0002-8964-6160; Steyerberg, Ewout/0000-0002-7787-0122 FU National Cancer Institute, National Institutes of Health under RFA [CA-95-011]; National Cancer Institute [R01CA132829, K24 CA113433] FX This work was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011, and through cooperative agreements with members of the Colon Cancer Family Registry and private investigators. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the CFRs, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the CFR.; Supported by the National Cancer Institute (grants R01CA132829 [to S. S.] and K24 CA113433 [to S. S.]). Recruitment, data collection, and genetic testing for the Colon Cancer Family Registry work were supported by the National Cancer Institute, National Institutes of Health (CA-95011), and through cooperative agreements with the members of the Colon Cancer Family Registry and principal investigators. NR 29 TC 78 Z9 80 U1 0 U2 4 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 JAN PY 2011 VL 140 IS 1 BP 73 EP + DI 10.1053/j.gastro.2010.08.021 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 697HF UT WOS:000285503200023 PM 20727894 ER PT J AU Rodriguez, L Flores, A Gilchrist, BF Goldstein, AM AF Rodriguez, Leonel Flores, Alejandro Gilchrist, Brian F. Goldstein, Allan M. TI Laparoscopic-assisted percutaneous endoscopic cecostomy in children with defecation disorders SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ANTEGRADE CONTINENCE ENEMA; SLOW-TRANSIT CONSTIPATION; FECAL INCONTINENCE; COLONIC ENEMA; MANAGEMENT; BUTTON AB Background: The antegrade continence enema (ACE) procedure has been widely used in the management of children with defecation disorders. The ACE procedure has undergone many technical modifications. We developed a safe and minimally invasive technique, the laparoscopic-assisted percutaneous endoscopic cecostomy (LAPEC). Objective: To compare LAPEC to laparoscopic cecostomy in terms of operative time, hospital length of stay, and procedure-related morbidity. Design: Retrospective review of children undergoing the ACE procedure. Setting: Two tertiary-care centers. Patients: This study involved children with defecation disorders. Intervention: The ACE procedure. Main Outcome Measurements: Procedure complications, length of stay, and operative time. Results: Fifty patients underwent LAPEC, and 15 underwent laparoscopic cecostomy. Of the LAPEC patients, 70% were male, with mean age 12 +/- 4.2 years, mean operative time 100.1 +/- 16.6 minutes, and mean length of stay 3.4 +/- 1.4 days. Of the laparoscopic cecostomy patients, 56% were male, with mean age 10.5 +/- 4 years, mean operative time 100.8 +/- 19.1 minutes, and mean length of stay 3.8 +/- 1.6 clays. There was no statistical difference between the 2 groups. The single intraoperative complication during LAPEC was a cecal hematoma. Postoperative complications after LAPEC included 6 patients with low-grade fever, 3 patients with tube dislodgement (2 treated by repeat LAPEC and the other by open surgery), and 2 patients with skin breakdown. Of the 50 LAPEC patients and their families, 48 were satisfied with the outcome. Limitations: Retrospective study. Conclusion: LAPEC is a safe, minimally invasive procedure for cecostomy placement in children with refractory constipation or fecal incontinence. (Gastrointest Endosc 2011;73:98-102.) C1 [Rodriguez, Leonel] Harvard Univ, Childrens Hosp Boston, Ctr Motil & Funct Gastrointestinal Disorders, Sch Med,Div Gastroenterol,Dept Pediat, Boston, MA 02115 USA. [Goldstein, Allan M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02115 USA. [Flores, Alejandro] Tufts Univ, Sch Med, Dept Pediat, Div Gastroenterol,Floating Hosp Children, Boston, MA 02111 USA. [Gilchrist, Brian F.] Elliot Hosp, Dept Pediat Surg, Manchester, NH USA. RP Rodriguez, L (reprint author), Harvard Univ, Childrens Hosp Boston, Ctr Motil & Funct Gastrointestinal Disorders, Sch Med,Div Gastroenterol,Dept Pediat, 300 Longwood Ave, Boston, MA 02115 USA. EM Leonel.rodriguez@childrens.harvard.edu NR 17 TC 10 Z9 10 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 JAN PY 2011 VL 73 IS 1 BP 98 EP 102 DI 10.1016/j.gie.2010.09.011 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 702QO UT WOS:000285909400014 PM 21184875 ER PT J AU Di Stefano, L Walker, JA Burgio, G Corona, DFV Mulligan, P Naar, AM Dyson, NJ AF Di Stefano, Luisa Walker, James A. Burgio, Giosalba Corona, Davide F. V. Mulligan, Peter Naeaer, Anders M. Dyson, Nicholas J. TI Functional antagonism between histone H3K4 demethylases in vivo SO GENES & DEVELOPMENT LA English DT Article DE Drosophila; histone demethylases; H3K4me; H3K9me; heterochromatin; Notch signaling ID POSITION-EFFECT VARIEGATION; DROSOPHILA-MELANOGASTER; HETEROCHROMATIN; METHYLATION; CHROMATIN; CELL; GENES; NOTCH; LSD1; COMPLEXES AB Dynamic regulation of histone modifications is critical during development, and aberrant activity of chromatin-modifying enzymes has been associated with diseases such as cancer. Histone demethylases have been shown to play a key role in eukaryotic gene transcription; however, little is known about how their activities are coordinated in vivo to regulate specific biological processes. In Drosophila, two enzymes, dLsd1 (Drosophila ortholog of lysine-specific demethylase 1) and Lid (little imaginal discs), demethylate histone H3 at Lys 4 (H3K4), a residue whose methylation is associated with actively transcribed genes. Our studies show that compound mutation of Lid and dLsd1 results in increased H3K4 methylation levels. However, unexpectedly, Lid mutations strongly suppress dLsd1 mutant phenotypes. Investigation of the basis for this antagonism revealed that Lid opposes the functions of dLsd1 and the histone methyltransferase Su(var)3-9 in promoting heterochromatin spreading at heterochromatin-euchromatin boundaries. Moreover, our data reveal a novel role for dLsd1 in Notch signaling in Drosophila, and a complex network of interactions between dLsd1, Lid, and Notch signaling at euchromatic genes. These findings illustrate the complexity of functional interplay between histone demethylases in vivo, providing insights into the epigenetic regulation of heterochromatin/euchromatin boundaries by Lid and dLsd1 and showing their involvement in Notch pathway-specific control of gene expression in euchromatin. C1 [Di Stefano, Luisa; Walker, James A.; Mulligan, Peter; Naeaer, Anders M.; Dyson, Nicholas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Di Stefano, Luisa] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Walker, James A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Burgio, Giosalba; Corona, Davide F. V.] Univ Palermo, Dipartimento Biol Cellulare & Sviluppo, I-90128 Palermo, Italy. [Burgio, Giosalba; Corona, Davide F. V.] Univ Palermo, Ist Telethon Dulbecco, I-90128 Palermo, Italy. [Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Dyson, NJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu RI Corona, Davide/H-8467-2012 FU NIH [GM81607, GM53203, CA64402, GM071449]; Leukemia and Lymphoma Society; DoD [W81XWH-09-1-0487]; FIRC; Fondazione Telethon; Giovanni Armenise Harvard Foundation; MIUR; HFSP; AIRC; EMBO FX We thank Dr. Spyros Artanavis-Tsakonas, Dr. James Kennison, Dr. Jessica Treisman, and Dr. Chao Ting Wu for providing fly stocks, and members of the Dyson laboratory for technical assistance and helpful discussion. We thank Dr. Kristian Helin for critical reading of the manuscript. This study was supported by NIH grants GM81607, GM53203, and CA64402 to N.J.D., and GM071449 to A.M.N. L.D.S. was supported by a fellowship from the Leukemia and Lymphoma Society. J.A.W. was supported by a grant from the DoD (W81XWH-09-1-0487). G.B. was supported by a FIRC Fellowship, and D.C. was supported by Fondazione Telethon, Giovanni Armenise Harvard Foundation, MIUR-PRIN, HFSP, AIRC, and EMBO-YIP. N.J.D. is the Saltonstall Scholar of the Massachusetts General Hospital Cancer Center. NR 35 TC 30 Z9 30 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 2011 VL 25 IS 1 BP 17 EP 28 DI 10.1101/gad.1983711 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 702BT UT WOS:000285870300003 PM 21205864 ER PT J AU Manning, AK LaValley, M Liu, CT Rice, K An, P Liu, YM Miljkovic, I Rasmussen-Torvik, L Harris, TB Province, MA Borecki, IB Florez, JC Meigs, JB Cupples, LA Dupuis, J AF Manning, Alisa K. LaValley, Michael Liu, Ching-Ti Rice, Kenneth An, Ping Liu, Yongmei Miljkovic, Iva Rasmussen-Torvik, Laura Harris, Tamara B. Province, Michael A. Borecki, Ingrid B. Florez, Jose C. Meigs, James B. Cupples, L. Adrienne Dupuis, Josee TI Meta-Analysis of Gene-Environment Interaction: Joint Estimation of SNP and SNP x Environment Regression Coefficients SO GENETIC EPIDEMIOLOGY LA English DT Article DE 2 degree of freedom meta-analysis; joint meta-analysis; PPARG; gene-environment interaction meta-analysis ID GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES RISK; PRO12ALA POLYMORPHISM; DESIGN; HEART; OBJECTIVES; HEALTH; GAMMA AB Introduction: Genetic discoveries are validated through the meta-analysis of genome-wide association scans in large international consortia. Because environmental variables may interact with genetic factors, investigation of differing genetic effects for distinct levels of an environmental exposure in these large consortia may yield additional susceptibility loci undetected by main effects analysis. We describe a method of joint meta-analysis (JMA) of SNP and SNP by Environment (SNP x E) regression coefficients for use in gene-environment interaction studies. Methods: In testing SNP x E interactions, one approach uses a two degree of freedom test to identify genetic variants that influence the trait of interest. This approach detects both main and interaction effects between the trait and the SNP. We propose a method to jointly meta-analyze the SNP and SNP x E coefficients using multivariate generalized least squares. This approach provides confidence intervals of the two estimates, a joint significance test for SNP and SNP x E terms, and a test of homogeneity across samples. Results: We present a simulation study comparing this method to four other methods of meta-analysis and demonstrate that the JMA performs better than the others when both main and interaction effects are present. Additionally, we implemented our methods in a meta-analysis of the association between SNPs from the type 2 diabetes-associated gene PPARG and log-transformed fasting insulin levels and interaction by body mass index in a combined sample of 19,466 individuals from five cohorts. Genet. Epidemiol. 35:11-18, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Manning, Alisa K.; LaValley, Michael; Liu, Ching-Ti; Cupples, L. Adrienne; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [An, Ping; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Liu, Yongmei] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Miljkovic, Iva] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA. [Rasmussen-Torvik, Laura] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Harris, Tamara B.] NIA, Geriatr Epidemiol Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Cupples, L. Adrienne; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Manning, AK (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. EM amanning@bu.edu; dupuis@bu.edu RI Rice, Kenneth/A-4150-2013 OI Rice, Kenneth/0000-0001-5779-4495 FU National Heart, Lung and Blood Institute [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Department of Medicine at Boston University School of Medicine and Boston Medical Center; Doris Duke Charitable Foundation; National Institute on Aging; National Institute for Diabetes and Digestive and Kidney Diseases [R01 DK078616, K24 DK080140, K23 DK65978, K01 DK083029]; NIA [N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C, HHSN268200625226C, 5R01 HL08770003]; National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, U01HG004402, N01-HC- 85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL087652, 5R01 HL08821502]; National Institute of Neurological Disorders and Stroke; National Center for Research Resources [M01RR00069]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491, 5R01 DK07568102, 5R01 DK06833603] FX Contract grant sponsor: National Heart, Lung and Blood Institute's Framingham Heart Study; Contract grant number: N01-HC-25195; Contract grant sponsor: Affymetrix, Inc; Contract grant number: N02-HL-6-4278; Contract grant sponsors: Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center, Massachusetts General Hospital Physician Scientist Development Award and a Doris Duke Charitable Foundation Clinical Scientist Development Award, National Institute on Aging; National Institute for Diabetes and Digestive and Kidney Diseases; Contract grant numbers: R01 DK078616; K24 DK080140; K23 DK65978; K01 DK083029; Contract grant sponsor: NIA; Contract grant numbers: N01AG62101; N01AG62103; N01AG62106; 1R01AG032098-01A1; Contract grant sponsor: National Institutes of Health; Contract grant numbers: HHSN268200782096C; HHSN268200625226C; 5R01 HL08770003; Contract grant sponsor: National Heart, Lung, and Blood Institute; Contract grant numbers: N01-HC-55015; N01-HC-55016; N01-HC-55018; N01-HC-55019; N01-HC-55020; N01-HC-55021; N01-HC-55022; R01HL087641; R01HL59367; R01HL086694; U01HG004402; N01-HC- 85079; N01-HC-85086; N01-HC-35129; N01 HC-15103; N01 HC-55222; N01-HC-75150; N01-HC-45133; U01 HL080295; R01 HL087652; 5R01 HL08821502; Contract grant sponsors: National Institute of Neurological Disorders and Stroke; National Center for Research Resources; Contract grant number: M01RR00069; Contract grant sponsor: National Institute of Diabetes and Digestive and Kidney Diseases; Contract grant numbers: DK063491; 5R01 DK07568102; 5R01 DK06833603. NR 29 TC 54 Z9 54 U1 2 U2 10 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 JAN PY 2011 VL 35 IS 1 BP 11 EP 18 DI 10.1002/gepi.20546 PG 8 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 705RQ UT WOS:000286156000002 PM 21181894 ER PT J AU Chen, YW Meyer, CA Liu, T Li, W Liu, JS Liu, XS AF Chen, Yiwen Meyer, Clifford A. Liu, Tao Li, Wei Liu, Jun S. Liu, Xiaole Shirley TI MM-ChIP enables integrative analysis of cross-platform and between-laboratory ChIP-chip or ChIP-seq data SO GENOME BIOLOGY LA English DT Review ID GENOME-WIDE ANALYSIS; CHROMATIN STATE; JOINT ANALYSIS; BINDING-SITES; INSIGHTS; MODEL; MAPS AB The ChIP-chip and ChIP-seq techniques enable genome-wide mapping of in vivo protein-DNA interactions and chromatin states. The cross-platform and between-laboratory variation poses a challenge to the comparison and integration of results from different ChIP experiments. We describe a novel method, MM-ChIP, which integrates information from cross-platform and between-laboratory ChIP-chip or ChIP-seq datasets. It improves both the sensitivity and the specificity of detecting ChIP-enriched regions, and is a useful meta-analysis tool for driving discoveries from multiple data sources. C1 [Chen, Yiwen; Meyer, Clifford A.; Liu, Tao; Liu, Xiaole Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Chen, Yiwen; Meyer, Clifford A.; Liu, Tao; Liu, Xiaole Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Li, Wei] Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Li, Wei] Tongji Univ, Dept Bioinformat, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. [Liu, Jun S.] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Liu, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM xsliu@jimmy.harvard.edu RI Liu, Tao/G-3585-2010; OI Liu, Tao/0000-0002-8818-8313; Liu, Tao/0000-0003-0446-9001 FU NIH [HG004069, DK62434] FX We would like to thank the three anonymous reviewers for their insightful comments, which greatly helped improve this manuscript. This work was partially funded by NIH grants HG004069 and DK62434. NR 29 TC 14 Z9 14 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 2 AR R11 DI 10.1186/gb-2011-12-2-r11 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 748BS UT WOS:000289365600007 PM 21284836 ER PT J AU Liu, T Ortiz, JA Taing, L Meyer, CA Lee, B Zhang, Y Shin, H Wong, SS Ma, J Lei, Y Pape, UJ Poidinger, M Chen, YW Yeung, K Brown, M Turpaz, Y Liu, XS AF Liu, Tao Ortiz, Jorge A. Taing, Len Meyer, Clifford A. Lee, Bernett Zhang, Yong Shin, Hyunjin Wong, Swee S. Ma, Jian Lei, Ying Pape, Utz J. Poidinger, Michael Chen, Yiwen Yeung, Kevin Brown, Myles Turpaz, Yaron Liu, X. Shirley TI Cistrome: an integrative platform for transcriptional regulation studies SO GENOME BIOLOGY LA English DT Article ID MODEL-BASED ANALYSIS; DIFFERENTIAL EXPRESSION ANALYSIS; CHIP-SEQ DATA; GENE-EXPRESSION; GENOME; SITES; BIOCONDUCTOR; ARCHIVE; SYSTEM; ARRAYS AB The increasing volume of ChIP-chip and ChIP-seq data being generated creates a challenge for standard, integrative and reproducible bioinformatics data analysis platforms. We developed a web-based application called Cistrome, based on the Galaxy open source framework. In addition to the standard Galaxy functions, Cistrome has 29 ChIP-chip- and ChIP-seq-specific tools in three major categories, from preliminary peak calling and correlation analyses to downstream genome feature association, gene expression analyses, and motif discovery. Cistrome is available at http://cistrome.org/ap/. C1 [Liu, Tao; Taing, Len; Shin, Hyunjin; Brown, Myles; Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Liu, Tao; Taing, Len; Meyer, Clifford A.; Shin, Hyunjin; Pape, Utz J.; Chen, Yiwen; Liu, X. Shirley] Harvard Univ, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Liu, Tao; Taing, Len; Meyer, Clifford A.; Shin, Hyunjin; Pape, Utz J.; Chen, Yiwen; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Ortiz, Jorge A.; Lee, Bernett; Wong, Swee S.; Poidinger, Michael; Yeung, Kevin; Turpaz, Yaron] Lilly Singapore Ctr Drug Discovery, Singapore 138648, Singapore. [Ortiz, Jorge A.] Beijing Genom Inst, Shenzhen 518083, Peoples R China. [Lee, Bernett; Poidinger, Michael] Singapore Immunol Network, Singapore 138648, Singapore. [Zhang, Yong; Ma, Jian] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. [Wong, Swee S.] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Lei, Ying] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Yeung, Kevin] Jardine Lloyd Thompson Asia, Singapore 048583, Singapore. [Brown, Myles] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Turpaz, Yaron] AstraZeneca Pharmaceut LP, Waltham, MA 02451 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. EM myles_brown@dfci.harvard.edu; yaron.turpaz@astrazeneca.com; xsliu@jimmy.harvard.edu RI Liu, Tao/G-3585-2010; Zhang, Yong/B-4838-2011; OI Liu, Tao/0000-0002-8818-8313; Zhang, Yong/0000-0001-6316-2734; Poidinger, Michael/0000-0002-1047-2277; Brown, Myles/0000-0002-8213-1658; Liu, Tao/0000-0003-0446-9001 FU Dana-Farber Cancer Institute; National Basic Research Program of China grant 973 Program [2010CB944904]; NIH [HG004069-04S1, DK074967, DK062434] FX Cistrome was developed by the Cistrome team at both the Dana-Farber Cancer Institute and Eli Lilly and Company. We thank Lingling Shen, Wenbo Wang, Jacqueline Wentz, Josiah Altschuler and Kar Joon Chew for their contributions to the system implementation. We also thank the many collaborators who gave us suggestions and feedback. This work is supported by the Dana-Farber Cancer Institute High Tech and Campaign Technology Fund (XSL), the National Basic Research Program of China grant 973 Program No. 2010CB944904 (YZ), NIH grants HG004069-04S1 (LT), DK074967 (MB) and DK062434 (TL). NR 40 TC 203 Z9 203 U1 3 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 8 AR R83 DI 10.1186/gb-2011-12-8-r83 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 843CI UT WOS:000296649500013 PM 21859476 ER PT J AU Mermel, CH Schumacher, SE Hill, B Meyerson, ML Beroukhim, R Getz, G AF Mermel, Craig H. Schumacher, Steven E. Hill, Barbara Meyerson, Matthew L. Beroukhim, Rameen Getz, Gad TI GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers SO GENOME BIOLOGY LA English DT Article ID CIRCULAR BINARY SEGMENTATION; ARRAY CGH DATA; MICROARRAY DATA; HIGH-RESOLUTION; HUMAN BREAST; GENOME; ABERRATIONS; LUNG; IDENTIFICATION; REARRANGEMENT AB We describe methods with enhanced power and specificity to identify genes targeted by somatic copy-number alterations (SCNAs) that drive cancer growth. By separating SCNA profiles into underlying arm-level and focal alterations, we improve the estimation of background rates for each category. We additionally describe a probabilistic method for defining the boundaries of selected-for SCNA regions with user-defined confidence. Here we detail this revised computational approach, GISTIC2.0, and validate its performance in real and simulated datasets. C1 [Mermel, Craig H.; Schumacher, Steven E.; Hill, Barbara; Meyerson, Matthew L.; Beroukhim, Rameen; Getz, Gad] Broad Inst MIT & Harvard, Canc Program, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Mermel, Craig H.; Schumacher, Steven E.; Meyerson, Matthew L.