FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Singh, A Corcoran, P Thomas, M Lewis, B Ayares, D Reimann, K Horvath, K Mohiuddin, M AF Singh, A. Corcoran, P. Thomas, M. Lewis, B. Ayares, D. Reimann, K. Horvath, K. Mohiuddin, M. TI Costimulation Blockade With Anti CD40 Antibody Maintains CD4+and Treg Cell Numbers in Pig To Baboon Cardiac Transplantation Model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Singh, A.; Corcoran, P.; Horvath, K.; Mohiuddin, M.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. [Thomas, M.; Lewis, B.] NIH, Bethesda, MD 20892 USA. [Ayares, D.] Revivicor Inc, Blacksburgh, VA USA. [Reimann, K.] Mass Biol, Bethesda, MD USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA 1424 BP 30 EP 30 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033300097 ER PT J AU Wood, S Feng, J He, S Marquez, V Bishop, D Zhang, Y AF Wood, S. Feng, J. He, S. Marquez, V. Bishop, D. Zhang, Y. TI Inhibition of Histone Methylation Induces Long-Term Survival of Vascularized Cardiac Allografts and Preserves the Third-Party T Cell Immunity. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Wood, S.; Feng, J.; Bishop, D.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [He, S.; Zhang, Y.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Marquez, V.] NIH, Biol Chem Lab, Ctr Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA 2109 BP 35 EP 35 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033300114 ER PT J AU Randhawa, P Pastrana, D Zeng, G Berger, M Hariharan, S Ron, S Buck, C AF Randhawa, P. Pastrana, D. Zeng, G. Berger, M. Hariharan, S. Ron, S. Buck, C. TI Neutralizing Antibodies For Polyomavirus BK (BKV) in Intravenous Immunoglobulins: Pre-Clinical Studies. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Randhawa, P.; Zeng, G.; Hariharan, S.; Ron, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Pastrana, D.; Buck, C.] NCI, Lab Cellular Oncol, Bethesda, MD 20892 USA. [Berger, M.] CSL Behring, Immunol R&D, King Of Prussia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA 727 BP 85 EP 85 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033300263 ER PT J AU Nickerson, P Wiebe, C Formica, R Tinckam, K Poggio, E Bunnapradist, S Gibson, I Rush, D Samaniego, M Gaber, O Ilke, D Bridges, N Fairchild, R Hricik, D Heeger, P AF Nickerson, P. Wiebe, C. Formica, R. Tinckam, K. Poggio, E. Bunnapradist, S. Gibson, I. Rush, D. Samaniego, M. Gaber, O. Ilke, D. Bridges, N. Fairchild, R. Hricik, D. Heeger, P. TI Epitope Mismatch Predicts De Novo DSA After CNI Withdrawal in Low-Risk Kidney Transplant Recipients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Nickerson, P.; Wiebe, C.; Gibson, I.; Rush, D.] UM, Winnipeg, MB, Canada. [Formica, R.] Yale, New Haven, CT USA. [Tinckam, K.] UHN, Toronto, ON, Canada. [Poggio, E.; Fairchild, R.] Cleveland Clin, Cleveland, OH 44106 USA. [Bunnapradist, S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Samaniego, M.] UoM, Ann Arbor, MI USA. [Gaber, O.] MTC, Houston, TX USA. [Ilke, D.] Rho, Chapel Hill, NC USA. [Bridges, N.] NIH, Bethesda, MD 20892 USA. [Hricik, D.] UHCMC, Cleveland, OH USA. [Heeger, P.] MSSM, New York, NY USA. NR 0 TC 0 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA 2888 BP 137 EP 137 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033300423 ER PT J AU Olthoff, K Chang, B Christie, J Levitsky, J Emond, J Bridges, N Sledge, T Shaked, A AF Olthoff, K. Chang, B. Christie, J. Levitsky, J. Emond, J. Bridges, N. Sledge, T. Shaked, A. TI Immediate Post-Reperfusion PBL Activation Associated With Liver Early Allograft Dysfunction (EAD). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Olthoff, K.; Chang, B.; Christie, J.; Shaked, A.] Univ Penn, Philadelphia, PA 19104 USA. [Levitsky, J.] Northwestern Univ, Chicago, IL 60611 USA. [Emond, J.] Columbia Univ, New York, NY USA. [Bridges, N.; Sledge, T.] NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA 1332 BP 224 EP 224 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301012 ER PT J AU Formica, R Nickerson, P Poggio, E Tinckam, K Rush, D Gibson, I Fairchild, R Bridges, N Ikle, D Samaniego, M Graber, O Bunnapradist, S Armstrong, B Heeger, P Hricik, D AF Formica, R. Nickerson, P. Poggio, E. Tinckam, K. Rush, D. Gibson, I. Fairchild, R. Bridges, N. Ikle, D. Samaniego, M. Graber, O. Bunnapradist, S. Armstrong, B. Heeger, P. Hricik, D. TI Immune Monitoring and Tacrolimus (Tac) Withdrawal in Low Risk Recipients of Kidney Transplants - Results of CTOT09. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Formica, R.] Yale Univ, New Haven, CT USA. [Nickerson, P.; Rush, D.; Gibson, I.] UM, Winnipeg, MB, Canada. [Poggio, E.; Fairchild, R.] Cleveland Clin, Cleveland, OH USA. [Tinckam, K.] UHN, Toronto, ON, Canada. [Bridges, N.] NIH, Bethesda, MD 20892 USA. [Ikle, D.; Armstrong, B.] Rho, Chapel Hill, NC USA. [Samaniego, M.] UoM, Ann Arbor, MI USA. [Graber, O.] MTC, Houston, TX USA. [Bunnapradist, S.] Univ Calif Los Angeles, Los Angeles, CA USA. MSSM, New York, NY USA. [Heeger, P.] UHCMC, Cleveland, OH USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA 1436 BP 225 EP 225 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301018 ER PT J AU Arron, S Yankis, E Raymond, A McCulloch, C Engels, E AF Arron, S. Yankis, E. Raymond, A. McCulloch, C. Engels, E. TI Increased Mortality in Transplant Recipients With a History of Pretransplant Melanoma SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Arron, S.; Raymond, A.; McCulloch, C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yankis, E.; Engels, E.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA A529 BP 240 EP 240 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301067 ER PT J AU Kalil, R Lynch, C Engels, E AF Kalil, R. Lynch, C. Engels, E. TI Risk of Cancer in Kidney Retransplants Compared To Primary Kidney Transplants in The Transplant Cancer Match Study SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Kalil, R.; Lynch, C.] Univ Iowa, Iowa City, IA USA. [Engels, E.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA A528 BP 240 EP 240 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301066 ER PT J AU Yanik, E Snyder, J Clarke, C Engels, E AF Yanik, E. Snyder, J. Clarke, C. Engels, E. TI Cancer Risk Patterns Among End Stage Renal Disease Patients During Intervals of Kidney Transplant Function and Non-Function SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Yanik, E.] NCI, Rockville, MD USA. [Snyder, J.] Univ Minnesota, Minneapolis, MN USA. [Clarke, C.] Canc Prevent Inst Calif, Fremont, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA A532 BP 241 EP 242 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301070 ER PT J AU Yanik, E Gustafson, S Kasiske, B Israni, A Snyder, J Engels, E Segev, D AF Yanik, E. Gustafson, S. Kasiske, B. Israni, A. Snyder, J. Engels, E. Segev, D. TI Sirolimus Use and Cancer Incidence Among U. S. Kidney Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Yanik, E.; Engels, E.] NCI, Rockville, MD USA. [Gustafson, S.; Kasiske, B.; Israni, A.; Snyder, J.] Sci Registry Transplant Recipients, Minneapolis, MN USA. [Segev, D.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA A534 BP 242 EP 242 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301072 ER PT J AU Putheti, P Ding, R Naqvi, R Medeiros, M Sharma, V Kuchibhotla, S LeBeau, P Ikle, D Muthukumar, T Dadhania, D Myers, K Ingelfinger, J McDonald, R Liu, J Spaneas, L Williams, N Bridges, N Harmon, W Suthanthiran, M Strom, T AF Putheti, P. Ding, R. Naqvi, R. Medeiros, M. Sharma, V. Kuchibhotla, S. LeBeau, P. Ikle, D. Muthukumar, T. Dadhania, D. Myers, K. Ingelfinger, J. McDonald, R. Liu, J. Spaneas, L. Williams, N. Bridges, N. Harmon, W. Suthanthiran, M. Strom, T. TI Gene-Expression Profiles of Peripheral Blood Cells and of Allograft Biopsies Are Associated With Acute Rejection in Pediatric Renal Allograft Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Putheti, P.; Kuchibhotla, S.; Ingelfinger, J.; Spaneas, L.; Harmon, W.; Strom, T.] HMS, Boston, MA USA. [Ding, R.; Naqvi, R.; Medeiros, M.; Sharma, V.; Muthukumar, T.; Dadhania, D.; Suthanthiran, M.] WCMC, New York, NY USA. [LeBeau, P.; Ikle, D.] Rho, Chapel Hill, NC USA. [Liu, J.] PPD, Morrisville, NC USA. [Williams, N.; Bridges, N.] NIAID, Bethesda, MD 20892 USA. [Myers, K.] CHOP UPenn, Philadelphia, PA USA. [McDonald, R.] Seattle Childrens UW, Seattle, WA USA. RI Medeiros, Mara/B-9230-2015 OI Medeiros, Mara/0000-0002-6848-8933 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA C1528 BP 324 EP 324 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301383 ER PT J AU Li, Z Xu, X Feng, X Farber, J Young, N Murphy, P AF Li, Z. Xu, X. Feng, X. Farber, J. Young, N. Murphy, P. TI Clodronate-Induced Macrophage Depletion of Mice Receiving Bone Marrow Allotransplantation Enhances Hematopoietic Chimerism and Donor-Specific Skin Allograft Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Li, Z.; Xu, X.; Farber, J.; Murphy, P.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Feng, X.; Young, N.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA D2770 BP 395 EP 395 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301647 ER PT J AU Mohiuddin, M Singh, A Corcoran, P Hoyt, R Thomas, M Eckhaus, M Lewis, B Clark, T Phelps, C Ayares, D Reimann, K Horvath, K AF Mohiuddin, M. Singh, A. Corcoran, P. Hoyt, R. Thomas, M. Eckhaus, M. Lewis, B. Clark, T. Phelps, C. Ayares, D. Reimann, K. Horvath, K. TI Long Term GalKO.hCD46. hTBM Pig Cardiac Xenograft Survival in Baboon May Be Dependent On Dose and Duration of Anti CD40 (2C10R4) Antibody. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Mohiuddin, M.; Singh, A.; Corcoran, P.; Horvath, K.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. [Hoyt, R.; Thomas, M.; Eckhaus, M.; Lewis, B.; Clark, T.] NIH, Bethesda, MD 20892 USA. [Phelps, C.; Ayares, D.] Revivicor Inc, Blacksburgh, VA USA. [Reimann, K.] Mass Biol, Boston, MA USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA D2844 BP 415 EP 415 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301721 ER PT J AU Mohiuddin, M Singh, A Corcoran, P Hoyt, R Thomas, M Lewis, B Clark, T Klymiuk, N Wolf, E Reimann, K Ayares, D Horvath, K AF Mohiuddin, M. Singh, A. Corcoran, P. Hoyt, R. Thomas, M. Lewis, B. Clark, T. Klymiuk, N. Wolf, E. Reimann, K. Ayares, D. Horvath, K. TI Normal Histology and Contractility of a Cardiac Xenograft For 450+Days: A Case Report. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Mohiuddin, M.; Singh, A.; Corcoran, P.; Horvath, K.] NHLBI, Cardiathorac Surg Res Program, NIH, Bethesda, MD 20892 USA. [Hoyt, R.; Thomas, M.; Lewis, B.; Clark, T.] NIH, Bethesda, MD 20892 USA. [Ayares, D.] Revivicor Inc, Blacksburg, VA USA. [Reimann, K.] Mass Biol, Boston, MA USA. [Klymiuk, N.; Wolf, E.] LMU, Munich, Germany. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA D2848 BP 416 EP 416 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033301725 ER PT J AU Daly, K Starling, R Armstrong, B Ikle, D Bridges, N Chandraker, A Sayegh, M Stehlik, J Heeger, P Briscoe, D AF Daly, K. Starling, R. Armstrong, B. Ikle, D. Bridges, N. Chandraker, A. Sayegh, M. Stehlik, J. Heeger, P. Briscoe, D. TI Changes in Plasma Levels of VEGF-C and Endothelin-1 During the First Post-Transplant Year Are Predictive of Cardiac Allograft Vasculopathy: Results From the CTOT-05 Study. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Daly, K.; Briscoe, D.] Boston Childrens Hosp, Boston, MA USA. [Starling, R.] Cleveland Clin, Cleveland, OH 44106 USA. [Armstrong, B.; Ikle, D.] Rho, Chapel Hill, NC USA. [Bridges, N.] NIH, Bethesda, MD 20892 USA. [Chandraker, A.; Sayegh, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Stehlik, J.] Univ Utah, Salt Lake City, UT USA. [Heeger, P.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA A23 BP 878 EP 878 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033304023 ER PT J AU Hricik, D Augustine, J Poggio, E Fairchild, R Nickerson, P Rush, D Gibson, I Formica, R Goebel, J Newell, K Spain, K Ikle, D Bridges, N Heeger, P AF Hricik, D. Augustine, J. Poggio, E. Fairchild, R. Nickerson, P. Rush, D. Gibson, I. Formica, R. Goebel, J. Newell, K. Spain, K. Ikle, D. Bridges, N. Heeger, P. TI Rabbit ATG Induction Overcomes the Negative Influence of Pretransplant Memory T Cells On Posttransplant GFR: Results From the CTOT01 Kidney Transplant Trial SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Hricik, D.; Augustine, J.] UH Case Med Ctr, Cleveland, OH USA. [Poggio, E.; Fairchild, R.] Cleveland Clin, Cleveland, OH 44106 USA. [Nickerson, P.; Rush, D.; Gibson, I.] Univ Manitoba, Winnipeg, MB, Canada. [Formica, R.] Yale Univ, New Haven, CT USA. [Goebel, J.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Newell, K.] Emory Univ, Atlanta, GA 30322 USA. [Spain, K.; Ikle, D.] Rho, Chapel Hill, NC USA. [Bridges, N.] NIAID, NIH, Bethesda, MD 20892 USA. [Heeger, P.] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA B775 BP 892 EP 893 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033304077 ER PT J AU Chang, B Christie, J Olthoff, K Emond, J Levitsky, J Bridges, N Sledge, T Ikle, D Shaked, A AF Chang, B. Christie, J. Olthoff, K. Emond, J. Levitsky, J. Bridges, N. Sledge, T. Ikle, D. Shaked, A. TI Dynamic Inflammatory Gene Expression Profiles Among Patients With and Without Acute Cellular Rejection (ACR) During the First Post- Transplant Year. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Chang, B.; Christie, J.; Olthoff, K.; Shaked, A.] Univ Penn, Philadelphia, PA 19104 USA. [Emond, J.] Columbia Univ, New York, NY USA. [Levitsky, J.] Northwestern Univ, Chicago, IL 60611 USA. [Bridges, N.; Sledge, T.] NIDDK, Bethesda, MD 20892 USA. [Ikle, D.] RhoFed, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA D2345 BP 901 EP 902 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033304110 ER PT J AU Shaked, O Chang, B Tobias, J Demetris, A Suthanthiran, M Feng, S Punch, J Reyes, J Levitsky, J Klintmalm, G Zimmerman, M DesMarais, M Kopeskie, H Priore, A Morrison, Y Bridges, N Sayre, P Shaked, A AF Shaked, O. Chang, B. Tobias, J. Demetris, A. Suthanthiran, M. Feng, S. Punch, J. Reyes, J. Levitsky, J. Klintmalm, G. Zimmerman, M. DesMarais, M. Kopeskie, H. Priore, A. Morrison, Y. Bridges, N. Sayre, P. Shaked, A. TI Whole Blood mRNA to Detect Hepatic Inflammation and Fibrosis in Post-Liver Transplant Patients With HCV. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT World Transplant Congress CY JUL 26-31, 2014 CL San Francisco, CA C1 [Shaked, O.; Chang, B.; Tobias, J.; Shaked, A.] UPenn, Philadelphia, PA USA. [Demetris, A.] UPMC, Pittsburgh, PA USA. [Suthanthiran, M.] Cornell, New York, NY USA. [Feng, S.; DesMarais, M.; Sayre, P.] UCSF, San Francisco, CA USA. [Punch, J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Reyes, J.] Univ Wisconsin, Madison, WI 53706 USA. [Levitsky, J.] Northwestern Univ, Chicago, IL 60611 USA. [Klintmalm, G.] Baylor Univ, Dallas, TX USA. [Zimmerman, M.] Univ Colorado, Denver, CO 80202 USA. [Priore, A.; Morrison, Y.; Bridges, N.] NIAID, Bethesda, MD 20892 USA. [Kopeskie, H.] RhoFed, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 SU 3 MA D2356 BP 905 EP 905 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ9LU UT WOS:000338033304121 ER PT J AU Bradley, MC Motterlini, N Padmanabhan, S Cahir, C Williams, T Fahey, T Hughes, CM AF Bradley, Marie C. Motterlini, Nicola Padmanabhan, Shivani Cahir, Caitriona Williams, Tim Fahey, Tom Hughes, Carmel M. TI Potentially inappropriate prescribing among older people in the United Kingdom SO BMC GERIATRICS LA English DT Article DE Potentially inappropriate prescribing; Older people; Screening tool of older persons potentially inappropriate Prescriptions (STOPP); CPRD ID ADVERSE DRUG EVENTS; PROTON PUMP INHIBITORS; STOPP SCREENING TOOL; MEDICATION USE; BEERS CRITERIA; PRIMARY-CARE; PERSONS PRESCRIPTIONS; PRIMARY PREVENTION; CONSENSUS PANEL; ELDERLY-PEOPLE AB Background: Potentially inappropriate prescribing (PIP) in older people is associated with increases in morbidity, hospitalisation and mortality. The objective of this study was to estimate the prevalence of and factors associated with PIP, among those aged >= 70 years, in the United Kingdom, using a comprehensive set of prescribing indicators and comparing these to estimates obtained from a truncated set of the same indicators. Methods: A retrospective cross-sectional study was carried out in the UK Clinical Practice Research Datalink (CPRD), in 2007. Participants included those aged >= 70 years, in CPRD. Fifty-two PIP indicators from the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria were applied to data on prescribed drugs and clinical diagnoses. Overall prevalence of PIP and prevalence according to individual STOPP criteria were estimated. The relationship between PIP and polypharmacy (>= 4 medications), comorbidity, age, and gender was examined. A truncated, subset of 28 STOPP criteria that were used in two previous studies, were further applied to the data to facilitate comparison. Results: Using 52 indicators, the overall prevalence of PIP in the study population (n = 1,019,491) was 29%. The most common examples of PIP were therapeutic duplication (11.9%), followed by use of aspirin with no indication (11.3%) and inappropriate use of proton pump inhibitors (PPIs) (3.7%). PIP was strongly associated with polypharmacy (Odds Ratio 18.2, 95% Confidence Intervals, 18.0-18.4, P < 0.05). PIP was more common in those aged 70-74 years vs. 85 years or more and in males. Application of the smaller subset of the STOPP criteria resulted in a lower PIP prevalence at 14.9% (95% CIs 14.8-14.9%) (n = 151,598). The most common PIP issues identified with this subset were use of PPIs at maximum dose for > 8 weeks, NSAIDs for > 3 months, and use of long-term neuroleptics. Conclusions: PIP was prevalent in the UK and increased with polypharmacy. Application of the comprehensive set of STOPP criteria allowed more accurate estimation of PIP compared to the subset of criteria used in previous studies. These findings may provide a focus for targeted interventions to reduce PIP. C1 [Hughes, Carmel M.] NCI, Clin & Translat Epidemiol Branch, Rockville, MD 20850 USA. [Motterlini, Nicola; Fahey, Tom] Royal Coll Surgeons Ireland, Dept Gen Practice, HRB Ctr Primary Care Res, Dublin 2, Ireland. [Cahir, Caitriona] Univ Dublin Trinity Coll, Dept Pharmacol & Therapeut, Dublin 2, Ireland. [Padmanabhan, Shivani; Williams, Tim] Med & Healthcare Prod Regulatory Agcy, London, England. [Bradley, Marie C.] NCI, Clin & Translat Epidemiol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA. RP Bradley, MC (reprint author), NCI, Clin & Translat Epidemiol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,4E320, Rockville, MD 20850 USA. EM marie.bradley@nih.gov RI Fahey, Tom/C-9367-2012; CPRD, CPRD/B-9594-2017; OI Fahey, Tom/0000-0002-5896-5783; Cahir, Caitriona/0000-0002-7137-5737 FU Health Research Board, Ireland [HRC-2007-1] FX The Health Research Board, Ireland, provided financial support for this study: grant reference HRC-2007-1. NR 46 TC 23 Z9 24 U1 2 U2 16 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. PD JUN 1 PY 2014 VL 14 AR 72 DI 10.1186/1471-2318-14-72 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AK9KT UT WOS:000338746700001 PM 24919523 ER PT J AU Ma, XF Adelstein, RS AF Ma, Xuefei Adelstein, Robert S. TI A Point Mutation in Myh10 Causes Major Defects in Heart Development and Body Wall Closure SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE apoptosis; cell adhesion; double outlet right ventricle; ectopia cordis; hernia, diaphragmatic; nonmuscle myosin type IIA ID NONMUSCLE MYOSIN-II; PROXIMAL OUTFLOW TRACT; HEAVY-CHAIN GENE; CLEFT-LIP; CELL-ADHESION; MYH9-RELATED DISEASE; DOWN-REGULATION; LIGHT-CHAIN; ROCK-I; PALATE AB Background-The 3 isoforms of nonmuscle myosin (NM) II (NMII-A, NMII-B, and NMII-C) play various roles during mouse embryonic development. Previous work, using knockout and hypomorphic mice, showed that Myh10 encoding myosin heavy chain II-B is critical for cardiac and brain development. Ablating or decreasing NMII-B by 80% results in cardiac (ventricular septal defect, double outlet of the right ventricle) and brain defects but not midline fusion defects. Neither NMII-A nor II-C seems to play roles in early myocardial development. Methods and Results-We had previously generated point mutant knock-in mice and now report novel findings as a result of expressing motor-deficient NMII-B at wild-type levels. Homozygous mice die at embryonic day 14.5 in cardiac failure, exhibiting abnormalities not seen in NMII-B null and hypomorphic mice: a failure in midline fusion resulting in a cleft palate, ectopia cordis, and a large omphalocele. Fusion of the sternum and endocardial cushions is impaired in the mutant mice associated with a failure in apoptosis of the mesenchymal cells. Failure to disassemble myocyte cell-cell adhesions during cardiac outflow tract development contributes to impaired outflow tract myocardialization and displacement of the aorta to the right ventricle. Conclusions-Expression of motor-impaired NMII-B disrupts normal ventral body wall closure because of a dominant-negative effect. This is not because of the loss of NMII-B function but rather a gain-of-function resulting from prolonged cross-linking of NMII-B to actin filaments, thereby interfering with the dynamics of actomyosin cytoskeletal structure. Furthermore, impaired NMII-B motor activity inhibits outflow tract myocardialization, leading to mislocalization of the aorta. C1 [Ma, Xuefei; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Ma, XF (reprint author), NIH, Bldg 10,Room 6C-104,10 Ctr Dr,MSC 1583, Bethesda, MD 20892 USA. EM MaX@nhlbi.nih.gov OI Adelstein, Robert/0000-0002-8683-2144 FU Division of Intramural Research, National Heart, Lung, and Blood Institute FX This research was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute. NR 40 TC 5 Z9 5 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2014 VL 7 IS 3 BP 257 EP 265 DI 10.1161/CIRCGENETICS.113.000455 PG 9 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AK1VY UT WOS:000338207300006 PM 24825879 ER PT J AU Saxena, R Bjonnes, A Prescott, J Dib, P Natt, P Lane, J Lerner, M Cooper, JA Ye, YQ Li, KW Maubaret, CG Codd, V Brackett, D Mirabello, L Kraft, P Dinney, CP Stowell, D Peyton, M Ralhan, S Wander, GS Mehra, NK Salpea, KD Gu, J Wu, XF Mangino, M Hunter, DJ De Vivo, I Humphries, SE Samani, NJ Spector, TD Savage, SA Sanghera, DK AF Saxena, Richa Bjonnes, Andrew Prescott, Jennifer Dib, Patrick Natt, Praveen Lane, Jacqueline Lerner, Megan Cooper, Jackie A. Ye, Yuanqing Li, Ka Wah Maubaret, Cecilia G. Codd, Veryan Brackett, Daniel Mirabello, Lisa Kraft, Peter Dinney, Colin P. Stowell, Donald Peyton, Marvin Ralhan, Sarju Wander, Gurpreet S. Mehra, Narinder K. Salpea, Klelia D. Gu, Jian Wu, Xifeng Mangino, Massimo Hunter, David J. De Vivo, Immaculata Humphries, Steve E. Samani, Nilesh J. Spector, Tim D. Savage, Sharon A. Sanghera, Dharambir K. TI Genome-Wide Association Study Identifies Variants in Casein Kinase II (CSNK2A2) to be Associated With Leukocyte Telomere Length in a Punjabi Sikh Diabetic Cohort SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE cardiovascular diseases; diabetes mellitus, type 2; genome-wide association study; telomere length ID CORONARY-HEART-DISEASE; ASIAN INDIAN SIKHS; WHITE BLOOD-CELLS; GENETIC-VARIATION; GENOTYPE IMPUTATION; ATHEROSCLEROSIS; LOCUS; RISK; SHORTER; PROTEIN AB Background-Telomere length is a heritable trait, and short telomere length has been associated with multiple chronic diseases. We investigated the relationship of relative leukocyte telomere length with cardiometabolic risk and performed the first genome-wide association study and meta-analysis to identify variants influencing relative telomere length in a population of Sikhs from South Asia. Methods and Results-Our results revealed a significant independent association of shorter relative telomere length with type 2 diabetes mellitus and heart disease. Our discovery genome-wide association study (n=1616) was followed by stage 1 replication of 25 top signals (P<10(-6)) in an additional Sikhs (n=2397). On combined discovery and stage 1 metaanalysis (n=4013), we identified a novel relative telomere length locus at chromosome 16q21 represented by an intronic variant (rs74019828) in the CSNK2A2 gene (beta=-0.38; P=4.5x10(-8)). We further tested 3 top variants by genotyping in UK cardiovascular disease (UKCVD) (whites n=2952) for stage 2. Next, we performed in silico replication of 139 top signals (P<10(-5)) in UK Twin, Nurses Heart Study, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and MD Anderson Cancer Controls (n=10033) and joint meta-analysis (n=16998). The observed signal in CSNK2A2 was confined to South Asians and could not be replicated in whites because of significant difference in allele frequencies (P<0.001). CSNK2A2 phosphorylates telomeric repeat binding factor 1 and plays an important role for regulation of telomere length homoeostasis. Conclusions-By identification of a novel signal in telomere pathway genes, our study provides new molecular insight into the underlying mechanism that may regulate telomere length and its association with human aging and cardiometabolic pathophysiology. C1 [Saxena, Richa; Bjonnes, Andrew; Lane, Jacqueline] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Prescott, Jennifer; Hunter, David J.; De Vivo, Immaculata] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA. [Prescott, Jennifer; Hunter, David J.; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA USA. [Saxena, Richa; Bjonnes, Andrew; Lane, Jacqueline; Hunter, David J.] Massachusetts Inst Technol & Harvard, Broad Ins, Cambridge, MA USA. [Dib, Patrick; Natt, Praveen; Sanghera, Dharambir K.] Univ Oklahoma, Dept Pediat, Coll Med, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Lerner, Megan; Brackett, Daniel; Stowell, Donald; Peyton, Marvin] Univ Oklahoma, Dept Surg, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Prescott, Jennifer; Kraft, Peter; Hunter, David J.; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Cooper, Jackie A.; Li, Ka Wah; Maubaret, Cecilia G.; Salpea, Klelia D.; Humphries, Steve E.] UCL, BHF Labs, Inst Cardiovasc Sci, London, England. [Ye, Yuanqing; Gu, Jian; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Codd, Veryan; Mangino, Massimo; Samani, Nilesh J.; Spector, Tim D.] Glenfield Hosp, Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Mirabello, Lisa; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Dinney, Colin P.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Ralhan, Sarju; Wander, Gurpreet S.] Hero DMC Heart Inst, Ludhiana, Punjab, India. [Mehra, Narinder K.] All India Inst Med Sci & Res, New Delhi, India. RP Sanghera, DK (reprint author), Univ Oklahoma, Dept Pediat, Coll Med, Hlth Sci Ctr, 940 Stanton L Young Blvd,Rm 317 BMSB, Oklahoma City, OK 73104 USA. EM Dharambir-sanghera@ouhsc.edu RI Savage, Sharon/B-9747-2015; mangino, massimo/F-5134-2011; OI Savage, Sharon/0000-0001-6006-0740; mangino, massimo/0000-0002-2167-7470; Humphries, Stephen E/0000-0002-8221-6547 FU National Institutes of Health - National Institute of Diabetes and Digestive and Kidney Diseases [R01DK082766]; National Genome Research Institute [NOT-HG-11-009]; Vice President for Research Bridge grant from University of Oklahoma Health Sciences Center, Oklahoma City, OK FX This work was partly supported by National Institutes of Health grants-R01DK082766 funded by the National Institute of Diabetes and Digestive and Kidney Diseases and NOT-HG-11-009 funded by National Genome Research Institute and Vice President for Research Bridge grant from University of Oklahoma Health Sciences Center, Oklahoma City, OK. The genotyping and analysis for UKCVD was supported by the British Heart Foundation (PG08/008). Study-specific funding sources for the replication studies are provided in the Material in the Data Supplement. NR 53 TC 7 Z9 7 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2014 VL 7 IS 3 BP 287 EP 295 DI 10.1161/CIRCGENETICS.113.000412 PG 9 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AK1VY UT WOS:000338207300009 PM 24795349 ER PT J AU Guan, WH Steffen, BT Lemaitre, RN Wu, JHY Tanaka, T Manichaikul, A Foy, M Rich, SS Wang, L Nettleton, JA Tang, WH Gu, X Bandinelli, S King, IB McKnight, B Psaty, BM Siscovick, D Djousse, L Chen, YDI Ferrucci, L Fornage, M Mozafarrian, D Tsai, MY Steffen, LM AF Guan, Weihua Steffen, Brian T. Lemaitre, Rozenn N. Wu, Jason H. Y. Tanaka, Toshiko Manichaikul, Ani Foy, Millennia Rich, Stephen S. Wang, Lu Nettleton, Jennifer A. Tang, Weihong Gu, Xiangjun Bandinelli, Stafania King, Irena B. McKnight, Barbara Psaty, Bruce M. Siscovick, David Djousse, Luc Chen, Yii-Der Ida Ferrucci, Luigi Fornage, Myriam Mozafarrian, Dariush Tsai, Michael Y. Steffen, Lyn M. TI Genome-Wide Association Study of Plasma N6 Polyunsaturated Fatty Acids Within the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE epidemiology; genome-wide association study; N6 fatty acids; polyunsaturated fatty acids ID ACUTE MYOCARDIAL-INFARCTION; FADS GENETIC-VARIANTS; ARACHIDONIC-ACID; ADIPOSE-TISSUE; DISEASE; POPULATION; ATHEROSCLEROSIS; DIETARY; DESIGN; GENOTYPES AB Background-Omega6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase (FADS) genes, determine the composition of n6 PUFAs. Methods and Results-To elucidate undiscovered biological pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with 6 plasma n6 PUFAs in 8631 white adults (55% women) across 5 prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-GLA, arachidonic acid, and adrenic acid were expressed as percentage of total fatty acids. We performed linear regression with robust SEs to test for single-nucleotide polymorphism-fatty acid associations, with pooling using inverse-variance-weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118; P=8.1x10(-9); near NRBF2), on chromosome 16 with LA, GLA, dihomo-GLA, and arachidonic acid (rs16966952; P=1.2x10(-15), 5.0x10(-11), 7.6x10(-65), and 2.4x10(-10), respectively; NTAN1), and on chromosome 6 with adrenic acid after adjustment for arachidonic acid (rs3134950; P=2.1x10(-10); AGPAT1). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and arachidonic acid, and further observed novel genome-wide significant association of this cluster with GLA, dihomo-GLA, and adrenic acid (P=2.3x10(-72), 2.6x10(-151), and 6.3x10(-140), respectively). Conclusions-Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition. C1 [Guan, Weihua] Univ Minnesota, Div Biostat, Sch Publ Hlth, Minneapolis, MN 55454 USA. [Steffen, Brian T.; Tsai, Michael Y.] Univ Minnesota, Sch Publ Med, Minneapolis, MN 55454 USA. [Tang, Weihong; Steffen, Lyn M.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA. [Lemaitre, Rozenn N.; McKnight, Barbara; Psaty, Bruce M.; Siscovick, David] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Lemaitre, Rozenn N.; McKnight, Barbara; Psaty, Bruce M.; Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.; Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.; Siscovick, David] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Wu, Jason H. Y.; Wang, Lu; Mozafarrian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA. [Mozafarrian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wu, Jason H. Y.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Manichaikul, Ani; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Manichaikul, Ani] Univ Virginia, Div Biostat & Epidemiol, Charlottesville, VA USA. [Foy, Millennia; Gu, Xiangjun; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA. [Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA. [Bandinelli, Stafania] ASF, Geriatr Rehabil Unit, Florence, Italy. [King, Irena B.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Djousse, Luc] Harvard Univ, Sch Med, Div Aging, Brigham & Womens Hosp,Dept Med, Cambridge, MA 02138 USA. [Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA. [Chen, Yii-Der Ida] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA. [Mozafarrian, Dariush] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Sch Med, Boston, MA 02115 USA. RP Steffen, LM (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, 1300 South Second St,Suite 300, Minneapolis, MN 55454 USA. EM steffen@umn.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute (NHLBI) [HL105756]; NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C]; National Human Genome Research Institute (NHGRI) [U01HG004402]; National Institutes of Health (NIH) [HSN268200625226C]; NIH Roadmap for Medical Research [UL1RR025005]; National Institute of Neurological Disorders and Stroke; National Institute on Aging (NIA) [AG023629]; National Center for Advancing Translational Sciences, CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center [DK063491]; NHGRI [U01-HG-004729, U01-HG-004446, U01-HG-004424]; Italian Ministry of Health [ICS110.1/RF97.71]; US NIA [263 MD 9164, 263 MD 821336]; Intramural research program of the NIA, NIH, Baltimore, MD; K01 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIKDD) [5K01DK082729-02]; NHLBI. [HL105756, N01HC85086, HL080295, HL087652, HL085710, N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, N01-HC-45204, R01-HL-084099, N01-HC-95159, N01-HC-95160]; The NHLBI [HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; The NHLBI. [N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, RR-024156, N02HL64278, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083] FX Infrastructure for the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium is supported, in part, by the National Heart, Lung, and Blood Institute (NHLBI) grant HL105756. The Atherosclerosis Risk in Communities (ARIC) Study is performed as a collaborative study supported by NHLBI contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute (NHGRI) contract U01HG004402; and National Institutes of Health (NIH) contract HSN268200625226C. Infrastructure was partly supported by grant number UL1RR025005, a component of the NIH Roadmap for Medical Research. The Cardiovascular Health Study (CHS) was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants HL080295, HL087652, and HL105756 from the NHLBI, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by AG023629 from the National Institute on Aging (NIA). The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The fatty acid measurements were supported by grant HL085710 from NHLBI. The Coronary Artery Risk Development in Young Adults (CARDIA) study is funded by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, and N01-HC-45204 from the NHLBI to the CARDIA investigators. Genotyping of the CARDIA participants was supported by grants U01-HG-004729, U01-HG-004446, and U01-HG-004424 from the NHGRI and R01-HL-084099 from the NHLBI to Dr Foy. The Invecchiare in Chianti (InCHIANTI) study baseline (1998-2000) was supported as a targeted project (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the US NIA Contracts 263 MD 9164 and 263 MD 821336 and was supported, in part, by the Intramural research program of the NIA, NIH, Baltimore, MD. The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health Association Resource (SHARe) were supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the NHLBI. Funding for MESA SHARe genotyping was provided by NHLBI Contract N02HL64278. Dr Nettleton was supported by a K01 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIKDD) (5K01DK082729-02). NR 49 TC 9 Z9 9 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2014 VL 7 IS 3 BP 321 EP 331 DI 10.1161/CIRCGENETICS.113.000208 PG 11 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AK1VY UT WOS:000338207300013 PM 24823311 ER PT J AU Lin, HH Wang, M Brody, JA Bis, JC Dupuis, J Lumley, T McKnight, B Rice, KM Sitlani, CM Reid, JG Bressler, J Liu, XM Davis, BC Johnson, AD O'Donnell, CJ Kovar, CL Dinh, H Wu, YQ Newsham, I Chen, H Broka, A DeStefano, AL Gupta, M Lunetta, KL Liu, CT White, CC Xing, CH Zhou, YH Benjamin, EJ Schnabel, RB Heckbert, SR Psaty, BM Muzny, DM Cupples, LA Morrison, AC Boerwinkle, E AF Lin, Honghuang Wang, Min Brody, Jennifer A. Bis, Joshua C. Dupuis, Josee Lumley, Thomas McKnight, Barbara Rice, Kenneth M. Sitlani, Colleen M. Reid, Jeffrey G. Bressler, Jan Liu, Xiaoming Davis, Brian C. Johnson, Andrew D. O'Donnell, Christopher J. Kovar, Christie L. Dinh, Huyen Wu, Yuanqing Newsham, Irene Chen, Han Broka, Andi DeStefano, Anita L. Gupta, Mayetri Lunetta, Kathryn L. Liu, Ching-Ti White, Charles C. Xing, Chuanhua Zhou, Yanhua Benjamin, Emelia J. Schnabel, Renate B. Heckbert, Susan R. Psaty, Bruce M. Muzny, Donna M. Cupples, L. Adrienne Morrison, Alanna C. Boerwinkle, Eric TI Strategies to Design and Analyze Targeted Sequencing Data Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE epidemiology; genetics; sampling studies ID KERNEL ASSOCIATION TEST; WIDE ASSOCIATION; QUANTITATIVE TRAITS; RARE VARIANTS; ANNOTATION; DISEASE; MUTATIONS; FRAILTY; SAMPLES; MODELS AB Background-Genome-wide association studies have identified thousands of genetic variants that influence a variety of diseases and health-related quantitative traits. However, the causal variants underlying the majority of genetic associations remain unknown. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study aims to follow up genome-wide association study signals and identify novel associations of the allelic spectrum of identified variants with cardiovascular-related traits. Methods and Results-The study included 4231 participants from 3 CHARGE cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, and the Framingham Heart Study. We used a case-cohort design in which we selected both a random sample of participants and participants with extreme phenotypes for each of 14 traits. We sequenced and analyzed 77 genomic loci, which had previously been associated with >= 1 of 14 phenotypes. A total of 52 736 variants were characterized by sequencing and passed our stringent quality control criteria. For common variants (minor allele frequency >= 1%), we performed unweighted regression analyses to obtain P values for associations and weighted regression analyses to obtain effect estimates that accounted for the sampling design. For rare variants, we applied 2 approaches: collapsed aggregate statistics and joint analysis of variants using the sequence kernel association test. Conclusions-We sequenced 77 genomic loci in participants from 3 cohorts. We established a set of filters to identify high-quality variants and implemented statistical and bioinformatics strategies to analyze the sequence data and identify potentially functional variants within genome-wide association study loci. C1 [Lin, Honghuang; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Lin, Honghuang; Dupuis, Josee; Johnson, Andrew D.; O'Donnell, Christopher J.; DeStefano, Anita L.; Lunetta, Kathryn L.; Benjamin, Emelia J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA. [Wang, Min; Reid, Jeffrey G.; Kovar, Christie L.; Dinh, Huyen; Wu, Yuanqing; Newsham, Irene; Muzny, Donna M.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Brody, Jennifer A.; Bis, Joshua C.; Sitlani, Colleen M.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [McKnight, Barbara; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Dupuis, Josee; Chen, Han; DeStefano, Anita L.; Gupta, Mayetri; Lunetta, Kathryn L.; Liu, Ching-Ti; White, Charles C.; Xing, Chuanhua; Zhou, Yanhua; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand. [Bressler, Jan; Liu, Xiaoming; Davis, Brian C.; Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Broka, Andi] Boston Univ, LinGA Comp Resource, Boston, MA 02118 USA. [Schnabel, Renate B.] Univ Heart Ctr, Dept Gen & Intervent Cardiol, Hamburg, Germany. [Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Muzny, DM (reprint author), Baylor Coll Med, Human Genome Sequencing Ctr, Rm N1621, Houston, TX 77030 USA. EM donnam@bcm.edu; adrienne@bu.edu RI Johnson, Andrew/G-6520-2013; OI Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336; Chen, Han/0000-0002-9510-4923 FU National Institutes of Health through the American Recovery and Reinvestment Act [5RC2HL102419]; NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C, HHSN2682011000011C, HHSN2682011000012C]; Boston University [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; National Investigation Agency [AG-023629, AG-15928, AG-20098, AG-027058]; the NHLBI [N01-HC-25195, N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222]; NHLBI. [N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, HL087652, HL105756]; [R01HL087641]; [R01HL59367]; [R01HL086694] FX Support for Building on genome-wide association studies (GWAS) for the National Heart, Lung, and Blood Institute (NHLBI) diseases: the US Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study (CHARGE) consortium was provided by the National Institutes of Health through the American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Data for Building on GWAS for NHLBI-diseases: the US CHARGE consortium was provided by Eric Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC) Study, L. A. Cupples, principal investigator for the Framingham Heart Study, and Bruce Psaty, principal investigator for the Cardiovascular Health Study (CHS). Sequencing was carried out at the Baylor Genome Center (U54 HG003273). The ARIC Study is performed as a collaborative study supported by the NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C, HHSN2682011000011C, and HHSN2682011000012C) and R01HL087641, R01HL59367, and R01HL086694. We thank the staff and participants of the ARIC study for their important contributions. The Framingham Heart Study (FHS) is performed and supported by the NHLBI in collaboration with Boston University (Contract No. N01-HC-25195), and its contract with Affymetrix, Inc, for genome-wide genotyping services (Contract No. N02-HL-6-4278), for quality control by FHS investigators using genotypes in the SNP Health Association Resource (SHARe) project. A portion of this research was performed using the Linux Cluster for Genetic Analysis (LinGA) computing resources at Boston University Medical Campus. This CHS research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C and by NHLBI grants HL080295, HL087652, and HL105756 with additional contribution from National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Investigation Agency. See also http://www.chs-nhlbi.org/pi.htm. NR 38 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2014 VL 7 IS 3 BP 335 EP 343 DI 10.1161/CIRCGENETICS.113.000350 PG 9 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AK1VY UT WOS:000338207300015 PM 24951659 ER PT J AU Liu, CT Young, KL Brody, JA Olden, M Wojczynski, MK Heard-Costa, N Li, G Morrison, AC Muzny, D Gibbs, RA Reid, JG Shao, YM Zhou, YH Boerwinkle, E Heiss, G Wagenknecht, L McKnight, B Borecki, IB Fox, CS North, KE Cupples, LA AF Liu, Ching-Ti Young, Kristin L. Brody, Jennifer A. Olden, Matthias Wojczynski, Mary K. Heard-Costa, Nancy Li, Guo Morrison, Alanna C. Muzny, Donna Gibbs, Richard A. Reid, Jeffrey G. Shao, Yaming Zhou, Yanhua Boerwinkle, Eric Heiss, Gerardo Wagenknecht, Lynne McKnight, Barbara Borecki, Ingrid B. Fox, Caroline S. North, Kari E. Cupples, L. Adrienne TI Sequence Variation in TMEM18 in Association With Body Mass Index Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE body mass index; genetic association studies ID EARLY-ONSET OBESITY; LIFE-COURSE; GENE-EXPRESSION; FTO GENE; VARIANTS; BMI; ADOLESCENTS; MUTATIONS; CHILDREN; DATABASE AB Background-Genome-wide association studies for body mass index (BMI) previously identified a locus near TMEM18. We conducted targeted sequencing of this region to investigate the role of common, low-frequency, and rare variants influencing BMI. Methods and Results-We sequenced TMEM18 and regions downstream of TMEM18 on chromosome 2 in 3976 individuals of European ancestry from 3 community-based cohorts (Atherosclerosis Risk in Communities, Cardiovascular Health Study, and Framingham Heart Study), including 200 adults selected for high BMI. We examined the association between BMI and variants identified in the region from nucleotide position 586 432 to 677 539 (hg18). Rare variants (minor allele frequency, <1%) were analyzed using a burden test and the sequence kernel association test. Results from the 3 cohort studies were meta-analyzed. We estimate that mean BMI is 0.43 kg/m(2) higher for each copy of the G allele of single-nucleotide polymorphism rs7596758 (minor allele frequency, 29%; P=3.46x10(-4)) using a Bonferroni threshold of P<4.6x10(-4). Analyses conditional on previous genome-wide association study single-nucleotide polymorphisms associated with BMI in the region led to attenuation of this signal and uncovered another independent (r(2)<0.2), statistically significant association, rs186019316 (P=2.11x10(-4)). Both rs186019316 and rs7596758 or proxies are located in transcription factor binding regions. No significant association with rare variants was found in either the exons of TMEM18 or the 3' genome-wide association study region. Conclusions-Targeted sequencing around TMEM18 identified 2 novel BMI variants with possible regulatory function. C1 [Liu, Ching-Ti; Zhou, Yanhua; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Young, Kristin L.; Shao, Yaming; Heiss, Gerardo; North, Kari E.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Young, Kristin L.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Brody, Jennifer A.; Li, Guo; McKnight, Barbara] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Olden, Matthias; Heard-Costa, Nancy; Fox, Caroline S.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA. [Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Sch Med, St Louis, MO USA. [Heard-Costa, Nancy] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02118 USA. [Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Div Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Houston, TX 77030 USA. [Muzny, Donna; Gibbs, Richard A.; Reid, Jeffrey G.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Wagenknecht, Lynne] Wake Forest Baptist Med Ctr, Dept Epidemiol & Prevent, Winston Salem, NC USA. [McKnight, Barbara] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. RP Liu, CT (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,CT3, Boston, MA 02118 USA. EM ctliu@bu.edu; adrienne@bu.edu RI Young, Kristin/B-5792-2008 OI Young, Kristin/0000-0003-0070-6145 FU National Institutes of Health through the American Recovery and Reinvestment Act [5RC2HL102419]; NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C, HHSN2682011000011C, HHSN2682011000012C]; Boston University [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; National Institute of Diabetes and Digestive and Kidney Diseases/Baylor Genome Center [R01-DK-8925601, R01-DK-075681, U54 HG003273]; the NHLBI [N01-HC-25195, N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081]; NHLBI. [N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, HL087652, HL105756]; [R01HL087641]; [R01HL59367]; [R01HL086694] FX Support for Building on Genome-Wide Association Studies (GWAS) for National Heart, Lung, and Blood Institute (NHLBI) Diseases: The US CHARGE Consortium was provided by the National Institutes of Health through the American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Data for Building on GWAS for NHLBI-Diseases: The US CHARGE Consortium was provided by Eric Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC) study; L. Adrienne Cupples, principal investigator for the Framingham Heart Study (FHS); and Bruce Psaty, principal investigator for the Cardiovascular Health Study (CHS). The ARIC study is performed as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C, HHSN2682011000011C, and HHSN2682011000012C), R01HL087641, R01HL59367, and R01HL086694. FHS is conducted and supported by the NHLBI in collaboration with Boston University (contract no. N01-HC-25195) and its contract with Affymetrix, Inc, for genome-wide genotyping services (contract no. N02-HL-6-4278), for quality control by FHS investigators using genotypes in the SNP Health Association Resource project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The CHS research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C, and NHLBI grants HL080295, HL087652, HL105756 with additional contribution from National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. See also http://www.chs-nhlbi.org/pi.htm. This work was partially supported by R01-DK-8925601 and R01-DK-075681 (Ingrid B. Borecki, principal investigator) from National Institute of Diabetes and Digestive and Kidney Diseases/Baylor Genome Center (grant no. U54 HG003273). NR 32 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2014 VL 7 IS 3 BP 344 EP 349 DI 10.1161/CIRCGENETICS.13.000067 PG 6 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AK1VY UT WOS:000338207300016 PM 24951660 ER PT J AU London, SJ Gao, W Gharib, SA Hancock, DB Wilk, JB House, JS Gibbs, RA Muzny, DM Lumley, T Franceschini, N North, KE Psaty, BM Kovar, CL Coresh, J Zhou, YH Heckbert, SR Brody, JA Morrison, AC Dupuis, J AF London, Stephanie J. Gao, Wei Gharib, Sina A. Hancock, Dana B. Wilk, Jemma B. House, John S. Gibbs, Richard A. Muzny, Donna M. Lumley, Thomas Franceschini, Nora North, Kari E. Psaty, Bruce M. Kovar, Christie L. Coresh, Josef Zhou, Yanhua Heckbert, Susan R. Brody, Jennifer A. Morrison, Alanna C. Dupuis, Josee TI ADAM19 and HTR4 Variants and Pulmonary Function Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE Airway Obstruction; genome-wide association study; lung; polymorphism, genetic; pulmonary disease, chronic obstructive; respiratory function tests; sequence analysis, DNA ID NECROSIS-FACTOR-ALPHA; LUNG-FUNCTION; WIDE ASSOCIATION; EPITHELIAL-CELLS; DISEASE; POPULATION; EXPRESSION; MORTALITY; SEROTONIN; DATABASE AB Background-The pulmonary function measures of forced expiratory volume in 1 second (FEV1) and its ratio to forced vital capacity (FVC) are used in the diagnosis and monitoring of lung diseases and predict cardiovascular mortality in the general population. Genome-wide association studies (GWASs) have identified numerous loci associated with FEV1 and FEV1/FVC, but the causal variants remain uncertain. We hypothesized that novel or rare variants poorly tagged by GWASs may explain the significant associations between FEV1/FVC and 2 genes: ADAM19 and HTR4. Methods and Results-We sequenced ADAM19 and its promoter region along with the approximate to 21-kb portion of HTR4 harboring GWAS single-nucleotide polymorphisms for pulmonary function and analyzed associations with FEV1/FVC among 3983 participants of European ancestry from Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Meta-analysis of common variants in each region identified statistically significant associations (316 tests; P<1.58x10(-4)) with FEV1/FVC for 14 ADAM19 single-nucleotide polymorphisms and 24 HTR4 single-nucleotide polymorphisms. After conditioning on the sentinel GWASs hit in each gene (ADAM19 rs1422795, minor allele frequency=0.33 and HTR4 rs11168048, minor allele frequency=0.40], 1 single-nucleotide polymorphism remained statistically significant (ADAM19 rs13155908, minor allele frequency=0.12; P=1.56x10(-4)). Analysis of rare variants (minor allele frequency <1%) using sequence kernel association test did not identify associations with either region. Conclusions-Sequencing identified 1 common variant associated with FEV1/FVC independent of the sentinel ADAM19 GWAS hit and supports the original HTR4 GWAS findings. Rare variants do not seem to underlie GWAS associations with pulmonary function for common variants in ADAM19 and HTR4. C1 [London, Stephanie J.; Hancock, Dana B.] NIEHS, Epidemiol Branch, Div Intramural Res, NIH,US Dept HHS, Res Triangle Pk, NC 27709 USA. [London, Stephanie J.; House, John S.] NIEHS, Lab Resp Biol, Div Intramural Res, NIH,US Dept HHS, Res Triangle Pk, NC 27709 USA. [Gao, Wei; Zhou, Yanhua; Dupuis, Josee] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. [Gharib, Sina A.] Univ Washington, Dept Med, Ctr Lung Biol, Div Pulm & Crit Care Med, Seattle, WA USA. [Psaty, Bruce M.; Heckbert, Susan R.; Brody, Jennifer A.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Hancock, Dana B.] Res Triangle Inst, Behav Hlth Epidemiol Program, Res Triangle Pk, NC 27709 USA. [Wilk, Jemma B.] Pfizer Global Res & Dev, Precis Med, Cambridge, MA USA. [Gibbs, Richard A.; Muzny, Donna M.; Kovar, Christie L.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand. [Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA. RP London, SJ (reprint author), NIEHS, 111 TW Alexander Dr,POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov OI Hancock, Dana/0000-0003-2240-3604; House, John S./0000-0002-8447-7871; London, Stephanie/0000-0003-4911-5290 FU National Institutes of Health (NIH) through the American Recovery and Reinvestment Act (ARRA) [5RC2HL102419]; NHLBI [HL105756, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C, HHSN2682011000011C, HHSN2682011000012C]; National Human Genome Research Institute [U01HG004402]; NIH [HHSN268200625226C]; NIH and NIH Roadmap for Medical Research [UL1RR025005]; Boston University [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; National Institute on Aging [AG023629]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences; the NHLBI [N01-HC-25195, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080]; NHLBI. [N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652]; [R01HL087641]; [R01HL59367]; [R01HL086694]; [U54 HG003273] FX Funding support for Building on GWAS for National Heart, Lung, and Blood Institute (NHLBI) diseases: the US CHARGE Consortium was provided by the National Institutes of Health (NIH) through the American Recovery and Reinvestment Act of 2009 (ARRA; 5RC2HL102419). Data for Building on GWAS for NHLBI diseases: the US CHARGE Consortium was provided by Eric Boerwinkle on behalf of the ARIC study, L. Adrienne Cupples, principal investigator for the Framingham Heart Study, and Bruce Psaty, principal investigator for the Cardiovascular Health Study. Infrastructure for the CHARGE Consortium is supported in part by NHLBI grant HL105756. The ARIC study is performed as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C, HHSN2682011000011C, and HHSN2682011000012C) R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. Infrastructure was partly supported by grant No. UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. The Framingham Heart Study is conducted and supported by the NHLBI in collaboration with Boston University (contract No. N01-HC-25195) and its contract with Affymetrix, Inc., for genome-wide genotyping services (contract No. N02-HL-6-4278) and for quality control by Framingham Heart Study investigators using genotypes in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Clusters for Genetic Analysis computing resources at Boston University Medical Campus. The Human Genome Sequencing Center at Baylor College of Medicine is supported by U54 HG003273. The research within CHS was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and NHLBI grants HL080295, HL087652, and HL105756, with additional contributions from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG023629 from the National Institute on Aging. This work was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 39 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2014 VL 7 IS 3 BP 350 EP 358 DI 10.1161/CIRCGENETICS.113.000066 PG 9 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AK1VY UT WOS:000338207300017 PM 24951661 ER PT J AU Bis, JC White, CC Franceschini, N Brody, J Zhang, XL Muzny, D Santibanez, J Gibbs, R Liu, XM Lin, HH Boerwinkle, E Psaty, BM North, KE Cupples, LA O'Donnell, CJ AF Bis, Joshua C. White, Charles C. Franceschini, Nora Brody, Jennifer Zhang, Xiaoling Muzny, Donna Santibanez, Jireh Gibbs, Richard Liu, Xiaoming Lin, Honghuang Boerwinkle, Eric Psaty, Bruce M. North, Kari E. Cupples, L. Adrienne O'Donnell, Christopher J. CA CHARGE Subclinical Atherosclerosis TI Sequencing of 2 Subclinical Atherosclerosis Candidate Regions in 3669 Individuals Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE atherosclerosis; carotid artery, common; epidemiology; genetics; plaque, atherosclerotic; sequence analysis, DNA ID INTIMA-MEDIA THICKNESS; KERNEL ASSOCIATION TEST; WIDE ASSOCIATION; TASK-FORCE; METAANALYSIS; VARIANTS; RISK; LOCI; DESIGN; FRAMINGHAM AB Background-Atherosclerosis, the precursor to coronary heart disease and stroke, is characterized by an accumulation of fatty cells in the arterial intimal-medial layers. Common carotid intima media thickness (cIMT) and plaque are subclinical atherosclerosis measures that predict cardiovascular disease events. Previously, genome-wide association studies demonstrated evidence for association with cIMT (SLC17A4) and plaque (PIK3CG). Methods and Results-We sequenced 120 kb around SLC17A4 (6p22.2) and 251 kb around PIK3CG (7q22.3) among 3669 European ancestry participants from the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), and Framingham Heart Study (FHS) in Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Primary analyses focused on 438 common variants (minor allele frequency >= 1%), which were independently meta-analyzed. A 3' untranslated region CCDC71L variant (rs2286149), upstream from PIK3CG, was the most significant finding in cIMT (P=0.00033) and plaque (P=0.0004) analyses. A SLC17A4 intronic variant was also associated with cIMT (P=0.008). Both were in low linkage disequilibrium with the genome-wide association study single nucleotide polymorphisms. Gene-based tests including T1 count and sequence kernel association test for rare variants (minor allele frequency <1%) did not yield statistically significant associations. However, we observed nominal associations for rare variants in CCDC71L and SLC17A3 with cIMT and of the entire 7q22 region with plaque (P=0.05). Conclusions-Common and rare variants in PIK3CG and SLC17A4 regions demonstrated modest association with subclinical atherosclerosis traits. Although not conclusive, these findings may help to understand the genetic architecture of regions previously implicated by genome-wide association studies and identify variants within these regions for further investigation in larger samples. C1 [Bis, Joshua C.; Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Bis, Joshua C.; Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA. [White, Charles C.; Zhang, Xiaoling; Lin, Honghuang; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [White, Charles C.; Cupples, L. Adrienne] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. [Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Muzny, Donna; Santibanez, Jireh; Gibbs, Richard; Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Liu, Xiaoming; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Lin, Honghuang] Boston Univ, Dept Med, Sch Med, Boston, MA 02215 USA. [Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Liu, Xiaoming; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. RP Bis, JC (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM joshbis@uw.edu OI Lin, Honghuang/0000-0003-3043-3942 FU National Institutes of Health through the American Recovery and Reinvestment Act [5RC2HL102419]; National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100 008C, HHSN268201100009C, HHSN2682011000010C, HHSN268 2011000011C, HHSN2682011000012C]; Boston University [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; National Institute on Aging (NIA) [AG023629]; National Center for Advancing Translational Sciences, CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]; the NHLBI [N01-HC-25195, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC85085, N01HC45133]; NHLBI [HL080295, HL087652, HL105756, HL103612, HL120393]; [R01HL087641]; [R01HL59367]; [R01HL086694] FX Funding support for Building on GWAS for NHLBI-Diseases: The US CHARGE Consortium was provided by the National Institutes of Health through the American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Data for Building on GWAS for NHLBI-Diseases: The US CHARGE Consortium were provided by Eric Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC) study; L. Adrienne Cupples, principal investigator for the Framingham Heart Study (FHS); and Bruce Psaty, principal investigator for the Cardiovascular Health Study. Sequencing was performed at the Baylor Genome Center (U54 HG003273). The ARIC study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100 008C, HHSN268201100009C, HHSN2682011000010C, HHSN268 2011000011C, and HHSN2682011000012C), R01HL087641, R01HL59367, and R01HL086694. The authors thank the staff and participants of the ARIC study for their important contributions. The FHS is conducted and supported by the NHLBI in collaboration with Boston University (contract no. N01-HC-25195), and its contract with Affymetrix, Inc, for genome-wide genotyping services (contract no. N02-HL-6-4278), for quality control by FHS investigators using genotypes in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA) computing resources at Boston University Medical Campus. This Cardiovascular Health Study research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC85085, N01HC45133; and NHLBI grants HL080295, HL087652, HL105756, HL103612, and HL120393 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org/. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 31 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2014 VL 7 IS 3 BP 359 EP 364 DI 10.1161/CIRCGENETICS.113.000116 PG 6 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AK1VY UT WOS:000338207300018 PM 24951662 ER PT J AU Magnani, JW Brody, JA Prins, BP Arking, DE Lin, HH Yin, XY Liu, CT Morrison, AC Zhang, F Spector, TD Alonso, A Bis, JC Heckbert, SR Lumley, T Sitlani, CM Cupples, A Lubitz, SA Soliman, EZ Pulit, SL Newton-Cheh, C O'Donnell, CJ Ellinor, PT Benjamin, EJ Muzny, DM Gibbs, RA Santibanez, J Taylor, HA Rotter, JI Lange, LA Psaty, BM Jackson, R Rich, SS Boerwinkle, E Jamshidi, Y Sotoodehnia, N AF Magnani, Jared W. Brody, Jennifer A. Prins, Bram P. Arking, Dan E. Lin, Honghuang Yin, Xiaoyan Liu, Ching-Ti Morrison, Alanna C. Zhang, Feng Spector, Tim D. Alonso, Alvaro Bis, Joshua C. Heckbert, Susan R. Lumley, Thomas Sitlani, Colleen M. Cupples, Adrienne Lubitz, Steven A. Soliman, Elsayed Z. Pulit, Sara L. Newton-Cheh, Christopher O'Donnell, Christopher J. Ellinor, Patrick T. Benjamin, Emelia J. Muzny, Donna M. Gibbs, Richard A. Santibanez, Jireh Taylor, Herman A. Rotter, Jerome I. Lange, Leslie A. Psaty, Bruce M. Jackson, Rebecca Rich, Stephen S. Boerwinkle, Eric Jamshidi, Yalda Sotoodehnia, Nona CA CHARGE Consortium NHLBIs Exome Sequencing UK10K TI Sequencing of SCN5A Identifies Rare and Common Variants Associated With Cardiac Conduction: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE electrocardiography; genomics ID SICK SINUS SYNDROME; LONG QT SYNDROME; SODIUM-CHANNEL; QRS DURATION; PR INTERVAL; DILATED CARDIOMYOPATHY; WIDE ASSOCIATION; CODING VARIANTS; MUTATIONS; DISEASE AB Background-The cardiac sodium channel SCN5A regulates atrioventricular and ventricular conduction. Genetic variants in this gene are associated with PR and QRS intervals. We sought to characterize further the contribution of rare and common coding variation in SCN5A to cardiac conduction. Methods and Results-In Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study, we performed targeted exonic sequencing of SCN5A (n=3699, European ancestry individuals) and identified 4 common (minor allele frequency >1%) and 157 rare variants. Common and rare SCN5A coding variants were examined for association with PR and QRS intervals through meta-analysis of European ancestry participants from CHARGE, National Heart, Lung, and Blood Institute's Exome Sequencing Project (n=607), and the UK10K (n=1275) and by examining Exome Sequencing Project African ancestry participants (n=972). Rare coding SCN5A variants in aggregate were associated with PR interval in European and African ancestry participants (P=1.3x10(-3)). Three common variants were associated with PR and QRS interval duration among European ancestry participants and one among African ancestry participants. These included 2 well-known missense variants: rs1805124 (H558R) was associated with PR and QRS shortening in European ancestry participants (P=6.25x10(-4) and P=5.2x10(-3), respectively) and rs7626962 (S1102Y) was associated with PR shortening in those of African ancestry (P=2.82x10(-3)). Among European ancestry participants, 2 novel synonymous variants, rs1805126 and rs6599230, were associated with cardiac conduction. Our top signal, rs1805126 was associated with PR and QRS lengthening (P=3.35x10(-7) and P=2.69x10(-4), respectively) and rs6599230 was associated with PR shortening (P=2.67x10(-5)). Conclusions-By sequencing SCN5A, we identified novel common and rare coding variants associated with cardiac conduction. C1 [Magnani, Jared W.; Lin, Honghuang; Yin, Xiaoyan; Liu, Ching-Ti; Cupples, Adrienne; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Magnani, Jared W.; Lin, Honghuang; Yin, Xiaoyan; Liu, Ching-Ti; Cupples, Adrienne; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Boston, MA 02118 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Lin, Honghuang] Boston Univ, Sch Med, Sect Computat Biomed, Boston, MA 02118 USA. [Brody, Jennifer A.; Bis, Joshua C.; Heckbert, Susan R.; Sitlani, Colleen M.; Psaty, Bruce M.; Sotoodehnia, Nona] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Prins, Bram P.; Zhang, Feng; Jamshidi, Yalda] St Georges Univ London, Human Genet Res Ctr, London, England. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Yin, Xiaoyan; Liu, Ching-Ti; Cupples, Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Zhang, Feng; Spector, Tim D.] Kings Coll London, Dept Twin Res, St Thomas Hosp, London WC2R 2LS, England. [Zhang, Feng; Spector, Tim D.] Kings Coll London, Genet Epidemiol Unit, St Thomas Hosp, London WC2R 2LS, England. [Alonso, Alvaro] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand. [Lubitz, Steven A.; Pulit, Sara L.; Newton-Cheh, Christopher; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Lubitz, Steven A.; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr, Winston Salem, NC USA. [Pulit, Sara L.; Newton-Cheh, Christopher] Broad Inst, Cambridge, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Muzny, Donna M.; Gibbs, Richard A.; Santibanez, Jireh; Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MI USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA. [Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Jackson, Rebecca] Ohio State Univ, Dept Med, Wexner Med Ctr, Columbus, OH 43210 USA. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 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; nsotoo@uw.edu RI Alonso, Alvaro/A-4917-2010; OI Alonso, Alvaro/0000-0002-2225-8323; Jamshidi, Yalda/0000-0003-0151-6482; Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health (NIH) through the American Recovery and Reinvestment Act [5RC2HL102419]; NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN26820110 0009C, HHSN2682011000010C, HHSN2682011000011C, HHSN2682011000012C]; Boston University [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Boston University School of Medicine Department of Medicine Career Investment Award; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute on Aging [AG023629]; Wellcome Trust [WT091310]; ENGAGE project [HEALTH-F4-2007-201413]; Department of Health via the National Institute for Health Research (NIHR); British Heart Foundation [PG/12/38/29615]; the NHLBI [N01-HC-25195, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079]; NHLBI. [N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652, HL105756]; [6R01-NS 17950NIH]; [1RO1HL092577]; [1R01 HL102214l]; [1RC1HL101056]; [5R21DA027021]; [1RO1HL104156]; [K23HL11472]; [1K24HL105780]; [1R03AG045075] FX Funding support for building on Genome-wide association studies (GWAS) for National Heart, Lung, and Blood Institute (NHLBI) diseases: the US Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium Targeted Sequencing Study was provided by the National Institutes of Health (NIH) through the American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Data for building on GWAS for NHLBI diseases: the US CHARGE Consortium was provided by Dr Boerwinkle on behalf of the Atherosclerosis Risk in Communities (ARIC) Study, Dr Cupples, principal investigator for the Framingham Heart Study, and Dr Psaty, principal investigator for the Cardiovascular Health Study. The ARIC Study is performed as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN26820110 0009C, HHSN2682011000010C, HHSN2682011000011C, and HHSN2682011000012C). The Framingham Heart Study is conducted and supported by the NHLBI in collaboration with Boston University (contract No. N01-HC-25195) and its contract with Affymetrix, Inc, for genome-wide genotyping services (contract No. N02-HL-6-4278), for quality control by Framingham Heart Study investigators using genotypes in the SNP Health Association Resource (SHARe) project. This project was supported by 6R01-NS 17950NIH, 1RO1HL092577, 1R01 HL102214l, 1RC1HL101056, 5R21DA027021, 1RO1HL104156, K23HL11472, 1K24HL105780, and 1R03AG045075. Dr Magnani is further supported by a Boston University School of Medicine Department of Medicine Career Investment Award. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Cardiovascular Health Study (CHS): This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and NHLBI grants HL080295, HL087652, and HL105756 with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through AG023629 from the National Institute on Aging. A full list of CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. UK10K: The UK10K project was funded by the Wellcome Trust award WT091310. Twins UK (TUK): TUK was funded by the Wellcome Trust and ENGAGE project grant agreement HEALTH-F4-2007-201413. The study also receives support from the Department of Health via the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London. Dr Spector is an NIHR senior Investigator and ERC Senior Researcher. Funding for the project was also provided by the British Heart Foundation grant PG/12/38/29615 (Dr Jamshidi). NR 46 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2014 VL 7 IS 3 BP 365 EP 373 DI 10.1161/CIRCGENETICS.113.000098 PG 9 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AK1VY UT WOS:000338207300019 PM 24951663 ER PT J AU Cornes, BK Brody, JA Nikpoor, N Morrison, AC Dang, HCP Ahn, BS Wang, S Dauriz, M Barzilay, JI Dupuis, J Florez, JC Coresh, J Gibbs, RA Kao, WHL Liu, CT McKnight, B Muzny, D Pankow, JS Reid, JG White, CC Johnson, AD Wong, TY Psaty, BM Boerwinkle, E Rotter, JI Siscovick, DS Sladek, R Meigs, JB AF Cornes, Belinda K. Brody, Jennifer A. Nikpoor, Naghmeh Morrison, Alanna C. Huan Chu Pham Dang Ahn, Byung Soo Wang, Shuai Dauriz, Marco Barzilay, Joshua I. Dupuis, Josee Florez, Jose C. Coresh, Josef Gibbs, Richard A. Kao, W. H. Linda Liu, Ching-Ti McKnight, Barbara Muzny, Donna Pankow, James S. Reid, Jeffrey G. White, Charles C. Johnson, Andrew D. Wong, Tien Y. Psaty, Bruce M. Boerwinkle, Eric Rotter, Jerome I. Siscovick, David S. Sladek, Robert Meigs, James B. TI Association of Levels of Fasting Glucose and Insulin With Rare Variants at the Chromosome 11p11.2-MADD Locus Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genetic epidemiology; glucose; human genetics; insulin; molecular genetics ID HUMAN GENE-EXPRESSION; TRANSCRIPTION FACTOR; CARDIOVASCULAR HEALTH; WIDE ASSOCIATION; GLYCEMIC TRAITS; BETA-CELL; DNA; POPULATION; RISK; PATHOPHYSIOLOGY AB Background-Common variation at the 11p11.2 locus, encompassing MADD, ACP2, NR1H3, MYBPC3, and SPI1, has been associated in genome-wide association studies with fasting glucose and insulin (FI). In the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study, we sequenced 5 gene regions at 11p11.2 to identify rare, potentially functional variants influencing fasting glucose or FI levels. Methods and Results-Sequencing (mean depth, 38x) across 16.1 kb in 3566 individuals without diabetes mellitus identified 653 variants, 79.9% of which were rare (minor allele frequency <1%) and novel. We analyzed rare variants in 5 gene regions with FI or fasting glucose using the sequence kernel association test. At NR1H3, 53 rare variants were jointly associated with FI (P=2.73x10(-3)); of these, 7 were predicted to have regulatory function and showed association with FI (P=1.28x10(-3)). Conditioning on 2 previously associated variants at MADD (rs7944584, rs10838687) did not attenuate this association, suggesting that there are >2 independent signals at 11p11.2. One predicted regulatory variant, chr11: 47227430 (hg18; minor allele frequency=0.00068), contributed 20.6% to the overall sequence kernel association test score at NR1H3, lies in intron 2 of NR1H3, and is a predicted binding site for forkhead box A1 (FOXA1), a transcription factor associated with insulin regulation. In human HepG2 hepatoma cells, the rare chr11: 47227430 A allele disrupted FOXA1 binding and reduced FOXA1-dependent transcriptional activity. Conclusions-Sequencing at 11p11.2-NR1H3 identified rare variation associated with FI. One variant, chr11: 47227430, seems to be functional, with the rare A allele reducing transcription factor FOXA1 binding and FOXA1-dependent transcriptional activity. C1 [Cornes, Belinda K.; Dauriz, Marco; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Boston, MA 02114 USA. [Cornes, Belinda K.; Dauriz, Marco; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Brody, Jennifer A.; McKnight, Barbara; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [McKnight, Barbara] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Nikpoor, Naghmeh; Huan Chu Pham Dang; Ahn, Byung Soo; Sladek, Robert] McGill Univ, Fac Med, Dept Human Genet, Montreal, PQ, Canada. [Nikpoor, Naghmeh; Huan Chu Pham Dang; Ahn, Byung Soo; Sladek, Robert] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA. [Gibbs, Richard A.; Muzny, Donna; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genome Sequencing Ctr, Baylor Coll Med, Houston, TX 77030 USA. [Wang, Shuai; Dupuis, Josee; Liu, Ching-Ti; White, Charles C.