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mermel, Craig H.; Schumacher, Steven E.; Meyerson, Matthew L.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Mermel, Craig H.; Schumacher, Steven E.; Meyerson, Matthew L.; Beroukhim, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. RP Beroukhim, R (reprint author), Broad Inst MIT & Harvard, Canc Program, Cambridge Ctr 7, Cambridge, MA 02142 USA. EM Rameen_Beroukhim@dfci.harvard.edu; gadgetz@broadinstitute.org RI Meyerson, Matthew/E-7123-2012; Schumacher, Steven/E-9821-2013 OI Schumacher, Steven/0000-0002-6819-5647 FU Genome Characterization Center [U24CA143867]; National Institute of General Medical Sciences [T32GM07753]; NIH [K08CA122833]; V Foundation Scholarship; Doris Duke Charitable Foundation FX This work was supported by a Genome Characterization Center Grant (U24CA143867) awarded as part of the NCI/NHGRI funded Cancer Genome Atlas (TCGA) project. CHM was supported by Medical Scientist Training Program (MSTP) Award Number T32GM07753 from the National Institute of General Medical Sciences. RB was supported by NIH K08CA122833, a V Foundation Scholarship, and the Doris Duke Charitable Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. NR 44 TC 344 Z9 346 U1 1 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 4 AR R41 DI 10.1186/gb-2011-12-4-r41 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 794BW UT WOS:000292871100009 PM 21527027 ER PT J AU Segata, N Izard, J Waldron, L Gevers, D Miropolsky, L Garrett, WS Huttenhower, C AF Segata, Nicola Izard, Jacques Waldron, Levi Gevers, Dirk Miropolsky, Larisa Garrett, Wendy S. Huttenhower, Curtis TI Metagenomic biomarker discovery and explanation SO GENOME BIOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; MARINE MICROBIAL DIVERSITY; GENOME-WIDE ASSOCIATION; ULCERATIVE-COLITIS; GUT MICROBIOME; CROHNS-DISEASE; FECAL BACTERIOTHERAPY; CAMPYLOBACTER-JEJUNI; RARE BIOSPHERE; OVARIAN-CANCER AB This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/. C1 [Segata, Nicola; Waldron, Levi; Miropolsky, Larisa; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Izard, Jacques] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Izard, Jacques] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Gevers, Dirk] Broad Inst MIT & Harvard, Microbial Sequencing Ctr, Cambridge Ctr 7, Cambridge, MA 02142 USA. [Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Garrett, Wendy S.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Huttenhower, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. EM chuttenh@hsph.harvard.edu RI Izard, Jacques/A-6074-2012; OI Izard, Jacques/0000-0002-5904-5436; Waldron, Levi/0000-0003-2725-0694; Huttenhower, Curtis/0000-0002-1110-0096; Segata, Nicola/0000-0002-1583-5794 FU National Institute of Dental and Craniofacial Research [DE017106]; NIH [AI078942, 1R01HG005969]; Burroughs Wellcome Fund FX We would like to thank the entire Human Microbiome Project consortium, including the four sequencing centers (the Broad Institute, Washington University, Baylor College of Medicine, and the J Craig Venter Institute), associated investigators from many additional institutions, and the NIH Office of the Director Roadmap Initiative. This work was supported in part by grant DE017106 from the National Institute of Dental and Craniofacial Research (JI), NIH grants AI078942 (WSG) and Burroughs Wellcome Fund (WSG), and was funded by NIH 1R01HG005969 to CH. NR 113 TC 578 Z9 584 U1 30 U2 142 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 6 AR R60 DI 10.1186/gb-2011-12-6-r60 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 843BF UT WOS:000296646600008 PM 21702898 ER PT J AU Huang, CM Florez, JC AF Huang, Chunmei Florez, Jose C. TI Pharmacogenetics in type 2 diabetes: potential implications for clinical practice SO GENOME MEDICINE LA English DT Review DE Type 2 diabetes; pharmacogenetics; genome-wide association studies; single nucleotide polymorphisms; sulfonylureas; metformin; thiazolidinediones} AB Pharmacogenetic research aims to study how genetic variation may influence drug efficacy and/or toxicity; pharmacogenomics expands this quest to the entire genome. Pharmacogenetic findings may help to uncover new drug targets, illuminate pathophysiology, clarify disease heterogeneity, aid in the fine-mapping of genetic associations, and contribute to personalized treatment. In diabetes, there is precedent for the successful application of pharmacogenetic concepts to monogenic forms of the disease, such as maturity onset diabetes of the young or neonatal diabetes. Whether similar insights will be produced for the common form of type 2 diabetes remains to be seen. With recent advances in genetic approaches, the successive application of candidate gene studies, large-scale genotyping studies and genome-wide association studies has begun to generate suggestive results that may lead to changes in clinical practice. However, many potential barriers to the translation of pharmacogenetic discoveries to the clinical management of diabetes still remain. Here, we offer a contemporary overview of the field in its current state, identify potential obstacles, and highlight future directions. C1 [Huang, Chunmei] Massachusetts Gen Hosp, Dept Med, Renal Div, Boston, MA 02114 USA. [Huang, Chunmei; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Huang, Chunmei; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Bldg, Boston, MA 02114 USA. EM jcflorez@partners.org FU NIH/NIDDK [R01 DK072041, R01 DK088214]; Clinician Scientist Development Award; Doris Duke Charitable Foundation; NIH [5 T32 DK007540-25] FX JCF is supported by NIH/NIDDK R01 DK072041 and R01 DK088214 and a Clinician Scientist Development Award granted by the Doris Duke Charitable Foundation. CH is supported by NIH training grant 5 T32 DK007540-25. NR 77 TC 13 Z9 13 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2011 VL 3 AR 76 DI 10.1186/gm292 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA V27QJ UT WOS:000208627400076 PM 22126607 ER PT J AU Kim, J Orkin, SH AF Kim, Jonghwan Orkin, Stuart H. TI Embryonic stem cell-specific signatures in cancer: insights into genomic regulatory networks and implications for medicine SO GENOME MEDICINE LA English DT Review AB Embryonic stem (ES) cells are of great interest as a model system for studying early developmental processes and because of their potential therapeutic applications in regenerative medicine. Obtaining a systematic understanding of the mechanisms that control the 'stemness' - self-renewal and pluripotency - of ES cells relies on high-throughput tools to define gene expression and regulatory networks at the genome level. Such recently developed systems biology approaches have revealed highly interconnected networks in which multiple regulatory factors act in combination. Interestingly, stem cells and cancer cells share some properties, notably self-renewal and a block in differentiation. Recently, several groups reported that expression signatures that are specific to ES cells are also found in many human cancers and in mouse cancer models, suggesting that these shared features might inform new approaches for cancer therapy. Here, we briefly summarize the key transcriptional regulators that contribute to the pluripotency of ES cells, the factors that account for the common gene expression patterns of ES and cancer cells, and the implications of these observations for future clinical applications. C1 [Kim, Jonghwan] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA. [Orkin, Stuart H.] Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Dept Pediat Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS) [K99/R00GM088384] FX We thank Andrew J Woo for critical reading of the manuscript. SHO is an investigator at the Howard Hughes Medical Institute. JK is supported by the National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS) grant K99/R00GM088384. NR 81 TC 30 Z9 31 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2011 VL 3 AR 75 DI 10.1186/gm291 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA V27QJ UT WOS:000208627400075 PM 22126538 ER PT J AU Onder, TT Daley, GQ AF Onder, Tamer T. Daley, George Q. TI microRNAs become macro players in somatic cell reprogramming SO GENOME MEDICINE LA English DT Editorial Material AB Embryonic stem cell specific microRNAs (miRNAs) have previously been shown to enhance the efficiency of transcription-factor-based reprogramming. However, whether reprogramming could be achieved entirely by miRNAs remained unclear. A recent report shows that the expression of the miR-302/367 cluster of miRNAs can directly reprogram somatic cells without the use of any transcription factors. This new method raises interesting questions about the mechanisms of reprogramming and is likely to facilitate the generation of induced pluripotent stem cells for potential future clinical use. C1 [Onder, Tamer T.; Daley, George Q.] Childrens Hosp Boston, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Manton Ctr Orphan Dis Res,Howard Hughes Med Inst, Boston, MA 02115 USA. [Onder, Tamer T.; Daley, George Q.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. [Onder, Tamer T.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp Boston, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Manton Ctr Orphan Dis Res,Howard Hughes Med Inst, Boston, MA 02115 USA. EM George.daley@childrens.harvard.edu RI Onder, Tamer /H-3330-2013 OI Onder, Tamer /0000-0002-2372-9158 NR 10 TC 5 Z9 6 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2011 VL 3 AR 40 DI 10.1186/gm256 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA V27QJ UT WOS:000208627400040 PM 21699744 ER PT J AU Orkin, SH AF Orkin, Stuart H. TI Genome Medicine: stem cells, genomics and translational research SO GENOME MEDICINE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02116 USA. RP Orkin, SH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02116 USA. EM stuart_orkin@dfci.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2011 VL 3 AR 34 DI 10.1186/gm250 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA V27QJ UT WOS:000208627400034 PM 21658298 ER PT J AU Weir, GC Cavelti-Weder, C Bonner-Weir, S AF Weir, Gordon C. Cavelti-Weder, Claudia Bonner-Weir, Susan TI Stem cell approaches for diabetes: towards beta cell replacement SO GENOME MEDICINE LA English DT Review DE Beta cell; embryonic stem cell; islet; islet regeneration AB Stem cells hold great promise for pancreatic beta cell replacement therapy for diabetes. In type 1 diabetes, beta cells are mostly destroyed, and in type 2 diabetes beta cell numbers are reduced by 40% to 60%. The proof-of-principle that cellular transplants of pancreatic islets, which contain insulin-secreting beta cells, can reverse the hyperglycemia of type 1 diabetes has been established, and there is now a need to find an adequate source of islet cells. Human embryonic stem cells can be directed to become fully developed beta cells and there is expectation that induced pluripotent stem (iPS) cells can be similarly directed. iPS cells can also be generated from patients with diabetes to allow studies of the genomics and pathogenesis of the disease. Some alternative approaches for replacing beta cells include finding ways to enhance the replication of existing beta cells, stimulating neogenesis (the formation of new islets in postnatal life), and reprogramming of pancreatic exocrine cells to insulin-producing cells. Stem-cell-based approaches could also be used for modulation of the immune system in type 1 diabetes, or to address the problems of obesity and insulin resistance in type 2 diabetes. Herein, we review recent advances in our understanding of diabetes and beta cell biology at the genomic level, and we discuss how stem-cell-based approaches might be used for replacing beta cells and for treating diabetes. C1 [Weir, Gordon C.] Joslin Diabet Ctr, Div Res, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Cell & Regenerat Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU Joslin Diabetes and Endocrinology Research Center (DERC) [NIH RC4 DK090781-01, R01 DK 66056, P30 DK36836]; Juvenile Diabetes Research Foundation [2008-522, 2007-1063, 2008-641]; Swiss National Foundation; Diabetes Research and Wellness Foundation FX Supported by: NIH RC4 DK090781-01 (GCW), R01 DK 66056 (SBW) and P30 DK36836 Joslin Diabetes and Endocrinology Research Center (DERC); Juvenile Diabetes Research Foundation 2008-522 and 2007-1063 (GCW) and 2008-641 (SBW); the Swiss National Foundation (CCW) and the Diabetes Research and Wellness Foundation (GCW). All of the authors contributed to writing the manuscript. NR 76 TC 24 Z9 25 U1 2 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2011 VL 3 AR 61 DI 10.1186/gm277 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA V27QJ UT WOS:000208627400061 PM 21951399 ER PT J AU Thorrez, L Laudadio, I Van Deun, K Quintens, R Hendrickx, N Granvik, M Lemaire, K Schraenen, A Van Lommel, L Lehnert, S Aguayo-Mazzucato, C Rui, CX Gilon, P Van Mechelen, I Bonner-Weir, S Lemaigre, F Schuit, F AF Thorrez, Lieven Laudadio, Ilaria Van Deun, Katrijn Quintens, Roel Hendrickx, Nico Granvik, Mikaela Lemaire, Katleen Schraenen, Anica Van Lommel, Leentje Lehnert, Stefan Aguayo-Mazzucato, Cristina Rui Cheng-Xue Gilon, Patrick Van Mechelen, Iven Bonner-Weir, Susan Lemaigre, Frederic Schuit, Frans TI Tissue-specific disallowance of housekeeping genes: The other face of cell differentiation SO GENOME RESEARCH LA English DT Article ID PANCREATIC BETA-CELLS; EMBRYONIC STEM-CELLS; DNA METHYLATION; EXPRESSION; MICRORNAS; IDENTIFICATION; MOUSE; LIVER; HYPOGLYCEMIA; HYPOTHESIS AB We report on a hitherto poorly characterized class of genes that are expressed in all tissues, except in one. Often, these genes have been classified as housekeeping genes, based on their nearly ubiquitous expression. However, the specific repression in one tissue defines a special class of "disallowed genes.'' In this paper, we used the intersection-union test to screen for such genes in a multi-tissue panel of genome-wide mRNA expression data. We propose that disallowed genes need to be repressed in the specific target tissue to ensure correct tissue function. We provide mechanistic data of repression with two metabolic examples, exercise-induced inappropriate insulin release and interference with ketogenesis in liver. Developmentally, this repression is established during tissue maturation in the early postnatal period involving epigenetic changes in histone methylation. In addition, tissue-specific expression of microRNAs can further diminish these repressed mRNAs. Together, we provide a systematic analysis of tissue-specific repression of housekeeping genes, a phenomenon that has not been studied so far on a genome-wide basis and, when perturbed, can lead to human disease. C1 [Thorrez, Lieven; Quintens, Roel; Hendrickx, Nico; Granvik, Mikaela; Lemaire, Katleen; Schraenen, Anica; Van Lommel, Leentje; Lehnert, Stefan; Schuit, Frans] Katholieke Univ Leuven, Dept Mol Cell Biol, Gene Express Unit, B-3000 Louvain, Belgium. [Thorrez, Lieven] Katholieke Univ Leuven, Dept Elect Engn, ESAT SCD, B-3000 Louvain, Belgium. [Thorrez, Lieven; Van Deun, Katrijn; Quintens, Roel; Hendrickx, Nico; Granvik, Mikaela; Lemaire, Katleen; Schraenen, Anica; Van Lommel, Leentje; Lehnert, Stefan; Van Mechelen, Iven; Schuit, Frans] Katholieke Univ Leuven, Ctr Computat Syst Biol, B-3000 Louvain, Belgium. [Laudadio, Ilaria; Lemaigre, Frederic] Catholic Univ Louvain, de Duve Inst, B-1200 Brussels, Belgium. [Aguayo-Mazzucato, Cristina; Bonner-Weir, Susan] Harvard Univ, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. [Rui Cheng-Xue; Gilon, Patrick] Univ Louvain, Fac Med, Unite Endocrinol & Metab, B-1200 Brussels, Belgium. RP Schuit, F (reprint author), Katholieke Univ Leuven, Dept Mol Cell Biol, Gene Express Unit, B-3000 Louvain, Belgium. EM frans.schuit@med.kuleuven.be RI Thorrez, Lieven/A-2583-2011 OI Thorrez, Lieven/0000-0002-5896-6823 FU K.U. Leuven [GOA/2004/11, GOA/2005/04, GOA/2009/10, CoE EF/05/007]; Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO) [G.0733.09N]; Belgian Science Policy [PAI 6/20, 6/40]; D.G. Higher Education and Scientific Research of the French Community of Belgium; Juvenile Diabetes Research Foundation (JDRF) [2006-182, 2007-685]; National Institutes of Health (NIH) [NIH R01 DK 66056]; Televie (Belgium) FX This study was supported by research grants from K.U. Leuven (GOA/2004/11, GOA/2005/04, GOA/2009/10, and CoE EF/05/007), Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO grant G.0733.09N), the Belgian Science Policy (Interuniversity Attraction Poles Program (PAI 6/20 and 6/40), the D.G. Higher Education and Scientific Research of the French Community of Belgium, the Juvenile Diabetes Research Foundation (JDRF grants 2006-182, 2007-685), and the National Institutes of Health (NIH R01 DK 66056). P.G. is Research Director at the FNRS, and I.L. holds a fellowship from Televie (Belgium). We thank Joris Van Arensbergen for providing the data used in Supplemental Figure S6 and Sabine Cordi for technical assistance. NR 52 TC 69 Z9 69 U1 1 U2 7 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 J9 GENOME RES JI Genome Res. PD JAN PY 2011 VL 21 IS 1 BP 95 EP 105 DI 10.1101/gr.109173.110 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 702BC UT WOS:000285868300010 PM 21088282 ER PT J AU Tucker, J AF Tucker, Joseph TI Passage to manhood: Youth migration, heroin and AIDS in Southwest China SO GLOBAL PUBLIC HEALTH LA English DT Book Review C1 [Tucker, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tucker, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jtucker4@partners.org NR 1 TC 0 Z9 0 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1744-1692 J9 GLOB PUBLIC HEALTH JI Glob. Public Health PY 2011 VL 6 IS 6 BP 684 EP 685 DI 10.1080/17441692.2011.589396 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 825FE UT WOS:000295255600010 ER PT J AU Mak, RH Halasz, LM Tanaka, CK Ancukiewicz, M Schultz, DJ Russell, AH Viswanathan, AN AF Mak, Raymond H. Halasz, Lia M. Tanaka, Cynthia K. Ancukiewicz, Marek Schultz, Delray J. Russell, Anthony H. Viswanathan, Akila N. TI Outcomes after radiation therapy with concurrent weekly platinum-based chemotherapy or every-3-4-week 5-fluorouracil-containing regimens for squamous cell carcinoma of the vulva SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Chemotherapy; Radiotherapy; Squamous cell carcinoma; Vulvar cancer ID LOCALLY ADVANCED-CARCINOMA; GYNECOLOGIC-ONCOLOGY-GROUP; ADVANCED CERVICAL-CANCER; PELVIC NODE RESECTION; PREOPERATIVE CHEMORADIATION; MITOMYCIN-C; RADICAL SURGERY; RADIOTHERAPY; CISPLATIN; TRIAL AB Objective. To compare outcomes in patients with squamous cell carcinoma (SCC) of the vulva treated with radiation (RT) and concurrent weekly platinum-based or every-3-4-week regimens containing 5-fluorouracil (5-FU). Methods. Records of 44 patients with vulvar SCC treated with concurrent chemotherapy and radiation (chemoRT) from 1988 to 2008 were reviewed. Rates of disease-free survival (DFS), overall survival (OS), locoregional recurrence (LRR), and distant metastases (DM) were estimated using the Kaplan-Meier method. Results. The median age was 63 years (range, 44-90), 84.1% of patients had ECOG performance status 0-1, and patients had FIGO Stage II (n = 6), III (n = 31), or IVA (n = 7) disease. Patients were treated preoperatively (n = 10), postoperatively (n = 10), or without surgery (n = 24). The median RT dose to the vulva was 50.2 Gray (range, 22-75). Concurrent chemotherapy regimens included weekly platinum (n = 16) or every 3-4 week regimens with 5-FU as the backbone (n = 28). With a median follow-up of 31.5 months, there was no significant difference in 2-year OS (74.5% vs. 70.0%; p = 0.65), DFS (61.9% vs. 56.0%; p = 0.85), LRR (31.3% vs. 32.9%; p = 0.93), or DM (6.3% vs. 10.6%; p = 0.81) between the weekly platinum and every-3-4-week 5-FU regimens. Twenty patients (45.4%) recurred: 16 LRR, 2 DM, and 2 with both. The clinical and pathologic complete response rates were 58.8% (20/34), and 53.8% (14/26), respectively. There was a higher proportion of grade 3 or higher acute non-skin toxicities in patients receiving every-3-4-week 5-RI (46.1% vs. 13.3%; p = 0.07), but more grade 3 or higher skin toxicity in patients receiving weekly platinum (62.5% vs. 32.0%; p = 0.01). Conclusion. OS, response rates, and recurrence rates were not significantly different after RT with concurrent weekly platinum-based versus every-3-4-week regimens containing 5-FU for vulvar SCC. (C) 2010 Elsevier Inc. All rights reserved. C1 [Mak, Raymond H.; Halasz, Lia M.] Harvard Radiat Oncol Program, Boston, MA USA. [Tanaka, Cynthia K.; Viswanathan, Akila N.