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Dauriz, Marco] Univ Verona, Div Endocrinol Diabet & Metab, Dept Med, Sch Med, I-37100 Verona, Italy. [Dauriz, Marco] Hosp Trust Verona, Verona, Italy. [Barzilay, Joshua I.] Kaiser Permanente Georgia, Div Endocrinol, Atlanta, GA USA. [Barzilay, Joshua I.] Emory Univ, Sch Med, Atlanta, GA USA. [Dupuis, Josee; Johnson, Andrew D.] NHLBI, Framingham Heart Study, Cardiovasc Epidemiol & Human Genom Ctr, Framingham, MA USA. [Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Coresh, Josef] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. [Coresh, Josef; Kao, W. H. Linda; Reid, Jeffrey G.] Johns Hopkins Univ, Dept Epidemiol, Johns Hopkins Univ Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Wong, Tien Y.] Duke NUS Grad Med Sch, Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore. [Wong, Tien Y.] Natl Univ Singapore, Dept Ophthalmol, Yong Loo Lin Sch Med, Singapore 117548, Singapore. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr Torrance, Inst Translat Genom & Populat Sci, Los Angeles Biomed Reasearch Inst, Torrance, CA USA. [Rotter, Jerome I.] Harbor UCLA Med Ctr Torrance, Dept Pediat, Torrance, CA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org RI Johnson, Andrew/G-6520-2013; Dauriz, Marco/S-5843-2016; OI Dauriz, Marco/0000-0002-5542-5941; Sladek, Robert/0000-0002-2730-1204; Pankow, James/0000-0001-7076-483X FU National Institutes of Health (NIH) through the American Recovery and Reinvestment Act (ARRA) [5RC2HL102419]; Baylor Genome Center [U54 HG003273]; National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C, HHSN2682011000011C, HHSN2682011000012C]; Boston University [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; American Diabetes Association Mentored Post Doctoral Fellowship Award; National Institute on Aging (NIA) [AG023629]; the NHLBI [N01-HC-25195, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080]; NHLBI. [N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652, HL105756]; [R01DK078616]; [K24 DK080140] FX Funding support for Building on GWAS for NHLBI-diseases: the US CHARGE Consortium was provided by the National Institutes of Health (NIH) through the American Recovery and Reinvestment Act of 2009 (ARRA; 5RC2HL102419). Data for Building on GWAS for NHLBI-diseases: the US CHARGE Consortium was provided by Dr Boerwinkle on behalf of the ARIC study, L. Adrienne Cupples, principal investigator for the FHS, and Dr Psaty, principal investigator for the CHS. Support was also received from the Baylor Genome Center (U54 HG003273). The ARIC study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C, HHSN2682011000011C, and HHSN2682011000012C). The FHS is conducted and supported by the NHLBI in collaboration with Boston University (contract No. N01-HC-25195), and its contract with Affymetrix, Inc, for genome-wide genotyping services (contract No. N02-HL-6-4278) and for quality control by FHS investigators using genotypes in the SNP Health Association Resource (SHARe) project. A portion of this research was conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. This research is also supported by R01DK078616, K24 DK080140 and an American Diabetes Association Mentored Post Doctoral Fellowship Award (Dr Meigs). This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants HL080295, HL087652, HL105756 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at https://chs-nhlbi.org/pi. NR 46 TC 4 Z9 4 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X EI 1942-3268 J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2014 VL 7 IS 3 BP 374 EP 382 DI 10.1161/CIRCGENETICS.113.000169 PG 9 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA AK1VY UT WOS:000338207300020 PM 24951664 ER PT J AU Ward, MM AF Ward, Michael M. TI Update on the American College of Rheumatology/Spondyloarthritis Research and Treatment Network/Spondylitis Association of America axial spondyloarhtritis treatment guidelines project SO CLINICAL RHEUMATOLOGY LA English DT Article DE Ankylosing spondylitis; Axial spondyloarthritis; Guidelines AB The American College of Rheumatology, the Spondyloarthritis Research and Treatment Network, and the Spondylitis Association of America have begun collaborating on a project to develop treatment guidelines for axial spondyloarthritis. The project will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method, which is based on systematic literature reviews and quantitative evidence summaries, to develop treatment recommendations for the use of pharmacological interventions, rehabilitation, surgery, preventive care, and disease monitoring in patients with ankylosing spondylitis and axial spondyloarthritis. C1 NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMSD, Intramural Res Program, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. NR 1 TC 2 Z9 3 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0770-3198 EI 1434-9949 J9 CLIN RHEUMATOL JI Clin. Rheumatol. PD JUN PY 2014 VL 33 IS 6 BP 739 EP 740 DI 10.1007/s10067-014-2660-9 PG 2 WC Rheumatology SC Rheumatology GA AK3KW UT WOS:000338323800002 PM 24810702 ER PT J AU Lanzer, P Boehm, M Sorribas, V Thiriet, M Janzen, J Zeller, T St Hilaire, C Shanahan, C AF Lanzer, Peter Boehm, Manfred Sorribas, Victor Thiriet, Marc Janzen, Jan Zeller, Thomas St Hilaire, Cynthia Shanahan, Catherine TI Medial vascular calcification revisited: review and perspectives SO EUROPEAN HEART JOURNAL LA English DT Review DE Vascular calcifications; Monckeberg's media sclerosis; Vascular molecular biology and genetics; Vascular function ID SMOOTH-MUSCLE-CELLS; CALCIUM-PHOSPHATE DEPOSITION; AMERICAN-HEART-ASSOCIATION; CHRONIC KIDNEY-DISEASE; FETUIN-A LEVELS; ARTERIAL CALCIFICATION; ATHEROSCLEROTIC LESIONS; CARDIOVASCULAR-DISEASE; MONCKEBERGS SCLEROSIS; CORONARY-ARTERIES AB Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area. C1 [Lanzer, Peter] Bitterfeld Wolfen gGmbH, Hlth Care Ctr Bitterfeld, Dept Internal Med, Div Cardiovasc Dis, D-06749 Bitterfeld, Germany. [Boehm, Manfred; St Hilaire, Cynthia] NIH, Ctr Mol Med, Bethesda, MD 20892 USA. [Sorribas, Victor] Univ Zaragoza, Mol Toxicol Lab, Zaragoza, Spain. [Thiriet, Marc] Natl Inst Res Comp Sci & Control, Paris, France. [Janzen, Jan] VascPath, Bern, Switzerland. [Zeller, Thomas] Univ Heart Ctr Freiburg, Bad Krozingen, Germany. [Shanahan, Catherine] Kings Coll London, Div Cardiovasc, London, England. RP Lanzer, P (reprint author), Bitterfeld Wolfen gGmbH, Hlth Care Ctr Bitterfeld, Dept Internal Med, Div Cardiovasc Dis, Friedrich Ludwig Jahn Str 2, D-06749 Bitterfeld, Germany. EM planzer@gzbiwo.de OI Sorribas, Victor/0000-0003-3457-323X; St. Hilaire, Cynthia/0000-0003-1871-6915 FU British Heart Foundation [RG/11/14/29056] NR 135 TC 54 Z9 63 U1 3 U2 41 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JUN PY 2014 VL 35 IS 23 BP 1515 EP U24 DI 10.1093/eurheartj/ehu163 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AK0OF UT WOS:000338112700010 PM 24740885 ER PT J AU Guy, GP Yabroff, KR Ekwueme, DU Smith, AW Dowling, EC Rechis, R Nutt, S Richardson, LC AF Guy, Gery P., Jr. Yabroff, K. Robin Ekwueme, Donatus U. Smith, Ashley Wilder Dowling, Emily C. Rechis, Ruth Nutt, Stephanie Richardson, Lisa C. TI Estimating The Health And Economic Burden Of Cancer Among Those Diagnosed As Adolescents And Young Adults SO HEALTH AFFAIRS LA English DT Article ID UNITED-STATES; SURVIVORS; PRODUCTIVITY; PREVALENCE; IMPACT; CHALLENGES; COSTS; CARE AB Adolescent and young adult cancer survivors-those who were ages 15-39 at their first cancer diagnosis-have important health limitations. These survivors are at risk for higher health care expenditures and lost productivity, compared to adults without a history of cancer. Using Medical Expenditure Panel Survey data, we present nationally representative estimates of the economic burden among people who were diagnosed with cancer in adolescence or young adulthood. Our findings demonstrate that surviving cancer at this age is associated with a substantial economic burden. Compared to adults without a history of cancer, adolescent and young adult cancer survivors had excess annual medical expenditures of $3,170 per person and excess annual productivity losses of $2,250 per person. Multifaceted prevention strategies, including education and sustained intervention programs to ensure access to lifelong risk-based follow-up care, may be effective ways to improve the economic outcomes associated with cancer survivorship in this population. C1 [Guy, Gery P., Jr.] Ctr Dis Control & Prevent CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA. [Yabroff, K. Robin; Smith, Ashley Wilder] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ekwueme, Donatus U.] CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA. [Dowling, Emily C.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Rechis, Ruth] LIVESTRONG Fdn, Austin, TX USA. [Nutt, Stephanie] LIVESTRONG Fdn, Res & Evaluat Team, Austin, TX USA. [Richardson, Lisa C.] CDC, Div Blood Disorders, Atlanta, GA 30333 USA. RP Guy, GP (reprint author), Ctr Dis Control & Prevent CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA. EM irm2@cdc.gov FU Intramural CDC HHS [CC999999] NR 31 TC 17 Z9 18 U1 7 U2 14 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUN PY 2014 VL 33 IS 6 BP 1024 EP 1031 DI 10.1377/hlthaff.2013.1425 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA AK1PL UT WOS:000338187200014 PM 24889952 ER PT J AU Campbell, MC Ranciaro, A Zinshteyn, D Rawlings-Goss, R Hirbo, J Thompson, S Woldemeskel, D Froment, A Omar, SA Bodo, JM Nyambo, T Belay, G Drayna, D Breslin, PAS Tishkoff, SA AF Campbell, Michael C. Ranciaro, Alessia Zinshteyn, Daniel Rawlings-Goss, Renata Hirbo, Jibril Thompson, Simon Woldemeskel, Dawit Froment, Alain Omar, Sabah A. Bodo, Jean-Marie Nyambo, Thomas Belay, Gurja Drayna, Dennis Breslin, Paul A. S. Tishkoff, Sarah A. TI Limited evidence for adaptive evolution and functional effect of allelic variation at rs702424 in the promoter of the TAS2R16 bitter taste receptor gene in Africa SO JOURNAL OF HUMAN GENETICS LA English DT Article ID SELECTION; SENSITIVITY; INFECTION; HISTORY; PTC AB Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and F-ST statistics in diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that nucleotide position 516 is likely the site under selection at TAS2R16. Moreover, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans. C1 [Campbell, Michael C.; Ranciaro, Alessia; Rawlings-Goss, Renata; Hirbo, Jibril; Thompson, Simon; Woldemeskel, Dawit; Tishkoff, Sarah A.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Zinshteyn, Daniel; Tishkoff, Sarah A.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Woldemeskel, Dawit; Belay, Gurja] Univ Addis Ababa, Dept Biol, Addis Ababa, Ethiopia. [Froment, Alain] IRD MNHN, UMR 208, Paris, France. [Omar, Sabah A.] Kenya Govt Med Res Ctr, Ctr Biotechnol & Allied Sci, Nairobi, Kenya. [Bodo, Jean-Marie] Minist Sci Res & Innovat, Yaounde, Cameroon. [Nyambo, Thomas] Muhimbili Univ Hlth & Allied Sci, Dept Biochem, Dar Es Salaam, Tanzania. [Drayna, Dennis] NIDCD, NIH, Rockville, MD USA. [Breslin, Paul A. S.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Breslin, Paul A. S.] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. RP Tishkoff, SA (reprint author), Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. EM tishkoff@mail.med.upenn.edu FU US National Science Foundation [BCS-0552486, BCS-0827436]; US National Institutes of Health [R01GM076637, 5DP1ES022577 05, RO1 DC02995] FX We thank Fathya Abdo, Eva Aluvalla, Godfrey Lema, Birhanu Mekaunintie, Alemayehu Moges, Hussein Musa, Lilian Nyindodo and Solomon Taye who helped with the field work, and the various institutions in West Central, Central and East Africa for their generous support. We thank Dongbo Hu and Wen-Ya Ko for useful discussions. We also offer our deepest appreciation to the many Africans who generously donated their DNA and time so that we can learn more about African genetic diversity. This work was supported by the US National Science Foundation (grant numbers BCS-0552486, BCS-0827436), US National Institutes of Health (grant numbers R01GM076637, 5DP1ES022577 05) to SAT and US National Institutes of Health (grant number RO1 DC02995) to PASB. NR 15 TC 0 Z9 0 U1 3 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 EI 1435-232X J9 J HUM GENET JI J. Hum. Genet. PD JUN PY 2014 VL 59 IS 6 BP 349 EP 352 DI 10.1038/jhg.2014.29 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA AK1PC UT WOS:000338186000011 PM 24785689 ER PT J AU Shimizu, N Ueno, K Kurita, E Shin, SW Nishihara, T Amano, T Anzai, M Kishigami, S Kato, H Mitani, T Hosoi, Y Matsumoto, K AF Shimizu, Natsumi Ueno, Kimihiro Kurita, Ena Shin, Seung-Wook Nishihara, Takuji Amano, Tomoko Anzai, Masayuki Kishigami, Satoshi Kato, Hiromi Mitani, Tasuku Hosoi, Yoshihiko Matsumoto, Kazuya TI Possible Role of ZPAC, Zygote-specific Proteasome Assembly Chaperone, During Spermatogenesis in the Mouse SO JOURNAL OF REPRODUCTION AND DEVELOPMENT LA English DT Article DE Spermatogenesis; Ubiquitin-proteasome system; Zygote-specific proteasome assembly chaperone (ZPAC) ID GERM-CELL APOPTOSIS; EXPERIMENTAL CRYPTORCHIDISM; TESTIS; MICE; ACTIVATION; EXPRESSION; CLEARANCE; HISTONES; INSIGHTS; REMOVAL AB In the mammalian testis, the ubiquitin-proteasome system plays important roles in the process that promotes the formation of mature sperm. We recently identified zygote-specific proteasome assembly chaperone (ZPAC), which is specifically expressed in the mouse gonads and zygote. ZPAC mediates a unique proteasome assembly pathway in the zygote, but the expression profile and function of ZPAC in the testis is not fully understood. In this study, we investigated the possible role of ZPAC during mouse spermatogenesis. First, we analyzed the expression of ZPAC and 20S proteasome subunit alpha 4/PSMA7 in the adult mouse testis. ZPAC and alpha 4 were expressed in spermatogonia, spermatocytes, and round spermatids. In elongating spermatids, ZPAC was expressed until step 10, whereas expression of alpha 4 persisted until step 12. We then examined the expression profile of ZPAC and alpha 4 in a mouse model of experimental unilateral cryptorchidism. Consistent with appearance of morphologically impaired germ cells following cryptorchidism, the ZPAC protein level was significantly decreased at 4 days post induction of experimental cryptorchidism (D4) compared with the intact testis, although the amount of alpha 4 protein persisted at least until D10. Moreover, intense ZPAC staining was co-localized with staining of annexin V, an early indicator of apoptosis in mammalian cells, in germ cells of cryptorchid testis, but ZPAC was also expressed in germ cells showing no detectable expression of annexin V. These results suggest that ZPAC plays a role during spermatogenesis and raises the possibility that 20S proteasome mediated by ZPAC may be involved in the regulation of germ cell survival during spermatogenesis. C1 [Shimizu, Natsumi; Nishihara, Takuji; Amano, Tomoko; Anzai, Masayuki; Kishigami, Satoshi; Kato, Hiromi; Mitani, Tasuku; Hosoi, Yoshihiko; Matsumoto, Kazuya] Kinki Univ, Grad Sch Biol Oriented Sci & Technol, Lab Mol Dev Biol, Wakayama 6496493, Japan. [Ueno, Kimihiro; Kurita, Ena] Kinki Univ, Fac Biol Oriented Sci & Technol, Lab Mol Dev Biol, Wakayama 6496493, Japan. [Shin, Seung-Wook] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. [Anzai, Masayuki; Kato, Hiromi; Mitani, Tasuku] Kinki Univ, Inst Adv Technol, Wakayama 6420017, Japan. RP Matsumoto, K (reprint author), Kinki Univ, Grad Sch Biol Oriented Sci & Technol, Lab Mol Dev Biol, Wakayama 6496493, Japan. FU Japan Society for the Promotion of Science [25292189]; INAMORI Foundation FX This study was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science 25292189 (to KM), and a grant from the INAMORI Foundation (to KM). NR 34 TC 2 Z9 2 U1 4 U2 5 PU SOCIETY REPRODUCTION & DEVELOPMENT-SRD PI TSUKUBA PA C/O KAZUHIRO KIKUCHI, PHD DVM, NATL INST AGROBIOLOGICAL SCIENCES KANNONDAI 2-1-2, TSUKUBA, IBARAKI 305-8602, JAPAN SN 0916-8818 J9 J REPROD DEVELOP JI J. Reprod. Dev. PD JUN PY 2014 VL 60 IS 3 BP 179 EP 186 PG 8 WC Agriculture, Dairy & Animal Science; Reproductive Biology SC Agriculture; Reproductive Biology GA AK2TF UT WOS:000338271700002 PM 24583807 ER PT J AU Wittig, JH Richmond, BJ AF Wittig, John H., Jr. Richmond, Barry J. TI Monkeys rely on recency of stimulus repetition when solving short-term memory tasks SO LEARNING & MEMORY LA English DT Article ID INFERIOR TEMPORAL CORTEX; VISUAL WORKING-MEMORY; RECOGNITION MEMORY; LONG-TERM; FAMILIARITY; MACAQUE; MECHANISMS; ANTERIOR; REPRESENTATION; NEURONS AB Seven monkeys performed variants of two short-term memory tasks that others have used to differentiate between selective and nonselective memory mechanisms. The first task was to view a list of sequentially presented images and identify whether a test matched any image from the list, but not a distractor from a preceding list. Performance was best when the test matched the most recently presented image. Response rates depended linearly on recency of repetition whether the test matched a sample from the current list or a distractor from a preceding list, suggesting nonselective memorization of all images viewed instead of just the sample images. The second task was to remember just the first image in a list selectively and ignore subsequent distractors. False alarms occurred frequently when the test matched a distractor presented near the beginning of the sequence. In a pilot experiment, response rates depended linearly on recency of repetition irrespective of whether the test matched the first image or a distractor, again suggesting nonselective memorization of all images instead of just the first image. Modification of the second task improved recognition of the first image, but did not abolish use of recency. Monkeys appear to perform nonspatial visual short-term memory tasks often ( or exclusively) using a single, nonselective, memory mechanism that conveys the recency of stimulus repetition. C1 [Wittig, John H., Jr.; Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bldg 9, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov FU Intramural Research Program of the National Institute of Mental Health FX We thank Adin Horovitz and Evan Masseau for assisting with data collection, and Mark Eldridge and Brian Scott for their critical comments that helped improve the manuscript. The views expressed in this article do not necessarily represent the views of the NIMH, NIH, or the US Government. This study was supported by the Intramural Research Program of the National Institute of Mental Health. NR 34 TC 3 Z9 3 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1072-0502 EI 1549-5485 J9 LEARN MEMORY JI Learn. Mem. PD JUN PY 2014 VL 21 IS 6 BP 325 EP 333 DI 10.1101/lm.034181.113 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AK5ZM UT WOS:000338506200004 PM 25171424 ER PT J AU Bugreev, DV Huang, F Mazina, OM Pezza, RJ Voloshin, ON Camerini-Otero, RD Mazin, AV AF Bugreev, Dmitry V. Huang, Fei Mazina, Olga M. Pezza, Roberto J. Voloshin, Oleg N. Camerini-Otero, R. Daniel Mazin, Alexander V. TI HOP2-MND1 modulates RAD51 binding to nucleotides and DNA SO NATURE COMMUNICATIONS LA English DT Article ID DOUBLE-STRAND BREAK; COLI RECA PROTEIN; MEIOTIC RECOMBINATION; HOMOLOGOUS RECOMBINATION; COMPLEX-FORMATION; ATP HYDROLYSIS; HOP2 PROTEIN; MEIOSIS; REPAIR; DMC1 AB The HOP2-MND1 heterodimer is required for progression of homologous recombination in eukaryotes. In vitro, HOP2-MND1 stimulates the DNA strand exchange activities of RAD51 and DMC1. We demonstrate that HOP2-MND1 induces changes in the conformation of RAD51 that profoundly alter the basic properties of RAD51. HOP2-MND1 enhances the interaction of RAD51 with nucleotide cofactors and modifies its DNA-binding specificity in a manner that stimulates DNA strand exchange. It enables RAD51 DNA strand exchange in the absence of divalent metal ions required for ATP binding and offsets the effect of the K133A mutation that disrupts ATP binding. During nucleoprotein formation HOP2-MND1 helps to load RAD51 on ssDNA restricting its dsDNA-binding and during the homology search it promotes dsDNA binding removing the inhibitory effect of ssDNA. The magnitude of the changes induced in RAD51 defines HOP2-MND1 as a 'molecular trigger' of RAD51 DNA strand exchange. C1 [Bugreev, Dmitry V.; Huang, Fei; Mazina, Olga M.; Mazin, Alexander V.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA. [Pezza, Roberto J.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Dept Cell Biol, Oklahoma City, OK 73104 USA. [Voloshin, Oleg N.; Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Camerini-Otero, RD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. EM camerini@mail.nih.gov; amazin@drexelmed.edu FU NIH [CA100839, DA033981, MH097512, GM103636]; Leukemia and Lymphoma Society Scholar Award [1054-09]; W.M. Keck Foundation Award; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank P. Sung (Yale) for the hRAD51 expression vector. We thank members of the Camerini-Otero and Mazin labs for comments and discussion. This work was supported by the NIH grants CA100839, DA033981, MH097512, the Leukemia and Lymphoma Society Scholar Award 1054-09, W.M. Keck Foundation Award (to A. V. M.), the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (to R.D.C.-O.), and the NIH grant GM103636 (to R.J.P.). NR 57 TC 12 Z9 12 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2014 VL 5 AR 4198 DI 10.1038/ncomms5198 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AL0TC UT WOS:000338838700023 PM 24943459 ER PT J AU Cammas, A Sanchez, BJ Lian, XJ Dormoy-Raclet, V van der Giessen, K de Silanes, IL Ma, J Wilusz, C Richardson, J Gorospe, M Millevoi, S Giovarelli, M Gherzi, R Di Marco, S Gallouzi, IE AF Cammas, Anne Sanchez, Brenda Janice Lian, Xian Jin Dormoy-Raclet, Virginie van der Giessen, Kate Lopez de Silanes, Isabel Ma, Jennifer Wilusz, Carol Richardson, John Gorospe, Myriam Millevoi, Stefania Giovarelli, Matteo Gherzi, Roberto Di Marco, Sergio Gallouzi, Imed-Eddine TI Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation SO NATURE COMMUNICATIONS LA English DT Article ID BINDING PROTEIN HUR; AU-RICH ELEMENTS; EMBRYONIC-DEVELOPMENT; CELL DIFFERENTIATION; GENE-EXPRESSION; HEAT-SHOCK; DECAY; STABILIZATION; DEGRADATION; PHOSPHORYLATION AB HuR promotes myogenesis by stabilizing the MyoD, myogenin and p21 mRNAs during the fusion of muscle cells to form myotubes. Here we show that HuR, via a novel mRNA destabilizing activity, promotes the early steps of myogenesis by reducing the expression of the cell cycle promoter nucleophosmin (NPM). Depletion of HuR stabilizes the NPM mRNA, increases NPM protein levels and inhibits myogenesis, while its overexpression elicits the opposite effects. NPM mRNA destabilization involves the association of HuR with the decay factor KSRP as well as the ribonuclease PARN and the exosome. The C terminus of HuR mediates the formation of the HuR-KSRP complex and is sufficient for maintaining a low level of the NPM mRNA as well as promoting the commitment of muscle cells to myogenesis. We therefore propose a model whereby the downregulation of the NPM mRNA, mediated by HuR, KSRP and its associated ribonucleases, is required for proper myogenesis. C1 [Cammas, Anne; Sanchez, Brenda Janice; Lian, Xian Jin; Dormoy-Raclet, Virginie; van der Giessen, Kate; Ma, Jennifer; Di Marco, Sergio; Gallouzi, Imed-Eddine] McGill Univ, Dept Biochem, Goodman Canc Ctr, Montreal, PQ H3G 1Y6, Canada. [Cammas, Anne; Millevoi, Stefania] Ctr Rech Cancerol Toulouse, INSERM, UMR 1037, F-31432 Toulouse, France. [Lopez de Silanes, Isabel] Spanish Natl Canc Res Ctr CNIO Telomeres & Telome, Mol Oncol Program, Madrid 28029, Spain. [Wilusz, Carol] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Richardson, John] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. [Gorospe, Myriam] NIA, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Giovarelli, Matteo; Gherzi, Roberto] Ist Nazl Ric Cancro IST, Lab Gene Express Regulat, I-16132 Genoa, Italy. RP Gallouzi, IE (reprint author), McGill Univ, Dept Biochem, Goodman Canc Ctr, McIntyre Bldg Room 915B, Montreal, PQ H3G 1Y6, Canada. EM imed.gallouzi@mcgill.ca RI CAMMAS, Anne/M-7238-2014; Millevoi, Stefania/M-7244-2014; Giovarelli, Matteo/K-1573-2016; Lopez de Silanes, Isabel/K-4962-2015; OI Millevoi, Stefania/0000-0003-1659-3552; Lopez de Silanes, Isabel/0000-0001-6762-9792; Di Marco, Sergio/0000-0002-4039-0600 FU Canderal scholarship for PDFs; Peter Quinlan Fellowship in Oncolgy; Canadian Cancer Society; CIHR [MOP-89798]; NIA-IRP, NIH; AIRC [IG 2010-2012]; AICR [10-0527] FX We thank Dr C. von Roretz for critical review of this manuscript and insightful discussion. We are grateful to Veronique Sauve and Dr Kalle Gehring for their help with the BIACORE experiments. A. C. is a recipient of the Canderal scholarship for PDFs (2010-2011) as well as the Peter Quinlan Fellowship in Oncolgy (2011-2012). V.D.-R. is a Research Fellow of the Terry Fox foundation through an award from the Canadian Cancer Society (former National Cancer Institute of Canada). This work was supported by a CIHR (MOP-89798) operating grant to I.-E. G. M. G. is supported by the NIA-IRP, NIH. R. G. is supported by grants from AIRC (IG 2010-2012) and AICR (No. 10-0527). I.-E. G. is a recipient of a TierII Canada Research Chair. NR 59 TC 9 Z9 9 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2014 VL 5 AR 4190 DI 10.1038/ncomms5190 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AL0TC UT WOS:000338838700015 PM 24969639 ER PT J AU Wang, HC DeRose, EF London, RE Shears, SB AF Wang, Huanchen DeRose, Eugene F. London, Robert E. Shears, Stephen B. TI IP6K structure and the molecular determinants of catalytic specificity in an inositol phosphate kinase family SO NATURE COMMUNICATIONS LA English DT Article ID DIPHOSPHOINOSITOL POLYPHOSPHATE PHOSPHOHYDROLASE; HEXAKISPHOSPHATE KINASE; CRYSTAL-STRUCTURE; 1,3,4,5,6-PENTAKISPHOSPHATE 2-KINASE; 1,4,5-TRISPHOSPHATE 3-KINASE; GENE DELETION; CELL-SURVIVAL; PYROPHOSPHATES; MULTIKINASE; METABOLISM AB Inositol trisphosphate kinases (IP3Ks) and inositol hexakisphosphate kinases (IP6Ks) each regulate specialized signalling activities by phosphorylating either InsP(3) or InsP(6) respectively. The molecular basis for these different kinase activities can be illuminated by a structural description of IP6K. Here we describe the crystal structure of an Entamoeba histolytica hybrid IP6K/IP3K, an enzymatic parallel to a 'living fossil'. Through molecular modelling and mutagenesis, we extrapolated our findings to human IP6K2, which retains vestigial IP3K activity. Two structural elements, an alpha-helical pair and a rare, two-turn 3(10) helix, together forge a substrate-binding pocket with an open clamshell geometry. InsP(6) forms substantial contacts with both structural elements. Relative to InsP(6), enzyme-bound InsP(3) rotates 55 degrees closer to the a-helices, which provide most of the protein's interactions with InsP(3). These data reveal the molecular determinants of IP6K activity, and suggest an unusual evolutionary trajectory for a primordial kinase that could have favored efficient bifunctionality, before propagation of separate IP3Ks and IP6Ks. C1 [Wang, Huanchen; Shears, Stephen B.] NIEHS, Inositol Signaling Grp, NIH, Res Triangle Pk, NC 27709 USA. [DeRose, Eugene F.; London, Robert E.] NIEHS, Nucl Magnet Resonance Grp, NIH, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), NIEHS, Inositol Signaling Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Programme of the NIH, National Institute of Environmental Health Sciences. We thank T. M. Hall and L. C. Pedersen for discussions and critical reading of the manuscript, the NIEHS Collaborative crystallography group, the Advanced Photon Source (APS) Southeast Regional Collaborative Access Team (SER-CAT) 22-ID and 22-BM beam lines for assistance with crystallographic data collection. NR 55 TC 9 Z9 10 U1 4 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUN PY 2014 VL 5 AR 4178 DI 10.1038/ncomms5178 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AL0TC UT WOS:000338838700003 PM 24956979 ER PT J AU Buchanan, ND Block, R Smith, AW Tai, E AF Buchanan, Natasha D. Block, Rebecca Smith, Ashley Wilder Tai, Eric TI Psychosocial Barriers and Facilitators to Clinical Trial Enrollment and Adherence for Adolescents With Cancer SO PEDIATRICS LA English DT Article DE adherence; adolescent; cancer survivors; clinical trial; enrollment; psychosocial ID EDUCATION SHARE PROGRAM; YOUNG-ADULT CANCER; CHILDHOOD-CANCER; LYMPHOBLASTIC-LEUKEMIA; SURVIVOR HEALTH; CONSENT FORMS; PARTICIPATION; CHILDREN; ISSUES; EXPERIENCES AB Adolescents (aged 15-19 years) have not experienced the same survival gains as children and older adults diagnosed with cancer. Poor clinical trial enrollment and adherence rates among adolescents may account for some of this disparity. Although biological, regulatory, systemic, and practice-related challenges to clinical trial enrollment and adherence have been examined, studies of psychosocial factors, which can serve as barriers or facilitators to enrollment and adherence, are limited. To bring attention to these psychological factors, we reviewed existing literature on psychosocial barriers and facilitators that can affect an adolescent's decision to enroll and adhere to a clinical trial. We also provide potential strategies to address psychosocial factors affecting clinical trial accrual and adherence. C1 [Buchanan, Natasha D.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Epidemiol & Appl Res Branch, Atlanta, GA 30341 USA. [Tai, Eric] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Comprehens Canc Control Branch, Atlanta, GA 30341 USA. [Block, Rebecca] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Smith, Ashley Wilder] NCI, Outcomes Res Branch, Bethesda, MD 20892 USA. RP Buchanan, ND (reprint author), Ctr Dis Control & Prevent, 4770 Buford Highway NE,MS K-55, Atlanta, GA 30341 USA. EM nbuchanan@cdc.gov NR 64 TC 3 Z9 3 U1 1 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JUN PY 2014 VL 133 SU 3 BP S123 EP S130 DI 10.1542/peds.2014-01221 PG 8 WC Pediatrics SC Pediatrics GA AK3TG UT WOS:000338347000008 PM 24918211 ER PT J AU Zhang, XX Chen, L Dang, X Liu, JL Ito, Y Sun, WJ AF Zhang, Xinxin Chen, Lin Dang, Xuan Liu, Jianli Ito, Yoichiro Sun, Wenji TI Neuroprotective Effects of Total Steroid Saponins on Cerebral Ischemia Injuries in an Animal Model of Focal Ischemia/Reperfusion SO PLANTA MEDICA LA English DT Article DE Dioscorea zingiberensis; Dioscoreaceae; steroid saponins; middle cerebral artery occlusion; ischemia-reperfusion; anti-edema; anti-oxidative ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; ARTERY OCCLUSION; ACTIVATION; STROKE; RATS; REPERFUSION; ERK1/2; BLOOD AB Total steroid saponins isolated from Dioscorea zingiberensis are a unique traditional Chinese medicine known for its potential usage in various types of diseases. However, there is little evidence about its neuroprotective effect in transient focal ischemia-reperfusion cerebral injury. Therefore, the current study was carried out to investigate the effect of total steroid saponins on neuroprotection and its potential mechanisms in the rat ischemia-reperfusion model by middle cerebral artery occlusion for 90 min. The rats were each treated with total steroid saponins (30 mg/kg, 10 mg/kg, and 3 mg/kg) or nimodipine (20 mg/kg) daily for 6 days before middle cerebral artery occlusion. Then, the neurological deficit score, cerebral infarct volume, and brain water content were measured at 24 h after reperfusion. Meanwhile, the histopathological changes and AQP-4 protein activities were examined in hippocampal CA1 and the cortex of ipsilateral ischemic cerebral hemisphere by hematoxylin-eosin staining and immunohistochemistry, respectively. The indices of oxidative stress in the serum were also obtained, and NF-kappa B and ERK 1/2 protein expressions in the injured brain were evaluated by Western blotting. The results indicated that the pre-treatment with these drugs not only significantly reduced cerebral infarct volume, brain water content and improved neurological deficit score, but also restored neuronal morphology and decreased the AQP-4 positive cells in CA1 and the cortex. Moreover, it markedly restored the level of oxidant stress markers (CAT, SOD, MDA, NO and iNOS) to their normal range in serum. In addition, the increased NF-kappa B and ERK 1/2 protein expressions were alleviated as compared with the ischemia-reperfusion group. These findings demonstrate that total steroid saponins exhibit promising neuroprotection effects against the transient focal ischemia-reperfusion cerebral injury in the rat experimental model and the underlying mechanisms might be mediated through inhibition of anti-edema as well as anti-oxidative effects by inactivation of NF-kappa B and ERK 1/2 signalling pathway. C1 [Zhang, Xinxin; Chen, Lin; Dang, Xuan; Liu, Jianli; Sun, Wenji] NW Univ Xian, Biomed Key Lab Shaanxi Prov, Xian 710069, Peoples R China. [Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM itoy@nhlbi.nih.gov; cxbml@nwu.edu.cn FU Intramural NIH HHS [Z99 HL999999] NR 28 TC 5 Z9 6 U1 2 U2 9 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 EI 1439-0221 J9 PLANTA MED JI Planta Med. PD JUN PY 2014 VL 80 IS 8-9 BP 637 EP 644 DI 10.1055/s-0034-1368584 PG 8 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AJ9NX UT WOS:000338039800006 PM 24963614 ER PT J AU Ellis, TC Jain, S Linowski, AK Rike, K Bestor, A Rosa, PA Halpern, M Kurhanewicz, S Jewett, MW AF Ellis, Tisha Choudhury Jain, Sunny Linowski, Angelika K. Rike, Kelli Bestor, Aaron Rosa, Patricia A. Halpern, Micah Kurhanewicz, Stephanie Jewett, Mollie W. TI In Vivo Expression Technology Identifies a Novel Virulence Factor Critical for Borrelia burgdorferi Persistence in Mice (vol 9, e1003567, 2013) SO PLOS PATHOGENS LA English DT Correction ID LYME-DISEASE SPIROCHETE; VLSE ANTIGENIC VARIATION; LINEAR PLASMIDS 1P25; GENE-EXPRESSION; BACTERIAL VIRULENCE; MAMMALIAN HOST; INFECTIOUS CYCLE; TICK VECTOR; IMMUNO-PCR; T-CELLS AB Analysis of the transcriptome of Borrelia burgdorferi, the causative agent of Lyme disease, during infection has proven difficult due to the low spirochete loads in the mammalian tissues. To overcome this challenge, we have developed an In Vivo Expression Technology (IVET) system for identification of B. burgdorferi genes expressed during an active murine infection. Spirochetes lacking linear plasmid (lp) 25 are non-infectious yet highly transformable. Mouse infection can be restored to these spirochetes by expression of the essential lp25-encoded pncA gene alone. Therefore, this IVET-based approach selects for in vivo-expressed promoters that drive expression of pncA resulting in the recovery of infectious spirochetes lacking lp25 following a three week infection in mice. Screening of approximately 15,000 clones in mice identified 289 unique in vivo-expressed DNA fragments from across all 22 replicons of the B. burgdorferi B31 genome. The in vivo-expressed candidate genes putatively encode proteins in various functional categories including antigenicity, metabolism, motility, nutrient transport and unknown functions. Candidate gene bbk46 on essential virulence plasmid lp36 was found to be highly induced in vivo and to be RpoS-independent. The bbk46 gene was dispensable for B. burgdorferi infection in mice. Our findings highlight the power of the IVET-based approach for identification of B. burgdorferi in vivo-expressed genes, which might not be discovered using other genome-wide gene expression methods. Further investigation of the novel in vivo-expressed candidate genes will contribute to advancing the understanding of molecular mechanisms of B. burgdorferi survival and pathogenicity in the mammalian host. C1 [Ellis, Tisha Choudhury; Jain, Sunny; Linowski, Angelika K.; Rike, Kelli; Halpern, Micah; Kurhanewicz, Stephanie; Jewett, Mollie W.] Univ Cent Florida Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32827 USA. [Bestor, Aaron; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Jewett, MW (reprint author), Univ Cent Florida Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32827 USA. EM Mollie.Jewett@ucf.edu FU NIAID NIH HHS [K22 AI081730, R01 AI099094] NR 84 TC 1 Z9 1 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2014 VL 10 IS 6 AR e1004260 DI 10.1371/journal.ppat.1004260 PG 18 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AK1SV UT WOS:000338197400058 PM 24950221 ER PT J AU Magadan, JG Altman, MO Ince, WL Hickman, HD Stevens, J Chevalier, A Baker, D Wilson, PC Ahmed, R Bennink, JR Yewdell, JW AF Magadan, Javier G. Altman, Meghan O. Ince, William L. Hickman, Heather D. Stevens, James Chevalier, Aaron Baker, David Wilson, Patrick C. Ahmed, Rafi Bennink, Jack R. Yewdell, Jonathan W. TI Biogenesis of Influenza A Virus Hemagglutinin Cross-Protective Stem Epitopes SO PLOS PATHOGENS LA English DT Article ID STALK-SPECIFIC ANTIBODIES; MEMORY B-CELLS; MONOCLONAL-ANTIBODIES; INTRACELLULAR-TRANSPORT; RECEPTOR-BINDING; IMMUNE-RESPONSE; GLYCOPROTEIN; NEUTRALIZATION; VACCINATION; TRIMERIZATION AB Antigenic variation in the globular domain of influenza A virus (IAV) hemagglutinin (HA) precludes effective immunity to this major human pathogen. Although the HA stem is highly conserved between influenza virus strains, HA stem-reactive antibodies (StRAbs) were long considered biologically inert. It is now clear, however, that StRAbs reduce viral replication in animal models and protect against pathogenicity and death, supporting the potential of HA stem-based immunogens as drift-resistant vaccines. Optimally designing StRAb-inducing immunogens and understanding StRAb effector functions require thorough comprehension of HA stem structure and antigenicity. Here, we study the biogenesis of HA stem epitopes recognized in cells infected with various drifted IAV H1N1 strains using mouse and human StRAbs. Using a novel immunofluorescence (IF)-based assay, we find that human StRAbs bind monomeric HA in the endoplasmic reticulum (ER) and trimerized HA in the Golgi complex (GC) with similar high avidity, potentially good news for producing effective monomeric HA stem immunogens. Though HA stem epitopes are nestled among several N-linked oligosaccharides, glycosylation is not required for full antigenicity. Rather, as N-linked glycans increase in size during intracellular transport of HA through the GC, StRAb binding becomes temperature-sensitive, binding poorly to HA at 4 degrees C and well at 37 degrees C. A de novo designed, 65-residue protein binds the mature HA stem independently of temperature, consistent with a lack of N-linked oligosaccharide steric hindrance due to its small size. Likewise, StRAbs bind recombinant HA carrying simple N-linked glycans in a temperature-independent manner. Chemical cross-linking experiments show that N-linked oligosaccharides likely influence StRAb binding by direct local effects rather than by globally modifying the conformational flexibility of HA. Our findings indicate that StRAb binding to HA is precarious, raising the possibility that sufficient immune pressure on the HA stem region could select for viral escape mutants with increased steric hindrance from N-linked glycans. C1 [Magadan, Javier G.; Altman, Meghan O.; Ince, William L.; Hickman, Heather D.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Stevens, James] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. [Chevalier, Aaron; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Wilson, Patrick C.] Univ Chicago, Knapp Ctr Lupus & Immunol Res, Dept Med, Sect Rheumatol,Comm Immunol, Chicago, IL 60637 USA. [Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Emory Vaccine Ctr, Atlanta, GA 30322 USA. RP Magadan, JG (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM jyewdell@niaid.nih.gov RI Altman, Meghan/J-2975-2015 OI Altman, Meghan/0000-0002-8910-9074 FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 2 Z9 2 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2014 VL 10 IS 6 AR e1004204 DI 10.1371/journal.ppat.1004204 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AK1SV UT WOS:000338197400038 PM 24945804 ER PT J AU Sully, EK Malachowa, N Elmore, BO Alexander, SM Femling, JK Gray, BM DeLeo, FR Otto, M Cheung, AL Edwards, BS Sklar, LA Horswill, AR Hall, PR Gresham, HD AF Sully, Erin K. Malachowa, Natalia Elmore, Bradley O. Alexander, Susan M. Femling, Jon K. Gray, Brian M. DeLeo, Frank R. Otto, Michael Cheung, Ambrose L. Edwards, Bruce S. Sklar, Larry A. Horswill, Alexander R. Hall, Pamela R. Gresham, Hattie D. TI Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus aureus Promotes Host Defense with Minimal Impact on Resistance SO PLOS PATHOGENS LA English DT Article ID GLOBAL GENE-EXPRESSION; NADPH OXIDASE; LYTTR DOMAIN; VIRULENCE; SKIN; ANTIBIOTICS; IDENTIFICATION; INFECTION; DISCOVERY; DISEASE AB Bacterial signaling systems are prime drug targets for combating the global health threat of antibiotic resistant bacterial infections including those caused by Staphylococcus aureus. S. aureus is the primary cause of acute bacterial skin and soft tissue infections (SSTIs) and the quorum sensing operon agr is causally associated with these. Whether efficacious chemical inhibitors of agr signaling can be developed that promote host defense against SSTIs while sparing the normal microbiota of the skin is unknown. In a high throughput screen, we identified a small molecule inhibitor (SMI), savirin (S. aureus virulence inhibitor) that disrupted agr-mediated quorum sensing in this pathogen but not in the important skin commensal Staphylococcus epidermidis. Mechanistic studies employing electrophoretic mobility shift assays and a novel AgrA activation reporter strain revealed the transcriptional regulator AgrA as the target of inhibition within the pathogen, preventing virulence gene upregulation. Consistent with its minimal impact on exponential phase growth, including skin microbiota members, savirin did not provoke stress responses or membrane dysfunction induced by conventional antibiotics as determined by transcriptional profiling and membrane potential and integrity studies. Importantly, savirin was efficacious in two murine skin infection models, abating tissue injury and selectively promoting clearance of agr+ but not Delta agr bacteria when administered at the time of infection or delayed until maximal abscess development. The mechanism of enhanced host defense involved in part enhanced intracellular killing of agr+ but not Delta agr in macrophages and by low pH. Notably, resistance or tolerance to savirin inhibition of agr was not observed after multiple passages either in vivo or in vitro where under the same conditions resistance to growth inhibition was induced after passage with conventional antibiotics. Therefore, chemical inhibitors can selectively target AgrA in S. aureus to promote host defense while sparing agr signaling in S. epidermidis and limiting resistance development. C1 [Sully, Erin K.; Alexander, Susan M.; Gray, Brian M.; Gresham, Hattie D.] New Mexico Vet Affairs Med Ctr, Res Serv, Albuquerque, NM 87108 USA. [Sully, Erin K.; Gresham, Hattie D.] Univ New Mexico, Sch Med, Div Infect Dis, Dept Internal Med, Albuquerque, NM 87131 USA. [Malachowa, Natalia; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. [Elmore, Bradley O.; Gray, Brian M.; Hall, Pamela R.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. [Femling, Jon K.] Univ New Mexico, Dept Emergency Med, Albuquerque, NM 87131 USA. [Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. [Cheung, Ambrose L.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Microbiol, Hanover, NH 03756 USA. [Edwards, Bruce S.; Sklar, Larry A.] Univ New Mexico, Sch Med, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Edwards, Bruce S.; Sklar, Larry A.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA. [Horswill, Alexander R.] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA. RP Sully, EK (reprint author), New Mexico Vet Affairs Med Ctr, Res Serv, Albuquerque, NM 87108 USA. EM phall@salud.unm.edu RI Hall, Pamela/O-5402-2016; OI Hall, Pamela/0000-0003-2367-3382; DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115 FU Department of Veterans Affairs; Intramural Research Program of the NIAID, NIH; NIH [X01MH078952, R01 AI091917, U54MH084690, U54MH074425, AT007052]; Infectious Diseases and Inflammation Training grant [T32 AI007538]; IRACDA [5K12 GM088021] FX This work was supported by the Department of Veterans Affairs (HDG), the Intramural Research Program of the NIAID, NIH (FRD, MO), and NIH grants X01MH078952 (HDG), R01 AI091917 (PRH), U54MH084690 (LAS), U54MH074425 (LAS), and AT007052 (ARH). EKS was supported by T32 AI007538 Infectious Diseases and Inflammation Training grant, and BMG was supported by IRACDA training grant 5K12 GM088021. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 57 Z9 58 U1 11 U2 56 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2014 VL 10 IS 6 AR e1004174 DI 10.1371/journal.ppat.1004174 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA AK1SV UT WOS:000338197400017 PM 24945495 ER PT J AU Slugina, MA Boris, KV Kakimzhanova, AA Kochieva, EZ AF Slugina, M. A. Boris, K. V. Kakimzhanova, A. A. Kochieva, E. Z. TI Intraspecific polymorphism of the sucrose synthase genes in Russian and Kazakh potato cultivars SO RUSSIAN JOURNAL OF GENETICS LA English DT Article ID SOLANUM-TUBEROSUM; PLANTS AB In 12 different Russian and Kazakh potato cultivars, the polymorphism of the glucosyltransferase domain of the sucrose synthase gene was first examined, as well as the polymorphism of the sucrose synthase domain fragment of the same gene in the potato cultivars of Kazakh breed. It was demonstrated that the examined sequences contained point mutations, as well as insertions and deletions, including those not described earlier. Amino acid substitutions specific to heat- and drought-tolerant varieties were also identified and could be associated with the development of abiotic stress resistance. C1 [Slugina, M. A.; Boris, K. V.; Kochieva, E. Z.] Russian Acad Sci, Bioengn Ctr, Moscow 117312, Russia. [Boris, K. V.] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119991, Russia. [Kakimzhanova, A. A.] Natl Biotechnol Ctr, Astana 010000, Kazakhstan. [Kochieva, E. Z.] Moscow MV Lomonosov State Univ, Dept Biotechnol, Fac Biol, Moscow 119991, Russia. RP Slugina, MA (reprint author), Russian Acad Sci, Bioengn Ctr, Moscow 117312, Russia. EM docboris@mail.ru OI Kakimzhanova, Almagul/0000-0002-7797-6867 FU Russian Foundation for Basic Research [12-04-32291]; Program of the Presidium of the Russian Academy of Sciences (Molecular and Cellular Biology) FX This study was supported by the Russian Foundation for Basic Research (grant no. 12-04-32291) and the Program of the Presidium of the Russian Academy of Sciences (Molecular and Cellular Biology). NR 14 TC 2 Z9 2 U1 0 U2 4 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 1022-7954 EI 1608-3369 J9 RUSS J GENET+ JI Russ. J. Genet. PD JUN PY 2014 VL 50 IS 6 BP 593 EP 597 DI 10.1134/S1022795414060118 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA AK2VT UT WOS:000338278400007 ER PT J AU Zhang, Y Chang, YCE Louis, JM Wang, YF Harrison, RW Weber, IT AF Zhang, Ying Chang, Yu-Chung E. Louis, John M. Wang, Yuan-Fang Harrison, Robert W. Weber, Irene T. TI Structures of Darunavir-Resistant HIV-1 Protease Mutant Reveal Atypical Binding of Darunavir to Wide Open Flaps SO ACS CHEMICAL BIOLOGY LA English DT Article ID RESOLUTION CRYSTAL-STRUCTURES; CLINICAL INHIBITORS; DRUG-RESISTANCE; IN-VITRO; TMC114; GENERATION; STABILITY; VARIANTS; SITES AB The molecular basis for high resistance to clinical inhibitors of HIV-1 protease (PR) was examined for the variant designated PRP51 that was selected for resistance to darunavir (DRV). High resolution crystal structures of PRP51 with the active site D25N mutation revealed a ligand-free form and an inhibitor-bound form showing a unique binding site and orientation for DRV. This inactivating mutation is known to increase the dimer dissociation constant and decrease DRV affinity of PR The PRP51-D25N dimers were in the open conformation with widely separated flaps, as reported for other highly resistant variants. PRP51-D25N dimer bound two DRV molecules and showed larger separation of 8.7 angstrom between the closest atoms of the two flaps compared with 4.4 angstrom for the ligand-free structure of this mutant. The ligand-free structure, however, lacked van der Waals contacts between Ile50 and Pro81' from the other subunit in the dimer, unlike the majority of PR structures. DRV is bound inside the active site cavity; however, the inhibitor is oriented almost perpendicular to its typical position and exhibits only 2 direct hydrogen bond and two water-mediated interactions with atoms of PRP51-D25N compared with 11 hydrogen bond interactions seen for DRV bound in the typical position in wild-type enzyme. The atypical location of DRV may provide opportunities for design of novel inhibitors targeting the open conformation of PR drug-resistant mutants. C1 [Zhang, Ying; Weber, Irene T.] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. [Chang, Yu-Chung E.; Wang, Yuan-Fang; Harrison, Robert W.; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. [Harrison, Robert W.] Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA. [Louis, John M.] NIDDK, Chem Phys Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Weber, IT (reprint author), Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. EM iweber@gsu.edu FU National Institute of General Medical Sciences of the National Institutes of Health [U01GM062920]; Georgia State University Center for Diagnostics and Therapeutics Doctoral Fellowship; NIDDK; Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH; U.S. Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38] FX This work was supported in part by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number U01GM062920 (I.T.W. and R.W.H.) and by the Georgia State University Center for Diagnostics and Therapeutics Doctoral Fellowship (Y.Z.) and by the Intramural Research Program of the NIDDK and the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. X-ray data were collected at the Southeast Regional Collaborative Access Team (SER-CAT) beamline 22BM at the Advanced Photon Source, Argonne National Laboratory. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under Contract No. W-31-109-Eng-38. Darunavir was obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH. NR 34 TC 7 Z9 7 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JUN PY 2014 VL 9 IS 6 BP 1351 EP 1358 DI 10.1021/cb4008875 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AJ7IN UT WOS:000337870500017 PM 24738918 ER PT J AU Nikolaidis, NM White, MR Allen, K Tripathi, S Qi, L McDonald, B Taubenberger, J Seaton, BA McCormack, FX Crouch, EC Hartshorn, KL AF Nikolaidis, Nikolaos M. White, Mitchell R. Allen, Kimberly Tripathi, Shweta Qi, Li McDonald, Barbara Taubenberger, Jeffery Seaton, Barbara A. McCormack, Francis X. Crouch, Erika C. Hartshorn, Kevan L. TI Mutations flanking the carbohydrate binding site of surfactant protein D confer antiviral activity for pandemic influenza A viruses SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE collectin; innate immunity; mouse ID LECTIN DOMAINS; HEMAGGLUTININ; COLLECTINS; MICE; RECOGNITION; INHIBITION; INFECTION; EMPHYSEMA; LIGANDS AB We recently reported that a trimeric neck and carbohydrate recognition domain (NCRD) fragment of human surfactant protein D (SP- D), a host defense lectin, with combinatorial substitutions at the 325 and 343 positions (D325A + R343V) exhibits markedly increased antiviral activity for seasonal strains of influenza A virus (IAV). The NCRD binds to glycan- rich viral envelope proteins including hemagglutinin (HA). We now show that replacement of D325 with serine to create D325S + R343V provided equal or increased neutralizing activity compared with D325A + R343V. The activity of the double mutants was significantly greater than that of either single mutant (D325A/S or R343V). D325A + R343V and D325S + R343V also strongly inhibited HA activity, and markedly aggregated, the 1968 pandemic H3N2 strain, Aichi68. D325S + R343V significantly reduced viral loads and mortality of mice infected with Aichi68, whereas wild- type SP- D NCRD did not. The pandemic H1N1 strains of 1918 and 2009 have only one N- linked glycan side on the head region of the HA and are fully resistant to inhibition by native SP- D. Importantly, we now show that D325A + R343V and D325S + R343V inhibited Cal09 H1N1 and related strains, and reduced uptake of Ca109 by epithelial cells. Inhibition of Cal09 was mediated by the lectin activity of the NCRDs. All known human pandemic strains have at least one glycan attachment on the top or side of the HA head, and our results indicate that they may be susceptible to inhibition by modified host defense lectins. C1 [Nikolaidis, Nikolaos M.; McCormack, Francis X.] Univ Cincinnati, Div Pulm & Crit Care Med, Cincinnati, OH USA. [White, Mitchell R.; Tripathi, Shweta; Hartshorn, Kevan L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Seaton, Barbara A.] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. [Allen, Kimberly; McDonald, Barbara; Crouch, Erika C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Qi, Li; Taubenberger, Jeffery] NIAID, Bethesda, MD 20892 USA. RP Hartshorn, KL (reprint author), Boston Univ, Sch Med, EBRC 414,650 Albany St, Boston, MA 02118 USA. EM khartsho@bu.edu OI McCormack, Francis/0000-0001-7168-9464 FU National Institutes of Health [PO1-AI-083222, RO1-HL-069031]; National Institute of Allergy and Infectious Diseases FX This work was supported by National Institutes of Health Grants PO1-AI-083222 to B. A. Seaton, K. L. Hartshorn, and F. McCormack; and RO1-HL-069031 to K. L. Hartshorn; and by National Institute of Allergy and Infectious Diseases intramural research support to L. Qi and J. Taubenberger. NR 29 TC 2 Z9 2 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUN PY 2014 VL 306 IS 11 BP L1036 EP L1044 DI 10.1152/ajplung.00035.2014 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA AJ7SE UT WOS:000337896600009 PM 24705721 ER PT J AU Stober, VP Szczesniak, C Childress, Q Heise, RL Bortner, C Hollingsworth, JW Neuringer, IP Palmer, SM Garantziotis, S AF Stober, Vandy P. Szczesniak, Christopher Childress, Quiana Heise, Rebecca L. Bortner, Carl Hollingsworth, John W. Neuringer, Isabel P. Palmer, Scott M. Garantziotis, Stavros TI Bronchial epithelial injury in the context of alloimmunity promotes lymphocytic bronchiolitis through hyaluronan expression SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE endoplasmic reticulum stress; lung rejection ID ENDOPLASMIC-RETICULUM STRESS; HUMAN LUNG TRANSPLANTATION; AIRWAY; CELLS; DISEASE; INFLAMMATION; NAPHTHALENE; FIBROSIS; CYTOTOXICITY; METABOLITES AB Epithelial injury is often detected in lung allografts, however, its relation to rejection pathogenesis is unknown. We hypothesized that sterile epithelial injury can lead to alloimmune activation in the lung. We performed adoptive transfer of mismatched splenocytes into recombinant activating gene 1 (Rag1)-deficient mice to induce an alloimmune status and then exposed these mice to naphthalene to induce sterile epithelial injury. We evaluated lungs for presence of alloimmune lung injury, endoplasmic reticulum (ER) stress, and hyaluronan expression, examined the effect of ER stress induction on hyaluronan expression and lymphocyte trapping by bronchial epithelia in vitro, and examined airways from patients with bronchiolitis obliterans syndrome and normal controls histologically. We found that Rag1deficient mice that received mismatched splenocytes and naphthalene injection displayed bronchial epithelial ER stress, peribronchial hyaluronan expression, and lymphocytic bronchitis. Bronchial epithelial ER stress led to the expression of lymphocyte-trapping hyaluronan cables in vitro. Blockade of hyaluronan binding ameliorated naphthalene- induced lymphocytic bronchitis. ER stress was present histologically in > 40% of bronchial epithelia of BOS patients and associated with subepithelial hyaluronan deposition. We conclude that sterile bronchial epithelial injury in the context of alloimmunity can lead to sustained ER stress and promote allograft rejection through hyaluronan expression. C1 [Stober, Vandy P.; Szczesniak, Christopher; Childress, Quiana; Heise, Rebecca L.; Bortner, Carl; Garantziotis, Stavros] NIEHS, Res Triangle Pk, NC 27709 USA. [Hollingsworth, John W.; Palmer, Scott M.] Duke Univ, Med Ctr, Durham, NC USA. [Neuringer, Isabel P.] Univ North Carolina Hosp, Chapel Hill, NC USA. RP Garantziotis, S (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM garantziotis@niehs.nih.gov RI Heise, Rebecca/N-7797-2016; Garantziotis, Stavros/A-6903-2009 OI Heise, Rebecca/0000-0002-6602-6700; Garantziotis, Stavros/0000-0003-4007-375X FU Division of Intramural Research of the National Institutes of Health (NIH); National Institute of Environmental Health Sciences; NIH [ES-016126, ES-020350, HL-091140] FX Research was supported in part by the Division of Intramural Research of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences. J. W. Hollingsworth appreciates support provided by the NIH, including Grants ES-016126 and ES-020350. S. M. Palmer receives support by the NIH, including Grant HL-091140. NR 33 TC 7 Z9 7 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUN PY 2014 VL 306 IS 11 BP L1045 EP L1055 DI 10.1152/ajplung.00353.2013 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA AJ7SE UT WOS:000337896600010 PM 24748604 ER PT J AU Friesen, MC Locke, SJ Tornow, C Chen, YC Koh, DH Stewart, PA Purdue, M Colt, JS AF Friesen, Melissa C. Locke, Sarah J. Tornow, Carina Chen, Yu-Cheng Koh, Dong-Hee Stewart, Patricia A. Purdue, Mark Colt, Joanne S. TI Systematically Extracting Metal- and Solvent-Related Occupational Information from Free-Text Responses to Lifetime Occupational History Questionnaires SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE cadmium; chlorinated solvents; exposure assessment methodology; lead ID RENAL-CELL CARCINOMA; DECISION RULES; EXPOSURE; WHITE AB Objectives: Lifetime occupational history (OH) questionnaires often use open-ended questions to capture detailed information about study participants' jobs. Exposure assessors use this information, along with responses to job-and industry-specific questionnaires, to assign exposure estimates on a job-by-job basis. An alternative approach is to use information from the OH responses and the job-and industry-specific questionnaires to develop programmable decision rules for assigning exposures. As a first step in this process, we developed a systematic approach to extract the free-text OH responses and convert them into standardized variables that represented exposure scenarios. Methods: Our study population comprised 2408 subjects, reporting 11 991 jobs, from a case-control study of renal cell carcinoma. Each subject completed a lifetime OH questionnaire that included verbatim responses, for each job, to open-ended questions including job title, main tasks and activities (task), tools and equipment used (tools), and chemicals and materials handled (chemicals). Based on a review of the literature, we identified exposure scenarios (occupations, industries, tasks/tools/chemicals) expected to involve possible exposure to chlorinated solvents, trichloroethylene (TCE) in particular, lead, and cadmium. We then used a SAS macro to review the information reported by study participants to identify jobs associated with each exposure scenario; this was done using previously coded standardized occupation and industry classification codes, and a priori lists of associated key words and phrases related to possibly exposed tasks, tools, and chemicals. Exposure variables representing the occupation, industry, and task/tool/chemicals exposure scenarios were added to the work history records of the study respondents. Our identification of possibly TCE-exposed scenarios in the OH responses was compared to an expert's independently assigned probability ratings to evaluate whether we missed identifying possibly exposed jobs. Results: Our process added exposure variables for 52 occupation groups, 43 industry groups, and 46 task/tool/chemical scenarios to the data set of OH responses. Across all four agents, we identified possibly exposed task/tool/chemical exposure scenarios in 44-51% of the jobs in possibly exposed occupations. Possibly exposed task/tool/chemical exposure scenarios were found in a nontrivial 9-14% of the jobs not in possibly exposed occupations, suggesting that our process identified important information that would not be captured using occupation alone. Our extraction process was sensitive: for jobs where our extraction of OH responses identified no exposure scenarios and for which the sole source of information was the OH responses, only 0.1% were assessed as possibly exposed to TCE by the expert. Conclusions: Our systematic extraction of OH information found useful information in the task/chemicals/tools responses that was relatively easy to extract and that was not available from the occupational or industry information. The extracted variables can be used as inputs in the development of decision rules, especially for jobs where no additional information, such as job-and industry-specific questionnaires, is available. C1 [Friesen, Melissa C.; Locke, Sarah J.; Chen, Yu-Cheng; Koh, Dong-Hee; Stewart, Patricia A.; Purdue, Mark; Colt, Joanne S.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Tornow, Carina] WESTAT Corp, Rockville, MD 20850 USA. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA 22207 USA. RP Friesen, MC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8106,MSC 7240, Bethesda, MD 20892 USA. EM friesenmc@mail.nih.gov RI Friesen, Melissa/A-5362-2009 FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health [Z01 CP10122-19, Z01 CP010136-19] FX Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (Z01 CP10122-19; Z01 CP010136-19). NR 14 TC 1 Z9 1 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 EI 1475-3162 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD JUN PY 2014 VL 58 IS 5 BP 612 EP 624 DI 10.1093/annhyg/meu012 PG 13 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA AK0MN UT WOS:000338107300008 PM 24590110 ER PT J AU Skuladottir, H Wilcox, AJ Ma, C Lammer, EJ Rasmussen, SA Werler, MM Shaw, GM Carmichael, SL AF Skuladottir, Hildur Wilcox, Allen J. Ma, Chen Lammer, Edward J. Rasmussen, Sonja A. Werler, Martha M. Shaw, Gary M. Carmichael, Suzan L. TI Corticosteroid Use and Risk of Orofacial Clefts SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE orofacial clefts; cleft lip and palate; corticosteroids; birth defects; pregnancy ID BIRTH-DEFECTS PREVENTION; TOPICAL CORTICOSTEROIDS; ORAL CLEFTS; DRUG-USE; PREGNANCY; PALATE; EXPOSURE; LIP AB Background: Maternal use of corticosteroids during early pregnancy has been inconsistently associated with orofacial clefts in the offspring. A previous report from the National Birth Defect Prevention Study (NBDPS), using data from 1997 to 2002, found an association with cleft lip and palate (odds ratio, 1.7; 95% confidence interval [CI], 1.1-2.6), but not cleft palate only (odds ratio, 0.5, 95% CI, 0.2-1.3). From 2003 to 2009, the study population more than doubled in size, and our objective was to assess this association in the more recent data. Methods: The NBDPS is an ongoing multi-state population-based case-control study of birth defects, with ascertainment of cases and controls born since 1997. We assessed the association of corticosteroids and orofacial clefts using data from 2372 cleft cases and 5922 controls born from 2003 to 2009. Maternal corticosteroid exposure was based on telephone interviews. Results: The overall association of corticosteroids and cleft lip and palate in the new data was 1.0 (95% CI, 0.7-1.4). There was little evidence of associations between specific corticosteroid components or timing and clefts. Conclusion: In contrast to the 1997 to 2002 data from the NBDPS, the 2003 to 2009 data show no association between maternal corticosteroid use and cleft lip and palate in the offspring. (C) 2014 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. C1 [Skuladottir, Hildur] Haukeland Hosp, Dept Plast Surg, N-5021 Bergen, Norway. [Skuladottir, Hildur] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5020 Bergen, Norway. [Wilcox, Allen J.] NIEHS, NIH, Durham, NC USA. [Ma, Chen; Shaw, Gary M.; Carmichael, Suzan L.] Stanford Univ, Dept Pediat, Div Neonatol & Dev Med, Sch Med, Stanford, CA 94305 USA. [Lammer, Edward J.] Childrens Hosp Oakland Res Inst, Oakland, CA USA. [Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Werler, Martha M.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. RP Skuladottir, H (reprint author), Haukeland Hosp, Dept Plast Surg, Jonas Lies Vei 67, N-5021 Bergen, Norway. EM hildur.skuladottir@gmail.com OI Wilcox, Allen/0000-0002-3376-1311 FU NCBDD CDC HHS [U01-DD-001033, U01-DD-000489] NR 24 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUN PY 2014 VL 100 IS 6 BP 499 EP 506 DI 10.1002/bdra.23248 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA AJ9MU UT WOS:000338036300006 PM 24777675 ER PT J AU Lionakis, MS Netea, MG Holland, SM AF Lionakis, Michail S. Netea, Mihai G. Holland, Steven M. TI Mendelian Genetics of Human Susceptibility to Fungal Infection SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; HYPER-IGE SYNDROME; CHRONIC MUCOCUTANEOUS CANDIDIASIS; POLYENDOCRINE SYNDROME TYPE-1; HEREDITARY MYELOPEROXIDASE DEFICIENCY; ANHIDROTIC ECTODERMAL DYSPLASIA; ACUTE MYELOID-LEUKEMIA; SYNDROME TYPE-I; AUTOSOMAL-DOMINANT; ASPERGILLUS-FUMIGATUS AB A recent surge in newly described inborn errors of immune function-related genes that result in susceptibility to fungal disease has greatly enhanced our understanding of the cellular and molecular basis of antifungal immune responses. Characterization of single-gene defects that predispose to various combinations of superficial and deep-seated infections caused by yeasts, molds, and dimorphic fungi has unmasked the critical role of novel molecules and signaling pathways in mucosal and systemic antifungal host defense. These experiments of nature offer a unique opportunity for developing new knowledge in immunological research and form the foundation for devising immune-based therapeutic approaches for patients infected with fungal pathogens. C1 [Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands. [Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Inst Infect Inflammat & Immun N4i, NL-6525 ED Nijmegen, Netherlands. [Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Lionakis, MS (reprint author), NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM lionakism@niaid.nih.gov RI Netea, Mihai/N-5155-2014 FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; ERC Consolidator Grant [310372] FX This work is supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. M. G. N. is supported by an ERC Consolidator Grant (No. 310372). NR 120 TC 6 Z9 6 U1 1 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 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD JUN PY 2014 VL 4 IS 6 AR a019638 DI 10.1101/cshperspect.a019638 PG 21 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AJ9IC UT WOS:000338021000008 ER PT J AU Voorspoels, W Storms, G Longenecker, J Verheyen, S Weinberger, DR Elvevag, B AF Voorspoels, Wouter Storms, Gert Longenecker, Julia Verheyen, Steven Weinberger, Daniel R. Elvevag, Brita TI Deriving semantic structure from category fluency: Clustering techniques and their pitfalls SO CORTEX LA English DT Article DE Category fluency; Similarity; Schizophrenia; Semantic deficits; Sampling ID VERBAL FLUENCY; SCHIZOPHRENIC-PATIENTS; INSTANTIATION PRINCIPLE; HEALTHY-ADULTS; MEMORY; ORGANIZATION; DEFICITS; RECALL; ALZHEIMERS; RETRIEVAL AB Assessing verbal output in category fluency tasks provides a sensitive indicator of cortical dysfunction. The most common metrics are the overall number of words produced and the number of errors. Two main observations have been made about the structure of the output, first that there is a temporal component to it with words being generated in spurts, and second that the clustering pattern may reflect a search for meanings such that the 'clustering' is attributable to the activation of a specific semantic field in memory. A number of sophisticated approaches to examining the structure of this clustering have been developed, and a core theme is that the similarity relations between category members will reveal the mental semantic structure of the category underlying an individual's responses, which can then be visualized by a number of algorithms, such as MDS, hierarchical clustering, ADD-TREE, ADCLUS or SVD. Such approaches have been applied to a variety of neurological and psychiatric populations, and the general conclusion has been that the clinical condition systematically distorts the semantic structure in the patients, as compared to the healthy controls. In the present paper we explore this approach to understanding semantic structure using category fluency data. On the basis of a large pool of patients with schizophrenia (n = 204) and healthy control participants (n = 204), we find that the methods are problematic and unreliable to the extent that it is not possible to conclude that any putative difference reflects a systematic difference between the semantic representations in patients and controls. Moreover, taking into account the unreliability of the methods, we find that the most probable conclusion to be made is that no difference in underlying semantic representation exists. The consequences of these findings to understanding semantic structure, and the use of category fluency data, in cortical dysfunction are discussed. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Voorspoels, Wouter; Storms, Gert; Verheyen, Steven] Katholieke Univ Leuven, Dept Psychol, B-3000 Louvain, Belgium. [Longenecker, Julia; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Elvevag, Brita] Univ Tromso, Dept Clin Med, Psychiat Res Grp, N-9001 Tromso, Norway. [Elvevag, Brita] Univ Hosp North Norway, Norwegian Ctr Integrated Care & Telemed NST, Tromso, Norway. RP Storms, G (reprint author), Katholieke Univ Leuven, Dept Psychol, Tiensestr 102, B-3000 Louvain, Belgium. EM Gert.Storms@ppw.kuleuven.be FU Intramural Research Program of the National Institutes of Health, National Institute of Mental Health; Northern Norwegian Regional Health Authority FX WV and SV are postdoctoral fellows at the Research Foundation - Flanders. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Mental Health. BE was supported by the Northern Norwegian Regional Health Authority (Helse Nord RHF). None of the funding agencies had any further role in study design, data analysis and interpretation, or in the writing of the report and decision to submit for publication. NR 57 TC 11 Z9 12 U1 6 U2 15 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 EI 1973-8102 J9 CORTEX JI Cortex PD JUN PY 2014 VL 55 SI SI BP 130 EP 147 DI 10.1016/j.cortex.2013.09.006 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AJ5ZY UT WOS:000337770700012 PM 24275165 ER PT J AU Rosenstein, M Diaz-Asper, C Foltz, PW Elvevag, B AF Rosenstein, Mark Diaz-Asper, Catherine Foltz, Peter W. Elvevag, Brita TI A computational language approach to modeling prose recall in schizophrenia SO CORTEX LA English DT Article DE Episodic memory; Wechsler memory scale; Text analysis; Latent semantic analysis ID LATENT SEMANTIC ANALYSIS; COGNITIVE IMPAIRMENTS; MEMORY IMPAIRMENT; RELATIVE RISK; VERBAL MEMORY; DISORDER; POLYMORPHISM; METHODOLOGY; MEDICATIONS; MECHANISMS AB Many cortical disorders are associated with memory problems. In schizophrenia, verbal memory deficits are a hallmark feature. However, the exact nature of this deficit remains elusive. Modeling aspects of language features used in memory recall have the potential to provide means for measuring these verbal processes. We employ computational language approaches to assess time-varying semantic and sequential properties of prose recall at various retrieval intervals (immediate, 30 min and 24 h later) in patients with schizophrenia, unaffected siblings and healthy unrelated control participants. First, we model the recall data to quantify the degradation of performance with increasing retrieval interval and the effect of diagnosis (i.e., group membership) on performance. Next we model the human scoring of recall performance using an n-gram language sequence technique, and then with a semantic feature based on Latent Semantic Analysis. These models show that automated analyses of the recalls can produce scores that accurately mimic human scoring. The final analysis addresses the validity of this approach by ascertaining the ability to predict group membership from models built on the two classes of language features. Taken individually, the semantic feature is most predictive, while a model combining the features improves accuracy of group membership prediction slightly above the semantic feature alone as well as over the human rating approach. We discuss the implications for cognitive neuroscience of such a computational approach in exploring the mechanisms of prose recall. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Rosenstein, Mark; Foltz, Peter W.] Pearson Knowledge Technol, Boulder, CO USA. [Diaz-Asper, Catherine] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Foltz, Peter W.] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA. [Elvevag, Brita] Univ Tromso, Dept Clin Med, Psychiat Res Grp, N-9001 Tromso, Norway. [Elvevag, Brita] Univ Hosp North Norway, Norwegian Ctr Integrated Care & Telemed NST, Tromso, Norway. RP Rosenstein, M (reprint author), Pearson, 4940 Pearl East Circle,Suite 200, Boulder, CO 80301 USA. EM mark.rosenstein@pearson.com FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, USA; Northern Norwegian Regional Health Authority, Helse Nord RHF FX We gratefully acknowledge Daniel R. Weinberger M.D., for making the data available, which were collected via the Clinical Brain Disorders (NIMH) Schizophrenia Sibling Study (D.R. Weinberger, PI). This research was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, USA. We are also thankful for assistance from Julia Longenecker M. Phil. and Krista Wisner B.A. Brita Elvevag was funded by the Northern Norwegian Regional Health Authority, Helse Nord RHF, and Peter Foltz and Mark Rosenstein are employees of Pearson, the publisher of the Wechsler test utilized in the paper, which partially supported their work as part of their employment. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 2 Z9 2 U1 0 U2 8 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 EI 1973-8102 J9 CORTEX JI Cortex PD JUN PY 2014 VL 55 SI SI BP 148 EP 166 DI 10.1016/j.cortex.2014.01.021 PG 19 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AJ5ZY UT WOS:000337770700013 PM 24709122 ER PT J AU Nicodemus, KK Elvevag, B Foltz, PW Rosenstein, M Diaz-Asper, C Weinberger, DR AF Nicodemus, Kristin K. Elvevag, Brita Foltz, Peter W. Rosenstein, Mark Diaz-Asper, Catherine Weinberger, Daniel R. TI Category fluency, latent semantic analysis and schizophrenia: a candidate gene approach SO CORTEX LA English DT Article DE Cognition; Verbal learning and recall; Gene; Latent semantic analysis; Schizophrenia ID NEUROCOGNITIVE PHENOTYPES; INTERMEDIATE PHENOTYPES; PSYCHIATRIC GENETICS; SUSCEPTIBILITY GENE; COGNITIVE-PROCESSES; ZNF804A; ASSOCIATION; DISC1; RISK; VARIANTS AB Background: Category fluency is a widely used task that relies on multiple neurocognitive processes and is a sensitive assay of cortical dysfunction, including in schizophrenia. The test requires naming of as many words belonging to a certain category (e.g., animals) as possible within a short period of time. The core metrics are the overall number of words produced and the number of errors, namely non-members generated for a target category. We combine a computational linguistic approach with a candidate gene approach to examine the genetic architecture of this traditional fluency measure. Methods: In addition to the standard metric of overall word count, we applied a computational approach to semantics, Latent Semantic Analysis (LSA), to analyse the clustering pattern of the categories generated, as it likely reflects the search in memory for meanings. Also, since fluency performance probably also recruits verbal learning and recall processes, we included two standard measures of this cognitive process: the Wechsler Memory Scale and California Verbal Learning Test (CVLT). To explore the genetic architecture of traditional and LSA-derived fluency measures we employed a candidate gene approach focused on SNPs with known function that were available from a recent genome-wide association study (GWAS) of schizophrenia. The selected candidate genes were associated with language and speech, verbal learning and recall processes, and processing speed. A total of 39 coding SNPs were included for analysis in 665 subjects. Results and discussion: Given the modest sample size, the results should be regarded as exploratory and preliminary. Nevertheless, the data clearly illustrate how extracting the meaning from participants' responses, by analysing the actual content of words, generates useful and neurocognitively viable metrics. We discuss three replicated SNPs in the genes ZNF804A, DISCI. and KIAA0319, as well as the potential for computational analyses of linguistic and textual data in other genomics tasks. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Nicodemus, Kristin K.] Univ Dublin Trinity Coll, St Jamess Hosp, Trinity Ctr Hlth Sci, Neuropsychiat Genet Res Grp,Dept Psychiat, Dublin 8, Ireland. [Elvevag, Brita] Univ Tromso, Dept Clin Med, Psychiat Res Grp, N-9001 Tromso, Norway. [Elvevag, Brita] Univ Hosp North Norway, Norwegian Ctr Integrated Care & Telemed NST, Tromso, Norway. [Foltz, Peter W.; Rosenstein, Mark] Pearson Knowledge Technol, Boulder, CO USA. [Foltz, Peter W.] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA. [Diaz-Asper, Catherine; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. [Weinberger, Daniel R.] Johns Hopkins Sch Med, Inst Genom Med, Baltimore, MD USA. RP Nicodemus, KK (reprint author), Univ Dublin Trinity Coll, St Jamess Hosp, Trinity Ctr Hlth Sci, Neuropsychiat Genet Res Grp,Dept Psychiat, Dublin 8, Ireland. EM nicodemk@tcd.ie FU Science Foundation Ireland; Marie-Curie Action COFUND [11/SIRG/B2183]; Northern Norwegian Regional Health Authority (Helse Nord RHF); Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, USA FX This publication has emanated from research conducted with the financial support of Science Foundation Ireland and the Marie-Curie Action COFUND under Grant Number 11/SIRG/B2183 to Dr. Nicodemus. Dr. Elvevag was supported by the Northern Norwegian Regional Health Authority (Helse Nord RHF). All calculations were performed on the Lonsdale cluster maintained by the Trinity Centre for High Performance Computing. This cluster was funded through grants from Science Foundation Ireland. This research was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, USA. NR 58 TC 13 Z9 14 U1 1 U2 8 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 EI 1973-8102 J9 CORTEX JI Cortex PD JUN PY 2014 VL 55 SI SI BP 182 EP 191 DI 10.1016/j.cortex.2013.12.004 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA AJ5ZY UT WOS:000337770700015 PM 24447899 ER PT J AU Kane, A Deenick, EK Ma, CS Cook, MC Uzel, G Tangye, SG AF Kane, Alisa Deenick, Elissa K. Ma, Cindy S. Cook, Matthew C. Uzel, Gulbu Tangye, Stuart G. TI STAT3 is a central regulator of lymphocyte differentiation and function SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HYPER-IGE SYNDROME; SECRETING PLASMA-CELLS; CD4(+) T-CELLS; SIGNAL TRANSDUCER; B-CELLS; ANTIBODY-RESPONSES; HYPERIMMUNOGLOBULINEMIA-E; STAT3-DEPENDENT MANNER; IL-21 RECEPTOR; JOBS SYNDROME AB Signalling in lymphocytes through cytokine receptors is critical for their development, activation and differentiation into effector cells that mediate protection against pathogens and provide the host with protective immunological memory. The essential role of cytokine signalling has been established not only by the generation and examination of gene-targeted mice, but also 'Experiments of Nature' whereby monogenic mutations cause primary immunodeficient conditions characterised by impaired immunity to infectious diseases due to compromised lymphocyte function. Mutations in STAT3 cause autosomal dominant hyper-IgE syndrome. Here, we will review how the study of STAT3-deficient individuals has revealed non-redundant functions of STAT3 and specific cytokines in human lymphocyte biology, and have delineated mechanisms underlying the distinct clinical features of autosomal dominant hyper-IgE syndrome. C1 [Kane, Alisa; Deenick, Elissa K.; Ma, Cindy S.; Tangye, Stuart G.] St Vincents Hosp, Garvan Inst Med Res, Immunol Res Program, Immunol & Immunodeficiency Grp, Darlinghurst, NSW 2010, Australia. [Kane, Alisa; Deenick, Elissa K.; Ma, Cindy S.; Tangye, Stuart G.] Univ New S Wales, St Vincents Clin Sch, Darlinghurst, NSW, Australia. [Cook, Matthew C.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 0200, Australia. [Cook, Matthew C.] Canberra Hosp, Dept Immunol, Canberra, ACT, Australia. [Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Tangye, SG (reprint author), St Vincents Hosp, Garvan Inst Med Res, Immunol Res Program, Immunol & Immunodeficiency Grp, Darlinghurst, NSW 2010, Australia. EM s.tangye@garvan.org.au OI Deenick, Elissa/0000-0002-9271-0004; Cook, Matthew/0000-0002-3331-9363 FU National Health and Medical Research Council of Australia FX Research performed in the authors' labs is supported by grants and fellowships awarded by the National Health and Medical Research Council of Australia. NR 59 TC 22 Z9 24 U1 0 U2 20 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2014 VL 28 BP 49 EP 57 DI 10.1016/j.coi.2014.01.015 PG 9 WC Immunology SC Immunology GA AJ7BX UT WOS:000337853300010 PM 24594518 ER PT J AU Kruse, AC Hu, JX Kobilka, BK Wess, J AF Kruse, Andrew C. Hu, Jianxin Kobilka, Brian K. Wess, Juergen TI Muscarinic acetylcholine receptor X-ray structures: potential implications for drug development SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; ALLOSTERIC MODULATION; CRYSTAL-STRUCTURE; TIOTROPIUM; MICE; LIGANDS AB Muscarinic acetylcholine receptor antagonists are widely used as bronchodilating drugs in pulmonary medicine. The therapeutic efficacy of these agents depends on the blockade of M-3 muscarinic receptors expressed on airway smooth muscle cells. All muscarinic antagonists currently used as bronchodilating agents show high affinity for all five muscarinic receptor subtypes, thus increasing the likelihood of unwanted side effects. Recent X-ray crystallographic studies have provided detailed structural information about the nature of the orthosteric muscarinic binding site (the conventional acetylcholine binding site) and an 'outer' receptor cavity that can bind allosteric (non-orthosteric) drugs. These new findings should guide the development of selective M-3 receptor blockers that have little or no effect on other muscarinic receptor subtypes. C1 [Kruse, Andrew C.; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Hu, Jianxin; Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, Bethesda, MD USA. RP Kruse, AC (reprint author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. EM akruse@stanford.edu; jurgenw@helix.nih.gov FU National Science Foundation Graduate Research Fellowship; National Science Foundation [CHE-1223785]; National Institutes of Health [U19GM106990]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NIH FX The structural studies summarized in this review were supported by a National Science Foundation Graduate Research Fellowship to ACK and by National Science Foundation grant CHE-1223785 and National Institutes of Health grant U19GM106990 to BKK. The work of JH and JW was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH. We thank all of our coworkers and collaborators for their invaluable contributions to the work summarized in this chapter. NR 26 TC 10 Z9 11 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 EI 1471-4973 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD JUN PY 2014 VL 16 BP 24 EP 30 DI 10.1016/j.coph.2014.02.006 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK0HU UT WOS:000338094300006 PM 24662799 ER PT J AU Sepeta, LN Berl, MM Theodore, WH Xu, B Roopchansingh, V Shih, S Barrett, L Terwilliger, V Emery, E Germeyan, S Suthana, N Bookheimer, SY Gaillard, WD AF Sepeta, L. N. Berl, M. M. Theodore, W. H. Xu, B. Roopchansingh, V Shih, S. Barrett, L. Terwilliger, V Emery, E. Germeyan, S. Suthana, N. Bookheimer, S. Y. Gaillard, W. D. TI LATERALIZATION OF HIPPOCAMPAL ACTIVATION FOR SURGICAL GUIDANCE IN REFRACTORY PEDIATRIC EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 11th European Congress on Epileptology CY JUN 29-JUL 03, 2014 CL Stockholm, SWEDEN C1 [Sepeta, L. N.; Berl, M. M.; Terwilliger, V; Emery, E.; Gaillard, W. D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Theodore, W. H.; Xu, B.; Roopchansingh, V; Germeyan, S.; Gaillard, W. D.] NIH, Bethesda, MD 20892 USA. [Barrett, L.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Suthana, N.; Bookheimer, S. Y.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD JUN PY 2014 VL 55 SU 2 SI SI MA p467 BP 152 EP 152 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA AJ8TA UT WOS:000337979300454 ER PT J AU O'Reilly, M Federoff, HJ Fong, YM Kohn, DB Patterson, AP Ahmed, N Asokan, A Boye, SE Crystal, RG De Oliveira, S Gargiulo, L Harper, SQ Ikeda, Y Jambou, R Montgomery, M Prograis, L Rosenthal, E Sterman, DH Vandenberghe, LH Zoloth, L Abedi, M Adair, J Adusumilli, PS Goins, WF Gray, J Monahan, P Popplewell, L Sena-Esteves, M Tannous, B Weber, T Wierda, W Gopal-Srivastava, R McDonald, CL Rosenblum, D Corrigan-Curay, J AF O'Reilly, Marina Federoff, Howard J. Fong, Yuman Kohn, Donald B. Patterson, Amy P. Ahmed, Nabil Asokan, Aravind Boye, Shannon E. Crystal, Ronald G. De Oliveira, Satiro Gargiulo, Linda Harper, Scott Q. Ikeda, Yasuhiro Jambou, Robert Montgomery, Maureen Prograis, Lawrence Rosenthal, Eugene Sterman, Daniel H. Vandenberghe, Luk H. Zoloth, Laurie Abedi, Mehrdad Adair, Jennifer Adusumilli, Prasad S. Goins, William F. Gray, Jhanelle Monahan, Paul Popplewell, Leslie Sena-Esteves, Miguel Tannous, Bakhos Weber, Thomas Wierda, William Gopal-Srivastava, Rashmi McDonald, Cheryl L. Rosenblum, Daniel Corrigan-Curay, Jacqueline TI Gene Therapy: Charting a Future Course-Summary of a National Institutes of Health Workshop, April 12, 2013 SO HUMAN GENE THERAPY LA English DT Review ID LEBER CONGENITAL AMAUROSIS; CHIMERIC ANTIGEN RECEPTOR; HEMATOPOIETIC STEM/PROGENITOR CELLS; MODIFIED T-CELLS; ADENOASSOCIATED VIRUS; CANCER-IMMUNOTHERAPY; HEMOPHILIA-B; EFFICACY; SAFETY; EXPRESSION AB Recently, the gene therapy field has begun to experience clinical successes in a number of different diseases using various approaches and vectors. The workshop Gene Therapy: Charting a Future Course, sponsored by the National Institutes of Health (NIH) Office of Biotechnology Activities, brought together early and mid-career researchers to discuss the key scientific challenges and opportunities, ethical and communication issues, and NIH and foundation resources available to facilitate further clinical advances. C1 [O'Reilly, Marina; Patterson, Amy P.; Gargiulo, Linda; Jambou, Robert; Montgomery, Maureen; Rosenthal, Eugene; Corrigan-Curay, Jacqueline] Off Director, Off Sci Policy, Bethesda, MD 20892 USA. [Prograis, Lawrence] NIAID, Bethesda, MD 20892 USA. [Gopal-Srivastava, Rashmi; Rosenblum, Daniel] Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [McDonald, Cheryl L.] NHLBI, NIH, Bethesda, MD 20892 USA. [Federoff, Howard J.] Georgetown Univ, Med Ctr, Washington, DC 20057 USA. [Fong, Yuman; Popplewell, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Kohn, Donald B.; De Oliveira, Satiro] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ahmed, Nabil] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Asokan, Aravind; Monahan, Paul] Univ N Carolina, Chapel Hill, NC 27599 USA. [Boye, Shannon E.] Univ Florida, Gainesville, FL 32605 USA. [Crystal, Ronald G.] Weill Cornell Med Coll, Dept Med Genet, New York, NY 10065 USA. [Harper, Scott Q.] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA. [Ikeda, Yasuhiro] Mayo Clin, Rochester, MN 55905 USA. [Sterman, Daniel H.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Vandenberghe, Luk H.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Vandenberghe, Luk H.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Zoloth, Laurie] Northwestern Univ, Evanston, IL 60208 USA. [Abedi, Mehrdad] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA. [Adair, Jennifer] Fred Hutchinson Canc Res Ctr, Seattle, WA 98102 USA. [Adusumilli, Prasad S.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Goins, William F.] Univ Pittsburgh, Pittsburgh, PA 15219 USA. [Gray, Jhanelle] H Lee Mofitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Tannous, Bakhos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Weber, Thomas] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Wierda, William] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Corrigan-Curay, J (reprint author), NIH, Off Biotechnol Act, 6705 Rockledge Dr,Suite 750, Bethesda, MD 20892 USA. EM corrigaja@od.nih.gov RI Weber, Thomas/A-2363-2008; De Oliveira, Satiro/D-8860-2014; Kohn, Donald/N-5085-2016 OI Weber, Thomas/0000-0002-0494-0484; De Oliveira, Satiro/0000-0002-8181-7316; Kohn, Donald/0000-0003-1840-6087 FU Foundation Fighting Blindness; Massachusetts Eye and Ear Infirmary (Boston, MA); Genelux; Roche; Asklepios Biopharmaceutical; Baxter Biologics FX N.A. has patent applications in the field of T-cell and gene-modified T-cell therapy for cancer. The Center for Cell and Gene Therapy (CAGT) has research collaboration with Celgene Inc. to develop CAR-based therapeutics that is administered by Baylor College of Medicine. L. H. V. is inventor on gene therapy-related patents that are licensed to various pharmaceutical and biotechnological companies, holds equity in GenSight Biologics, consults for Novartis and GenSight Biologics, and receives funding from the Foundation Fighting Blindness and the Massachusetts Eye and Ear Infirmary (Boston, MA). He has been employed by the University of Pennsylvania and the Massachusetts Eye and Ear Infirmary. Y.F. is a paid advisor for Genelux and consultant to Roche. H.F. is a founder and advisor to MedGenesis. P.M.'s university receives or has received funding to support basic science research work in the author's laboratory from Asklepios Biopharmaceutical and Baxter Biologics. He has received remuneration for consulting work and for speaking from Asklepios Biopharmaceutical and Baxter Biologics. NR 47 TC 8 Z9 8 U1 1 U2 17 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD JUN PY 2014 VL 25 IS 6 BP 488 EP 497 DI 10.1089/hum.2014.045 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AJ8JR UT WOS:000337949900004 PM 24773122 ER PT J AU Zhang, H Kathawala, RJ Wang, YJ Zhang, YK Patel, A Shukla, S Robey, RW Talele, TT Ashby, CR Ambudkar, SV Bates, SE Fu, LW Chen, ZS AF Zhang, Hui Kathawala, Rishil J. Wang, Yi-Jun Zhang, Yun-Kai Patel, Atish Shukla, Suneet Robey, Robert W. Talele, Tanaji T. Ashby, Charles R., Jr. Ambudkar, Suresh V. Bates, Susan E. Fu, Li-Wu Chen, Zhe-Sheng TI Linsitinib (OSI-906) antagonizes ATP-binding cassette subfamily G member 2 and subfamily C member 10-mediated drug resistance SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Linsitinib; Multi-drug resistance; ABCG2; ABCC10; Tyrosine kinase inhibitor ID MULTIDRUG-RESISTANCE; ACQUIRED MUTATIONS; ABC TRANSPORTERS; PROTEIN ABCG2; CANCER; INHIBITOR; CELLS; QUANTITATION; EFFLUX; SPECIFICITY AB In this study we investigated the effect of linsitinib on the reversal of multidrug resistance (MDR) mediated by the overexpression of the ATP-binding cassette (ABC) subfamily members ABCB1, ABCG2, ABCC1 and ABCC10. Our results indicate for the first time that linsitinib significantly potentiate the effect of anti-neoplastic drugs mitoxantrone (MX) and SN-38 in ABCG2-overexpressing cells; paclitaxel, docetaxel and vinblastine in ABCC10-overexpressing cells. Linsitinib moderately enhanced the cytotoxicity of vincristine in cell lines overexpressing ABCB1, whereas it did not alter the cytotoxicity of substrates of ABCC1. Furthermore, linsitinib significantly increased the intracellular accumulation and decreased the efflux of [H-3]-MX in ABCG2-overexpressing cells and [H-3]-paclitaxel in ABCC10-overexpressing cells. However, linsitinib, at a concentration that reversed MDR, did not significantly alter the expression levels of either the ABCG2 or ABCC10 transporter proteins. Furthermore, linsitinib did not significantly alter the intracellular localization of ABCG2 or ABCC10. Moreover, linsitinib stimulated the ATPase activity of ABCG2 in a concentration-dependent manner. Overall, our study suggests that linsitinib attenuates ABCG2- and ABCC10-mediated MDR by directly inhibiting their function as opposed to altering ABCG2 or ABCC10 protein expression. Published by Elsevier Ltd. C1 [Zhang, Hui; Kathawala, Rishil J.; Wang, Yi-Jun; Zhang, Yun-Kai; Patel, Atish; Talele, Tanaji T.; Ashby, Charles R., Jr.; Chen, Zhe-Sheng] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Queens, NY 11439 USA. [Zhang, Hui; Fu, Li-Wu] Sun Yat Sen Univ, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China. [Shukla, Suneet; Ambudkar, Suresh V.] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Robey, Robert W.; Bates, Susan E.] NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chen, ZS (reprint author), St Johns Univ, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. EM fulw@mail.sysu.edu.cn; chenz@stjohns.edu RI Wang, Yi-Jun/K-3218-2016; Patel, Atish/J-4699-2014 OI Patel, Atish/0000-0002-5549-9166 FU NIH [1R15CA143701]; St. John's University Research Seed Grant [579-1110-7002]; Major Science and Technology Project of The National Natural Sciences Foundation of China [81072669, 81061160507]; Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported by funds from NIH (No. 1R15CA143701) and St. John's University Research Seed Grant (No. 579-1110-7002) to Z.S. Chen, The Major Science and Technology Project of The National Natural Sciences Foundation of China Grant (No. 81072669 and No. 81061160507) to L.W. Fu. Drs. S. Shukla, R.W. Robey, S.V. Ambudkar and S.E. Bates were supported by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research. We are grateful to late Dr. Gary Kruh (University of Illinois at Chicago) for providing ABCC10 plasmid. We thank Dr. Mark F. Rosenberg (University of Manchester, Manchester, UK) and Dr. Zsolt Bikadi (Virtua Drug Ltd., Budapest, Hungary) for providing coordinates of ABCG2 homology model. NR 34 TC 8 Z9 8 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 EI 1878-5875 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD JUN PY 2014 VL 51 BP 111 EP 119 DI 10.1016/j.biocel.2014.03.026 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AJ6BL UT WOS:000337774600016 PM 24726739 ER PT J AU Chew, EY AF Chew, Emily Y. TI Vitamins and Minerals, for Eyes Only? SO JAMA OPHTHALMOLOGY LA English DT Editorial Material ID MACULAR DEGENERATION; CLINICAL-TRIAL; BETA-CAROTENE; SUPPLEMENTATION; ZINC C1 [Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov NR 9 TC 0 Z9 0 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6165 EI 2168-6173 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JUN PY 2014 VL 132 IS 6 BP 665 EP 666 DI 10.1001/jamaophthalmol.2014.643 PG 2 WC Ophthalmology SC Ophthalmology GA AJ7PQ UT WOS:000337889000001 PM 24651887 ER PT J AU Zhang, R Cairelli, MJ Fiszman, M Rosemblat, G Kilicoglu, H Rindflesch, TC Pakhomov, SV Melton, GB AF Zhang, Rui Cairelli, Michael J. Fiszman, Marcelo Rosemblat, Graciela Kilicoglu, Halil Rindflesch, Thomas C. Pakhomov, Serguei V. Melton, Genevieve B. TI Using semantic predications to uncover drug-drug interactions in clinical data SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Drug-drug interactions; MEDLINE; SemRep; SemMedDB; Natural language processing; Semantic predication ID BIOMEDICAL TEXT; DISCOVERY; INHIBITION; KNOWLEDGE; CYP; IDENTIFICATION; INFORMATION; PERSPECTIVE; SYSTEM; MODEL AB In this study we report on potential drug-drug interactions between drugs occurring in patient clinical data. Results are based on relationships in SemMedDB, a database of structured knowledge extracted from all MEDLINE citations (titles and abstracts) using SemRep. The core of our methodology is to construct two potential drug-drug interaction schemas, based on relationships extracted from SemMedDB. In the first schema, Drug1 and Drug2 interact through Drug1's effect on some gene, which in turn affects Drug2. In the second, Drug1 affects Gene1, while Drug2 affects Gene2. Gene1 and Gene2, together, then have an effect on some biological function. After checking each drug pair from the medication lists of each of 22 patients, we found 19 known and 62 unknown drug-drug interactions using both schemas. For example, our results suggest that the interaction of Lisinopril, an ACE inhibitor commonly prescribed for hypertension, and the antidepressant sertraline can potentially increase the likelihood and possibly the severity of psoriasis. We also assessed the relationships extracted by SemRep from a linguistic perspective and found that the precision of SemRep was 0.58 for 300 randomly selected sentences from MEDLINE. Our study demonstrates that the use of structured knowledge in the form of relationships from the biomedical literature can support the discovery of potential drug-drug interactions occurring in patient clinical data. Moreover, SemMedDB provides a good knowledge resource for expanding the range of drugs, genes, and biological functions considered as elements in various drug-drug interaction pathways. (C) 2014 Elsevier Inc. All rights reserved. C1 [Zhang, Rui; Pakhomov, Serguei V.; Melton, Genevieve B.] Univ Minnesota, Inst Hlth Informat, Minneapolis, MN USA. [Cairelli, Michael J.; Fiszman, Marcelo; Rosemblat, Graciela; Kilicoglu, Halil; Rindflesch, Thomas C.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA. [Pakhomov, Serguei V.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. [Melton, Genevieve B.] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. RP Cairelli, MJ (reprint author), BG 38A Rm 9N912A,8600 Rockville Pike, Bethesda, MD 20892 USA. EM zhan1386@umn.edu; cairellimj@mail.nih.gov; fiszmanm@mail.nih.gov; grosemblat@mail.nih.gov; kilicogluh@mail.nih.gov; trindflesch@mail.nih.gov; pakh0002@umn.edu; gmelton@umn.edu FU Intramural Research Program of the NIH, National Library of Medicine FX This research was supported in part by an appointment to the NLM Research Participation Program, which is administered by the Oak Ridge Institute for Science and Education through an inter-agency agreement between the U.S. Department of Energy and the National Library of Medicine. This project was supported in part by the Intramural Research Program of the NIH, National Library of Medicine. NR 44 TC 4 Z9 4 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 1532-0464 EI 1532-0480 J9 J BIOMED INFORM JI J. Biomed. Inform. PD JUN PY 2014 VL 49 BP 134 EP 147 DI 10.1016/j.jbi.2014.01.004 PG 14 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA AJ6AN UT WOS:000337772200014 PM 24448204 ER PT J AU Dufresne, SF Marr, KA Sydnor, E Staab, JF Karp, JE Lu, K Zhang, SAX Lavallee, C Perl, TM Neofytos, D AF Dufresne, Simon F. Marr, Kieren A. Sydnor, Emily Staab, Janet F. Karp, Judith E. Lu, Kit Zhang, Sean X. Lavallee, Christian Perl, Trish M. Neofytos, Dionysios TI Epidemiology of Candida kefyr in Patients with Hematologic Malignancies SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; KLUYVEROMYCES-MARXIANUS; NEUTROPENIC PATIENTS; EMERGING PATHOGEN; SPOILAGE YEASTS; FUNGEMIA; ALBICANS; PCR; COLONIZATION; LEUKEMIA AB Candida kefyr is an emerging pathogen among patients with hematologic malignancies (HM). We performed a retrospective study at Johns Hopkins Hospital to evaluate the epidemiology of C. kefyr colonization and infection in HM patients between 2004 and 2010. Eighty-three patients were colonized and/or infected with C. kefyr, with 8 (9.6%) having invasive candidiasis (IC). The yearly incidence of C. kefyr colonization and candidemia increased over the study period (P < 0.01), particularly after 2009. In 2010, C. kefyr caused 16.7% of candidemia episodes. The monthly incidence of C. kefyr was higher during the summer throughout the study. In a cohort of patients with acute myelogenic leukemia receiving induction chemotherapy, risks for C. kefyr colonization included the summer season (odds ratio [OR], 3.1; P = 0.03); administration of an azole (OR, 0.06; P < 0.001) or amphotericin B (OR, 0.35; P = 0.05) was protective. Fingerprinting of 16 isolates by repetitive sequence-based PCR showed that all were different genotypes. The epidemiology of C. kefyr candidemia was evaluated in another hospital in Montreal, Canada; data confirmed higher rates of C. kefyr infection in the summer. C. kefyr appears to be increasing in HM patients, with prominent summer seasonality. These findings raise questions about the effect of antifungal agents and health care exposures (e.g., yogurt) on the epidemiology of this yeast. C1 [Dufresne, Simon F.; Marr, Kieren A.; Sydnor, Emily; Staab, Janet F.; Perl, Trish M.; Neofytos, Dionysios] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [Dufresne, Simon F.; Lavallee, Christian] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. [Marr, Kieren A.; Karp, Judith E.; Lu, Kit] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Baltimore, MD USA. [Sydnor, Emily] Univ Utah, Div Infect Dis, Salt Lake City, UT USA. [Lu, Kit] NIH, Dept Hematol, Bethesda, MD 20892 USA. [Zhang, Sean X.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Perl, Trish M.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Marr, KA (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. EM kmarr4@jhmi.edu FU Astellas Pharma Inc.; Pfizer Inc. [WS297422]; National Institutes of Health grant K24 [AI085118]; National Cancer Institute [2P30-06973-48]; drug development grant [U01 CA70095]; Universite de Montreal and Hopital Maisonneuve-Rosemont; Astellas; Merck; Pfizer; Sigma Tau; Medimmune; CDC; VA; IBIS Biosciences/Abbott Molecular; AdvanDx Corporation; University of Montreal, Maisonneuve-Rosemont Hospital FX This work was partly supported by a grant from Astellas Pharma Inc., a grant from Pfizer Inc. (WS297422), the National Institutes of Health grant K24 (AI085118, to K. A. M.), a National Cancer Institute grant (2P30-06973-48, to J.E.K.), a drug development grant (U01 CA70095, to J.E.K.), and fellowship grants from Universite de Montreal and Hopital Maisonneuve-Rosemont (to S. F. D.).; K. A. M. has been a consultant/advisor for Astellas, Merck, and Pfizer and has received research grants from Astellas, Merck, Pfizer, and Sigma Tau. T. M. P. has received research grants from Medimmune, Merck, CDC, and VA and has been an advisor for Pfizer. S. X. Z. has received research contract funds from IBIS Biosciences/Abbott Molecular and AdvanDx Corporation. S. F. D. has received research funding from University of Montreal, Maisonneuve-Rosemont Hospital, and Pfizer; has consulted for Merck; and has moderated a conference for Pfizer. D. N. has received research grants from Pfizer and has served on advisory boards or as a consultant for Roche and Astellas. NR 42 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2014 VL 52 IS 6 BP 1830 EP 1837 DI 10.1128/JCM.00131-14 PG 8 WC Microbiology SC Microbiology GA AJ7YZ UT WOS:000337919500005 PM 24622105 ER PT J AU Drame, PM Fink, DL Kamgno, J Herrick, JA Nutman, TB AF Drame, Papa M. Fink, Doran L. Kamgno, Joseph Herrick, Jesica A. Nutman, Thomas B. TI Loop-Mediated Isothermal Amplification for Rapid and Semiquantitative Detection of Loa loa Infection SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SERIOUS ADVERSE EVENTS; DIAGNOSTIC SENSITIVITY; COLORIMETRIC DETECTION; MANSONELLA-PERSTANS; MASS TREATMENT; LOIASIS; IVERMECTIN; MALARIA; FILARIASIS; BLUE AB Rapid and accurate tests are currently needed to identify individuals with high levels of Loa loa microfilaria (mf), so that these individuals may be excluded from mass ivermectin administration campaigns against onchocerciasis and lymphatic filariasis being conducted in areas where Onchocerca volvulus, Wuchereria bancrofti, and L. loa are coendemic. To address this need, colorimetric loop-mediated isothermal amplification (LAMP) assays targeting the L. loa-specific gene sequences LLMF72 and LLMF342 were developed for the detection and quantification of L. loa microfilaremia. Both LAMP assays were highly specific (100%) for L. loa infection compared to the absence of infection or infection with related filarial pathogens. The LLMF72-based LAMP assay showed greater analytic sensitivity (limit of detection, 0.1 pg/ml of genomic DNA [gDNA] and/or 5 mf/ml) than the LLMF342-based LAMP assay (10 pg/ml of gDNA and/or 50 mf/ml), and its analytic sensitivity was similar to that of LLMF72-based quantitative PCR (qPCR). A high level of correlation was observed between microfilaria counts as determined by LLMF72-based qPCR and time to positivity by the LAMP assay, and performance measures of sensitivity, specificity, and positive and negative predictive values were similar for both assays when applied to field-collected clinical samples. By simply varying the run time, the LAMP assay was able to accurately distinguish individuals at risk for serious adverse events (SAEs) after exposure to ivermectin, using thresholds of >5,000 mf/ml and >30,000 mf/ml as indicators of increasing levels of risk. In summary, LLMF72 LAMP represents a new molecular diagnostic tool that is readily applicable as a point-of-care method for L. loa microfilarial detection and quantification in resource-limited countries where L. loa infection is endemic. C1 [Drame, Papa M.; Fink, Doran L.; Herrick, Jesica A.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Kamgno, Joseph] Ctr Res Filariasis & Trop Dis, Yaounde, Cameroon. [Kamgno, Joseph] Univ Yaounde, Fac Med & Biomed Sci, Yaounde, Cameroon. RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM TNUTMAN@niaid.nih.gov FU Division of Intramural Research (DIR) of the NIAID FX The Division of Intramural Research (DIR) of the NIAID provided all of the funds for this study. NR 45 TC 12 Z9 13 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2014 VL 52 IS 6 BP 2071 EP 2077 DI 10.1128/JCM.00525-14 PG 7 WC Microbiology SC Microbiology GA AJ7YZ UT WOS:000337919500036 PM 24696020 ER PT J AU Taylor, G Wyld, S Valarcher, JF Guzman, E Thom, M Widdison, S Buchholz, UJ AF Taylor, Geraldine Wyld, Sara Valarcher, Jean-Francois Guzman, Efrain Thom, Michelle Widdison, Stephanie Buchholz, Ursula J. TI Recombinant bovine respiratory syncytial virus with deletion of the SH gene induces increased apoptosis and pro-inflammatory cytokines in vitro, and is attenuated and induces protective immunity in calves SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID SMALL HYDROPHOBIC PROTEIN; INFLUENZA-VIRUS; MEMBRANE-PERMEABILITY; MONOCLONAL-ANTIBODIES; CELL-CULTURE; INFECTION; RESPONSES; VACCINE; DISEASE; INTERLEUKIN-1 AB Bovine respiratory syncytial virus (BRSV) causes inflammation and obstruction of the small airways, leading to severe respiratory disease in young calves. The virus is closely related to human (H)RSV, a major cause of bronchiolitis and pneumonia in young children. The ability to manipulate the genome of RSV has provided opportunities for the development of stable, live attenuated RSV vaccines. The role of the SH protein in the pathogenesis of BRSV was evaluated in vitro and in vivo using a recombinant (r)BRSV in which the SH gene had been deleted. Infection of bovine epithelial cells and monocytes with rBRSV Delta SH, in vitro, resulted in an increase in apoptosis, and higher levels of TNF-alpha and IL-1 beta compared with cells infected with parental, wildtype (WT) rBRSV. Although replication of rBRSV Delta SH and WT rBRSV, in vitro, were similar, the replication of rBRSV Delta SH was moderately reduced in the lower, but not the upper, respiratory tract of experimentally infected calves. Despite the greater ability of rBRSV Delta SH to induce proinflammatory cytokines, in vitro, the pulmonary inflammatory response in rBRSV Delta SH-infected calves was significantly reduced compared with that in calves inoculated with WT rBRSV, 6 days previously. Virus lacking SH appeared to be as immunogenic and effective in inducing resistance to virulent virus challenge, 6 months later, as the parental rBRSV. These findings suggest that rBRSV Delta SH may be an ideal live attenuated virus vaccine candidate, combining safety with a high level of immunogenicity. C1 [Taylor, Geraldine; Wyld, Sara; Valarcher, Jean-Francois; Guzman, Efrain; Thom, Michelle; Widdison, Stephanie] Pirbright Inst, Woking GU24 0NF, Surrey, England. [Buchholz, Ursula J.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Taylor, G (reprint author), Pirbright Inst, Woking GU24 0NF, Surrey, England. EM geraldine.taylor@pirbright.ac.uk RI Institute, Pirbright/K-4476-2014; OI Guzman, Efrain/0000-0002-1583-2964 FU European Commission [EC 5th FP-RSV Vac QLK2-CT-1999-00443]; Department for Environment, Food and Rural Affairs, UK; BBSRC Institute Strategic Programme on Livestock Viral Diseases at the Pirbright Institute; Intramural Research Program of the NIH, NIAID FX This work was supported by the European Commission (EC 5th FP-RSV Vac QLK2-CT-1999-00443), the Department for Environment, Food and Rural Affairs, UK and the BBSRC Institute Strategic Programme on Livestock Viral Diseases at the Pirbright Institute. U. J. B. was supported by the Intramural Research Program of the NIH, NIAID. We thank Animal Services at the Pirbright Institute for all their help and Dr Simon Gubbins, Pirbright Institute, for statistical advice. NR 45 TC 9 Z9 10 U1 2 U2 9 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD JUN PY 2014 VL 95 BP 1244 EP 1254 DI 10.1099/vir.0.064931-0 PN 6 PG 11 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA AK1LN UT WOS:000338176700005 PM 24700100 ER PT J AU Yeager, DS Johnson, R Spitzer, BJ Trzesniewski, KH Powers, J Dweck, CS AF Yeager, David Scott Johnson, Rebecca Spitzer, Brian James Trzesniewski, Kali H. Powers, Joseph Dweck, Carol S. TI The Far-Reaching Effects of Believing People Can Change: Implicit Theories of Personality Shape Stress, Health, and Achievement During Adolescence SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article DE implicit theories; stress; health; ostracism; psychological interventions ID SOCIAL-PSYCHOLOGICAL INTERVENTIONS; SELF-AFFIRMATION; STEREOTYPE THREAT; MIDDLE SCHOOL; POWER; STUDENTS; AGGRESSION; IDENTITY; VICTIMIZATION; INTELLIGENCE AB The belief that personality is fixed (an entity theory of personality) can give rise to negative reactions to social adversities. Three studies showed that when social adversity is common-at the transition to high school-an entity theory can affect overall stress, health, and achievement. Study 1 showed that an entity theory of personality, measured during the 1st month of 9th grade, predicted more negative immediate reactions to social adversity and, at the end of the year, greater stress, poorer health, and lower grades in school. Studies 2 and 3, both experiments, tested a brief intervention that taught a malleable (incremental) theory of personality-the belief that people can change. The incremental theory group showed less negative reactions to an immediate experience of social adversity and, 8 months later, reported lower overall stress and physical illness. They also achieved better academic performance over the year. Discussion centers on the power of targeted psychological interventions to effect far-reaching and long-term change by shifting interpretations of recurring adversities during developmental transitions. C1 [Yeager, David Scott] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA. [Johnson, Rebecca] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Spitzer, Brian James] NYU, Steinhardt Sch Culture Educ & Human Dev, New York, NY 10003 USA. [Trzesniewski, Kali H.] Univ Calif Davis, Dept Human Dev, Davis, CA USA. [Powers, Joseph] Stanford Univ, Grad Sch Educ, Stanford, CA 94305 USA. [Dweck, Carol S.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Yeager, DS (reprint author), 108 East Dean Keeton Stop A8000, Austin, TX 78712 USA. EM dyeager@utexas.edu OI Yeager, David/0000-0002-8522-9503 NR 101 TC 26 Z9 27 U1 12 U2 86 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 EI 1939-1315 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD JUN PY 2014 VL 106 IS 6 BP 867 EP 884 DI 10.1037/a0036335 PG 18 WC Psychology, Social SC Psychology GA AJ7SN UT WOS:000337897500001 PM 24841093 ER PT J AU Sayah, R Farah, J Donadille, L Herault, J Delacroix, S De Marzi, L De Oliveira, A Vabre, I Stichelbaut, F Lee, C Bolch, WE Clairand, I AF Sayah, R. Farah, J. Donadille, L. Herault, J. Delacroix, S. De Marzi, L. De Oliveira, A. Vabre, I. Stichelbaut, F. Lee, C. Bolch, W. E. Clairand, I. TI Secondary neutron doses received by paediatric patients during intracranial proton therapy treatments SO JOURNAL OF RADIOLOGICAL PROTECTION LA English DT Article DE proton therapy; passive scattering; stray neutron doses; pediatric and adult patients; intracranial treatments ID MONTE-CARLO SIMULATIONS; RADIATION-THERAPY; STRAY RADIATION; 2ND CANCER; EQUIVALENT; RADIOTHERAPY; PHANTOMS; FIELD; RISK; IRRADIATION AB This paper's goal is to assess secondary neutron doses received by paediatric patients treated for intracranial tumours using a 178 MeV proton beam. The MCNPX Monte Carlo model of the proton therapy facility, previously validated through experimental measurements for both proton and neutron dosimetry, was used. First, absorbed dose was calculated for organs located outside the clinical target volume using a series of hybrid computational phantoms for different ages and considering a realistic treatment plan. In general, secondary neutron dose was found to decrease as the distance to the treatment field increases and as the patient age increases. In addition, secondary neutron doses were studied as a function of the beam incidence. Next, neutron equivalent dose was assessed using organ-specific energy-dependent radiation weighting factors determined from Monte Carlo simulations of neutron spectra at each organ. The equivalent dose was found to reach a maximum value of similar to 155 mSv at the level of the breasts for a delivery of 49 proton Gy to an intracranial tumour of a one-year-old female patient. Finally, a thorough comparison of the calculation results with published data demonstrated the dependence of neutron dose on the treatment configuration and proved the need for facility-specific and treatment-dependent neutron dose calculations. C1 [Sayah, R.; Farah, J.; Donadille, L.; Clairand, I.] PRP HOM SDE, IRSN, F-92262 Fontenay Aux Roses, France. [Herault, J.] CAL Cyclotron Biomed, F-06200 Nice, France. [Delacroix, S.; De Marzi, L.; De Oliveira, A.] Inst Curie, Ctr Protontherapie Orsay ICPO, F-91898 Orsay, France. [Vabre, I.] IPN, F-91406 Orsay, France. [Stichelbaut, F.] IBA, B-1348 Louvain, Belgium. [Lee, C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. [Bolch, W. E.] Univ Florida, Dept Nucl & Radiol, Gainesville, FL 32611 USA. [Bolch, W. E.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA. RP Sayah, R (reprint author), PRP HOM SDE, IRSN, BP17, F-92262 Fontenay Aux Roses, France. EM jad.farah@irsn.fr RI Lee, Choonsik/C-9023-2015 OI Lee, Choonsik/0000-0003-4289-9870 NR 40 TC 4 Z9 4 U1 0 U2 8 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0952-4746 EI 1361-6498 J9 J RADIOL PROT JI J. Radiol. Prot. PD JUN PY 2014 VL 34 IS 2 BP 279 EP 296 DI 10.1088/0952-4746/34/2/279 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AJ7US UT WOS:000337904600009 PM 24704989 ER PT J AU Lee, E Lamart, S Little, MP Lee, C AF Lee, Eunah Lamart, Stephanie Little, Mark P. Lee, Choonsik TI Database of normalised computed tomography dose index for retrospective CT dosimetry SO JOURNAL OF RADIOLOGICAL PROTECTION LA English DT Article DE computed tomography dose index; CT dose survey; dose reconstruction ID CANCER-RISK; SCANS; SCANNERS AB Volumetric computed tomography dose index (CTDIvol) is an important dose descriptor to reconstruct organ doses for patients combined with the organ dose calculated from computational human phantoms coupled with Monte Carlo transport techniques. CTDIvol can be derived from weighted CTDI (CTDIw) normalised to the tube current-time product (mGy/100 mAs), using knowledge of tube current-time product (mAs), tube potential (kVp), type of CTDI phantoms (head or body), and pitch. The normalised CTDIw is one of the characteristics of a CT scanner but not readily available from the literature. In the current study, we established a comprehensive database of normalised CTDIw values based on multiple data sources: the ImPACT dose survey from the United Kingdom, the CT-Expo dose calculation program, and surveys performed by the US Food and Drug Administration (FDA) and the National Lung Screening Trial (NLST). From the sources, the CTDIw values for a total of 68, 138, 30, and 13 scanner model groups were collected, respectively. The different scanner groups from the four data sources were sorted and merged into 162 scanner groups for eight manufacturers including General Electric (GE), Siemens, Philips, Toshiba, Elscint, Picker, Shimadzu, and Hitachi. To fill in missing CTDI values, a method based on exponential regression analysis was developed based on the existing data. Once the database was completed, two different analyses of data variability were performed. First, we averaged CTDI values for each scanner in the different data sources and analysed the variability of the average CTDI values across the different scanner models within a given manufacturer. Among the four major manufacturers, Toshiba and Philips showed the greatest coefficient of variation (COV) (=standard deviation/mean) for the head and body normalised CTDIw values, 39% and 54%, respectively. Second, the variation across the different data sources was analysed for CT scanners where more than two data sources were involved. The CTDI values for the scanners from Siemens showed the greatest variation across the data sources, being about four times greater than the variation of Toshiba scanners. The established CTDI database will be used for the reconstruction of CTDIvol and then the estimation of individualised organ doses for retrospective patient cohorts in epidemiologic studies. C1 [Lee, Eunah; Lamart, Stephanie; Little, Mark P.; Lee, Choonsik] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. RP Lee, E (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. EM leechoonsik@mail.nih.gov RI Lee, Choonsik/C-9023-2015; OI Lee, Choonsik/0000-0003-4289-9870; Little, Mark/0000-0003-0980-7567 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This work was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 14 TC 6 Z9 6 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0952-4746 EI 1361-6498 J9 J RADIOL PROT JI J. Radiol. Prot. PD JUN PY 2014 VL 34 IS 2 BP 363 EP 388 DI 10.1088/0952-4746/34/2/363 PG 26 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AJ7US UT WOS:000337904600016 PM 24727361 ER PT J AU Han, EY Lee, C Mcguire, L Bolch, WE AF Han, Eun Young Lee, Choonsik Mcguire, Lynn Bolch, Wesley E. TI A practical guideline for the release of patients treated by I-131 based on Monte Carlo dose calculations for family members SO JOURNAL OF RADIOLOGICAL PROTECTION LA English DT Article DE guideline; I-131; Monte Carlo ID THERAPY; EXPOSURE; POINT; LINE AB We recently published effective doses per time-integrated activity (mSv MBq(-1) s(-1)) for paediatric and adult family members exposed to an adult patient released from hospital following I-131 therapy. In the present study, we intend to provide medical physicists with a methodology to estimate family member effective dose in daily clinical practice because the duration of post-radiation precautions for the patient-family member exposure scenario has not been explicitly delineated based on the effective dose. Four different exposure scenarios are considered in this study including (1) a patient and a family member standing face to face, (2) a patient and a family member lying side by side, (3) an adult female patient holding a newborn child to her chest and (4) a one-year-old child standing on the lap of an adult female patient following her I-131 therapy. The results of this study suggest that an adult female hyperthyroidism (HT) patient who was administered with 740 MBq should keep a distance of 100 cm from a 15-year-old child for six days and the same distance from other adults for seven days. The HT female patient should avoid holding a newborn against her chest for at least 16 days following hospital discharge, and a female patient treated with 5550 MBq for differentiated thyroid cancer should not hold her newborn child for at least 15 days following hospital discharge. This study also gives dose coefficients allowing one to predict age-specific effective doses to family members given the measured dose rate (mSv h(-1)) of the patient. In conclusion, effective dose-based patient release criteria with a modified NRC two-component model provide a site medical physicist with less restrictive and age-specific radiation precaution guidance as they fully consider a patient's iodine biokinetics and photon attenuation within both the patient and the exposed family members. C1 [Han, Eun Young] Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA. [Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Mcguire, Lynn] Univ Arkansas Med Sci, Dept Radiol, Div Nucl Med, Little Rock, AR 72205 USA. [Bolch, Wesley E.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA. RP Han, EY (reprint author), Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA. EM eyhan@uams.edu RI Lee, Choonsik/C-9023-2015 OI Lee, Choonsik/0000-0003-4289-9870 NR 16 TC 3 Z9 3 U1 0 U2 6 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0952-4746 EI 1361-6498 J9 J RADIOL PROT JI J. Radiol. Prot. PD JUN PY 2014 VL 34 IS 2 BP N7 EP N17 DI 10.1088/0952-4746/34/2/N7 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AJ7US UT WOS:000337904600003 PM 24705486 ER PT J AU Yoo, SS Jorgensen, TJ Kennedy, AR Boice, JD Shapiro, A Hu, TCC Moyer, BR Grace, MB Kelloff, GJ Fenech, M Prasanna, PGS Coleman, CN AF Yoo, Stephen S. Jorgensen, Timothy J. Kennedy, Ann R. Boice, John D., Jr. Shapiro, Alla Hu, Tom C-C Moyer, Brian R. Grace, Marcy B. Kelloff, Gary J. Fenech, Michael Prasanna, Pataje G. S. Coleman, C. Norman TI Mitigating the risk of radiation-induced cancers: limitations and paradigms in drug development SO JOURNAL OF RADIOLOGICAL PROTECTION LA English DT Review DE radiation-induced cancer; radiation mitigator; radioprotector; radiation risk ID PERIPHERAL-BLOOD LYMPHOCYTES; DICENTRIC CHROMOSOME ASSAY; GRADE PROSTATE-CANCER; BOWMAN-BIRK INHIBITOR; PHOSPHORIBOSYL TRANSFERASE LOCUS; NUTRITION INTERVENTION TRIALS; SPORADIC COLORECTAL ADENOMAS; DISEASE-SPECIFIC MORTALITY; BLOCK MICRONUCLEUS ASSAY; ATM-DEFICIENT MICE AB The United States radiation medical countermeasures (MCM) programme for radiological and nuclear incidents has been focusing on developing mitigators for the acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and biodosimetry technologies to provide radiation dose assessments for guiding treatment. Because a nuclear accident or terrorist incident could potentially expose a large number of people to low to moderate doses of ionising radiation, and thus increase their excess lifetime cancer risk, there is an interest in developing mitigators for this purpose. This article discusses the current status, issues, and challenges regarding development of mitigators against radiation-induced cancers. The challenges of developing mitigators for ARS include: the long latency between exposure and cancer manifestation, limitations of animal models, potential side effects of the mitigator itself, potential need for long-term use, the complexity of human trials to demonstrate effectiveness, and statistical power constraints for measuring health risks (and reduction of health risks after mitigation) following relatively low radiation doses (< 0 :75 Gy). Nevertheless, progress in the understanding of the molecular mechanisms resulting in radiation injury, along with parallel progress in dose assessment technologies, make this an opportune, if not critical, time to invest in research strategies that result in the development of agents to lower the risk of radiation-induced cancers for populations that survive a significant radiation exposure incident. C1 [Yoo, Stephen S.; Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Jorgensen, Timothy J.] Georgetown Univ, Sch Med, Dept Radiat Med, Washington, DC USA. [Kennedy, Ann R.] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Boice, John D., Jr.] Vanderbilt Univ Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med, Div Epidemiol, Nashville, TN USA. [Boice, John D., Jr.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA. [Shapiro, Alla] US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Emergency Coordinat, Silver Spring, MD USA. [Hu, Tom C-C; Moyer, Brian R.; Grace, Marcy B.] BARDA, Dept Hlth & Human Serv, Div CBRN Countermeasures, Off Assistant Secretary Preparedness & Response,O, Washington, DC USA. [Kelloff, Gary J.] NCI, Canc Imaging Program, Div Canc Treatment & Diag, NIH, Bethesda, MD USA. [Fenech, Michael] Commonwealth Sci & Ind Res Org, Adelaide, SA, Australia. RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, 9609 Med Ctr Dr 3W102, Bethesda, MD 20892 USA. FU NCI's Radiation Research Program FX NCI's Radiation Research Program supported this work. The views expressed are those of the authors; no endorsement by NCI or other agencies has been given or inferred. This article has been reviewed by FDA and determined not to be consistent with Agency's views or policies. It reflects only the views and opinions of the author. Authors would like to acknowledge and thank the critical reading and review of the manuscript by Drs Rosemary Roberts and Joanne Holmes, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, USA. NR 172 TC 3 Z9 3 U1 0 U2 16 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0952-4746 EI 1361-6498 J9 J RADIOL PROT JI J. Radiol. Prot. PD JUN PY 2014 VL 34 IS 2 BP R25 EP R52 DI 10.1088/0952-4746/34/2/R25 PG 28 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AJ7US UT WOS:000337904600002 PM 24727460 ER PT J AU Tempero, M AF Tempero, Margaret TI Embracing Team-Based Oncology Care SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Tempero, Margaret] Univ Calif San Francisco, Pancreas Ctr, San Francisco, CA 94143 USA. [Tempero, Margaret] ASCO, Alexandria, VA USA. [Tempero, Margaret] NCI, Clin Oncol Study Sect, Bethesda, MD 20892 USA. [Tempero, Margaret] Mayo Clin, Rochester, MN USA. [Tempero, Margaret] UAB Minnesota, Birmingham, AL USA. [Tempero, Margaret] Univ Arizona, GI SPORE, Tucson, AZ 85721 USA. [Tempero, Margaret] Alberta Canada Canc Board, Lustgarten Fdn, Pancreat Canc Act Network, Fdn 5, Edmonton, AB, Canada. [Tempero, Margaret] EORTC, Brussels, Belgium. [Tempero, Margaret] Univ Calif San Francisco, Div Med Oncol, San Francisco, CA 94143 USA. [Tempero, Margaret] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Tempero, M (reprint author), Univ Calif San Francisco, Pancreas Ctr, San Francisco, CA 94143 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JUN PY 2014 VL 12 IS 6 BP 845 EP 845 PG 1 WC Oncology SC Oncology GA AJ5GF UT WOS:000337710000001 PM 24925194 ER PT J AU Noguchi, S Ogawa, M Kawahara, G Malicdan, MC Nishino, I AF Noguchi, Satoru Ogawa, Megumu Kawahara, Genri Malicdan, May Christine Nishino, Ichizo TI Allele-specific Gene Silencing of Mutant mRNA Restores Cellular Function in Ullrich Congenital Muscular Dystrophy Fibroblasts SO MOLECULAR THERAPY-NUCLEIC ACIDS LA English DT Article DE allele-specific; autosomal dominant inheritance; Co16a1; gene silencing; muscular dystrophy; siRNA ID COLLAGEN-VI DEFICIENCY; DISEASE; COMMON; SARCOLEMMA; MUTATIONS; SECRETION; SEQUENCE; CHAINS AB Ullrich congenital muscular dystrophy (UCMD) is an inherited muscle disorder characterized clinically by muscle weakness, distal joint hyperlaxity, and proximal joint contractures. Sporadic and recessive mutations in the three collagen VI genes, COL6A1, COL6A2, and COL6A3, are reported to be causative. In the sporadic forms, a heterozygous point mutation causing glycine substitution in the triple helical domain has been identified in higher rate. In this study, we examined the efficacy of siRNAs, which target point mutation site, on specific knockdown toward transcripts from mutant allele and evaluated consequent cellular phenotype of UCMD fibroblasts. We evaluated the effect of siRNAs targeted to silence-specific COL6A1 alleles in UCMD fibroblasts, where simultaneous expression of both wild-type and mutant collagen VI resulted in defective collagen localization. Addition of mutant-specific siRNAs allowed normal extracellular localization of collagen VI surrounding fibroblasts, suggesting selective inhibition of mutant collagen VI. Targeting the single-nucleotide COL6A1 c.850G>A (p.G284R) mutation responsible a sporadic autosomal dominant form of UCMD can potently and selectively block expression of mutant collagen VI. These results suggest that allele-specific knockdown of the mutant mRNA can potentially be considered as a therapeutic procedure in UCMD due to COL6A1 point mutations. C1 [Noguchi, Satoru; Ogawa, Megumu; Kawahara, Genri; Malicdan, May Christine; Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Dept Neuromuscular Res, Natl Inst Neurosci, Translat Med Ctr, Kodaira, Tokyo 1878502, Japan. [Noguchi, Satoru; Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Translat Med Ctr, Dept Clin Dev, Kodaira, Tokyo 1878502, Japan. [Kawahara, Genri] Childrens Hosp Boston, Div Genet, Program Genom, Boston, MA USA. [Malicdan, May Christine] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Noguchi, S (reprint author), Natl Ctr Neurol & Psychiat, Dept Neuromuscular Res, Natl Inst Neurosci, 4-1-1 Ogawahigashi Cho, Kodaira, Tokyo 1878502, Japan. EM noguchi@ncnp.go.jp OI Nishino, Ichizo/0000-0001-9452-112X FU Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP [25-5]; Research on Rare and intractable disease from the Ministry of Health, Labour and Welfare, Japan; JSPS KAKENHI [23390236, 26293214] FX We thank Takahiro Yonekawa (NCNP) for helpful discussion. This study was partially supported by Intramural Research Grant (25-5) for Neurological and Psychiatric Disorders of NCNP to S.N., by Research on Rare and intractable disease from the Ministry of Health, Labour and Welfare to I.N., Japan and by JSPS KAKENHI (23390236, 26293214) to S.N. The authors declared no conflict of interest. NR 25 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2162-2531 J9 MOL THER-NUCL ACIDS JI Mol. Ther.-Nucl. Acids PD JUN PY 2014 VL 3 AR e171 DI 10.1038/mtna.2014.22 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AK0BA UT WOS:000338076400005 PM 24959844 ER PT J AU Ahsan, S Raabe, E Haffner, M Warren, K Quezado, M Ballester, L Nazarian, J Eberhart, C Rodriguez, F AF Ahsan, Sama Raabe, Eric Haffner, Michael Warren, Katherine Quezado, Martha Ballester, Leomar Nazarian, Javad Eberhart, Charles Rodriguez, Fausto TI INCREASED 5-HYDROXYMETHYLCYTOSINE AND DECREASED 5-METHYLCYTOSINE ARE INDICATORS OF GLOBAL EPIGENETIC DYSREGULATION IN DIFFUSE INTRINSIC PONTINE GLIOMA SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 28-JUL 02, 2014 CL Singapore, SINGAPORE C1 [Ahsan, Sama] Johns Hopkins Dept Pediat Hematol Oncol, Baltimore, MD USA. [Raabe, Eric] Johns Hopkins Dept Pediat Oncol, Baltimore, MD USA. [Haffner, Michael] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Warren, Katherine] NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Quezado, Martha; Ballester, Leomar] NIH, Pathol Lab, Bethesda, MD 20892 USA. [Nazarian, Javad] Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA. [Eberhart, Charles; Rodriguez, Fausto] Johns Hopkins Univ Hosp, Div Neuropathol, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2014 VL 16 SU 1 MA HG-044 BP 50 EP 51 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AJ8AK UT WOS:000337924200191 ER PT J AU Grasso, C Truffaux, N Berlow, N Liu, LN Debily, MA Davis, L Huang, E Woo, P Tang, YJ Ponnuswami, A Chen, S Huang, YL Hutt-Cabezas, M Warren, K Dret, L Meltzer, P Mao, H Quezado, M van Vuurden, D Abraham, J Fouladi, M Svalina, MN Wang, N Hawkins, C Raabe, E Hulleman, E Li, XN Keller, C Spellman, PT Pal, R Grill, J Monje, M AF Grasso, Catherine Truffaux, Nathalene Berlow, Noah Liu, Lining Debily, Marie-Anne Davis, Lara Huang, Elaine Woo, Pamelyn Tang, Yujie Ponnuswami, Anitha Chen, Spenser Huang, Yulun Huett-Cabezas, Marianne Warren, Katherine Dret, Ludivine Meltzer, Paul Mao, Hua Quezado, Martha van Vuurden, Dannis Abraham, Jinu Fouladi, Maryam Svalina, Matthew N. Wang, Nicholas Hawkins, Cynthia Raabe, Eric Hulleman, Esther Li, Xiao-Nan Keller, Charles Spellman, Paul T. Pal, Ranadip Grill, Jacques Monje, Michelle TI FUNCTIONALLY-DEFINED THERAPEUTIC TARGETS IN DIFFUSE INTRINSIC PONTINE GLIOMA: A REPORT OF THE CHILDREN'S ONCOLOGY GROUP DIPG PRECLINICAL CONSORTIUM SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 28-JUL 02, 2014 CL Singapore, SINGAPORE C1 [Grasso, Catherine; Wang, Nicholas; Spellman, Paul T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Truffaux, Nathalene; Debily, Marie-Anne; Dret, Ludivine; Grill, Jacques] Inst Gustave Roussy, Villejuif, France. [Truffaux, Nathalene; Debily, Marie-Anne; Dret, Ludivine; Grill, Jacques] Univ Paris 11, Villejuif, France. [Berlow, Noah] Texas Tech Univ, Lubbock, TX 79409 USA. [Liu, Lining; Woo, Pamelyn; Tang, Yujie; Ponnuswami, Anitha; Chen, Spenser; Pal, Ranadip; Monje, Michelle] Stanford Univ, Stanford, CA 94305 USA. Univ Evry Val dEssone, Evry, France. [Davis, Lara; Huang, Elaine; Abraham, Jinu; Svalina, Matthew N.; Keller, Charles] Pape Family Pediat Res Inst, Portland, OR USA. [Huang, Yulun; Mao, Hua; Li, Xiao-Nan] Texas Childrens Canc Ctr, Houston, TX USA. Soochow Univ, Affiliated Hosp 1, Suzhou, Peoples R China. [Huett-Cabezas, Marianne; Raabe, Eric] Johns Hopkins Univ, Baltimore, MD USA. [Warren, Katherine; Meltzer, Paul; Quezado, Martha] NCI, Bethesda, MD 20892 USA. [van Vuurden, Dannis; Hulleman, Esther] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Fouladi, Maryam] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Hawkins, Cynthia] Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2014 VL 16 SU 1 MA HG-047 BP 51 EP 51 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AJ8AK UT WOS:000337924200194 ER PT J AU Shandilya, S McCully, C Murphy, R Akshintala, S Cole, D Macallister, RP Cruz, R Widemann, B Warren, K AF Shandilya, Shaefali McCully, Cynthia Murphy, Robert Akshintala, Srivandana Cole, Diane Macallister, Rhonda Pung Cruz, Rafael Widemann, Brigitte Warren, Katherine TI INTRANASAL DELIVERY OF CHEMOTHERAPEUTIC AGENTS IN A NON-HUMAN PRIMATE MODEL SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 28-JUL 02, 2014 CL Singapore, SINGAPORE C1 [Shandilya, Shaefali; McCully, Cynthia; Murphy, Robert; Akshintala, Srivandana; Cole, Diane; Macallister, Rhonda Pung; Cruz, Rafael; Widemann, Brigitte; Warren, Katherine] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2014 VL 16 SU 1 MA HG-052 BP 53 EP 53 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AJ8AK UT WOS:000337924200199 ER PT J AU Fouladi, M Bartels, U Warren, K Hassal, T Baugh, J Kirkendall, J Doughman, R Leach, J Jones, B Miles, L Hawkins, C Bouffet, E Hargrave, D Grill, J Jones, C Jacques, T Savage, S Goldman, S Leary, S Packer, R Saunders, D Wesseling, P Varlet, P van Vuurden, D AF Fouladi, Maryam Bartels, Ute Warren, Kathy Hassal, Tim Baugh, Joshua Kirkendall, Jenavieve Doughman, Renee Leach, James Jones, Blaise Miles, Lili Hawkins, Cynthia Bouffet, Eric Hargrave, Darren Grill, Jacques Jones, Chris Jacques, Thomas Savage, Sharon Goldman, Stewart Leary, Sarah Packer, Roger Saunders, Dawn Wesseling, Peter Varlet, Pascale van Vuurden, Dannis TI ESTABLISHMENT OF AN INTERNATIONAL DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) REGISTRY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 28-JUL 02, 2014 CL Singapore, SINGAPORE C1 [Fouladi, Maryam; Baugh, Joshua; Kirkendall, Jenavieve; Doughman, Renee; Leach, James; Jones, Blaise; Miles, Lili] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Bartels, Ute; Hawkins, Cynthia; Bouffet, Eric] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Warren, Kathy; Savage, Sharon] NIH, Bethesda, MD 20892 USA. [Hassal, Tim] Royal Childrens Hosp, Brisbane, Qld, Australia. [Hargrave, Darren; Saunders, Dawn] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Grill, Jacques] Inst Gustave Roussy, Villejuif, France. [Jones, Chris] Inst Canc Res, Sutton, Surrey, England. [Jacques, Thomas] UCL, Child Hlth, London, England. [Goldman, Stewart] Lurie Childrens Hosp, Chicago, IL USA. [Leary, Sarah] Seattle Childrens Hosp, Seattle, WA USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Wesseling, Peter] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Varlet, Pascale] Hop St Anne, F-75674 Paris, France. [van Vuurden, Dannis] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. RI Wesseling, P./H-8114-2014; Jacques, Thomas/C-2209-2008 OI Wesseling, P./0000-0001-5453-5201; Jacques, Thomas/0000-0002-7833-2158 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2014 VL 16 SU 1 MA HG-074 BP 58 EP 59 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AJ8AK UT WOS:000337924200221 ER PT J AU Fisher, MJ Widemann, BC Dombi, E Wolters, P Cantor, A Vinks, A Parentesis, J Ullrich, N Gutmann, D Viskochil, D Tonsgard, J Korf, B Packer, R Weiss, B AF Fisher, Michael J. Widemann, Brigitte C. Dombi, Eva Wolters, Pamela Cantor, Alan Vinks, Alexander Parentesis, John Ullrich, Nicole Gutmann, David Viskochil, David Tonsgard, James Korf, Bruce Packer, Roger Weiss, Brian TI PHASE 2 STUDY OF THE MTOR INHIBITOR SIROLIMUS FOR PROGRESSIVE NF1-ASSOCIATED PLEXIFORM NEUROFIBROMAS (PN): A NEUROFIBROMATOSIS CLINICAL TRIALS CONSORTIUM STUDY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 28-JUL 02, 2014 CL Singapore, SINGAPORE C1 [Fisher, Michael J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Widemann, Brigitte C.; Dombi, Eva; Wolters, Pamela] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Cantor, Alan; Korf, Bruce] Univ Alabama Birmingham, Birmingham, AL USA. [Vinks, Alexander; Parentesis, John; Weiss, Brian] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Ullrich, Nicole] Childrens Hosp, Boston, MA 02115 USA. [Gutmann, David] Washington Univ, St Louis, MO USA. [Viskochil, David] Primary Childrens Med Ctr, Salt Lake City, UT USA. [Tonsgard, James] Univ Chicago, Chicago, IL 60637 USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2014 VL 16 SU 1 MA RTU-009 BP 129 EP 129 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AJ8AK UT WOS:000337924200493 ER PT J AU Fisher, MJ Marcus, L Weiss, B Kim, A Dombi, E Baldwin, A Whitcomb, P Martin, S Gillespie, A Doyle, A Widemann, BC AF Fisher, Michael J. Marcus, Leigh Weiss, Brian Kim, AeRang Dombi, Eva Baldwin, Andrea Whitcomb, Patricia Martin, Staci Gillespie, Andrea Doyle, Austin Widemann, Brigitte C. TI SELUMETINIB (AZD6244) HYDROGEN SULFATE, A MEK1/2 INHIBITOR, IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1 (NF1) AND INOPERABLE PLEXIFORM NEUROFIBROMAS (PNS): A PHASE I STUDY SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO) CY JUN 28-JUL 02, 2014 CL Singapore, SINGAPORE C1 [Dombi, Eva; Baldwin, Andrea; Whitcomb, Patricia; Martin, Staci; Gillespie, Andrea; Doyle, Austin; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Fisher, Michael J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Marcus, Leigh; Kim, AeRang] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Weiss, Brian] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2014 VL 16 SU 1 MA RTU-010 BP 129 EP 129 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AJ8AK UT WOS:000337924200494 ER PT J AU Okoli, T Traba, J Sack, M AF Okoli, Tracy Traba, Javier Sack, Michael TI Acetylation in the control of the NLRP3 inflammasome SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Virtual Poster Symposium of the American-College-of-Clinical-Pharmacy CY MAY 20-21, 2014 CL ELECTR NETWORK SP Amer Coll Clin Pharm C1 [Okoli, Tracy] Belmont Univ, Coll Pharm, Nashville, TN USA. [Traba, Javier; Sack, Michael] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 EI 1875-9114 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUN PY 2014 VL 34 IS 6 MA 141 BP E113 EP E113 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AJ5BV UT WOS:000337696600144 ER PT J AU Martin, A Simmons, WK Beauchamp, MS Gotts, SJ AF Martin, Alex Simmons, W. Kyle Beauchamp, Michael S. Gotts, Stephen J. TI Is a single 'hub', with lots of spokes, an accurate description of the neural architecture of action semantics? Comment on "Action semantics: A unifying conceptual framework for the selective use of multimodal and modality-specific object knowledge" by van Elk, van Schie and Bekkering SO PHYSICS OF LIFE REVIEWS LA English DT Editorial Material ID ANATOMY; NETWORKS; CORTEX; BRAIN C1 [Martin, Alex; Gotts, Stephen J.] NIMH, NIH, Bethesda, MD 20892 USA. [Simmons, W. Kyle] Laureate Inst Brain Res, Tulsa, OK USA. [Simmons, W. Kyle] Univ Tulsa, Tulsa, OK 74104 USA. [Beauchamp, Michael S.] Univ Texas Houston, Sch Med, Dept Neurobiol & Anat, Houston, TX 77225 USA. RP Martin, A (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. RI Simmons, William/K-8925-2015 OI Simmons, William/0000-0002-0399-9003 NR 16 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1571-0645 EI 1873-1457 J9 PHYS LIFE REV JI Phys. Life Rev. PD JUN PY 2014 VL 11 IS 2 BP 261 EP 262 DI 10.1016/j.plrev.2014.01.002 PG 2 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA AJ8UH UT WOS:000337982800021 PM 24461375 ER PT J AU Rynes, KN Rohrbaugh, MJ Lebensohn-Chialvo, F Shoham, V AF Rynes, Kristina N. Rohrbaugh, Michael J. Lebensohn-Chialvo, Florencia Shoham, Varda TI Parallel Demand-Withdraw Processes in Family Therapy for Adolescent Drug Abuse SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE demand-withdraw interaction; adolescent substance abuse; family therapy; BSFT; process-outcome research ID SUBSTANCE USE; EXTERNALIZING BEHAVIORS; MARITAL INTERACTION; PROBLEM DRINKING; COMMUNICATION; GENDER; CHILD; ALCOHOLISM; CONFLICT; EFFICACY AB Isomorphism, or parallel process, occurs in family therapy when patterns of therapist-client interaction replicate problematic interaction patterns within the family. This study investigated parallel demand-withdraw processes in brief strategic family therapy (BSFT) for adolescent drug abuse, hypothesizing that therapist-demand/adolescent-withdraw interaction (TD/AW) cycles observed early in treatment would predict poor adolescent outcomes at follow-up for families who exhibited entrenched parent-demand/adolescent-withdraw interaction (PD/AW) before treatment began. Participants were 91 families who received at least four sessions of BSFT in a multisite clinical trial on adolescent drug abuse (Robbins et al., 2011). Prior to receiving therapy, families completed videotaped family interaction tasks from which trained observers coded PD/AW. Another team of raters coded TD/AW during two early BSFT sessions. The main dependent variable was the number of drug-use days that adolescents reported in timeline follow-back interviews 7 to 12 months after family therapy began. Zero-inflated Poisson regression analyses supported the main hypothesis, showing that PD/AW and TD/AW interacted to predict adolescent drug use at follow-up. For adolescents in high PD/AW families, higher levels of TD/AW predicted significant increases in drug use at follow-up, whereas for low PD/AW families, TD/AW and follow-up drug use were unrelated. Results suggest that attending to parallel demand-withdraw processes in parent-adolescent and therapist-adolescent dyads may be useful in family therapy for substance-using adolescents. C1 [Rynes, Kristina N.] Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87106 USA. [Rohrbaugh, Michael J.; Lebensohn-Chialvo, Florencia; Shoham, Varda] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. [Shoham, Varda] NIMH, Bethesda, MD 20892 USA. RP Rynes, KN (reprint author), Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, 2650 Yale Blvd SE,MSC11-6280, Albuquerque, NM 87106 USA. EM krynes@unm.edu FU NIAAA NIH HHS [T32-AA0018108-01A1, T32 AA018108]; NIDA NIH HHS [U10-DA13720, U10 DA013720, U10-DA15815, R01-DA17539-01, R01 DA017539, U10 DA015815] NR 58 TC 1 Z9 1 U1 5 U2 11 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X EI 1939-1501 J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2014 VL 28 IS 2 BP 420 EP 430 DI 10.1037/a0031812 PG 11 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA AJ7XW UT WOS:000337915800012 PM 23438248 ER PT J AU Bhutani, M Landgren, O AF Bhutani, M. Landgren, O. TI Imaging in smoldering (asymptomatic) multiple myeloma. Past, present and future SO RADIOLOGE LA German DT Article DE Skeletal survey; Computed tomography; Magnetic resonance imaging; Positron-emission tomography; Survival ID STEM-CELL TRANSPLANTATION; WHOLE-BODY MRI; APPARENT DIFFUSION-COEFFICIENT; HIGH-RISK MYELOMA; BONE-MARROW; F-18-FDG PET/CT; PROGNOSTIC-SIGNIFICANCE; EMISSION-TOMOGRAPHY; PRECURSOR DISEASE; SKELETAL SURVEY AB Emerging clinical trial data support treatment of high-risk smoldering multiple myeloma (SMM) upon diagnosis, and not only at the time of progression to symptomatic complications (multiple myeloma). Early detection of bone and/or bone marrow involvement by sensitive imaging modalities may help define SMM patients at a high risk of progression. Current (2011) consensus guidelines recognize skeletal survey as a cornerstone modality for assessment of bone involvement at initial diagnosis and during follow-up of SMM. Skeletal survey has severe limitations related to underdetection of bone lesions and also provides no information on bone marrow abnormalities. Modern imaging strategies such as fluorodeoxyglucose positron-emission tomography/CT (FDG PET/CT) and MRI, in conjunction with functional innovations, provide improved estimates of global abnormalities in the bone marrow and bone compartments. These methods have the potential to objectively quantify early transformation from SMM to multiple myeloma. Although frequently used for staging and risk prognostication in multiple myeloma, modern imaging techniques have only been evaluated to a limited extent in SMM. Scant data in SMM indicate the prognostic value of two or more MRI-detected focal bone marrow abnormalities, which, if present, predict rapid progression to multiple myeloma. Data evaluating the role of FDG PET/CT in detecting early bone marrow abnormalities as an aid to predicting risk or directing treatment in SMM is currently lacking. The superior specificity and sensitivity of modern imaging techniques compared to skeletal survey suggest that these should have a place in standard practice management of patients at a high risk of SMM progression. The model imaging of the future should be an all-in-one strategy offering high diagnostic performance for bone marrow abnormalities and low-volume bone lesions, as well as allowing monitoring by minimizing radiation exposure and the need for contrast agents. Newer imaging techniques need to be validated in prospective clinical trials assessing the SMM to multiple myeloma transition, with the aim of enabling appropriate management decisions. Efforts are also needed to improve the costs and availability of whole-body MRI and/or FDG PET/CT, in order to facilitate their widespread adoption as first-line detection modalities. Future clinical trials of therapeutic agents using earlier detection strategies will have to be carefully designed and take into consideration the risk of lead-time and length-time biases, which might falsely demonstrate longer overall survival. The English full text version of this article is available at SpringerLink (under "Supplemental"). C1 [Bhutani, M.; Landgren, O.] NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 10 Room 13N240, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov NR 54 TC 4 Z9 4 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-832X EI 1432-2102 J9 RADIOLOGE JI Radiologe PD JUN PY 2014 VL 54 IS 6 BP 572 EP + DI 10.1007/s00117-014-2694-7 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AJ6GM UT WOS:000337789000007 PM 24927659 ER PT J AU Liu, SH Moayeri, M Leppla, SH AF Liu, Shihui Moayeri, Mahtab Leppla, Stephen H. TI Anthrax lethal and edema toxins in anthrax pathogenesis SO TRENDS IN MICROBIOLOGY LA English DT Review DE anthrax; capillary morphogenesis protein 2; edema toxin; lethal toxin; tumor endothelial marker 8 ID CAPILLARY MORPHOGENESIS PROTEIN-2; KINASE 1/2 ACTIVITY; BACILLUS-ANTHRACIS; INHALATION ANTHRAX; SYSTEMIC ANTHRAX; BARRIER FUNCTION; IN-VIVO; RECEPTOR; INTERNALIZATION; HOST AB The pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. B. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the USA. The exotoxins secreted by B. anthracis use capillary morphogenesis protein 2 (CMG2) as the major toxin receptor and play essential roles in pathogenesis during the entire course of the disease. This review focuses on the activities of anthrax toxins and their roles in initial and late stages of anthrax infection. C1 [Liu, Shihui; Moayeri, Mahtab; Leppla, Stephen H.] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Liu, SH (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM shliu@niaid.nih.gov; nimoayeri@niaid.nih.gov; sleppla@niaid.nih.gov FU intramural research programs of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the intramural research programs of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 98 TC 47 Z9 53 U1 5 U2 48 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X EI 1878-4380 J9 TRENDS MICROBIOL JI Trends Microbiol. PD JUN PY 2014 VL 22 IS 6 BP 317 EP 325 DI 10.1016/j.tim.2014.02.012 PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA AJ7JR UT WOS:000337873500005 PM 24684968 ER PT J AU Friend, DM Kravitz, AV AF Friend, Danielle M. Kravitz, Alexxai V. TI Working together: basal ganglia pathways in action selection SO TRENDS IN NEUROSCIENCES LA English DT Editorial Material ID NEURONS; EXPECTATION; DISORDERS; STRIATUM; MOVEMENT AB Jin, Tecuapetla, and Costa combined in vivo electrophysiology with optogenetic-identification to examine firing in multiple basal ganglia nuclei during rapid motor sequences. Their results support a model of basal ganglia function in which co-activation of the direct and indirect pathways facilitate appropriate, while inhibiting competing, motor programs. C1 [Friend, Danielle M.; Kravitz, Alexxai V.] NIDDK, Bethesda, MD 20814 USA. [Kravitz, Alexxai V.] NIDA, Baltimore, MD USA. RP Kravitz, AV (reprint author), NIDDK, NIH, Bldg 10,Room 5-5932 10 Ctr Dr, Bethesda, MD 20814 USA. EM lex.kravitz@nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 15 TC 13 Z9 14 U1 1 U2 17 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUN PY 2014 VL 37 IS 6 BP 301 EP 303 DI 10.1016/j.tins.2014.04.004 PG 3 WC Neurosciences SC Neurosciences & Neurology GA AJ7ML UT WOS:000337880700001 PM 24816402 ER PT J AU Cuthbert, BN AF Cuthbert, Bruce N. CA NIMH RDoC Workgrp TI The RDoC framework: continuing commentary SO WORLD PSYCHIATRY LA English DT Editorial Material C1 [Cuthbert, Bruce N.; NIMH RDoC Workgrp] NIMH, Bethesda, MD 20892 USA. RP Cuthbert, BN (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA. NR 4 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1723-8617 EI 2051-5545 J9 WORLD PSYCHIATRY JI World Psychiatry PD JUN PY 2014 VL 13 IS 2 BP 196 EP 197 DI 10.1002/wps.20140 PG 2 WC Psychiatry SC Psychiatry GA AJ3SS UT WOS:000337588300023 PM 24890074 ER PT J AU Afonin, KA Kasprzak, WK Bindewald, E Kireeva, M Viard, M Kashlev, M Shapiro, BA AF Afonin, Kirill A. Kasprzak, Wojciech K. Bindewald, Eckart Kireeva, Maria Viard, Mathias Kashlev, Mikhail Shapiro, Bruce A. TI In Silico Design and Enzymatic Synthesis of Functional RNA Nanoparticles SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID SECONDARY STRUCTURE PREDICTION; RNA/DNA HYBRID DUPLEXES; SPLIT FUNCTIONALITIES; BUILDING-BLOCKS; EMERGING FIELD; DNA HYBRIDS; POLYMERASE; DELIVERY; SIRNA; ELONGATION AB CONSPECTUS: The use of RNAs as scaffolds for biomedical applications has several advantages compared with other existing nanomaterials. These include (i) programmability, (ii) precise control over folding and self-assembly, (iii) natural functionalities as exemplified by ribozymes, riboswitches, RNAi, editing, splicing, and inherent translation and transcription control mechanisms, (iv) biocompatibility, (v) relatively low immune response, and (vi) relatively low cost and ease of production. We have tapped into several of these properties and functionalities to construct RNA-based functional nanoparticles (RNA NPs). In several cases, the structural core and the functional components of the NPs are inherent in the same construct. This permits control over the spatial disposition of the components, intracellular availability, and precise stoichiometry. To enable the generation of RNA NPs, a pipeline is being developed. On one end, it encompasses the rational design and various computational schemes that promote design of the RNA-based nanoconstructs, ultimately producing a set of sequences consisting of RNA or RNA DNA hybrids, which can assemble into the designed construct. On On the other end of the pipeline is an experimental component, which takes the produced sequences and uses them to initialize and characterize their proper assembly and then test the resulting RNA NPs for their function and delivery in cell culture and animal models. An important aspect of this pipeline is the feedback that constantly occurs between the computational and the experimental parts, which synergizes the refinement of both the algorithmic methodologies and the experimental protocols. The utility of this approach is depicted by the several examples described in this Account (nanocubes, nanorings, and RNA DNA hybrids). Of particular interest, from the computational viewpoint, is that in most cases, first a three-dimensional representation of the assembly is produced, and only then are algorithms applied to generate the sequences that will assemble into the designated three-dimensional construct. This is opposite to the usual practice of predicting RNA structures from a given sequence, that is, the RNA folding problem. To be considered is the generation of sequences that upon assembly have the proper intra- or interstrand interactions (or both). Of particular interest from the experimental point of view is the determination and characterization of the proper thermodynamic, kinetic, functionality, and delivery protocols. Assembly of RNA NPs from individual single-stranded RNAs can be accomplished by one-pot techniques under the proper thermal and buffer conditions or, potentially more interestingly, by the use of various RNA polymerases that can promote the formation of RNA NPs cotransciptionally from specifically designed DNA templates. Also of importance is the delivery of the RNA NPs to the cells of interest in vitro or in vivo. Nonmodified RNAs rapidly degrade in blood serum and have difficulties crossing biological membranes due to their negative charge. These problems can be overcome by using, for example, polycationic lipid-based carriers. Our work involves the use of bolaamphiphiles, which are amphipathic compounds with positively charged hydrophilic head groups at each end connected by a hydrophobic chain. We have correlated results from molecular dynamics computations with various experiments to understand the characteristics of such delivery agents. C1 [Afonin, Kirill A.; Viard, Mathias; Shapiro, Bruce A.] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Kasprzak, Wojciech K.; Bindewald, Eckart; Viard, Mathias] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA. [Kireeva, Maria; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM shapirbr@mail.nih.gov FU Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; National Institutes of Health, Center for Cancer Research FX This publication has been funded in part with federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under Contract HHSN261200800001E. This research was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 75 TC 18 Z9 18 U1 2 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 EI 1520-4898 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD JUN PY 2014 VL 47 IS 6 BP 1731 EP 1741 DI 10.1021/ar400329z PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA AJ4KL UT WOS:000337645100011 PM 24758371 ER PT J AU Leeds, PR Yu, FS Wan, ZF Chiu, CT Zhang, YM Leng, Y Linares, GR Chuang, DM AF Leeds, Peter R. Yu, Fengshan Wan, Zhifei Chiu, Chi-Tso Zhang, Yumin Leng, Yan Linares, Gabriel R. Chuang, De-Maw TI A New Avenue for Lithium: Intervention in Traumatic Brain Injury SO ACS CHEMICAL NEUROSCIENCE LA English DT Review DE Anti-inflammation; behavioral deficits and cognitive improvements; combined therapy treatment; controlled cortical impact; functional recovery; GSK-3 (glycogen synthase kinase-3) inhibitor; lithium; mood stabilizer; neuroprotection; neuroregeneration; preclinical model; TBI (traumatic brain injury) ID GLYCOGEN-SYNTHASE KINASE-3; ENDOTHELIAL GROWTH-FACTOR; AMYLOID PRECURSOR PROTEIN; MOOD STABILIZERS LITHIUM; FOCAL CEREBRAL-ISCHEMIA; NEURAL PROGENITOR CELLS; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; N-ACETYL-ASPARTATE; RAT DENTATE GYRUS AB Traumatic brain injury (TBI) is a leading cause of disability and death from trauma to central nervous system (CNS) tissues. For patients who survive the initial injury, TBI can lead to neurodegeneration as well as cognitive and motor deficits, and is even a risk factor for the future development of neurodegenerative disorders such as Alzheimer's disease. Preclinical studies of multiple neuropathological and neurodegenerative disorders have shown that lithium, which is primarily used to treat bipolar disorder, has considerable neuroprotective effects. Indeed, emerging evidence now suggests that lithium can also mitigate neurological deficits incurred from TBI. Lithium exerts neuroprotective effects and stimulates neurogenesis via multiple signaling pathways; it inhibits glycogen synthase kinase-3 (GSK-3), upregulates neurotrophins and growth factors (e.g., brain-derived neurotrophic factor (BDNF)), modulates inflammatory molecules, upregulates neuroprotective factors (e.g., B-cell lymphoma-2 (Bcl-2), heat shock protein 70 (HSP-70)), and concomitantly downregulates pro-apoptotic factors. In various experimental TB1 paradigms, lithium has been shown to reduce neuronal death, microglial activation, cyclooxygenase-2 induction, amyloid-beta (A beta), and hyperphosphorylated tau levels, to preserve blood-brain barrier integrity, to mitigate neurological deficits and psychiatric disturbance, and to improve learning and memory outcome. Given that lithium exerts multiple therapeutic effects across an array of CNS disorders, including promising results in preclinical models of TB!, additional clinical research is clearly warranted to determine its therapeutic attributes for combating TBI. Here, we review lithium's exciting potential in ameliorating physiological as well as cognitive deficits induced by TBI. C1 [Leeds, Peter R.; Yu, Fengshan; Wan, Zhifei; Chiu, Chi-Tso; Leng, Yan; Linares, Gabriel R.; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Yu, Fengshan; Zhang, Yumin; Chuang, De-Maw] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Yu, Fengshan; Zhang, Yumin; Chuang, De-Maw] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov FU Department of Defense in the Center for Neuroscience and Regenerative Medicine (CNRM); Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS) FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS), and the Department of Defense in the Center for Neuroscience and Regenerative Medicine (CNRM). NR 174 TC 16 Z9 18 U1 1 U2 42 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD JUN PY 2014 VL 5 IS 6 BP 422 EP 433 DI 10.1021/cn500040g PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA AJ5KF UT WOS:000337720400004 PM 24697257 ER PT J AU Rapoport, SI AF Rapoport, Stanley I. TI Lithium and the Other Mood Stabilizers Effective in Bipolar Disorder Target the Rat Brain Arachidonic Acid Cascade SO ACS CHEMICAL NEUROSCIENCE LA English DT Review DE Lithium; bipolar disorder; arachidonic acid; carbamazepine; mood stabilizers; valproic acid; rat; brain; antidepressant; antipsychotics; biotype ID POSTMORTEM FRONTAL-CORTEX; ACYL-COA SYNTHETASES; PHOSPHOLIPASE A(2); DOCOSAHEXAENOIC ACID; UNANESTHETIZED RAT; VALPROIC ACID; DOUBLE-BLIND; IMAGING NEUROINFLAMMATION; CYCLOOXYGENASE-1 AND-2; TREATMENT DECREASES AB This Review evaluates the arachidonic acid (AA, 20:4n-6) cascade hypothesis for the actions of lithium and other FDA-approved mood stabilizers in bipolar disorder (BD). The hypothesis is based on evidence in unanesthetized rats that chronically administered lithium, carbamazepine, valproate, or lamotrigine each downregulated brain AA metabolism, and it is consistent with reported upregulated AA cascade markers in post-mortem BD brain. In the rats, each mood stabilizer reduced AA turnover in brain phospholipids, cyclooxygenase-2 expression, and prostaglandin E-2 concentration. Lithium and carbamazepine also reduced expression of cytosolic phospholipase A, (cPLA(2)) IVA, which releases AA from membrane phospholipids, whereas valproate uncompetitively inhibited in vitro acyl-CoA synthetase-4, which recycles AA into phospholipid. Topiramate and gabapentin, proven ineffective in BD, changed rat brain AA metabolism minimally. On the other hand, the atypical antipsychotics olanzapine and clozapine, which show efficacy in BD, decreased rat brain AA metabolism by reducing plasma AA availability. Each of the four approved mood stabilizers also dampened brain AA signaling during glutamatergic NMDA and dopaminergic D-2 receptor activation, while lithium enhanced the signal during cholinergic muscarinic receptor activation. In BD patients, such signaling effects might normalize the neurotransmission imbalance proposed to cause disease symptoms. Additionally, the antidepressants fluoxetine and imipramine, which tend to switch BD depression to mania, IVA increased AA turnover and cPLA, A expression in rat brain, suggesting that brain AA metabolism is higher in BD mania than depression. The AA hypothesis for mood stabilizer action is consistent with reports that low-dose aspirin reduced morbidity in patients taking lithium, and that high n-3 and/or low n-6 polyunsaturated fatty acid diets, which in rats reduce brain AA metabolism, were effective in BD and migraine patients. C1 NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA. EM sir@mail.nih.gov FU Intramural Program of the National Institute on Aging FX This work was entirely supported by the Intramural Program of the National Institute on Aging. NR 100 TC 21 Z9 21 U1 4 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD JUN PY 2014 VL 5 IS 6 BP 459 EP 467 DI 10.1021/cn500058v PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA AJ5KF UT WOS:000337720400008 PM 24786695 ER PT J AU Liu, ZH Smith, CB AF Liu, Zhonghua Smith, Carolyn Beebe TI Lithium: A Promising Treatment for Fragile X Syndrome SO ACS CHEMICAL NEUROSCIENCE LA English DT Review DE Fragile X syndrome; FMR1; FMRP; intellectual disability; autism; dendritic spines; glycogen synthase kinase-3 (GSK-3) ID MENTAL-RETARDATION PROTEIN; LONG-TERM POTENTIATION; FMR1 KNOCKOUT MICE; MEDIAL FRONTAL-CORTEX; MOUSE MODEL; SYNAPTIC PLASTICITY; INCREASED RATES; MESSENGER-RNAS; DROSOPHILA; MEMORY AB Fragile X syndrome (FXS) is an inherited disorder that results in intellectual disability and a characteristic behavioral profile that includes autism spectrum disorder, attention deficit hyperactivity disorder, sensory hypersensitivity, hyperarousal, and anxiety. The epigenetic silencing of FMR1 and the consequent absence of its protein product, FMRP, is the most common cause of fragile X. The development of animal models of fragile X syndrome 20 years ago has produced a considerable increase in our understanding of the consequences of the absence of FMRP on the structure and function of the nervous system. Some of the insights gained have led to proposals of treatment strategies that are based on cellular and molecular changes observed in animals lacking FMRP. One such proposal is treatment with lithium, a drug with a long history of clinical efficacy in psychiatry and a drug with newly described uses in degenerative disorders of the nervous system. Lithium treatment has been studied extensively in both mouse and fruit fly models of FXS, and it has been shown to reverse numerous behavioral, physiological, cellular, and molecular phenotypes. A report of a pilot clinical trial on a limited number of adult FXS patients indicated that measurable improvements in behavior and function were seen after 2 months of lithium treatment. A double-blind clinical trial of lithium treatment in FXS patients is now needed. C1 [Liu, Zhonghua; Smith, Carolyn Beebe] NIMH, Sect Neuroadaptat & Prot Metab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Smith, CB (reprint author), NIMH, NIH, Bldg 10,Room 54,10 Ctr Dr,MSC 1298, Bethesda, MD 20892 USA. EM beebe@mail.nih.gov FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services. NR 77 TC 5 Z9 5 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD JUN PY 2014 VL 5 IS 6 BP 477 EP 483 DI 10.1021/cn500077p PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA AJ5KF UT WOS:000337720400010 PM 24814569 ER PT J AU Blough, BE Landavazo, A Partilla, JS Baumann, MH Decker, AM Page, KM Rothman, RB AF Blough, Bruce E. Landavazo, Antonio Partilla, John S. Baumann, Michael H. Decker, Ann M. Page, Kevin M. Rothman, Richard B. TI Hybrid Dopamine Uptake Blocker-Serotonin Releaser Ligands: A New Twist on Transporter-Focused Therapeutics SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Dopamine uptake inhibitors; serotonin releasers; serotonin receptor; cocaine; methamphetamine ID BIOGENIC-AMINE TRANSPORTERS; IN-VITRO; BUPROPION; HYDROXYBUPROPION; METHCATHINONE; METABOLITES AB As part of our program to study neurotransmitter releasers, we report herein a class of hybrid dopamine reuptake inhibitors that display serotonin releasing activity. Hybrid compounds are interesting since they increase the design. potential of transporter related compounds and hence represent a novel and unexplored strategy for therapeutic drug discovery. A series of N-alkylpropiophenones was synthesized and assessed for uptake inhibition and release activity using rat brain synaptosomes. Substitution on the aromatic ring yielded compounds that maintained hybrid activity, with the two disubstituted analogues (PAL-787 and PAL-820) having the most potent hybrid activity. C1 [Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.] RTI Int, Ctr Drug Discovery, Discovery Sci Technol, Res Triangle Pk, NC 27709 USA. [Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Blough, BE (reprint author), RTI Int, Ctr Drug Discovery, Discovery Sci Technol, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA. EM beb@rti.org FU National Institute on Drug Abuse [DA12970]; National Institute on Drug Abuse, NIH FX Funding was provided by the National Institute on Drug Abuse (DA12970). Aspects of this work were supported by the Intramural Research Program, National Institute on Drug Abuse, NIH. NR 17 TC 13 Z9 13 U1 0 U2 3 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 JUN PY 2014 VL 5 IS 6 BP 623 EP 627 DI 10.1021/ml500113s PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AJ2OM UT WOS:000337497200004 PM 24944732 ER PT J AU Kumar, V Banala, AK Garcia, EG Cao, JJ Keck, TM Bonifazi, A Deschamps, JR Newman, AH AF Kumar, Vivek Banala, Ashwini K. Garcia, Erick G. Cao, Jianjing Keck, Thomas M. Bonifazi, Alessandro Deschamps, Jeffery R. Newman, Amy Hauck TI Chiral Resolution and Serendipitous Fluorination Reaction for the Selective Dopamine D3 Receptor Antagonist BAK2-66 SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE DAST; asymmetric catalysis; enantioselectivity; dopamine ID D-3; PERSPECTIVE; SUBTYPE; BINDING AB The improved chiral synthesis of the selective dopamine D3 receptor (D3R) antagonist (R)-N-(4-(4-(2,3-dichlorophenyl)piperazin- I -yl) -3-hydroxybutyl)1H-indole-2carboxamide ((R)-PG648) is described. The same chiral secondary alcohol intermediate was used to prepare the enantiomers of a 3-F-benzofuranyl analogue, BAK 2-66. The absolute configurations of the 3-F enantiomers were assigned from their X-ray crystal structures that confirmed retention of configuration during fluorination with N,N-diethylaminosulfur trifluoride (DAST). (R)-BAK2-66 showed higher D3R affinity and selectivity than its (S)-enantiomer; however, it had lower D3R affinity and enantioselectivity than (R)-PG648. Further, importance of the 4-atom linker length between the aryl amide and 4-phenylpiperazine was demonstrated with the 4-fluorobutylproduct (8). C1 [Kumar, Vivek; Banala, Ashwini K.; Garcia, Erick G.; Cao, Jianjing; Keck, Thomas M.; Bonifazi, Alessandro; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Deschamps, Jeffery R.] Naval Res Lab, Washington, DC 20375 USA. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov RI Kumar, Vivek/F-6183-2016; Keck, Thomas/G-9798-2012 OI Keck, Thomas/0000-0003-1845-9373 FU NIDA Intramural Research Program, National Institutes of Health, Department of Health and Human Services; NIH Visiting Fellowship; NIH Postdoctoral Intramural Research Training Award (IRTA) Fellowship; NIDA [Y1-DA1101]; Naval Research Laboratory (NRL) FX This research was funded by the NIDA Intramural Research Program, National Institutes of Health, Department of Health and Human Services. V.K. was supported by an NIH Visiting Fellowship, and T.M.K. was supported by an NIH Postdoctoral Intramural Research Training Award (IRTA) Fellowship. The X-ray crystallographic studies were supported by NIDA through Interagency Agreement #Y1-DA1101 with the Naval Research Laboratory (NRL). NR 22 TC 8 Z9 8 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 JUN PY 2014 VL 5 IS 6 BP 647 EP 651 DI 10.1021/ml500006v PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AJ2OM UT WOS:000337497200009 PM 24944737 ER PT J AU Kumar, V Rahbek-Clemmensen, T Billesbolle, CB Jorgensen, TN Gether, U Newman, AH AF Kumar, Vivek Rahbek-Clemmensen, Troels Billesbolle, Christian B. Jorgensen, Trine Nygaard Gether, Ulrik Newman, Amy Hauck TI Novel and High Affinity Fluorescent Ligands for the Serotonin Transporter Based on (S)-Citalopram SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Fluorescent ligand; SERT; citalopram; rhodamine ID DOPAMINE TRANSPORTER; ANALOGS; PROBES; DESIGN AB Novel rhodamine-labeled ligands, based on (S)citalopram, were synthesized and evaluated for uptake inhibition at the human serotonin, dopamine, and norepinephrine transporters (hSERT, hDAT, and hNET, respectively) and for binding at SERT, in transiently transfected COS7 cells. Compound 14 demonstrated high affinity binding and selectivity for SERT (K-i; = 3 nM). Visualization of SERT, using confocal laser scanning microscopy, validated compound 14 as a novel tool for studying SERT expression and distribution in living cells. C1 [Kumar, Vivek; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Rahbek-Clemmensen, Troels; Billesbolle, Christian B.; Jorgensen, Trine Nygaard; Gether, Ulrik] Univ Copenhagen, Fac Hlth & Med Sci, Mol Neuropharmacol Lab, DK-2200 Copenhagen N, Denmark. [Rahbek-Clemmensen, Troels; Billesbolle, Christian B.; Jorgensen, Trine Nygaard; Gether, Ulrik] Univ Copenhagen, Fac Hlth & Med Sci, Ctr Pharmacogen, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov RI Kumar, Vivek/F-6183-2016; OI Rahbek-Clemmensen, Troels/0000-0003-2067-5411; Gether, Ulrik/0000-0002-0020-3807 FU NIDA Intramural Research Program; National Institute of Health [P01 DA 12408]; Danish Medical Research Council; Lundbeck Foundation Center for Biomembranes in Nanomedicine; NIH Visiting Fellowship FX This research was funded by the NIDA Intramural Research Program and by the National Institute of Health Grants P01 DA 12408 (to U.G.), the Danish Medical Research Council (to U.G.), and the Lundbeck Foundation Center for Biomembranes in Nanomedicine (to U.G.). V.K. was supported by an NIH Visiting Fellowship. NR 15 TC 5 Z9 5 U1 0 U2 7 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 JUN PY 2014 VL 5 IS 6 BP 696 EP 699 DI 10.1021/ml5000806 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AJ2OM UT WOS:000337497200018 PM 24944746 ER PT J AU Miller, RA Harrison, DE Astle, CM Fernandez, E Flurkey, K Han, M Javors, MA Li, XN Nadon, NL Nelson, JF Pletcher, S Salmon, AB Sharp, ZD Van Roekel, S Winkleman, L Strong, R AF Miller, Richard A. Harrison, David E. Astle, Clinton M. Fernandez, Elizabeth Flurkey, Kevin Han, Melissa Javors, Martin A. Li, Xinna Nadon, Nancy L. Nelson, James F. Pletcher, Scott Salmon, Adam B. Sharp, Zelton Dave Van Roekel, Sabrina Winkleman, Lynn Strong, Randy TI Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction SO AGING CELL LA English DT Article DE aging; caloric restriction; glucose; IGF-1; insulin; longevity; mouse; mTOR; rapamycin; xenobiotic metabolism ID GENETICALLY HETEROGENEOUS MICE; INTERVENTIONS TESTING PROGRAM; AMES DWARF MICE; INSULIN SENSITIVITY; EXTENSION; LONGEVITY; TOR; RESISTANCE; PATHWAY; GENES AB Rapamycin, an inhibitor of mTOR kinase, increased median lifespan of genetically heterogeneous mice by 23% (males) to 26% (females) when tested at a dose threefold higher than that used in our previous studies; maximal longevity was also increased in both sexes. Rapamycin increased lifespan more in females than in males at each dose evaluated, perhaps reflecting sexual dimorphism in blood levels of this drug. Some of the endocrine and metabolic changes seen in diet-restricted mice are not seen in mice exposed to rapamycin, and the pattern of expression of hepatic genes involved in xenobiotic metabolism is also quite distinct in rapamycin-treated and diet-restricted mice, suggesting that these two interventions for extending mouse lifespan differ in many respects. C1 [Miller, Richard A.; Han, Melissa; Li, Xinna; Van Roekel, Sabrina; Winkleman, Lynn] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Miller, Richard A.; Han, Melissa; Li, Xinna; Pletcher, Scott; Van Roekel, Sabrina; Winkleman, Lynn] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. [Harrison, David E.; Astle, Clinton M.; Flurkey, Kevin] Jackson Lab, Bar Harbor, ME 04609 USA. [Fernandez, Elizabeth; Strong, Randy] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Fernandez, Elizabeth; Strong, Randy] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA. [Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Nadon, Nancy L.] NIA, Div Aging Biol, Bethesda, MD 20892 USA. [Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Nelson, James F.; Salmon, Adam B.; Sharp, Zelton Dave; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Pletcher, Scott] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78245 USA. RP Miller, RA (reprint author), Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. EM millerr@umich.edu FU NIH [AG022303, AG031736, AG022307, AG013319, AG022308, CA034196]; Department of Veterans Affairs FX This work was supported by NIH grants AG022303, AG031736 (RAM), AG022307, AG013319 (RS), and AG022308 (DEH), with important facilities supported by CA034196 (DEH) and the Department of Veterans Affairs (RS), We thank Lili Deng and Andrzej Galecki for statistical assistance, Jeff Halter for comments on an early draft of the paper, and Lisa Burmeister, Vivian Diaz, Nelson Durgin, Vicki Ingalls, Amanda Keedle, and Pam J Krason for technical assistance. NR 46 TC 103 Z9 105 U1 4 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD JUN PY 2014 VL 13 IS 3 BP 468 EP 477 DI 10.1111/acel.12194 PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA AJ2VV UT WOS:000337523400009 PM 24341993 ER PT J AU Tapocik, JD Schank, JR Mayo, CL Damazdic, R Pincus, A King, C Koenig, JI Heilig, M Elmer, GI AF Tapocik, J. D. Schank, J. R. Mayo, C. L. Damazdic, R. Pincus, A. King, C. Koenig, J. I. Heilig, M. Elmer, G. I. TI A RAT MODEL OF PTSD LEADS TO NEURONAL ACTIVATION OF THE LATERAL SUBREGION OF THE LATERAL HABENULA AND ESCALATED CONTEXT-INDUCED ALCOHOL CONSUMPTION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0055 BP 14A EP 14A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700056 ER PT J AU Vatsalya, V Schwandt, M Ramchandani, VA George, DT AF Vatsalya, V. Schwandt, M. Ramchandani, V. A. George, D. T. TI CHARACTERIZATION OF POLYUNSATURATED FATTY ACIDS WITH IMMUNE AND HEPATIC MARKERS IN HIV DIAGNOSED ALCOHOL DEPENDENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Vatsalya, V.; Schwandt, M.; Ramchandani, V. A.; George, D. T.] NIAAA, Lab Clin & Translat Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0087 BP 22A EP 22A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700088 ER PT J AU Vatsalya, V Ramchandani, VA Leggio, L AF Vatsalya, V. Ramchandani, V. A. Leggio, L. TI CARDIOVASCULAR ASSESSMENT BETWEEN TITRATION AND MAINTAINENCE DOSE OF TREATMENT WITH QUETIAPINE FUMARATE IN VERY HEAVY DRINKERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Vatsalya, V.; Ramchandani, V. A.; Leggio, L.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. RI Leggio, Lorenzo/M-2972-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0190 BP 48A EP 48A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700191 ER PT J AU Vatsalya, V Umhau, J Schwandt, M Phillip, M Ramchandani, VA George, DT AF Vatsalya, V. Umhau, J. Schwandt, M. Phillip, M. Ramchandani, V. A. George, D. T. TI METABOLIC VARIABILITY IN PLASMA FATTY ACIDS CONCENTRATION COULD SERVE AS POTENTIAL BIOMARKER IN HCV COMORBID ALCOHOL DEPENDENT PATIENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Vatsalya, V.; Umhau, J.; Schwandt, M.; Phillip, M.; Ramchandani, V. A.; George, D. T.] NIAAA, Lab Clin & Translat Sci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0189 BP 48A EP 48A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700190 ER PT J AU Breslow, RA Dong, C White, A Chen, CM Yoon, YH Yi, H AF Breslow, R. A. Dong, C. White, A. Chen, C. M. Yoon, Y-H. Yi, H. TI ALCOHOL-INTERACTIVE PRESCRIPTION DRUG USE: PREVALENCE BY DRINKING STATUS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Breslow, R. A.; Dong, C.; White, A.; Chen, C. M.; Yoon, Y-H.; Yi, H.] NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0246 BP 62A EP 62A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700247 ER PT J AU Pickering, RP Chou, P Grant, BF AF Pickering, R. P. Chou, P. Grant, B. F. TI ALCOHOL DEPENDENCE INCIDENCE BY BEVERAGE PREFERENCE: RESULTS OF THE NATIONAL EPIDEMIOLOGIC SURVEY ON ALCOHOL AND RELATED CONDITIONS (NESARC I&II) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Pickering, R. P.; Chou, P.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0255 BP 64A EP 64A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700256 ER PT J AU Saha, TD Grant, BF AF Saha, T. D. Grant, B. F. TI DIMENSIONALITY AND SCALE PROPERTIES OF DSM-5 ALCOHOL USE DISORDER SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Saha, T. D.; Grant, B. F.] NIAAA, LEB, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0256 BP 64A EP 64A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700257 ER PT J AU Barbier, E Tapocik, J Johnstone, A Schank, J Zhou, Z Yuan, Q Goldman, D Wahlestedt, C Heilig, M AF Barbier, E. Tapocik, J. Johnstone, A. Schank, J. Zhou, Z. Yuan, Q. Goldman, D. Wahlestedt, C. Heilig, M. TI ROLE OF HISTONE MODIFYING ENZYMES PRDM2 AND KDM6B IN ALCOHOL-RELATED BEHAVIORS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Barbier, E.; Tapocik, J.; Schank, J.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. [Zhou, Z.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. [Johnstone, A.; Wahlestedt, C.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0317 BP 80A EP 80A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700318 ER PT J AU Carlson, VCC Carlson, TL Lovinger, DM AF Carlson, V. C. Cuzon Carlson, T. L. Lovinger, D. M. TI DIFFERENT ACUTE ETHANOL EFFECTS ON GABAERGIC-MEDIATED POSTSYNAPTIC CURRENT FREQUENCY ONTO MSNS OF THE DORSOLATERAL AND DORSOMEDIAL STRIATUM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Carlson, V. C. Cuzon; Carlson, T. L.] Oregon Hlth & Sci Univ, Oregon Natl Primate Ctr, Beaverton, OR USA. [Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0352 BP 88A EP 88A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700353 ER PT J AU Carlson, VCC Grant, KA Lovinger, DM AF Carlson, V. C. Cuzon Grant, K. A. Lovinger, D. M. TI AGE OF ONSET AND GENDER AFFECTS ETHANOL INTAKE AND SYNAPTIC TRANSMISSION ONTO MEDIUM SPINY NEURONS IN THE PUTAMEN OF THE RHESUSMONKEY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Carlson, V. C. Cuzon; Grant, K. A.] Oregon Hlth & Sci Univ, Oregon Natl Primate Ctr, Beaverton, OR USA. [Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0351 BP 88A EP 88A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700352 ER PT J AU Augier, E Dulman, RS Heilig, M AF Augier, Eric Dulman, Russell S. Heilig, Markus TI A NEW MODEL OF COMPULSIVE ALCOHOL INTAKE IN RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Augier, Eric; Dulman, Russell S.; Heilig, Markus] NIAAA, NIH, Sect Mol Pathophysiol, Lab Clin & Translat Studies, Bethesda, MD 28092 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0396 BP 99A EP 99A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700397 ER PT J AU Banerjee, A Abdelmegeed, MA Jang, SH Song, BJ AF Banerjee, A. Abdelmegeed, M. A. Jang, S. H. Song, B. J. TI LEPTIN INDUCED HIGHER HEPATIC STEATOSIS AND INFLAMMATION IN BINGE ALCOHOL-EXPOSED HIV TRANSGENIC RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Banerjee, A.; Abdelmegeed, M. A.; Jang, S. H.; Song, B. J.] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0412 BP 103A EP 103A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700413 ER PT J AU Abdelmegeed, MA Banerjee, A Jang, S Yun, JW Yoo, SH Song, BJ AF Abdelmegeed, M. A. Banerjee, A. Jang, S. Yun, J. W. Yoo, S. H. Song, B. J. TI THE ROLE OF CYTOCHROME P450 2E1 (CYP2E1) IN THE DEVELOPMENT OF HIGH FAT WESTERN DIET-INDUCED HEPATIC FIBROGENESIS WITHOUT OR WITH ETHANOL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20892 USA. Seoul Natl Univ, Coll Med, Seoul 110, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0413 BP 104A EP 104A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700414 ER PT J AU Feng, DC Li, YM Xu, MJ Wang, H Wang, Y Gao, B AF Feng, Dechun Li, Yongmei Xu, Ming-Jiang Wang, Hua Wang, Yan Gao, Bin TI AGING AGGRAVATES ALCOHOLIC LIVER INJURY IN MICE BY DOWNREGULATING HEPATIC SIRTUIN 1 AND INHIBITING AUTOPHAGY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Feng, Dechun; Li, Yongmei; Xu, Ming-Jiang; Wang, Hua; Wang, Yan; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0423 BP 106A EP 106A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700424 ER PT J AU Yun, JW Son, MJ Abdelmegeed, MA Banerjee, A Morgan, TR Yoo, SH Song, BJ AF Yun, J. W. Son, M. J. Abdelmegeed, M. A. Banerjee, A. Morgan, T. R. Yoo, S. H. Song, B. J. TI BINGE ALCOHOL PROMOTES HYPOXIC LIVER INJURY THROUGH A CYP2E1-HIF-1 alpha-DEPENDENT APOPTOSIS PATHWAY IN MICE AND HUMANS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 NIAAA, Lab Memb Biochem & Biophys, Rockville, MD 20892 USA. Seoul Natl Univ, Coll Med, Seoul 151, South Korea. VA Long Beach Hosp, Long Beach, CA 90701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0426 BP 107A EP 107A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700427 ER PT J AU N'Gouemo, P Allard, JS Lovinger, DM AF N'Gouemo, P. Allard, J. S. Lovinger, D. M. TI UPREGULATION OF CAV1.2 L-TYPE CHANNELS PRECEDES THE ONSET OF ALCOHOL WITHDRAWAL SEIZURE SUSCEPTIBILITY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [N'Gouemo, P.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20057 USA. [Allard, J. S.] Howard Univ, Col Med, Dept Physiol & Biophys, Washington, DC 20059 USA. [Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0435 BP 109A EP 109A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700436 ER PT J AU Schuebel, KE Blackistone, K Mordi, I Yuan, Q Idrus, N Thomas, JD Goldman, D AF Schuebel, K. E. Blackistone, K. Mordi, I. Yuan, Q. Idrus, N. Thomas, J. D. Goldman, D. TI WHOLE GENOME DNA CYTOSINE METHYLATION PROFILING IN A RAT MODEL OF FASD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Schuebel, K. E.; Blackistone, K.; Mordi, I.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Idrus, N.; Thomas, J. D.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0460 BP 115A EP 115A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700461 ER PT J AU Yan, J Schwandt, ML Cho, SB Stangl, BL Kwako, LE Dick, DM Kendler, KS Leggio, L Momenan, R Heilig, M Ramchandani, VA AF Yan, J. Schwandt, M. L. Cho, S. B. Stangl, B. L. Kwako, L. E. Dick, D. M. Kendler, K. S. Leggio, L. Momenan, R. Heilig, M. Ramchandani, V. A. TI LATENT CLASS ANALYSIS OF NON-TREATMENT SEEKING SOCIAL DRINKERS REVEAL 3 EMPIRICAL CLASSES WITH DIFFERENCES IN RISK FOR ALCOHOL-RELATED PHENOTYPES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Yan, J.; Schwandt, M. L.; Stangl, B. L.; Kwako, L. E.; Leggio, L.; Momenan, R.; Heilig, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, LCTS, NIH, Bethesda, MD 20892 USA. [Yan, J.; Cho, S. B.; Dick, D. M.; Kendler, K. S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. RI Leggio, Lorenzo/M-2972-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0495 BP 124A EP 124A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700496 ER PT J AU Falk, DE Litten, Z Ryan, ML Fertig, JB AF Falk, D. E. Litten, Z. Ryan, M. L. Fertig, J. B. CA Natl Inst Alcohol Abuse Alcoholism TI A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL ASSESSING THE EFFICACY OF VARENICLINE TARTRATE FOR ALCOHOL DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Falk, D. E.; Litten, Z.; Ryan, M. L.; Fertig, J. B.; Natl Inst Alcohol Abuse Alcoholism] NIAAA, Div Treatment & Recovery Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0554 BP 139A EP 139A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700555 ER PT J AU Sanjuan, PM Rice, SL Witkiewitz, K Mandler, RN Crandall, C Bogenschutz, MP AF Sanjuan, P. M. Rice, S. L. Witkiewitz, K. Mandler, R. N. Crandall, C. Bogenschutz, M. P. TI ALCOHOL, TOBACCO, AND DRUG USE AMONG EMERGENCY DEPARTMENT PATIENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 UNM, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87106 USA. UNM, Hlth Sci Ctr, Albuquerque, NM 87106 USA. NIDA, Clin Trials Network, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0562 BP 141A EP 141A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700563 ER PT J AU Hingson, RW Zha, W White, A AF Hingson, R. W. Zha, W. White, A. TI MAGNITUDE OF AND TRENDS IN ALCOHOL-RELATED MORTALITY AND MORBIDITY AMONG US COLLEGE STUDENTS, 1998-2010 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Hingson, R. W.; Zha, W.; White, A.] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0579 BP 145A EP 145A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700580 ER PT J AU Spagnolo, PA Schwandt, ML Momenan, R Ramchandani, VA Heilig, M George, DT AF Spagnolo, P. A. Schwandt, M. L. Momenan, R. Ramchandani, V. A. Heilig, M. George, D. T. TI EFFECTS OF FAAH RS324420 SNP IN CO-MORBID ALCOHOL DEPENDENCE AND POSTTRAUMATIC STRESS DISORDER SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Spagnolo, P. A.; Schwandt, M. L.; Momenan, R.; Ramchandani, V. A.; Heilig, M.; George, D. T.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0585 BP 147A EP 147A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700586 ER PT J AU Enoch, MA Hodgkinson, C Gorodetsky, E Marietta, C Roy, A Goldman, D AF Enoch, M. -A. Hodgkinson, C. Gorodetsky, E. Marietta, C. Roy, A. Goldman, D. TI VARIATION IN GENES IMPLICATED IN GABA SYNTHESIS, SYNAPTIC TRANSMISSION AND RE-UPTAKE ARE PREDICTORS FOR ALCOHOLISM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Enoch, M. -A.; Hodgkinson, C.; Gorodetsky, E.; Marietta, C.; Roy, A.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0592 BP 148A EP 148A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700593 ER PT J AU Lee, MR Oot, EN Schwandt, ML Hodgkinson, CA Goldman, D Heilig, M Ramchandani, VA Leggio, L AF Lee, M. R. Oot, E. N. Schwandt, M. L. Hodgkinson, C. A. Goldman, D. Heilig, M. Ramchandani, V. A. Leggio, L. TI ON THE LINK BETWEEN OXYTOCIN SIGNALING AND ALCOHOL REWARD: POSSIBLE ROLE OF THE CD38 RS3796863 POLYMORPHISM IN ALCOHOL-INDUCED BRAIN DOPAMINE RELEASE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Lee, M. R.; Oot, E. N.; Schwandt, M. L.; Hodgkinson, C. A.; Goldman, D.; Heilig, M.; Ramchandani, V. A.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIDA,NIH, Bethesda, MD 20892 USA. RI Leggio, Lorenzo/M-2972-2016 NR 0 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0593 BP 149A EP 149A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700594 ER PT J AU Gowin, JL Vatsalya, V Momenan, R Schwandt, ML Bartlett, S Heilig, M Ramchandani, VA AF Gowin, J. L. Vatsalya, V. Momenan, R. Schwandt, M. L. Bartlett, S. Heilig, M. Ramchandani, V. A. TI ATTENUATION OF AMYGDALA RESPONSE TO ALCOHOL CUES BY VARENICLINE IN HEAVY DRINKERS: ASSOCIATION WITH SELF-ADMINISTRATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Gowin, J. L.; Vatsalya, V.; Momenan, R.; Schwandt, M. L.; Bartlett, S.; Heilig, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0620 BP 155A EP 155A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700621 ER PT J AU Zywiak, WH Swift, RM McGeary, JE Leggio, L Kenna, GA AF Zywiak, W. H. Swift, R. M. McGeary, J. E. Leggio, L. Kenna, G. A. TI DETECTING MEDICATION EFFECTS BY EXAMINING PRECURSORS OF RECENT HEAVY DRINKING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Pacific Inst Res & Eval, Pawtucket, RI 02860 USA. Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. Providence VA, Providence, RI 02912 USA. NIAAA, Bethesda, MD 20892 USA. NIDA, Bethesda, MD 20892 USA. RI Leggio, Lorenzo/M-2972-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0638 BP 160A EP 160A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700639 ER PT J AU Zhang, L Xiong, W Homanics, GE Lovinger, DM AF Zhang, Li Xiong, Wei Homanics, Gregg E. Lovinger, David M. TI INVOLVEMENT OF GLYCINE RECEPTORS IN LOW DOSE ETHANOL AND THC INDUCED MOTOR IMPAIRMENT IN MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Zhang, Li; Xiong, Wei; Lovinger, David M.] NIAAA, NIH, Bethesda, MD USA. [Homanics, Gregg E.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0648 BP 162A EP 162A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700649 ER PT J AU Jury, NJ Holmes, A AF Jury, N. J. Holmes, A. TI EFFECTS OF CHRONIC INTERMITTENT ETHANOL VAPOR EXPOSURE IN ADOLESCENT AND FEMALE MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Jury, N. J.; Holmes, A.] NIAAA, Lab Behav & Genom Neurosci, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0670 BP 168A EP 168A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700671 ER PT J AU Karlsson, C Schank, JR Rehman, F Barbier, E Salomon, M Tapocik, J Thorsell, A Heilig, M AF Karlsson, C. Schank, J. R. Rehman, F. Barbier, E. Salomon, M. Tapocik, J. Thorsell, A. Heilig, M. TI PROINFLAMMATORY SIGNALING REGULATES VOLUNTARY ALCOHOL INTAKE AND ESCALATION OF CONSUMPTION AFTER EXPOSURE TO SOCIAL DEFEAT STRESS IN MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Karlsson, C.; Schank, J. R.; Rehman, F.; Barbier, E.; Salomon, M.; Tapocik, J.; Heilig, M.] NIAAA, Lab Clin & Transl Studies, NIH, Bethesda, MD USA. [Karlsson, C.] KI, Dept Clin Neurosci, Stockholm, Sweden. [Thorsell, A.] LiU, Dept Clin & Exp Med, Linkoping, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0669 BP 168A EP 168A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700670 ER PT J AU Hisada, M Zhang, X Ota, Y Gao, B Williams, GM Sun, Z AF Hisada, M. Zhang, X. Ota, Y. Gao, B. Williams, G. M. Sun, Z. TI CHRONIC ALCOHOL CONSUMPTION INDUCED MITOCHONDRIAL DAN DAMAGES TO BONE MARROW STEM CELLS RESULTS IN FIBROSIS OF REDUCED SIZE LIVER GRAFTS IN RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. NIAAA, Lab Liver Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0680 BP 170A EP 170A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700681 ER PT J AU Bertola, A Xu, MJ Deng, C Gao, B AF Bertola, A. Xu, M. J. Deng, C. Gao, B. TI HEPATOCYTE- AND MYELOID CELL-SPECIFIC DELETION OF SIRTUIN-6 PREVENTS ALCOHOL-INDUCED HEPATOCELLULAR DAMAGE IN MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Bertola, A.; Xu, M. J.; Deng, C.; Gao, B.] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0682 BP 171A EP 171A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700683 ER PT J AU Zhai, R Wesson, R Wang, Y Lin, Q Munivenkatappa, RB Gao, B Sun, Z AF Zhai, R. Wesson, R. Wang, Y. Lin, Q. Munivenkatappa, R. B. Gao, B. Sun, Z. TI DELAYED LIVER REGENERATION AND INCREASED CD133 STEM CELLS AFTER 85% PARTIAL HEPATECTOMY IN A RAT MODEL OF CHRONIC PLUS BINGE ETHANOL FEEDING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. NIAAA, Lab Liver Dis, NIH, Bethesda, MD 21085 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0681 BP 171A EP 171A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700682 ER PT J AU Mathews, S Feng, D Gao, B AF Mathews, S. Feng, D. Gao, B. TI INVARIANT NATURAL KILLER T CELLS CONTRIBUTE TO CHRONIC PLUS BINGE ETHANOL-MEDIATED LIVER INJURY BY PROMOTING HEPATIC NEUTROPHIL INFILTRATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Mathews, S.; Feng, D.; Gao, B.] NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0686 BP 172A EP 172A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700687 ER PT J AU Wang, H Bertola, A Xu, MJ Feng, D Yin, S Wang, Y Li, J Gao, B AF Wang, H. Bertola, A. Xu, M. J. Feng, D. Yin, S. Wang, Y. Li, J. Gao, B. TI LONG-TERM PLUS MULTIPLE BINGE ETHANOL FEEDING INDUCES STEATOHEPATITIS AND FIBROSIS IN AGED MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Wang, H.; Li, J.] Anhui Med Univ, Inst Liver Dis, Hefei 230032, Peoples R China. [Wang, H.; Bertola, A.; Xu, M. J.; Feng, D.; Yin, S.; Wang, Y.; Gao, B.] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0699 BP 175A EP 175A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700700 ER PT J AU Grodin, EN Kerich, MJ Heilig, M Schumann, G Momenan, R AF Grodin, E. N. Kerich, M. J. Heilig, M. Schumann, G. Momenan, R. TI ADOLESCENTS WITH AND WITHOUT ALCOHOL PROBLEMS: RESPONSE TO REWARD ANTICIPATION AND FEEDBACK SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Grodin, E. N.; Kerich, M. J.; Heilig, M.; Momenan, R.] NIAAA, LCTS, NIH, Bethesda, MD USA. [Schumann, G.] MRC Social Genet & Dev Psychiat Ctr, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0741 BP 186A EP 186A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700742 ER PT J AU Stangl, BL Zametkin, M Ramchandani, VA AF Stangl, B. L. Zametkin, M. Ramchandani, V. A. TI CHARACTERIZATION OF OPERANT INTRAVENOUS ALCOHOL SELF-ADMINISTRATION IN HUMANS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Stangl, B. L.; Zametkin, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0746 BP 187A EP 187A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700747 ER PT J AU Huang, B Grant, BF Chou, SP Smith, SM Saha, TD Ruan, WJ Goldstein, RB Jung, J Zhang, H Pickering, RP AF Huang, B. Grant, B. F. Chou, S. P. Smith, S. M. Saha, T. D. Ruan, W. J. Goldstein, R. B. Jung, J. Zhang, H. Pickering, R. P. TI PROSPECTIVE ASSOCIATION BETWEEN ALCOHOL CONSUMPTION AND MAJOR DEPRESSION: NATIONAL EPIDEMIOLOGIC SURVEY ON ALCOHOL AND RELATED CONDITIONS, 2001-2005 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Huang, B.; Grant, B. F.; Chou, S. P.; Smith, S. M.; Saha, T. D.; Ruan, W. J.; Goldstein, R. B.; Jung, J.; Zhang, H.; Pickering, R. P.] NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0785 BP 197A EP 197A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523700786 ER PT J AU Hagman, BT Schonfeld, L AF Hagman, B. T. Schonfeld, L. TI COLLEGE STUDENTS WHO ENDORSE A SUB-THRESHOLD NUMBER OF DSM-5 ALCOHOL USE DISORDER CRITERIA: THE NEW DIAGNOSTIC ORPHAN SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Hagman, B. T.; Schonfeld, L.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0810 BP 203A EP 203A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701010 ER PT J AU Suchankova, P Yan, J Schwandt, ML Stangl, BL Jerlhag, E Engel, JA Hodgkinson, CA Goldman, D Heilig, M Ramchandani, VA Leggio, L AF Suchankova, P. Yan, J. Schwandt, M. L. Stangl, B. L. Jerlhag, E. Engel, J. A. Hodgkinson, C. A. Goldman, D. Heilig, M. Ramchandani, V. A. Leggio, L. TI GENETIC VARIATION AT THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR GENE LOCUS IS ASSOCIATED WITH ALCOHOL USE DISORDER SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Suchankova, P.; Yan, J.; Schwandt, M. L.; Stangl, B. L.; Jerlhag, E.; Engel, J. A.; Hodgkinson, C. A.; Goldman, D.; Heilig, M.; Ramchandani, V. A.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIDA,NIH, Bethesda, MD 20892 USA. RI Leggio, Lorenzo/M-2972-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0879 BP 220A EP 220A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701079 ER PT J AU Suchankova, P Oot, EN Dias, AA Yan, J Schwandt, ML Stangl, BL Jerlhag, E Engel, JA Hodgkinson, CA Goldman, D Ye, T Kleinman, J Heilig, M Ramchandani, VA Leggio, L AF Suchankova, P. Oot, E. N. Dias, A. A. Yan, J. Schwandt, M. L. Stangl, B. L. Jerlhag, E. Engel, J. A. Hodgkinson, C. A. Goldman, D. Ye, T. Kleinman, J. Heilig, M. Ramchandani, V. A. Leggio, L. TI GENETIC VARIATIONS IN THE GHRELIN SYSTEM ARE ASSOCIATED WITH ALCOHOL DEPENDENCE AND ALCOHOL DRINKING BEHAVIORS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Suchankova, P.; Oot, E. N.; Dias, A. A.; Yan, J.; Schwandt, M. L.; Stangl, B. L.; Jerlhag, E.; Engel, J. A.; Hodgkinson, C. A.; Goldman, D.; Ye, T.; Kleinman, J.; Heilig, M.; Ramchandani, V. A.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIDA,NIH, Bethesda, MD 20892 USA. RI Leggio, Lorenzo/M-2972-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0878 BP 220A EP 220A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701078 ER PT J AU Zhu, X Mathur, K Cortes, CR Momenan, R AF Zhu, X. Mathur, K. Cortes, C. R. Momenan, R. TI CHANGES IN BRAIN NETWORKS IN ALCOHOLICS: A RESTING-STATE FMRI STUDY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Zhu, X.; Mathur, K.; Cortes, C. R.; Momenan, R.] NIAAA, Sect Brain Electrophysiol & Imaging, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0935 BP 234A EP 234A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701135 ER PT J AU Collins, MA Tajuddin, N Moon, KH Nixon, K Neafsey, EJ Kim, HY AF Collins, M. A. Tajuddin, N. Moon, K. -H. Nixon, K. Neafsey, E. J. Kim, H. -Y. TI PARP-1 AND OXIDATIVE STRESS GOVERN BINGE ETHANOL-DEPENDENT NEUROINFLAMMATION AND NEURODEGENERATION IN ADULT RAT BRAIN SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Collins, M. A.; Tajuddin, N.; Moon, K. -H.; Neafsey, E. J.] Loyola Univ, Sch Med, Dept Mol Pharmacol, Maywood, IL 60153 USA. [Nixon, K.] Univ Kentucky, Dept Pharmaceut Sci, Lexington, KY 40536 USA. [Kim, H. -Y.] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 0980 BP 245A EP 245A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701180 ER PT J AU Vatsalya, V Stangl, B Schmidt, V Ramchandani, VA AF Vatsalya, V. Stangl, B. Schmidt, V. Ramchandani, V. A. TI CHARACTERIZATION OF HANGOVER SYMPTOMS FOLLOWING ACUTE INTRAVENOUS ALCOHOL ADMINISTRATION: PREDICTORS AND CLINICAL CONSEQUENCES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Vatsalya, V.; Stangl, B.; Schmidt, V.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 1086 BP 272A EP 272A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701285 ER PT J AU McGinnis, K Tate, J Bryant, K Fiellin, D Justice, A AF McGinnis, K. Tate, J. Bryant, K. Fiellin, D. Justice, A. TI SENSITIVITY TO ALCOHOL INTOXICATION EFFECTS BY HIV STATUS AND TREATMENT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. CT VA Healthcare Syst, Vet Aging Cohort Study, West Haven, CT USA. Yale Univ, New Haven, CT USA. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 1131 BP 283A EP 283A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701330 ER PT J AU Aziz, A Brothers, S Cameron, M Heilig, M Mittapalli, G Roberts, E Wahlestedt, C Thorsell, A AF Aziz, A. Brothers, S. Cameron, M. Heilig, M. Mittapalli, G. Roberts, E. Wahlestedt, C. Thorsell, A. TI A NOVEL, BRAIN PENETRANT NPY-Y2R ANTAGONIST IN ANIMAL MODELS OF ALCOHOL-INTAKE AND ANXIETY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Aziz, A.; Thorsell, A.] Linkoping Univ, S-58183 Linkoping, Sweden. [Brothers, S.; Wahlestedt, C.] Univ Miami, Miami, FL USA. [Cameron, M.] Scripps Res Inst, Trans Res Inst, Jupiter, FL USA. [Heilig, M.] NIAAA, NIH, Bethesda, MD USA. [Mittapalli, G.; Roberts, E.] Scripps Res Inst, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 016 BP 296A EP 296A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701383 ER PT J AU Kenna, G Columbo, G Zywiak, W Caputo, F Swift, R Addolorato, G Fricchione, S Brickley, M Haass-Koffler, C Leggio, L AF Kenna, G. Columbo, G. Zywiak, W. Caputo, F. Swift, R. Addolorato, G. Fricchione, S. Brickley, M. Haass-Koffler, C. Leggio, L. TI METADOXINE FOR ACUTE ALCOHOL TOXICITY, ALCOHOLISM AND ALCOHOLIC LIVER DISEASE: PRECLINICAL AND CLINICAL FINDINGS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Kenna, G.; Columbo, G.; Zywiak, W.; Caputo, F.; Swift, R.; Addolorato, G.; Fricchione, S.; Brickley, M.; Haass-Koffler, C.; Leggio, L.] Brown Univ, NIAAA, Providence, RI 02912 USA. [Kenna, G.; Columbo, G.; Zywiak, W.; Caputo, F.; Swift, R.; Addolorato, G.; Fricchione, S.; Brickley, M.; Haass-Koffler, C.; Leggio, L.] Brown Univ, NIDA, Providence, RI 02912 USA. [Kenna, G.; Columbo, G.; Zywiak, W.; Caputo, F.; Swift, R.; Addolorato, G.; Fricchione, S.; Brickley, M.; Haass-Koffler, C.; Leggio, L.] Univ Cagliari, Catholic Univ Rome, SS Annunziata Hosp, Cento, IT, Italy. RI Leggio, Lorenzo/M-2972-2016 NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 072 BP 310A EP 310A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701439 ER PT J AU Enoch, MA AF Enoch, M. -A. TI GENETIC INFLUENCES ON THE LEVEL OF RESPONSE TO ALCOHOL: IMPLICATIONS FOR NEW TREATMENT APPROACHES FOR ALCOHOL USE DISORDERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Enoch, M. -A.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 103 BP 318A EP 318A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701470 ER PT J AU Heilig, M Thorsell, A Rice, KC Malanga, CJ Robinson, JE AF Heilig, M. Thorsell, A. Rice, K. C. Malanga, C. J. Robinson, J. E. TI A DUAL MECHANISM FOR NEUROKININ 1 (NK1) RECEPTOR ANTAGONISM AS A THERAPEUTIC TARGET IN ADDICTIVE DISORDERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Heilig, M.; Thorsell, A.; Rice, K. C.; Malanga, C. J.; Robinson, J. E.] NIAAA, Intramural Res Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 183 BP 338A EP 338A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701550 ER PT J AU Heilig, M Sommer, W Thorsell, A Malanga, CJ Bilbao, A Robinson, JE AF Heilig, M. Sommer, W. Thorsell, A. Malanga, C. J. Bilbao, A. Robinson, J. E. TI A HUMANIZED MOUSE MODEL OF THE MU-OPIOID RECEPTOR (OPRM1) GENE A118G POLYMORPHISM: DEMONSTRATION OF ALTERED ALCOHOL AND OPIOID RESPONSES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Heilig, M.] NIAAA, Bethesda, MD USA. [Heilig, M.; Thorsell, A.] Linkoping Univ, Linkoping, Sweden. [Sommer, W.; Bilbao, A.] Cent Inst Mental Hlth, Mannheim, Germany. [Malanga, C. J.; Robinson, J. E.] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 211 BP 345A EP 345A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701578 ER PT J AU Lovinger, DM AF Lovinger, D. M. TI ETHANOL INDUCED HABIT FORMATION IN MICE AND MONKEYS: ROLE OF STRIATAL GABAERGIC TRANSMISSION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 222 BP 348A EP 348A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701589 ER PT J AU Kwako, LE Schwandt, ML Grodin, EN Momenan, R Heilig, M Hommer, DW George, DT Ramchandani, VA AF Kwako, L. E. Schwandt, M. L. Grodin, E. N. Momenan, R. Heilig, M. Hommer, D. W. George, D. T. Ramchandani, V. A. TI EARLY LIFE STRESS, ALCOHOL DEPENDENCE, AND POST-TRAUMATIC STRESS DISORDER: EVIDENCE FOR DISRUPTIONS IN PHYSIOLOGIC OUTCOMES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Kwako, L. E.; Schwandt, M. L.; Grodin, E. N.; Momenan, R.; Heilig, M.; Hommer, D. W.; George, D. T.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 251 BP 355A EP 355A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701618 ER PT J AU Schwandt, ML Stangl, B Huang, MC Kwako, L Heilig, M Hommer, DW George, DT Ramchandani, VA AF Schwandt, M. L. Stangl, B. Huang, M. -C. Kwako, L. Heilig, M. Hommer, D. W. George, D. T. Ramchandani, V. A. TI EARLY LIFE STRESS AND TRAUMA: PREVALENCE IN ALCOHOL DEPENDENT AND NON-DEPENDENT DRINKERS, AND ASSOCIATIONS WITH ALCOHOL-RELATED PHENOTYPES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Schwandt, M. L.; Stangl, B.; Huang, M. -C.; Kwako, L.; Heilig, M.; Hommer, D. W.; George, D. T.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI MA 250 BP 355A EP 355A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701617 ER PT J AU Adinoff, B Gu, H Merrick, C McHugh, M Devous, MD Briggs, R Sunderajan, P Yang, Y Stein, EA AF Adinoff, B. Gu, H. Merrick, C. McHugh, M. Devous, M. D. Briggs, R. Sunderajan, P. Yang, Y. Stein, E. A. TI LOCALIZED AND FUNCTIONALLY CONNECTED NEURAL PREDICTORS OF RELAPSE IN COCAINE DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism (RSA) / 17th Congress of the International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA) CY JUN 21-25, 2014 CL Bellevue, WA SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism C1 [Adinoff, B.] VA North Texas Hlth Care Syst, Dallas, TX USA. [Adinoff, B.; Sunderajan, P.] UT Southwestern Med Ctr, Dept Psychiat, Dallas, TX USA. [Gu, H.; McHugh, M.] NIDA, Intramural Res Program, Neuroimaging Res Branch, Baltimore, MD USA. [Merrick, C.] UT Dallas, Dept Cognit Neurosci, Dallas, TX USA. [Devous, M. D.; Yang, Y.; Stein, E. A.] UT Southwestern Med Ctr, Dallas, TX USA. [Briggs, R.] UT Southwestern Med Ctr, Dept Radiol, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 SU 1 SI SI BP 385A EP 385A PG 1 WC Substance Abuse SC Substance Abuse GA AJ2VX UT WOS:000337523701644 ER PT J AU Li, HH Tyburski, JB Wang, YW Strawn, S Moon, BH Kallakury, BVS Gonzalez, FJ Fornace, AJ AF Li, Heng-Hong Tyburski, John B. Wang, Yi-Wen Strawn, Steve Moon, Bo-Hyun Kallakury, Bhaskar V. S. Gonzalez, Frank J. Fornace, Albert J. TI Modulation of Fatty Acid and Bile Acid Metabolism By Peroxisome Proliferator-Activated Receptor Protects Against Alcoholic Liver Disease SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Ppara-Null Mice; Fibrogenesis; Metabolic Pathways; Transcriptomics; Metabolomics ID HEPATIC STELLATE CELLS; HEPATOCYTE PROLIFERATION; LIPID-METABOLISM; BINDING PROTEIN; GROWTH-FACTOR; PPAR-ALPHA; EXPRESSION; METABOLOMICS; OXIDATION; PATHWAYS AB Background Chronic alcohol intake affects liver function and causes hepatic pathological changes. It has been shown that peroxisome proliferator-activated receptor (PPAR)-null mice developed more pronounced hepatic changes than wild-type (WT) mice after chronic exposure to a diet containing 4% alcohol. The remarkable similarity between the histopathology of alcoholic liver disease (ALD) in Ppara-null model and in humans, and the fact that PPAR expression and activity in human liver are less than one-tenth of those in WT mouse liver make Ppara-null a good system to investigate ALD. Methods In this study, the Ppara-null model was used to elucidate the dynamic regulation of PPAR activity during chronic alcohol intake. Hepatic transcriptomic and metabolomic analyses were used to examine alterations of gene expression and metabolites associated with pathological changes. The changes triggered by alcohol consumption on gene expression and metabolites in Ppara-null mice were compared with those in WT mice. Results The results showed that in the presence of PPAR, 3 major metabolic pathways in mitochondria, namely the fatty acid -oxidation, the tricarboxylic acid cycle, and the electron transfer chain, were induced in response to a 2-month alcohol feeding, while these responses were greatly reduced in the absence of PPAR. In line with the transcriptional modulations of these metabolic pathways, a progressive accumulation of triglycerides, a robust increase in hepatic cholic acid and its derivatives, and a strong induction of fibrogenesis genes were observed exclusively in alcohol-fed Ppara-null mice. Conclusions These observations indicate that PPAR plays a protective role to enhance mitochondrial function in response to chronic alcohol consumption by adaptive transcriptional activation and suggest that activation of this nuclear receptor may be of therapeutic value in the treatment for ALD. C1 [Li, Heng-Hong; Tyburski, John B.; Wang, Yi-Wen; Strawn, Steve; Moon, Bo-Hyun; Fornace, Albert J.] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA. [Kallakury, Bhaskar V. S.] Georgetown Univ, Dept Pathol, Med Ctr, Washington, DC 20057 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Li, HH (reprint author), Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA. EM hl234@georgetown.edu FU NIEHS, NIH [U01ES016013]; NIAAA, NIH [R01AA018863] FX This study was funded by grant U01ES016013 from NIEHS, NIH, and grant R01AA018863 from NIAAA, NIH. NR 40 TC 9 Z9 9 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 IS 6 BP 1520 EP 1531 DI 10.1111/acer.12424 PG 12 WC Substance Abuse SC Substance Abuse GA AJ2SI UT WOS:000337511400005 PM 24773203 ER PT J AU Kenna, GA Zywiak, WH Swift, RM McGeary, JE Clifford, JS Shoaff, JR Vuittonet, C Fricchione, S Brickley, M Beaucage, K Haass-Koffler, CL Leggio, L AF Kenna, George A. Zywiak, William H. Swift, Robert M. McGeary, John E. Clifford, James S. Shoaff, Jessica R. Vuittonet, Cynthia Fricchione, Samuel Brickley, Michael Beaucage, Kayla Haass-Koffler, Carolina L. Leggio, Lorenzo TI Ondansetron Reduces Naturalistic Drinking in Nontreatment-Seeking Alcohol-Dependent Individuals with the LL 5-HTTLPR Genotype: A Laboratory Study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE 5-HTTLPR; Alcoholism; Genotype; Ondansetron; Sertraline ID SEROTONIN TRANSPORTER GENE; SERTRALINE TREATMENT; CONTROLLED-TRIAL; ASSOCIATION; ABUSE; PHARMACOTHERAPY; POLYMORPHISM; VALIDATION; INSTRUMENT; DISORDERS AB Background One hypothesis suggests that the differential response to ondansetron- and serotonin-specific re-uptake inhibitors (SSRIs) may be due to a functional polymorphism of the 5-HTTLPR promoter region in SLC6A4, the gene that codes for the serotonin transporter (5-HTT). The LL 5-HTTLPR genotype is postulated to be specifically sensitive to the effects of ondansetron with SS/SL 5-HTTLPR genotypes sensitive to SSRIs. This study tests this hypothesis by matching nontreatment-seeking alcohol-dependent (AD) individuals with LL genotype to ondansetron and SS/SL genotypes to the SSRI sertraline, and mismatching them assessing naturalistic and bar-laboratory alcohol drinking. Methods Seventy-seven AD individuals were randomized to 1 of 2 counterbalanced arms to receive sertraline 200mg/d or ondansetron 0.5mg/d for 3weeks followed by an alcohol self-administration experiment (ASAE) and then received placebo for 3weeks followed by a second ASAE. Individuals then received the alternate drug for 3weeks followed by a third ASAE. Drinks per drinking day (DDD with drinks in standard drinking units) for 7days prior to each ASAE and milliliters consumed during each ASAE were the primary outcomes. Results Fifty-five participants completed the study. The genotypexorder interaction was significant, F(1, 47)=8.42, p=0.006, for DDD. Three analyses of covariance were conducted for DDD during the week before each ASAE. Ondansetron compared to sertraline resulted in a significant reduction in DDD during the week before the first, F(1, 47)=7.64, p=0.008, but not the third ASAE. There was no difference in milliliters consumed during each ASAE. Conclusions This study modestly supports the hypothesis that ondansetron may reduce DDD in AD individuals with the LL genotype as measured naturalistically. By contrast, there was no support that ondansetron reduces drinking during the ASAEs or that sertraline reduces alcohol use in individuals who have SS/SL genotypes. We provide limited support that ondansetron may reduce drinking in nontreatment-seeking individuals with the LL genotype. C1 [Kenna, George A.; Zywiak, William H.; Swift, Robert M.; McGeary, John E.