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Tanaka, Cynthia K.; Ancukiewicz, Marek; Russell, Anthony H.; Viswanathan, Akila N.] Harvard Univ, Sch Med, Boston, MA USA. [Ancukiewicz, Marek; Russell, Anthony H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Schultz, Delray J.] Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol ASB1, 75 Francis St,I2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu NR 32 TC 15 Z9 15 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 JAN PY 2011 VL 120 IS 1 BP 101 EP 107 DI 10.1016/j.ygyno.2010.09.004 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 701NO UT WOS:000285824800019 PM 20950845 ER PT J AU Chang, HL Pieretti-Vanmarcke, R Nicolaou, F Li, XL Wei, XL MacLaughlin, DT Donahoe, PK AF Chang, Henry L. Pieretti-Vanmarcke, Rafael Nicolaou, Fotini Li, Xianlin Wei, Xiaolong MacLaughlin, David T. Donahoe, Patricia K. TI Mullerian Inhibiting Substance inhibits invasion and migration of epithelial cancer cell lines SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Mullerian Inhibiting Substance; Anti-Mullerian hormone; Cell migration; Cell invasion ID HUMAN OVARIAN-CANCER; II RECEPTOR GENE; DUCT REGRESSION; IN-VITRO; DEVELOPMENTAL EXPRESSION; MESENCHYMAL CELLS; TUMOR-GROWTH; HORMONE; RAT; PROTEIN AB Objective. Given the fact that Mullerian Inhibiting Substance (MIS) causes complex remodeling of the urogenital ridge and regression of the Mullerian ducts during male embryonic development, we examined whether MIS could affect similar cell properties such as migration and invasion that could contribute ultimately to micro-metastasis of cancers arising from Mullerian tissues. MIS receptor expressing cell lines found to be invasive and migratory in vivo are examined in an in vivo assay that is cost-effective. Methods. We designed in vitro and in vivo experiments to determine if MIS inhibited the movement of cancer lines IGROV-1, HEp3, MDA-MB-231, and HT1080 in cell culture invasion/migration chamber assays and in chick embryo metastasis assays. Results. MIS, at concentrations below those that inhibit cell proliferation, blocked in vitro invasion and in vivo migration of epithelial cancer cells that express the MIS receptor. Conclusions. While our laboratory has previously established MIS as an inhibitor of cancer cell proliferation using in vitro assays and in vivo xenografts, we now show that MIS can also inhibit in vivo tumor migration. (C) 2010 Elsevier Inc. All rights reserved. C1 [Chang, Henry L.; Pieretti-Vanmarcke, Rafael; Nicolaou, Fotini; Li, Xianlin; Wei, Xiaolong; MacLaughlin, David T.; Donahoe, Patricia K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, 185 Cambridge St,CPZN 6-100, Boston, MA 02114 USA. EM pdonahoe@partners.org FU NIH [T32CA071345-11, CA17393]; American Pediatric Surgical Association; Scott Foundation; Ovarian Cancer Research Fund; McBride Family; commons Development Group, Inc; Brigham and Women's SPORE grant [5P50CA105009-03]; Harvard Stem Cell Institute [DP-0010-07-00]; NIH/NCI [5R01CA017393]; Gerald Austen Fund FX H.L.C. was supported by NIH/MGH T32 in Cancer Biology T32CA071345-11 and was the recipient of the Judah Folkman Award of the American Pediatric Surgical Association for this work. X.L received the Hoopes Prize from Harvard University for work contributing to this manuscript; she was funded by the Scott Foundation. D.T.M. was supported by NIH CA17393, the Ovarian Cancer Research Fund, the McBride Family Fund, and the commons Development Group, Inc. P.K.D. was funded by a Brigham and Women's SPORE grant 5P50CA105009-03, a Harvard Stem Cell Institute grant DP-0010-07-00, the NIH/NCI grant 5R01CA017393, the McBride Family Fund, and the Gerald Austen Fund. NR 44 TC 15 Z9 19 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2011 VL 120 IS 1 BP 128 EP 134 DI 10.1016/j.ygyno.2010.09.017 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 701NO UT WOS:000285824800023 PM 21056908 ER PT J AU Viswanathan, AN Erickson, BE Rownd, J AF Viswanathan, Akila N. Erickson, Beth E. Rownd, Jason BE Viswanathan, AN Kirisits, C Erickson, BE Potter, R TI Image-Based Approaches to Interstitial Brachytherapy SO GYNECOLOGIC RADIATION THERAPY: NOVEL APPROACHES TO IMAGE-GUIDANCE AND MANAGEMENT LA English DT Article; Book Chapter ID CERVICAL-CANCER; GYNECOLOGIC MALIGNANCIES; INTRACAVITARY BRACHYTHERAPY; VIENNA APPLICATOR; CARCINOMA; IMPLANTS C1 [Viswanathan, Akila N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Erickson, Beth E.; Rownd, Jason] Med Coll Wisconsin Clin, Froedtert Hosp, Dept Radiat Oncol, Milwaukee, WI 53266 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu; berickson@mcw.edu; jrownd@mcw.edu; aviswanathan@lroc.harvard.edu; berickson@mcw.edu NR 20 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY PY 2011 BP 247 EP 259 DI 10.1007/978-3-540-68958-4_24 PG 13 WC Oncology; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA BSW10 UT WOS:000285943500024 ER PT B AU Growdon, JH AF Growdon, John H. BE Budson, AE Kowall, NW TI The Handbook of Alzheimer's Disease and Other Dementias Foreword SO HANDBOOK OF ALZHEIMER'S DISEASE AND OTHER DEMENTIAS SE Wiley-Blackwell Handbooks of Behavioral Neuroscience LA English DT Editorial Material; Book Chapter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. RP Growdon, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-4443-4408-0; 978-1-4051-6828-1 J9 WILEY-BL HB BEHAV SC PY 2011 BP XII EP XIV D2 10.1002/9781444344110 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA BA6XJ UT WOS:000337300200001 ER PT B AU Budson, AE Kowall, NW AF Budson, Andrew E. Kowall, Neil W. BE Budson, AE Kowall, NW TI The Handbook of Alzheimer's Disease and Other Dementias Preface SO HANDBOOK OF ALZHEIMER'S DISEASE AND OTHER DEMENTIAS SE Wiley-Blackwell Handbooks of Behavioral Neuroscience LA English DT Editorial Material; Book Chapter C1 [Budson, Andrew E.; Kowall, Neil W.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Budson, Andrew E.; Kowall, Neil W.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Budson, Andrew E.] VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, Boston, MA USA. [Budson, Andrew E.; Kowall, Neil W.] VA Boston Healthcare Syst, Geriatr Res Educ Clin Ctr, Boston, MA USA. [Budson, Andrew E.] Brigham & Womens Hosp, Memory Disorders Unit, Div Cognit & Behav Neurol, Dept Neurol, Boston, MA 02115 USA. [Budson, Andrew E.; Kowall, Neil W.] Harvard Univ, Sch Med, Boston, MA USA. [Kowall, Neil W.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Kowall, Neil W.] VA Boston Healthcare Syst, Neurol Serv, Boston, MA USA. RP Budson, AE (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-4443-4408-0; 978-1-4051-6828-1 J9 WILEY-BL HB BEHAV SC PY 2011 BP XV EP XV D2 10.1002/9781444344110 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA BA6XJ UT WOS:000337300200002 ER PT B AU Kowall, NW AF Kowall, Neil W. BE Budson, AE Kowall, NW TI Rational Therapeutics for Alzheimer's Disease and Other Dementias SO HANDBOOK OF ALZHEIMER'S DISEASE AND OTHER DEMENTIAS SE Wiley-Blackwell Handbooks of Behavioral Neuroscience LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE DECLINE; CLINICAL-TRIALS; MOUSE MODEL; RISK; AD; IMMUNIZATION; PREVENTION; INHIBITION; THERAPIES C1 [Kowall, Neil W.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Kowall, Neil W.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Kowall, Neil W.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Kowall, Neil W.] VA Boston Healthcare Syst, Neurol Serv, Boston, MA USA. [Kowall, Neil W.] VA Boston Healthcare Syst, Geriatr Res Educ Clin Ctr, Boston, MA USA. [Kowall, Neil W.] Harvard Univ, Sch Med, Boston, MA USA. RP Kowall, NW (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 55 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-4443-4408-0; 978-1-4051-6828-1 J9 WILEY-BL HB BEHAV SC PY 2011 BP 301 EP 311 D2 10.1002/9781444344110 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA BA6XJ UT WOS:000337300200012 ER PT B AU Budson, AE AF Budson, Andrew E. BE Budson, AE Kowall, NW TI Memory Dysfunction in Dementia SO HANDBOOK OF ALZHEIMER'S DISEASE AND OTHER DEMENTIAS SE Wiley-Blackwell Handbooks of Behavioral Neuroscience LA English DT Article; Book Chapter ID PARKINSONS-DISEASE DEMENTIA; MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; WORKING-MEMORY; PARIETAL CORTEX; PREFRONTAL CORTEX; EPISODIC MEMORY; BRAIN ACTIVITY; LEWY-BODIES; FRONTAL-CORTEX C1 [Budson, Andrew E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Budson, Andrew E.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Budson, Andrew E.] VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, Boston, MA USA. [Budson, Andrew E.] VA Boston Healthcare Syst, Geriatr Res Educ Clin Ctr, Boston, MA USA. [Budson, Andrew E.] Brigham & Womens Hosp, Memory Disorders Unit, Div Cognit & Behav Neurol, Dept Neurol, Boston, MA 02115 USA. [Budson, Andrew E.] Harvard Univ, Sch Med, Boston, MA USA. RP Budson, AE (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. NR 85 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-4443-4408-0; 978-1-4051-6828-1 J9 WILEY-BL HB BEHAV SC PY 2011 BP 315 EP 335 D2 10.1002/9781444344110 PG 21 WC Clinical Neurology SC Neurosciences & Neurology GA BA6XJ UT WOS:000337300200013 ER PT B AU Wright, CI AF Wright, Christopher I. BE Budson, AE Kowall, NW TI Emotion and Behavior in Alzheimer's Disease and Other Dementias SO HANDBOOK OF ALZHEIMER'S DISEASE AND OTHER DEMENTIAS SE Wiley-Blackwell Handbooks of Behavioral Neuroscience LA English DT Article; Book Chapter ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; ATYPICAL ANTIPSYCHOTIC MEDICATIONS; CHOLINE-ACETYLTRANSFERASE ACTIVITY; FRONTOTEMPORAL LOBAR DEGENERATION; HUMAN AMYGDALA ACTIVATION; PLACEBO-CONTROLLED TRIAL; NURSING-HOME PLACEMENT; LEWY BODIES; NEUROPSYCHIATRIC SYMPTOMS C1 [Wright, Christopher I.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Psychiat, Lab Aging & Emot, Charlestown, MA 02129 USA. [Wright, Christopher I.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Dept Neurol, Boston, MA 02115 USA. [Wright, Christopher I.] Harvard Univ, Sch Med, Boston, MA USA. RP Wright, CI (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Psychiat, Lab Aging & Emot, Charlestown, MA 02129 USA. NR 299 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-4443-4408-0; 978-1-4051-6828-1 J9 WILEY-BL HB BEHAV SC PY 2011 BP 416 EP 456 D2 10.1002/9781444344110 PG 41 WC Clinical Neurology SC Neurosciences & Neurology GA BA6XJ UT WOS:000337300200016 ER PT B AU Dickerson, BC AF Dickerson, Bradford C. BE Budson, AE Kowall, NW TI Molecular Neuroimaging of the Dementias From Scientific Insights to Clinical Applications SO HANDBOOK OF ALZHEIMER'S DISEASE AND OTHER DEMENTIAS SE Wiley-Blackwell Handbooks of Behavioral Neuroscience LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; FRONTOTEMPORAL LOBAR DEGENERATION; ACETYLCHOLINE ESTERASE-ACTIVITY; REGIONAL CEREBRAL METABOLISM; PROBABLE ALZHEIMERS-DISEASE; GLUCOSE-METABOLISM; FDG-PET; PARKINSONS-DISEASE; AMYLOID BURDEN C1 [Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Dickerson, Bradford C.] Massachusetts Gen Hosp, Alzheimers Dis Res Ctr, Boston, MA 02114 USA. [Dickerson, Bradford C.] Brigham & Womens Hosp, Memory Disorders Unit, Div Cognit & Behav Neurol, Dept Neurol, Boston, MA 02115 USA. [Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. NR 99 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, WEST SUSSEX PO19 8SQ, ENGLAND BN 978-1-4443-4408-0; 978-1-4051-6828-1 J9 WILEY-BL HB BEHAV SC PY 2011 BP 557 EP 574 D2 10.1002/9781444344110 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA BA6XJ UT WOS:000337300200021 ER PT S AU Ho, L Chen, LH Wang, J Zhao, W Talcott, ST Ono, K Teplow, D Humala, N Cheng, A Percival, SS Ferruzzi, M Janle, E Dickstein, DL Pasinetti, GM AF Ho, Lap Chen, Ling Hong Wang, Jun Zhao, Wei Talcott, Stephen T. Ono, Kenjiro Teplow, David Humala, Nelson Cheng, Alice Percival, Susan S. Ferruzzi, Mario Janle, Elsa Dickstein, Dara L. Pasinetti, Giulio Maria BE Casadesus, G TI Heterogeneity in Red Wine Polyphenolic Contents Differentially Influences Alzheimer's Disease-Type Neuropathology and Cognitive Deterioration SO HANDBOOK OF ANIMAL MODELS IN ALZHEIMER'S DISEASE SE Advances in Alzheimers Disease LA English DT Article; Book Chapter DE Alzheimer's disease dementia; amyloid-beta protein precursor (A beta PP); high-molecular weight amyloid-beta oligomer species; polyphenols ID PHOTOINDUCED CROSS-LINKING; MOUSE MODEL; UNMODIFIED PROTEINS; TRANSGENIC MOUSE; ELLAGIC ACID; IN-VITRO; BETA; OLIGOMERS; DEFICITS; PLAQUES AB We recently found that moderate consumption of two un-related red wines generate from different grape species, a Cabernet Sauvignon and a muscadine wine that are characterized by distinct component composition of polyphenolic compounds, significantly attenuated the development of Alzheimer's disease (AD)-type brain pathology and memory deterioration in a transgenic AD mouse model. Interestingly, our evidence suggests that the two red wines attenuated AD phenotypes through independent mechanisms. In particular, we previously found that treatment with Cabernet Sauvignon reduced the generation of AD-type beta-amyloid (A beta) peptides. In contrast, evidence from our present study suggests that muscadine treatment attenuates A beta neuropathology and A beta-related cognitive deterioration in Tg2576 mice by interfering with the oligomerization of A beta molecules to soluble high-molecular-weight A beta oligomer species that are responsible for initiating a cascade of cellular events resulting in cognitive decline. Collectively, our observations suggest that distinct polyphenolic compounds from red wines may be bioavailable at the organism level and beneficially modulate AD phenotypes through multiple A beta-related mechanisms. Results from these studies suggest the possibility of developing a "combination" of dietary polyphenolic compounds for AD prevention and/or therapy by modulating multiple A beta-related mechanisms. C1 [Ho, Lap; Chen, Ling Hong; Wang, Jun; Zhao, Wei; Humala, Nelson; Cheng, Alice; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Ho, Lap; Pasinetti, Giulio Maria] James J Peters VA Med Ctr, Geriatr Res & Clin Ctr, Bronx, NY USA. [Talcott, Stephen T.] Texas A&M Univ, Dept Nutr & Food Sci, College Stn, TX USA. [Ono, Kenjiro; Teplow, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Percival, Susan S.] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. [Ferruzzi, Mario; Janle, Elsa] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA. [Dickstein, Dara L.; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. RP Ho, L (reprint author), Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. EM Lap.Ho@mssm.edu NR 38 TC 0 Z9 0 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-5727 BN 978-1-60750-733-8; 978-1-60750-732-1 J9 ADV ALZH DIS PY 2011 VL 1 BP 263 EP 275 DI 10.3233/978-1-60750-733-8-263 PG 13 WC Neurosciences SC Neurosciences & Neurology GA BC2XS UT WOS:000351444800020 ER PT J AU Stengel, A Tache, Y AF Stengel, Andreas Tache, Yvette BE Preedy, VR Watson, RR Martin, CR TI The Physiological Relationships Between the Brainstem, Vagal Stimulation, and Feeding SO HANDBOOK OF BEHAVIOR, FOOD AND NUTRITION LA English DT Article; Book Chapter ID GLUCAGON-LIKE PEPTIDE-1; IMPLANTABLE GASTRIC STIMULATION; PLASMA GHRELIN LEVELS; INHIBITS FOOD-INTAKE; INDUCED WEIGHT-LOSS; ELECTRICAL-STIMULATION; MORBID-OBESITY; LONG-TERM; SYNERGISTIC INTERACTION; INTRAVENOUS-INFUSION C1 [Stengel, Andreas; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90095 USA. [Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis, Los Angeles, CA 90095 USA. [Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Stengel, A (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Bldg 115,Room 117, Los Angeles, CA 90095 USA. EM astengel@mednet.ucla.edu NR 83 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-92270-6 PY 2011 BP 817 EP 828 DI 10.1007/978-0-387-92271-3_54 D2 10.1007/978-0-387-92271-3 PG 12 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA BDE45 UT WOS:000312946600056 ER PT S AU Fennema-Notestine, C Panizzon, MS Thompson, WR Chen, CH Eyler, LT Fischl, B Franz, CE Grant, MD Jak, AJ Jernigan, TL Lyons, MJ Neale, MC Seidman, LJ Tsuang, MT Xian, H Dale, AM Kremen, WS AF Fennema-Notestine, Christine Panizzon, Matthew S. Thompson, Wesley R. Chen, Chi-Hua Eyler, Lisa T. Fischl, Bruce Franz, Carol E. Grant, Michael D. Jak, Amy J. Jernigan, Terry L. Lyons, Michael J. Neale, Michael C. Seidman, Larry J. Tsuang, Ming T. Xian, Hong Dale, Anders M. Kremen, William S. BE Ashford, JW Rosen, A Adamson, M Bayley, P Sabri, O Furst, A Black, SE Weiner, M TI Presence of ApoE epsilon 4 Allele Associated with Thinner Frontal Cortex in Middle Age SO HANDBOOK OF IMAGING THE ALZHEIMER BRAIN SE Advances in Alzheimers Disease LA English DT Article; Book Chapter DE Magnetic resonance imaging; cerebral cortex; brain; frontal lobe; apolipoproteins E; apolipoprotein E2; apolipoprotein E3; apolipoprotein E4; genetic association studies; aging ID APOLIPOPROTEIN-E EPSILON-4; FAMILIAL ALZHEIMER-DISEASE; MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; VIETNAM ERA TWIN; HIPPOCAMPAL VOLUME; CORTICAL THICKNESSES; LONGITUDINAL CHANGES; NORMAL INDIVIDUALS AB The presence of an ApoE epsilon 4 allele (epsilon 4+) increases the risk of developing Alzheimer's disease (AD). Previous studies support an adverse relationship between epsilon 4+ status and brain structure and function in mild cognitive impairment and AD; in contrast, the presence of an epsilon 2 allele may be protective. Whether these findings reflect disease-related effects or pre-existing endophenotypes, however, remains unclear. The present study examined the influence of ApoE allele status on brain structure solely during middle-age in a large, national sample. Participants were 482 men, ages 51-59, from the Vietnam Era Twin Study of Aging (VETSA). T1-weighted images were used in volumetric segmentation and cortical surface reconstruction methods to measure regional volume and thickness. Primary linear mixed effects models predicted structural measures with ApoE status (epsilon 3/3, epsilon 2/3, epsilon 3/4) and control variables for effects of site, non-independence of twin data, age, and average cranial vault or cortical thickness. Relative to the epsilon 3/3 group, the epsilon 3/4 group demonstrated significantly thinner cortex in superior frontal and left rostral and right caudal midfrontal regions; there were no significant effects of epsilon 4 status on any temporal lobe measures. The epsilon 2/3 group demonstrated significantly thicker right parahippocampal cortex relative to the epsilon 3/3 group. The ApoE epsilon 4 allele may influence cortical thickness in frontal areas, which are later developing regions thought to be more susceptible to the natural aging process. Previous conflicting findings for mesial temporal regions may be driven by the inclusion of older individuals, who may evidence preclinical manifestations of disease, and by unexamined moderators of epsilon 4-related effects. The presence of the epsilon 2 allele was related to thicker cortex, supporting a protective role. Ongoing follow-up of the VETSA sample may shed light on the potential for age-and disease-related mediation of the influence of ApoE allele status. C1 [Fennema-Notestine, Christine; Panizzon, Matthew S.; Thompson, Wesley R.; Chen, Chi-Hua; Eyler, Lisa T.; Franz, Carol E.; Jak, Amy J.; Jernigan, Terry L.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Fennema-Notestine, Christine; Jernigan, Terry L.; Dale, Anders M.] Univ Calif San Diego, Sch Med, Dept Radiol, La Jolla, CA 92093 USA. [Eyler, Lisa T.; Jak, Amy J.; Kremen, William S.] Vet Adm San Diego Healthcare Syst, San Diego, CA USA. [Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fischl, Bruce] Harvard Univ, Sch Med, Boston, MA USA. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Grant, Michael D.; Lyons, Michael J.; Seidman, Larry J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Jernigan, Terry L.] Univ Calif San Diego, Sch Med, Dept Cognit Sci, La Jolla, CA 92093 USA. [Jernigan, Terry L.] Univ Calif San Diego, Ctr Human Dev, La Jolla, CA 92093 USA. [Neale, Michael C.] Virginia Commonwealth Univ, Sch Med, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Tsuang, Ming T.] Sch Publ Hlth, Boston, MA USA. [Xian, Hong] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Fennema-Notestine, C (reprint author), Univ Calif San Diego, Sch Med, 9500 Gilman Dr 0738, La Jolla, CA 92093 USA. EM Fennema@UCSD.edu NR 74 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-5727 BN 978-1-60750-793-2; 978-1-60750-792-5 J9 ADV ALZH DIS PY 2011 VL 2 BP 77 EP 88 DI 10.3233/978-1-60750-793-2-77 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BC2XT UT WOS:000351445400009 ER PT S AU Canu, E McLaren, DG Fitzgerald, ME Bendlin, BB Zoccatelli, G Alessandrini, F Pizzini, FB Ricciardi, GK Beltramello, A Johnson, SC Frisoni, GB AF Canu, Elisa McLaren, Donald G. Fitzgerald, Michele E. Bendlin, Barbara B. Zoccatelli, Giada Alessandrini, Franco Pizzini, Francesca B. Ricciardi, Giuseppe K. Beltramello, Alberto Johnson, Sterling C. Frisoni, Giovanni B. BE Ashford, JW Rosen, A Adamson, M Bayley, P Sabri, O Furst, A Black, SE Weiner, M TI Mapping the Structural Brain Changes in Alzheimer's Disease: The Independent Contribution of Two Imaging Modalities SO HANDBOOK OF IMAGING THE ALZHEIMER BRAIN SE Advances in Alzheimers Disease LA English DT Article; Book Chapter DE Diffusion Tensor Imaging (DTI); Alzheimer's disease (AD); Microstructure; Fractional Anisotropy (FA); Mean Diffusivity (MD) ID MILD COGNITIVE IMPAIRMENT; WHITE-MATTER CHANGES; MOTOR CORTEX INVOLVEMENT; AGE-RELATED-CHANGES; IN-VIVO; CORPUS-CALLOSUM; NEURODEGENERATIVE DISORDERS; AMYLOID DEPOSITS; TRACT INTEGRITY; WATER DIFFUSION AB The macrostructural atrophy of Alzheimer's disease (AD) has been fully described. Current literature reports that also microstructural alterations occur in AD since the early stages. However, whether the microstructural changes offer unique information independent from macrostructural atrophy is unclear. Aim of this study is to define the independent contribution of macrostructural atrophy and microstructural alterations on AD pathology. The study involved 17 moderate to severe AD patients and 13 healthy controls. All participants underwent conventional and non conventional MRI (respectively, T1-weighted and diffusion-weighted MR scanning). We processed the images in order to obtain gray and white matter volumes to assess macrostructural atrophy, and fractional anisotropy and mean diffusivity to assess the microstructural damage. Analyses of covariance between patients and controls were performed to investigate microstructural tissue damage independent of macrostructural tissue loss, and viceversa, voxel by voxel. We observed microstructural differences, independent of macrostructural atrophy, between patients and controls in temporal and retrosplenial regions, as well as in thalamus, corticopontine tracts, striatum and precentral gyrus. Volumetric differences, independent of microstructural alterations, were observed mainly in the entorhinal cortex, posterior cingulum, and splenium. Measures of microstructural damage provide unique information not obtainable with volumetric mapping in regions known to be pivotal in AD as well as in others thought to be spared. This work expands the understanding of the topography of pathological changes in AD that can be captured with imaging techniques. C1 [Canu, Elisa; Frisoni, Giovanni B.] Natl Ctr Res & Care Alzheimers & Mental Dis, LENITEM Lab Epidemiol Neuroimaging & Telemed, IRCCS Ctr San Giovanni Dio FBF, Brescia, Italy. [McLaren, Donald G.; Fitzgerald, Michele E.; Bendlin, Barbara B.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [McLaren, Donald G.] Univ Wisconsin, Neurosci Training Program, Madison, WI USA. [McLaren, Donald G.; Fitzgerald, Michele E.; Bendlin, Barbara B.; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Zoccatelli, Giada; Alessandrini, Franco; Pizzini, Francesca B.; Ricciardi, Giuseppe K.; Beltramello, Alberto] Osped Civile, Serv Neuroradiol, I-37126 Verona, Italy. RP Frisoni, GB (reprint author), IRCCS San Giovanni Dio FBF, LENITEM Lab Epidemiol Neuroimaging & Telemed, Via Pilastroni 4, I-25125 Brescia, Italy. EM gfrisoni@fatebenefratelli.it RI Pizzini, Francesca Bendetta/O-5291-2016; Canu, Elisa/K-1423-2016 OI Pizzini, Francesca Bendetta/0000-0002-6285-0989; Canu, Elisa/0000-0001-5804-3378 NR 68 TC 0 Z9 0 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-5727 BN 978-1-60750-793-2; 978-1-60750-792-5 J9 ADV ALZH DIS PY 2011 VL 2 BP 487 EP 498 DI 10.3233/978-1-60750-793-2-487 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BC2XT UT WOS:000351445400042 ER PT J AU Baugh, CW Venkatesh, AK Bohan, JS AF Baugh, Christopher W. Venkatesh, Arjun K. Bohan, J. Stephen TI Emergency department observation units: A clinical and financial benefit for hospitals SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article DE emergency medicine; emergency service; health services needs and demands; hospital; observation unit; review ID RANDOMIZED CONTROLLED-TRIAL; PAIN OBSERVATION UNIT; CHEST-PAIN; PATIENT SATISFACTION; DIAGNOSTIC PROTOCOL; ASTHMA; CARE; PROFITABILITY; MANAGEMENT; ADMISSION AB Introduction: There are nearly 120 million visits to emergency departments each year, one for every three people in the United States. Fifty percent of all hospital admissions come from this group, a marked change from the mid-1990s when the emergency department was a source of only a third of admissions. As the population increases and ages, the growth rate for emergency department visits and the resulting admissions will exceed historical trends creating a surge in demand for inpatient beds. Background: Current health care reform efforts are highlighting deficiencies in access, cost, and quality of care in the United States. The need for more inpatient capacity brings attention to short-stay admissions and whether they are necessary. Emergency department observation units provide a suitable alternate venue for many such patients at lower cost without adversely affecting access or quality. Methods: This article serves as a literature synthesis in support of observation units, with special emphasis on the clinical and financial aspects of their use. The observation medicine literature was reviewed using PubMed, and selected sources were used to summarize the current state of practice. In addition, the authors introduce a novel conceptual framework around measures of observation unit efficiency. Findings and Practice Implications: Observation units provide high-quality and efficient care to patients with common complaints seen in the emergency department. More frequent use of observation can increase patient safety and satisfaction while decreasing unnecessary inpatient admissions and improving fiscal performance for both emergency departments and the hospitals in which they operate. For institutions with the volume to justify the fixed costs of operating an observation unit, the dominant strategy for all stakeholders is to create one. C1 [Baugh, Christopher W.] Brigham & Womens Hosp, Dept Emergency Med, Emergency Dept Observat Unit, Boston, MA 02115 USA. [Baugh, Christopher W.; Bohan, J. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Venkatesh, Arjun K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Venkatesh, Arjun K.] Harvard Affiliated Emergency Med Residency, Boston, MA USA. RP Baugh, CW (reprint author), Brigham & Womens Hosp, Dept Emergency Med, Emergency Dept Observat Unit, 75 Francis St, Boston, MA 02115 USA. EM cbaugh@partners.org NR 41 TC 46 Z9 46 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD JAN-MAR PY 2011 VL 36 IS 1 BP 28 EP 37 DI 10.1097/HMR.0b013e3181f3c035 PG 10 WC Health Policy & Services SC Health Care Sciences & Services GA 694WM UT WOS:000285331600005 PM 21157228 ER PT S AU Kang, JX AF Kang, Jing X. BE Simopoulos, AP TI The Omega-6/Omega-3 Fatty Acid Ratio in Chronic Diseases: Animal Models and Molecular Aspects SO HEALTHY AGRICULTURE, HEALTHY NUTRITION, HEALTHY PEOPLE SE World Review of Nutrition and Dietetics LA English DT Proceedings Paper; Book Chapter CT Inaugural Conference of the World-Council-on-Genetic-Nutrition-and-Fitness-for-Health CY OCT 05-08, 2010 CL Olympia, GREECE SP Minist Hlth & Social Solidar, Hellen Sports Res Inst, Olymp Athlet Ctr Athens, Greek Org Football Prognost SA, Nutrilite Hlth Inst, Hellen Amer Univ, Hellen Amer Union, Int Union Nutr Sci, Int Soc Nutrigent, Nutrgenom ID FAT-1 TRANSGENIC MICE; MAMMARY-GLAND; OMEGA-3-FATTY-ACIDS; INFLAMMATION; COLITIS; CANCER; RESISTANCE; STRENGTH; GROWTH; RICH C1 Massachusetts Gen Hosp, Lab Lipid Med & Technol, Charlestown, MA 02129 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, 149 13th St,Room 4433, Charlestown, MA 02129 USA. EM jxkang@partners.org FU NCI NIH HHS [R01 CA113605, CA113605] NR 31 TC 10 Z9 10 U1 1 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-8055-9779-1 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2011 VL 102 BP 22 EP 29 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BWP47 UT WOS:000294441100005 PM 21865816 ER PT B AU Mahida, S Rienstra, M Sinner, MF Lubitz, SA Ellinor, PT Kaab, S AF Mahida, Saagar Rienstra, Michiel Sinner, Moritz F. Lubitz, Steven A. Ellinor, Patrick T. Kaeaeb, Stefan BE Tripathi, ON Ravens, U Sanguinetti, MC TI Genetics of Atrial Fibrillation SO HEART RATE AND RHYTHM: MOLECULAR BASIS, PHARMACOLOGICAL MODULATION AND CLINICAL IMPLICATIONS LA English DT Article; Book Chapter ID OF-FUNCTION MUTATION; SODIUM-CHANNEL MUTATIONS; GENOME-WIDE ASSOCIATION; SHORT QT SYNDROME; FAMILIAL AGGREGATION; PR INTERVAL; CHROMOSOME 4Q25; COMMON VARIANTS; KCNQ1 MUTATION; HEART-FAILURE C1 [Sinner, Moritz F.; Kaeaeb, Stefan] Univ Munich, Dept Med 1, Klinikum Grosshadern, D-81377 Munich, Germany. [Mahida, Saagar; Rienstra, Michiel; Sinner, Moritz F.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Sinner, Moritz F.] NHLBIs Framingham Heart Study, Framingham, MA USA. [Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mahida, S (reprint author), Univ Munich, Dept Med 1, Klinikum Grosshadern, Marchioninistr 15, D-81377 Munich, Germany. EM stefan.kaab@med.uni-muenchen.de NR 80 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-3-642-17574-9 PY 2011 BP 485 EP 499 DI 10.1007/978-3-642-17575-6_27 D2 10.1007/978-3-642-17575-6 PG 15 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy; Toxicology SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy; Toxicology GA BVJ55 UT WOS:000291666400027 ER PT J AU Magnani, JW Gorodeski, EZ Johnson, VM Sullivan, LM Hamburg, NM Benjamin, EJ Ellinor, PT AF Magnani, Jared W. Gorodeski, Eiran Z. Johnson, Victor M. Sullivan, Lisa M. Hamburg, Naomi M. Benjamin, Emelia J. Ellinor, Patrick T. TI P wave duration is associated with cardiovascular and all-cause mortality outcomes: the National Health and Nutrition Examination Survey SO HEART RHYTHM LA English DT Article DE Electrocardiography; Epidemiology; mortality; Risk factors; NHANES; P waves ID CONGESTIVE-HEART-FAILURE; LONG QT SYNDROME; ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; DISPERSION; STROKE; RISK; POPULATION; AGE AB BACKGROUND P wave indices are an intermediate phenotype modulated by atrial conduction and electrophysiology. Their clinical correlates and association with all-cause mortality have received limited scrutiny. OBJECTIVE To determine the relationship between P wave indices and cardiovascular and all-cause mortality in the National Health and Nutrition Examination Survey (NHANES), a highly representative United States sample. METHODS NHANES III (1988-1994) quantified PR interval and P wave duration and amplitude. Mortality data through 2006 were obtained from National Death Index (NDI) records. RESULTS Of 8,561 subjects with electrocardiograms (ECGs), 7,486 (mean age 60.0 +/- 13.3 years., 51.9% women, 50.1% ethnic minorities) had ECGs in sinus rhythm, linked mortality data, and complete assessments. Over a median 8.6-year follow-up (range 0.1-12.2 years), there were 679 cardiovascular deaths and 1,559 all-cause mortality deaths. Older age, male sex, and higher body mass index were significantly associated with greater PR interval and P wave duration and with lower P wave amplitude. African Americans had higher mean values of all three P wave indices. In a multivariable model adjusting for cardiovascular risk factors, P wave duration was the only P wave index significantly associated with cardiovascular mortality (hazard ratio [HR] 1.13, per 1 standard deviation [SD], 95% confidence interval [CI] 1.04 -1.23; P = 004) and all-cause mortality (HR 1.06 per 1 SD; 95% CI 1.00-1.13; P = .050). CONCLUSIONS In a highly representative U. S. sample, P wave duration was significantly associated with increased cardiovascular and all-cause mortality. P wave duration may reflect subclinical disease and merits elucidation as a marker of risk for adverse outcomes. C1 [Magnani, Jared W.; Hamburg, Naomi M.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Gorodeski, Eiran Z.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Johnson, Victor M.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Hamburg, Naomi/0000-0001-5504-5589; Gorodeski, Eiran/0000-0003-3756-8831; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF2190028]; National Institutes of Health [RC1HL101056, HL092577] FX This research was funded by American Heart Association Award 09FTF2190028 and by grants from the National Institutes of Health (RC1HL101056; HL092577). NR 40 TC 29 Z9 30 U1 0 U2 5 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 JAN PY 2011 VL 8 IS 1 BP 93 EP 100 DI 10.1016/j.hrthm.2010.09.020 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 698VW UT WOS:000285622700020 PM 20868770 ER PT S AU Kuter, DJ AF Kuter, David J. BE Lyman, GH Dale, DC TI Romiplostim SO HEMATOPOIETIC GROWTH FACTORS IN ONCOLOGY SE Cancer Treatment and Research LA English DT Article; Book Chapter ID IMMUNE THROMBOCYTOPENIC PURPURA; MYELODYSPLASTIC-SYNDROME MDS; MEGAKARYOCYTE GROWTH; PLATELET PRODUCTION; CYTOKINE RECEPTOR; PATIENTS PTS; THROMBOPOIETIN RECEPTOR; HEPATITIS-C; CHRONIC ITP; IN-VITRO AB Thrombocytopenia is a common clinical problem associated with a wide range of medical conditions including immune thrombocytopenia (ITP), chemotherapy-induced thrombocytopenia (CIT), hepatitis C-related thrombocytopenia, and myelodysplastic syndromes (MDS). Until recently, the only treatments for thrombocytopenia were to alleviate the underlying cause or to provide platelet transfusions. With the discovery and recent clinical availability of thrombopoietin (TPO) mimetics, a new treatment option has emerged. Two TPO mimetics are currently clinically available for treating ITP: romiplostim (an injectable peptide TPO mimetic) and eltrombopag (a non-peptide, orally available TPO mimetic). This chapter reviews the development, biology, and clinical trials with romiplostim. With few adverse effects, romiplostim is effective in raising the platelet count in over 80% of ITP patients, allowing them to discontinue other therapies, reduce the need for splenectomy, and improve their quality of life. Long-term theoretical side effects of romiplostim treatment include reticulin formation, thromboembolism, and antibody formation to romiplostim. A practical way of using romiplostim is provided: a higher starting dose of 3 mg/kg is recommended along with efforts to avoid withholding the close. Future studies will assess the utility of romiplostim in CIT, hepatitis-C related thrombocytopenia, and MDS. C1 Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. EM kuter.david@mgh.harvard.edu NR 40 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-1-4419-7072-5 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2011 VL 157 BP 267 EP 288 DI 10.1007/978-1-4419-7073-2_16 D2 10.1007/978-1-4419-7073-2 PG 22 WC Oncology; Hematology SC Oncology; Hematology GA BSJ61 UT WOS:000284721500016 PM 21052962 ER PT J AU Kornek, M Popov, Y Libermann, TA Afdhal, NH Schuppan, D AF Kornek, Miroslaw Popov, Yury Libermann, Towia A. Afdhal, Nezam H. Schuppan, Detlef TI Human T Cell Microparticles Circulate in Blood of Hepatitis Patients and Induce Fibrolytic Activation of Hepatic Stellate Cells SO HEPATOLOGY LA English DT Article ID COLLAGENASE GENE-EXPRESSION; MATRIX-METALLOPROTEINASE; IN-VIVO; KAPPA-B; EMMPRIN; CD147; FIBROGENESIS; PLATELETS; RECEPTOR; INFLAMMATION AB Microparticles (MPs) are small cell membrane vesicles that are released from cells during apoptosis or activation. Although circulating platelet MPs have been studied in some detail, the existence and functional role of T cell MPs remain elusive. We show that blood from patients with active hepatitis C (alanine aminotransferase [ALT] level >100 IU/mL) contains elevated numbers of T cell MPs compared with patients with mild hepatitis C (ALT <40 IU/mL) and healthy controls. T cell MPs fuse with cell membranes of hepatic stellate cells (HSCs), the major effector cells for excess matrix deposition in liver fibrosis and cirrhosis. MP uptake is partly intercellular adhesion molecule 1 dependent and leads to activation of nuclear factor kappa B and extracellular signal-regulated kinases 1 and 2 and subsequent up-regulation of fibrolytic genes in HSCs, down-regulation of procollagen alpha 1 (I) messenger RNA, and blunting of profibrogenic activities of transforming growth factor beta 1. Ex vivo, the induced fibrolytic activity is evident in MPs derived from activated CD4+ T cells and is highest in MPs derived from activated and apoptotic CD8+ T cells. Mass spectrometry, fluorescence-activated cell sorting analysis, and function blocking antibodies revealed CD147/Emmprin as a candidate transmembrane molecule in HSC fibrolytic activation by CD8+ T cell MPs. Conclusion: Circulating T cell MPs are a novel diagnostic marker for inflammatory liver diseases, and in vivo induction of T cell MPs may be a novel strategy to induce regression of liver fibrosis. (HEPATOLOGY 2011;53:230-242) C1 [Schuppan, Detlef] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. [Libermann, Towia A.] Beth Israel Deaconess Med Ctr, BIDMC Genom & Prote Ctr, Boston, MA 02215 USA. RP Schuppan, D (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, 330 Brookline Ave, Boston, MA 02215 USA. EM dschuppa@bidmc.harvard.edu OI Kornek, Miroslaw/0000-0002-1682-1765; Libermann, Towia/0000-0002-4006-8179; Popov, Yury V./0000-0001-7973-942X FU NIDDK NIH HHS [R21 DK075857, R21 DK075857-02] NR 36 TC 45 Z9 46 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2011 VL 53 IS 1 BP 230 EP 242 DI 10.1002/hep.23999 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 709AB UT WOS:000286406300025 PM 20979056 ER PT J AU Bassett, IV Chetty, S Giddy, J Reddy, S Bishop, K Lu, Z Losina, E Freedberg, KA Walensky, RP AF Bassett, I. V. Chetty, S. Giddy, J. Reddy, S. Bishop, K. Lu, Z. Losina, E. Freedberg, K. A. Walensky, R. P. TI Screening for acute HIV infection in South Africa: finding acute and chronic disease SO HIV MEDICINE LA English DT Article DE acute HIV; Africa; HIV screening; HIV seropositivity; rapid HIV test ID VIRUS TYPE-1 INFECTION; REAL-TIME; TRANSMISSION; TESTS; RNA; UGANDA; PREVENTION; EXPERIENCE; RAKAI AB Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate the strategy of using pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening programme in an out-patient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and, if this was positive, quantitative RNA, enzyme immunoassay and Western blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered to have had false negative rapid antibody tests. Results Nine hundred and ninety-four participants were enrolled with either negative (n = 976) or discordant (n = 18) rapid test results. Eleven [1.1%; 95% confidence interval (CI) 0.6-2.0%] had acute HIV infection, and an additional 20 (2.0%; 95% CI 1.3-3.1%) had chronic HIV infection (false negative rapid test). Conclusions One per cent of out-patients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. C1 [Bassett, I. V.; Freedberg, K. A.; Walensky, R. P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bassett, I. V.; Lu, Z.; Losina, E.; Freedberg, K. A.; Walensky, R. P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Chetty, S.; Giddy, J.] McCord Hosp, Durban, South Africa. [Reddy, S.; Bishop, K.] Univ KwaZulu Natal, HIV Pathogenesis Program, Durban, South Africa. [Lu, Z.; Losina, E.; Freedberg, K. A.; Walensky, R. P.] Harvard Ctr AIDS Res CFAR, Boston, MA USA. [Losina, E.; Freedberg, K. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, E.; Freedberg, K. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, E.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Walensky, R. P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Bassett, IV (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ibassett@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X; Bishop, Karen/0000-0003-4935-7708 FU National Institute of Allergy and Infectious Diseases (Harvard Center for AIDS Research) [K23 AI 068458, R01 AI058736, K24 AI062476, R0I AI 067073, P30 AI42851]; National Institute of Mental Health [R01 MH073445]; Doris Duke Charitable Foundation FX We would like to thank Slindile Mbhele and Kriebashnie Nair for their technical assistance. We are grateful to the HIV counsellors in the McCord Hospital out-patient department for their outstanding work in enrolling patients into the study: Esme Kelly Nkosi, Pepsi (Shamla) Pillay, and Sibongile Hadebe. This work was supported in part by the National Institute of Allergy and Infectious Diseases: K23 AI 068458; R01 AI058736; K24 AI062476; R0I AI 067073; P30 AI42851 (Harvard Center for AIDS Research); The National Institute of Mental Health: R01 MH073445; and The Doris Duke Charitable Foundation, Clinical Scientist Development Award (RPW). No conflicts of interest exist concerning the authors or content of this article. NR 32 TC 18 Z9 18 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-2662 J9 HIV MED JI HIV Med. PD JAN PY 2011 VL 12 IS 1 BP 46 EP 53 DI 10.1111/j.1468-1293.2010.00850.x PG 8 WC Infectious Diseases SC Infectious Diseases GA 689XC UT WOS:000284963200007 PM 20553336 ER PT J AU Lee, PH Bergen, SE Perlis, RH Sullivan, PF Sklar, P Smoller, JW Purcell, SM AF Lee, Phil H. Bergen, Sarah E. Perlis, Roy H. Sullivan, Patrick F. Sklar, Pamela Smoller, Jordan W. Purcell, Shaun M. TI Modifiers and Subtype-Specific Analyses in Whole-Genome Association Studies: A Likelihood Framework SO HUMAN HEREDITY LA English DT Article DE Cross-disorder analysis; Modifier effects; Subtype analysis; Whole-genome association study ID BIPOLAR DISORDER; MAXIMUM-LIKELIHOOD; ISCHEMIC-STROKE; DEPRESSION; RISK; SCHIZOPHRENIA; MODEL; ALCOHOL; ILLNESS; GENES AB Objective: We propose new statistical methods for analyzing genetic case/control association data in which cases can be further classified into subtypes, for example, based on clinical features. The primary utility of our work is the ability to distinguish between subtype-specific and modifier effects of genetic variants within a single testing framework. Methods: A range of disease/subtype causal models are defined for genetic variants involving subtype-specific and modifier effects. We present a log-linear modeling framework enabling comparison between these causal models and selection of the best-fit model. Results: We evaluate and compare the analytic power and model selection performance of the proposed work with standard two-group-based association tests. Simulation studies demonstrate that our approach has similar or greater power than the traditional approach over a range of causal models. We also report empirical findings about the impact of misspecification of subtype frequency during model selection, and extend the application of the proposed work to the cross-disorder association studies of multiple diseases. Conclusion: Whether a variant is a disease risk factor, is subtype specific, or modifies disease features has important consequences for the interpretation and follow-up of genetic associations. Our framework provides a simple, systematic way to evaluate and describe associations involving such subtype-specific or modifier effects. Copyright (C) 2011 S. Karger AG, Basel C1 [Lee, Phil H.; Bergen, Sarah E.; Perlis, Roy H.; Smoller, Jordan W.; Purcell, Shaun M.] Harvard Univ, Sch Med, Psychiat & Neurodev Genet Unit, Dept Psychiat,Ctr Human Genet Res, Boston, MA 02114 USA. [Lee, Phil H.; Purcell, Shaun M.] Harvard Univ, Sch Med, Analyt & Translat Genet Unit, Dept Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lee, Phil H.; Bergen, Sarah E.; Perlis, Roy H.; Smoller, Jordan W.; Purcell, Shaun M.] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Lee, Phil H.; Bergen, Sarah E.; Perlis, Roy H.; Smoller, Jordan W.; Purcell, Shaun M.] MIT, Cambridge, MA 02139 USA. [Sklar, Pamela; Purcell, Shaun M.] Mt Sinai Sch Med, Div Psychiat Genom, Dept Psychiat, New York, NY USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet Psychiat & Epidemiol, Chapel Hill, NC USA. RP Purcell, SM (reprint author), Harvard Univ, Sch Med, Psychiat & Neurodev Genet Unit, Dept Psychiat,Ctr Human Genet Res, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM shaun@pngu.mgh.harvard.edu RI Bergen, Sarah/I-8313-2012; OI Bergen, Sarah/0000-0002-5888-0034 NR 29 TC 9 Z9 9 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2011 VL 72 IS 1 BP 10 EP 20 DI 10.1159/000327158 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 818OW UT WOS:000294763800002 PM 21849790 ER PT J AU Puppala, S Coletta, DK Schneider, J Hu, SL Farook, VS Dyer, TD Arya, R Blangero, J Duggirala, R DeFronzo, RA Jenkinson, CP AF Puppala, Sobha Coletta, Dawn K. Schneider, Jennifer Hu, Shirley L. Farook, Vidya S. Dyer, Thomas D. Arya, Rector Blangero, John Duggirala, Ravindranath DeFronzo, Ralph A. Jenkinson, Christopher P. TI Genome-Wide Linkage Screen for Systolic Blood Pressure in the Veterans Administration Genetic Epidemiology Study (VAGES) of Mexican-Americans and Confirmation of a Major Susceptibility Locus on Chromosome 6q14.1 SO HUMAN HEREDITY LA English DT Article DE Hypertension; Linkage; Antihypertensive medication; Genetic location; Heritability ID ESSENTIAL-HYPERTENSION; UNITED-STATES; ASSOCIATION; SCAN; METAANALYSIS; SEGREGATION; PREVALENCE; PEDIGREES; COMMITTEE; DISEASE AB Objective: Hypertension or high blood pressure is a strong correlate of diseases such as obesity and type 2 diabetes. We conducted a genome-wide linkage screen to identify susceptibility genes influencing systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Mexican-Americans from the Veterans Administration Genetic Epidemiology Study (VAGES). Methods: Using data from 1,089 individuals distributed across 266 families, we performed a multipoint linkage analysis to localize susceptibility loci for SBP and DBP by applying two models. In model 1, we added a sensible constant to the observed BP values in treated subjects [Tobin et al.; Stat Med 2005;24:2911-2935] to account for antihypertensive use (i.e. 15 and 10 mm Hg to SBP and DBP values, respectively). In model 2, we fixed values of 140 mm Hg for SBP and 90 mm Hg for DBP, if the treated values were less than the standard referenced treatment thresholds of 140/90 mm Hg for hypertensive status. However, if the observed treated BP values were found to be above these standard treatment thresholds, the actual observed treated BP values were retained in order not to reduce them by substitution of the treatment threshold values. Results: The multipoint linkage analysis revealed strong linkage signals for SBP compared with DBP. The strongest evidence for linkage of SBP (model 1, LOD = 5.0; model 2, LOD = 3.6) was found on chromosome 6q14.1 near the marker D6S1031 (89 cM) in both models. In addition, some evidence for SBP linkage occurred on chromosomes 1q, 4p, and 16p. Most importantly, our major SBP linkage finding on chromosome 6q near marker D6S1031 was independently confirmed in a Caucasian population (LOD = 3.3). In summary, our study found evidence for a major locus on chromosome 6q influencing SBP levels in Mexican-Americans. Copyright (C) 2011 S. Karger AG, Basel C1 [DeFronzo, Ralph A.; Jenkinson, Christopher P.] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, Dept Med, San Antonio, TX 78229 USA. [Puppala, Sobha; Schneider, Jennifer; Farook, Vidya S.; Dyer, Thomas D.; Blangero, John; Duggirala, Ravindranath; Jenkinson, Christopher P.] Univ Texas Hlth Sci Ctr San Antonio, SW Fdn Biomed Res, San Antonio, TX 78229 USA. [Hu, Shirley L.; DeFronzo, Ralph A.; Jenkinson, Christopher P.] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Arya, Rector] Univ Texas Hlth Sci Ctr San Antonio, Div Clin Epidemiol, San Antonio, TX 78229 USA. [Coletta, Dawn K.] Arizona State Univ, Ctr Metab Biol, Tempe, AZ USA. [Coletta, Dawn K.] Arizona State Univ, Sch Life Sci, Tempe, AZ USA. RP Jenkinson, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM jenkinsonc@uthscsa.edu RI Coletta, Dawn/G-6382-2016; OI Coletta, Dawn/0000-0001-5819-5152 FU National Institutes of Health [DK42273, DK47482, DK53889, DK70746, MH59490]; American Heart Association; Veterans Administration FX We thank Marcel J. Fourcaudot and Lenore M. Rodriguez for their excellent technical assistance. We thank our nurses, James King, John Kincaid, Rose Kaminski-Graham, and Norma Diaz, for their excellent care of the patients throughout the study. This work was supported by a Veterans Administration Epidemiologic grant. This study was also supported in part by grants from the National Institutes of Health (DK42273, DK47482, DK53889, DK70746, and MH59490), and by an American Heart Association National Scientist Development Grant. We thank the Center for Inherited Disease Research (CIDR) for providing a genome scan using the VAGES data. We thank the participants of the VAGES and are grateful for their participation and cooperation. NR 55 TC 11 Z9 11 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2011 VL 71 IS 1 BP 1 EP 10 DI 10.1159/000323143 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 758IG UT WOS:000290157200001 PM 21293138 ER PT J AU Sun, N Yoon, TJ Lee, H Andress, W Weissleder, R Ham, D AF Sun, Nan Yoon, Tae-Jong Lee, Hakho Andress, William Weissleder, Ralph Ham, Donhee TI Palm NMR and 1-Chip NMR SO IEEE JOURNAL OF SOLID-STATE CIRCUITS LA English DT Article; Proceedings Paper CT International Solid-State Circuits Conference (ISSCC) CY FEB 07-11, 2010 CL San Francisco, CA DE Biosensors; CMOS; radio-frequency integrated circuits(RFICs); lab on a chip; nuclear magnetic resonance (NMR) ID NUCLEAR-MAGNETIC-RESONANCE; BIOSENSOR; CELLS AB In our earlier work, we developed a 2-kg NMR system, which was 60X lighter, 40X smaller, yet 60X more spin-mass sensitive than a 120-kg state-of-the-art commercial benchtop system. Here we report on two new nuclear magnetic resonance (NMR) systems that represent further orders-of-magnitude size reduction and lab-on-a-chip capability. The first system, which weighs 0.1 kg and can be held in the palm of a hand, is the smallest NMR system ever built, and is 1200X lighter, 1200X smaller, yet 150X more spin-mass sensitive than the commercial system. It is enabled by combining the physics of NMR with a CMOS RF transceiver. The second system, which even integrates a sample coil, directly interfaces the CMOS chip with a sample for lab-on-a-chip operation. The two systems detect biological objects such as avidin, human chorionic gonadotropin, and human bladder cancer cells. C1 [Sun, Nan; Andress, William; Ham, Donhee] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Yoon, Tae-Jong; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. RP Sun, N (reprint author), Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA. EM nansun@seas.harvard.edu NR 18 TC 48 Z9 49 U1 2 U2 20 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9200 J9 IEEE J SOLID-ST CIRC JI IEEE J. Solid-State Circuit PD JAN PY 2011 VL 46 IS 1 BP 342 EP 352 DI 10.1109/JSSC.2010.2074630 PG 11 WC Engineering, Electrical & Electronic SC Engineering GA 701RD UT WOS:000285839200030 ER PT J AU Takahashi, K Chang, WC Takahashi, M Paylov, V Ishida, Y La Bonte, L Shi, L Fujita, T Stahl, GL Van Cott, EM AF Takahashi, Kazue Chang, Wei-Chuan Takahashi, Minoru Paylov, Vasile Ishida, Yumi La Bonte, Laura Shi, Lei Fujita, Teizo Stahl, Gregory L. Van Cott, Elizabeth M. TI Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation SO IMMUNOBIOLOGY LA English DT Article DE Mannose-binding lectin; MASP; Deficiency; Infection; Coagulation; Inflammation ID C-REACTIVE PROTEIN; WAVE-FORM ANALYSIS; PLASMINOGEN-ACTIVATOR INHIBITOR-1; PATTERN-RECOGNITION MOLECULE; SERINE-PROTEASE; STAPHYLOCOCCUS-AUREUS; EARLY IDENTIFICATION; COMPLEMENT PATHWAY; INNATE IMMUNITY; MICE AB The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3 deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus infected MBL null mice developed disseminated intravascular coagulation (DIC), which was associated with elevated blood IL-6 levels (but not TNF-alpha and multi-organ inflammatory responses). Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases. (C) 2010 Elsevier GmbH. All rights reserved. C1 [Takahashi, Kazue; Chang, Wei-Chuan; Shi, Lei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Dev Immunol Program, Boston, MA 02114 USA. [Takahashi, Minoru; Ishida, Yumi; Fujita, Teizo] Fukushima Med Univ, Dept Immunol, Sch Med, Fukushima 9601295, Japan. [Paylov, Vasile; La Bonte, Laura; Stahl, Gregory L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med,Ctr Expt T, Boston, MA 02115 USA. [Van Cott, Elizabeth M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Takahashi, K (reprint author), 55 Fruit St,GRJ1402, Boston, MA 02114 USA. EM ktakahashi1@partners.org FU NIH NIH [R21 AI077081, U01 AI074503, R01HL52886, RC1HL099130, R01HL56086, R56HL056086, R21HL092469]; MECSSTJ; CREST; STA FX The work was supported by grants from NIH NIH: KT, WC, and SM by R21 AI077081 and U01 AI074503; GS and LL by R01HL52886, RC1HL099130, R01HL56086, R56HL056086, R21HL092469; and TF, MT and YI by MECSSTJ and CREST and STA. We thank Dr. Michael C. Carroll, Jean C. Lee and Enzon Pharmaceuticals for providing C3 null mice breeding pairs. S. aureus and rhMBL, respectively. We also thank Dr. Andrew Kolodziej and Ms. Sheree McClear for providing the fibrin clot assay protocol and excellent technical assistance, respectively. NR 58 TC 39 Z9 40 U1 0 U2 5 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD JAN-FEB PY 2011 VL 216 IS 1-2 BP 96 EP 102 DI 10.1016/j.imbio.2010.02.005 PG 7 WC Immunology SC Immunology GA 708ZP UT WOS:000286403300012 PM 20399528 ER PT J AU Larsen, ME Kloverpris, H Stryhn, A Koofhethile, CK Sims, S Ndung'u, T Goulder, P Buus, S Nielsen, M AF Larsen, Malene Erup Kloverpris, Henrik Stryhn, Anette Koofhethile, Catherine K. Sims, Stuart Ndung'u, Thumbi Goulder, Philip Buus, Soren Nielsen, Morten TI HLArestrictor-a tool for patient-specific predictions of HLA restriction elements and optimal epitopes within peptides SO IMMUNOGENETICS LA English DT Article DE HLA restriction; Epitope prediction; MHC class I; Peptide binding; T cell epitope validation; HLA tetramer validation ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL RESPONSES; BINDING-AFFINITY; VACCINIA VIRUS; HIV AB Traditionally, T cell epitope discovery requires considerable amounts of tedious, slow, and costly experimental work. During the last decade, prediction tools have emerged as essential tools allowing researchers to select a manageable list of epitope candidates to test from a larger peptide, protein, or even proteome. However, no current tools address the complexity caused by the highly polymorphic nature of the restricting HLA molecules, which effectively individualizes T cell responses. To fill this gap, we here present an easy-to-use prediction tool named HLArestrictor (http://www.cbs.dtu.dk/services/HLArestrictor), which is based on the highly versatile and accurate NetMHCpan predictor, which here has been optimized for the identification of both the MHC restriction element and the corresponding minimal epitope of a T cell response in a given individual. As input, it requires high-resolution (i.e., 4-digit) HLA typing of the individual. HLArestrictor then predicts all 8-11mer peptide binders within one or more larger peptides and provides an overview of the predicted HLA restrictions and minimal epitopes. The method was tested on a large dataset of HIV IFN gamma ELIspot peptide responses and was shown to identify HLA restrictions and minimal epitopes for about 90% of the positive peptide/patient pairs while rejecting more than 95% of the negative peptide-HLA pairs. Furthermore, for 18 peptide/HLA tetramer validated responses, HLArestrictor in all cases predicted both the HLA restriction element and minimal epitope. Thus, HLArestrictor should be a valuable tool in any T cell epitope discovery process aimed at identifying new epitopes from infectious diseases and other disease models. C1 [Larsen, Malene Erup; Nielsen, Morten] Tech Univ Denmark, Ctr Biol Sequence Anal, DTU Syst Biol, DK-2800 Lyngby, Denmark. [Kloverpris, Henrik; Koofhethile, Catherine K.; Sims, Stuart; Goulder, Philip] Univ Oxford, Oxford OX1 3SY, England. [Stryhn, Anette; Buus, Soren] Univ Copenhagen, Expt Immunol Lab, Fac Hlth Sci, Copenhagen, Denmark. [Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Durban, South Africa. [Ndung'u, Thumbi] Massachusetts Gen Hosp, Ragon Inst, MIT, Charlestown, MA 02129 USA. [Ndung'u, Thumbi] Harvard