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. [Kenna, George A.; Zywiak, William H.; Swift, Robert M.; McGeary, John E.; Shoaff, Jessica R.; Fricchione, Samuel; Brickley, Michael; Haass-Koffler, Carolina L.; Leggio, Lorenzo] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Zywiak, William H.] Pacific Inst Res & Evaluat, Decis Sci Inst, Pawtucket, RI USA. [Swift, Robert M.; McGeary, John E.; Beaucage, Kayla] Providence VA Med Ctr, Providence, RI USA. [Clifford, James S.] Virginia Commonwealth Univ, Richmond, VA USA. [Vuittonet, Cynthia] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Leggio, Lorenzo] Brown Univ, Dept Behav & Social Sci, Providence, RI 02912 USA. RP Kenna, GA (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box G-S121-5, Providence, RI 02912 USA. EM George_Kenna@Brown.edu RI Leggio, Lorenzo/M-2972-2016 FU National Institute on Alcohol Abuse and Alcoholism [R01-AA016079]; Medical Research Service Department of Veteran Affairs; CT Laboratories; [1S10RR023457-01A1] FX This work was supported by the National Institute on Alcohol Abuse and Alcoholism grant R01-AA016079 (PI: Kenna), Shared Equipment grants (ShEEP) from the Medical Research Service Department of Veteran Affairs, and 1S10RR023457-01A1 (PI: McGeary). Dr. Swift has received travel and honorarium from D&A Pharma, and Drs. Kenna and Swift have received consultant fees from CT Laboratories. The other authors report no financial interests or potential conflicts of interest to declare. NR 35 TC 8 Z9 9 U1 3 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 IS 6 BP 1567 EP 1574 DI 10.1111/acer.12410 PG 8 WC Substance Abuse SC Substance Abuse GA AJ2SI UT WOS:000337511400010 PM 24773166 ER PT J AU Lovallo, WR Enoch, MA Yechiam, E Glahn, DC Acheson, A Sorocco, KH Hodgkinson, CA Kim, B Cohoon, AJ Vincent, AS Goldman, D AF Lovallo, William R. Enoch, Mary-Anne Yechiam, Eldad Glahn, David C. Acheson, Ashley Sorocco, Kristen H. Hodgkinson, Colin A. Kim, Bojeong Cohoon, Andrew J. Vincent, Andrea S. Goldman, David TI Differential Impact of Serotonin Transporter Activity on Temperament and Behavior in Persons with a Family History of Alcoholism in the Oklahoma Family Health Patterns Project SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Serotonin Transporter; Family History of Alcoholism; Anxiety; Depression ID RISK TASK BART; SUBSTANCE USE DISORDERS; PSYCHOPATHIC TRAITS; IMPULSIVE BEHAVIOR; PREFRONTAL CORTEX; ALLELIC VARIATION; POLYMORPHISM; 5-HTTLPR; GENE; MEN AB Background Central serotonergic (5-HT) function is implicated in pathways to alcohol dependence, including dysphoria manifested by symptoms of anxiety and depression. However, little is known about genetic variation in central 5-HT function and its potential impact on temperament and behavior in persons with a family history of alcoholism (FH+). Methods We tested 314 healthy young adults (23.5years of age, 57% female; 193 FH- and 121 FH+) enrolled in the Oklahoma Family Health Patterns project, a study of alcoholism risk in relation to temperament and behavioral dyscontrol. Dysphoria was assessed using the Eysenck neuroticism and Beck depression scales, and Cloninger's Tridimensional Personality Questionnaire. Risk taking was assessed with the Iowa Gambling Task (IGT) and Balloon Analogue Response Task (BART). All subjects were genotyped for a functional polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4). Results FH+ subjects with the gain-of-function 5-HTTLPR genotype scored higher in neuroticism, harm avoidance, and symptoms of depression (p-values0.03). No effect of 5-HTTLPR genotype was seen in FH-. FH+ carriers of the gain-of-function 5-HTTLPR genotype played to minimize their frequency of losses in the IGT, whereas FH- carriers played a balanced strategy (p<0.003). No 5-HTTLPR effects were seen in the BART. Results were unaffected by sex, education, drug use, and antisocial characteristics. Conclusions The functional 5-HTTLPR polymorphism predicted significant variation in negative moods and poorer affect regulation in FH+ persons, with possible consequences for behavior, as seen in a simulated gambling task. This pattern may contribute to a drinking pattern that is compensatory for such affective tendencies. C1 [Lovallo, William R.] Univ Oklahoma, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Oklahoma City, OK 73190 USA. [Lovallo, William R.; Sorocco, Kristen H.; Cohoon, Andrew J.] Vet Affairs Med Ctr, Behav Sci Labs, Oklahoma City, OK 73104 USA. [Enoch, Mary-Anne; Hodgkinson, Colin A.; Kim, Bojeong; Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD USA. [Yechiam, Eldad] Technion Israel Inst Technol, Haifa, Israel. [Glahn, David C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Glahn, David C.] Olin Neuropsychiat Res Ctr, Inst Living, Hartford, CT USA. [Acheson, Ashley] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Acheson, Ashley] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Sorocco, Kristen H.] Univ Oklahoma, Hlth Sci Ctr, Donald W Reynolds Dept Geriatr Med, Oklahoma City, OK USA. [Vincent, Andrea S.] Univ Oklahoma, Cognit Sci Res Ctr, Norman, OK 73019 USA. RP Lovallo, WR (reprint author), Vet Affairs Med Ctr, Behav Sci Labs 151A, 921 NE 13th St, Oklahoma City, OK 73104 USA. EM bill@mindbody1.org RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Department of Veterans Affairs Medical Research Service [M01 RR014467]; National Council on Research Resources [R01AA019691, R01 AA012207]; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health; Israel Science Foundation [199/12] FX This work was supported in part by the Department of Veterans Affairs Medical Research Service, grant M01 RR014467; National Council on Research Resources, grants R01AA019691 and R01 AA012207; and the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. The content is solely the view of the authors and does not necessarily represent the official view of the National Institutes of Health or the Department of Veterans Affairs. The involvement of EY was made possible by grant 199/12 from the Israel Science Foundation. NR 53 TC 5 Z9 5 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 IS 6 BP 1575 EP 1581 DI 10.1111/acer.12412 PG 7 WC Substance Abuse SC Substance Abuse GA AJ2SI UT WOS:000337511400011 PM 24796636 ER PT J AU Bolnick, JM Karana, R Chiang, PJ Kilburn, BA Romero, R Diamond, MP Smith, SM Armant, DR AF Bolnick, Jay M. Karana, Rita Chiang, Po J. Kilburn, Brian A. Romero, Roberto Diamond, Michael P. Smith, Susan M. Armant, D. Randall TI Apoptosis of Alcohol-Exposed Human Placental Cytotrophoblast Cells is Downstream of Intracellular Calcium Signaling SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Trophoblast; Alcohol; Apoptosis; Calcium; Intracellular Signaling; Intrauterine Growth Restriction; Fetal Alcohol Spectrum Disorder ID INTRAUTERINE GROWTH-RETARDATION; PHOSPHOLIPASE-C INHIBITOR; PREIMPLANTATION DEVELOPMENT; BETA-CATENIN; ETHANOL; TRANSIENT; RELEASE; DEATH; NEURONS; U73122 AB Background Apoptosis is induced by ethanol (EtOH) in human placental trophoblast cells, possibly disrupting placentation and contributing to intrauterine growth restriction in fetal alcohol spectrum disorder (FASD). EtOH induces programmed cell death in several embryonic tissues by raising intracellular Ca2+. Therefore, the role of Ca2+ signaling in EtOH-induced apoptosis was examined using human first trimester cytotrophoblast cell lines, examining the hypothesis that apoptosis is dependent on intracellular Ca2+ signaling. Methods Using HTR-8/SVneo and SW.71 cytotrophoblast cell lines, real-time intracellular Ca2+ concentration was monitored by fluo-4 epifluorescence microscopy and apoptosis was assessed by flow cytometry of cells fluorescently labeled for DNA fragmentation (TUNEL) and annexin V binding. Results Intracellular Ca2+ concentrations increased synchronously in all cells within 10seconds of exposure to 50mM EtOH, but not at lower EtOH concentrations (10 to 25mM) incapable of inducing apoptosis. Trophoblast cells treated with inhibitors of Ca2+ signaling (BAPTA-AM, U73122, xestospongin D, BAPTA, SKF-96365) produced no intracellular Ca2+ transients after exposure to 50mM EtOH and were protected from cell death induced by EtOH. Conclusions EtOH-induced apoptosis in human cytotrophoblast cells, identified by DNA fragmentation and externalized phosphatidylserine, was dependent upon Ca2+ signaling. Both intracellular Ca2+ mobilization and extracellular Ca2+ influx were required, as well as phosphatidylinositol signaling. Inhibition by SKF-96365 suggests that the capacitative Ca2+ entry mechanism that utilizes TRPC channels was activated by EtOH. Apoptosis occurs downstream of Ca2+ signaling in trophoblasts and may contribute to placental insufficiency and poor fetal growth associated with FASD. C1 [Bolnick, Jay M.; Karana, Rita; Chiang, Po J.; Kilburn, Brian A.; Romero, Roberto; Armant, D. Randall] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Diamond, Michael P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA USA. [Smith, Susan M.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Armant, D. Randall] Wayne State Univ, Dept Anat & Cell Biol, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA. [Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA. RP Armant, DR (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Mott Ctr Human Growth & Dev, 275 East Hancock St, Detroit, MI 48201 USA. EM D.Armant@wayne.edu OI Diamond, Michael/0000-0001-6353-4489; Armant, D. Randall/0000-0001-5904-9325 FU NIH [R37AA11085, R21HD071408]; NICHD, NIH FX This research was supported by NIH grant R37AA11085 to SMS, R21HD071408 to DRA, and the Intramural Research Program of the NICHD, NIH. NR 40 TC 9 Z9 10 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2014 VL 38 IS 6 BP 1646 EP 1653 DI 10.1111/acer.12417 PG 8 WC Substance Abuse SC Substance Abuse GA AJ2SI UT WOS:000337511400019 PM 24889927 ER PT J AU Samuels, J Shugart, YY Wang, Y Grados, MA Bienvenu, OJ Pinto, A Rauch, SL Greenberg, BD Knowles, JA Fyer, AJ Piacentini, J Pauls, DL Cullen, B Rasmussen, SA Stewart, SE Geller, DA Maher, BS Goes, FS Murphy, DL McCracken, JT Riddle, MA Nestadt, G AF Samuels, Jack Shugart, Yin Yao Wang, Ying Grados, Marco A. Bienvenu, O. Joseph Pinto, Anthony Rauch, Scott L. Greenberg, Benjamin D. Knowles, James A. Fyer, Abby J. Piacentini, John Pauls, David L. Cullen, Bernadette Rasmussen, Steven A. Stewart, S. Evelyn Geller, Dan A. Maher, Brion S. Goes, Fernando S. Murphy, Dennis L. McCracken, James T. Riddle, Mark A. Nestadt, Gerald TI Clinical Correlates and Genetic Linkage of Social and Communication Difficulties in Families with Obsessive-Compulsive Disorder: Results From the OCD Collaborative Genetics Study SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE obsessive-compulsive disorder; OCD; pragmatics; genetic linkage ID BROAD AUTISM PHENOTYPE; PSYCHIATRIC-DISORDERS; ASPERGER-SYNDROME; CHILDREN; PARENTS; INDIVIDUALS; PERSONALITY; BEHAVIORS; TRAITS; SCAN AB Some individuals with obsessive-compulsive disorder (OCD) have autistic-like traits, including deficits in social and communication behaviors (pragmatics). The objective of this study was to determine if pragmatic impairment aggregates in OCD families and discriminates a clinically and genetically distinct subtype of OCD. We conducted clinical examinations on, and collected DNA samples from, 706 individuals with OCD in 221 multiply affected OCD families. Using the Pragmatic Rating Scale (PRS), we compared the prevalence of pragmatic impairment in OCD-affected relatives of probands with and without pragmatic impairment. We also compared clinical features of OCD-affected individuals in families having at least one, versus no, individual with pragmatic impairment, and assessed for linkage to OCD in the two groups of families. The odds of pragmatic impairment were substantially greater in OCD-affected relatives of probands with pragmatic impairment. Individuals in high-PRS families had greater odds of separation anxiety disorder and social phobia, and a greater number of schizotypal personality traits. In high-PRS families, there was suggestive linkage to OCD on chromosome 12 at marker D12S1064 and on chromosome X at marker DXS7132 whereas, in low-PRS families, there was suggestive linkage to chromosome 3 at marker D3S2398. Pragmatic impairment aggregates in OCD families. Separation anxiety disorder, social phobia, and schizotypal personality traits are part of a clinical spectrum associated with pragmatic impairment in these families. Specific regions of chromosomes 12 and X are linked to OCD in high-PRS families. Thus, pragmatic impairment may distinguish a clinically and genetically homogeneous subtype of OCD. (C) 2014 Wiley Periodicals, Inc. C1 [Samuels, Jack; Wang, Ying; Grados, Marco A.; Bienvenu, O. Joseph; Cullen, Bernadette; Goes, Fernando S.; Riddle, Mark A.; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Shugart, Yin Yao] NIMH, Genom Res Branch, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA. [Pinto, Anthony; Fyer, Abby J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [Pinto, Anthony; Fyer, Abby J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Rauch, Scott L.; Geller, Dan A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Greenberg, Benjamin D.; Rasmussen, Steven A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Knowles, James A.] Univ So Calif, Dept Psychiat, Sch Med, Los Angeles, CA USA. [Piacentini, John; McCracken, James T.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Pauls, David L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Pauls, David L.] Harvard Univ, Sch Med, Boston, MA USA. [Stewart, S. Evelyn] Univ British Columbia, Fac Med, Dept Psychiat, Vancouver Fac Med, Vancouver, BC, Canada. [Maher, Brion S.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Samuels, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 550 N Broadway 901, Baltimore, MD 21205 USA. EM jacks@jhmi.edu RI Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905; Stewart, S. Evelyn/0000-0002-0994-6383 FU National Institutes of Health [R01-MH-50214, R01MH071507, K23-MH-64543, NIH/NCRR/OPD-GCRC RR00052]; James E. Marshall OCD Foundation FX Grant sponsor: National Institutes of Health; Grant numbers: R01-MH-50214, R01MH071507, K23-MH-64543, NIH/NCRR/OPD-GCRC RR00052; Grant sponsor: James E. Marshall OCD Foundation. NR 57 TC 3 Z9 3 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN PY 2014 VL 165 IS 4 BP 326 EP 336 DI 10.1002/ajmg.b.32235 PG 11 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA AJ4UX UT WOS:000337674600006 PM 24798771 ER PT J AU Mirzaa, GM Paciorkowski, AR AF Mirzaa, Ghayda M. Paciorkowski, Alex R. TI Introduction: Brain malformations SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE brain malformations; genetics; review ID MENTAL-RETARDATION; MUTATIONS; CONFIRMATION; HETEROTOPIA; HYPOPLASIA; PHENOTYPE; DISORDER; DISEASE; MODEL; LIS1 AB This issue of the American Journal of Medical Genetics Seminar Series Part C is dedicated to congenital brain malformations with a special focus on the molecular mechanisms underlying this fascinating, and often complex, group of developmental brain disorders. As with most genetic disorders, the past few years have witnessed a dramatic leap in our understanding of the molecular basis of these malformations that include both constitutional and post-zygotic (or mosaic) genetic aberrations. This is best exemplified by the recent identification of mutations within components of the PI3K-AKT-mTOR pathway in hemimegalencephaly and megalencephaly syndromes, and the rapidly increased identification of mutations within the tubulin family in a broad range of cortical and non-cortical brain malformations. These discoveries, particularly of the emerging tubulinopathies spectrum, have not only expanded our knowledge of these disorders but challenge our existing, and perhaps overly simplistic, classification of these malformations based on the primary neuronal stage at which the abnormality occurs. It is our hope that this series will facilitate a deeper understanding of these malformations beyond their clinical and neuroimaging features and syndromic associations to their molecular and pathway underpinnings. We believe this knowledge will most certainly be instrumental as we move into the era of delineating genotype-phenotype correlations and, ultimately, pathway-based therapies. (c) 2014 Wiley Periodicals, Inc. C1 [Mirzaa, Ghayda M.] Seattle Childrens Hosp, Dept Human Genet, Seattle, WA USA. [Mirzaa, Ghayda M.] Seattle Childrens Res Inst, Seattle, WA USA. [Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Paciorkowski, Alex R.] NINDS, Ctr Neural Dev & Dis, Supported Res Program Genet Causes Dev Brain Diso, Bethesda, MD 20892 USA. RP Paciorkowski, AR (reprint author), Univ Rochester, Med Ctr Neurol, 601 Elmwood Ave, Rochester, NY 14642 USA. EM alex_paciorkowski@urmc.rochester.edu FU NINDS FX Dr. Paciorkowski is a clinical neurogeneticist at the University of Rochester Medical Center, and principal investigator at the Center for Neural Development & Disease with a NINDS-supported research program in the genetic causes of developmental brain disorders. NR 24 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4868 EI 1552-4876 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD JUN PY 2014 VL 166 IS 2 SI SI BP 117 EP 123 DI 10.1002/ajmg.c.31404 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AJ4HF UT WOS:000337633800001 PM 24853778 ER PT J AU Seltzer, LE Paciorkowski, AR AF Seltzer, Laurie E. Paciorkowski, Alex R. TI Genetic disorders associated with postnatal microcephaly SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Review DE postnatal microcephaly; Angelman syndrome; MECP2-related disorder; Christianson syndrome; CASK; CDKL5; FOXG1; Pitt-Hopkins syndrome; Rubinstein-Taybi syndrome; Warburg MICRO syndrome; Cockayne syndrome; Cerebral-oculo-facial skeletal syndrome ID RUBINSTEIN-TAYBI-SYNDROME; PITT-HOPKINS-SYNDROME; WARBURG MICRO SYNDROME; SEVERE MENTAL-RETARDATION; OF-FUNCTION MUTATIONS; FACIO-SKELETAL SYNDROME; PRADER-WILLI SYNDROMES; SYNDROME GROUP-B; RETT-SYNDROME; COCKAYNE-SYNDROME AB Several genetic disorders are characterized by normal head size at birth, followed by deceleration in head growth resulting in postnatal microcephaly. Among these are classic disorders such as Angelman syndrome and MECP2-related disorder (formerly Rett syndrome), as well as more recently described clinical entities associated with mutations in CASK, CDKL5, CREBBP, and EP300 (Rubinstein-Taybi syndrome), FOXG1, SLC9A6 (Christianson syndrome), and TCF4 (Pitt-Hopkins syndrome). These disorders can be identified clinically by phenotyping across multiple neurodevelopmental and neurobehavioral realms, and enough data are available to recognize these postnatal microcephaly disorders as separate diagnostic entities in their own right. A second diagnostic grouping, comprised of Warburg MICRO syndrome, Cockayne syndrome, and Cerebral-oculo-facial skeletal syndrome, share similar features of somatic growth failure, ophthalmologic, and dysmorphologic features. Many postnatal microcephaly syndromes are caused by mutations in genes important in the regulation of gene expression in the developing forebrain and hindbrain, although important synaptic structural genes also play a role. This is an emerging group of disorders with a fascinating combination of brain malformations, specific epilepsies, movement disorders, and other complex neurobehavioral abnormalities. (c) 2014 Wiley Periodicals, Inc. C1 [Seltzer, Laurie E.; Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Paciorkowski, Alex R.] NINDS, Ctr Neural Dev & Dis, Supported Res Program Genet Causes Dev Brain Diso, Bethesda, MD 20892 USA. RP Paciorkowski, AR (reprint author), Univ Rochester, Med Ctr, 601 Elmwood Ave, Rochester, NY 14642 USA. EM alex_paciorkowski@urmc.rochester.edu FU National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) [K12NS066098, K08NS078054] FX We wish to thank our research families for their participation and support of our work. Dr. Seltzer is supported by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) award number K12NS066098 and Dr. Paciorkowski by award number K08NS078054. The authors have no financial disclosures. NR 131 TC 10 Z9 10 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4868 EI 1552-4876 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD JUN PY 2014 VL 166 IS 2 SI SI BP 140 EP 155 DI 10.1002/ajmg.c.31400 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA AJ4HF UT WOS:000337633800003 PM 24839169 ER PT J AU Mirzaa, GM Poduri, A AF Mirzaa, Ghayda M. Poduri, Annapurna TI Megalencephaly and hemimegalencephaly: Breakthroughs in molecular etiology SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE megalencephaly; hemimegalencephaly; polymicrogyria; somatic mosaicism; overgrowth; PI3K-AKT-mTOR pathway; Ras; MAPK pathway ID AUTISM SPECTRUM DISORDERS; MARMORATA TELANGIECTATICA CONGENITA; RILEY-RUVALCABA-SYNDROME; ACTIVATING MUTATIONS; CUTIS MARMORATA; PTEN GENE; CYCLIN D2; BEHAVIORAL ABNORMALITIES; CAPILLARY MALFORMATION; GERMLINE MUTATIONS AB Megalencephaly (MEG) is a developmental disorder characterized by brain overgrowth that occurs due to either increased number or size of neurons and glial cells. The former may be due to either increased neuronal proliferation or decreased apoptosis. The degree of brain overgrowth may be extensive, ranging from generalized MEG affecting the entire cortex-as with mutations in PTEN (phosphatase and tensin homolog on chromosome ten)-to unilateral hemispheric malformations-as in classic hemimegalencephaly (HME). On the other hand, some lesions are more focal or segmental. These developmental brain abnormalities may occur in isolation in some individuals, whereas others occur in the context of a syndrome involving dysmorphic features, skin findings, or other organ system involvement. Brain overgrowth disorders are often associated with malformations of cortical development, resulting in increased risk of epilepsy, intellectual disability, and autistic features, and some are associated with hydrocephalus. The past few years have witnessed a dramatic leap in our understanding of the molecular basis of brain overgrowth, particularly the identification of mosaic (or post-zygotic) mutations in core components of key cellular pathways such as the phosphatidylinositol 3-kinase (PI3K)-vakt murine thymoma viral oncogene homolog (AKT)-mTOR pathway. These molecular insights have broadened our view of brain overgrowth disorders that now appear to span a wide spectrum of overlapping phenotypic, neuroimaging, and neuropathologic features and molecular pathogenesis. These molecular advances also bring to light the possibility of pathway-based therapies for these often medically devastating developmental disorders. (c) 2014 Wiley Periodicals, Inc. C1 [Mirzaa, Ghayda M.] Seattle Childrens Hosp, Dept Human Genet, Seattle, WA USA. [Mirzaa, Ghayda M.] Seattle Childrens Res Inst, Seattle, WA USA. [Poduri, Annapurna] Boston Childrens Hosp, Div Epilepsy & Clin Electrophysiol, Dept Neurol, Hosp Epilepsy Genet Program, Boston, MA USA. [Poduri, Annapurna] NINDS, Supported Ctr, Bethesda, MD 20892 USA. RP Mirzaa, GM (reprint author), Univ Washington, Div Med Genet, Dept Pediat, Ctr Integrat Brain Res,Seattle Childrens Res Inst, 1900 9th Ave, Seattle, WA 98101 USA. EM gmirzaa@uw.edu; annapurna.poduri@childrens.harvard.edu FU NINDS [NS069784] FX The authors thank our patients and their families for their valuable and ongoing contributions and support of our research. A. P. was supported by the NINDS (NS069784). NR 67 TC 22 Z9 24 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4868 EI 1552-4876 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD JUN PY 2014 VL 166 IS 2 SI SI BP 156 EP 172 DI 10.1002/ajmg.c.31401 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA AJ4HF UT WOS:000337633800004 PM 24888963 ER PT J AU Engels, EA Castenson, D Pfeiffer, RM Kahn, A Pawlish, K Goodman, MT Nalesnik, MA Israni, AK Snyder, J Kasiske, B AF Engels, E. A. Castenson, D. Pfeiffer, R. M. Kahn, A. Pawlish, K. Goodman, M. T. Nalesnik, M. A. Israni, A. K. Snyder, J. Kasiske, B. TI Cancers Among US Organ Donors: A Comparison of Transplant and Cancer Registry Diagnoses SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Cancer; donor evaluation; organ donation ID MALIGNANT-MELANOMA; DISEASE TRANSMISSION; MULTIORGAN DONOR; RENAL-ALLOGRAFT; PROSTATE-CANCER; TUMOR; ADENOCARCINOMA; RECIPIENTS; CARCINOMA; RISK AB Transmission of cancer is a life-threatening complication of transplantation. Monitoring transplantation practice requires complete recording of donor cancers. The US Scientific Registry of Transplant Recipients (SRTR) captures cancers in deceased donors (beginning in 1994) and living donors (2004). We linked the SRTR (52 599 donors, 110 762 transplants) with state cancer registries. Cancer registries identified cancers in 519 donors: 373 deceased donors (0.9%) and 146 living donors (1.2%). Among deceased donors, 50.7% of cancers were brain tumors. Among living donors, 54.0% were diagnosed after donation; most were cancers common in the general population (e. g. breast, prostate). There were 1063 deceased donors with cancer diagnosed in the SRTR or cancer registry, and the SRTR lacked a cancer diagnosis for 107 (10.1%) of these. There were 103 living donors with cancer before or at donation, diagnosed in the SRTR or cancer registry, and the SRTR did not have a cancer diagnosis for 43 (41.7%) of these. The SRTR does not record cancers after donation in living donors and so missed 81 cancers documented in cancer registries. In conclusion, donor cancers are uncommon, but lack of documentation of some cases highlights a need for improved ascertainment and reporting by organ procurement organizations and transplant programs. C1 [Engels, E. A.; Pfeiffer, R. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Castenson, D.] Informat Management Serv Inc, Rockville, MD USA. [Kahn, A.] New York State Canc Registry, Albany, NY USA. [Pawlish, K.] New Jersey Dept Hlth, Trenton, NJ USA. [Goodman, M. T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Nalesnik, M. A.] Univ Pittsburgh, Med Ctr, Div Transplantat & Hepat Pathol, Pittsburgh, PA USA. [Israni, A. K.; Snyder, J.; Kasiske, B.] Minneapolis Med Res Fdn Inc, Sci Registry Transplant Recipients, Minneapolis, MN USA. [Israni, A. K.; Kasiske, B.] Univ Minnesota, Dept Med, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM engelse@exchange.nih.gov FU Intramural Research Program of the National Cancer Institute; Arbor Research Collaborative for Health in Ann Arbor, MI [HHSH234200537009C]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: California [1U58 DP000807-01]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Colorado [U58 DP000848-04]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Georgia [5U58DP003875-01]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Illinois [5658DP000805-04]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Michigan [5U58DP000812-03]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: New Jersey [1US58/DP0039311-01]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: New York [U58DP0038789]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: North Carolina [U58DP000832]; National Program of Cancer Registries of the Centers for Disease Control and Prevention: Texas [5U58DP000824-04]; SEER Program of the National Cancer Institute: California [HHSN261201000036C, HHSN261201000035C, HHSN261201000034C]; SEER Program of the National Cancer Institute: Connecticut [HHSN261201000024C]; SEER Program of the National Cancer Institute: Hawaii [HHSN261201000037C, N01-PC-35137, N01-PC-35139]; SEER Program of the National Cancer Institute: Iowa [HSN261201000032C, N01-PC-35143]; SEER Program of the National Cancer Institute: New Jersey [HHSN261201000027C, N01-PC-2010-0027]; SEER Program of the National Cancer Institute: Seattle-Puget Sound [N01-PC-35142]; SEER Program of the National Cancer Institute: Utah [HHSN261201000026C]; state of California; state of Colorado; state of Connecticut; state of Illinois; state of Iowa; state of New Jersey; state of New York (Cancer Surveillance Improvement Initiative) [14-2491]; state of Texas; state of Washington; Fred Hutchinson Cancer Research Center in Seattle, WA FX The authors thank Monica Lin and James Bowman (Health Resources and Services Administration) and Maureen McBride and Sarah Taranto (United Network for Organ Sharing) for their thoughtful advice on this study and comments on the manuscript. We also acknowledge the support and assistance provided by individuals at the Health Resources and Services Administration, the SRTR (Paul Newkirk), and the following cancer registries: the states of California (Tina Clarke), Colorado (Jack Finch), Connecticut (Lou Gonsalves), Georgia(Rana Bayakly), Hawaii (Brenda Hernandez), Iowa(Charles Lynch), Illinois (Lori Koch), Michigan (Glenn Copeland), New Jersey (Xiaoling Niu), New York, North Carolina (Chandrika Rao), Texas (Beatriz Gutierrez) and Utah (Janna Harrell) and the Seattle-Puget Sound area of Washington (Margaret Madeleine). We also thank analysts at Information Management Services for programming support (Matthew Chaloux, Michael Curry, Ruth Parsons). The views expressed in this paper are those of the authors and should not be interpreted to reflect the views or policies of the National Cancer Institute, Health Resources and Services Administration, SRTR, cancer registries or their contractors. This research was supported in part by the Intramural Research Program of the National Cancer Institute. During the initial period when registry linkages were performed, the SRTR was managed by Arbor Research Collaborative for Health in Ann Arbor, MI (contract HHSH234200537009C); beginning in September 2010, the SRTR was managed by Minneapolis Medical Research Foundation in Minneapolis, MN (HHSH250201000018C). The following cancer registries were supported by the National Program of Cancer Registries of the Centers for Disease Control and Prevention: California (agreement 1U58 DP000807-01), Colorado (U58 DP000848-04), Georgia (5U58DP003875-01), Illinois (5658DP000805-04), Michigan (5U58DP000812-03), New Jersey (1US58/DP0039311-01), New York (U58DP0038789), North Carolina (U58DP000832) and Texas (5U58DP000824-04). The following cancer registries were supported by the SEER Program of the National Cancer Institute: California (contracts HHSN261201000036C, HHSN261201000035C and HHSN261201000034C), Connecticut (HHSN261201000024C), Hawaii (HHSN261201000037C, N01-PC-35137 and N01-PC-35139), Iowa (HSN261201000032C and N01-PC-35143), New Jersey (HHSN261201000027C and N01-PC-2010-0027), Seattle-Puget Sound (N01-PC-35142) and Utah (HHSN261201000026C). Additional support was provided by the states of California, Colorado, Connecticut, Illinois, Iowa, New Jersey, New York (Cancer Surveillance Improvement Initiative 14-2491), Texas and Washington, as well as the Fred Hutchinson Cancer Research Center in Seattle, WA. NR 32 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2014 VL 14 IS 6 BP 1376 EP 1382 DI 10.1111/ajt.12683 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA AJ2UP UT WOS:000337519500019 PM 24712385 ER PT J AU Canna, SW Costa-Reis, P Bernal, WE Chu, NS Sullivan, KE Paessler, ME Behrens, EM AF Canna, Scott W. Costa-Reis, Patricia Bernal, William E. Chu, Niansheng Sullivan, Kathleen E. Paessler, Michele E. Behrens, Edward M. TI Alternative Activation of Laser-Captured Murine Hemophagocytes SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID MACROPHAGE ACTIVATION; HETEROGENEITY; RESPONSES; ANEMIA AB Objective. Hemophagocytes (HPCs) are activated macrophages that have engulfed other hematopoietic cells. Although HPCs are rarely identified in normal spleen tissue and bone marrow, an excess of these macrophages characterizes many cytokine storm syndromes, particularly macrophage activation syndrome and hemophagocytic lymphohistiocytosis. This study was undertaken to assess the functions of HPCs and their significance in acute inflammatory conditions. Methods. HPCs were generated in wild-type mice using repeated stimulation with Toll-like receptor 9 (TLR-9) and interleukin-10 receptor blockade. RNA was extracted from HPCs that had been isolated by laser-captured microdissection. Transcriptional profiles of the HPCs were then compared to those of resting splenic macrophages. In addition, bone marrow samples were obtained from a diverse cohort of patients in whom excess hemophagocytosis was identified by clinical bone marrow biopsy or aspiration. The bone marrow samples were analyzed by immunohistochemistry for markers of classic (CD64) or alternative (CD163 and CD206) macrophage activation. Results. Differential gene expression and gene set enrichment analyses of murine HPCs identified upregulation of genes and gene sets associated with alternative activation of HPCs. Immunohistochemical analyses of HPCs in human bone marrow samples showed universal staining of HPCs for CD163, but rarely for CD206 or CD64. Conclusion. Laser-captured murine TLR-9induced HPCs had a transcriptional profile similar to that of alternatively activated macrophages. In addition, HPC expression of CD163 was confirmed in a uniquely diverse cohort of patients with hemophagocytic syndromes. Collectively, these data support the hypothesis that HPCs have both immunoregulatory and clean-up functions. C1 [Canna, Scott W.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Costa-Reis, Patricia; Chu, Niansheng; Sullivan, Kathleen E.; Paessler, Michele E.; Behrens, Edward M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Bernal, William E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sullivan, Kathleen E.; Paessler, Michele E.; Behrens, Edward M.] Univ Penn, Philadelphia, PA 19104 USA. RP Canna, SW (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr,Bldg 10,Room 13C103, Bethesda, MD 20892 USA. EM scott.canna@nih.gov OI Canna, Scott/0000-0003-3837-5337 FU Histiocytosis Association; NIH [F32-AI-98337, K08-AI-79396]; Rheumatology Research Foundation Scientist Development award; Fundacao Calouste Gulbenkian; Fundacao para a Ciencia e a Tecnologia; Howard Hughes Medical Institute Early Career Physician Scientist award; Arthritis Foundation Innovative Research grant FX Supported by a grant from the Histiocytosis Association. Dr. Canna's work was supported by NIH grant F32-AI-98337 and a Rheumatology Research Foundation Scientist Development award. Dr. Costa-Reis' work was supported by the Fundacao Calouste Gulbenkian and the Fundacao para a Ciencia e a Tecnologia. Dr. Behrens' work was supported by NIH grant K08-AI-79396, a Howard Hughes Medical Institute Early Career Physician Scientist award, and an Arthritis Foundation Innovative Research grant. NR 15 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JUN PY 2014 VL 66 IS 6 BP 1666 EP 1671 DI 10.1002/art.38379 PG 6 WC Rheumatology SC Rheumatology GA AJ0SL UT WOS:000337366200029 PM 24470386 ER PT J AU Kim, EJ Abramowitz, LK Bond, MR Love, DC Kang, DW Leucke, HF Kang, DW Ahn, JS Hanover, JA AF Kim, Eun J. Abramowitz, Lara K. Bond, Michelle R. Love, Dona C. Kang, Dong W. Leucke, Hans F. Kang, Dae W. Ahn, Jong-Seog Hanover, John A. TI Versatile O-GlcNAc Transferase Assay for High-Throughput Identification of Enzyme Variants, Substrates, and Inhibitors SO BIOCONJUGATE CHEMISTRY LA English DT Article ID INSULIN-RESISTANCE; TETRATRICOPEPTIDE REPEATS; CYTOSOLIC PROTEINS; GLYCOSYLATION; MECHANISM; PHOSPHORYLATION; GLCNACYLATION; ISOFORMS; NUCLEAR; DOMAIN AB The dynamic glycosylation of serine/threonine residues on nucleocytoplasmic proteins with a single N-acetylglucosamine (O-GlcNAcylation) is critical for many important cellular processes. Cellular O-GlcNAc levels are highly regulated by two enzymes: O-GlcNAc transferase (OGT) is responsible for GlcNAc addition and O-GlcNAcase (OGA) is responsible for removal of the sugar. The lack of a rapid and simple method for monitoring OCT activity has impeded the efficient discovery of potent OCT inhibitors. In this study we describe a novel, single-well OGT enzyme assay that utilizes 6 X His-tagged substrates, a chemoselective chemical reaction, and unpurified OCT. The high-throughput Ni-NTA Plate OCT Assay will facilitate discovery of potent OGT-specific inhibitors on versatile substrates and the characterization of new enzyme variants. C1 [Kim, Eun J.] Daegu Univ, Dept Sci Educ Chem Major, Gyeongbuk 712714, South Korea. [Abramowitz, Lara K.; Bond, Michelle R.; Love, Dona C.; Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. [Leucke, Hans F.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Kang, Dong W.] Catholic Univ Daegu, Dept Pharmaceut Sci & Technol, Gyeongbuk 712702, South Korea. [Kang, Dae W.] Changwon Natl Univ, Coll Nat Sci, Dept Biochem & Hlth Sci, Chang Won 641773, South Korea. [Ahn, Jong-Seog] Korea Res Inst Biosci & Biotechnol KRIBB, Biotherapeut Res Inst, Chem Biol Res Ctr, Cheongwon 363883, South Korea. RP Kim, EJ (reprint author), Daegu Univ, Dept Sci Educ Chem Major, Gyeongbuk 712714, South Korea. EM eunkim@daegu.ac.kr; jah@helix.nih.gov FU NIDDK intramural funds (NIH); National Research Foundation of Korea [2011-0027257] FX This work was supported by NIDDK intramural funds (NIH) and the National Research Foundation of Korea (2011-0027257). NR 37 TC 4 Z9 4 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUN PY 2014 VL 25 IS 6 BP 1025 EP 1030 DI 10.1021/bc5001774 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA AJ5KB UT WOS:000337720000001 PM 24866374 ER PT J AU Lee, JA Biel, NM Kozikowski, RT Siemann, DW Sorg, BS AF Lee, Jennifer A. Biel, Nikolett M. Kozikowski, Raymond T. Siemann, Dietmar W. Sorg, Brian S. TI In vivo spectral and fluorescence microscopy comparison of microvascular function after treatment with OXi4503, Sunitinib and their combination in Caki-2 tumors SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID VASCULAR-DISRUPTING AGENTS; DORSAL WINDOW CHAMBER; COMBRETASTATIN A-4 PHOSPHATE; HUMAN-MELANOMA XENOGRAFTS; BLOOD-FLOW; ANTIANGIOGENIC THERAPY; INTRAVITAL MICROSCOPY; HEMOGLOBIN SATURATION; COMBINING AVASTIN; TARGETING AGENTS AB Vascular targeting agents on their own have been shown to be insufficient for complete treatment of solid tumors, emphasizing the importance of studying the vascular effects of these drugs for their use with conventional therapies in the clinic. First-pass fluorescence imaging combined with hyperspectral imaging of hemoglobin saturation of microvessels in the murine dorsal window chamber model provides an easily implementable, low cost method to analyze tumor vascular response to these agents in real-time. In this study, the authors utilized these methods to spectroscopically demonstrate distinct vessel structure, blood flow and oxygenation changes in human Caki-2 renal cell carcinoma following treatment with OXi4503 alone, Sunitinib alone and both drugs together. We showed that treatment with OXi4503 plus Sunitinib destroyed existing tumor microvessels, inhibited blood vessel recovery and impaired Caki-2 tumor growth significantly more than either treatment alone. (C) 2014 Optical Society of America C1 [Lee, Jennifer A.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32610 USA. [Biel, Nikolett M.] Univ Florida, Coll Med, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA. [Kozikowski, Raymond T.] Ventana Med Syst Inc, Tucson, AZ 85755 USA. [Siemann, Dietmar W.] Univ Florida, Coll Med, Dept Radiat Oncol, Gainesville, FL 32610 USA. [Sorg, Brian S.] NCI, Canc Diag Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. RP Lee, JA (reprint author), Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Biomed Sci Bldg, Gainesville, FL 32610 USA. EM jalee2@ufl.edu FU Bankhead-Coley Cancer Research Program of the Florida Department of Health; National Cancer Institute (US Public Health Service) [R01 CA084408] FX This work was supported in part by a grant from the Bankhead-Coley Cancer Research Program of the Florida Department of Health (Brian S. Sorg) and in part by a grant from the National Cancer Institute (US Public Health Service grant R01 CA084408; (Dietmar W. Siemann)). NR 58 TC 6 Z9 6 U1 2 U2 11 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 JUN 1 PY 2014 VL 5 IS 6 BP 1965 EP 1979 DI 10.1364/BOE.5.001965 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA AJ2QM UT WOS:000337503900021 PM 24940553 ER PT J AU Chen, BJ Qin, J AF Chen, Baojiang Qin, Jing TI Test the reliability of doubly robust estimation with missing response data SO BIOMETRICS LA English DT Article DE Auxiliary; Doubly robust; Estimating equation; Goodness of fit; Missing data ID SURROGATE END-POINTS; CLINICAL-TRIALS; INCOMPLETE DATA; REGRESSION; MODELS; RESIDUALS; CHECKING AB In statistical inference, one has to make sure that the underlying regression model is correctly specified otherwise the resulting estimation may be biased. Model checking is an important method to detect any departure of the regression model from the true one. Missing data are a ubiquitous problem in social and medical studies. If the underlying regression model is correctly specified, recent researches show great popularity of the doubly robust (DR) estimates method for handling missing data because of its robustness to the misspecification of either the missing data model or the conditional mean model, that is, the model for the conditional expectation of true regression model conditioning on the observed quantities. However, little work has been devoted to the goodness of fit test for DR estimates method. In this article, we propose a testing method to assess the reliability of the estimator derived from the DR estimating equation with possibly missing response and always observed auxiliary variables. Numerical studies demonstrate that the proposed test can control type I errors well. Furthermore the proposed method can detect departures from model assumptions in the marginal mean model of interest powerfully. A real dementia data set is used to illustrate the method for the diagnosis of model misspecification in the problem of missing response with an always observed auxiliary variable for cross-sectional data. C1 [Chen, Baojiang] Univ Nebraska, Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE 68198 USA. [Qin, Jing] NIAID, NIH, Bethesda, MD 20892 USA. RP Chen, BJ (reprint author), Univ Nebraska, Med Ctr, Coll Publ Hlth, Dept Biostat, 600 S 42nd St, Omaha, NE 68198 USA. EM baojiang.chen@unmc.edu FU National Institute on Aging [U01AG016976] FX The authors thank the Editor, associated editor, and two referees for their constructive comments and suggestions, which have improved this article greatly. Dr Chen was supported in part by National Institute on Aging grant U01AG016976. NR 31 TC 0 Z9 0 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD JUN PY 2014 VL 70 IS 2 BP 289 EP 298 DI 10.1111/biom.12150 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA AJ4DK UT WOS:000337621000005 PM 24571677 ER PT J AU Falzarano, D Feldmann, H AF Falzarano, Darryl Feldmann, Heinz TI Possible leap ahead in filovirus therapeutics SO CELL RESEARCH LA English DT Editorial Material ID EBOLA-VIRUS INFECTION; POSTEXPOSURE PROTECTION; NONHUMAN-PRIMATES; HEMORRHAGIC-FEVER C1 [Falzarano, Darryl; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA. RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA. EM feldmannh@niaid.nih.gov NR 12 TC 10 Z9 14 U1 0 U2 17 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JUN PY 2014 VL 24 IS 6 BP 647 EP 648 DI 10.1038/cr.2014.49 PG 2 WC Cell Biology SC Cell Biology GA AJ4XL UT WOS:000337682900004 PM 24732011 ER PT J AU Xu, YS Xu, LL Zhao, M Xu, CG Fan, YL Pierce, SK Liu, WL AF Xu, Yinsheng Xu, Liling Zhao, Meng Xu, ChenGuang Fan, Yilin Pierce, Susan K. Liu, Wanli TI No receptor stands alone: IgG B-cell receptor intrinsic and extrinsic mechanisms contribute to antibody memory SO CELL RESEARCH LA English DT Review DE B-cell receptor; antibody response; B-cell memory; plasma cell; germinal center ID RESONANCE ENERGY-TRANSFER; SINGLE-MOLECULE TRACKING; GERMINAL CENTER REACTION; ANTIGEN RECEPTOR; LYMPH-NODE; TRANSCRIPTION FACTOR; PLASMA-MEMBRANE; SIGNAL-TRANSDUCTION; SUBCAPSULAR SINUS; SECRETING CELLS AB Acquired immunological memory is a striking phenomenon. A lethal epidemic sweeps through a naive population, many die but those who survive are never "attacked twice - never at least fatally", as the historian Thucydides observed in 430 BCE. Antibody memory is critical for protection against many human infectious diseases and is the basis for nearly all current human vaccines. Antibody memory is encoded, in part, in isotype-switched immunoglobulin (Ig)G-expressing memory B cells that are generated in the primary response to antigen and give rise to rapid, high-affinity and high-titered antibody responses upon challenge with the same antigen. How IgG-B-cell receptors (BCRs) and antigen-induced IgG-BCR signaling contribute to memory antibody responses are not fully understood. In this review, we summarize exciting new advances that are revealing the cellular and molecular mechanisms at play in antibody memory and discuss how studies using different experimental approaches will help elucidate the complex phenomenon of B-cell memory. C1 [Xu, Yinsheng; Xu, Liling; Zhao, Meng; Xu, ChenGuang; Fan, Yilin; Liu, Wanli] Tsinghua Univ, Sch Life Sci, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China. [Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Xu, Yinsheng; Liu, Wanli] Tsinghua Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Beijing 100084, Peoples R China. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM spierce@nih.gov; liuwanli@biomed.tsinghua.edu.cn FU Ministry of Science and Technology of China [2014CB542500-03, 2014AA020527]; National Natural Science Foundation of China [81361120384, 31270913]; Beijing Natural Science Foundation [5132016]; PhD Programs Foundation of Ministry of Education of China [20130002110059, 201200021200076]; New Century Excellent Talents program in University of Ministry of Education of China [NCET-12-0299]; One-Thousand-Youth-Talents program of Chinese Central Government [2069999-3]; Tsinghua University Initiative Scientifc Research Program [2013Z1089279] FX This work was supported by the Ministry of Science and Technology of China (2014CB542500-03, 2014AA020527), the National Natural Science Foundation of China (81361120384, 31270913), the Beijing Natural Science Foundation (5132016), the PhD Programs Foundation of Ministry of Education of China (20130002110059, 201200021200076), the New Century Excellent Talents program in University of Ministry of Education of China (NCET-12-0299), the One-Thousand-Youth-Talents program (2069999-3) of Chinese Central Government, and Tsinghua University Initiative Scientifc Research Program (2013Z1089279). Wanli Liu expresses his heartfelt thanks to Dr Susan K Pierce for her inculcated mentoring in his postdoctoral trainings. NR 81 TC 9 Z9 9 U1 4 U2 11 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JUN PY 2014 VL 24 IS 6 BP 651 EP 664 DI 10.1038/cr.2014.65 PG 14 WC Cell Biology SC Cell Biology GA AJ4XL UT WOS:000337682900006 PM 24839903 ER PT J AU Andrade, BB Kumar, NP Sridhar, R Banurekha, VV Jawahar, MS Nutman, TB Sher, A Babu, S AF Andrade, Bruno B. Kumar, Nathella Pavan Sridhar, Rathinam Banurekha, Vaithilingam V. Jawahar, Mohideen S. Nutman, Thomas B. Sher, Alan Babu, Subash TI Heightened Plasma Levels of Heme Oxygenase-1 and Tissue Inhibitor of Metalloproteinase-4 as Well as Elevated Peripheral Neutrophil Counts Are Associated With TB-Diabetes Comorbidity SO CHEST LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; MATRIX METALLOPROTEINASES; PULMONARY TUBERCULOSIS; OXIDATIVE STRESS; MICE; BIOMARKERS; CELLS; MATRIX-METALLOPROTEINASE-9; INFLAMMATION; EXPRESSION AB Background: The increased prevalence of type 2 diabetes mellitus (T2DM) in countries endemic for TB poses a serious complication in the clinical management of this major infectious disease. Understanding the impact of T2DM on TB and the determinants of comorbidity is critical in responding to this growing public health problem with better therapeutic approaches. Here, we performed an exploratory study assessing a series of biologic parameters that could serve as markers of pathogenesis in TB with T2DM. Methods: Cross-sectional analyses of levels of heme oxygenase-1 (HO-1), acute phase proteins, tissue metalloproteinases, and tissue inhibitors of metalloproteinase (TIMPs) as well as cytokines and chemokines were performed in plasma samples from individuals with active pulmonary TB or with coincident TB and T2DM from South India. Results: Compared with patients with TB without diabetes, those with coincident T2DM exhibited increased Mycobacterium tuberculosis bacillary loads in sputum. Plasma levels of HO-1 but not of other acute phase proteins were higher in patients with TB and T2DM than in patients without diabetes, independent of bacillary sputum loads. HO-1 concentrations also positively correlated with random plasma glucose, circulating glycosylated hemoglobin, and low-density lipoprotein levels. Moreover, patients with coincident TB and T2DM exhibited increased plasma levels of TIMP-4 and elevated peripheral blood neutrophil counts, which, when considered together with HO-1, resulted in increased power to discriminate individuals with active TB with and without T2DM. Conclusions: Elevated plasma levels of HO-1 and TIMP-4 and peripheral blood neutrophil counts are potential single and combined markers of pathogenesis in TB and T2DM. C1 [Andrade, Bruno B.; Sher, Alan] NIH, Immunobiol Sect, Bethesda, MD 20892 USA. [Nutman, Thomas B.; Babu, Subash] NIH, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. [Kumar, Nathella Pavan; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.] Int Ctr Excellence Res, Madras, Tamil Nadu, India. [Kumar, Nathella Pavan; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.] Natl Inst Res TB, Madras, Tamil Nadu, India. [Sridhar, Rathinam] Govt Stanley Med Hosp, Madras, Tamil Nadu, India. RP Andrade, BB (reprint author), NIH, Parasit Dis Lab, 50 S Dr,Room 6146, Bethesda, MD 20892 USA. EM andradebd@niaid.nih.gov RI Andrade, Bruno/J-9111-2012 OI Andrade, Bruno/0000-0001-6833-3811 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 31 TC 6 Z9 6 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2014 VL 145 IS 6 BP 1244 EP 1254 DI 10.1378/chest.13-1799 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AJ0OV UT WOS:000337355600017 PM 24458266 ER PT J AU Demehri, S Yockey, LJ Visness, CM Jaffee, KF Turkoz, A Wood, RA O'Connor, GT Kattan, M Gern, JE Gergen, PJ Holtzman, M Bloomberg, G Kopan, R AF Demehri, S. Yockey, L. J. Visness, C. M. Jaffee, K. F. Turkoz, A. Wood, R. A. O'Connor, G. T. Kattan, M. Gern, J. E. Gergen, P. J. Holtzman, M. Bloomberg, G. Kopan, R. TI Circulating TSLP associates with decreased wheezing in non-atopic preschool children: data from the URECA birth cohort SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE atopy; birth cohort; preschool wheeze; recurrent wheeze; TSLP; URECA ID THYMIC STROMAL LYMPHOPOIETIN; AGGRAVATES EXPERIMENTAL ASTHMA; ATOPIC-DERMATITIS; MOUSE SKIN; INFLAMMATION; KERATINOCYTES; EXPRESSION; VITAMIN-D3; TRIGGER; CELLS AB Background Mouse models of atopic march suggest that systemic, skin-derived thymic stromal lymphopoietin (TSLP) mediates progression from eczema to asthma. Objective We investigated whether circulating TSLP is associated with eczema, allergic sensitization, or recurrent wheezing in young children. Methods A prospective analysis of the relationship between plasma levels of TSLP to allergic sensitization and recurrent wheezing was conducted in the birth cohort from the Urban Environment and Childhood Asthma (URECA) study. Plasma TSLP levels were measured at 1, 2, and 3years of age and analysed for correlation with clinical parameters in each of the three years. Only those children with consecutive samples for all three years were included in this analysis. Results We detected TSLP in 33% of 236 children for whom plasma samples were available for all three years. Overall, a consistently significant association was not found between TSLP and eczema or allergic sensitization. With regard to recurrent wheezing, children with detectable TSLP at one year of age were significantly less likely to experience recurrent wheezing by 3years compared with those children without detectable TSLP, but this was only seen in children without aeroallergen sensitization at 3years (P<0.01). Conclusions and Clinical Relevance Contrary to our expectations, circulating TSLP was not significantly associated with eczema, allergen sensitization, or recurrent wheezing during the first three years of life. Early presence of circulating TSLP was significantly associated with reduced incidence of recurrent wheeze in those children not sensitized to aeroallergen. These findings suggest a possible underlying distinction between pathogenesis of developing atopic vs. non-atopic recurrent wheeze. C1 [Demehri, S.; Yockey, L. J.; Turkoz, A.; Holtzman, M.; Bloomberg, G.; Kopan, R.] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Visness, C. M.; Jaffee, K. F.] Rho Fed Syst Div Inc, Chapel Hill, NC USA. [Wood, R. A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [O'Connor, G. T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kattan, M.] Columbia Univ, Sch Med, New York, NY USA. [Gern, J. E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Gergen, P. J.] NIH, Div Allergy Immunol & Transplantat, Bethesda, MD USA. [Kopan, R.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Div Dev Biol,Med Ctr, Cincinnati, OH USA. RP Bloomberg, G (reprint author), Washington Univ, Sch Med, St Louis Childrens Hosp, Div Allergy & Pulm Med, 5 S 30,One Childrens Pl, St Louis, MO 63110 USA. EM Bloomberg@kids.wustl.edu; Raphael.kopan@cchmc.org FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [NO1-AI-25496, NO1-AI-25482, HHSN 272200900052C, HHSN2722010000521]; National Center for Research Resources, National Institutes of Health [RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156]; Lincoln Diagnostics; Children's Discovery Institute of Washington University; St. Louis Children's Hospital; American Asthma Foundation [09-0234] FX This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under Contract Numbers NO1-AI-25496, NO1-AI-25482, HHSN 272200900052C, and HHSN2722010000521. Additional support was provided by the National Center for Research Resources, National Institutes of Health, under Grants RR00052, M01RR00533, 1UL1RR025771, M01RR00071, and 1UL1RR024156; and from Lincoln Diagnostics (which provided Multi-Test (R)). Additional funding for this project was provided by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital. RK was funded in part by the American Asthma Foundation (grant 09-0234). NR 25 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-7894 EI 1365-2222 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD JUN PY 2014 VL 44 IS 6 BP 851 EP 857 DI 10.1111/cea.12270 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA AJ2XT UT WOS:000337529100007 PM 24397611 ER PT J AU Lockett, S Verma, C Brafman, A Gudla, P Nandy, K Mimaki, Y Fuchs, PL Jaja, J Reilly, KM Beutler, J Turbyville, TJ AF Lockett, Stephen Verma, Chrissie Brafman, Alla Gudla, Prabhakar Nandy, Kaustav Mimaki, Yoshihiro Fuchs, Philip L. Jaja, Joseph Reilly, Karlyne M. Beutler, John Turbyville, Thomas J. TI Quantitative analysis of F-actin redistribution in astrocytoma cells treated with candidate pharmaceuticals SO CYTOMETRY PART A LA English DT Article DE fibrillar actin; image analysis; pattern analysis; cytoskeleton; anti-cancer drugs; artificial neural network; fluorescence microscopy ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; MICROSCOPY IMAGES; NATURAL-PRODUCTS; MYOSIN-II; ORGANIZATION; LAMELLIPODIA; CYTOSKELETON; MECHANISMS; NETWORKS; CALCIUM AB Actin fibers (F-actin) control the shape and internal organization of cells, and generate force. It has been long appreciated that these functions are tightly coupled, and in some cases drive cell behavior and cell fate. The distribution and dynamics of F-actin is different in cancer versus normal cells and in response to small molecules, including actin-targeting natural products and anticancer drugs. Therefore, quantifying actin structural changes from high resolution fluorescence micrographs is necessary for further understanding actin cytoskeleton dynamics and phenotypic consequences of drug interactions on cells. We applied an artificial neural network algorithm, which used image intensity and anisotropy measurements, to quantitatively classify F-actin subcellular features into actin along the edges of cells, actin at the protrusions of cells, internal fibers and punctate signals. The algorithm measured significant increase in F-actin at cell edges with concomitant decrease in internal punctate actin in astrocytoma cells lacking functional neurofibromin and p53 when treated with three structurally-distinct anticancer small molecules: OSW1, Schweinfurthin A (SA) and a synthetic marine compound 23'-dehydroxycephalostatin 1. Distinctly different changes were measured in cells treated with the actin inhibitor cytochalasin B. These measurements support published reports that SA acts on F-actin in NF1-/- neurofibromin deficient cancer cells through changes in Rho signaling. Quantitative pattern analysis of cells has wide applications for understanding mechanisms of small molecules, because many anti-cancer drugs directly or indirectly target cytoskeletal proteins. Furthermore, quantitative information about the actin cytoskeleton may make it possible to further understand cell fate decisions using mathematically testable models. Published 2014 Wiley Periodicals Inc. C1 [Lockett, Stephen; Brafman, Alla; Gudla, Prabhakar; Nandy, Kaustav; Turbyville, Thomas J.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res FNLCR, Opt Microscopy & Anal Lab, Frederick, MD USA. [Verma, Chrissie] VMware Inc, Cambridge, MA USA. [Mimaki, Yoshihiro] Tokyo Univ Pharm & Life Sci, Sch Pharm, Hachioji, Tokyo 1920392, Japan. [Fuchs, Philip L.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Jaja, Joseph] Univ Maryland, College Pk, MD 20742 USA. [Reilly, Karlyne M.] Natl Canc Inst Frederick NCI F, Mouse Canc Genet Program, Frederick, MD USA. [Beutler, John] NCI F, Mol Targets Lab, Frederick, MD USA. RP Lockett, S (reprint author), Frederick Natl Lab Canc Res, Rm 104A,POB B, Frederick, MD 21702 USA. EM locketts@mail.nih.gov FU National Cancer Institute; National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the National Institutes of Health, National Cancer Institute; Center for Cancer Research FX Grant sponsors: National Cancer Institute and National Institutes of Health, Grant number: HHSN261200800001E; Grant sponsors: Intramural Research Program of the National Institutes of Health, National Cancer Institute and Center for Cancer Research. NR 42 TC 2 Z9 2 U1 3 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 EI 1552-4930 J9 CYTOM PART A JI Cytom. Part A PD JUN PY 2014 VL 85A IS 6 BP 512 EP 521 DI 10.1002/cyto.a.22442 PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AJ2WS UT WOS:000337525900008 PM 24515854 ER PT J AU Margolis, KL O'Connor, PJ Morgan, TM Buse, JB Cohen, RM Cushman, WC Cutler, JA Evans, GW Gerstein, HC Grimm, RH Lipkin, EW Narayan, KMV Riddle, MC Sood, A Goff, DC AF Margolis, Karen L. O'Connor, Patrick J. Morgan, Timothy M. Buse, John B. Cohen, Robert M. Cushman, William C. Cutler, Jeffrey A. Evans, Gregory W. Gerstein, Hertzel C. Grimm, Richard H., Jr. Lipkin, Edward W. Narayan, K. M. Venkat Riddle, Matthew C., Jr. Sood, Ajay Goff, David C., Jr. TI Outcomes of Combined Cardiovascular Risk Factor Management Strategies in Type 2 Diabetes: The ACCORD Randomized Trial SO DIABETES CARE LA English DT Article ID INTENSIVE BLOOD-PRESSURE; MULTIFACTORIAL INTERVENTION; MICROVASCULAR OUTCOMES; MELLITUS; THERAPY; RATIONALE; MORTALITY; TARGETS; DISEASE; DESIGN AB OBJECTIVE To compare effects of combinations of standard and intensive treatment of glycemia and either blood pressure (BP) or lipids in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. RESEARCH DESIGN AND METHODS ACCORD enrolled 10,251 type 2 diabetes patients aged 40-79 years at high risk for cardiovascular disease (CVD) events. Participants were randomly assigned to hemoglobin A(1c), goals of <6.0% (<42 mmol/mol; intensive glycemia) or 7.0-7.9% (53-63 mmol/mol; standard glycemia) and then randomized a second time to either 1) systolic BP goals of <120 mmHg (intensive BP) or <140 mmHg (standard BP) or 2) simvastatin plus fenofibrate (intensive lipid) or simvastatin plus placebo (standard lipid). Proportional hazards models were used to assess combinations of treatment assignments on the composite primary (deaths due to CVD, nonfatal myocardial infarction [MI], and nonfatal stroke) and secondary outcomes. RESULTS In the BP trial, risk of the primary outcome was lower in the groups intensively treated for glycemia (hazard ratio [HR] 0.67; 95% CI 0.50-0.91), BP (HR 0.74; 95% CI 0.55-1.00), or both (HR 0.71; 95% CI 0.52-0.96) compared with combined standard BP and glycemia treatment. For secondary outcomes, MI was significantly reduced by intensive glycemia treatment and stroke by intensive BP treatment; most other HRs were neutral or favored intensive treatment groups. In the lipid trial, the general pattern of results showed no evidence of benefit of intensive regimens (whether single or combined) compared with combined standard lipid and glycemia treatment. The mortality HR was 1.33 (95% CI 1.02-1.74) in the standard lipid/intensive glycemia group compared with the standard lipid/standard glycemia group. CONCLUSIONS In the ACCORD BP trial, compared with combined standard treatment, intensive BP or intensive glycemia treatment alone improved major CVD outcomes, without additional benefit from combining the two. In the ACCORD lipid trial, neither intensive lipid nor glycemia treatment produced an overall benefit, but intensive glycemia treatment increased mortality. C1 [Margolis, Karen L.; O'Connor, Patrick J.] HealthPartners Inst Educ & Res, Minneapolis, MN 55440 USA. [Morgan, Timothy M.; Evans, Gregory W.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Buse, John B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Cohen, Robert M.] Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. [Cohen, Robert M.] Univ Cincinnati, Cincinnati, OH USA. [Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA. [Cutler, Jeffrey A.] NHLBI, Bethesda, MD 20892 USA. [Gerstein, Hertzel C.] McMaster Univ, Hamilton, ON, Canada. [Grimm, Richard H., Jr.] Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. [Lipkin, Edward W.] Univ Washington, Seattle, WA 98195 USA. [Narayan, K. M. Venkat] Emory Univ, Atlanta, GA 30322 USA. [Riddle, Matthew C., Jr.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Sood, Ajay] Louis Stokes Vet Affairs Med Ctr, Cleveland, OH USA. [Sood, Ajay] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Goff, David C., Jr.] Colorado Sch Publ Hlth, Aurora, CO USA. RP Margolis, KL (reprint author), HealthPartners Inst Educ & Res, Minneapolis, MN 55440 USA. EM karen.l.margolis@healthpartners.com RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 FU NHLBI [N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01HC-95183, N01-HC-95184, IAA-Y1-HC-9035, IAA-Y1-HC-1010]; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; NHLBI; NIH FX This work was supported by the NHLBI (contracts N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01HC-95183, N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC-1010) and partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute and by General Clinical Research Centers at many sites. Substudies within the ACCORD trial on cost-effectiveness and health-related quality of life were supported by the Centers for Disease Control and Prevention. All authors were supported by NIH grant funds for the ACCORD trial during the study. K.L.M. has NIH studies with funds going to her institution and assumes all responsibility for the work as a whole. W.C.C. reports grants from NHLBI and NIH during the conduct of the study. The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceuticals, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi, and Schering-Plough. NR 23 TC 38 Z9 41 U1 2 U2 9 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 JUN PY 2014 VL 37 IS 6 BP 1721 EP 1728 DI 10.2337/dc13-2334 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AJ5RX UT WOS:000337746100050 PM 24595629 ER PT J AU Mejia, E Buraka, M Alonso, A Larraga, V Kunkel, TA Bebenek, K Garcia-Diaz, M AF Mejia, Edison Buraka, Matthew Alonso, Ana Larraga, Vicente Kunkel, Thomas A. Bebenek, Katarzyna Garcia-Diaz, Miguel TI Structures of the Leishmania infantum polymerase beta SO DNA REPAIR LA English DT Article DE DNA repair; Leishmaniasis; DNA polymerase; Family X ID HUMAN DNA-POLYMERASE; BASE-EXCISION-REPAIR; MURINE TERMINAL DEOXYNUCLEOTIDYLTRANSFERASE; 5'-DEOXYRIBOSE-5-PHOSPHATE LYASE ACTIVITY; CRYSTAL-STRUCTURES; CATALYTIC CYCLE; STRAND MISALIGNMENT; POL LAMBDA; FIDELITY; MECHANISM AB Protozoans of the genus Leishmania, the pathogenic agent causing leishmaniasis, encode the family X DNA polymerase Li Pol beta. Here, we report the first crystal structures of Li Pol beta. Our pre- and post-catalytic structures show that the polymerase adopts the common family X DNA polymerase fold. However, in contrast to other family X DNA polymerases, the dNTP-induced conformational changes in Li Pol beta are much more subtle. Moreover, pre- and post-catalytic structures reveal that Li Pol beta interacts with the template strand through a nonconserved, variable region known as loop3. Li Pol beta Delta Ioop3 mutants display a higher catalytic rate, catalytic efficiency and overall error rates with respect to WT Li Pol beta. These results further demonstrate the subtle structural variability that exists within this family of enzymes and provides insight into how this variability underlies the substantial functional differences among their members. (C) 2014 Elsevier B.V. All rights reserved. C1 [Mejia, Edison; Buraka, Matthew; Garcia-Diaz, Miguel] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. [Alonso, Ana; Larraga, Vicente] CSIC, Ctr Invest Biol, E-28040 Madrid, Spain. [Kunkel, Thomas A.; Bebenek, Katarzyna] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Bebenek, K (reprint author), SUNY Stony Brook, BST 7-120, Stony Brook, NY 11733 USA. EM bebenek@niehs.nih.gov; miguel.garcia-diaz@stonybrook.edu FU Offices of Biological and Environmental Research and of Basic Energy Sciences of the US Department of Energy; National Center for Research Resources of the National Institutes of Health; Fundacion Ramon Areces; MICINN [AGL2010-21806-C02-01)]; [R01-GM100021]; [ROD ES015421] FX We thank the NSLS Protein Crystallography group. NSLS beamlines x25 and x29 are mainly supported by the Offices of Biological and Environmental Research and of Basic Energy Sciences of the US Department of Energy, and the National Center for Research Resources of the National Institutes of Health. This work was supported by R01-GM100021 and ROD ES015421 to MGD. AA and VL thank the Fundacion Ramon Areces and MICINN (AGL2010-21806-C02-01) for funding. NR 48 TC 1 Z9 1 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD JUN PY 2014 VL 18 BP 1 EP 9 DI 10.1016/j.dnarep.2014.03.001 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA AJ4PP UT WOS:000337658600001 PM 24666693 ER PT J AU Makarova, AV McElhinny, SAN Watts, BE Kunkel, TA Burgers, PM AF Makarova, Alena V. McElhinny, Stephanie A. Nick Watts, Brian E. Kunkel, Thomas A. Burgers, Peter M. TI Ribonucleotide incorporation by yeast DNA polymerase zeta SO DNA REPAIR LA English DT Article DE Ribonucleotides; Mutagenesis; DNA polymerase; Translesion synthesis ID DOUBLE-STRAND BREAK; SACCHAROMYCES-CEREVISIAE; REV1 PROTEIN; MUTAGENESIS; COMPLEX; REPAIR; DELTA; PCNA AB During replication in yeast, the three B family DNA replicases frequently incorporate ribonucleotides (rNMPs) into DNA, and their presence in the nuclear genome can affect genome stability. This prompted us to examine ribonucleotide incorporation by the fourth B family member, Pol zeta, the enzyme responsible for the majority of damage-induced mutagenesis in eukaryotes. We first show that Pol inserts rNMPs into DNA and can extend primer termini containing 3'-ribonucleotides. We then measure rNMP incorporation by Pol in the presence of its cofactors, RPA, RFC and PCNA and at normal cellular dNTP and rNTP concentrations that exist under unstressed conditions. Under these conditions, Pol zeta stably incorporates one rNMP for every 200-300 dNMPs incorporated, a frequency that is slightly higher than for the high fidelity replicative DNA polymerases. Under damage-induced conditions wherein cellular dNTP concentrations are elevated 5-fold, Pol zeta only incorporates one rNMP per 1300 dNMPs. Functional interaction of Pol zeta with the mutasome assembly factor Rev1 gives comparable rNMP incorporation frequencies. These results suggest that ribonucleotide incorporation into DNA during Pol zeta-mediated mutagenesis in vivo may be rare. (C) 2014 Elsevier B.V. All rights reserved. C1 [Makarova, Alena V.; Burgers, Peter M.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. [McElhinny, Stephanie A. Nick; Watts, Brian E.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [McElhinny, Stephanie A. Nick; Watts, Brian E.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Burgers, PM (reprint author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. EM burgers@biochem.wustl.edu RI Makarova, Alena/I-1338-2014 FU National Institutes of Health [GM032431]; Division of Intramural Research of the National Institutes of Health, National Institute on Environmental Health Sciences [Z01 ES065089] FX The authors thank Carrie Stith for help with protein purification. This work was supported in part by Grant GM032431 from the National Institutes of Health to P.M.B. and by Project Z01 ES065089 from the Division of Intramural Research of the National Institutes of Health, National Institute on Environmental Health Sciences, to T.A.K. NR 25 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD JUN PY 2014 VL 18 BP 63 EP 67 DI 10.1016/j.dnarep.2014.02.017 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA AJ4PP UT WOS:000337658600007 PM 24674899 ER PT J AU Ira, G Nussenzweig, A AF Ira, Grzegorz Nussenzweig, Andre TI A new Riff: Rif1 eats its cake and has it too SO EMBO REPORTS LA English DT Editorial Material ID END RESECTION; DNA-REPAIR; REPLICATION AB Rif1 protein is present in eukaryotic cells from yeast to human. In yeast, Rif1 is important for telomere homeostasis. Despite conservation in its domain organization, human Rif1 is not part of the telomere complex but was recently reported to work at DNA double-strand breaks (DSBs) with 53BP1 to inhibit 50 strand degradation (resection) and stimulate a subset of nonhomologous end-joining (NHEJ) reactions. Martina et al [1] report in this issue of EMBO reports that yeast Rif1 is also recruited to DSBs, but in contrast to its human counterpart, it promotes resection. The authors propose that Rif1 stimulates resection by limiting the access of Rad9, an ortholog of 53BP1, to DSBs. C1 [Ira, Grzegorz] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Nussenzweig, Andre] NCI, Lab Genome Integr, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ira, G (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM gira@bcm.edu FU NIGMS NIH HHS [R01 GM080600] NR 10 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-221X EI 1469-3178 J9 EMBO REP JI EMBO Rep. PD JUN PY 2014 VL 15 IS 6 BP 622 EP 624 DI 10.1002/embr.201438825 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AJ0QL UT WOS:000337360300003 PM 24769453 ER PT J AU Hayes, DJ Jupp, B Sawiak, SJ Merlo, E Caprioli, D Dalley, JW AF Hayes, Dave J. Jupp, Bianca Sawiak, Steve J. Merlo, Emiliano Caprioli, Daniele Dalley, Jeffrey W. TI Brain -aminobutyric acid: a neglected role in impulsivity SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE dopamine; GABA; noradrenaline; nucleus accumbens; prefrontal cortex ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; REACTION-TIME-TASK; SUBSTANCE-USE DISORDERS; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS CORE; GABA(A) RECEPTOR ACTIVATION; INHIBITORY RESPONSE CONTROL; MEDIAL PREFRONTAL CORTEX; DECISION-MAKING AB The investigation of impulsivity as a core marker of several major neuropsychiatric disorders has been greatly influenced by the therapeutic efficacy of drugs that block the reuptake of dopamine and noradrenaline in the brain. As a result, research into the neural mechanisms of impulsivity has focused on the catecholamine systems as the loci responsible for the expression of impulsive behaviour and the primary mechanism of action of clinically effective drugs for attention-deficit hyperactivity disorder (ADHD). However, abnormalities in the catecholamine systems alone are unlikely to account for the full diversity and complexity of impulsivity subtypes, nor can they fully explain co-morbid brain disorders such as drug addiction. Here we review the lesser-studied role of -aminobutyric acid (GABA) in impulsivity, a major target of the dopaminergic and noradrenergic systems in the prefrontal cortex and striatum, and consider how abnormalities in this inhibitory neurotransmitter might contribute to several forms of impulsive behaviour in humans and experimental animals. Our analysis reveals several promising leads for future research that may help inform the development of new therapies for disorders of impulse control. C1 [Hayes, Dave J.] Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. [Hayes, Dave J.] Univ Toronto, Div Neurosurg, Toronto, ON, Canada. [Hayes, Dave J.] Univ Ottawa, Mental Hlth Res Inst, Ottawa, ON, Canada. [Hayes, Dave J.; Jupp, Bianca; Sawiak, Steve J.; Merlo, Emiliano; Dalley, Jeffrey W.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. [Sawiak, Steve J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Wolfson Brain Imaging Ctr, Cambridge CB2 3EB, England. [Caprioli, Daniele] NIDA, Baltimore, MD USA. [Dalley, Jeffrey W.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. [Hayes, Dave J.; Jupp, Bianca; Merlo, Emiliano; Dalley, Jeffrey W.] Univ Cambridge, Dept Psychol, Cambridge CB2 3EB, England. RP Dalley, JW (reprint author), Univ Cambridge, Dept Psychol, Cambridge CB2 3EB, England. EM jwd20@cam.ac.uk RI Sawiak, Stephen/I-8944-2012; hayes, dave/C-7809-2013 OI Sawiak, Stephen/0000-0003-4210-9816; hayes, dave/0000-0001-9474-8770 FU Medical Research Council (MRC) [G0701500, G0802729, MRC G1000183, WT 093875/Z/10/Z]; Wellcome Trust (WT) [MRC G1000183, WT 093875/Z/10/Z]; MRC Imperial College-Cambridge University-Manchester University (ICCAM) strategic cluster [G1000018]; Royal Society; National Health and MRC of Australia; AXA Research Fund; Canadian Institutes of Health Research (CIHR) FX The work was supported by Medical Research Council (MRC) grants to J.W.D. (G0701500; G0802729) and by a joint core award from the MRC and Wellcome Trust (WT) in support of the Behavioural and Clinical Neuroscience Institute at Cambridge University (MRC G1000183; WT 093875/Z/10/Z). We also acknowledge funding support within the MRC Imperial College-Cambridge University-Manchester University (ICCAM) strategic cluster (G1000018). E. M. was supported by a Royal Society Newton International Fellowship. B.J. was supported by Fellowships from the National Health and MRC of Australia and the AXA Research Fund. D.J.H. was funded through a Canadian Institutes of Health Research (CIHR) Postdoctoral Fellowship. NR 163 TC 16 Z9 17 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X EI 1460-9568 J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUN PY 2014 VL 39 IS 11 SI SI BP 1921 EP 1932 DI 10.1111/ejn.12485 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AJ3BT UT WOS:000337540800019 PM 24460847 ER PT J AU Thakur, SA Nyska, A White, KL Smith, MJ Auttachoat, W Germolec, DR AF Thakur, Sheetal A. Nyska, Abraham White, Kimber L., Jr. Smith, Matthew J. Auttachoat, Wimolnut Germolec, Dori R. TI Immunomodulatory activity of orphan drug Elmiron (R) in female B6C3F1/N mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Immunotoxicity; Orphan drug; Sodium pentosan polysulfate; Interstitial cystitis ID POLYSULFATE-INDUCED THROMBOCYTOPENIA; PHASE-I TRIAL; PENTOSAN POLYSULFATE; INTERSTITIAL CYSTITIS; DENDRITIC CELLS; DRINKING-WATER; ANTIBODY; BLADDER; GAVAGE; ELISA AB Interstitial cystitis (IC) is a chronic disorder characterized by bladder discomfort and urinary urgency in the absence of identifiable infection. Despite the expanding use in IC treatment and other chronic conditions, the effects of Elmiron treatment on immune system remain unknown. Therefore, female B6C3F1/N mice were orally administered Elmiron (R) daily for 28-days at doses of 63, 125, 250, 500 or 1000 mg/kg to evaluate its immunomodulatory effects. Mice treated with Elmiron (R) had a significant increase in absolute numbers of splenic macrophages (63, 500 and 1000 mg/kg) and natural killer (NK) cells (250 and 1000 mg/kg). Elmiron (R) treatment did not affect the humoral immune response or T cell proliferative response. However, innate immune responses such as phagocytosis by liver macrophages (1000 mg/kg) and NK cell activity were enhanced (500 and 1000 mg/kg). Further analysis using a disease resistance model showed that Elmiron (R)-treated mice demonstrated significantly increased anti-tumor activity against B16F10 melanoma cells at the 500 and 1000 mg/kg doses. Collectively, we conclude that Elmiron (R) administration stimulates the immune system, increasing numbers of specific cell populations and enhancing macrophage phagocytosis and NK cell activity in female B6C3F1/N mice. This augmentation may have largely contributed to the reduced number of B16F10 melanoma tumors. (C) 2014 Published by Elsevier Ltd. C1 [Thakur, Sheetal A.; Germolec, Dori R.] Natl Inst Environm Hlth Sci, Toxicol Branch, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Nyska, Abraham] Integrated Syst Lab, Res Triangle Pk, NC USA. [White, Kimber L., Jr.; Smith, Matthew J.; Auttachoat, Wimolnut] Virginia Commonwealth Univ, Richmond, VA USA. RP Germolec, DR (reprint author), Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, 111 TW Alexander Dr,POB 12233,MD K2-15, Res Triangle Pk, NC 27709 USA. EM thakursa@niehs.nih.gov; germolec@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX This research was supported by the NIH, National Institute of Environmental Health Sciences. The authors would like to thank William M. Gwinn, Ph.D. (DNTP/NIEHS) and Kymberly M. Gowdy, Ph.D. (DIR/NIEHS) for their critical and editorial review. NR 42 TC 0 Z9 0 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUN PY 2014 VL 68 BP 196 EP 203 DI 10.1016/j.fct.2014.03.015 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA AJ4NL UT WOS:000337653000021 PM 24657363 ER PT J AU Raggi, C Factor, VM Seo, D Holczbauer, A Gillen, MC Marquardt, JU Andersen, JB Durkin, M Thorgeirsson, SS AF Raggi, Chiara Factor, Valentina M. Seo, Daekwan Holczbauer, Agnes Gillen, Matthew C. Marquardt, Jens U. Andersen, Jesper B. Durkin, Marian Thorgeirsson, Snorri S. TI Epigenetic Reprogramming Modulates Malignant Properties of Human Liver Cancer SO HEPATOLOGY LA English DT Article ID STEM-CELL FATE; DNA METHYLATION; SELF-RENEWAL; HETEROGENEITY; MODELS; AGENTS; GENES; CD133; SLUG AB Reversal of DNA hypermethylation and associated gene silencing is an emerging cancer therapy approach. Here we addressed the impact of epigenetic alterations and cellular context on functional and transcriptional reprogramming of hepatocellular carcinoma (HCC) cells. Our strategy employed a 3-day treatment of established and primary human HCC-derived cell lines grown as a monolayer at various cell densities with the DNMT1 inhibitor zebularine (ZEB) followed by a 3D culture to identify cells endowed with selfrenewal potential. Differences in self-renewal, gene expression, tumorigenicity, and metastatic potential of spheres at generations G1-G5 were examined. Transient ZEB exposure produced differential cell density-dependent responses. In cells grown at low density, ZEB caused a remarkable increase in self-renewal and tumorigenicity associated with long-lasting gene expression changes characterized by a stable overexpression of cancer stem cell-related and key epithelial-mesenchymal transition genes. These effects persisted after restoration of DNMT1 expression. In contrast, at high cell density, ZEB caused a gradual decrease in self-renewal and tumorigenicty, and up-regulation of apoptosis- and differentiation-related genes. A permanent reduction of DNMT1 protein using short hairpin RNA (shRNA)-mediated DNMT1 silencing rendered HCC cells insensitive both to cell density and ZEB effects. Similarly, WRL68 and HepG2 hepatoblastoma cells expressing low DNMT1 basal levels also possessed a high self-renewal, irrespective of cell density or ZEB exposure. Spheres formed by low-density cells treated with ZEB or shDNMT1 displayed a high molecular similarity which was sustained through consecutive generations, confirming the essential role of DNMT1 depletion in the enhancement of cancer stem cell properties. Conclusion: These results identify DNA methylation as a key epigenetic regulatory mechanism determining the pool of cancer stem cells in liver cancer and possibly other solid tumors. C1 [Raggi, Chiara; Factor, Valentina M.; Seo, Daekwan; Holczbauer, Agnes; Gillen, Matthew C.; Marquardt, Jens U.; Andersen, Jesper B.; Durkin, Marian; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37 Room 4146A,MSC 4262, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov OI Andersen , Jesper B/0000-0003-1760-5244; RAGGI, Chiara/0000-0003-2473-3535 FU GEO [GSE47932] FX We thank E.A. Conner for help with animal procedures, B. Taylor and S. Banerjee for assistance with flow cytometry, and T. Hoang for help with immunohistochemistry. Transcript profiling: GEO accession number: GSE47932. NR 37 TC 18 Z9 20 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JUN PY 2014 VL 59 IS 6 BP 2251 EP 2262 DI 10.1002/hep.27026 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AJ3LF UT WOS:000337567100026 PM 24449497 ER PT J AU Wang, AS Pfeiffer, RM Morgan, TR O'Brien, TR AF Wang, Alan S. Pfeiffer, Ruth M. Morgan, Timothy R. O'Brien, Thomas R. TI Hepatitis C Genotype 1 Virus With Low Viral Load and Rapid Virologic Response to Peginterferon/Ribavirin Obviates a Protease Inhibitorl SO HEPATOLOGY LA English DT Letter ID IL28B C1 [Wang, Alan S.; O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. RP Wang, AS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA CP005782-18] NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JUN PY 2014 VL 59 IS 6 BP 2423 EP 2424 DI 10.1002/hep.26771 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AJ3LF UT WOS:000337567100045 PM 24122888 ER PT J AU White, JT DeSanto, CL Gibbons, C Lardner, CK Panakos, A Rais, S Sharp, K Sullivan, SD Tidhar, W Wright, L Berrigan, D Heideman, PD AF White, Jordan T. DeSanto, Cori L. Gibbons, Connie Lardner, Casey K. Panakos, Andrew Rais, Salehin Sharp, Kathy Sullivan, Shannon D. Tidhar, Wendy Wright, Leanne Berrigan, David Heideman, Paul D. TI Insulins, leptin and feeding in a population of Peromyscus leucopus (white-footed mouse) with variable fertility SO HORMONES AND BEHAVIOR LA English DT Review DE Genetic variation; Natural population; Leptin; Insulin Insulin-like growth factor 1; Energetics; Reproduction; Photoperiod; Food intake; Calorie adjustment ID GROWTH-FACTOR-I; REPRODUCTIVE PHOTORESPONSIVENESS; PHOTOPERIODIC CONTROL; GENETIC-VARIATION; ENERGY-BALANCE; BODY-WEIGHT; FOOD-INTAKE; NEUROENDOCRINE MECHANISMS; NEUROPEPTIDE-Y; MICE AB Natural populations display a variety of reproductive responses to environmental cues, but the underlying physiology that causes these responses is-largely unknown. This study tested the hypothesis that heritable variation in reproductive traits can be described by heritable variation in concentrations of hormones critical to both energy balance and reproduction. To test this hypothesis, we used mouse lines derived from a wild population and selectively bred for response to short day photoperiod. Reproductive and metabolic traits of Peromyscus leuco pus display heritable variation when held in short photoperiods typical of winter. Our two lines of mice have phenotypes spanning the full range of variation observed in nature in winter. We tested male and female mice for heritable variation in fasted serum concentrations of three hormones involved in energetic regulation: leptin, insulin-like growth factor 1 (IGF-1) and insulin, as well as the effects of exogenous leptin and a high energy diet on reproductive maturation. Exogenous leptin decreased food intake, but protected males from the reduction in testis mass caused by equivalent food restriction in pair-fed, saline-infused controls. A high energy diet resulted in calorie adjustment by the mice, and failed to alter reproductive phenotype. Concentrations of the three hormones did not differ significantly between selection lines but had correlations with measures of food intake, fertility, blood glucose, and/or body mass. There was evidence of interactions between reproductive traits and hormones related to energy balance and reproduction, but this study did not find evidence that variation in these hormones caused variation in reproductive phenotype. (C) 2014 Published by Elsevier Inc. C1 [White, Jordan T.; DeSanto, Cori L.; Gibbons, Connie; Lardner, Casey K.; Panakos, Andrew; Rais, Salehin; Sharp, Kathy; Sullivan, Shannon D.; Tidhar, Wendy; Wright, Leanne; Heideman, Paul D.] Coll William & Mary, Dept Biol, Williamsburg, VA 23187 USA. [White, Jordan T.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Berrigan, David] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. RP Heideman, PD (reprint author), Coll William & Mary, Dept Biol, POB 8795, Williamsburg, VA 23187 USA. EM jtwhite@email.wm.edu; desantoc@wusm.wustl.edu; connie.gibbons@gmail.com; cklardner@email.wm.edu; andrew.panakos@gmail.com; sr5z@virginia.edu; kathy_r_sharp@yahoo.com; Shannon.D.Sullivan@Medstar.net; wtidhar@yahoo.co.uk; Lmpina@gmail.com; berrigad@mail.nih.gov; pdheid@wm.edu OI White, Jordan/0000-0003-3202-4181; Lardner, Casey/0000-0002-3993-3153 FU National Institutes of Health [R15-HD068962]; ALSAM Foundation; Howard Hughes Medical Institute Undergraduate Education Program Grant; Charles Center of the College of William and Mary FX We thank three anonymous reviewers for helpful comments and suggestions that improved the manuscript significantly. Thanks to P. Kaseloo, E. Bradley, P. Zwollo, M. Leu, J. Pittman, and H. Murphy for technical assistance. M. Crowell assisted with data collection, and L Wright-Jackson with animal care. Recombinant leptin was provided by Amgen, Inc. Funding was provided by the National Institutes of Health (R15-HD068962), from a Howard Hughes Medical Institute Undergraduate Education Program Grant to the College of William and Mary, by the ALSAM Foundation, and the Charles Center of the College of William and Mary. NR 53 TC 3 Z9 3 U1 3 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X EI 1095-6867 J9 HORM BEHAV JI Horm. Behav. PD JUN PY 2014 VL 66 IS 1 SI SI BP 169 EP 179 DI 10.1016/j.yhbeh.2014.02.006 PG 11 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA AJ3FB UT WOS:000337550800015 PM 24583085 ER PT J AU Hu, Y Xiao, HT Shi, TC Oppenheim, JJ Chen, X AF Hu, Ya Xiao, Haitao Shi, Tingchen Oppenheim, Joost J. Chen, Xin TI Progranulin promotes tumour necrosis factor-induced proliferation of suppressive mouse CD4+Foxp3+regulatory T cells SO IMMUNOLOGY LA English DT Article DE progranulin; proliferation; regulatory T cells; tumour necrosis factor; tumour necrosis factor receptor type 2 ID FRONTOTEMPORAL LOBAR DEGENERATION; AUTOIMMUNE-DISEASE; REGULATORY-CELLS; TNF RECEPTORS; GROWTH-FACTOR; DRUG TARGET; MICE; INFLAMMATION; INDUCTION; PATHWAY AB Progranulin (PGRN) is a pleiotropic growth factor with immunosuppressive properties. Recently, it was reported that PGRN was an antagonist of tumour necrosis factor (TNF) receptors, preferentially for TNFR2. However, we and others showed that TNF-TNFR2 interaction was critical for the activation and expansion of functional CD4+Foxp3+ regulatory T (Treg) cells. We therefore examined the effect of PGRN on the proliferation of naturally occurring murine suppressive Treg cells induced by TNF. Consistent with our previous reports, TNF overcame the hyporesponsiveness of highly purified Treg cells to T-cell receptor stimulation. Furthermore, in the presence of interleukin-2, TNF preferentially stimulated proliferation of Treg cells contained in unfractionated CD4 cells. These effects of TNF on suppressive Treg cells were markedly increased by exogenous PGRN. TNF and TNFR2 interactions are required for this effect of PGRN, because the PGRN by itself did not stimulate Treg cell proliferation. The effect of PGRN on Treg cells was abrogated by antibody against TNFR2, and Treg cells deficient in TNFR2 also failed to respond to PGRN. Furthermore, PGRN also enhanced the proliferative responses of effector T cells to TNF, but to a lesser extent than that of Treg cells, presumably caused by the different levels of TNFR2 expression on these two subsets of CD4 cells. Hence, our data clearly show that PGRN promotes, rather than inhibits, the functional consequence of TNF-TNFR2 interaction on Treg cells. C1 [Hu, Ya; Xiao, Haitao; Shi, Tingchen; Oppenheim, Joost J.; Chen, Xin] NCI, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Hu, Ya] Yangtze Univ, Sch Med, Jinzhou, Hubei, Peoples R China. [Chen, Xin] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Chen, X (reprint author), NCI, LMI, Bldg 560,Rm 31-19,1050 Boyles St,POB B, Frederick, MD 21702 USA. EM oppenhej@mail.nih.gov; chenxin@mail.nih.gov RI Chen, Xin/I-6601-2015 OI Chen, Xin/0000-0002-2628-4027 FU National Cancer Institute, National Institutes of Health [HHSN26120080001E]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors thank Drs O.M. Zack Howard and Qiong Zhou, Ms Trivett L. Anna and Ms Czarra T. Kelli for their help in this study. We thank the NCI-Frederick Cancer Inflammation Program Fluorescence Cytometry core for expert technical assistance with flow cytometry. NR 32 TC 9 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 EI 1365-2567 J9 IMMUNOLOGY JI Immunology PD JUN PY 2014 VL 142 IS 2 BP 193 EP 201 DI 10.1111/imm.12241 PG 9 WC Immunology SC Immunology GA AJ3AC UT WOS:000337536000004 PM 24383743 ER PT J AU Brite, J Laughon, SK Troendle, J Mills, J AF Brite, J. Laughon, S. k Troendle, J. Mills, J. TI Maternal overweight and obesity and risk of congenital heart defects in offspring SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE prepregnancy BMI; congenital heart defects ID ADVERSE PREGNANCY OUTCOMES; BODY-MASS INDEX; BIRTH-DEFECTS; HYPERGLYCEMIA; ANOMALIES AB OBJECTIVE: Obesity is a risk factor for congenital heart defects (CHDs), but whether risk is independent of abnormal glucose metabolism remains unknown. Data on whether overweight status increases the risk are also conflicting. RESEARCH DESIGN AND METHODS: We included 121 815 deliveries from a cohort study, the Consortium on Safe Labor (CSL), after excluding women with pregestational diabetes as recorded in the electronic medical record. CHD was identified via medical record discharge summaries. Adjusted odds ratios (ORs) for any CHD were calculated for prepregnancy body mass index (BMI) categories of overweight (25-<30 kgm(-2)), obese (30-<40 kgm(-2)) and morbidly obese (>= 40 kgm(-2)) compared with normal weight (18.5-<25 kgm(-2)) women, and for specific CHD with obese groups combined (>= 30 kgm(-2)). A subanalysis adjusting for oral glucose tolerance test (OGTT) results where available was performed as a proxy for potential abnormal glucose metabolism present at the time of organogenesis. RESULTS: There were 1388 (1%) infants with CHD. Overweight (OR = 1.15, 95% confidence interval (95% CI): 1.01-1.32), obese (OR = 1.26, 95% CI: 1.09-1.44) and morbidly obese (OR = 1.34, 95% CI: 1.02-1.76) women had greater OR of having a neonate with CHD than normal weight women (P<0.001 for trend). Obese women (BMI >= 30 kgm(-2)) had higher OR of having an infant with conotruncal defects (OR = 1.33, 95% CI: 1.03-1.72), atrial septal defects (OR = 1.22, 95% CI: 1.04-1.43) and ventricular septal defects (OR = 1.38, 95% CI: 1.06-1.79). Being obese remained a significant predictor of CHD risk after adjusting for OGTT. CONCLUSION: Increasing maternal weight class was associated with an increased risk for CHD. In obese women, abnormal glucose metabolism did not completely explain the increased risk for CHD; the possibility that other obesity-related factors are teratogenic requires further investigation. C1 [Brite, J.; Laughon, S. k; Mills, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, Bethesda, MD USA. [Brite, J.] CUNY, Hunter Coll, Sch Publ Hlth, New York, NY USA. [Brite, J.] CUNY, CIDR, Inst Demog Res, New York, NY USA. [Troendle, J.] NHLBI, Div Cardiovasc Sci, Off Biostat Res, Bethesda, MD 20892 USA. RP Laughon, SK (reprint author), NICHD, Epidemiol Branch, NIH, 6100 Executive Blvd,Room 7B03, Rockville, MD 20852 USA. EM laughonsk@mail.nih.gov OI Grantz, Katherine/0000-0003-0276-8534 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN267200603425C] FX Institutions involved in the Consortium include, in alphabetical order: Baystate Medical Center, Springfield, MA; Cedars-Sinai Medical Center Burnes Allen Research Center, Los Angeles, CA; Christiana Care Health System, Newark, DE; Georgetown University Hospital, MedStar Health, Washington, DC; Indiana University Clarian Health, Indianapolis, IN; Intermountain Healthcare and the University of Utah, Salt Lake City, Utah; Maimonides Medical Center, Brooklyn, NY; MetroHealth Medical Center, Cleveland, OH; Summa Health System, Akron City Hospital, Akron, OH; The EMMES Corporation, Rockville, MD (Data Coordinating Center); University of Illinois at Chicago, Chicago, IL; University of Miami, Miami, FL; and University of Texas Health Science Center at Houston, Houston, Texas. The named authors alone are responsible for the views expressed in this manuscript, which does not necessarily represent the decisions or the stated policy of the NICHD. JB, SKL, JT and JM were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health. The data included in this paper were obtained from the Consortium on Safe Labor, which was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, through Contract No. HHSN267200603425C. NR 24 TC 12 Z9 12 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD JUN PY 2014 VL 38 IS 6 BP 878 EP 882 DI 10.1038/ijo.2013.244 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AJ2PJ UT WOS:000337499900018 PM 24362506 ER PT J AU Braithwaite, RS Nucifora, KA Kessler, J Toohey, C Li, LF Mentor, SM Uhler, LM Roberts, MS Galvani, A Bryant, K AF Braithwaite, Ronald S. Nucifora, Kimberly A. Kessler, Jason Toohey, Christopher Li, Lingfeng Mentor, Sherry M. Uhler, Lauren M. Roberts, Mark S. Galvani, Alison Bryant, Kendall TI How Inexpensive Does an Alcohol Intervention in Kenya Need to be in Order to Deliver Favorable Value by Reducing HIV-Related Morbidity and Mortality? SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID SUB-SAHARAN AFRICAN; ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; INFECTED PATIENTS; UNPROTECTED SEX; WOMEN; ADHERENCE; MEN; PATTERNS; DRINKING C1 [Braithwaite, Ronald S.; Nucifora, Kimberly A.; Kessler, Jason; Toohey, Christopher; Li, Lingfeng; Mentor, Sherry M.; Uhler, Lauren M.] NYU, Sch Med, Dept Populat Hlth, New York, NY 10012 USA. [Roberts, Mark S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA. [Galvani, Alison] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Bryant, Kendall] NIAAA, NIH, Bethesda, MD USA. RP Braithwaite, RS (reprint author), NYU, Sch Med, Dept Populat Hlth, New York, NY 10012 USA. FU NIAAA NIH HHS [R01 AA017385] NR 36 TC 3 Z9 3 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUN 1 PY 2014 VL 66 IS 2 BP E54 EP E58 DI 10.1097/QAI.0000000000000140 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AJ4YJ UT WOS:000337685800006 PM 24828269 ER PT J AU Moraga, NB Poma, HR Amoroso, MJ Rajal, VB AF Beatriz Moraga, Norma Ramiro Poma, Hugo Julia Amoroso, Maria Beatriz Rajal, Veronica TI Isolation and characterization of indigenous Streptomyces and Lentzea strains from soils containing boron compounds in Argentina SO JOURNAL OF BASIC MICROBIOLOGY LA English DT Article DE Actinobacteria; Boron-tolerance; Streptomyces, Lentzea; Boron contaminated soils ID SP NOV.; BORIC-ACID; BACTERIUM; TOLERANT; IDENTIFICATION; SEQUENCE; GENE; BIOSYNTHESIS; HALOTOLERANT; BOROMYCIN AB The Salta Province - in the northwest of Argentina - is the main worldwide producer of hydroboracite and leads in exports of boron mineral and its derivatives in Latin America. In addition to the natural presence of boron compounds in the soils, there are others contaminated due to the boron mining industry. Although some bacteria are known to require boron for their growth or to be capable of storing boron, no studies have been published about Streptomyces or Lentzea genera's capacity to tolerate high boron concentrations, or about their metabolic capacities in boron contaminated environments. The results of this research show the isolation and molecular characterization of eight strains belonging to the actinobacteria phylum collected from different soils contaminated with high boron concentration in Salta state. The boron tolerance assays, which show that three of the strains were able to tolerate up 60-80 mM boron, demonstrate the potential capability of this group of bacteria to grow and maybe to remove boron from the environment. They appear to be promising, considering that these microorganisms are infrequent pathogens, are metabolically versatile and many Streptomyces can synthesize boron containing metabolites. C1 [Beatriz Moraga, Norma; Ramiro Poma, Hugo; Beatriz Rajal, Veronica] CONICET UNSa, Inst Invest Ind Quim INIQUI, RA-4400 Salta, Argentina. [Beatriz Moraga, Norma; Beatriz Rajal, Veronica] Univ Nacl Salta, Fac Ingn, Salta, Argentina. [Julia Amoroso, Maria] Consejo Nacl Invest Cient & Tecn, Planta Proc Ind & Microbiol PROIMI, San Miguel De Tucuman, Argentina. [Julia Amoroso, Maria] Univ Nacl Tucuman, Fac Bioquim Quim & Farm, San Miguel De Tucuman, Argentina. [Beatriz Rajal, Veronica] Univ Calif Davis, Fogarty Int Ctr, Davis, CA 95616 USA. RP Rajal, VB (reprint author), CONICET UNSa, Inst Invest Ind Quim INIQUI, Avda Bolivia 5150, RA-4400 Salta, Argentina. EM vbrajal@gmail.com FU National Institute of Health - Fogarty International Center [D43 TW005718]; National Institute of Environmental Health Sciences; Consejo de Investigaciones de la Universidad Nacional de Salta (Salta, Argentina) [1669, 1798]; Consejo Nacional de Investigaciones Cientificas y Tecnicas FX This project was partially supported by National Institute of Health Grant # D43 TW005718 funded by the Fogarty International Center and the National Institute of Environmental Health Sciences. It was also funded by the Consejo de Investigaciones de la Universidad Nacional de Salta (Salta, Argentina) through the research projects No 1669 and 1798. Norma Moraga and Ramiro Poma are recipients of graduate fellowships from Consejo Nacional de Investigaciones Cientificas y Tecnicas. The authors would like to thank Dr. Jerold Last for his help with the English corrections and Oscar Gamboni for his technical assistance. NR 50 TC 1 Z9 1 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0233-111X EI 1521-4028 J9 J BASIC MICROB JI J. Basic Microbiol. PD JUN PY 2014 VL 54 IS 6 SI SI BP 568 EP 577 DI 10.1002/jobm.201200714 PG 10 WC Microbiology SC Microbiology GA AJ4TU UT WOS:000337670000012 PM 23686918 ER PT J AU Shacham, R Steinberg, I Gandjbakhche, AH Gannot, I AF Shacham, Ranit Steinberg, Idan Gandjbakhche, Amir H. Gannot, Israel TI Monitoring LITT thermal penetration depth using real-time analysis of backscattered light SO JOURNAL OF BIOPHOTONICS LA English DT Article DE backscattering; laser interstitial thermal therapy; Monte-Carlo method; optical properties ID LASER-INDUCED THERMOTHERAPY; OPTICAL-PROPERTIES; LIVER-TUMORS; TISSUE; NM; CO2-LASER; SKIN AB Real-time monitoring of the thermal penetration depth (TPD) is essential in various clinical procedures, such as Laser Interstitial Thermal Therapy (LITT). MRI is commonly used to this end, though bulky and expensive. In this paper, we present an alternative novel method for an optical feedback system based on changes in the diffused reflection from the tissue during treatment. Monte-Carlo simulation was used to deduce the relations between the backscattered pattern and the TPD. Several methods of image analysis are developed for TPD estimation. Each yields a set of parameters which are linearly dependent on the TPD. In order to test these experimentally, tissue samples were monitored in-vitro during treatment at multiple wavelengths. The SNR and coefficient of determination were used to compare the various methods and wavelengths and to determine the preferred method. Such system and algorithms may be used for real-time in-vivo control during laser thermotherapy and other clinical procedures. [GRAPHICS] Setup (right) and image analysis (left) preformed on tissue sample for estimation of the Thermal Penetration Depth (TPD). C1 [Shacham, Ranit; Steinberg, Idan; Gannot, Israel] Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. [Gandjbakhche, Amir H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Gannot, I (reprint author), Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. EM gannot@eng.tau.ac.il OI Steinberg, Idan/0000-0002-1592-8026 FU Ela Kodesz Foundation, Tel-Aviv University FX The authors would like to thank Dr. Moshe Ben-David for his help in planning the in-vitro experiments and data analysis. In addition, the authors would like to thank the Ela Kodesz Foundation, Tel-Aviv University, for their partial support of this research. NR 18 TC 0 Z9 0 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1864-063X EI 1864-0648 J9 J BIOPHOTONICS JI J. Biophotonics PD JUN PY 2014 VL 7 IS 6 BP 381 EP 391 DI 10.1002/jbio.201200082 PG 11 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA AJ5CQ UT WOS:000337699300003 PM 23192946 ER PT J AU Persoskie, A Kaufman, AR Leyva, B AF Persoskie, Alexander Kaufman, Annette R. Leyva, Bryan TI Receiving and Adhering to Lifestyle Modification Counseling for Hypertension: Disparities Between Smokers and Nonsmokers SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID HIGH BLOOD-PRESSURE; JOINT NATIONAL COMMITTEE; UNITED-STATES; SOCIAL DESIRABILITY; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; 7TH REPORT; HEALTH; ADULTS; ADVICE AB Hypertensive patients who smoke are in particular need of lifestyle modification counseling because they are at increased risk for poorer outcomes. The authors examined whether hypertensive smokers were more or less likely than nonsmokers to report receiving recommendations for diet, salt intake, exercise, alcohol use, and medication and whether receipt of recommendations was differentially associated with lifestyle changes among smokers vs nonsmokers. In an analysis of data from the 2011 Behavioral Risk Factor Surveillance System on a representative sample of hypertensive adults from 9 US states (N=23,093), smokers were less likely than nonsmokers to report being told by a provider to exercise (odds ratio [OR], 0.66; P<.001) and change their diet (OR, 0.83; P<.05). Receiving dietary recommendations was more strongly associated with self-reported dietary improvements among smokers (OR, 7.08; P<.001) compared with nonsmokers (OR, 4.17; P<.001) P<.01. Delivery of counseling may vary by smoking status. When provided, lifestyle counseling may be equally or more effective for smokers compared with nonsmokers. C1 [Persoskie, Alexander] NCI, Basic Biobehav & Psychol Sci Branch, Bethesda, MD 20892 USA. [Kaufman, Annette R.] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. [Leyva, Bryan] NCI, Proc Care Res Branch, Bethesda, MD 20892 USA. RP Persoskie, A (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 3E204,MSC 9761, Bethesda, MD 20892 USA. EM persoskieai@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 45 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUN PY 2014 VL 16 IS 6 BP 429 EP 436 DI 10.1111/jch.12314 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AJ3XE UT WOS:000337600400010 PM 24713034 ER PT J AU Shah, RV Abbasi, SA Yamal, JM Davis, BR Barzilay, J Einhorn, PT Goldfine, A AF Shah, Ravi V. Abbasi, Siddique A. Yamal, Jose-Miguel Davis, Barry R. Barzilay, Joshua Einhorn, Paula T. Goldfine, Allison CA ALLHAT Collaborative Res Grp TI Impaired Fasting Glucose and Body Mass Index as Determinants of Mortality in ALLHAT: Is the Obesity Paradox Real? SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article ID CORONARY-HEART-DISEASE; FAT DISTRIBUTION; RISK; ASSOCIATION; ADULTS; HYPERTENSION; METAANALYSIS; OVERWEIGHT; WEIGHT; STROKE AB Emerging literature suggests that obesity may be protective against mortality and cardiovascular outcomes, while dysglycemia may worsen outcomes regardless of obesity. The authors measured the association of weight, smoking, and glycemia with mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Among 5423 ALLHAT participants without established diabetes or cardiovascular disease, 3980 (73%) had normal fasting glucose and 1443 (27%) had impaired fasting glucose (IFG) levels at study entry. After a median of 4.9years follow-up, 554 (10%) had died (37% cardiovascular). IFG was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02-1.50), while obesity was associated with lower all-cause mortality (adjusted HR, 0.76; 95% CI, 0.60-0.96). However, after excluding underweight individuals (body mass index [BMI] <22kg/m2) and smokers, neither obesity nor IFG was associated with all-cause mortality, but IFG identifies individuals at greater risk in the nonobese population. Although obesity appeared protective against mortality, this association was not significant in never-smokers or after exclusion of BMI <22kg/m2. The obesity paradox may result from confounding by a sicker, underweight referent population and smoking. C1 [Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Abbasi, Siddique A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yamal, Jose-Miguel; Davis, Barry R.] Univ Texas Houston, Sch Publ Hlth, Div Biostat, Houston, TX 77030 USA. [Barzilay, Joshua] Kaiser Permanente Georgia, Gwinnett Comprehens Med Ctr, Duluth, GA USA. [Einhorn, Paula T.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Goldfine, Allison] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Yamal, JM (reprint author), Univ Texas Houston, Sch Publ Hlth, Coordinating Ctr Clin Trials, 1200 Pressler St, Houston, TX 77030 USA. EM jose-miguel.yamal@uth.tmc.edu OI Abbasi, Siddique/0000-0002-9601-7565 FU National Heart, Lung, and Blood Institute [NO1-HC-35130, HHSN268201100036C]; American Heart Association Post-Doctoral Research Award; Pfizer, Inc. FX This study was supported by contracts NO1-HC-35130 and HHSN268201100036C with the National Heart, Lung, and Blood Institute and an American Heart Association Post-Doctoral Research Award to Dr Shah. The ALLHAT investigators acknowledge study medications contributed by Pfizer, Inc (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin) and financial support provided by Pfizer, Inc. NR 32 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 EI 1751-7176 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD JUN PY 2014 VL 16 IS 6 BP 451 EP 458 DI 10.1111/jch.12325 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AJ3XE UT WOS:000337600400013 PM 24779706 ER PT J AU Kukke, SN Paine, RW Chao, CC de Campos, AC Hallett, M AF Kukke, Sahana N. Paine, Rainer W. Chao, Chi-Chao de Campos, Ana C. Hallett, Mark TI Efficient and Reliable Characterization of the Corticospinal System Using Transcranial Magnetic Stimulation SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Transcranial magnetic stimulation; Recruitment curve; Input-output curve; Motor threshold ID HUMAN MOTOR CORTEX; INPUT-OUTPUT PROPERTIES; LOW-FREQUENCY; HUMAN-BRAIN; MUSCLE; RELIABILITY; PATHWAY; REPRESENTATIONS; POTENTIALS; THRESHOLD AB Purpose: The purpose of this study is to develop a method to reliably characterize multiple features of the corticospinal system in a more efficient manner than typically done in transcranial magnetic stimulation studies. Methods: Forty transcranial magnetic stimulation pulses of varying intensity were given over the first dorsal interosseous motor hot spot in 10 healthy adults. The first dorsal interosseous motor-evoked potential size was recorded during rest and activation to create recruitment curves. The Boltzmann sigmoidal function was fit to the data, and parameters relating to maximal motor-evoked potential size, curve slope, and stimulus intensity leading to half-maximal motor-evoked potential size were computed from the curve fit. Results: Good to excellent test-retest reliability was found for all corticospinal parameters at rest and during activation with 40 transcranial magnetic stimulation pulses. Conclusions: Through the use of curve fitting, important features of the corticospinal system can be determined with fewer stimuli than typically used for the same information. Determining the recruitment curve provides a basis to understand the state of the corticospinal system and select subject-specific parameters for transcranial magnetic stimulation testing quickly and without unnecessary exposure to magnetic stimulation. This method can be useful in individuals who have difficulty in maintaining stillness, including children and patients with motor disorders. C1 [Kukke, Sahana N.; Paine, Rainer W.; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Kukke, Sahana N.; de Campos, Ana C.] NIH, Funct & Appl Biomech Lab, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Chao, Chi-Chao] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 7D3710 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov OI Chao, Chi-Chao/0000-0001-6499-5789; Kukke, Sahana/0000-0002-1359-6136 FU NIH, National Institute of Neurological Disorders and Stroke FX Supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. NR 28 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 EI 1537-1603 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUN PY 2014 VL 31 IS 3 BP 246 EP 252 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AJ0OS UT WOS:000337355300013 PM 24887609 ER PT J AU Brown, GT Patel, V Lee, CCR AF Brown, Gregory Thomas Patel, Vishal Lee, Chyi-Chia Richard TI Cutaneous metastasis of prostate cancer: a case report and review of the literature with bioinformatics analysis of multiple healthcare delivery networks SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE cutaneous neoplasm; dermatopathology; metastatic carcinoma; cutaneous metastasis ID MARY-JOSEPH-NODULE; SKIN METASTASES; CARCINOMA; ADENOCARCINOMA; PENILE; MANIFESTATION; LESIONS; SCALP; CHEST AB Distant cutaneous metastases of prostate carcinomas are extremely rare, despite its high incidence and prevalence. Most cases are either a result of local extension, such as into seminal vesicles or distant metastases to bone. Few cases of true cutaneous metastatic prostate carcinoma exist in the literature. Clinically, cutaneous prostate carcinoma has been reported to mimic many other conditions, such as cellulitis, sebaceous cysts, zosteriform lesions, telangectasias and more, resulting in poor recognition. We report a case of distant cutaneous metastasis of prostate carcinoma and recent review of the literature with an analysis of de-identified patient records from multiple healthcare delivery networks. A diagnosis of metastatic prostate carcinoma may have been easily overlooked given the location and nature of the rash. Reviewing case reports and using aggregated electronic health records (EHRs), we find that fewer than 0.1% of all prostate carcinomas result in cutaneous metastases, compared with much higher rates in other types of cancers. Coupled with the low frequency of metastases to skin, careful consideration must be taken when evaluating a rash in a patient with a prior history of cancer. A complete clinical history and strong suspicion would be required to make a diagnosis of cutaneous metastases of the prostate. C1 [Brown, Gregory Thomas; Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Patel, Vishal] Case Western Reserve Univ, Ctr Prote & Bioinformat, Cleveland, OH 44106 USA. [Patel, Vishal] MetroHlth Syst, Ctr Clin Informat Res & Educ, Cleveland, OH USA. RP Lee, CCR (reprint author), NIH, Bldg 10,Rm 2B50,10 Ctr Dr, Bethesda, MD 20814 USA. EM leechy@mail.nih.gov RI Lee, Chyi-Chia/I-1938-2013 OI Lee, Chyi-Chia/0000-0002-5306-7781 NR 42 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JUN PY 2014 VL 41 IS 6 BP 524 EP 528 DI 10.1111/cup.12296 PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA AJ2VO UT WOS:000337522600009 PM 24456209 ER PT J AU Trifiro, G Coloma, PM Rijnbeek, PR Romio, S Mosseveld, B Weibel, D Bonhoeffer, J Schuemie, M van der Lei, J Sturkenboom, M AF Trifiro, G. Coloma, P. M. Rijnbeek, P. R. Romio, S. Mosseveld, B. Weibel, D. Bonhoeffer, J. Schuemie, M. van der Lei, J. Sturkenboom, M. TI Combining multiple healthcare databases for postmarketing drug and vaccine safety surveillance: why and how? SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE claims database; drug monitoring; electronic health records; product surveillance; postmarketing; vaccine ID MEDICAL-PRODUCT-SAFETY; ACTIVE SURVEILLANCE; PHARMACOEPIDEMIOLOGY; NETWORK; PHARMACOVIGILANCE; PROJECT; FOOD AB A growing number of international initiatives (e. g. EU-ADR, Sentinel, OMOP, PROTECT and VAESCO) are based on the combined use of multiple healthcare databases for the conduct of active surveillance studies in the area of drug and vaccine safety. The motivation behind combining multiple healthcare databases is the earlier detection and validation, and hence earlier management, of potential safety issues. Overall, the combination of multiple healthcare databases increases statistical sample size and heterogeneity of exposure for postmarketing drug and vaccine safety surveillance, despite posing several technical challenges. Healthcare databases generally differ by underlying healthcare systems, type of information collected, drug/vaccine and medical event coding systems and language. Therefore, harmonization of medical data extraction through homogeneous coding algorithms across highly different databases is necessary. Although no standard procedure is currently available to achieve this, several approaches have been developed in recent projects. Another main challenge involves choosing the work models for data management and analyses whilst respecting country-specific regulations in terms of data privacy and anonymization. Dedicated software (e. g. Jerboa) has been produced to deal with privacy issues by sharing only anonymized and aggregated data using a common data model. Finally, storage and safe access to the data from different databases requires the development of a proper remote research environment. The aim of this review is to provide a summary of the potential, disadvantages, methodological issues and possible solutions concerning the conduct of postmarketing multidatabase drug and vaccine safety studies, as demonstrated by several international initiatives. C1 [Trifiro, G.; Coloma, P. M.; Rijnbeek, P. R.; Romio, S.; Mosseveld, B.; Weibel, D.; Schuemie, M.; van der Lei, J.; Sturkenboom, M.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Trifiro, G.] Univ Messina, Dept Clin & Expt Med, Messina, Italy. [Romio, S.] Univ Milano Bicocca, Dept Clin & Prevent Med, Milan, Italy. [Bonhoeffer, J.] Brighton Collaborat Fdn, Brighton, E Sussex, England. [Bonhoeffer, J.] Univ Basel, Univ Childrens Hosp Basel, Basel, Switzerland. [Schuemie, M.] Janssen Res & Dev LLC, Titusville, NJ USA. [Schuemie, M.] Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD USA. RP Trifiro, G (reprint author), Erasmus Univ, Med Ctr, Dept Med Informat, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. EM g.trifiro@erasmusmc.nl RI Trifiro, Gianluca/K-9744-2016 OI Trifiro, Gianluca/0000-0003-1147-7296 FU AstraZeneca; Pfizer; Lilly; Boehiinger FX Miriam Sturkenboom is running a research group that occasionally performs studies for pharmaceutical companies according to unconditional grants These companies include AstraZeneca, Pfizer, Lilly and Boehiinger. She has also been a consultant to Pfizer Novartis, Consumer Health, Servier, Celgene and Lundbeck on issues not related to the study. The other authors have no conflicts of interest to declare. NR 33 TC 24 Z9 24 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-6820 EI 1365-2796 J9 J INTERN MED JI J. Intern. Med. PD JUN PY 2014 VL 275 IS 6 BP 551 EP 561 DI 10.1111/joim.12159 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA AJ6FY UT WOS:000337787300002 PM 24635221 ER PT J AU Mamais, A Cookson, MR AF Mamais, Adamantios Cookson, Mark R. TI LRRK2: dropping (kinase) inhibitions and seeking an (immune) response SO JOURNAL OF NEUROCHEMISTRY LA English DT Editorial Material ID ASSOCIATION; DISEASE; ERK5 C1 [Mamais, Adamantios; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov FU Intramural NIH HHS [Z01 AG000948-01] NR 14 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2014 VL 129 IS 6 BP 895 EP 897 DI 10.1111/jnc.12691 PG 3 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AJ5WI UT WOS:000337760500001 PM 24661004 ER PT J AU Szalay, KZ Nussinov, R Csermely, P AF Szalay, Kristof Z. Nussinov, Ruth Csermely, Peter TI Attractor Structures of Signaling Networks: Consequences of Different Conformational Barcode Dynamics and Their Relations to Network-Based Drug Design SO MOLECULAR INFORMATICS LA English DT Article DE Adaptation strategies; Attractors; Conformational barcodes; Drug design strategies; Fuzzy systems; Molecular memory; Network dynamics; Network plasticity; Network rigidity ID SELECTION; PROTEINS; DISORDER AB Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10% noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor. C1 [Szalay, Kristof Z.; Csermely, Peter] Semmelweis Univ, Dept Med Chem, H-1094 Budapest, Hungary. [Nussinov, Ruth] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Szalay, KZ (reprint author), Semmelweis Univ, Dept Med Chem, Tuzolto Str 37-47, H-1094 Budapest, Hungary. EM peter.csermely@med.semmelweis-univ.hu OI Szalay, Kristof/0000-0001-7876-3516 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Hungarian National Science Foundation [OTKA K83314]; NIH, National Cancer Institute, Center for Cancer Research FX Authors thank to the anonymous reviewers of this paper for their suggestions, and Reviewer 1 highlighting an important conclusion of the current work on the robustness of the Turbine method, which we inserted as the concluding two sentences of our paper. Daniel V. Veres's (Department of Medical Chemistry, Semmelweis University, Budapest, Hungary, www.linkgroup.hu) contribution to Figure 1 is kindly acknowledged. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract Number HHSN261200800001E and by a research grant from the Hungarian National Science Foundation (OTKA K83314). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 24 TC 3 Z9 3 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1868-1743 EI 1868-1751 J9 MOL INFORM JI Mol. Inf. PD JUN PY 2014 VL 33 IS 6-7 SI SI BP 463 EP 468 DI 10.1002/minf.201400029 PG 6 WC Chemistry, Medicinal; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology SC Pharmacology & Pharmacy; Computer Science; Mathematical & Computational Biology GA AJ4EO UT WOS:000337624900010 PM 27485984 ER PT J AU Noinaj, N Buchanan, SK AF Noinaj, Nicholas Buchanan, Susan K. TI FhaC takes a bow to FHA in the two-partner do-si-do SO MOLECULAR MICROBIOLOGY LA English DT Article ID GRAM-NEGATIVE BACTERIA; TPSB TRANSPORTER FHAC; FILAMENTOUS HEMAGGLUTININ; SECRETION; MEMBRANE; DOMAINS; PATHWAY AB FhaC is an outer membrane transporter from Bordetella pertussis belonging to the two-partner secretion (TPS) pathway with its primary role being the secretion of the virulence factor filamentous haemagglutinin (FHA). FhaC serves as a model transporter of the TPS pathway and significant work has been done to characterize the role of FhaC in FHA secretion. Recent studies characterized interactions between FHA and the POTRA domains of FhaC, suggesting that secretion may involve a successive translocation mechanism mediated by -augmentation and/or electrostatic interactions. Moreover, it was also shown that reconstituted FhaC is necessary and sufficient to transport FHA into proteoliposomes. While the crystal structure of FhaC clearly suggests a role in transport, the putative transport pore is plugged by an N-terminal -helix (H1 helix) that occludes access by FHA. Therefore, it has been proposed that the H1 helix must be expelled from the pore in order for secretion of FHA to occur. However, this has yet to be shown experimentally. Guerin etal. (2014) report the first direct experimental evidence to show that the FhaC H1 helix is quite dynamic and exchanges between closed and open states upon interaction with FHA. C1 [Noinaj, Nicholas; Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Buchanan, SK (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. EM skbuchan@helix.nih.gov FU Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX NN and SKB are supported by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. NR 9 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 2014 VL 92 IS 6 BP 1155 EP 1158 DI 10.1111/mmi.12627 PG 4 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA AJ3TA UT WOS:000337589100001 PM 24798489 ER PT J AU Liu, R Baird, D Park, Y Freedman, ND Huang, XM Hollenbeck, A Blair, A Chen, HL AF Liu, Rui Baird, Donna Park, Yikyung Freedman, Neal D. Huang, Xuemei Hollenbeck, Albert Blair, Aaron Chen, Honglei TI Female Reproductive Factors, Menopausal Hormone Use, and Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Article DE reproductive factors; Parkinson's disease; cohort studies; menopausal hormone therapy ID NIGROSTRIATAL DOPAMINERGIC SYSTEM; POSTMENOPAUSAL ESTROGEN USE; UNDERWENT OOPHORECTOMY; COGNITIVE IMPAIRMENT; GENDER-DIFFERENCES; INCREASED RISK; WOMEN; PROGESTERONE; DEMENTIA; 17-BETA-ESTRADIOL AB The objective of this study was to examine the associations of reproductive factors and exogenous hormone use with risk of Parkinson's disease (PD) among postmenopausal women. The study comprised 119,166 postmenopausal women aged 50 to 71 years in the NIH-AARP Diet and Health Study, who completed a baseline questionnaire in 1995-1996 and a follow-up survey in 2004-2006. A total of 410 selfreported PD diagnoses were identified between 1995 and 2006. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. PD risk was not significantly associated with female reproductive factors including age at menarche, age at first live birth, parity, and age at menopause. For example, compared with women with natural menopause at age 50 to 54 years, the ORs were 1.18, (95% CI, 0.78-1.79) for women with natural menopause aged <45, 1.19 (95% CI, 0.88-1.61) for those aged 45 to 49, and 1.33 (95% CI, 0.91-1.93) for those aged 55 or older. We found that oral contraceptive use for >= 10 years (vs. never used) was associated with lower PD risk (OR, 0.59; 95% CI, 0.38-0.92), but shorter use showed no association. Use of menopausal hormone therapy showed inconsistent results. Compared with non-hormone users at baseline, current hormone users for <5 years showed a higher risk of PD (OR, 1.52; 95% CI, 1.11-2.08). However, no associations were observed for past hormone users or current users of >= 5 years. Overall, this large prospective study provides little support for an association between female reproductive factors and PD risk. Our findings on long-term oral contraceptive use and current hormone therapy warrant further investigations. (C) 2013 International Parkinson and Movement Disorder Society C1 [Liu, Rui; Baird, Donna; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Park, Yikyung; Freedman, Neal D.; Blair, Aaron] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov RI Freedman, Neal/B-9741-2015; Baird, Donna/D-5214-2017; OI Freedman, Neal/0000-0003-0074-1098; Baird, Donna/0000-0002-5544-2653; Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X FU NIH, the National Institute Neurological Disorders and Stroke [R01-NS060722, U01-NS082151]; NIH, National Institute of Environmental Health Sciences [Z01-ES-101986]; NIH, National Cancer Institute [Z01 CP010196-02] FX This study was supported in part by the intramural and extramural research programs of the NIH, the National Institute Neurological Disorders and Stroke (R01-NS060722, U01-NS082151), the National Institute of Environmental Health Sciences (Z01-ES-101986), and the National Cancer Institute (Z01 CP010196-02). NR 35 TC 10 Z9 10 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN PY 2014 VL 29 IS 7 BP 889 EP 896 DI 10.1002/mds.25771 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA AJ4TZ UT WOS:000337670600013 PM 24352877 ER PT J AU Savage, SW Zald, DH Cowan, RL Volkow, ND Marks-Shulman, PA Kessler, RM Abumrad, NN Dunn, JP AF Savage, Shane W. Zald, David H. Cowan, Ronald L. Volkow, Nora D. Marks-Shulman, Pamela A. Kessler, Robert M. Abumrad, Naji N. Dunn, Julia P. TI Regulation of Novelty Seeking by Midbrain Dopamine D2/D3 Signaling and Ghrelin is Altered in Obesity SO OBESITY LA English DT Article ID BRAIN DOPAMINE; FOOD REWARD; WEIGHT-LOSS; IN-VIVO; NEURONS; BINDING; INDIVIDUALS; RECEPTORS; MICE; PERSONALITY AB Objective To investigate the relationship of novelty seeking traits (NS) with midbrain dopamine (DA) receptors and acyl ghrelin levels (AG) in normal weight (NW) and obese females.NS predict addictive behaviors and are hypothesized to contribute to eating behaviors. In healthy, NS are negatively associated with DA receptors in the substantia nigra (SN). The influence of obesity on the regulation of NS by DA signaling and AG was hypothesized. Methods PET scanning to measure DA type 2/type 3 receptor (D2/D3R) binding potential (BPND) in the SN was used. Participants completed Tridimensional Personality Questionnaire-Novelty-Seeking Scale (TPQ-NS) and AG were measured. Results In eight NW and 19 obese (BMI 22 vs 38 kg/m2), TPQ-NS (16 vs 15) and SN D2/D3R BPND (2.48 vs 2.66) were similar, while AG higher (256 vs 60, P<0.01), respectively. D2/D3R BPND and TPQ-NS had a negative relationship in NW (r=-0.7) but not in obese (0.10). AG and TPQ-NS were positively correlated in NW (r=0.9) but not in obese (0.10). D2R BPND and AG were negatively correlated in NW (r=-0.8) but positively in obese (r=0.6). Conclusion Obese do not maintain posited regulatory relationships for NS to either midbrain D2/D3R availability or AG present in NW. Also opposite relationships exist for NW and obese between SN D2/D3R availability and AG. The altered regulation of NS in obesity needs to be further explored. C1 [Savage, Shane W.; Zald, David H.; Cowan, Ronald L.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37235 USA. [Zald, David H.; Cowan, Ronald L.; Kessler, Robert M.] Vanderbilt Univ, Sch Med, Dept Radiol, Nashville, TN 37235 USA. [Zald, David H.] Vanderbilt Univ, Sch Med, Dept Psychol, Nashville, TN 37235 USA. [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. [Marks-Shulman, Pamela A.; Abumrad, Naji N.] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37235 USA. [Dunn, Julia P.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37235 USA. RP Dunn, JP (reprint author), Vanderbilt Univ, Sch Med, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA. EM julia.dunn@va.gov FU National Institutes of Health (NIH) from the National Center for Research Resources (Vanderbilt Clinical and Translational Science Award) [UL1-RR-024975]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [DK-20593]; NIDDK (Vanderbilt Digestive Disease Research Center) [DK-058404]; National Institute of Environmental Health Sciences (Vanderbilt Environmental Health Science Scholars Program) [K12-ESO15855]; NIDDK [DK-70860] FX This study was supported by National Institutes of Health (NIH) grants UL1-RR-024975 from the National Center for Research Resources (Vanderbilt Clinical and Translational Science Award), DK-20593 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; Vanderbilt Diabetes Research and Training Award), DK-058404 from NIDDK (Vanderbilt Digestive Disease Research Center), K12-ESO15855 from the National Institute of Environmental Health Sciences (Vanderbilt Environmental Health Science Scholars Program) to J.P.D., and DK-70860 from the NIDDK to N.N.A. NR 40 TC 7 Z9 7 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD JUN PY 2014 VL 22 IS 6 BP 1452 EP 1457 DI 10.1002/oby.20690 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA AJ3AM UT WOS:000337537000011 PM 24415718 ER PT J AU Lafferty, MK Fantry, L Bryant, J Jones, O Hammoud, D Weitzmann, MN Lewis, GK Garzino-Demo, A Reid, W AF Lafferty, Mark K. Fantry, Lori Bryant, Joseph Jones, Odell Hammoud, Dima Weitzmann, M. Neale Lewis, George K. Garzino-Demo, Alfredo Reid, William TI Elevated suppressor of cytokine signaling-1 (SOCS-1): a mechanism for dysregulated osteoclastogenesis in HIV transgenic rats SO PATHOGENS AND DISEASE LA English DT Article DE SOCS-1; HIV-1; osteoclast; osteoporosis ID BONE-MINERAL DENSITY; VIRUS-INFECTED WOMEN; B LIGAND RANKL; ANTIRETROVIRAL THERAPY; T-CELLS; RECEPTOR ACTIVATOR; IFN-GAMMA; OSTEOPROTEGERIN LIGAND; INHIBITORY FACTOR; CROSS-TALK AB Accelerated bone loss leading to osteopenia, osteoporosis, and bone fracture is a major health problem that is increasingly common in human immunodeficiency virus (HIV)-infected patients. The underlying pathogenesis is unclear but occurs in both treatment naive and individuals receiving antiretroviral therapies. We developed an HIV-1 transgenic rat that exhibits many key features of HIV disease including HIV-1-induced changes in bone mineral density (BMD). A key determinant in the rate of bone loss is the differentiation of osteoclasts, the cells responsible for bone resorption. We found HIV-1 transgenic osteoclast precursors (OCP) express higher levels of suppressor of cytokine signaling-1 (SOCS-1) and TNF receptor-associated factor 6 (TRAF6) and are resistant to interferon-gamma (IFN-) mediated suppression of osteoclast differentiation. Our data suggest that dysregulated SOCS-1 expression by HIV-1 transgenic OCP promotes osteoclastogenesis leading to the accelerated bone loss observed in this animal model. We propose that elevated SOCS-1 expression in OCP antagonizes the inhibitory effects of IFN- and enhances receptor activator of NF-kB ligand (RANKL) signaling that drives osteoclast differentiation and activation. Understanding the molecular mechanisms of HIV-associated BMD changes has the potential to detect and treat bone metabolism disturbances early and improve the quality of life in patients. C1 [Lafferty, Mark K.; Lewis, George K.; Garzino-Demo, Alfredo; Reid, William] Univ Maryland, Sch Med, Inst Human Virol, Div Basic Sci & Vaccine Res, Baltimore, MD 21201 USA. [Lafferty, Mark K.; Lewis, George K.; Garzino-Demo, Alfredo; Reid, William] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Fantry, Lori] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Fantry, Lori; Bryant, Joseph] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Bryant, Joseph] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Bryant, Joseph; Jones, Odell] Univ Maryland, Sch Med, Anim Models Div, Inst Human Virol, Baltimore, MD 21201 USA. [Hammoud, Dima; Reid, William] NIH, Ctr Clin, Baltimore, MD 21201 USA. [Weitzmann, M. Neale] Emory Univ, Sch Med, Div Endocrinol & Metab & Lipids, Atlanta, GA 30322 USA. [Weitzmann, M. Neale] Atlanta Vet Affairs Med Ctr, Decatur, GA 30033 USA. [Weitzmann, M. Neale] Emory Univ, Winship Canc Inst, Sch Med, Atlanta, GA 30322 USA. RP Reid, W (reprint author), NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Ctr Clin, Baltimore, MD 21201 USA. EM william.reid@nih.gov RI Hammoud, Dima/C-2286-2015 FU National Institute of Allergy and Infectious Diseases, NIH [R01A1063171, R01AI087181]; National Institute of Neurological Disorders And Stroke, NIH [R01NS066842] FX We thank Dr Marvin Reitz for his critical reading of this manuscript. We also thank Dr Bryan Taylor, manager of the Core facility at the Institute of Human Virology, for his technical assistance. This study was supported by National Institute of Allergy and Infectious Diseases, NIH grants R01A1063171 and R01AI087181 and National Institute of Neurological Disorders And Stroke, NIH grant R01NS066842. The authors declare no competing financial interests. NR 63 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2049-632X J9 PATHOG DIS JI Pathog. Dis. PD JUN PY 2014 VL 71 IS 1 BP 81 EP 89 DI 10.1111/2049-632X.12117 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AJ3PB UT WOS:000337577900009 PM 24376119 ER PT J AU Sturdevant, GL Zhou, B Carlson, JH Whitmire, WM Song, LH Caldwell, HD AF Sturdevant, Gail L. Zhou, Bing Carlson, John H. Whitmire, William M. Song, Lihua Caldwell, Harlan D. TI Infectivity of urogenital Chlamydia trachomatis plasmid-deficient, CT135-null, and double-deficient strains in female mice SO PATHOGENS AND DISEASE LA English DT Article DE Chlamydiae; plasmid; CT135; mouse infectivity ID TRANSCRIPTIONAL REGULATOR; MEMBRANE-PROTEIN; VIRULENCE FACTOR; GENITAL-TRACT; VACCINE; GENES AB Chlamydia trachomatis is the most common cause of human bacterial sexually transmitted infections and is the world's leading cause of infectious preventable blindness. The chlamydial 7.5-kb plasmid and chromosomal gene CT135 have been shown to be important virulence factors in both nonhuman primate and mouse infection models. Chlamydia trachomatis plasmid-deficient urogenital isolates and a predicted CT135 null mutant have been evaluated independently in the female mouse genital tract model and both have been shown to reduce infectivity and virulence. However, these attenuating phenotypes have not been evaluated collectively in the murine model. Here, we test the infectivity of C.trachomatis serovar D strains in the mouse model that are plasmid-deficient, CT135 disrupted, or possess a combination of these attenuating genotypes. We find that the presence of the plasmid results in infections with higher infectious burdens, whereas CT135 facilitates a more protracted or chronic infection. Not unexpectedly, a combination of these genetic deficiencies resulted in a strain with enhanced infection attenuation characteristics. C1 [Sturdevant, Gail L.; Zhou, Bing; Carlson, John H.; Whitmire, William M.; Song, Lihua; Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. [Song, Lihua] Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China. RP Caldwell, HD (reprint author), NIAID, NIH, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM hcaldwell@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Kelly Matteson, Anita Mora, and Dan Sturdevant for editorial assistance, graphics preparation, and statistical analyses, respectively. This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 19 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2049-632X J9 PATHOG DIS JI Pathog. Dis. PD JUN PY 2014 VL 71 IS 1 BP 90 EP 92 DI 10.1111/2049-632X.12121 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AJ3PB UT WOS:000337577900010 PM 24376189 ER PT J AU Miller, AC Rosati, SF Suffredini, AF Schrump, DS AF Miller, Andrew C. Rosati, Shannon F. Suffredini, Anthony F. Schrump, David S. TI A systematic review and pooled analysis of CPR-associated cardiovascular and thoracic injuries SO RESUSCITATION LA English DT Review DE CPR; Cardiopulmonary resuscitation; Automated compression devices; Vascular injury; Cardiac injury; Thoracic injury ID ACUTE MYOCARDIAL-INFARCTION; CHEST CARDIAC MASSAGE; DECOMPRESSION CARDIOPULMONARY-RESUSCITATION; RIGHT-VENTRICULAR RUPTURE; MAJOR BLEEDING COMPLICATIONS; 2010 INTERNATIONAL CONSENSUS; BASIC LIFE-SUPPORT; THROMBOLYTIC THERAPY; PULMONARY-EMBOLISM; ACD-CPR AB Objective: The incidence of thoracic injuries resulting from cardiopulmonary resuscitation (CPR) is not well characterized. We describe a case in which a CPR-associated atrial rupture was identified with ultrasound and successfully managed in the intensive care unit with a bedside thoracotomy and atrial repair. We then describe a systematic review with pooled data analysis of CPR-associated cardiovascular, pulmonary, pleural, and thoracic wall injuries. Data sources: PubMed, Scopus, EMBASE, and Web of Science were searched to identify relevant published studies. Unpublished studies were identified by searching the Australian and New Zealand Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform, Cochrane Library, ClinicalTrials.gov, Current Controlled Trials, and Google. Study selection: Inclusion criteria for the pooled analysis were any clinical or autopsy study in which (a) patients underwent cardiopulmonary resuscitation, (b) chest compressions were administered either manually or with the assistance of active compression-decompression devices, and (c) autopsy or dedicated imaging assessments were conducted to identify complications. Exclusion criteria for the pooled analysis were pre-clinical studies, case reports and abstracts. Data extraction: Nine-hundred twenty-eight potentially relevant references were identified. Twenty-seven references met inclusion criteria. Data synthesis: A systematic review of the literature is provided with pooled data analysis. Conclusions: The incidence of reported CPR-associated cardiovascular and thoracic wall injuries varies widely. CPR with active compression-decompression devices has a higher reported incidence of cardiopulmonary injuries. Bedside ultrasound may be a useful adjunct to assess and risk-stratify patients to identify serious or life-threatening CPR-associated injuries. Published by Elsevier Ireland Ltd. C1 [Miller, Andrew C.; Suffredini, Anthony F.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. [Rosati, Shannon F.; Schrump, David S.] NCI, Surg Branch, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA. RP Miller, AC (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bldg 10,Rm 2C-145,10 Ctr Dr, Bethesda, MD 20892 USA. EM Andrew.Miller3@nih.gov OI Miller, Andrew/0000-0001-8474-5090 FU Intramural Research Program of the Clinical Center; National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the Clinical Center and the National Cancer Institute, National Institutes of Health. NR 99 TC 27 Z9 27 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD JUN PY 2014 VL 85 IS 6 BP 724 EP 731 DI 10.1016/j.resuscitation.2014.01.028 PG 8 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA AJ0GY UT WOS:000337329600019 PM 24525116 ER PT J AU Bosch-Marce, M Seetharaman, S Kurtz, J Mohan, KVK Wagner, SJ Atreya, CD AF Bosch-Marce, Marta Seetharaman, Shalini Kurtz, James Mohan, Ketha V. K. Wagner, Stephen J. Atreya, Chintamani D. TI Leukoreduced whole blood-derived platelets treated with antimicrobial peptides maintain in vitro properties during storage SO TRANSFUSION LA English DT Article ID SIMULATED SHIPPING CONDITIONS; COMBINED IMMUNODEFICIENT MICE; APHERESIS PLATELETS; 7-DAY STORAGE; AGITATION; PERIODS; VIVO; MECHANISMS; SURVIVAL; PLASMA AB Background Bacterial sepsis is still a complication in patients transfused with stored platelets (PLTs). We have recently demonstrated that selected antimicrobial peptides (AMPs) have bactericidal activity in bacteria-spiked PLTs. In a subsequent preclinical study, we have also shown that these AMPs do not elicit antibody response in rabbits and treatment of PLTs before transfusion does not affect their in vivo recovery and survival in severe combined immunodeficient mice. Here we have selected two such AMPs, Arg-Trp (RW) repeats of tri- and tetra-peptides (RW3 and RW4) in combination (i.e., cocktail), and evaluated their effect on the in vitro properties of PLTs. Study Design and Methods Leukoreduced ABO- and D-identical whole blood-derived PLT concentrates were pooled and divided into two 60-mL aliquots in CLX storage bags. On Day 0, one bag received a peptide cocktail of RW3plusRW4 at 0.01mmol/L final concentration (test) and the other bag received only phosphate-buffered saline (PBS), the AMP solvent (control). The treated PLTs were stored for 7 days at 20 to 24 degrees C. Samples were collected on Days 1, 5, and 7 to evaluate the in vitro properties of PLTs with standard assays. Results In vitro properties of the RW3plusRW4 cocktail-treated PLTs were similar to those incubated with PBS only. There were no significant differences between the control and test PLTs during the 7-day storage. Conclusion Leukoreduced whole blood-derived PLTs treated with a mixture of RW3 and RW4 peptides maintain their in vitro properties during 7 days of storage. C1 [Bosch-Marce, Marta; Mohan, Ketha V. K.; Atreya, Chintamani D.] US FDA, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Sect Cell Biol, Bethesda, MD 20014 USA. [Seetharaman, Shalini; Kurtz, James; Wagner, Stephen J.] Amer Red Cross, Blood Components Dept, Rockville, MD USA. RP Atreya, CD (reprint author), Bldg 29A,Room 2C-11,NIH Campus, Bethesda, MD 20892 USA. EM chintamani.atreya@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER) FX MBM is the recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intraagency agreement between the US Department of Energy and the US Food and Drug Administration. The authors thank Ms Sandhya Kulkarni for her help with timely procurement of materials used in this work. NR 32 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD JUN PY 2014 VL 54 IS 6 BP 1604 EP 1609 DI 10.1111/trf.12534 PG 6 WC Hematology SC Hematology GA AJ3TU UT WOS:000337591200024 PM 24410697 ER PT J AU Valsangkar, B Chen, C Wohltjen, H Mullan, F AF Valsangkar, Bina Chen, Candice Wohltjen, Hannah Mullan, Fitzhugh TI Do Medical School Mission Statements Align With the Nation's Health Care Needs? SO ACADEMIC MEDICINE LA English DT Editorial Material AB Problem To quantify the relative prevalence of traditional (education, research, service) and emerging (prevention, diversity, primary care, distribution, cost control) themes in medical school mission statements. Approach In 2011, the authors obtained and analyzed the mission statements from 136 MD-granting and 34 DO-granting medical schools. They read each for the presence of traditional and emerging themes and then compared the mission statements by category of school (MD-granting versus DO-granting, level of National Institutes of Health funding, public versus private, date of initial accreditation [before or during/after 2000], and community-based versus non-community-based). Outcomes Traditional themes were common in medical school mission statement-seducation (170; 100%), research (146; 86%), and service (150; 88%). Emerging themes were less common-distribution (41; 24%), primary care (32; 19%), diversity (27; 16%), prevention (9; 5%), and cost control (2; 1%). DO-granting and community-based medical school mission statements cited the traditional theme of service and the emerging themes of primary care and distribution more frequently than those of MD-granting and non-community-based schools. Next Steps The traditional themes of education, research, and service dominate medical school mission statements. DO-granting and community-based medical schools, however, more often have incorporated the emerging themes of primary care and distribution. Although including emerging themes in a mission statement does not guarantee tangible results, omitting them suggests that the school has not embraced these issues. Without the engagement of established medical schools, the national health care problems represented by these emerging themes will not receive the attention they need. C1 [Valsangkar, Bina; Mullan, Fitzhugh] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Chen, Candice] Natl Inst Minor Hlth & Hlth Dispar, Bethesda, MD USA. [Chen, Candice; Wohltjen, Hannah; Mullan, Fitzhugh] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. RP Valsangkar, B (reprint author), 2000 L St NW,Suite 500, Washington, DC 20036 USA. EM bvalsangkar@savechildren.org FU National Institute of Minority Health and Health Disparities, National Institutes of Health FX Dr. Candice Chen is supported through a Disparities Research and Education Advancing Mission (DREAM) Career Transition Award from the National Institute of Minority Health and Health Disparities, National Institutes of Health. NR 10 TC 1 Z9 1 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JUN PY 2014 VL 89 IS 6 BP 892 EP 895 DI 10.1097/ACM.0000000000000241 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA AI8NU UT WOS:000337176300022 PM 24871240 ER PT J AU Buckheit, RW Sexauer, SB Sedaghat, AR Wilke, CO Laeyendecker, O Basseth, CR Blankson, JN AF Buckheit, Robert W., III Sexauer, Stephen B. Sedaghat, Ahmad R. Wilke, Claus O. Laeyendecker, Oliver Basseth, Christie R. Blankson, Joel N. TI Long-Term Control of Viral Replication in a Group O, Human Immunodeficiency Virus Type 1-Infected Individual SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Letter ID HIV-1; INFECTION; EVOLUTION; CAMEROON C1 [Buckheit, Robert W., III; Sexauer, Stephen B.; Laeyendecker, Oliver; Basseth, Christie R.; Blankson, Joel N.