Univ, Charlestown, MA 02129 USA. RP Nielsen, M (reprint author), Tech Univ Denmark, Ctr Biol Sequence Anal, DTU Syst Biol, Bldg 208, DK-2800 Lyngby, Denmark. EM mel@cbs.dtu.dk; henrik.kloverpris@paediatrics.ox.ac.uk; astryhn@sund.ku.dk; khei79@yahoo.com; stuart.sims@ndm.ox.ac.uk; Ndungu@ukzn.ac.za; Philip.Goulder@paediatrics.ox.ac.uk; sbuus@sund.ku.dk; mniel@cbs.dtu.dk RI Nielsen, Morten/E-7754-2011; OI Nielsen, Morten/0000-0001-7885-4311; Buus, Soren/0000-0001-8363-1999; Ndung'u, Thumbi/0000-0003-2962-3992 FU NIH (National Institute of Health) [HHSN272200900045C]; Danish Council for Independent Research Technology and Production Sciences [FTP 274-05-0582] FX This work was supported by a NIH (National Institute of Health) grant (contract no. HHSN272200900045C) and The Danish Council for Independent Research Technology and Production Sciences (FTP 274-05-0582). NR 26 TC 23 Z9 23 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 EI 1432-1211 J9 IMMUNOGENETICS JI Immunogenetics PD JAN PY 2011 VL 63 IS 1 BP 43 EP 55 DI 10.1007/s00251-010-0493-5 PG 13 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 702FO UT WOS:000285880200005 ER PT S AU Mohan, R Bortfeld, T AF Mohan, Radhe Bortfeld, Thomas BE Meyer, JL Dawson, LA Kavanagh, BD Purdy, JA Timmerman, R TI Proton Therapy: Clinical Gains through Current and Future Treatment Programs SO IMRT IGRT SBRT- ADVANCES IN THE TREATMENT PLANNING AND DELIVERY OF RADIOTHERAPY SE Frontiers of Radiation Therapy and Oncology LA English DT Article ID RADIATION-THERAPY; LUNG-TUMORS; BEAM; DELIVERY; MOTION; RANGE; VERIFICATION; IRRADIATION; EMISSION AB Proton beams can provide a substantial dosimetric advantage because of their unique depth-dose characteristics, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may allow escalation of tumor doses, potentially improving local control and survival while at the same time reducing toxicity and improving quality of life. While many of the steps in proton and photon treatment planning processes are similar, there are also significant differences. Some of these arise from the unique physical characteristics of protons, while others are the result of their greater vulnerability to uncertainties, especially from inter- and intrafractional variations in anatomy. These factors must be considered in designing margins and field-shaping devices, as well as in designing treatment plans as a whole and in evaluating them. Ongoing research is aimed at better estimation of these uncertainties and their impact on proton therapy, and reducing these uncertainties through image guidance, adaptive radiotherapy and the development of novel imaging devices and dose computation algorithms. For proton therapy delivery, intensity modulation techniques are already in use, and will continue to be developed and utilized increasingly. The advantages include greater flexibility in dose shaping for improved target coverage and reduced normal tissue dose, potential improvement in plan robustness, and improvement in clinical efficiency. A spectrum of imaging techniques can now be used to assist our understanding of proton dosimetry in the patient, and PET imaging is the one that is furthest developed toward the goal of in vivo dose imaging. To decrease the cost of proton therapy and increase its availability, many technical improvements and practical delivery technologies are being developed, including compact proton machines that will soon become clinically available. Copyright (C) 2011 S. Karger AG, Basel C1 [Mohan, Radhe] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bortfeld, Thomas] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP Mohan, R (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd,Unit 94, Houston, TX 77030 USA. EM rmohan@mdanderson.org NR 22 TC 6 Z9 6 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0071-9676 BN 978-3-80559-680-0 J9 FRONT RADIAT THER ON JI Front.Radiat.Ther.Oncol. PY 2011 VL 43 BP 440 EP 464 PG 25 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BVO76 UT WOS:000292117400023 PM 21625168 ER PT S AU DeLaney, TF AF DeLaney, Thomas F. BE Meyer, JL Dawson, LA Kavanagh, BD Purdy, JA Timmerman, R TI Proton Therapy in the Clinic SO IMRT IGRT SBRT- ADVANCES IN THE TREATMENT PLANNING AND DELIVERY OF RADIOTHERAPY SE Frontiers of Radiation Therapy and Oncology LA English DT Article ID MODULATED RADIATION-THERAPY; LUNG-TUMORS; X-RAY; PROSTATE; RADIOTHERAPY; CANCER; MEDULLOBLASTOMA; ADENOCARCINOMA; PHOTON; RISK AB The clinical advantage for proton radiotherapy over photon approaches is the marked reduction in integral dose to the patient, due to the absence of exit dose beyond the proton Bragg peak. The integral dose with protons is approximately 60% lower than that with any external beam photon technique. Pediatric patients, because of their developing normal tissues and anticipated length of remaining life, are likely to have the maximum clinical gain with the use of protons. Proton therapy may also allow treatment of some adult tumors to much more effective doses, because of normal tissue sparing distal to the tumor. Currently, the most commonly available proton treatment technology uses 3D conformal approaches based on (a) distal range modulation, (b) passive scattering of the proton beam in its x- and y-axes, and (c) lateral beam-shaping. It is anticipated that magnetic pencil beam scanning will become the dominant mode of proton delivery in the future, which will lower neutron scatter associated with passively scattered beam lines, reduce the need for expensive beam-shaping devices, and allow intensity-modulated proton radiotherapy. Proton treatment plans are more sensitive to variations in tumor size and normal tissue changes over the course of treatment than photon plans, and it is expected that adaptive radiation therapy will be increasingly important for proton therapy as well. While impressive treatment results have been reported with protons, their cost is higher than for photon IMRT. Hence, protons should ideally be employed for anatomic sites and tumors not well treated with photons. While protons appear cost-effective for pediatric tumors, their cost-effectiveness for treatment of some adult tumors, such as prostate cancer, is uncertain. Comparative studies have been proposed or are in progress to more rigorously assess their value for a variety of sites. The utility of proton therapy will be enhanced by technological developments that reduce its cost. Combinations of 3D protons with IMRT photons may offer improved treatment plans at lower cost than pure proton plans. Hypofractionation with proton therapy appears to be safe and cost-effective for many tumor sites, such as for selected liver, lung and pancreas cancers, and may yield significant reduction in the cost of a therapy course. Together, these offer practical strategies for expanding the clinical availability of proton therapy. Copyright (C) 2011 S. Karger AG, Basel C1 Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM tdelaney@partners.org NR 31 TC 23 Z9 23 U1 1 U2 9 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0071-9676 BN 978-3-80559-680-0 J9 FRONT RADIAT THER ON JI Front.Radiat.Ther.Oncol. PY 2011 VL 43 BP 465 EP 485 PG 21 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BVO76 UT WOS:000292117400024 PM 21625169 ER PT J AU Ellingson, K Muder, RR Jain, R Kleinbaum, D Feng, PJI Cunningham, C Squier, C Lloyd, J Edwards, J Gebski, V Jernigan, J AF Ellingson, Katherine Muder, Robert R. Jain, Rajiv Kleinbaum, David Feng, Pei-Jean I. Cunningham, Candace Squier, Cheryl Lloyd, Jon Edwards, Jonathan Gebski, Val Jernigan, John TI Sustained Reduction in the Clinical Incidence of Methicillin-Resistant Staphylococcus aureus Colonization or Infection Associated with a Multifaceted Infection Control Intervention SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INTENSIVE-CARE UNITS; NOSOCOMIAL INFECTION; HOSPITAL ADMISSION; BACTEREMIA; STATES; SURVEILLANCE; COMMUNITY; EPIDEMIOLOGY; PREVALENCE; MORTALITY AB OBJECTIVE. To assess the impact and sustainability of a multifaceted intervention to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission implemented in 3 chronologically overlapping phases at 1 hospital. DESIGN. Interrupted time-series analyses. SETTING. A Veterans Affairs hospital in the northeastern United States. PATIENTS AND PARTICIPANTS. Individuals admitted to acute care units from October 1, 1999, through September 30, 2008. To calculate the monthly clinical incidence of MRSA colonization or infection, the number of MRSA-positive cultures obtained from a clinical site more than 48 hours after admission among patients with no MRSA-positive clinical cultures during the previous year was divided by patient-days at risk. Secondary outcomes included clinical incidence of methicillin-sensitive S. aureus colonization or infection and incidence of MRSA bloodstream infections. INTERVENTIONS. The intervention-implemented in a surgical ward beginning October 2001, in a surgical intensive care unit beginning October 2003, and in all acute care units beginning July 2005-included systems and behavior change strategies to increase adherence to infection control precautions (eg, hand hygiene and active surveillance culturing for MRSA). RESULTS. Hospital-wide, the clinical incidence of MRSA colonization or infection decreased after initiation of the intervention in 2001, compared with the period before intervention (P = .002), and decreased by 61% (P < .001) in the 7-year postintervention period. In the postintervention period, the hospital-wide incidence of MRSA bloodstream infection decreased by 50% (P = .02), and the proportion of S. aureus isolates that were methicillin resistant decreased by 30% (P < .001). CONCLUSIONS. Sustained decreases in hospital-wide clinical incidence of MRSA colonization or infection, incidence of MRSA bloodstream infection, and proportion of S. aureus isolates resistant to methicillin followed implementation of a multifaceted prevention program at one Veterans Affairs hospital. Findings suggest that interventions designed to prevent transmission can impact endemic antimicrobial resistance problems. C1 [Ellingson, Katherine] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Muder, Robert R.; Jain, Rajiv; Cunningham, Candace; Squier, Cheryl; Lloyd, Jon] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gebski, Val] Univ Sydney, Camperdown, NSW, Australia. RP Ellingson, K (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Clifton Rd NE,MS A-31, Atlanta, GA 30333 USA. EM kellingson@cdc.gov NR 31 TC 36 Z9 37 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JAN PY 2011 VL 32 IS 1 BP 1 EP 8 DI 10.1086/657665 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 694IP UT WOS:000285290200001 PM 21133794 ER PT J AU Feng, PJI Kallen, AJ Ellingson, K Muder, R Jain, R Jernigan, JA AF Feng, Pei-Jean I. Kallen, Alexander J. Ellingson, Katherine Muder, Robert Jain, Rajiv Jernigan, John A. TI Clinical Incidence of Methicillin-Resistant Staphylococcus aureus (MRSA) Colonization or Infection as a Proxy Measure for MRSA Transmission in Acute Care Hospitals SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID ADMISSION; SURVEILLANCE; BACTEREMIA; MORTALITY; OUTCOMES; IMPACT AB BACKGROUND. The incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection has been used as a proxy measure for MRSA transmission, but incidence calculations vary depending on whether active surveillance culture (ASC) data are included. OBJECTIVE. To evaluate the relationship between incidences of MRSA colonization or infection calculated with and without ASCs in intensive care units and non-intensive care units. SETTING. A Veterans Affairs medical center. METHODS. From microbiology records, incidences of MRSA colonization or infection were calculated with and without ASC data. Correlation coefficients were calculated for the 2 measures, and Poisson regression was used to model temporal trends. A Poisson interaction model was used to test for differences in incidence trends modeled with and without ASCs. RESULTS. The incidence of MRSA colonization or infection calculated with ASCs was 4.9 times higher than that calculated without ASCs. Correlation coefficients for incidences with and without ASCs were 0.42 for intensive care units, 0.59 for non-intensive care units, and 0.48 hospital-wide. Trends over time for the hospital were similar with and without ASCs (incidence rate ratio with ASCs, 0.95 [95% confidence interval, 0.93-0.97]; incidence rate ratio without ASCs, 0.95 [95% confidence interval, 0.92-0.99]; P = .68). Without ASCs, 35% of prevalent cases were falsely classified as incident. CONCLUSIONS. At 1 Veterans Affairs medical center, the incidence of MRSA colonization or infection calculated solely on the basis of clinical culture results commonly misclassified incident cases and underestimated incidence, compared with measures that included ASCs; however, temporal changes were similar. These findings suggest that incidence measured without ASCs may not accurately reflect the magnitude of MRSA transmission but may be useful for monitoring transmission trends over time, a crucial element for evaluating the impact of prevention activities. C1 [Feng, Pei-Jean I.; Kallen, Alexander J.; Ellingson, Katherine; Jernigan, John A.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Muder, Robert; Jain, Rajiv] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Kallen, AJ (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS A-35, Atlanta, GA 30333 USA. EM ffp0@cdc.gov NR 16 TC 6 Z9 7 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JAN PY 2011 VL 32 IS 1 BP 20 EP 25 DI 10.1086/657668 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 694IP UT WOS:000285290200003 PM 21133793 ER PT J AU Siegel, CA Siegel, LS Hyams, JS Kugathasan, S Markowitz, J Rosh, JR Leleiko, N Mack, DR Crandall, W Evans, J Keljo, DJ Otley, AR Oliva-Hemker, M Farrior, S Langton, CR Wrobel, IT Wahbeh, G Quiros, JA Silber, G Bahar, RJ Sands, BE Dubinsky, MC AF Siegel, Corey A. Siegel, Lori S. Hyams, Jeffrey S. Kugathasan, Subra Markowitz, James Rosh, Joel R. Leleiko, Neal Mack, David R. Crandall, Wallace Evans, Jonathan Keljo, David J. Otley, Anthony R. Oliva-Hemker, Maria Farrior, Sharmayne Langton, Christine R. Wrobel, Iwona T. Wahbeh, Ghassan Quiros, J. Antonio Silber, Gary Bahar, Ron J. Sands, Bruce E. Dubinsky, Marla C. TI Real-time Tool to Display the Predicted Disease Course and Treatment Response for Children with Crohn's Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's; complication; prediction; model; pediatric ID TRIAL; RISK; INFLIXIMAB; BEHAVIOR; THERAPY; MARKERS AB Background: Immunomodulators and biologics are effective treatments for children with Crohn's disease (CD). The challenge of communicating the anticipated disease course with and without therapy to patients and parents is a barrier to the timely use of these agents. The aim of this project was to develop a tool to graphically display the predicted risks of CD and expected benefits of therapy. Methods: Using prospectively collected data from 796 pediatric CD patients we developed a model using system dynamics analysis (SDA). The primary model outcome is the probability of developing a CD-related complication. Input variables include patient and disease characteristics, magnitude of serologic immune responses expressed as the quartile sum score (QSS), and exposure to medical treatments. Results: Multivariate Cox proportional analyses show variables contributing a significant increase in the hazard ratio (HR) for a disease complication include female gender, older age at diagnosis, small bowel or perianal disease, and a higher QSS. As QSS increases, the HR for early use of corticosteroids increases, in contrast to a decreasing HR with early use of immunomodulators, early or late biologics, and early combination therapy. The concordance index for the model is 0.81. Using SDA, results of the Cox analyses are transformed into a simple graph displaying a real-time individualized probability of disease complication and treatment response. Conclusions: We have developed a tool to predict and communicate individualized risks of CD complications and how this is modified by treatment. Once validated, it can be used at the bedside to facilitate patient decision making. C1 [Siegel, Corey A.] Dartmouth Hitchcock Med Ctr, Dartmouth Hitchcock Inflammatory Bowel Dis Ctr, Lebanon, NH 03756 USA. [Siegel, Lori S.] Siegel Environm Dynam LLC, Hanover, NH USA. [Hyams, Jeffrey S.; Langton, Christine R.] Connecticut Childrens Med Ctr, Dept Pediat, Hartford, CT USA. [Kugathasan, Subra] Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Markowitz, James] Schneider Childrens Hosp, New Hyde Pk, NY USA. [Rosh, Joel R.] Morristown Mem Hosp, Dept Pediat, Morristown, NJ USA. [Leleiko, Neal] Hasbro Childrens Hosp, Dept Pediat, Providence, RI USA. [Mack, David R.] Childrens Hosp Eastern Ontario, Dept Pediat, Ottawa, ON K1H 8L1, Canada. [Crandall, Wallace] Nationwide Childrens Hosp, Dept Pediat, Columbus, OH USA. [Evans, Jonathan] Nemours Childrens Clin, Dept Pediat, Jacksonville, FL USA. [Keljo, David J.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Otley, Anthony R.] Dalhousie Univ, Dept Pediat, Halifax, NS, Canada. [Oliva-Hemker, Maria] Johns Hopkins Univ Hosp, Dept Pediat, Baltimore, MD 21287 USA. [Farrior, Sharmayne; Bahar, Ron J.; Dubinsky, Marla C.] Cedars Sinai Med Ctr, Dept Pediat, IBD Ctr, Los Angeles, CA 90048 USA. [Wrobel, Iwona T.] Alberta Childrens Prov Gen Hosp, Dept Pediat, Calgary, AB T2T 5C7, Canada. [Wahbeh, Ghassan] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA. [Quiros, J. Antonio] Calif Pacific Med Ctr, San Francisco, CA USA. [Silber, Gary] Phoenix Childrens Hosp, Dept Pediat, Phoenix, AZ USA. [Sands, Bruce E.] Massachusetts Gen Hosp, Gastrointestinal Unit, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Siegel, CA (reprint author), Dartmouth Hitchcock Med Ctr, Sect Gastroenterol & Hepatol, Ctr Inflammatory Bowel Dis, Lebanon, NH 03756 USA. EM corey.a.siegel@hitchcock.org OI leleiko, neal/0000-0001-7699-1400 FU CCFA; National Institute of Diabetes and Digestive and Kidney Diseases [K23DK078678, K23DK066248]; Abe and Claire Levine Chair in Pediatric IBD; Truman Katz Foundation; Abbott Laboratories; Centocor; Abbott; UCB; Prometheus Labs FX Dr. Siegel is supported by a CCFA career development award and by Grant Number K23DK078678 from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Dubinsky is supported by the Abe and Claire Levine Chair in Pediatric IBD, and Grant Number K23DK066248 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health. Dr. Ghassan is supported in part by the Truman Katz Foundation.; Dr. Siegel serves as a consultant to Abbott Laboratories and UCB. Dr. Dubinsky serves as a consultant to Abbott Laboratories, Centocor, Prometheus Labs, and UCB. Dr. Sands serves as a consultant to Abbott Laboratories, Centocor, Prometheus Labs, and UCB. Dr. Rosh serves as a consultant to Abbott Laboratories, Centocor and UCB, receives grant support from Abbott Laboratories and Centocor, and serves as a speaker for Abbott and Abbott Nutrition. Christine Langton receives salary support from Centocor. Dr. Hyams serves as a consultant to and receives research support from Abbott, Centocor, UCB. Dr. Markowitz serves as a consultant to and receives research support from Centocor and Prometheus Labs, and has received honoraria from Prometheus labs. Dr. Quiros serves as a consultant for UCB. Dartmouth-Hitchcock Medical Center and Cedars-Sinai Medical Center have a United States patent pending on intellectual property related to this work, filed on March 24, 2010 as Application serial number 61/163,024. Inventors are C.A. Siegel, L.S. Siegel, and M.C. Dubinsky. NR 16 TC 32 Z9 33 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2011 VL 17 IS 1 BP 30 EP 38 DI 10.1002/ibd.21386 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 693XK UT WOS:000285258500006 PM 20812335 ER PT J AU Sonnenberg, A Melton, SD Genta, RM AF Sonnenberg, Amnon Melton, Shelby D. Genta, Robert M. TI Frequent Occurrence of Gastritis and Duodenitis in Patients with Inflammatory Bowel Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE chronic active gastritis; Crohn's disease; duodenitis; epidemiology of gastritis; Helicobacter pylori; ulcerative colitis ID FOCALLY ENHANCED GASTRITIS; GASTROESOPHAGEAL-REFLUX DISEASE; HELICOBACTER-PYLORI; CROHNS-DISEASE; ULCERATIVE-COLITIS; SYDNEY SYSTEM; BIOPSIES; PREVALENCE; ANTRUM; BODY AB Background: The purpose was to study the epidemiology of Helicobacter-negative gastritis among a large group of patients with inflammatory bowel disease (IBD) and healthy controls. Methods: From a computerized database of surgical pathology reports we selected 5493 patients who underwent colonoscopy and upper gastrointestinal endoscopy with biopsy results from both procedures. The presence of gastritis and duodenitis was compared among 550 case subjects with IBD and 4943 healthy control subjects. The results are expressed as prevalence rates, as well as age- and sex-adjusted odds ratios with 95% confidence intervals. Results: Any type gastritis was found in 13% of controls and 25% of IBD patients (Crohn's disease [CD] 33%, ulcerative colitis [UC] 19%). Duodenitis was found in 1% of controls and 13% of IBD patients (CD 26%, UC 3%). In subjects younger than 18 years the prevalence of gastritis and duodenitis were 53% and 40% in CD, respectively, and 38% and 0% in UC, respectively. Similar prevalence rates were found in men and women. The odds ratio for Helicobacter-negative chronic active gastritis associated with CD was 11.7 (7.5-18.0) and with UC 2.8 (1.4-5.0). The corresponding values for focally enhanced gastritis were 40.1 (15.5-114.9) in CD and 0 in UC. Conclusions: Helicobacter-negative gastritis and duodenitis occur significantly more often in patients with IBD than healthy controls. Such upper gastrointestinal inflammation appears to be particularly common in CD and younger patients. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Genta, Robert M.] Caris Life Sci, Irving, TX USA. [Melton, Shelby D.; Genta, Robert M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Melton, Shelby D.; Genta, Robert M.] Dallas VA Med Ctr, Dallas, TX USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 33 TC 20 Z9 21 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2011 VL 17 IS 1 BP 39 EP 44 DI 10.1002/ibd.21356 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 693XK UT WOS:000285258500007 PM 20848539 ER PT J AU Subramanian, S Yajnik, V Sands, BE Cullen, G Korzenik, JR AF Subramanian, Sreedhar Yajnik, Vijay Sands, Bruce E. Cullen, Garret Korzenik, Joshua R. TI Characterization of Patients with Infliximab-induced Lupus Erythematosus and Outcomes After Retreatment with a Second Anti-TNF Agent SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE drug induced lupus erythematosus; anti-TNF therapy; inflammatory bowel diseases; infliximab ID ANTITUMOR NECROSIS FACTOR; DRUG-INDUCED LUPUS; CROHNS-DISEASE; CERTOLIZUMAB PEGOL; SERUM SICKNESS; ADALIMUMAB; ANTINUCLEAR; INFUSION; THERAPY; TRIAL AB Background: Drug-induced lupus erythematosus (DILE) due to infliximab therapy for inflammatory bowel disease (IBD) is an uncommon occurrence. It remains uncertain whether patients with infliximab-induced DILE could tolerate another antitumor necrosis factor (TNF) agent without recurrent DILE. Methods: We reviewed the case records of patients with infliximab-induced DILE diagnosed at our institute and noted details of their clinical and immunological profile at presentation. In addition, case notes of patients who were treated with a second anti-TNF agent were examined for evidence of recurrent DILE. Results: Thirteen patients with infliximab-induced DILE were identified with a female-to-male ratio of 11:2. Symmetric large joint arthralgias and high titers of antinuclear and antidouble-stranded DNA antibody were noted in all patients. Eight patients were retreated with a second anti-TNF agent (six certolizumab pegol and two adalimumab) of whom two patients (one adalimumab and certolizumab pegol each) developed recurrent DILE following 3 months of therapy with a second anti-TNF agent. One patient discontinued therapy after 2 months despite no recurrence of DILE, due to fear of side effects. Five patients remain well with no recurrence of DILE after a median of 5 months (range 26) therapy. Conclusions: Rechallenge with a further anti-TNF agent in patients who have developed DILE with infliximab is associated with a low rate of recurrence. C1 [Subramanian, Sreedhar] Royal Liverpool Univ Hosp, Dept Gastroenterol, Liverpool L7 8XP, Merseyside, England. [Yajnik, Vijay; Sands, Bruce E.; Cullen, Garret; Korzenik, Joshua R.] Massachusetts Gen Hosp, Gastrointestinal Unit, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. [Yajnik, Vijay; Sands, Bruce E.; Cullen, Garret; Korzenik, Joshua R.] Harvard Univ, Sch Med, Boston, MA USA. RP Subramanian, S (reprint author), Royal Liverpool Univ Hosp, Dept Gastroenterol, Prescot St, Liverpool L7 8XP, Merseyside, England. EM sreedhar.subramanian@rlbuht.nhs.uk FU Abbott; Bristol-Myers Squibb; Centocor; Elan; Millennium Pharmaceutical; Novartis Pharmaceuticals; Otsuka America Pharmaceutical FX S.S., G.C., and J.R.K. have no competing interests. V.Y. has consulting agreements with UCB, Millennium, and Elan. B.E.S. has served as a consultant or on a scientific advisory board for Abbott, Biogen/IDEC, Bristol-Myers Squibb, Centocor, Elan, Millennium Pharmaceuticals, Novartis Pharmaceuticals, Otsuka America Pharmaceuticals, and UCB; has received honoraria for speaking from Abbott, Schering-Plough, and UCB; and has received grant support from Abbott, Bristol-Myers Squibb, Centocor, Elan, Millennium Pharmaceutical, Novartis Pharmaceuticals, and Otsuka America Pharmaceutical. NR 27 TC 23 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JAN PY 2011 VL 17 IS 1 BP 99 EP 104 DI 10.1002/ibd.21370 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 693XK UT WOS:000285258500016 PM 20629183 ER PT J AU Katzman, MA Brawman-Mintzer, O Reyes, EB Olausson, B Liu, S Eriksson, H AF Katzman, Martin A. Brawman-Mintzer, Olga Reyes, Efren B. Olausson, Bengt Liu, Sherry Eriksson, Hans TI Extended release quetiapine fumarate (quetiapine XR) monotherapy as maintenance treatment for generalized anxiety disorder: a long-term, randomized, placebo-controlled trial SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE generalized anxiety disorder; maintenance; quetiapine ID TREATMENT-RESISTANT DEPRESSION; SEROTONIN REUPTAKE INHIBITORS; NATIONAL-COMORBIDITY-SURVEY; QUALITY-OF-LIFE; DOUBLE-BLIND; OPEN-LABEL; MAJOR DEPRESSION; PRIMARY-CARE; EFFICACY; AUGMENTATION AB The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) as maintenance monotherapy for patients with generalized anxiety disorder (GAD). Time-to-event (anxiety symptom recurrence; maximum 52 weeks) multicenter, randomized-withdrawal, parallel-group, double-blind, placebo-controlled study of quetiapine XR (50-300 mg/day) following open-label run-in (4-8 weeks) and open-label stabilization (>= 12 weeks). Primary variable: time from randomization to anxiety event. Secondary variables included: Hamilton Anxiety Rating Scale (HAM-A) total, HAM-A psychic/somatic anxiety factors, Clinical Global Impression-Severity of Illness (CGI-S), and Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) scores; adverse events (AE) reporting. Four hundred and thirty-two patients, stabilized on quetiapine XR, were randomized to continue quetiapine XR (N=216) or switch to placebo (N=216). Risk of anxiety symptom recurrence was significantly reduced by 81% for quetiapine XR versus placebo: hazard ratio = 0.19 (95% confidence interval 0.12-0.31; P < 0.001). Fewer patients receiving quetiapine XR (N=22, 10.2%) than placebo (N=84, 38.9%) experienced anxiety symptom recurrence. Significant differences were observed between quetiapine XR and placebo in: HAM-A total, psychic/somatic, CGI-S (all P < 0.001) and Q-LES-Q (P < 0.05) scores. AEs (>10%) during open-label treatment were dry mouth, sedation, somnolence, dizziness, fatigue, and constipation. During randomized treatment, the most common AEs for quetiapine XR were headache and nasopharyngitis. Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR, with tolerability results consistent with the known profile of quetiapine. Int Clin Psychopharmacol 26: 11-24 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Katzman, Martin A.] START Clin Mood & Anxiety Disorders, Toronto, ON M4W 2N4, Canada. [Katzman, Martin A.] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada. [Katzman, Martin A.] Lakehead Univ, Dept Psychol, Thunder Bay, ON, Canada. [Katzman, Martin A.] Lakehead Univ, Master Publ Hlth Program, Thunder Bay, ON P7B 5E1, Canada. [Brawman-Mintzer, Olga] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Brawman-Mintzer, Olga] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Reyes, Efren B.] Natl Ctr Mental Hlth, Mandaluyong City, Philippines. [Olausson, Bengt; Eriksson, Hans] AstraZeneca R&D, Sodertalje, Sweden. [Liu, Sherry] AstraZeneca, Wilmington, DE USA. RP Katzman, MA (reprint author), START Clin Mood & Anxiety Disorders, 32 Pk Rd, Toronto, ON M4W 2N4, Canada. EM mkatzman@startclinic.ca FU AstraZeneca [D1448C00012] FX The authors thank Catherine Hoare, Ph.D., from Complete Medical Communications, who provided medical writing support funded by AstraZeneca. The following investigators were involved in this study: Lawrence Adler, Diab Almhana, Donald Anderson, Gregory Asnis, Sarah Atkinson, Roy Autry, Michael Banov, Benny Barnhart, Bruce Berg, Brian Bortnick, Olga Brawman-Mintzer, Ronald Brenner, Edward Burdick, Joel Diamond, Nizar El-Khalili, John Heussy, Miguel Flores, Michael Greenbaum, Paul Gross, David Meyer, Valentin Isacescu, William Jeter, Michael Johnson, Zerrin Kayatekin, Gustavo Kinrys, Thomas Marbury, Paul Markovitz, Jorge Porras, Craig McCarthy, Irina Mezhebovsky, Amy Mulroy, John Prater, Alfredo Rivera, Angelo Sambunaris, Veronique Sebastian, Andrew Sedillo, Eric Smith, Phebe Tucker, Amit Vijapura, Robert Buynak, Kettlie Daniels, David Grubb, Margarita Nunez, Haydn Thomas, Reinaldo Verson, Daniel Vine, Ethan Kass, Andrew Goddard, Matthew Menza, Bijan Bastani (USA); Richard Bergeron, Gilbert Dru, Carlos Galarraga-Carrero, Martin Katzman, Roumen Milev, Michael Van Ameringen, Martin Tremblay, Serge Lessard, Pratap Chokka (Canada); Thomas George, Michael Theodoros, Bruce Lawford, Phillip Morris, Peter Farnbach, Jayashri Kulkarni (Australia); Hannu Koponen, Ulla Lepola, Liisa Lahdelma, Markku Timonen, Marko Sorvaniemi, Riitta Riihikangas (Finland); Klaus-Christian Steinwachs, Eugen Schlegel, Heike Benes, Gunther Karlbauer, H.-J. Gertz (Germany); Gabor Feller, Gabor Vincze, Sandor Koffler (Hungary); Kang-Seob Oh, Jin-Pyo Hong, Jeong-Ho Chae, Bum-Hee Yu (South Korea); B Bodalia, J Langan, Christopher Strang, Barry D Silvert, John Calvert, Krishna Korlipara, James Simpson, Alun Cooper, Ravi Pawa, John Robinson (United Kingdom); Konstantin Zhukov, Boris Tsygankov, Mikhail Ivanov, Boris Karvasarskii, Vladimir Vilianov, Valeriy Krasnov, Leonid Bardenshtein, Nataliya Dobrovolskaya (Russia); Ikke Siregar, Ashwin Kandouw, Anak Kusumawardhani (Indonesia); Efren Reyes, Alma Jimenez, Agnes Padilla (The Philippines). This study (Platinum; D1448C00012) was funded by AstraZeneca. NR 63 TC 38 Z9 39 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD JAN PY 2011 VL 26 IS 1 BP 11 EP 24 DI 10.1097/YIC.0b013e32833e34d9 PG 14 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 691MG UT WOS:000285083700002 PM 20881846 ER PT J AU Krobitsch, S Kazantsev, AG AF Krobitsch, Sylvia Kazantsev, Aleksey G. TI Huntington's disease: From molecular basis to therapeutic advances SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Neurodegeneration; Huntington's disease; Huntingtin; Neuroprotection ID NEURONAL INTRANUCLEAR INCLUSIONS; TRINUCLEOTIDE REPEAT; PROTEIN; BRAIN; AGGREGATION; DYSFUNCTION; TRANSCRIPTION; TOXICITY; MUTATION; MODEL AB Huntington's disease is an autosomal dominant genetic neurodegenerative disorder, which is characterized by progressive motor dysfunction, emotional disturbances, dementia, and weight loss. The disease is caused by pathological CAG-triplet repeat extension(s), encoding polyglutamines, within the gene product, huntingtin. Huntingtin is ubiquitously expressed through the body and is a protein of uncertain molecular function(s). Mutant huntingtin, containing pathologically extended polyglutamines causes the earliest and most dramatic neuropathologic changes in the neostriatum and cerebral cortex. Extended polyglutamines confer structural conformational changes to huntingtin, which gains novel properties, resulting in aberrant interactions with multiple cellular components. The diverse and variable aberrations mediated by mutant huntingtin perturb many cellular functions essential for neuronal homeostasis and underlie pleiotropic mechanisms of Huntington's disease pathogenesis. The only approved drug for Huntington's disease is a symptomatic treatment, tetrabenazine; thus, novel neuroprotective strategies, slowing, blocking and possibly reversing disease progression, are vital for developing effective therapies. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Krobitsch, Sylvia; Kazantsev, Aleksey G.] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Kazantsev, Aleksey G.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Kazantsev, AG (reprint author), Max Planck Inst Mol Genet, Ihnestr 63-73, D-14195 Berlin, Germany. EM Krobitsc@molgen.mpg.de; akazantsev@partners.org FU Alexander von Humboldt foundation; Max Planck Society FX We are grateful to the Alexander von Humboldt foundation and the Max Planck Society for supporting this work. We are also grateful to Dr. K. Kegel for critical and insightful comments. NR 30 TC 16 Z9 17 U1 3 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD JAN PY 2011 VL 43 IS 1 BP 20 EP 24 DI 10.1016/j.bioce1.2010.10.014 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 712RO UT WOS:000286684100005 PM 21056115 ER PT J AU Russell, R Anzueto, A Weisman, I AF Russell, Richard Anzueto, Antonio Weisman, Idelle TI Optimizing management of chronic obstructive pulmonary disease in the upcoming decade SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Review DE COPD; chronic obstructive pulmonary disease; long-acting bronchodilator; early treatment AB Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and mortality. Caring for patients with COPD, particularly those with advanced disease who experience frequent exacerbations, places a significant burden on health care budgets, and there is a global need to reduce the financial and personal burden of COPD. Evolving scientific evidence on the natural history and clinical course of COPD has fuelled a fundamental shift in our approach to the disease. The emergence of data highlighting the heterogeneity in rate of lung function decline has altered our perception of disease progression in COPD and our understanding of appropriate strategies for the management of stable disease. These data have demonstrated that early, effective, and prolonged bronchodilation has the potential to slow the rate of decline in lung function and to reduce the frequency of exacerbations that contribute to functional decline. The goals of therapy for COPD are no longer confined to controlling symptoms, reducing exacerbations, and maintaining quality of life, and slowing disease progression is now becoming an achievable aim. A challenge for the future will be to capitalize on these observations by improving the identification and diagnosis of patients with COPD early in the course of their disease, so that effective interventions can be introduced before the more advanced, disabling, and costly stages of the disease. Here we critically review emerging data that underpin the advances in our understanding of the clinical course and management of COPD, and evaluate both current and emerging pharmacologic options for effective maintenance treatment. C1 [Russell, Richard] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Thorac Med, London, England. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Weisman, Idelle] Pfizer Inc, Med Affairs, Resp, Primary Care Business Unit, New York, NY USA. RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd 111E, San Antonio, TX 78229 USA. EM anzueto@uthcsa.edu OI RUSSELL, RICHARD/0000-0002-3890-7201 NR 81 TC 12 Z9 13 U1 1 U2 4 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-9106 J9 INT J CHRONIC OBSTR JI Int. J. Chronic Obstr. Pulm. Dis. PY 2011 VL 6 BP 47 EP 61 DI 10.2147/COPD.S13758 PG 15 WC Respiratory System SC Respiratory System GA V28WB UT WOS:000208709800006 PM 21311693 ER PT J AU Cooper, CB Anzueto, A Decramer, M Celli, B Tashkin, DP Leimer, I Kesten, S AF Cooper, Christopher B. Anzueto, Antonio Decramer, Marc Celli, Bartolome Tashkin, Donald P. Leimer, Inge Kesten, Steven TI Tiotropium reduces risk of exacerbations irrespective of previous use of inhaled anticholinergics in placebo-controlled clinical trials SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE chronic obstructive pulmonary disease; clinical trials; exacerbations; inhaled anticholinergics; tiotropium AB Background: Data have highlighted the potential bias introduced by withdrawal of inhaled corticosteroids at randomization in chronic obstructive pulmonary disease trials examining inhaled corticosteroids. Analyses were conducted to determine whether this was true of inhaled anticholinergic withdrawal in tiotropium trials. Methods: A pooled analysis of randomized, double-blind, placebo-controlled, parallel-group tiotropium trials of at least six months' duration was performed. Trials had similar inclusion and exclusion criteria. Exacerbation definition was standardized. Patients were divided into two groups, ie, D (anticholinergics discontinued at randomization, previously prescribed) and ND (anticholinergics not discontinued, not previously prescribed). Results: Demographics were balanced between the D (n = 5846) and ND (n = 6317) groups, except for higher cumulative smoking (56 pack-years versus 48 pack-years), lower forced expiratory volume in one second (FEV1)/forced vital capacity (43% versus 48%), and lower baseline FEV1 (35.8% predicted versus 42.4% predicted) in the D group. In both groups, tiotropium reduced the risk for an exacerbation (hazard ratio [HR] = 0.83, P < 0.0001 [D] versus 0.79, P < 0.0001 [ND]) and a hospitalized exacerbation (HR = 0.85, P = 0.0467 versus 0.79, P = 0.0094). Tiotropium reduced the number of exacerbations per patient-year (rate ratio [RR] = 0.82, P < 0.0001 [D] versus RR = 0.80, P < 0.0001 [ND]) and associated hospitalizations per patient-year (RR = 0.88, P = 0.015 [D] versus RR = 0.74, P < 0.0001 [ND]). Conclusion: Tiotropium reduced exacerbations in patients who did and did not have anticholinergics discontinued upon randomization in clinical trials. C1 [Cooper, Christopher B.; Tashkin, Donald P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Decramer, Marc] Katholieke Univ Leuven, Louvain, Belgium. [Celli, Bartolome] Brigham & Womens Hosp, Boston, MA 02115 USA. [Leimer, Inge] Boehringer Ingelheim Int GmbH, Ingelheim, Germany. [Kesten, Steven] Uptake Med Corp, Tustin, CA USA. RP Cooper, CB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, 10833 Le Conte Ave,37-131 CHS, Los Angeles, CA 90095 USA. EM ccooper@mednet.ucla.edu FU Boehringer Ingelheim; Pfizer FX Preparation of this paper was funded jointly by Boehringer Ingelheim and Pfizer. The study design, collection, analysis, and interpretation