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Wilke, Claus O.] Ctr Computat Biol & Bioinformat, Sect Integrat Biol, Austin, TX USA. [Wilke, Claus O.] Univ Texas Austin, Inst Cell & Mol Biol, Austin, TX 78712 USA. [Laeyendecker, Oliver] NIAID, Div Intramural Res, NIH, Baltimore, MD USA. RP Blankson, JN (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 733 North Broadway,BRB 880, Baltimore, MD 21205 USA. EM jblanks@jhmi.edu OI Laeyendecker, Oliver/0000-0002-6429-4760; Wilke, Claus/0000-0002-7470-9261 FU NIGMS NIH HHS [T32 GM008752] NR 13 TC 2 Z9 2 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 2014 VL 30 IS 6 BP 511 EP 513 DI 10.1089/aid.2014.0054 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AI9CE UT WOS:000337224400001 PM 24798496 ER PT J AU Yao, L Gai, N Boutin, RD AF Yao, Lawrence Gai, Neville Boutin, Robert D. TI Axial Scan Orientation and the Tibial Tubercle-Trochlear Groove Distance: Error Analysis and Correction SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE knee; MRI; patellofemoral instability; tibial tubercle; trochlear groove ID PATELLAR INSTABILITY; TUBEROSITY; KNEE; CT AB OBJECTIVE. The tibial tubercle (TT)-trochlear groove (TG) distance is an important metric in the assessment of patellofemoral dysfunction and is routinely measured on axial MRI and CT. This study examines error in measurements of the TT-TG distance related to variance in axial MRI scan orientation. SUBJECTS AND METHODS. Isotropic 3D turbo spin-echo MRI of the extended knee was performed in 12 healthy subjects. The z-axis of the scanner defines the perpendicular to a routine axial plane, and the anatomic axial plane is parallel to the knee joint. Isotropic MRI was reformatted into routine and anatomic axial planes and in axial planes simulating 5 degrees of femoral adduction and abduction relative to the anatomic plane. A method for correcting the TT-TG distance to account for variable axial scan orientation is presented. RESULTS. Five degrees of simulated femoral abduction is associated with a mean increase in the TT-TG distance of 38% (SD = 17%), whereas 5 degrees of simulated femoral adduction is associated with a mean decrease in the TT-TG distance of 51% (SD = 39%). The average deviation of the routine axial plane from the anatomic axial plane was 5.0 degrees abduction (SD = 2.3 degrees). The simplest correction method reduced the mean discrepancy in the observed TT-TG distance by 68% and 72% in simulated femoral abduction and adduction, respectively. CONCLUSION. The TT-TG distance is sensitive to small changes in femoral alignment and should be interpreted with caution if axial image acquisition is not standardized. Knowing the vertical separation of the TT from the TG facilitates a simplified correction of the TT-TG distance, which is as effective as more complex corrections. C1 [Yao, Lawrence; Gai, Neville] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Boutin, Robert D.] Univ Calif, Dept Radiol, Sacramento, CA USA. RP Yao, L (reprint author), NIH, Ctr Clin, Dept Radiol & Imaging Sci, 10 Ctr Dr, Bethesda, MD 20892 USA. EM lyao@cc.nih.gov FU National Institutes of Health Clinical Center, Intramural Research Program FX This study was supported in part by the National Institutes of Health Clinical Center, Intramural Research Program. NR 14 TC 3 Z9 3 U1 0 U2 1 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 JUN PY 2014 VL 202 IS 6 BP 1291 EP 1296 DI 10.2214/AJR.13.11488 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI6DB UT WOS:000336959000037 PM 24848827 ER PT J AU Murphy, RA Bureyko, TF Miljkovic, I Cauley, JA Satterfield, S Hue, TF Klepin, HD Cummings, SR Newman, AB Harris, TB AF Murphy, Rachel A. Bureyko, Taylor F. Miljkovic, Iva Cauley, Jane A. Satterfield, Suzanne Hue, Trisha F. Klepin, Heidi D. Cummings, Steven R. Newman, Anne B. Harris, Tamara B. TI Association of total adiposity and computed tomographic measures of regional adiposity with incident cancer risk: a prospective population-based study of older adults SO APPLIED PHYSIOLOGY NUTRITION AND METABOLISM-PHYSIOLOGIE APPLIQUEE NUTRITION ET METABOLISME LA English DT Article DE obesity; weight; adipose; body fat; cancer incidence; cancer risk; aging ID BODY-MASS INDEX; WAIST CIRCUMFERENCE; FAT DISTRIBUTION; LUNG-CANCER; OBESITY; COHORT; HEALTH; WOMEN; OVERWEIGHT; WEIGHT AB Obesity is associated with increased risk of many types of cancer. Less is known regarding associations between adipose depots and cancer risk. We aimed to explore relationships between adipose depots, risk of cancer, and obesity-related cancer (per NCI definition) in participants initially aged 70-79 years without prevalent cancer (1179 men, 1340 women), and followed for incident cancer for 13 years. Measures included body mass index (BMI), total adipose tissue from dual-energy X-ray absorptiometry, and computed tomography measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, thigh intermuscular adipose tissue, and thigh muscle attenuation (Hounsfield unit, HU), where low HU indicates fatty infiltration. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models adjusted for demographics, lifestyle variables, and medical conditions. During follow-up, 617 participants developed cancer of which 224 were obesity-related cancers. Total adipose tissue and VAT were positively associated with cancer risk among women (HR 1.14, 95% CI 1.01-1.30 per SD increase; HR 1.15, 95% CI 1.02-1.30 per SD increase). There were no associations with cancer risk among men. Total adipose tissue was positively associated with obesity-related cancer risk among women (HR 1.23, 95% CI 1.03-1.46 per SD increase). VAT was positively associated with obesity-related cancer risk among men (HR 1.30, 95% CI 1.06-1.60 per SD increase) and remained associated even with adjustment for BMI (HR 1.40, 95% CI 1.08-1.82 per SD increase). These findings provide insight into relationships between specific adipose depots and cancer risk and suggest differential relationships among men and women. C1 [Murphy, Rachel A.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20814 USA. [Bureyko, Taylor F.] Univ Alberta, Dept Agr Food & Nutr Sci, Li Ka Shing Ctr 4 126, Edmonton, AB T6G 2E1, Canada. [Miljkovic, Iva; Cauley, Jane A.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Hlth Sci Ctr, Memphis, TN 38163 USA. [Hue, Trisha F.; Cummings, Steven R.] Calif Pacific Med Ctr Res Inst, San Francisco, CA 94120 USA. [Klepin, Heidi D.] Wake Forest Sch Med, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. RP Murphy, RA (reprint author), NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, 7201 Wisconsin Ave,3C-309, Bethesda, MD 20814 USA. EM Rachel.murphy@nih.gov RI Cauley, Jane/N-4836-2015; Newman, Anne B./C-6408-2013; OI Cauley, Jane/0000-0003-0752-4408; Newman, Anne B./0000-0002-0106-1150; Miljkovic, Iva/0000-0002-3155-9777 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050]; NINR [R01-NR-012459]; National Institutes of Health, National Institute on Aging; Banting Postdoctoral Fellowship FX This research was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103, N01-AG-6-2106; NIA grant R01-AG028050, and NINR grant R01-NR-012459. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. R.A.M. is supported by a Banting Postdoctoral Fellowship. NR 19 TC 4 Z9 4 U1 0 U2 5 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 1715-5312 EI 1715-5320 J9 APPL PHYSIOL NUTR ME JI Appl. Physiol. Nutr. Metab. PD JUN PY 2014 VL 39 IS 6 BP 687 EP 692 DI 10.1139/apnm-2013-0360 PG 6 WC Nutrition & Dietetics; Physiology; Sport Sciences SC Nutrition & Dietetics; Physiology; Sport Sciences GA AI8KZ UT WOS:000337164600006 PM 24869972 ER PT J AU Williams, JS Xiao, Y Brownell, I AF Williams, Jonathan S. Xiao, Ying Brownell, Isaac TI Low pH reprograms somatic murine cells into pluripotent stem cells A novel technique with therapeutic implications SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE induced pluripotent stem cells; embryonic stem cells; stimulus-triggered acquisition of pluripotency; blastocyst complementation assay; tumor infiltrating lymphocytes ID FIBROBLASTS; LYMPHOCYTES; GENERATION AB Induced pluripotent stem cells (iPSCs) are somatic cells that are reprogrammed into a state resembling embryonic stem cells (ESCs). iPSCs represent a promising technology with applications in cancer research, yet current methods used to generate iPSCs limit their translation to clinical use. In a recent Nature article, Obokata et al. detail a novel technique to generate pluripotent murine cells called stimulus-triggered acquisition of pluripotency (STAP). STAP eliminates the need for exogenous expression of reprogramming factors used in previous iPSC technologies, instead transforming somatic cells to pluripotency using physical and chemical stimuli. The authors found that STAP cells are generated at a 10-fold higher efficiency than prior iPSC technologies. STAP cells display several features of pluripotency, namely the expression of pluripotency-related genes (Oct4, Nanog, Sox2, Ecat1, Esg1, and Dax1), the ability to form teratomas in vivo, and the ability to produce viable, fertile mice in blastocyst complementation assays. Here, we review these findings on STAP and contrast it to previous iPSC technologies, while noting the potential of this method to generate autologous anti-tumor immune cells for cancer therapy. C1 [Williams, Jonathan S.; Xiao, Ying; Brownell, Isaac] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Brownell, I (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. EM isaac.brownell@nih.gov FU Intramural NIH HHS NR 10 TC 1 Z9 1 U1 0 U2 16 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUN PY 2014 VL 15 IS 6 BP 675 EP 677 DI 10.4161/cbt.28414 PG 3 WC Oncology SC Oncology GA AI8MC UT WOS:000337169500004 PM 24618709 ER PT J AU McAllister, F Pineda, DM Jimbo, M Lal, S Burkhart, RA Moughan, J Winter, KA Abdelmohsen, K Gorospe, M Acosta, AD Lankapalli, RH Winter, JM Yeo, CJ Witkiewicz, AK Iacobuzio-Donahue, CA Laheru, D Brody, JR AF McAllister, Florencia Pineda, Danielle M. Jimbo, Masaya Lal, Shruti Burkhart, Richard A. Moughan, Jennifer Winter, Kathryn A. Abdelmohsen, Kotb Gorospe, Myriam Acosta, Ana de Jesus Lankapalli, Rachana H. Winter, Jordan M. Yeo, Charles J. Witkiewicz, Agnieska K. Iacobuzio-Donahue, Christine A. Laheru, Daniel Brody, Jonathan R. TI dCK expression correlates with 5-fluorouracil efficacy and HuR cytoplasmic expression in pancreatic cancer A dual-institutional follow-up with the RTOG 9704 trial SO CANCER BIOLOGY & THERAPY LA English DT Article DE pancreatic cancer; gemcitabine; 5-fluorouracil; HuR; dCK ID THYMIDYLATE SYNTHASE EXPRESSION; RANDOMIZED CONTROLLED-TRIAL; MISMATCH REPAIR STATUS; PLUS FOLINIC ACID; ADJUVANT CHEMOTHERAPY; DEOXYCYTIDINE KINASE; COLORECTAL-CANCER; PREDICTIVE MARKER; COLON-CANCER; CELL-LINES AB Deoxycytidine kinase (dCK) and human antigen R (HuR) have been associated with response to gemcitabine in small studies. The present study investigates the prognostic and predictive value of dCK and HuR expression levels for sensitivity to gemcitabine and 5-fluorouracil (5-FU) in a large phase III adjuvant trial with chemoradiation backbone in pancreatic ductal adenocarcinoma (PDA). The dCK and HuR expression levels were determined by immunohistochemistry on a tissue microarray of 165 resected PDAs from the Radiation Therapy Oncology Group (RTOG) 9704 trial. Association with overall survival (OS) and disease-free survival (DFS) status were analyzed using the log-rank test and the Cox proportional hazards model. Experiments with cultured PDA cells were performed to explore mechanisms linking dCK and HuR expression to drug sensitivity. dCK expression levels were associated with improved OS for all patients analyzed from RTOG 9704 (HR: 0.66, 95% CI [0.47-0.93], P = 0.015). In a subset analysis based on treatment arm, the effect was restricted to patients receiving 5-FU (HR: 0.53, 95% CI [0.33-0.85], P = 0.0078). Studies in cultured cells confirmed that dCK expression rendered cells more sensitive to 5-FU. HuR cytoplasmic expression was neither prognostic nor predictive of treatment response. Previous studies along with drug sensitivity and biochemical studies demonstrate that radiation interferes with HuR's regulatory effects on dCK, and could account for the negative findings herein based on the clinical study design (i.e., inclusion of radiation). Finally, we demonstrate that 5-FU can increase HuR function by enhancing HuR translocation from the nucleus to the cytoplasm, similar to the effect of gemcitabine in PDA cells. For the first time, in the pre-treatment tumor samples, dCK and HuR cytoplasmic expression were strongly correlated (chi-square P = 0.015). This dual-institutional follow up study, in a multi-institutional PDA randomized clinical trial, observed that dCK expression levels were prognostic and had predictive value for sensitivity to 5-FU. C1 [McAllister, Florencia; Acosta, Ana de Jesus; Lankapalli, Rachana H.; Iacobuzio-Donahue, Christine A.; Laheru, Daniel] Johns Hopkins Univ, Dept Med Oncol, Baltimore, MD USA. [McAllister, Florencia; Acosta, Ana de Jesus; Lankapalli, Rachana H.; Iacobuzio-Donahue, Christine A.; Laheru, Daniel] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [McAllister, Florencia] Johns Hopkins Univ, Dept Med, Div Clin Pharmacol, Baltimore, MD USA. [Pineda, Danielle M.; Jimbo, Masaya; Lal, Shruti; Burkhart, Richard A.; Winter, Jordan M.; Yeo, Charles J.; Brody, Jonathan R.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg,Div Surg Res, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA. [Moughan, Jennifer; Winter, Kathryn A.] RTOG Stat Ctr, Philadelphia, PA USA. [Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Witkiewicz, Agnieska K.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. RP Brody, JR (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg,Div Surg Res, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA. EM jonathan.brody@jefferson.edu OI Lal, Shruti/0000-0002-2091-4307 FU NIGMS [T32GMO66691]; Pancreatic Cancer Action Network-AACR Fellowship [12-40-25-MCAL]; Conquer Cancer Foundation Young Investigator Award; American Cancer Society; NIA-IRP, NIH; RTOG Translational Research Program (seed grant) [78]; RTOG grant [U10 CA21661]; CCOP grant from the National Cancer Institute (NCI) [U10 CA37422]; Pennsylvania Department of Health Formula Grant [4100057652] FX F.M. was supported by NIGMS T32GMO66691, 2012 Pancreatic Cancer Action Network-AACR Fellowship, in memory of Samuel Stroum, Grant Number 12-40-25-MCAL and Conquer Cancer Foundation Young Investigator Award 2012. J.R.B. was in part supported by resources provided by AACR-Pancreatic Cancer Action Network and A Research Scholar Grant from the American Cancer Society. M. G. and K. A. were supported by the NIA-IRP, NIH. This project was supported by the RTOG Translational Research Program (seed grant #78), RTOG grant U10 CA21661, CCOP grant U10 CA37422 from the National Cancer Institute (NCI), and the Pennsylvania Department of Health Formula Grant 4100057652. No part of this manuscript has been submitted to any other journal. NR 51 TC 13 Z9 14 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUN PY 2014 VL 15 IS 6 BP 688 EP 698 DI 10.4161/cbt.28413 PG 11 WC Oncology SC Oncology GA AI8MC UT WOS:000337169500007 PM 24618665 ER PT J AU Pastan, I Hassan, R AF Pastan, Ira Hassan, Raffit TI Discovery of Mesothelin and Exploiting It as a Target for Immunotherapy SO CANCER RESEARCH LA English DT Review ID MONOCLONAL-ANTIBODY MORAB-009; IMMUNOTOXIN SS1P; PHASE-I; RECOMBINANT IMMUNOTOXIN; ANTITUMOR-ACTIVITY; OVARIAN-CANCER; EXPRESSING MESOTHELIN; PLUS CYCLOPHOSPHAMIDE; LUNG ADENOCARCINOMA; POTENTIATING FACTOR AB We have recently reported that an immunotoxin targeting mesothelin produced durable major tumor regressions in patients with extensive treatment-refractory mesothelioma. These unprecedented tumor responses have prompted us to review how mesothelin was discovered and the advances that led to these tumor responses. This review is not comprehensive but focuses on major developments over the past 20 years since mesothelin was first identified in our laboratory. Mesothelin is a cell-surface glycoprotein whose expression in normal human tissues is restricted to mesothelial cells. Because it is highly expressed by many solid tumors, it is an attractive immunotherapy target. Antibody-based therapies currently in clinical trials include an immunotoxin, a chimeric monoclonal antibody, and an antibody drug conjugate. In addition, a mesothelin tumor vaccine and a mesothelin-chimeric antigen receptor are being evaluated in the clinic. SS1P, an anti-mesothelin immunotoxin, was the first mesothelin-directed therapy to enter the clinic, and its use showed that mesothelin- targeted therapy was safe in patients. More importantly, our recent work has shown that SS1P in combination with pentostatin and cyclophosphamide can result in durable tumor regression in patients with advanced mesothelioma and opens up the possibility that such an approach can benefit patients with many common cancers. C1 [Pastan, Ira; Hassan, Raffit] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov; hassanr@mail.nih.gov FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; CRADA; Roche Pharmaceuticals FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and a CRADA with Roche Pharmaceuticals. NR 47 TC 43 Z9 43 U1 3 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2014 VL 74 IS 11 BP 2907 EP 2912 DI 10.1158/0008-5472.CAN-14-0337 PG 6 WC Oncology SC Oncology GA AI8ML UT WOS:000337170600001 PM 24824231 ER PT J AU Ekenga, CC Parks, CG D'Aloisio, AA Deroo, LA Sandler, DP AF Ekenga, Christine C. Parks, Christine G. D'Aloisio, Aimee A. Deroo, Lisa A. Sandler, Dale P. TI Breast Cancer Risk after Occupational Solvent Exposure: the Influence of Timing and Setting SO CANCER RESEARCH LA English DT Article ID ORGANIC-SOLVENTS; ENDOCRINE DISRUPTORS; YOUNG-WOMEN; EARLY-LIFE; CHEMICALS; SMOKING; DISEASE AB Organic solvents are ubiquitous in occupational settings where they may contribute to risks for carcinogenesis. However, there is limited information on organic solvents as human breast carcinogens. We examined the relationship between occupational exposure to solvents and breast cancer in a prospective study of 47,661 women with an occupational history in the Sister Study cohort. Occupational solvent exposure was categorized using self-reported job-specific solvent use collected at baseline. Multivariable Cox regression analyses were used to assess breast cancer risk, adjusting for established breast cancer risk factors. A total of 1,798 women were diagnosed with breast cancer during follow-up, including 1,255 invasive cases. Overall the risk of invasive breast cancer was not associated with lifetime exposure to solvents [HR, 1.04; 95% confidence interval (CI), 0.88-1.24]. Parous women who worked with solvents before their first fullterm birth had an increased risk of estrogen receptor-positive invasive breast cancer compared with women who never worked with solvents (HR, 1.39; 95% CI, 1.03-1.86). A significantly elevated risk for estrogen receptor-positive invasive breast cancer was associated with solvent exposure among clinical laboratory technologists and technicians (HR, 2.00; 95% CI, 1.07-3.73). Occupational exposure to solvents before first birth, a critical period of breast tissue differentiation, may result in increased vulnerability for breast cancer. Our findings suggest a need for future studies in this area to focus on exposure time windows and solvent types in different occupational settings. (C) 2014 AACR. C1 [Ekenga, Christine C.; Parks, Christine G.; D'Aloisio, Aimee A.; Deroo, Lisa A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Deroo, Lisa A.] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway. RP Ekenga, CC (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM christine.ekenga@nih.gov OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018 FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z1A ES044005] FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z1A ES044005). NR 35 TC 6 Z9 6 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2014 VL 74 IS 11 BP 3076 EP 3083 DI 10.1158/0008-5472.CAN-13-2430 PG 8 WC Oncology SC Oncology GA AI8ML UT WOS:000337170600017 PM 24879566 ER PT J AU Layani-Bazar, A Skornick, I Berrebi, A Pauker, MH Noy, E Silberman, A Albeck, M Longo, DL Kalechman, Y Sredni, B AF Layani-Bazar, Adi Skornick, Itai Berrebi, Alain Pauker, Maor H. Noy, Elad Silberman, Alon Albeck, Michael Longo, Dan L. Kalechman, Yona Sredni, Benjamin TI Redox Modulation of Adjacent Thiols in VLA-4 by AS101 Converts Myeloid Leukemia Cells from a Drug-Resistant to Drug-Sensitive State SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; INTEGRIN ACTIVATION; PROTEIN THIOLS; LATE ANTIGEN-4; EXPRESSION; DOMAIN; ALPHA(IIB)BETA(3); CHEMOTHERAPY; SURVIVAL; ADHESION AB Interaction between the integrin VLA-4 on acute myelogenous leukemia (AML) cells with stromal fibronectin is a decisive factor in chemotherapeutic resistance. In this study, we provide a rationale for a drug repositioning strategy to blunt integrin activation in AML cells and restore their sensitivity to chemotherapy. Specifically, we demonstrate that the nontoxic tellurium compound AS101, currently being evaluated in clinical trials, can abrogate the acquired resistance of AML. Mechanistic investigations revealed that AS101 caused redox inactivation of adjacent thiols in the exofacial domain of VLA-4 after its ligation to stromal fibronectin. This effect triggered cytoskeletal conformational changes that decreased PI3K/Akt/Bcl2 signaling, an obligatory step in chemosensitization by AS101. In a mouse xenograft of AML derived from patient leukemic cells with high VLA-4 expression and activity, we demonstrated that AS101 abrogated drug resistance and prolonged survival in mice receiving chemotherapy. Decreased integrin activity was confirmed on AML cells in vivo. The chemosensitizing activity of AS101 persisted in hosts with defective adaptive and innate immunity, consistent with evidence that integrin deactivation was not mediated by heightening immune attack. Our findings provide a mechanistic rationale to reposition the experimental clinical agent, AS101, to degrade VLA-4-mediated chemoresistance and improve clinical responses in patients with AML. C1 [Layani-Bazar, Adi; Skornick, Itai; Pauker, Maor H.; Noy, Elad; Silberman, Alon; Kalechman, Yona; Sredni, Benjamin] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, CAIR Inst, Safdie AIDS & Immunol Res Ctr, IL-5290002 Ramat Gan, Israel. [Silberman, Alon; Albeck, Michael] Bar Ilan Univ, Dept Chem, IL-5290002 Ramat Gan, Israel. [Berrebi, Alain] Kaplan Med Ctr, Dept Hematol, Rehovot, Israel. [Longo, Dan L.] NIA, Lab Mol Biol & Immunol, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Sredni, B (reprint author), Bar Ilan Univ, Max & Anna Webb St, IL-5290002 Ramat Gan, Israel. EM srednib@mail.biu.ac.il FU Israel Cancer Association [20092012, 20080016]; Safdie Institute for AIDS and Immunology Research; Dr. Tovi Comet-Walerstein Cancer Research Chair; Dave and Florence Muskovitz Chair in Cancer Research FX This work was partly supported by grants from the Israel Cancer Association (20092012 and 20080016), The Safdie Institute for AIDS and Immunology Research, The Dr. Tovi Comet-Walerstein Cancer Research Chair, and The Dave and Florence Muskovitz Chair in Cancer Research. NR 48 TC 16 Z9 16 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2014 VL 74 IS 11 BP 3092 EP 3103 DI 10.1158/0008-5472.CAN-13-2159 PG 12 WC Oncology SC Oncology GA AI8ML UT WOS:000337170600019 PM 24699624 ER PT J AU Rahman, F Goldstein, DS AF Rahman, Faisal Goldstein, David S. TI Quantitative indices of baroreflex-sympathoneural function: application to patients with chronic autonomic failure SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Baroreflex; Chronic autonomic failure; Baroreflex-sympathoneural function; Sympathetic; Autonomic ID MULTIPLE SYSTEM ATROPHY; SENSITIVITY; INVOLVEMENT; HYPOTENSION; DISEASE AB Purpose Chronic autonomic failure syndromes such as Parkinson disease with orthostatic hypotension (PD + OH), multiple system atrophy (MSA), and pure autonomic failure (PAF) typically feature arterial baroreflex failure. Identifying baroreflex-sympathoneural failure from hemodynamic responses to the maneuver usually has been qualitative. We report quantitative methods for evaluating baroreflex-sympathoneural function, based on beatto- beat systolic blood pressure (BPs) responses to the Valsalva maneuver. Method Using the trapezoid rule, we calculated the area under the curve (baroreflex area, BRA) between baseline systolic blood pressure (BPs) and the BPs for each beat in Phase II (BRA-II) and Phase IV (BRA-IV) in 136 autonomic failure patients and 171 controls. The sum of the areas was defined as total BRA (BRA-T). We compared individual values by the BRA approach with those by other measures. Results Mean values for log BRA-II, BRA-IV, and BRAT were higher in PD + OH, PAF, and MSA than in controls (p < 0.001 each). The log of BRA-T correlated negatively with the fractional orthostatic change in total peripheral resistance (r = -0.41, p < 0.001), fractional orthostatic change in plasma norepinephrine (r = -0.27, p < 0.001), orthostatic change in BPs (r = -0.62, p < 0.001), fall in BPs in Phase II of the Valsalva (r = 0.58, p < 0.001), and log of baroreflex-cardiovagal slope (r = -0.40, p < 0.001). Areas under receiver operating characteristic curves were 0.85 for BRA-T and 0.89 for BRA-IV (p < 0.001). Conclusion The BRA approach provides quantitative measures of baroreflex-sympathoneural function. Chronic autonomic failure syndromes entail deficiencies of both the cardiovagal and sympathoneural limbs of the arterial baroreflex. C1 [Rahman, Faisal; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10 Room 5N220, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural NIH HHS NR 14 TC 3 Z9 3 U1 0 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0959-9851 EI 1619-1560 J9 CLIN AUTON RES JI Clin. Auton. Res. PD JUN PY 2014 VL 24 IS 3 BP 103 EP 110 DI 10.1007/s10286-014-0234-1 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AI9SI UT WOS:000337275500002 PM 24706176 ER PT J AU Thomas, DA AF Thomas, David A. TI Virtual Reality Research Continues to Progress at the National Institutes of Health SO CYBERPSYCHOLOGY BEHAVIOR AND SOCIAL NETWORKING LA English DT Editorial Material C1 NIDA, Div Clin & Behav Res, NIH, Bethesda, MD 20892 USA. RP Thomas, DA (reprint author), NIDA, Div Clin & Behav Res, NIH, Bethesda, MD 20892 USA. EM dthomas1@nida.nih.gov NR 1 TC 0 Z9 0 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2152-2715 EI 2152-2723 J9 CYBERPSYCH BEH SOC N JI Cyberpsychology Behav. Soc. Netw. PD JUN PY 2014 VL 17 IS 6 BP 334 EP 334 DI 10.1089/cyber.2014.1509 PG 1 WC Psychology, Social SC Psychology GA AI8QA UT WOS:000337184600003 PM 24892194 ER PT J AU Varadkar, P Despres, D Kraman, M Lozier, J Phadke, A Nagaraju, K Mccright, B AF Varadkar, Prajakta Despres, Daryl Kraman, Matthew Lozier, Julie Phadke, Aditi Nagaraju, Kanneboyina Mccright, Brent TI The protein phosphatase 2A B56 regulatory subunit is required for heart development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE protein phosphatase 2A regulatory B subunit; PP2A; PR61; ventricular septal defect; mouse heart development; cardiomyocyte ID SMOOTH-MUSCLE ACTIN; A-SUBUNIT; PP2A; MICE; EXPRESSION; PHOSPHORYLATION; DIFFERENTIATION; IDENTIFICATION; ALPHA; LOCALIZATION AB Background: Protein Phosphatase 2A (PP2A) function is controlled by regulatory subunits that modulate the activity of the catalytic subunit and direct the PP2A complex to specific intracellular locations. To study PP2A's role in signal transduction pathways that control growth and differentiation in vivo, a transgenic mouse lacking the B56 regulatory subunit of PP2A was made. Results: Lack of PP2A activity specific to the PP2A-B56 holoenzyme, resulted in the formation of an incomplete ventricular septum and a decrease in the number of ventricular cardiomyocytes. During cardiac development, B56 is expressed in the nucleus of -actinin-positive cardiomyocytes that contain Z-bands. The pattern of B56 expression correlated with the cardiomyocyte apoptosis we observed in B56-deficient mice during mid to late gestation. In addition to the cardiac phenotypes, mice lacking B56 have a decrease in locomotive coordination and gripping strength, indicating that B56 has a role in controlling PP2A activity required for efficient neuromuscular function. Conclusions: PP2A-B56 activity is required for efficient cardiomyocyte maturation and survival. The PP2A B56 regulatory subunit controls PP2A substrate specificity in vivo in a manner that cannot be fully compensated for by other B56 subunits. Developmental Dynamics 243:778-790, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Varadkar, Prajakta; Lozier, Julie; Mccright, Brent] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Despres, Daryl] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. [Kraman, Matthew] Univ Cambridge, Cambridge Res Inst, Cambridge, England. [Phadke, Aditi; Nagaraju, Kanneboyina] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Mccright, B (reprint author), 29 Lincoln Dr,Bldg 29B,Room 2NN08, Bethesda, MD 20892 USA. EM brenton.mccright@fda.hhs.gov FU US Department of Defense [W81XWH-09-1-0599] FX The preclinical phenotyping facility at CNMC is supported by a grant from US Department of Defense grant no. W81XWH-09-1-0599 to Dr. Nagaraju. NR 31 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 2014 VL 243 IS 6 BP 778 EP 790 DI 10.1002/dvdy.24111 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA AJ3SI UT WOS:000337587200004 PM 24425002 ER PT J AU Fourie, NH Peace, RM Abey, SK Sherwin, LB Rahim-Williams, B Smyser, PA Wiley, JW Henderson, WA AF Fourie, Nicolaas H. Peace, Ralph Michael Abey, Sarah K. Sherwin, LeeAnne B. Rahim-Williams, Bridgett Smyser, Paul A. Wiley, John W. Henderson, Wendy A. TI Elevated circulating miR-150 and miR-342-3p in patients with irritable bowel syndrome SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE Irritable bowel syndrome; MicroRNA; hsa-miRNA-150; hsa-miR-342-3p ID CALCIUM-CHANNELS; PAIN SYNDROME; ACTIVATION; INTESTINE; CELLS; IBS AB Background and aims: MicroRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression and are thus of interest as diagnostic markers, and as clues to etiology and targets of intervention. This pilot study examined whether circulating miRNAs are differentially expressed in patients with IBS. Methods: miRNA microarrays (NanoString) were run on the whole blood of 43 participants. Results: hsa-miR-150 and hsa-miR-342-3p were found to be significantly elevated (FDR adjusted p <= 0.05, >= 1.6 fold change) in IBS patients compared to healthy controls. Neither of these miRNAs showed any relationship to race or sex. hsa-miR-150 is associated with inflammatory bowel disorders and pain, and interacts with a protein kinase (AKT2) through which it may affect inflammatory pathways. hsa-miR-342-3p is predicted to interact with mRNAs involved in pain signaling, colonic motility, and smooth muscle function. Conclusions: This preliminary study reports the association of two miRNAs, detected in whole blood, with IBS. These miRNAs link to pain and inflammatory pathways both of which are thought to be dysregulated in IBS. Larger sample sizes are needed to confirm their importance and potential as biomarkers. Published by Elsevier Inc. C1 [Fourie, Nicolaas H.; Peace, Ralph Michael; Abey, Sarah K.; Sherwin, LeeAnne B.; Rahim-Williams, Bridgett; Smyser, Paul A.; Henderson, Wendy A.] Natl Inst Nursing Res, Digest Disorders Unit, NIH, DHHS, Bethesda, MD 20892 USA. [Peace, Ralph Michael] Howard Hughes Med Inst, Natl Inst Hlth Res Scholar, Chevy Chase, MD 20815 USA. [Rahim-Williams, Bridgett] Natl Inst Minor Hlth & Hlth Dispar, NIH, DHHS, Bethesda, MD 20892 USA. [Wiley, John W.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. RP Henderson, WA (reprint author), Natl Inst Nursing Res, Digest Disorders Unit, Div Intramural Res, NIH,DHHS, 10 Ctr Dr,Room 2-1341, Bethesda, MD 20892 USA. EM hendersw@mail.nih.gov OI Fourie, Nicolaas/0000-0002-5167-8570; Henderson, Wendy/0000-0003-3924-7118 FU U.S. Department of Health and Human Services; National Institutes of Health; National Institute of Nursing Research; Division of Intramural Research [1ZIANR000018-01-04]; Intramural Research Training Awards; National Institute on Minority Health and Health Disparities [1K22MD006143-01]; NIH Research Scholar RMP; Burroughs Wellcome Fund FX The authors acknowledge funding from the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Nursing Research, Division of Intramural Research to Wendy A. Henderson, 1ZIANR000018-01-04; Intramural Research Training Awards to Nicolaas H. Fourie, Ralph M. Peace, Sarah K. Abey, Leeanne B. Sherwin, and Paul A. Smyser; Howard Hughes-NIH Research Scholar RMP; Special support from the Burroughs Wellcome Fund to Ralph M. Peace. Training award to Bridgett Rahim-Williams supported by the National Institute on Minority Health and Health Disparities (1K22MD006143-01). NR 20 TC 25 Z9 25 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 EI 1096-0945 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD JUN PY 2014 VL 96 IS 3 BP 422 EP 425 DI 10.1016/j.yexmp.2014.04.009 PG 4 WC Pathology SC Pathology GA AI8YJ UT WOS:000337212600022 PM 24768587 ER PT J AU Ocean, AJ Christos, P Sparano, JA Shah, MA Yantiss, RK Cheng, J Lin, J Papetti, M Matulich, D Schnoll-Sussman, F Besanceney-Webler, C Xiang, J Ward, M Dilts, KT Keresztes, R Holloway, S Chen, EX Wright, JJ Lane, ME AF Ocean, Allyson J. Christos, Paul Sparano, Joseph A. Shah, Manish A. Yantiss, Rhonda K. Cheng, Jonathan Lin, Juan Papetti, Michael Matulich, Dan Schnoll-Sussman, Felice Besanceney-Webler, Christen Xiang, Jenny Ward, Maureen Dilts, Kaili Temple Keresztes, Roger Holloway, Shannon Chen, Eric X. Wright, John J. Lane, Maureen E. TI Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Bortezomib; Proteasome inhibitor; Irinotecan; Gastroesophageal junction; Adenocarcinoma; Combination therapy; Microarray ID PROTEASOME INHIBITOR PS-341; FACTOR-KAPPA-B; COLORECTAL-CANCER; GASTRIC-CANCER; GROWTH; APOPTOSIS; MYELOMA AB Purpose To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. Methods Forty-one patients with advanced GEJ (89 %) or gastric (11 %) adenocarcinoma received bortezomib (1.3 mg/m(2) days 1, 4, 8, 11) plus irinotecan (125 mg/m(2) days 1, 8) every 21 days as first line therapy (N = 29), or bortezomib alone as second line therapy (N = 12). The trial was designed to detect a 40 % response rate for the combination, and 20 % response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. Results Objective response occurred in 3 of 29 patients (10 %, 95 % confidence intervals [CI] 2 %, 27 %) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 %, 95 % CI 0 %, 39 %) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N = 2) or the combination (N = 10). Conclusions We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population. C1 [Ocean, Allyson J.; Christos, Paul; Shah, Manish A.; Yantiss, Rhonda K.; Schnoll-Sussman, Felice; Besanceney-Webler, Christen; Xiang, Jenny; Ward, Maureen; Dilts, Kaili Temple; Holloway, Shannon; Lane, Maureen E.] Weill Cornell Med Coll, New York, NY 10021 USA. [Sparano, Joseph A.; Papetti, Michael] Montefiore Med Ctr, Bronx, NY 10467 USA. [Sparano, Joseph A.; Lin, Juan; Papetti, Michael] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Cheng, Jonathan] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Matulich, Dan] Columbia Univ, New York, NY USA. [Keresztes, Roger] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA. [Chen, Eric X.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Lane, ME (reprint author), Weill Cornell Med Coll, New York, NY 10021 USA. EM mel2009@med.cornell.edu FU National Institute of Health, National Cancer Institute [N01-CM-62204, P30CA013330] FX The authors acknowledge the late Dr. Scott Wadler, our colleague and friend, who conceived of and designed this trial and founded the New York Cancer Consortium. He will be remembered for his skills as clinician, scholar, and mentor. This work was supported by the National Institute of Health, National Cancer Institute (N01-CM-62204, PI: Joseph A. Sparano and P30CA013330, PI: David Goldman, MD). NR 19 TC 4 Z9 4 U1 3 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 EI 1573-0646 J9 INVEST NEW DRUG JI Invest. New Drugs PD JUN PY 2014 VL 32 IS 3 BP 542 EP 548 DI 10.1007/s10637-014-0070-0 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AI7OU UT WOS:000337084000017 PM 24526575 ER PT J AU Habibi, M Chahal, H Opdahl, A Gjesdal, O Helle-Valle, TM Heckbert, SR McClelland, R Wu, CL Shea, S Hundley, G Bluemke, DA Lima, JAC AF Habibi, Mohammadali Chahal, Harjit Opdahl, Anders Gjesdal, Ola Helle-Valle, Thomas M. Heckbert, Susan R. McClelland, Robyn Wu, Colin Shea, Steven Hundley, Gregory Bluemke, David A. Lima, Joao A. C. TI Association of CMR-Measured LA Function With Heart Failure Development Results From the MESA Study Results From the MESA Study SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE feature-tracking MRI; heart failure; left atrial function; left atrial strain ID LEFT ATRIAL VOLUME; CARDIOVASCULAR MAGNETIC-RESONANCE; SPECKLE TRACKING ECHOCARDIOGRAPHY; VENTRICULAR SYSTOLIC FUNCTION; PRESERVED EJECTION FRACTION; MYOCARDIAL FEATURE TRACKING; END-DIASTOLIC PRESSURE; 2-DIMENSIONAL ECHOCARDIOGRAPHY; GREATER-THAN-OR-EQUAL-TO-65 YEARS; DEFORMATION ANALYSIS AB OBJECTIVES The goal of this study was to assess the association between left atrial (LA) volume and function measured with feature-tracking cardiac magnetic resonance (CMR) and development of heart failure (HF) in asymptomatic individuals. BACKGROUND. Whether alterations of LA structure and function precede or follow HF development remains incompletely understood. We hypothesized that significant alterations of LA deformation and architecture precede the development of HF in the general population. METHODS In a case-control study nested in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA volume and function assessed using CMR feature-tracking were compared between 112 participants with incident HF (mean age 68.4 +/- 8.2 years; 66% men) and 224 age- and sex-matched controls (mean age 67.7 +/- 8.9 years; 66% men). Participants were followed up for 8 years. All individuals were in normal sinus rhythm at the time of imaging, without any significant valvular abnormalities and free of clinical cardiovascular diseases. RESULTS Individuals with incident HF had greater maximal and minimal LA volume indexes (LAVI(min)) than control subjects (40 +/- 13 mm(3)/m(2) vs. 33 +/- 10 mm(3)/m(2) [p < 0.001] for maximal LA index and 25 +/- 11 mm(3)/m(2) vs. 17 +/- 7 mm(3)/m(2) [p < 0.001] for LAVI(min)). The HF case subjects also had smaller global peak longitudinal atrial strain (PLAS) (25 +/- 11% vs. 38 +/- 16%; p < 0.001) and lower LA emptying fraction (40 +/- 11% vs. 48 +/- 9%; p < 0.001) at baseline. After adjustment for traditional cardiovascular risk factors, left ventricular mass, and N-terminal pro-B-type natriuretic peptide, global PLAS (odds ratio: 0.36 per SD [95% confidence interval: 0.22 to 0.60]) and LAVI(min) (odds ratio: 1.65 per SD [95% confidence interval: 1.04 to 2.63]) were independently associated with incident HF. CONCLUSIONS Deteriorations in LA structure and function preceded development of HF. Lower global PLAS and higher LAVI(min), measured using CMR feature-tracking, were independent markers of incident HF in a multiethnic population of asymptomatic individuals. (C) 2014 by the American College of Cardiology Foundation C1 [Habibi, Mohammadali; Chahal, Harjit; Opdahl, Anders; Gjesdal, Ola; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. [Opdahl, Anders; Gjesdal, Ola; Helle-Valle, Thomas M.] Univ Oslo, Dept Cardiol, Oslo, Norway. [Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [McClelland, Robyn] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Wu, Colin] NHLBI, Off Biostat, Bethesda, MD 20892 USA. [Shea, Steven] Columbia Univ, Med Ctr, New York, NY USA. [Hundley, Gregory] Wake Forest Univ, Sch Med, Cardiol Sect, Winston Salem, NC 27109 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Blalock 524D,600 North Wolfe St, Baltimore, MD 21287 USA. EM jlima@jhmi.edu RI Gjesdal, Ola/C-1941-2015; Opdahl, Anders/I-7580-2015 OI Opdahl, Anders/0000-0002-0599-592X FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95168]; National Center for Research Resources, National Institutes of Health [UL1-RR-024156, UL1-RR-025005] FX This research was supported by contracts N01-HC-95159 through N01-HC-95166 and N01-HC-95168 from the National Heart, Lung, and Blood Institute and UL1-RR-024156 and UL1-RR-025005 from the National Center for Research Resources, National Institutes of Health. All authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sherif Nagueh, MD, served as Guest Editor for this paper. NR 45 TC 27 Z9 28 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JUN PY 2014 VL 7 IS 6 BP 570 EP 579 DI 10.1016/j.jcmg.2014.01.016 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AJ0HP UT WOS:000337331800005 PM 24813967 ER PT J AU Shaw, LJ Berman, DS Picard, MH Friedrich, MG Kwong, RY Stone, GW Senior, R Min, JK Hachamovitch, R Scherrer-Crosbie, M Mieres, JH Marwick, TH Phillips, LM Chaudhry, FA Pellikka, PA Slomka, P Arai, AE Iskandrian, AE Bateman, TM Heller, GV Miller, TD Nagel, E Goyal, A Borges-Neto, S Boden, WE Reynolds, HR Hochman, JS Maron, DJ Douglas, PS AF Shaw, Leslee J. Berman, Daniel S. Picard, Michael H. Friedrich, Matthias G. Kwong, Raymond Y. Stone, Gregg W. Senior, Roxy Min, James K. Hachamovitch, Rory Scherrer-Crosbie, Marielle Mieres, Jennifer H. Marwick, Thomas H. Phillips, Lawrence M. Chaudhry, Farooq A. Pellikka, Patricia A. Slomka, Piotr Arai, Andrew E. Iskandrian, Ami E. Bateman, Timothy M. Heller, Gary V. Miller, Todd D. Nagel, Eike Goyal, Abhinav Borges-Neto, Salvador Boden, William E. Reynolds, Harmony R. Hochman, Judith S. Maron, David J. Douglas, Pamela S. CA ISCHEMIA Trial Investigators TI Comparative Definitions for Moderate-Severe Ischemia in Stress Nuclear, Echocardiography, and Magnetic Resonance Imaging SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac imaging; ischemia; prognosis ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; VENTRICULAR EJECTION FRACTION; INCREMENTAL PROGNOSTIC VALUE; OPTIMAL MEDICAL THERAPY; MYOCARDIAL-PERFUSION SCINTIGRAPHY; AMERICAN-HEART-ASSOCIATION; EXERCISE ECHOCARDIOGRAPHY; RISK STRATIFICATION; REVASCULARIZATION PROCEDURES AB The lack of standardized reporting of the magnitude of ischemia on noninvasive imaging contributes to variability in translating the severity of ischemia across stress imaging modalities. We identified the risk of coronary artery disease (CAD) death or myocardial infarction (MI) associated with >= 10% ischemic myocardium on stress nuclear imaging as the risk threshold for stress echocardiography and cardiac magnetic resonance. A narrative review revealed that >= 10% ischemic myocardium on stress nuclear imaging was associated with a median rate of CAD death or MI of 4.9%/year (interquartile range: 3.75% to 5.3%). For stress echocardiography, >= 3 newly dysfunctional segments portend a median rate of CAD death or MI of 4.5%/year (interquartile range: 3.8% to 5.9%). Although imprecisely delineated, moderate-severe ischemia on cardiac magnetic resonance may be indicated by >= 4 of 32 stress perfusion defects or >= 3 dobutamine-induced dysfunctional segments. Risk-based thresholds can define equivalent amounts of ischemia across the stress imaging modalities, which will help to translate a common understanding of patient risk on which to guide subsequent management decisions. (C) 2014 by the American College of Cardiology Foundation C1 [Shaw, Leslee J.; Goyal, Abhinav] Emory Univ, Dept Med, Div Cardiol, Atlanta, GA 30324 USA. [Berman, Daniel S.] Cedars Sinai Med Ctr, Dept Med, Div Cardiac Imaging Nucl Cardiol, Los Angeles, CA 90048 USA. [Picard, Michael H.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Friedrich, Matthias G.] Montreal Heart Inst, Dept Med, Div Cardiol, Montreal, PQ H1T 1C8, Canada. [Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Stone, Gregg W.] Columbia Univ, New York Presbyterian Hosp, Med Ctr, Dept Med,Div Cardiol, New York, NY USA. [Senior, Roxy] Univ London Imperial Coll Sci Technol & Med, Dept Cardiovasc Med, Div Cardiol, London, England. [Min, James K.] Weill Cornell Med Coll, Dept Cardiovasc Med, Div Radiol, New York, NY USA. [Hachamovitch, Rory] Cleveland Clin Fdn, Dept Cardiovasc Med, Div Cardiol, Cleveland, OH 44195 USA. [Mieres, Jennifer H.] North Shore Long Isl Jewish Hosp, Dept Med, Div Cardiol, Manhasset, NY USA. [Marwick, Thomas H.] Menzies Res Inst Tasmania, Dept Med, Div Cardiol, Hobart, Tas, Australia. [Phillips, Lawrence M.; Reynolds, Harmony R.; Hochman, Judith S.] NYU, Med Ctr, Dept Med, Div Cardiol, New York, NY 10016 USA. [Chaudhry, Farooq A.] Icahn Sch Med Mt Sinai, Dept Med, Div Cardiol, New York, NY USA. [Pellikka, Patricia A.; Miller, Todd D.] Mayo Clin, Dept Med, Div Cardiovasc Med, Rochester, MN USA. [Slomka, Piotr] Cedars Sinai Med Ctr, Dept Med, Div Imaging, Los Angeles, CA 90048 USA. [Arai, Andrew E.] NHLBI, Dept Med, Div Cardiovasc Med, NIH, Bethesda, MD 20892 USA. [Iskandrian, Ami E.] Univ Alabama Birmingham, Dept Radiol, Div Cardiovasc Dis, Birmingham, AL USA. [Bateman, Timothy M.] St Lukes Mid Amer Heart Inst, Dept Med, Div Cardiol, Kansas City, MO USA. [Heller, Gary V.] Hartford Hosp, Hartford, CT 06115 USA. [Nagel, Eike] Kings Coll London, Dept Med, Div Cardiovasc Med, London, England. [Borges-Neto, Salvador] Duke Clin Res Inst, Dept Nucl Med, Div Radiol, Durham, NC USA. [Boden, William E.] Samuel S Stratton VA Med Ctr, Dept Med, Div Cardiol, Albany, NY USA. [Maron, David J.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Douglas, Pamela S.] Duke Clin Res Inst, Dept Med, Div Cardiol, Durham, NC USA. RP Shaw, LJ (reprint author), Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, 1462 Clifton Rd NE,Room 529, Atlanta, GA 30324 USA. EM lshaw3@emory.edu RI Nagel, Eike/C-6903-2008; OI Nagel, Eike/0000-0002-6044-950X; Reynolds, Harmony/0000-0003-0284-0655; Picard, Michael/0000-0002-9264-3243; Hochman, Judith/0000-0002-5889-5981 FU Astellas; Bracco Diagnostics Inc.; GE Healthcare; Philips Healthcare; Siemens; Lantheus Medical Imaging; Spectrum Dynamics; Bayer HealthCare; GlaxoSmithKline FX Dr. Shaw has received research support from Astellas and Bracco Diagnostics Inc. Dr. Friedrich is a board member, advisor, and shareholder for Circle Cardiovascular Imaging. Dr. Senior is a member of the speaker's bureau for and has received honoraria from Bracco Diagnostics Inc. and Philips Healthcare. Dr. Min is a member of the medical advisory board and speaker's bureau for and has received research support from GE Healthcare; is a member of the medical advisory board for Arineta Ltd.; has received research support from Philips Healthcare; and holds equity interest in TC3 and MDDX. Dr. Arai has received research support from Siemens. Dr. Iskandrian is a member of the advisory committee for Rapidscan Pharma. Dr. Bateman is a member of the advisory committee for and receives research support from Astellas, Lantheus Medical Imaging, GE Healthcare, and Spectrum Dynamics. Dr. Miller is a consultant for Astellas. Dr. Nagel has received research support from Philips Healthcare and Bayer HealthCare. Dr. Borges-Neto is a member of the speaker's bureau and advisory board for and has received grant support from Astellas and is a member of the advisory board for and has received grant support from GE Healthcare. Dr. Hochman has received a consulting fee and modest honoraria from GlaxoSmithKline. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 65 TC 34 Z9 34 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X EI 1876-7591 J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD JUN PY 2014 VL 7 IS 6 BP 593 EP 604 DI 10.1016/j.jcmg.2013.10.021 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AJ0HP UT WOS:000337331800008 PM 24925328 ER PT J AU Moissoglu, K Kiessling, V Wan, C Hoffman, BD Norambuena, A Tamm, LK Schwartz, MA AF Moissoglu, Konstadinos Kiessling, Volker Wan, Chen Hoffman, Brenton D. Norambuena, Andres Tamm, Lukas K. Schwartz, Martin Alexander TI Regulation of Rac1 translocation and activation by membrane domains and their boundaries SO JOURNAL OF CELL SCIENCE LA English DT Article DE Rac; FRET; Lipid rafts; Supported bilayers; Domain boundaries ID LIPID RAFTS; IN-VIVO; DISSOCIATION; PROTEINS; DYNAMICS; GTPASES; PLANAR; RHOGDI; CELLS; FRET AB The activation of Rac1 and related Rho GTPases involves dissociation from Rho GDP-dissociation inhibitor proteins and translocation to membranes, where they bind effectors. Previous studies have suggested that the binding of Rac1 to membranes requires, and colocalizes with, cholesterol-rich liquid-ordered (lo) membrane domains (lipid rafts). Here, we have developed a fluorescence resonance energy transfer ( FRET) assay that robustly detects Rac1 membrane targeting in living cells. Surprisingly, FRET with acceptor constructs that were targeted to either raft or non-raft areas indicated that Rac1 was present in both regions. Functional studies showed that Rac1 localization to non-raft regions decreased GTP loading as a result of inactivation by GTPase-activating proteins. In vitro, Rac1 translocation to supported lipid bilayers also required lo domains, yet Rac1 was concentrated in the liquiddisordered (ld) phase. Single-molecule analysis demonstrated that translocation occurred preferentially at lo-ld boundaries. These results, therefore, suggest that Rac1 translocates to the membrane at domain boundaries, then diffuses into raft and non-raft domains, which controls interactions. These findings resolve discrepancies in our understanding of Rac biology and identify novel mechanisms by which lipid rafts modulate Rho GTPase signaling. C1 [Moissoglu, Konstadinos; Hoffman, Brenton D.; Norambuena, Andres; Schwartz, Martin Alexander] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA. [Moissoglu, Konstadinos; Hoffman, Brenton D.; Norambuena, Andres; Schwartz, Martin Alexander] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. [Kiessling, Volker; Wan, Chen; Tamm, Lukas K.] Univ Virginia, Ctr Membrane Biol, Charlottesville, VA 22908 USA. [Kiessling, Volker; Wan, Chen; Tamm, Lukas K.] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. [Schwartz, Martin Alexander] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA. RP Moissoglu, K (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM konstadinos.moissoglu@nih.gov; martin.schwartz@yale.edu FU National Institutes of Health [R01 GM47214, U54 GM64346, P01 GM51329, R37 AI30577] FX This work was supported by the National Institutes of Health [grant numbers R01 GM47214, U54 GM64346 to M.A.S., P01 GM51329, R37 AI30577 to L. K. T.]. Deposited in PMC for release after 12 months. NR 27 TC 10 Z9 10 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD JUN 1 PY 2014 VL 127 IS 11 BP 2565 EP 2576 DI 10.1242/jcs.149088 PG 12 WC Cell Biology SC Cell Biology GA AI9AF UT WOS:000337217400018 PM 24695858 ER PT J AU Davis, AS Richter, A Becker, S Moyer, JE Sandouk, A Skinner, J Taubenberger, JK AF Davis, A. Sally Richter, Anke Becker, Steven Moyer, Jenna E. Sandouk, Aline Skinner, Jeff Taubenberger, Jeffery K. TI Characterizing and Diminishing Autofluorescence in Formalin-fixed Paraffin-embedded Human Respiratory Tissue SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE autofluorescence; formalin-fixation; paraffin-embedded tissue; immunohistochemistry; immunofluorescence; human; respiratory; confocal microscopy ID BACKGROUND AUTOFLUORESCENCE; IMMUNOFLUORESCENCE; REDUCTION; FLUORESCENCE; MICROSCOPY; COLLAGEN; CELLS AB Tissue autofluorescence frequently hampers visualization of immunofluorescent markers in formalin-fixed paraffin-embedded respiratory tissues. We assessed nine treatments reported to have efficacy in reducing autofluorescence in other tissue types. The three most efficacious were Eriochrome black T, Sudan black B and sodium borohydride, as measured using white light laser confocal (2) (multi-lambda) analysis. We also assessed the impact of steam antigen retrieval and serum application on human tracheal tissue autofluorescence. Functionally fitting this (2) data to 2-dimensional Gaussian surfaces revealed that steam antigen retrieval and serum application contribute minimally to autofluorescence and that the three treatments are disparately efficacious. Together, these studies provide a set of guidelines for diminishing autofluorescence in formalin-fixed paraffin-embedded human respiratory tissue. Additionally, these characterization techniques are transferable to similar questions in other tissue types, as demonstrated on frozen human liver tissue and paraffin-embedded mouse lung tissue fixed in different fixatives. C1 [Davis, A. Sally; Moyer, Jenna E.; Sandouk, Aline; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, NIH, Bethesda, MD 20892 USA. [Becker, Steven] NIAID, Bioimaging Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. [Skinner, Jeff] NIAID, Immunogenet Lab, Div Intramural Res, Bethesda, MD 20892 USA. [Richter, Anke] Naval Postgrad Sch, Def Resources Management Inst, Grad Sch Int Studies, Monterey, CA USA. [Davis, A. Sally] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC USA. RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov OI Davis, Anne/0000-0001-5711-3936; Skinner, Jeff/0000-0001-5697-0442 FU NIH; NIAID FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the intramural research funds of the NIH and the NIAID. NR 20 TC 4 Z9 4 U1 4 U2 19 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUN PY 2014 VL 62 IS 6 BP 405 EP 423 DI 10.1369/0022155414531549 PG 19 WC Cell Biology SC Cell Biology GA AJ3WN UT WOS:000337598700002 PM 24722432 ER PT J AU Rizvi, SM Salam, N Geng, J Qi, Y Bream, JH Duggal, P Hussain, SK Martinson, J Wolinsky, SM Carrington, M Raghavan, M AF Rizvi, Syed Monem Salam, Nasir Geng, Jie Qi, Ying Bream, Jay H. Duggal, Priya Hussain, Shehnaz K. Martinson, Jeremy Wolinsky, Steven M. Carrington, Mary Raghavan, Malini TI Distinct Assembly Profiles of HLA-B Molecules SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MHC CLASS-I; IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIGEN PRESENTATION; MONOCLONAL-ANTIBODIES; PEPTIDE PRESENTATION; HLA-B44 SUPERTYPE; HEAVY-CHAIN; TAPASIN; COMPLEX; HIV-1 AB MHC class I polymorphisms are known to influence outcomes in a number of infectious diseases, cancers, and inflammatory diseases. Human MHC class I H chains are encoded by the HLA-A, HLA-B, and HLA-C genes. These genes are highly polymorphic, with the HLA-B locus being the most variable. Each HLA class I protein binds to a distinct set of peptide Ags, which are presented to CD8(+) T cells. HLA-disease associations have been shown in some cases to link to the peptide-binding characteristics of individual HLA class I molecules. In this study, we show that polymorphisms at the HLA-B locus profoundly influence the assembly characteristics of HLA-B molecules and the stabilities of their peptide-deficient forms. In particular, dependence on the assembly factor tapasin is highly variable, with frequent occurrence of strongly tapasin-dependent or independent allotypes. Several polymorphic HLA-B residues located near the C-terminal end of the peptide are key determinants of tapasin-independent assembly. In vitro refolded forms of tapasin-independent allotypes assemble more readily with peptides compared to tapasin-dependent allotypes that belong to the same supertype, and, during refolding, reduced aggregation of tapasin-independent allotypes is observed. Paradoxically, in HIVinfected individuals, greater tapasin-independent HLA-B assembly confers more rapid progression to death, consistent with previous findings that some HLA-B allotypes shown to be tapasin independent are associated with rapid progression to multiple AIDS outcomes. Together, these findings demonstrate significant variations in the assembly of HLA-B molecules and indicate influences of HLA-B-folding patterns upon infectious disease outcomes. C1 [Rizvi, Syed Monem; Salam, Nasir; Geng, Jie; Raghavan, Malini] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. [Qi, Ying; Carrington, Mary] Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD 21702 USA. [Qi, Ying; Carrington, Mary] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA. [Qi, Ying; Carrington, Mary] Harvard Univ, Cambridge, MA 02139 USA. [Bream, Jay H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. [Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Hussain, Shehnaz K.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. [Hussain, Shehnaz K.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Martinson, Jeremy] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. [Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. RP Raghavan, M (reprint author), Univ Michigan, 5641 Med Sci Bldg 2,1150 West Med Ctr Dr, Ann Arbor, MI 48109 USA. EM malinir@umich.edu RI Salam, Nasir/C-8049-2015; OI Salam, Nasir/0000-0001-9133-1304; Martinson, Jeremy/0000-0003-4673-7238 FU National Institutes of Health [AI044115]; University of Michigan Medical School Protein Folding Disease Initiative; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; National Institute of Allergy and Infectious Diseases; National Cancer Institute FX This work was supported by National Institutes of Health Grant AI044115 (to M. R.) and in part by the University of Michigan Medical School Protein Folding Disease Initiative. This work utilized the DNA Sequencing and Hybridoma Cores of the University of Michigan Medical School. This work was also supported in part by Frederick National Laboratory for Cancer Research Contract HHSN261200800001E and by the Intramural Research Program of the National Institutes of Health, Frederick National Laboratory, Center for Cancer Research. Some data in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS) with centers (Principal Investigators) at: Johns Hopkins University Bloomberg School of Public Health (Joseph Margolick), U01-AI35042; Northwestern University (S. M. W.), U01-AI35039; University of California, Los Angeles (Roger Detels), U01-AI35040; University of Pittsburgh (Charles Rinaldo), U01-AI35041; the Center for Analysis and Management of MACS and Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases, with additional cofunding from the National Cancer Institute. NR 58 TC 15 Z9 15 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2014 VL 192 IS 11 BP 4967 EP 4976 DI 10.4049/jimmunol.1301670 PG 10 WC Immunology SC Immunology GA AI8MT UT WOS:000337171800007 PM 24790147 ER PT J AU Wu, ZL Chen, XC Liu, F Chen, W Wu, P Wieschhaus, AJ Chishti, AH Roche, PA Chen, WM Lin, TJ AF Wu, Zhengli Chen, Xiaochun Liu, Fang Chen, Wei Wu, Ping Wieschhaus, Adam J. Chishti, Athar H. Roche, Paul A. Chen, Wei-Min Lin, Tong-Jun TI Calpain-1 Contributes to IgE-Mediated Mast Cell Activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KINASE-C-ALPHA; KAPPA-B-ALPHA; MU-CALPAIN; CALCIUM; DEGRADATION; PLATELETS; SNAP-23; DEGRANULATION; NEURONS; PATHWAY AB Mast cells play a central role in allergy through secretion of both preformed and newly synthesized mediators. Mast cell mediator secretion is controlled by a complex network of signaling events. Despite intensive studies, signaling pathways in the regulation of Mast cell mediator secretion remain incompletely defined. In this study, we examined the role of calpain in IgE-dependent mast cell activation. IgE-mediated activation of mouse bone marrow-derived mast cells enhanced calpain activity. Inhibition of calpain activity by a number of calpain inhibitors reduced IgE-mediated mast cell degranulation both in vitro and in vivo. Calpain inhibitors blocked IgE-mediated TNF and IL-6 production in vitro and reduced late- phase allergic response in vivo. Importantly, mouse calpain-1 null bone marrow- derived mast cells showed reduced IgE-mediated mast cell degranulation in vitro and in vivo, diminished cytokine and chemokine production in vitro, and impaired late- phase allergic response in vivo. Further studies revealed that calpain-1 deficiency led to specific attenuation of IkB-NF-kB pathway and IKK-SNAP23 pathway, whereas calcium flux, MAPK, Akt, and NFAT pathway proceed normally in IgE- activated calpain-1 null mast cells. Thus, calpain-1 is identified as a novel regulator in IgE- mediated mast cell activation and could serve as a potential therapeutic target for the management of allergic inflammation. C1 [Wu, Zhengli; Liu, Fang; Wu, Ping; Lin, Tong-Jun] Dalhousie Univ, IWK Hlth Ctr, Dept Microbiol & Immunol, Halifax, NS B3K 6R8, Canada. [Wu, Zhengli; Liu, Fang; Wu, Ping; Lin, Tong-Jun] Dalhousie Univ, IWK Hlth Ctr, Dept Pediat, Halifax, NS B3K 6R8, Canada. [Chen, Xiaochun] Fujian Med Univ, Affiliated Union Hosp, Dept Neurol, Fuzhou 350001, Fujian, Peoples R China. [Chen, Wei] Jilin Univ, Coll Vet Med, Changchun 130062, Jilin, Peoples R China. [Wieschhaus, Adam J.; Chishti, Athar H.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Mol Physiol & Pharmacol, Boston, MA 02111 USA. [Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Chen, Wei-Min] Fujian Prov Hosp, Dept Hematol, Fuzhou 350000, Fujian, Peoples R China. RP Lin, TJ (reprint author), IWK Hlth Ctr, Dept Pediat, 5850 Univ Ave, Halifax, NS B3K 6R8, Canada. EM chenweiming@medmail.com.cn; tong-jun.lin@dal.ca FU Canadian Institutes of Health Research; Izaak Walton Killam Health Center; National Institutes of Health Grant [NIH-HL089517] FX This work was supported by grants from the Canadian Institutes of Health Research and the Izaak Walton Killam Health Center (to T.-J.L.) and National Institutes of Health Grant NIH-HL089517 (to A.H.C.). Z.W. is a recipient of a postdoctoral fellowship from the Izaak Walton Killam Health Center. NR 41 TC 5 Z9 5 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2014 VL 192 IS 11 BP 5130 EP 5139 DI 10.4049/jimmunol.1301677 PG 10 WC Immunology SC Immunology GA AI8MT UT WOS:000337171800024 PM 24760147 ER PT J AU Xu, LL Li, G Wang, J Fan, YL Wan, ZP Zhang, SS Shaheen, S Li, J Wang, L Yue, C Zhao, Y Wang, F Brzostowski, J Chen, YH Zheng, WJ Liu, WL AF Xu, Liling Li, Gen Wang, Jing Fan, Yilin Wan, Zhengpeng Zhang, Shaosen Shaheen, Samina Li, Jing Wang, Li Yue, Cai Zhao, Yan Wang, Fei Brzostowski, Joseph Chen, Ying-Hua Zheng, Wenjie Liu, Wanli TI Through an ITIM-Independent Mechanism the Fc gamma RIIB Blocks B Cell Activation by Disrupting the Colocalized Microclustering of the B Cell Receptor and CD19 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FAMILY-BASED ASSOCIATION; ANTIGEN RECEPTOR; LIPID RAFTS; CD19/CD21 COMPLEX; GENETIC SUSCEPTIBILITY; SIGNAL-TRANSDUCTION; AUTOIMMUNE-DISEASE; IMMUNE SYNAPSE; POLYMORPHISM AB B cell activation is regulated through the interplay of the BCR with the inhibitory coreceptor Fc gamma RIIB and the activating coreceptor CD19. Recent studies suggest that Ag-driven BCR microclusters are efficiently converted to a signaling active state on colocalization with CD19 microclusters. Using total internal reflection fluorescence microscopy-based, high-resolution, high-speed live-cell and molecule imaging approaches, we show that when co-ligated to the BCR, the Fc gamma RIIB can inhibit B cell activation by blocking the colocalization of BCR and CD19 microclusters within the B cell immunological synapse. Remarkably, this inhibitory function of FcgRIIB is dependent not on its well-characterized ITIM-containing cytoplasmic domain, but its transmembrane domain. Indeed, human primary B cells from systemic lupus erythematosus patients homozygous for gene encoding the loss-of-function transmembrane domain mutant Fc gamma RIIB-I232T fail to block the synaptic colocalization of the BCR with CD19, leading to dysregulated recruitment of downstream signaling molecule p-PI3K to membrane proximal signalosome. This inhibitory function of Fc gamma RIIB in impairing the spatial-temporal colocalization of BCR and CD19 microclusters in the B cell immunological synapse may help explain the hyper-reactive features of systemic lupus erythematosus patient B cells in reported studies. These observations may also provide new targets for therapies for systemic autoimmune disease. C1 [Xu, Liling; Li, Gen; Wang, Jing; Fan, Yilin; Wan, Zhengpeng; Zhang, Shaosen; Shaheen, Samina; Chen, Ying-Hua; Liu, Wanli] Tsinghua Univ, Sch Life Sci, Minist Educ, Key Lab Prot Sci, Beijing 100084, Peoples R China. [Xu, Liling; Li, Gen; Li, Jing; Wang, Li; Yue, Cai; Zhao, Yan; Zheng, Wenjie] Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Beijing 100730, Peoples R China. [Xu, Liling; Li, Gen; Li, Jing; Wang, Li; Yue, Cai; Zhao, Yan; Zheng, Wenjie] Chinese Acad Med Sci, Beijing 100730, Peoples R China. [Li, Jing; Wang, Li; Yue, Cai; Zhao, Yan; Zheng, Wenjie] Minist Educ, Key Lab Rheumatol & Clin Immunol, Beijing 100730, Peoples R China. [Wang, Fei] Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Peoples R China. [Brzostowski, Joseph] NIAID, Immunogenet Lab, Imaging Facil, NIH, Rockville, MD 20852 USA. [Liu, Wanli] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Collaborat Innovat Ctr Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China. RP Liu, WL (reprint author), Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. EM chenyh@mail.tsinghua.edu.cn; wenjzheng@gmail.com; liuwanli@biomed.tsinghua.edu.cn FU Ministry of Science and Technology of China [2014CB542500, 2014AA020527]; National Science Foundation of China [81361120384, 31270913]; Beijing Natural Science Foundation [5132016]; Ph.D. Programs Foundation of Ministry of Education of China [20130002110059, 20120002120007]; Tsinghua University Initiative Scientific Research Program [20131089279]; Chinese Medical Association [12040670367] FX This work was supported by the Ministry of Science and Technology of China (Grants 2014CB542500 and 2014AA020527), the National Science Foundation of China (Grants 81361120384 and 31270913), the Beijing Natural Science Foundation (Grant 5132016), the Ph.D. Programs Foundation of Ministry of Education of China (Grants 20130002110059 and 20120002120007), the Tsinghua University Initiative Scientific Research Program (Grant 20131089279), and the Chinese Medical Association (Grant 12040670367). NR 53 TC 6 Z9 9 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2014 VL 192 IS 11 BP 5179 EP 5191 DI 10.4049/jimmunol.1400101 PG 13 WC Immunology SC Immunology GA AI8MT UT WOS:000337171800029 PM 24790152 ER PT J AU Percopo, CM Dyer, KD Garcia-Crespo, KE Gabryszewski, SJ Shaffer, AL Domachowske, JB Rosenberg, HF AF Percopo, Caroline M. Dyer, Kimberly D. Garcia-Crespo, Katia E. Gabryszewski, Stanislaw J. Shaffer, Arthur L., III Domachowske, Joseph B. Rosenberg, Helene F. TI B Cells Are Not Essential for Lactobacillus-Mediated Protection against Lethal Pneumovirus Infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLUENZA-VIRUS INFECTION; LYMPHOID-TISSUE IBALT; INNATE IMMUNITY; MICE; PNEUMONIA; RESISTANCE; MACROPHAGES; ACTIVATION; PATHOLOGY; ANTIBODY AB We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice, a property known as heterologous immunity. Lactobacillus priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. Because B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, in this study we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway Igs IgG, IgA, and IgM and lung tissues with dense, B cell (B220(+))-enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of BALT. No B cells were detected in lung tissue of Lactobacillus-primed B cell deficient mu MT mice or Jh mice, and Lactobacillus-primed mu MT mice had no characteristic infiltrates or airway Igs. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-gamma and CXCL10 in both wild-type and Lactobacillus-primed mu MT mice. Furthermore, Lactobacillus plantarum-primed, B cell-deficient mu MTand Jh mice were fully protected from an otherwise lethal pneumonia virus of mice infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection. C1 [Percopo, Caroline M.; Dyer, Kimberly D.; Garcia-Crespo, Katia E.; Gabryszewski, Stanislaw J.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, NIH, Bethesda, MD 20892 USA. [Shaffer, Arthur L., III] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. [Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. RP Rosenberg, HF (reprint author), NIAID, Bldg 10,Room 11C215,MSC 1883,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases Division of Intramural Research [AI000943] FX This work was supported by National Institute of Allergy and Infectious Diseases Division of Intramural Research AI000943 (to H.F.R.). NR 40 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2014 VL 192 IS 11 BP 5265 EP 5272 DI 10.4049/jimmunol.1400087 PG 8 WC Immunology SC Immunology GA AI8MT UT WOS:000337171800037 PM 24748495 ER PT J AU Ramirez, CM Lin, CS Abdelmohsen, K Goedeke, L Yoon, JH Madrigal-Matute, J Martin-Ventura, JL Vo, DT Uren, PJ Penalva, LO Gorospe, M Fernandez-Hernando, C AF Ramirez, Cristina M. Lin, Chin Sheng Abdelmohsen, Kotb Goedeke, Leigh Yoon, Je-Hyun Madrigal-Matute, Julio Martin-Ventura, Jose L. Vo, Dat T. Uren, Philip J. Penalva, Luiz O. Gorospe, Myriam Fernandez-Hernando, Carlos TI RNA binding protein HuR regulates the expression of ABCA1 SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ATP binding cassette transporter A1; human antigen R; posttranscriptional regulation; lipid homeostasis; cholesterol efflux ID HIGH-DENSITY-LIPOPROTEIN; CASSETTE TRANSPORTER A1; CHOLESTEROL EFFLUX; POSTTRANSCRIPTIONAL REGULATION; OXIDATIVE STRESS; LIPID-METABOLISM; MESSENGER-RNAS; TRANSLATION; MICRORNAS; DISEASE AB ABCA1 is a major regulator of cellular cholesterol efflux and plasma HDL biogenesis. Even though the transcriptional activation of ABCA1 is well established, the posttranscriptional regulation of ABCA1 expression is poorly understood. Here, we investigate the potential contribution of the RNA binding protein (RBP) human antigen R (HuR) on the posttranscriptional regulation of ABCA1 expression. RNA immunoprecipitation assays demonstrate a direct interaction between HuR and ABCA1 mRNA. We found that HuR binds to the 3' untranslated region of ABCA1 and increases ABCA1 translation, while HuR silencing reduces ABCA1 expression and cholesterol efflux to ApoA1 in human hepatic (Huh-7) and monocytic (THP-1) cells. Interestingly, cellular cholesterol levels regulate the expression, intracellular localization, and interaction between HuR and ABCA1 mRNA. Finally, we found that HuR expression was significantly increased in macrophages from human atherosclerotic plaques, suggesting an important role for this RBP in controlling macrophage cholesterol metabolism in vivo. In summary, we have identified HuR as a novel posttranscriptional regulator of ABCA1 expression and cellular cholesterol homeostasis, thereby opening new avenues for increasing cholesterol efflux from atherosclerotic foam macrophages and raising circulating HDL cholesterol levels. C1 [Ramirez, Cristina M.; Goedeke, Leigh; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, Dept Comparat Med, New Haven, CT 06520 USA. [Ramirez, Cristina M.; Lin, Chin Sheng; Goedeke, Leigh; Madrigal-Matute, Julio; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Med, New York, NY 10016 USA. [Ramirez, Cristina M.; Lin, Chin Sheng; Goedeke, Leigh; Madrigal-Matute, Julio; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. [Lin, Chin Sheng] Triserv Gen Hosp, Natl Def Med Ctr, Div Cardiol, Dept Med, Taipei, Taiwan. [Abdelmohsen, Kotb; Yoon, Je-Hyun; Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Martin-Ventura, Jose L.] Univ Autonoma Madrid, IIS Fundac Jimenez Diaz, Vasc Res Lab, Madrid 28040, Spain. [Vo, Dat T.; Penalva, Luiz O.