of data were funded by Boehringer Ingelheim and Pfizer. NR 27 TC 5 Z9 5 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-9106 J9 INT J CHRONIC OBSTR JI Int. J. Chronic Obstr. Pulm. Dis. PY 2011 VL 6 BP 269 EP 275 DI 10.2147/COPD.S17864 PG 7 WC Respiratory System SC Respiratory System GA V28WB UT WOS:000208709800030 PM 21845038 ER PT J AU Mou, XY Kesari, S Wen, PY Huang, XD AF Mou, Xiaoyang Kesari, Santosh Wen, Patrick Y. Huang, Xudong TI Crude drugs as anticancer agents SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE LA English DT Review DE Crude drug; cancer; inflammation; cell cycle; apoptosis AB Although tremendous progress has been made in basic cancer biology and in the development of novel cancer treatments, cancer remains a leading cause of death in the world. The etiopathogenesis of cancer is complex. Besides genetic predisposition, known environmental factors associated with cancer are: diet, lifestyle, and environmental toxins. Toxicity of drugs and eventual relapse of cancers contribute to high cancer death rates. Current therapeutic interventions for cancer-surgery, chemotherapy, radiotherapy, thermotherapy, etc. are far from being curative for many forms of cancer. Chemotherapy, in particular, though the most commonly used cancer treatment, is usually associated with side effects with varying degrees of severity. The purpose of this brief review is to assemble current literature on some crude drugs and to focus on their beneficial roles and drug targets in cancer therapy and chemoprevention. Although their pharmacological mechanisms and biochemical roles in cancer biology and tumor chemoprevention are not fully understood, crude drugs are believed to have nutriceutical effects upon cancer patients. C1 [Mou, Xiaoyang; Huang, Xudong] Brigham & Womens Hosp, Conjugate & Med Chem Lab, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02115 USA. [Mou, Xiaoyang; Wen, Patrick Y.; Huang, Xudong] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kesari, Santosh] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dana Faber Canc Inst, Dept Med Oncol, Dept Neurol, Boston, MA 02115 USA. RP Huang, XD (reprint author), Brigham & Womens Hosp, Conjugate & Med Chem Lab, Div Nucl Med & Mol Imaging, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM xhuang3@partners.org RI Kesari, Santosh/E-8461-2013 FU Radiology Department of Brigham and Women's Hospital (BWH) FX This work has been supported by the research funds from Radiology Department of Brigham and Women's Hospital (BWH). We thank Ms. Kim Lawson at BWH Radiology Department for her extremely helpful comments and editing of our manuscript. NR 63 TC 7 Z9 8 U1 0 U2 1 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1940-5901 J9 INT J CLIN EXP MED JI Int. J. Clin. Exp. Med. PY 2011 VL 4 IS 1 BP 17 EP 25 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V28ST UT WOS:000208701200003 PM 21394282 ER PT J AU Nicosia, RF Zorzi, P Ligresti, G Morishita, A Aplin, AC AF Nicosia, Roberto F. Zorzi, Penelope Ligresti, Giovanni Morishita, Ann Aplin, Alfred C. TI Paracrine regulation of angiogenesis by different cell types in the aorta ring model SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE VEGF; bFGF; PDGF; angiopoietin; MMP; TIMP; microarray ID ENDOTHELIAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; FACTOR INDUCE EXPRESSION; SMOOTH-MUSCLE CELLS; RAT AORTA; IN-VITRO; COLLAGEN GEL; INFLAMMATORY CYTOKINES; CARCINOMA-CELLS; CLOT CULTURE AB The development of blood vessels during angiogenesis is the result of paracrine interactions between tube-forming endothelial cells and angiogenic factor-producing nonendothelial cells. This process can be reproduced and studied under chemically defined culture conditions by culturing vascular explants in three-dimensional gels of extracellular matrix. Rings of rat or mouse aorta cultured in collagen, fibrin or basement membrane gels produce angiogenic outgrowths composed of a mixed population of endothelial cells and nonendothelial cells. Aortic angiogenesis is regulated by endogenous angiogenic factors, inflammatory cytokines, chemokines, extracellular matrix molecules, and proteolytic enzymes produced by cells of the vessel wall in response to the injury of the dissection procedure. In this paper, we review how macrophages, mural cells and fibroblasts regulate different stages of the angiogenic process, from the formation of immature endothelial sprouts to the reabsorption of the neovessels. We also describe how aortic cultures can be used to study interactions between angiogenic outgrowths and nonvascular cell types such as bone marrow macrophages, platelets or cancer cells. Morphologic, genetic and functional studies of this model have provided invaluable information on how vessels form, mature, interact with nonvascular cell types, and are eventually reabsorbed. Further analysis of the paracrine cross-talk between aortic endothelial and nonendothelial cells is likely to provide new insights into the angiogenic process and its key mechanisms. C1 [Nicosia, Roberto F.; Zorzi, Penelope; Ligresti, Giovanni; Morishita, Ann; Aplin, Alfred C.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Pathol Serv, Pathol & Lab Med S113, Seattle, WA 98108 USA. [Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Lab Med Serv, Seattle, WA 98108 USA. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Pathol Serv, Pathol & Lab Med S113, 1660 S Columbian Way, Seattle, WA 98108 USA. EM roberto.nicosia@va.gov FU National Heart, Lung, and Blood Institute [HL52585]; US Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory FX Supported by National Heart, Lung, and Blood Institute Grant HL52585 and Merit Review Grant from US Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research Program. NR 51 TC 23 Z9 24 U1 1 U2 3 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2011 VL 55 IS 4-5 SI SI BP 447 EP 453 DI 10.1387/ijdb.103222rn PG 7 WC Developmental Biology SC Developmental Biology GA 831RH UT WOS:000295748300014 PM 21858770 ER PT J AU Azar, AR Chopra, MP Cho, LY Coakley, E Rudolph, JL AF Azar, Armin R. Chopra, Mohit P. Cho, Lydia Y. Coakley, Eugenie Rudolph, James L. TI Remission in major depression: results from a geriatric primary care population SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depression; remission; primary care; aged ID LATE-LIFE DEPRESSION; NEUROPSYCHIATRIC INTERVIEW MINI; HEALTH-CARE; EXECUTIVE DYSFUNCTION; CARDIOVASCULAR HEALTH; TREATMENT OUTCOMES; RANDOMIZED-TRIAL; COMORBID ANXIETY; OLDER-ADULTS; PRISM-E AB Objectives: While a recent task force report recommended that remission from major depression be defined according to DSM criteria, most previous work has used depressive symptom rating scales. The current study sought to identify baseline factors associated with treatment outcome in major depression, diagnosed according to DSM-IV criteria. Methods: Data from the Primary Care Research in Substance Abuse and Mental Health for the Elderly (PRISM-E) study were utilized. This analysis focused on 792 geriatric primary care patients with major depression at baseline, which was randomized to services by a mental health professional in primary care or specialty settings. Major depression was diagnosed according to DSM-IV criteria based on a structured interview at baseline and 6 months. The primary outcome was the absence of any DSM-IV depressive disorder at six-month follow-up. Association with baseline demographic characteristics, comorbid anxiety disorder, 'at risk' drinking, number of co-occurring medical conditions, and depressive symptom severity was examined using multiple logistic regression modeling. Results: Remission occurred in 228 (29%) patients with completed follow-up assessments, while 564 (71%) did not remit. Factors which increased the odds of non-remission included comorbid anxiety (OR 1.60, 95% CI 1.11-2.31), female sex (OR 1.49, 95% CI 1.04-2.15), general medical comorbidity (OR 1.15, 95% CI 1.07-1.24), and increased baseline depressive symptom severity (OR 1.04, 95% CI 1.03-1.06). Conclusions: The findings underscore the importance of using DSM criteria to define remission from major depression, and suggest that concurrent measurement of depression severity, comorbid anxiety, and medical comorbidity are important in identifying patients requiring targeted interventions to optimize remission from major depression. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Azar, Armin R.; Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Azar, Armin R.; Chopra, Mohit P.; Cho, Lydia Y.; Rudolph, James L.] VA Boston Healthcare Syst, Boston, MA USA. [Azar, Armin R.; Chopra, Mohit P.; Cho, Lydia Y.; Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA. [Chopra, Mohit P.; Cho, Lydia Y.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Coakley, Eugenie] John Snow Inc, Boston, MA USA. RP Rudolph, JL (reprint author), Brigham & Womens Hosp, Div Aging, 75 Francis St, Boston, MA 02115 USA. EM jrudolph@partners.org RI Chopra, Mohit P/F-7250-2013 OI Chopra, Mohit P/0000-0002-9208-7224 FU Department of Psychiatry, Harvard Medical School; VA; NIH [5-R03-AG029861-02]; Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Mental Health Services (CMHS); Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Substance Abuse Treatment (CSAT); Substance Abuse and Mental Health Services Administration (SAMHSA), enter for Substance Abuse and Prevention (CSAP); Department of Veterans Affairs (VA); Health Resources and Services Administration (HRSA); Centers for Medicare and Medicaid Services (CMS) [UD1SM52229-04] FX Dr Azar was supported by the Kaplen Fellowship on Depression through the Department of Psychiatry, Harvard Medical School. Dr Rudolph is supported by a VA Rehabilitation Research and Development Career Development Award. Additional support was provided by NIH grant 5-R03-AG029861-02. This paper is the result of work supported with resources and the use of facilities at the VA Boston Healthcare System. The authors retained full independence in the conduct of this research.; PRISM-E is a collaborative research study funded by the Substance Abuse and Mental Health Services Administration (SAMHSA), including its three centers: Center for Mental Health Services (CMHS), Center for Substance Abuse Treatment (CSAT), and the Center for Substance Abuse and Prevention (CSAP). The Department of Veterans Affairs (VA), the Health Resources and Services Administration (HRSA), and the Centers for Medicare and Medicaid Services (CMS) provided additional support and funding (PI, PRISM-E Data Coordinating Center, Sue E. Levkoff, UD1SM52229-04). NR 30 TC 7 Z9 7 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JAN PY 2011 VL 26 IS 1 BP 48 EP 55 DI 10.1002/gps.2485 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 694PF UT WOS:000285309400007 PM 21157850 ER PT J AU Anderson, A Bramen, J Douglas, PK Lenartowicz, A Cho, A Culbertson, C Brody, AL Yuille, AL Cohen, MS AF Anderson, Ariana Bramen, Jennifer Douglas, Pamela K. Lenartowicz, Agatha Cho, Andrew Culbertson, Chris Brody, Arthur L. Yuille, Alan L. Cohen, Mark S. TI Large Sample Group Independent Component Analysis of Functional Magnetic Resonance Imaging Using Anatomical Atlas-Based Reduction and Bootstrapped Clustering SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY LA English DT Article DE fMRI; group ICA; bagging; clustering; bootstrap ID FMRI; DEPENDENCE AB Independent component analysis (ICA) is a popular method for the analysis of functional magnetic resonance imaging (fMRI) signals that is capable of revealing connected brain systems of functional significance. To be computationally tractable, estimating the independent components (ICs) inevitably requires one or more dimension reduction steps. Whereas most algorithms perform such reductions in the time domain, the input data are much more extensive in the spatial domain, and there is broad consensus that the brain obeys rules of localization of function into regions that are smaller in number than the number of voxels in a brain image. These functional units apparently reorganize dynamically into networks under different task conditions. Here we develop a new approach to ICA, producing group results by bagging and clustering over hundreds of pooled single-subject ICA results that have been projected to a lower-dimensional subspace. Averages of anatomically based regions are used to compress the single subject-ICA results prior to clustering and resampling via bagging. The computational advantages of this approach make it possible to perform group-level analyses on datasets consisting of hundreds of scan sessions by combining the results of within-subject analysis, while retaining the theoretical advantage of mimicking what is known of the functional organization of the brain. The result is a compact set of spatial activity patterns that are common and stable across scan sessions and across individuals. Such representations may be used in the context of statistical pattern recognition supporting real-time state classification. (C) 2011 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 21, 223-231, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ima.20286 C1 [Anderson, Ariana; Bramen, Jennifer; Douglas, Pamela K.; Lenartowicz, Agatha; Cho, Andrew; Culbertson, Chris; Brody, Arthur L.; Cohen, Mark S.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Brody, Arthur L.] Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Brody, Arthur L.] Greater Los Angeles VA Healthcare Syst, Dept Radiol, Los Angeles, CA USA. [Yuille, Alan L.] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA. [Yuille, Alan L.] Korea Univ, Dept Brain & Cognit Engn, Seoul 136713, South Korea. [Cohen, Mark S.] Univ Calif Los Angeles, Dept Biomed Engn Neurol Psychol Biomed Phys & Rad, Los Angeles, CA USA. RP Anderson, A (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. EM ariana82@ucla.edu RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU National Institute on Drug Abuse [DA026109, R01 DA20872]; Ministry of Education, Science and Technology [R31-2008-000-10008-0]; Veterans Affairs Type I Merit Review Award; Richard Metzner Chair in Clinical Neuropharmacology FX This work is supported by the National Institute on Drug Abuse under DA026109 to M. S. C and by WCU (World Class University) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (R31-2008-000-10008-0) to AY. The grant funding that supported the data collection was: the National Institute on Drug Abuse (A. L. B. [R01 DA20872]), a Veterans Affairs Type I Merit Review Award (A. L. B.), and an endowment from the Richard Metzner Chair in Clinical Neuropharmacology (A. L. B.). We thank Michael Durnhofer for maintaining the systems necessary for these data analyses. NR 32 TC 7 Z9 7 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0899-9457 J9 INT J IMAG SYST TECH JI Int. J. Imaging Syst. Technol. PY 2011 VL 21 IS 2 SI SI BP 223 EP 231 DI 10.1002/ima.20286 PG 9 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA 771KH UT WOS:000291155100013 PM 22049263 ER PT J AU Constantinou, C De Oliveira, CCF Mintzopoulos, D Busquets, S He, JX Kesarwan, M Mindrinos, M Rahme, LG Argiles, JM Tzika, AA AF Constantinou, Caterina Cristine Fontes De Oliveira, Cibely Mintzopoulos, Dionyssios Busquets, Silvia He, Jianxin Kesarwan, Meenu Mindrinos, Michael Rahme, Laurence G. Argiles, Josep M. Tzika, A. Aria TI Nuclear magnetic resonance in conjunction with functional genomics suggests mitochondrial dysfunction in a murine model of cancer cachexia SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE skeletal muscle; cancer cachexia; mitochondria; mitochondrial; PGC-1 beta; UCP3; FoXO3 alpha; microarrays; genomics ID LEWIS LUNG-CARCINOMA; UNCOUPLING PROTEIN-3 EXPRESSION; FOXO TRANSCRIPTION FACTORS; SKELETAL-MUSCLE ATROPHY; NECROSIS-FACTOR-ALPHA; OXIDATIVE STRESS; BURN-TRAUMA; GENE-EXPRESSION; P-31 NMR; IN-VIVO AB Cancer patients commonly suffer from cachexia, a syndrome in which tumors induce metabolic changes in the host that lead to massive loss in skeletal muscle mass. Using a preclinical mouse model of cancer cachexia, we tested the hypothesis that tumor inoculation causes a reduction in ATP synthesis and genome-wide aberrant expression in skeletal muscle. Mice implanted with Lewis lung carcinomas were examined by in vivo (31)P nuclear magnetic resonance (NMR). We examined ATP synthesis rate and the expression of genes that play key-regulatory roles in skeletal muscle metabolism. Our in vivo NMR results showed reduced ATP synthesis rate in tumor-bearing (TB) mice relative to control (C) mice, and were cross-validated with whole genome transcriptome data showing atypical expression levels of skeletal muscle regulatory genes such as peroxisomal proliferator activator receptor gamma coactivator 1 beta (PGC-1 beta), a major regulator of mitochondrial biogenesis and, mitochondrial uncoupling protein 3 (UCP3). Aberrant pattern of gene expression was also associated with genes involved in inflammation and immune response, protein and lipid catabolism, mitochondrial biogenesis and uncoupling, and inadequate oxidative stress defenses, and these effects led to cachexia. Our findings suggest that reduced ATP synthesis is linked to mitochondrial dysfunction, ultimately leading to skeletal muscle wasting and thus advance our understanding of skeletal muscle dysfunction suffered by cancer patients. This study represents a new line of research that can support the development of novel therapeutics in the molecular medicine of skeletal muscle wasting. Such therapeutics would have wide-spread applications not only for cancer patients, but also for many individuals suffering from other chronic or endstage diseases that exhibit muscle wasting, a condition for which only marginally effective treatments are currently available. C1 [Tzika, A. Aria] Harvard Univ, Sch Med, NMR Surg Lab, Dept Surg,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Constantinou, Caterina; Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Sch Med, NMR Surg Lab, Shriners Hosp, Boston, MA 02114 USA. [Constantinou, Caterina; He, Jianxin; Kesarwan, Meenu; Rahme, Laurence G.] Harvard Univ, Sch Med, Mol Surg Lab, Shriners Hosp, Boston, MA 02114 USA. [Constantinou, Caterina; He, Jianxin; Kesarwan, Meenu; Rahme, Laurence G.] Harvard Univ, Sch Med, Mol Surg Lab, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cristine Fontes De Oliveira, Cibely; Busquets, Silvia; Argiles, Josep M.] Univ Barcelona, Fac Biol, Canc Res Grp, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain. [Mintzopoulos, Dionyssios; Tzika, A. Aria] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Mindrinos, Michael] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, NMR Surg Lab, Dept Surg,Massachusetts Gen Hosp, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM argiles@porthos.bio.ub.es; atzika@hms.harvard.edu OI Busquets, Silvia/0000-0002-9319-3555; Constantinou, Caterina/0000-0003-3589-0739; Fontes-Oliveira, Cibely/0000-0003-1112-6015 FU National Institutes of Health (NIH) Center [P50GM021700]; Shriner's Hospital for Children [8893, 8892]; Programme Alban scholarship [E05D059293BR] FX This study was supported in part by a National Institutes of Health (NIH) Center Grant (P50GM021700) to Ronald G. Tompkins (A. Aria Tzika, Director of the NMR core), and Shriner's Hospital for Children research grants (no. 8893) to A. Aria Tzika, and (no. 8892) to Laurence G. Rahme. Cibely C. Fontes de Oliveira was supported by a Programme Alban scholarship (E05D059293BR). We also thank Ann Power Smith Ph.D. of Write Science Right for editorial assistance. NR 74 TC 23 Z9 24 U1 0 U2 4 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 JAN PY 2011 VL 27 IS 1 BP 15 EP 24 DI 10.3892/ijmm.2010.557 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 707NK UT WOS:000286293100002 PM 21069263 ER EF