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Uren, Philip J.] Univ So Calif, Los Angeles, CA 90089 USA. RP Fernandez-Hernando, C (reprint author), Yale Univ, Sch Med, Vasc Biol & Therapeut Program, Dept Comparat Med, 333 Cedar St, New Haven, CT 06520 USA. EM carlos.fernandez@yale.edu OI Ramirez, Cristina M/0000-0003-2589-0786 FU National Institutes of Health [R01HL107953, R01HL106063, 1F31AG043318]; American Heart Association [12POST9780016]; Tri-Service General Hospital [TSGH-C103-027]; National Institute on Aging-Intramural Research Program; National Institutes of Health FX This work was supported by National Institutes of Health Grants R01HL107953 and R01HL106063 (C.F-H.) and 1F31AG043318-01 (L. G.), and American Heart Association Grant 12POST9780016 (C. M. R.). C. S. Lin was supported by Tri-Service General Hospital (TSGH-C103-027). K. Abdelmohsen, J-H. Yoon, and M. Gorospe were supported by the National Institute on Aging-Intramural Research Program, the National Institutes of Health. NR 41 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD JUN PY 2014 VL 55 IS 6 BP 1066 EP 1076 DI 10.1194/jlr.M044925 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AI8BY UT WOS:000337130900008 PM 24729624 ER PT J AU Kim, DS Crosslin, DR Auer, PL Suzuki, SM Marsillach, J Burt, AA Gordon, AS Meschia, JF Nalls, MA Worrall, BB Longstreth, WT Gottesman, RF Furlong, CE Peters, U Rich, SS Nickerson, DA Jarvik, GP AF Kim, Daniel Seung Crosslin, David R. Auer, Paul L. Suzuki, Stephanie M. Marsillach, Judit Burt, Amber A. Gordon, Adam S. Meschia, James F. Nalls, Mike A. Worrall, Bradford B. Longstreth, W. T., Jr. Gottesman, Rebecca F. Furlong, Clement E. Peters, Ulrike Rich, Stephen S. Nickerson, Deborah A. Jarvik, Gail P. CA NHLBI Exome Sequencing Project TI Rare coding variation in paraoxonase-1 is associated with ischemic stroke in the NHLBI Exome Sequencing Project SO JOURNAL OF LIPID RESEARCH LA English DT Article DE rare variation; genetics; atherosclerosis ID MISSING HERITABILITY; VASCULAR-DISEASE; HEART-DISEASE; CHOLESTEROL; POLYMORPHISMS; DIETARY AB HDL-associated paraoxonase-1 (PON1) is an enzyme whose activity is associated with cerebrovascular disease. Common PON1 genetic variants have not been consistently associated with cerebrovascular disease. Rare coding variation that likely alters PON1 enzyme function may be more strongly associated with stroke. The National Heart, Lung, and Blood Institute Exome Sequencing Project sequenced the coding regions (exomes) of the genome for heart, lung, and blood-related phenotypes (including ischemic stroke). In this sample of 4,204 unrelated participants, 496 had verified, noncardioembolic ischemic stroke. After filtering, 28 nonsynonymous PON1 variants were identified. Analysis with the sequence kernel association test, adjusted for covariates, identified significant associations between PON1 variants and ischemic stroke (P = 3.01 x 10(-3)). Stratified analyses demonstrated a stronger association of PON1 variants with ischemic stroke in African ancestry (AA) participants (P = 5.03 x 10(-3)). Ethnic differences in the association between PON1 variants with stroke could be due to the effects of PON1(Val109Ile) (overall P = 7.88 x 10(-3); AA P = 6.52 x 10(- 4)), found at higher frequency in AA participants (1.16% vs. 0.02%) and whose protein is less stable than the common allele. In summary, rare genetic variation in PON1 was associated with ischemic stroke, with stronger associations identified in those of AA. Increased focus on PON1 enzyme function and its role in cerebrovascular disease is warranted. C1 [Kim, Daniel Seung; Crosslin, David R.; Suzuki, Stephanie M.; Marsillach, Judit; Burt, Amber A.; Furlong, Clement E.; Jarvik, Gail P.] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Kim, Daniel Seung; Crosslin, David R.; Marsillach, Judit; Gordon, Adam S.; Furlong, Clement E.; Nickerson, Deborah A.; Jarvik, Gail P.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA. [Auer, Paul L.; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Auer, Paul L.] Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Nalls, Mike A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Worrall, Bradford B.; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Longstreth, W. T., Jr.; Peters, Ulrike] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Gottesman, Rebecca F.] Johns Hopkins Univ, Sch Med, Dept Neurol, Cerebrovasc Div, Baltimore, MD 21205 USA. RP Jarvik, GP (reprint author), Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA. EM pair@u.washington.edu RI Jarvik, Gail/N-6476-2014; Marsillach, Judit/I-1329-2015 OI Jarvik, Gail/0000-0002-6710-8708; Marsillach, Judit/0000-0002-3061-6266 FU WA State Life Sciences Discovery Fund [265508]; National Heart, Lung, and Blood Institute (NHLBI); LungGO Sequencing Project [HL-102923]; Women's Health Initiative Sequencing Project [HL-102924]; BroadGO Sequencing Project [HL-102925]; SeattleGO Sequencing Project [HL-102926]; HeartGO Sequencing Project [HL-103010]; National Institutes of Health (NIH) [ES09883, T32ES007032]; Intramural Research Program of the National Institute of Aging, NIH [Z01 AG-000954-06]; Benjamin and Margaret Hall Endowed Fellowship in Genome Sciences; Markey Foundation award; NIH [5T31HG000035-18, 1F31MH101905-01] FX This work was supported in part by WA State Life Sciences Discovery Fund (265508, to the Northwest Institute of Genetic Medicine). The National Heart, Lung, and Blood Institute (NHLBI) funded the multicenter effort with the following grants: the LungGO Sequencing Project (HL-102923), the Women's Health Initiative Sequencing Project (HL-102924), the BroadGO Sequencing Project (HL-102925), the SeattleGO Sequencing Project (HL-102926), and the HeartGO Sequencing Project (HL-103010). This work was also supported by National Institutes of Health (NIH) Grants ES09883 and T32ES007032 (S. M. S.); the Intramural Research Program of the National Institute of Aging, NIH Project Z01 AG-000954-06 (M.A.N.); and the Benjamin and Margaret Hall Endowed Fellowship in Genome Sciences, a Markey Foundation award, and NIH Grants 5T31HG000035-18 and 1F31MH101905-01 (D. S. K.). Funding sources for specific cohorts are presented in the supplementary NHLBI Exome Sequencing Project (ESP) Banner. NR 20 TC 11 Z9 12 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 EI 1539-7262 J9 J LIPID RES JI J. Lipid Res. PD JUN PY 2014 VL 55 IS 6 BP 1173 EP 1178 DI 10.1194/jlr.P049247 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AI8BY UT WOS:000337130900018 PM 24711634 ER PT J AU Friedman, DI McDermott, MP Kieburtz, K Kupersmith, M Stoutenburg, A Keltner, JL Feldon, SE Schron, E Corbett, JJ Wall, M AF Friedman, Deborah I. McDermott, Michael P. Kieburtz, Karl Kupersmith, Mark Stoutenburg, Ann Keltner, John L. Feldon, Steven E. Schron, Eleanor Corbett, James J. Wall, Michael CA NORDIC IIHTT Study Grp TI The Idiopathic Intracranial Hypertension Treatment Trial: Design Considerations and Methods SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID RETINOL-BINDING-PROTEIN; QUALITY-OF-LIFE; PSEUDOTUMOR CEREBRI; WEIGHT-LOSS; PHONE INTERVENTIONS; CEREBROSPINAL-FLUID; VITAMIN-A; ACETAZOLAMIDE; PAPILLEDEMA; DEPRESSION AB Background: The objectives of this study were to present the rationale for the main aspects of the study design and describe the trial methodology for the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). Methods: Eligible candidates with mild visual field loss (automated perimetric mean deviation [PMD] 22 to 27 dB) were randomized to receive either acetazolamide or matching placebo tablets. Randomized participants were offered participation in a supervised dietary program. The primary outcome variable, PMD, was measured at 6 months. Additionally, cerebrospinal fluid from subjects and serum from study participants and matched controls were collected for genetic analysis and vitamin A studies. An ancillary optical coherence substudy was added to investigate the changes of papilledema in the optic nerve head and retina that correlate with Frisen grading, visual field deficits, and low-contrast visual acuity. Results: The randomized trial entered 165 participants from March 17, 2010, through November 27, 2012, from the United States and Canada. The primary outcome (month 6) visits were successfully completed by June 15, 2013. Blood specimens were obtained from 165 controls without IIH to investigate vitamin A metabolism and genetic markers of potential risk factors for IIH. Conclusions: The IIHTT is the first randomized, double-masked placebo-controlled trial to study the effectiveness of medical treatment for patients with IIH. (C) 2014 by North American Neuro-Ophthalmology Society C1 [Friedman, Deborah I.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA. [Friedman, Deborah I.] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA. [Feldon, Steven E.] Univ Rochester, Sch Med & Dent, Dept Ophthalmol, Rochester, NY USA. [McDermott, Michael P.; Feldon, Steven E.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Feldon, Steven E.] Univ Rochester, Sch Med & Dent, Dept Neurosurg, Rochester, NY USA. [Feldon, Steven E.] Univ Rochester, Sch Med & Dent, Dept Visual Sci, Rochester, NY USA. [Kieburtz, Karl; Stoutenburg, Ann] Univ Rochester, Sch Med & Dent, Ctr Human Expt Therapeut, Rochester, NY USA. [McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY USA. [Wall, Michael] Univ Iowa, Coll Med, Iowa City, IA USA. [Wall, Michael] Iowa City Vet Affairs Hlth Care Syst, Iowa City, IA USA. [Schron, Eleanor] NEI, Bethesda, MD 20892 USA. [Keltner, John L.] Univ Calif Davis, Med Ctr, Dept Ophthalmol & Vis Sci, Sacramento, CA 95817 USA. [Kupersmith, Mark] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Kupersmith, Mark] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. RP Friedman, DI (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd,MC 9036, Dallas, TX 75390 USA. EM Deborah.Friedman@utsouthwestern.edu OI Bruce, Beau/0000-0003-3003-2962 FU National Eye Institute [1U10EY017281-01A1, 1U10EY017387-01A1, 3U10EY017281-01A1S1, 3U10EY017281-01A1S2] FX Supported by National Eye Institute (1U10EY017281-01A1, 1U10EY017387-01A1, 3U10EY017281-01A1S1, 3U10EY017281-01A1S2). NR 54 TC 21 Z9 21 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 EI 1536-5166 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 2014 VL 34 IS 2 BP 107 EP 117 DI 10.1097/WNO.0000000000000114 PG 11 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA AI9IL UT WOS:000337246200002 PM 24739993 ER PT J AU Deyo, RA Dworkin, SF Amtmann, D Andersson, G Borenstein, D Carragee, E Carrino, J Chou, R Cook, K DeLitto, A Goertz, C Khalsa, P Loeser, J Mackey, S Panagis, J Rainville, J Tosteson, T Turk, D Von Korff, M Weinertt, DK AF Deyo, Richard A. Dworkin, Samuel F. Amtmann, Dagmar Andersson, Gunnar Borenstein, David Carragee, Eugene Carrino, John Chou, Roger Cook, Karon DeLitto, Anthony Goertz, Christine Khalsa, Partap Loeser, John Mackey, Sean Panagis, James Rainville, James Tosteson, Tor Turk, Dennis Von Korff, Michael Weinertt, Debra K. TI Report of the NIH Task Force on Research Standards for Chronic Low Back Pain SO JOURNAL OF PAIN LA English DT Article DE Low back pain; chronic low back pain; research standards; minimum dataset; NIH Task Force ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM PROMIS; FUNCTION ITEM BANK; QUALITY-OF-LIFE; PRIMARY-CARE; PROGNOSTIC APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES AB Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Therefore, NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum dataset to describe research participants (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. We expect that the RTF recommendations will become a dynamic document and undergo continual improvement. Perspective: A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. (C) 2014 by the American Pain Society. Published by Elsevier Inc. All rights reserved C1 [Deyo, Richard A.; Chou, Roger] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Dworkin, Samuel F.; Amtmann, Dagmar; Loeser, John; Turk, Dennis] Univ Washington, Seattle, WA 98195 USA. [Andersson, Gunnar] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Borenstein, David] George Washington Univ, Washington, DC USA. [Carragee, Eugene; Mackey, Sean] Stanford Univ, Stanford, CA 94305 USA. [Carrino, John] Johns Hopkins Univ, Baltimore, MD USA. [Cook, Karon] Northwestern Univ, Evanston, IL USA. [DeLitto, Anthony; Weinertt, Debra K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [DeLitto, Anthony; Weinertt, Debra K.] Univ Pittsburgh, Pittsburgh, PA USA. [Goertz, Christine] Palmer Coll Chiropract, Davenport, IA USA. [Khalsa, Partap] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Panagis, James] NIAMSD, Bethesda, MD 20892 USA. [Rainville, James] New England Baptist Hosp, Roxbury Crossing, MA USA. [Tosteson, Tor] Dartmouth Coll, Hanover, NH USA. [Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA. RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deyor@ohsu.edu FU National Center for Complementary and Alternative Medicine; National Institute for Arthritis, Musculoskeletal, and Skin Diseases FX This study was supported by the National Center for Complementary and Alternative Medicine and the National Institute for Arthritis, Musculoskeletal, and Skin Diseases. NR 127 TC 29 Z9 29 U1 9 U2 19 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JUN PY 2014 VL 15 IS 6 BP 569 EP 585 DI 10.1016/j.jpain.2014.03.005 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AJ0HM UT WOS:000337331400001 PM 24787228 ER PT J AU Beck, JD Youngblood, M Atkinson, JC Mauriello, S Kaste, LM Badner, VM Beaver, S Becerra, K Singer, R AF Beck, James D. Youngblood, Marston, Jr. Atkinson, Jane C. Mauriello, Sally Kaste, Linda M. Badner, Victor M. Beaver, Shirley Becerra, Karen Singer, Richard TI The prevalence of caries and tooth loss among participants in the Hispanic Community Health Study/Study of Latinos SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Hispanic; Latino; caries; tooth loss ID DESIGN AB Background. The Hispanic and Latino population is projected to increase from 16.7 percent to 30.0 percent by 2050. Previous U. S. national surveys had minimal representation of Hispanic and Latino participants other than Mexicans, despite evidence suggesting that Hispanic or Latino country of origin and degree of acculturation influence health outcomes in this population. In this article, the authors describe the prevalence and mean number of cavitated, decayed and filled surfaces, missing teeth and edentulism among Hispanics and Latinos of different national origins. Methods. Investigators in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)-Pa multicenter epidemiologic study funded by the National Heart, Lung, and Blood Institute with funds transferred from six other institutes, including the National Institute of Dental and Craniofacial Research-Pconducted in-Pperson examinations and interviews with more than 16,000 participants aged 18 to 74 years in four U. S. cities between March 2008 and June 2011. The investigators identified missing, filled and decayed teeth according to a modified version of methods used in the National Health and Nutrition Examination Survey. The authors computed prevalence estimates (weighted percentages), weighted means and standard errors for measures. Results. The prevalence of decayed surfaces ranged from 20.2 percent to 35.5 percent, depending on Hispanic or Latino background, whereas the prevalence of decayed and filled surfaces ranged from 82.7 percent to 87.0 percent, indicating substantial amounts of dental treatment. The prevalence of missing teeth ranged from 49.8 percent to 63.8 percent and differed according to Hispanic or Latino background. Significant differences in the mean number of decayed surfaces, decayed or filled surfaces and missing teeth according to Hispanic and Latino background existed within each of the age groups and between women and men. Conclusions. Oral health status differs according to Hispanic or Latino background, even with adjustment for age, sex and other characteristics. C1 [Beck, James D.; Mauriello, Sally] Univ N Carolina, Sch Dent, Dept Dent Ecol, Chapel Hill, NC 27599 USA. [Youngblood, Marston, Jr.] Hispan Community Hlth Study Study Latinos, Chapel Hill, NC USA. [Youngblood, Marston, Jr.] Univ N Carolina, Collaborat Studies Coordinating Ctr, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Atkinson, Jane C.] Natl Inst Dent & Craniofacial Res, Clin Res Ctr, Div Extramural Res, Bethesda, MD USA. [Kaste, Linda M.] Univ Illinois, Dept Pediat Dent, Coll Dent, Chicago, IL 60680 USA. [Badner, Victor M.] Yeshiva Univ, Albert Einstein Coll Med, Dept Dent, Bronx, NY USA. [Badner, Victor M.] Yeshiva Univ, Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA. [Badner, Victor M.] Yeshiva Univ, Albert Einstein Coll Med, Dept Dent, Jacobi Med Ctr, Bronx, NY USA. [Beaver, Shirley] Stanford Brown Coll, Dent Hyg Program, Skokie, IL USA. [Becerra, Karen] Gary & Mary West Hlth Inst, San Diego, CA USA. [Singer, Richard] Nova SE Univ, Coll Dent Med, Dept Orthodont, Ft Lauderdale, FL 33314 USA. RP Beck, JD (reprint author), Univ N Carolina, Sch Dent, Dept Dent Ecol, 1617 Koury Oral Hlth Sci Bldg,CB 7450, Chapel Hill, NC 27599 USA. EM james_beck@unc.edu FU National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina, Chapel Hill [N01-HC65233]; University of Miami [N01-HC65234]; Albert Einstein College of Medicine, Bronx [N01-HC65235]; Northwestern University, Evanston, Ill. [N01-HC65236]; San Diego State University [N01-HC65237]; NHLBI; National Center on Minority Health and Health Disparities; National Institute on Deafness and Other Communication Disorders; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Neurological Disorders and Stroke; National Institutes of Health Office of Dietary Supplements FX The Hispanic/Latino Community Health Study/Study of Latinos was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina, Chapel Hill (N01-HC65233); the University of Miami (N01-HC65234); Albert Einstein College of Medicine, Bronx, N.Y. (N01-HC65235); Northwestern University, Evanston, Ill. (N01-HC65236); and San Diego State University (N01-HC65237). The following institutes, centers and offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: the National Center on Minority Health and Health Disparities, the National Institute on Deafness and Other Communication Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health Office of Dietary Supplements. NR 20 TC 7 Z9 7 U1 1 U2 4 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUN PY 2014 VL 145 IS 6 BP 531 EP 540 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AI8MS UT WOS:000337171600006 PM 24878707 ER PT J AU Haley, DF Golin, C El-Sadr, W Hughes, JP Wang, J Isler, MR Mannheimer, S Kuo, I Lucas, J DiNenno, E Justman, J Frew, PM Emel, L Rompalo, A Polk, S Adimora, AA Rodriquez, L Soto-Torres, L Hodder, S AF Haley, Danielle F. Golin, Carol El-Sadr, Wafaa Hughes, James P. Wang, Jing Isler, Malika Roman Mannheimer, Sharon Kuo, Irene Lucas, Jonathan DiNenno, Elizabeth Justman, Jessica Frew, Paula M. Emel, Lynda Rompalo, Anne Polk, Sarah Adimora, Adaora A. Rodriquez, Lorenna Soto-Torres, Lydia Hodder, Sally CA HIV Prevention Trials Network HPTN TI Venue-Based Recruitment of Women at Elevated Risk for HIV: An HIV Prevention Trials Network Study SO JOURNAL OF WOMENS HEALTH LA English DT Article ID SEXUALLY-TRANSMITTED INFECTIONS; BEHAVIORAL SURVEILLANCE SYSTEM; VACCINE EFFICACY TRIALS; AFRICAN-AMERICAN WOMEN; UNITED-STATES; CLINICAL-TRIALS; INCARCERATION RATES; HEALTH DISPARITIES; SEX PARTNERS; US AB Background: The challenge of identifying and recruiting U. S. women at elevated risk for HIV acquisition impedes prevention studies and services. HIV Prevention Trials Network (HPTN) 064 was a U. S. multisite, longitudinal cohort study designed to estimate HIV incidence among women living in communities with prevalent HIV and poverty. Venue-based sampling (VBS) methodologies and participant and venue characteristics are described. Methods: Eligible women were recruited from 10 U. S. communities with prevalent HIV and poverty using VBS. Participant eligibility criteria included age 18-44 years, residing in a designated census tract/zip code, and self-report of at least one high-risk personal and/or male sexual partner characteristic associated with HIV acquisition (e. g., incarceration history). Ethnography was conducted to finalize recruitment areas and venues. Results: Eight thousand twenty-nine women were screened and 2,099 women were enrolled (88% black, median age 29 years) over 14 months. The majority of participants were recruited from outdoor venues (58%), retail spaces (18%), and social service organizations (13%). The proportion of women recruited per venue category varied by site. Most participants (73%) had both individual and partner characteristics that qualified them for the study; 14% were eligible based on partner risk only. Conclusion: VBS is a feasible and effective approach to rapidly recruit a population of women at enhanced risk for HIV in the United States. Such a recruitment approach is needed in order to engage women most at risk and requires strong community engagement. C1 [Haley, Danielle F.; Lucas, Jonathan] FHI 360, Durham, NC USA. [Haley, Danielle F.; Frew, Paula M.] Emory Univ, Dept Behav Sci & Hlth Educ, Rollins Sch Publ Hlth, Atlanta, GA 30033 USA. [Golin, Carol; Adimora, Adaora A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Golin, Carol; Adimora, Adaora A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [El-Sadr, Wafaa; Justman, Jessica] Columbia Univ, Mailman Sch Publ Hlth, Int Ctr AIDS Care & Treatment Programs, New York, NY USA. [Hughes, James P.; Wang, Jing; Emel, Lynda] Fred Hutchinson Canc Res Ctr, Dept Biostat, Seattle, WA 98104 USA. [Hughes, James P.] Univ Washington, Div Infect Dis, Seattle, WA 98195 USA. [Isler, Malika Roman] Univ N Carolina, Sch Med, Dept Social Med, Chapel Hill, NC USA. [Isler, Malika Roman] Univ N Carolina, North Carolina Translat & Clin Sci Inst, Chapel Hill, NC USA. [Mannheimer, Sharon] Columbia Univ, Harlem Hosp Ctr, New York, NY USA. [Mannheimer, Sharon] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Kuo, Irene] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. [DiNenno, Elizabeth] Ctr Dis Control & Prevent, Atlanta, GA USA. [Frew, Paula M.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA 30033 USA. [Rompalo, Anne; Polk, Sarah] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Rodriquez, Lorenna] Bronx Lebanon Hosp Ctr, New York, NY USA. [Soto-Torres, Lydia] NIAID, NIH, Bethesda, MD 20892 USA. [Hodder, Sally] Rutgers State Univ, New Jersey Med Sch, Newark, NJ 07102 USA. RP Haley, DF (reprint author), Emory Univ, Dept Behav Sci & Hlth Educ, 1518 Clifton Rd Northeast, Atlanta, GA 30033 USA. EM dfhaley@emory.edu OI Frew, Paula/0000-0002-3078-9124 FU National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse; National Institute of Mental Health [UM1 AI068619, U01-AI068613, UM1-AI068613]; Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University [5U1Al069466]; University of North Carolina Clinical Trials Unit [AI069423]; University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award [RR 025747]; University of North Carolina Center for AIDS Research [AI050410]; Emory University HIV/AIDS Clinical Trials Unit [5UO1AI069418]; Center for AIDS Research [P30 AI050409]; Clinical and Translational Science Award [UL1 RR025008]; Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit [5 UM1 AI069503-07]; Johns Hopkins Adult AIDS Clinical Trial Unit [AI069465]; Johns Hopkins Clinical and Translational Science Award [UL1 RR 25005]; HPTN Scholars Program; National Institute of Allergy and Infectious Disease; National Institute of Mental Health; Emory University Laney Graduate School Robert W. Woodruff Pre-Doctoral Fellowship; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Centers for Disease Control and Prevention; HPTN FX Funding for this study provided through grants from the National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, and National Institute of Mental Health (UM1 AI068619, U01-AI068613, and UM1-AI068613); Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University (5U1Al069466); University of North Carolina Clinical Trials Unit (AI069423); University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award (RR 025747); University of North Carolina Center for AIDS Research (AI050410); Emory University HIV/AIDS Clinical Trials Unit (5UO1AI069418), Center for AIDS Research (P30 AI050409), and Clinical and Translational Science Award (UL1 RR025008); The Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit(5 UM1 AI069503-07); The Johns Hopkins Adult AIDS Clinical Trial Unit (AI069465); The Johns Hopkins Clinical and Translational Science Award (UL1 RR 25005); and the HPTN Scholars Program funded by the National Institute of Allergy and Infectious Disease and the National Institute of Mental Health. The primary author's time has been supported in part by the Emory University Laney Graduate School Robert W. Woodruff Pre-Doctoral Fellowship.; The views expressed herein are those of the authors and do not necessarily represent the views of the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institutes of Health, the Centers for Disease Control and Prevention, the HPTN, or its funders. NR 58 TC 4 Z9 4 U1 1 U2 12 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD JUN PY 2014 VL 23 IS 6 BP 541 EP 551 DI 10.1089/jwh.2013.4654 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA AI9BT UT WOS:000337222700011 PM 24742266 ER PT J AU Whitson, HE Arnold, AM Yee, LM Mukamal, KJ Kizer, JR Djousse, L Ix, JH Siscovick, D Tracy, RP Thielke, SM Hirsch, C Newman, AB Zieman, S AF Whitson, Heather E. Arnold, Alice M. Yee, Laura M. Mukamal, Kenneth J. Kizer, Jorge R. Djousse, Luc Ix, Joachim H. Siscovick, David Tracy, Russell P. Thielke, Stephen M. Hirsch, Calvin Newman, Anne B. Zieman, Susan TI Serum Carboxymethyl-Lysine, Disability, and Frailty in Older Persons: The Cardiovascular Health Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Biomarkers; Disablement process; Epidemiology; Frailty; Metabolism ID GLYCATION END-PRODUCTS; DISEASE MORTALITY; OXIDATIVE STRESS; CROSS-LINKING; ADULTS; ENDPRODUCTS; WOMEN; COMPLICATIONS; PHENOTYPE; FOODS AB Background. Advanced glycation endproducts are biologically active compounds that accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML), a ubiquitous human advanced glycation endproduct, has been associated with age-related conditions and mortality. Our objective was to ascertain the relationship between CML and geriatric outcomes (disability and frailty) in a large cohort of older men and women. Methods. In 1996-1997, serum CML was measured in 3,373 Cardiovascular Health Study participants (mean age 78.1 +/- 4.8 years). Disability, defined as difficulty in any of six activities of daily living, was assessed every 6-12 months for 14 years. Frailty was defined according to five standard criteria at the 1996-1997 visit. Cox proportional hazard models estimated the relationship between CML and incident disability (N = 2,643). Logistic regression models estimated the relationship between CML and prevalent frailty. Results. Adjusting for multiple potential confounders, higher CML was associated with incident disability (hazard ratio per standard deviation [225 ng/mL] increase: 1.05, 95% CI 1.01-1.11). In men, odds of frailty increased with higher CML values (odds ratio = 1.30 per standard deviation, 95% CI 1.14-1.48), but the relationship was attenuated by adjustment for cognitive status, kidney function, and arthritis. CML was not associated with frailty in women. Conclusions. Higher serum CML levels in late life are associated with incident disability and prevalent frailty. Further work is needed to understand CML's value as a risk stratifier, biomarker, or target for interventions that promote healthy aging. C1 [Whitson, Heather E.] Duke Univ, Dept Med, Durham, NC USA. [Whitson, Heather E.] GRECC, Durham VA Med Ctr, Durham, NC USA. [Arnold, Alice M.; Yee, Laura M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Mukamal, Kenneth J.; Djousse, Luc] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Prevent & Family Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA. [Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA. [Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT USA. [Thielke, Stephen M.] Puget Sound VA Med Ctr, Seattle, WA USA. [Thielke, Stephen M.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Hirsch, Calvin] Univ Calif Davis, Dept Med, Davis, CA USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Zieman, Susan] NIA, NIH, Bethesda, MD 20892 USA. RP Whitson, HE (reprint author), DUMC 3003, Durham, NC 27710 USA. EM heather.whitson@duke.edu RI Newman, Anne/C-6408-2013; Djousse, Luc/F-5033-2017 OI Newman, Anne/0000-0002-0106-1150; Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute [HL094555, HL080295]; National Institute on Aging [AG-023629]; [HHSN268201200036C]; [N01-HHSN268200800007C]; [N01 HC-55222]; [N01-HC-85079]; [N01-HC-85080]; [N01-HC-85081]; [N01-HC-85082]; [N01-HC-85083]; [N01-HC-85086]; [K23 AG032867]; [5P30AG028716] FX This research was supported by contracts HHSN268201200036C, N01-HHSN268200800007C, N01 HC-55222, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85086, and grants HL094555 and HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke and by AG-023629 from the National Institute on Aging. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org. H.E.W. is supported by K23 AG032867 and 5P30AG028716. NR 33 TC 3 Z9 3 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2014 VL 69 IS 6 BP 710 EP 716 DI 10.1093/gerona/glt155 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AI8BI UT WOS:000337128500011 PM 24127427 ER PT J AU Murphy, RA Ip, EH Zhang, Q Boudreau, RM Cawthon, PM Newman, AB Tylavsky, FA Visser, M Goodpaster, BH Harris, TB AF Murphy, Rachel A. Ip, Edward H. Zhang, Qiang Boudreau, Robert M. Cawthon, Peggy M. Newman, Anne B. Tylavsky, Frances A. Visser, Marjolein Goodpaster, Bret H. Harris, Tamara B. CA Hlth Aging Body Composition Study TI Transition to Sarcopenia and Determinants of Transitions in Older Adults: A Population-Based Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Muscle; Aging; Physical function; Sarcopenia; Epidemiology ID DENSITY TESTING INTERVAL; VISCERAL ADIPOSE-TISSUE; SKELETAL-MUSCLE MASS; BODY-COMPOSITION; PHYSICAL-DISABILITY; MOBILITY DISABILITY; RACIAL-DIFFERENCES; RISK-FACTORS; HEALTH; WOMEN AB Background. Diagnostic criteria for sarcopenia from appendicular lean mass (ALM), strength, and performance have been proposed, but little is known regarding the progression of sarcopenia. We examined the time course of sarcopenia and determinants of transitioning toward and away from sarcopenia. Methods. ALM, gait speed, and grip strength were assessed seven times over 9 years in 2,928 initially well-functioning adults aged 70-79. Low ALM was defined as less than 7.95 kg/m(2) (men) or less than 6.24 kg/m(2) (women), low performance as gait speed less than 1.0 m/s, low strength as grip strength less than 30 kg (men) or less than 20 kg (women). Presarcopenia was defined as low ALM and sarcopenia as low ALM with low performance or low strength. Hidden Markov modeling was used to characterize states of ALM, strength, and performance and model transitions leading to sarcopenia and death. Determinants of transitioning toward and away from sarcopenia were examined with logistic regression. Results. Initially, 54% of participants had normal ALM, strength, and performance; 21% had presarcopenia; 5% had sarcopenia; and 20% had intermediate characteristics. Of participants with normal ALM, strength, and performance, 1% transitioned to presarcopenia and none transitioned to sarcopenia. The greatest transition to sarcopenia (7%) was in presarcopenic individuals. Low-functioning and sarcopenia states were more likely to lead to death (12% and 13%). Higher body mass index (p < .001) and pain (p = .05) predicted transition toward sarcopenia, whereas moderate activity predicted transition from presarcopenia to more normal states (p = .02). Conclusions. Pain, physical activity, and body mass index, potentially modifiable factors, are determinants of transitions. Promotion of health approaching old age is important as few individuals transition away from their initial state. C1 [Murphy, Rachel A.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20814 USA. [Ip, Edward H.; Zhang, Qiang] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15260 USA. [Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Visser, Marjolein] Vrije Univ Amsterdam, Dept Hlth Sci, Amsterdam, Netherlands. [Visser, Marjolein] EMGO Inst, Amsterdam, Netherlands. [Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands. [Goodpaster, Bret H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. RP Murphy, RA (reprint author), NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, 7201 Wisconsin Ave,3C-309, Bethesda, MD 20814 USA. EM Rachel.murphy@nih.gov RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research [R01-NR-012459, R01-AG031827A]; Intramural Research Program of the National Institutes of Health, National Institute on Aging; Banting Postdoctoral Fellowship FX This research was supported by National Institute on Aging (Contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106); National Institute on Aging (grant R01-AG028050); National Institute of Nursing Research (grants R01-NR-012459 and R01-AG031827A). This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. R.A.M. is supported by a Banting Postdoctoral Fellowship. NR 39 TC 12 Z9 12 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2014 VL 69 IS 6 BP 751 EP 758 DI 10.1093/gerona/glt131 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AI8BI UT WOS:000337128500016 PM 24013673 ER PT J AU Burch, JB Augustine, AD Frieden, LA Hadley, E Howcroft, TK Johnson, R Khalsa, PS Kohanski, RA Li, XL Macchiarini, F Niederehe, G Oh, YS Pawlyk, AC Rodriguez, H Rowland, JH Shen, GL Sierra, F Wise, BC AF Burch, John B. Augustine, Alison Deckhut Frieden, Leslie A. Hadley, Evan Howcroft, T. Kevin Johnson, Ron Khalsa, Partap S. Kohanski, Ronald A. Li, Xiao Ling Macchiarini, Francesca Niederehe, George Oh, Young S. Pawlyk, Aaron C. Rodriguez, Henry Rowland, Julia H. Shen, Grace L. Sierra, Felipe Wise, Bradley C. TI Advances in Geroscience: Impact on Healthspan and Chronic Disease SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Chronic disease; Geroscience AB Population aging is unprecedented, without parallel in human history, and the 21st century will witness even more rapid aging than did the century just past. Improvements in public health and medicine are having a profound effect on population demographics worldwide. By 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60 (http://unfpa.org/ageingreport/). Although we can reasonably expect to live longer today than past generations did, the age-related disease burden we will have to confront has not changed. With the proportion of older people among the global population being now higher than at any time in history and still expanding, maintaining health into old age (or healthspan) has become a new and urgent frontier for modern medicine. Geroscience is a cross-disciplinary field focused on understanding the relationships between the processes of aging and age-related chronic diseases. On October 30-31, 2013, the trans-National Institutes of Health GeroScience Interest Group hosted a Summit to promote collaborations between the aging and chronic disease research communities with the goal of developing innovative strategies to improve healthspan and reduce the burden of chronic disease. C1 [Burch, John B.] NIH, Ctr Sci Review, Bethesda, MD 20892 USA. [Augustine, Alison Deckhut] NIAID, Immunoregulat Sect, Basic Immunol Branch, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Frieden, Leslie A.] Natl Inst Dent & Craniofacial Res, Res Training & Career Dev Branch, Bethesda, MD USA. [Hadley, Evan] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Howcroft, T. Kevin] NCI, NIH, Div Canc Biol, Bethesda, MD 20892 USA. [Johnson, Ron] NCI, Canc Etiol Branch, DNA & Chromosome Aberrat Branch, Div Canc Biol, Bethesda, MD 20892 USA. [Khalsa, Partap S.] Natl Ctr Complementary & Alternat Med, Div Extramural Res, Bethesda, MD USA. [Kohanski, Ronald A.; Sierra, Felipe] NIA, Div Aging Biol, Bethesda, MD 20892 USA. [Li, Xiao Ling] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Macchiarini, Francesca] NIAID, Program Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Niederehe, George] NIMH, Geriatr & Aging Proc Res Branch, Bethesda, MD 20892 USA. [Oh, Young S.] NHLBI, Vasc Biol & Hypertens Branch, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Pawlyk, Aaron C.] NIDDK, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA. [Rodriguez, Henry] NCI, Off Canc Clin Prote Res, Off Director, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Shen, Grace L.] NEI, Retinal Dis Program, Div Extramural Res, NIH, Bethesda, MD 20892 USA. [Wise, Bradley C.] NIA, Neurobiol Aging Branch, Div Neurosci, Bethesda, MD 20892 USA. RP Kohanski, RA (reprint author), NIA, Div Aging Biol, Gateway Bldg,Suite 2C231,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM kohanskir@mail.nih.gov NR 0 TC 37 Z9 37 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2014 VL 69 SU 1 BP S1 EP S3 DI 10.1093/gerona/glu041 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA AI8BT UT WOS:000337130200001 PM 24833579 ER PT J AU Kristinsson, SY Anderson, WF Landgren, O AF Kristinsson, S. Y. Anderson, W. F. Landgren, O. TI Improved long-term survival in multiple myeloma up to the age of 80 years SO LEUKEMIA LA English DT Letter ID DEXAMETHASONE; LENALIDOMIDE C1 [Kristinsson, S. Y.] Karolinska Univ Hosp Solna, Dept Med, Div Hematol, Stockholm, Sweden. [Kristinsson, S. Y.] Karolinska Inst, Stockholm, Sweden. [Kristinsson, S. Y.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Kristinsson, S. Y.] Landspitali Natl Univ Hosp, Dept Hematol, Reykjavik, Iceland. [Anderson, W. F.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Landgren, O.] NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kristinsson, SY (reprint author), Karolinska Univ Hosp Solna, Dept Med, Div Hematol, Stockholm, Sweden. EM sigyngvi@hi.is RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 NR 16 TC 30 Z9 33 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JUN PY 2014 VL 28 IS 6 BP 1346 EP 1348 DI 10.1038/leu.2014.23 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA AI9DV UT WOS:000337230300021 PM 24418994 ER PT J AU Ebong, IA Watson, KE Goff, DC Bluemke, DA Srikanthan, P Horwich, T Bertoni, AG AF Ebong, Imo A. Watson, Karol E. Goff, David C., Jr. Bluemke, David A. Srikanthan, Preethi Horwich, Tamara Bertoni, Alain G. TI Age at menopause and incident heart failure: the Multi-Ethnic Study of Atherosclerosis SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Menopause; Heart failure; Estrogen ID METABOLIC RISK-FACTORS; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; MYOCARDIAL PERFORMANCE; HORMONE REPLACEMENT; MESA; OBESITY; ETHNICITY; ASSOCIATION; POPULATIONS AB Objective: This study aims to evaluate the associations of early menopause (menopause occurring before age 45 years) and age at menopause with incident heart failure (HF) in postmenopausal women. We also explored the associations of early menopause and age at menopause with left ventricular (LV) measures of structure and function in postmenopausal women. Methods: We included 2,947 postmenopausal women, aged 45 to 84 years without known cardiovascular disease (2000-2002), from the Multi-Ethnic Study of Atherosclerosis. Cox proportional hazards models were used to examine the associations of early menopause and age at menopause with incident HF. In 2,123 postmenopausal women in whom cardiac magnetic resonance imaging was obtained at baseline, we explored the associations of early menopause and age at menopause with LV measures using multivariable linear regression. Results: Across a median follow-up of 8.5 years, we observed 71 HF events. There were no significant interactions with ethnicity for incident HF (P-interaction > 0.05). In adjusted analysis, early menopause was associated with an increased risk of incident HF (hazard ratio, 1.66; 95% CI, 1.01-2.73), whereas every 1-year increase in age at menopause was associated with a decreased risk of incident HF (hazard ratio, 0.96; 95% CI, 0.94-0.99). We observed significant interactions between early menopause and ethnicity for LV mass-to-volume ratio (LVMVR; P-interaction = 0.02). In Chinese-American women, early menopause was associated with a higher LVMVR (+0.11; P = 0.0002), whereas every 1-year increase in age at menopause was associated with a lower LVMVR (-0.004; P = 0.04) at baseline. Conclusions: Older age at menopause is independently associated with a decreased risk of incident HF. Concentric LV remodeling, indicated by a higher LVMVR, is present in Chinese-American women who experienced early menopause at baseline. C1 [Ebong, Imo A.] Univ So Calif, Dept Med, Los Angeles, CA 90033 USA. [Watson, Karol E.; Horwich, Tamara] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90095 USA. [Goff, David C., Jr.] Colorado Sch Publ Hlth, Aurora, CO USA. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Srikanthan, Preethi] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27103 USA. [Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol, Winston Salem, NC 27103 USA. RP Ebong, IA (reprint author), Univ So Calif, Dept Med, 2020 Zonal Ave, Los Angeles, CA 90033 USA. EM ebong@usc.edu OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169] FX The Multi-Ethnic Study of Atherosclerosis was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 37 TC 17 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2014 VL 21 IS 6 BP 585 EP 591 DI 10.1097/gme.0000000000000138 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI8HR UT WOS:000337153300010 PM 24423934 ER PT J AU Gierach, GL Pfeiffer, RM Patel, DA Black, A Schairer, C Gill, A Brinton, LA Sherman, ME AF Gierach, Gretchen L. Pfeiffer, Ruth M. Patel, Deesha A. Black, Amanda Schairer, Catherine Gill, Abegail Brinton, Louise A. Sherman, Mark E. TI Long-term overall and disease-specific mortality associated with benign gynecologic surgery performed at different ages SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Bilateral oophorectomy; Cohort studies; Hysterectomy; Mortality ID FRAMINGHAM RISK SCORE; BILATERAL OOPHORECTOMY; OVARIAN CONSERVATION; HYSTERECTOMY; WOMEN; MENOPAUSE; HEALTH; SURVIVAL; THERAPY; COHORT AB Objective: As bilateral salpingo-oophorectomy is frequently performed with hysterectomy for nonmalignant conditions, defining health outcomes associated with benign bilateral salpingo-oophorectomy performed at different ages is critical. Methods: We assessed mortality risk associated with benign total abdominal hysterectomy or bilateral salpingo-oophorectomy among 52,846 Breast Cancer Detection Demonstration Project follow-up study participants. Surgery and risk factor data were ascertained via baseline interview (1979-1986) and three questionnaires (1987-1998). During follow-up through December 2005 (mean, 22.1 y), 13,734 deaths were identified. We estimated hazard ratios (HRs) and 95% CIs for overall and disease-specific mortality for total abdominal hysterectomy or bilateral salpingo-oophorectomy performed by age 35, 40, 45, 50, or 55 years, compared with not having surgery, using landmark analyses and multivariable Cox regression. Results: Undergoing bilateral salpingo-oophorectomy by age 35 years was associated with increased mortality risk (HR35 (y), 1.20; 95% CI, 1.08-1.34), which decreased with age (HR40 (y), 1.12; 95% CI, 1.04-1.21; HR45 (y), 1.10; 95% CI, 1.03-1.17). Total abdominal hysterectomy alone performed by age 40 years was associated with increased mortality risk to a lesser extent (HR40 y, 1.08; 95% CI, 1.01-1.15). Analyses based on matched propensity scores related to having gynecologic surgery yielded similar results. Elevated mortality risks were largely attributable to noncancer causes. Conclusions: Benign gynecologic surgeries among young women are associated with increased mortality risk, which attenuates with age. C1 [Gierach, Gretchen L.; Patel, Deesha A.; Brinton, Louise A.; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Pfeiffer, Ruth M.; Schairer, Catherine] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. [Black, Amanda] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Gill, Abegail] Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Bethesda, MD USA. RP Gierach, GL (reprint author), Rm 7-E108,MSC 9774,9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM gierachg@mail.nih.gov RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 FU National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 23 TC 11 Z9 11 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2014 VL 21 IS 6 BP 592 EP 601 DI 10.1097/gme.0000000000000118 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI8HR UT WOS:000337153300011 PM 24253486 ER PT J AU Glaser, RL Dimitrakakis, C AF Glaser, Rebecca L. Dimitrakakis, Constantine TI Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast cancer SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Testosterone; Anastrozole; Breast cancer; Intramammary; Neoadjuvant ID ANDROGEN RECEPTOR; ESTROGEN; EXPRESSION; ENDOCRINE; TISSUE; WOMEN; MEN AB Objective: Experimental and clinical data support the inhibitory effect of testosterone on breast tissue and breast cancer. However, testosterone is aromatized to estradiol, which exerts the opposite effect. The aim of this study was to determine the effect of testosterone, combined with the aromatase inhibitor anastrozole, on a hormone receptor positive, infiltrating ductal carcinoma in the neoadjuvant setting. Methods: To determine clinical response, we obtained serial ultrasonic measurements and mammograms before and after therapy. Three combination implants-each containing 60 mg of testosterone and 4 mg of anastrozole-were placed anterior, superior, and inferior to a 2.4-cm tumor in the left breast. Three additional testosterone-anastrozole implants were again placed peritumorally 48 days later. Results: By day 46, there was a sevenfold reduction in tumor volume, as measured on ultrasound. By week 13, we documented a 12-fold reduction in tumor volume, demonstrating a rapid logarithmic response to intramammary testosterone-anastrozole implant therapy, equating to a daily response rate of 2.78% and a tumor half-life of 23 days. Therapeutic systemic levels of testosterone were achieved without elevation of estradiol, further demonstrating the efficacy of anastrozole combined with testosterone. Conclusions: This novel therapy, delivered in the neoadjuvant setting, has the potential to identify early responders and to evaluate the effectiveness of therapy in vivo. This may prove to be a new approach to both local and systemic therapies for breast cancer in subgroups of patients. In addition, it can be used to reduce tumor volume, allowing for less surgical intervention and better cosmetic oncoplastic results. C1 [Glaser, Rebecca L.] Millennium Wellness Ctr, Dayton, OH USA. [Glaser, Rebecca L.] Wright State Univ, Boonshoft Sch Med, Dept Surg, Dayton, OH 45435 USA. [Dimitrakakis, Constantine] Univ Athens, Sch Med, Dept Ob Gyn 1, GR-11527 Athens, Greece. [Dimitrakakis, Constantine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Glaser, RL (reprint author), 228 East Spring Valley Rd, Dayton, OH 45458 USA. EM rglaser@woh.rr.com NR 20 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 EI 1530-0374 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JUN PY 2014 VL 21 IS 6 BP 673 EP 678 DI 10.1097/gme.0000000000000096 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI8HR UT WOS:000337153300021 PM 24149917 ER PT J AU Miao, HX Gomella, AA Chedid, N Chen, L Wen, H AF Miao, Houxun Gomella, Andrew A. Chedid, Nicholas Chen, Lei Wen, Han TI Fabrication of 200 nm Period Hard X-ray Phase Gratings SO NANO LETTERS LA English DT Article DE X-ray grating far-field interferometer; X-ray phase contrast imaging; nanoimprint lithography; cryogenic reactive ion etch; atomic layer deposition; electroplating ID DIFFRACTION GRATINGS; COMPACT SOURCE; INTERFEROMETER; DEPOSITION; GOLD AB Far field X-ray grating interferometry achieves extraordinary phase sensitivity in imaging weakly absorbing samples, provided that the grating period is within the transverse coherence length of the X-ray source. Here we describe a cost-efficient process to fabricate large area, 100 nm half-pitch hard X-ray phase gratings with an aspect ratio of 32. The nanometric gratings are suitable for ordinary compact X-ray sources having low spatial coherence, as demonstrated by X-ray diffraction experiments. C1 [Miao, Houxun; Gomella, Andrew A.; Chedid, Nicholas; Wen, Han] NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Chen, Lei] NIST, Ctr Nanoscale Sci & Technol, Gaithersburg, MD 20899 USA. RP Miao, HX (reprint author), NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM miaoh@mail.nih.gov; han.wen@nih.gov RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. FX We sincerely thank Eric Bennett, Gary Melvin, and Dumitru Mazilu of the National Heart, Lung, and Blood Institute of National Institutes of Health for their assistance in mechanical engineering and the staff of the Center for Nanoscale Science and Technology of National Institute of Standards and Technology for assistance on the fabrication. This work was supported by the Intramural Research Program of National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Certain commercial equipment, instruments, or materials (or suppliers) are identified in this paper to foster understanding. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose. NR 41 TC 4 Z9 4 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 EI 1530-6992 J9 NANO LETT JI Nano Lett. PD JUN PY 2014 VL 14 IS 6 BP 3453 EP 3458 DI 10.1021/nl5009713 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA AJ0JP UT WOS:000337337100073 PM 24845537 ER PT J AU Brooks, PJ Tagle, DA Groft, S AF Brooks, Philip J. Tagle, Danilo A. Groft, Steve TI Expanding rare disease drug trials based on shared molecular etiology SO NATURE BIOTECHNOLOGY LA English DT Article ID FAMILIAL DYSAUTONOMIA; CYSTIC-FIBROSIS; NONSENSE MUTATIONS; STORAGE DISORDERS; GENETIC-DISEASES; GAUCHER-DISEASE; SUPPRESSION; REPAIR; CHAPERONES; MECHANISM AB Current clinical trial approaches in rare disease test one drug on one indication defined by a clinical phenotype. For targeted drugs, grouping patients by molecular etiology would make much more sense. C1 [Brooks, Philip J.; Groft, Steve] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Tagle, Danilo A.] NIH, Off Special Initiat, Off Director, Natl Ctr Adv Translat Sci, Bethesda, MD USA. RP Brooks, PJ (reprint author), NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. EM pjbrooks@mail.nih.gov FU Intramural NIH HHS [Z99 TR999999] NR 44 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2014 VL 32 IS 6 BP 515 EP 518 DI 10.1038/nbt.2924 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AI9EV UT WOS:000337233800007 PM 24911489 ER PT J AU Milius, D Dove, ES Chalmers, D Dyke, SOM Kato, K Nicolas, P Ouellette, BFF Ozenberger, B Rodriguez, LL Zeps, N Joly, Y AF Milius, Djims Dove, Edward S. Chalmers, Donald Dyke, Stephanie O. M. Kato, Kazuto Nicolas, Pilar Ouellette, B. F. Francis Ozenberger, Brad Rodriguez, Laura L. Zeps, Nikolajs Joly, Yann TI The International Cancer Genome Consortium's evolving data-protection policies SO NATURE BIOTECHNOLOGY LA English DT Letter ID PRIVACY; ANONYMIZATION; GENOTYPES; LIMITS; ERA C1 [Milius, Djims; Dove, Edward S.; Joly, Yann] McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada. [Chalmers, Donald] Univ Tasmania, Fac Law, Hobart, Tas 7001, Australia. [Dyke, Stephanie O. M.] Wellcome Trust Sanger Inst, Cambridge, England. [Kato, Kazuto] Osaka Univ, Grad Sch Med, Dept Biomed Eth & Publ Policy, Osaka, Japan. [Nicolas, Pilar] Univ Basque Country, Univ Deusto, Interuniv Chair Law & Human Genome, E-48080 Bilbao, Spain. [Ouellette, B. F. Francis] Ontario Inst Canc Res, Informat & Biocomp Program, Toronto, ON, Canada. [Ouellette, B. F. Francis] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON, Canada. [Ozenberger, Brad; Rodriguez, Laura L.] NHGRI, NIH, Bethesda, MD 20892 USA. [Zeps, Nikolajs] Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia. RP Milius, D (reprint author), McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada. EM yann.joly@mail.mcgill.ca RI Chalmers, Don/J-7658-2014 OI Chalmers, Don/0000-0002-7925-8818 NR 28 TC 6 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2014 VL 32 IS 6 BP 519 EP 523 DI 10.1038/nbt.2926 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA AI9EV UT WOS:000337233800008 PM 24911490 ER PT J AU Johnson, LM Turkbey, B Figg, WD Choyke, PL AF Johnson, Linda M. Turkbey, Baris Figg, William D. Choyke, Peter L. TI Multiparametric MRI in prostate cancer management SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID CONTRAST-ENHANCED MRI; APPARENT DIFFUSION-COEFFICIENT; SEMINAL-VESICLE INVASION; RADICAL PROSTATECTOMY; 3 T; PERIPHERAL ZONE; TUMOR-DETECTION; ENDORECTAL MRI; EXTRACAPSULAR EXTENSION; POSTBIOPSY HEMORRHAGE AB Prostate cancer is the second most common cancer in men worldwide. The clinical behaviour of prostate cancer ranges from low-grade indolent tumours that never develop into clinically significant disease to aggressive, invasive tumours that may progress rapidly to metastatic disease and death. Therefore, there is an urgent clinical need to detect high-grade cancers and to differentiate them from the indolent, slow-growing tumours. Conventional methods of cancer detection-such as levels of prostate-specific antigen (PSA) in serum, digital rectal examination, and random biopsies-are limited in their sensitivity, specificity, or both. The combination of conventional anatomical MRI and functional magnet resonance sequences -known as multiparametric MRI (mp- MRI)- is emerging as an accurate tool for identifying clinically relevant tumours owing to its ability to localize them. In this Review, we discuss the value of mp-MRI in localized and metastatic prostate cancer, highlighting its role in the detection, staging, and treatment planning of prostate cancer. C1 [Johnson, Linda M.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA. [Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1182,Bldg 10, Bethesda, MD 20892 USA. EM turkbeyi@mail.nih.gov RI Figg Sr, William/M-2411-2016 FU NIH FX The authors would like to thank the NIH intramural funding programme for financial support. NR 103 TC 33 Z9 38 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 EI 1759-4782 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD JUN PY 2014 VL 11 IS 6 BP 346 EP 353 DI 10.1038/nrclinonc.2014.69 PG 8 WC Oncology SC Oncology GA AI8PR UT WOS:000337183300009 PM 24840072 ER PT J AU Birmingham, K Gradinaru, V Anikeeva, P Grill, WM Pikov, V McLaughlin, B Pasricha, P Weber, D Ludwig, K Famm, K AF Birmingham, Karen Gradinaru, Viviana Anikeeva, Polina Grill, Warren M. Pikov, Victor McLaughlin, Bryan Pasricha, Pankaj Weber, Douglas Ludwig, Kip Famm, Kristoffer TI Bioelectronic medicines: a research roadmap SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material C1 [Birmingham, Karen; Famm, Kristoffer] GlaxoSmithKline, Bioelect R&D, Stevenage SG1 2NY, Herts, England. [Gradinaru, Viviana] CALTECH, Pasadena, CA 91125 USA. [Anikeeva, Polina] MIT, Cambridge, MA 02139 USA. [Grill, Warren M.] Duke Univ, Durham, NC 27708 USA. [Pikov, Victor] Huntington Med Res Inst, Pasadena, CA 91105 USA. [McLaughlin, Bryan] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. [Pasricha, Pankaj] Johns Hopkins Univ, Sch Med, Johns Hopkins Ctr Neurogastroenterol, Baltimore, MD 21205 USA. [Weber, Douglas] Def Adv Res Projects Agcy, Biol Technol Off, Arlington, VA 22203 USA. [Ludwig, Kip] Natl Inst Neurol Disorders & Stroke, North Bethesda, MD 20852 USA. RP Famm, K (reprint author), GlaxoSmithKline, Bioelect R&D, Stevenage SG1 2NY, Herts, England. EM kristoffer.h.famm@gsk.com OI Grill, Warren/0000-0001-5240-6588 NR 5 TC 32 Z9 33 U1 5 U2 54 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JUN PY 2014 VL 13 IS 6 BP 399 EP 400 DI 10.1038/nrd4351 PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA AI8MA UT WOS:000337169000001 PM 24875080 ER PT J AU Holmstrom, KM Finkel, T AF Holmstroem, Kira M. Finkel, Toren TI Cellular mechanisms and physiological consequences of redox-dependent signalling SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID PROTEIN-TYROSINE PHOSPHATASES; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; LIFE-SPAN; STEM-CELLS; REVERSIBLE INACTIVATION; SELF-RENEWAL; CAENORHABDITIS-ELEGANS; SUPEROXIDE-PRODUCTION; METHIONINE OXIDATION AB Reactive oxygen species (ROS), which were originally characterized in terms of their harmful effects on cells and invading microorganisms, are increasingly implicated in various cell fate decisions and signal transduction pathways. The mechanism involved in ROS-dependent signalling involves the reversible oxidation and reduction of specific amino acids, with crucial reactive Cys residues being the most frequent target. In this Review, we discuss the sources of ROS within cells and what is known regarding how intracellular oxidant levels are regulated. We further discuss the recent observations that reduction-oxidation (redox)-dependent regulation has a crucial role in an ever-widening range of biological activities-from immune function to stem cell self-renewal, and from tumorigenesis to ageing. C1 [Holmstroem, Kira M.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA. EM finkelt@nih.gov OI Holmstrom, Kira/0000-0001-6434-7909 FU US National Institutes of Health (NIH) Intramural Funds; Leducq Foundation FX The authors are grateful to members of the Finkel laboratory for helpful comments and to I. Rovira for help in preparing the manuscript. This work was supported by US National Institutes of Health (NIH) Intramural Funds and The Leducq Foundation. NR 119 TC 250 Z9 257 U1 21 U2 110 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 EI 1471-0080 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JUN PY 2014 VL 15 IS 6 BP 411 EP 421 DI 10.1038/nrm3801 PG 11 WC Cell Biology SC Cell Biology GA AI9IE UT WOS:000337245500012 PM 24854789 ER PT J AU Daniels, RD Kubale, TL Yiin, JH Dahm, MM Hales, TR Baris, D Zahm, SH Beaumont, JJ Waters, KM Pinkerton, LE AF Daniels, Robert D. Kubale, Travis L. Yiin, James H. Dahm, Matthew M. Hales, Thomas R. Baris, Dalsu Zahm, Shelia H. Beaumont, James J. Waters, Kathleen M. Pinkerton, Lynne E. TI Mortality and cancer incidence in a pooled cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950-2009) SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID FLORIDA PROFESSIONAL FIREFIGHTERS; HEALTH INTERVIEW SURVEY; CENTRAL UNITED-STATES; TABLE ANALYSIS SYSTEM; FIRE FIGHTERS; OCCUPATIONAL EXPOSURES; INCIDENCE RATES; ALCOHOL-USE; TOBACCO USE; OBESITY AB Objectives To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009. Methods Mortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias. Results Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR = 0.99, 95% CI 0.97 to 1.01, n = 12 028). There was excess cancer mortality (SMR = 1.14, 95% CI 1.10 to 1.18, n = 3285) and incidence (SIR = 1.09, 95% CI 1.06 to 1.12, n = 4461) comprised mainly of digestive (SMR = 1.26, 95% CI 1.18 to 1.34, n = 928; SIR = 1.17, 95% CI 1.10 to 1.25, n = 930) and respiratory (SMR= 1.10, 95% CI 1.04 to 1.17, n = 1096; SIR = 1.16, 95% CI 1.08 to 1.24, n = 813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR= 2.00, 95% CI 1.03 to 3.49, n = 12; SIR = 2.29, 95% CI 1.60 to 3.19, n = 35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques. Conclusions Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting. C1 [Daniels, Robert D.; Kubale, Travis L.; Yiin, James H.; Dahm, Matthew M.; Hales, Thomas R.; Waters, Kathleen M.; Pinkerton, Lynne E.] NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. [Baris, Dalsu; Zahm, Shelia H.] NCI, Div Canc Epidemiol & Genet, Gaithersburg, MD USA. [Beaumont, James J.] UC Davis Dept Publ Hlth Sci, Sacramento, CA USA. RP Daniels, RD (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studies, 4676 Columbia Pkwy,Mailstop R-13, Cincinnati, OH 45226 USA. EM rtd2@cdc.gov RI Zahm, Shelia/B-5025-2015 FU National Institute for Occupational Safety and Health (NIOSH) by National Occupational Research Agenda (NORA); US Fire Administration (USFA); National Institutes of Health (NIH), National Cancer Institute (NCI) FX Research funding was provided by the National Institute for Occupational Safety and Health (NIOSH) by intramural award under the National Occupational Research Agenda (NORA), and by the US Fire Administration (USFA). This research was also supported, in part, by the intramural research programme of the National Institutes of Health (NIH), National Cancer Institute (NCI). NR 45 TC 28 Z9 29 U1 2 U2 19 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUN PY 2014 VL 71 IS 6 BP 388 EP 397 DI 10.1136/oemed-2013-101662 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI9MV UT WOS:000337257600003 PM 24142974 ER PT J AU Huynh, N Nicholson, BP Agron, E Clemons, TE Bressler, SB Rosenfeld, PJ Chew, EY AF Nancy Huynh Nicholson, Benjamin P. Agron, Elvira Clemons, Traci E. Bressler, Susan B. Rosenfeld, Philip J. Chew, Emily Y. CA Age-Related Eye Dis Study 2 Res Gr TI Visual Acuity after Cataract Surgery in Patients with Age-Related Macular Degeneration SO OPHTHALMOLOGY LA English DT Article ID HIGH-DOSE SUPPLEMENTATION; BEAVER DAM EYE; CLINICAL-TRIAL; BETA-CAROTENE; UNITED-STATES; VISION LOSS; VITAMIN-C; DISEASE; RANIBIZUMAB; RISK AB Objective: To evaluate visual acuity outcomes after cataract surgery in persons with varying degrees of severity of age-related macular degeneration (AMD). Design: Cohort study. Participants: A total of 1232 eyes of 793 participants who underwent cataract surgery during the Age-Related Eye Disease Study 2, a prospective, multicenter, randomized controlled trial of nutritional supplements for treatment of AMD. Methods: Preoperative and postoperative characteristics of participants who underwent cataract extraction during the 5-year trial were analyzed. Both clinical data and standardized red-reflex lens and fundus photographs were obtained at baseline and annually. Photographs were graded by a centralized reading center for cortical and posterior subcapsular lens opacities and for AMD severity. Cataract surgery was documented at annual study visits or by history during the 6-month telephone calls. Analyses were conducted using multivariate repeated-measures regression. Main Outcome Measures: Change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. Results: Adjusting for age at time of surgery, gender, interval between preoperative and postoperative visits, and type and severity of cataract, the mean changes in visual acuity were as follows: eyes with mild AMD (n = 30) gained 11.2 letters (95% confidence interval [CI], 6.9-15.5), eyes with moderate AMD (n = 346) gained 11.1 letters (95% CI, 9.1-13.2), eyes with severe AMD (n = 462) gained 8.7 letters (95% CI, 6.7-10.7), eyes with noncentral geographic atrophy (n = 70) gained 8.9 letters (95% CI, 5.8-12.1), and eyes with advanced AMD (central geographic atrophy, neovascular disease, or both; n = 324) gained 6.8 letters (95% CI, 4.9-8.8). The visual acuity gain across all AMD severity groups was statistically significant from preoperative values (P < 0.0001). Conclusions: Mean visual acuities improved significantly after cataract surgery across varying degrees of AMD severity. (C) 2014 by the American Academy of Ophthalmology. C1 [Nancy Huynh; Nicholson, Benjamin P.; Agron, Elvira; Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Clemons, Traci E.] EMMES Corp, Rockville, MD USA. [Bressler, Susan B.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA. RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Research to Prevent Blindness, Inc., New York, New York; National Eye Institute, National Institutes of Health, Bethesda, Maryland [HHS-N-260-2005-00007-C]; Administrative Data Base (ADB) [N01-EY-5-0007]; EMMES Corporation; Jaeb Center; Allergan, Bausch Lomb; Bayer Healthcare; Genentech, Lumenis, Inc.; Notal Vision Ltd; Novartis; Regeneron; Thrombogenics; Sanofi-Aventis FX The author(s) have made the following disclosure(s): Susan B. Bressler: Consultante-GlaxoSmithKline; Financial support-EMMES Corporation, the Jaeb Center, Allergan, Bausch & Lomb, Bayer Healthcare, Genentech, Lumenis, Inc., Notal Vision Ltd, Novartis, Regeneron, Thrombogenics, Sanofi-Aventis; Lecturere-Providers of continuing medical education materials; these grants are negotiated and administered by the School of Medicine, which receives the grants through the Office of Research Administration ( individual investigators who participate in such sponsored projects are not compensated directly by the sponsor but may receive salary or other support from the institution to support their effort on the projects). Philip J. Rosenfeld: Consultante-Oraya, Novartis, Chengdu Kanghong Biotech, Acucela, Thrombogenics, Canon; Financial support- Carl Zeiss Meditec, Alexion, Potentia, GlaxoSmithKline; Lecturer-Carl Zeiss Meditec, Allergan, Topcon.; Supported by Research to Prevent Blindness, Inc., New York, New York (Physician-Scientist grant to S. B. B.); the National Eye Institute, National Institutes of Health, Bethesda, Maryland (contract no.: HHS-N-260-2005-00007-C; Administrative Data Base (ADB) contract no.: N01-EY-5-0007). The sponsor and funding organization participated in the design and conduct of the study; collection, management, analysis, and interpretation of data; and the preparation, review, and approval of the manuscript. NR 28 TC 9 Z9 9 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 2014 VL 121 IS 6 BP 1229 EP 1236 DI 10.1016/j.ophtha.2013.12.035 PG 8 WC Ophthalmology SC Ophthalmology GA AJ0KG UT WOS:000337339100015 ER PT J AU Barnette, AR Horbar, JD Soll, RF Pfister, RH Nelson, KB Kenny, MJ Raju, TNK Bingham, PM Inder, TE AF Barnette, Alan R. Horbar, Jeffrey D. Soll, Roger F. Pfister, Robert H. Nelson, Karin B. Kenny, Michael J. Raju, Tonse N. K. Bingham, Peter M. Inder, Terrie E. TI Neuroimaging in the Evaluation of Neonatal Encephalopathy SO PEDIATRICS LA English DT Article DE neonatal encephalopathy; computed tomography; MRI; cranial ultrasound ID HYPOXIC-ISCHEMIC ENCEPHALOPATHY; RADIATION-EXPOSURE; NEWBORN ENCEPHALOPATHY; COMPUTED-TOMOGRAPHY; IONIZING-RADIATION; MATTER INJURY; RISK-FACTORS; CANCER; CT; ULTRASONOGRAPHY AB BACKGROUND AND OBJECTIVE: Computed tomography (CT) is still used for neuroimaging of infants with known or suspected neurologic disorders. Alternative neuroimaging options that do not expose the immature brain to radiation include MRI and cranial ultrasound. We aim to characterize and compare the use and findings of neuroimaging modalities, especially CT, in infants with neonatal encephalopathy. METHODS: The Vermont Oxford Network Neonatal Encephalopathy Registry enrolled 4171 infants (>= 36 weeks' gestation or treated with therapeutic hypothermia) between 2006 and 2010 who were diagnosed with encephalopathy in the first 3 days of life. Demographic, perinatal, and medical conditions were recorded, along with treatments, comorbidities, and outcomes. The modality, timing, and results of neuroimaging were also collected. RESULTS: CT scans were performed on 933 of 4107 (22.7%) infants, and 100 of 921 (10.9%) of those received multiple CT scans. Compared with MRI, CT provided less detailed evaluation of cerebral injury in areas of prognostic significance, but was more sensitive than cranial ultrasound for hemorrhage and deep brain structural abnormalities. CONCLUSIONS: CT is commonly used for neuroimaging in newborn infants with neonatal encephalopathy despite concerns over potential harm from radiation exposure. The diagnostic performance of CT is inferior to MRI in identifying neonatal brain injury. Our data suggest that using cranial ultrasound for screening, followed by MRI would be more appropriate than CT at any stage to evaluate infants with neonatal encephalopathy. C1 [Barnette, Alan R.] St Francis Med Ctr, Dept Pediat, Cape Girardeau, MO 63703 USA. [Barnette, Alan R.; Inder, Terrie E.] Washington Univ, St Louis Childrens Hosp, Sch Med, Edward Mallinckrodt Dept Pediat, St Louis, MO 63110 USA. [Inder, Terrie E.] Washington Univ, St Louis Childrens Hosp, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Inder, Terrie E.] Washington Univ, St Louis Childrens Hosp, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Horbar, Jeffrey D.; Soll, Roger F.; Pfister, Robert H.] Univ Vermont, Coll Med, Dept Pediat, Burlington, VT USA. [Bingham, Peter M.] Univ Vermont, Coll Med, Dept Neurol, Burlington, VT USA. [Kenny, Michael J.] Univ Vermont, Coll Med, Biostat Core, Burlington, VT USA. [Soll, Roger F.] Vermont Oxford Network, Burlington, VT USA. [Nelson, Karin B.] Childrens Hosp, Med Ctr, Dept Neurol, Washington, DC USA. [Nelson, Karin B.] NINDS, NIH, Bethesda, MD 20892 USA. [Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Barnette, AR (reprint author), St Francis Med Ctr, Dept Pediat, 211 St Francis Dr, Cape Girardeau, MO 63703 USA. EM abarnette@sfmc.net FU Doris Duke Charitable Foundation FX Dr Inder received support from the Doris Duke Charitable Foundation. NR 36 TC 8 Z9 9 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JUN PY 2014 VL 133 IS 6 BP E1508 EP E1517 DI 10.1542/peds.2013-4247 PG 10 WC Pediatrics SC Pediatrics GA AI8MY UT WOS:000337172600004 PM 24864165 ER PT J AU Husain, SR Ohya, Y Toguchida, J Puri, RK AF Husain, Syed R. Ohya, Yoshikazu Toguchida, Junya Puri, Raj K. TI Current Status of Multipotent Mesenchymal Stromal Cells SO TISSUE ENGINEERING PART B-REVIEWS LA English DT Editorial Material C1 [Husain, Syed R.; Puri, Raj K.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Ohya, Yoshikazu] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Kashiwa, Chiba, Japan. [Toguchida, Junya] Kyoto Univ, Inst Frontier Med Sci, Dept Tissue Regenerat, Kyoto, Japan. [Toguchida, Junya] Kyoto Univ, Ctr iPS Cell Res & Applicat, Dept Cell Growth & Differentiat, Kyoto, Japan. RP Husain, SR (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, HFM 735,NIH Bldg 29B,29 Lincoln Dr,MSC4555, Bethesda, MD 20892 USA. EM syed.husain@fda.hhs.gov NR 2 TC 2 Z9 2 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3368 EI 1937-3376 J9 TISSUE ENG PART B-RE JI Tissue Eng. Part B-Rev. PD JUN PY 2014 VL 20 IS 3 BP 189 EP 189 DI 10.1089/ten.teb.2014.0105 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AI9JU UT WOS:000337249700001 PM 24568643 ER PT J AU Stroncek, DF Sabatino, M Ren, JQ England, L Kuznetsov, SA Klein, HG Robey, PG AF Stroncek, David F. Sabatino, Marianna Ren, Jiaqiang England, Lee Kuznetsov, Sergei A. Klein, Harvey G. Robey, Pamela G. TI Establishing a Bone Marrow Stromal Cell Transplant Program at the National Institutes of Health Clinical Center SO TISSUE ENGINEERING PART B-REVIEWS LA English DT Article ID MESENCHYMAL STEM-CELLS; VERSUS-HOST-DISEASE; IN-VIVO; SENESCENCE; THERAPY; CULTURE; REPAIR; RECONSTRUCTION; DEFECTS AB A repository of cryopreserved bone marrow stromal cell (BMSC) products prepared from marrow aspirates of healthy subjects has been created and is being used to treat patients with inflammatory bowel disease, cardiovascular disease, and acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. New methods of manufacturing BMSCs are being investigated including the use of an automated bioreactor for BMSC expansion and the replacement of fetal bovine serum with human platelet lysate as a media supplement. Efforts are also being made to identify markers that can be used to assess the potency of BMSCs. C1 [Stroncek, David F.; Sabatino, Marianna; Ren, Jiaqiang; England, Lee; Klein, Harvey G.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Kuznetsov, Sergei A.; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU NCI; NIAID; NINDS; NIDCR; NIAMS; NIBIB; NHLBI FX The authors thank the entire staff of the Cell Processing Section, DTM, CC, NIH for their contributions to the BMSC TC. Funds for this program were contributed to the BMSC TC by the intramural research programs of the NCI, NIAID, NINDS, NINDS, NIDCR, NIAMS, NIBIB, and NHLBI. NR 37 TC 9 Z9 9 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3368 EI 1937-3376 J9 TISSUE ENG PART B-RE JI Tissue Eng. Part B-Rev. PD JUN PY 2014 VL 20 IS 3 BP 200 EP 205 DI 10.1089/ten.teb.2013.0529 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AI9JU UT WOS:000337249700003 PM 24368014 ER PT J AU Battiwalla, M Barrett, AJ AF Battiwalla, Minoo Barrett, A. John TI Bone Marrow Mesenchymal Stromal Cells to Treat Complications Following Allogeneic Stem Cell Transplantation SO TISSUE ENGINEERING PART B-REVIEWS LA English DT Article ID VERSUS-HOST-DISEASE; HEMATOLOGIC MALIGNANCY PATIENTS; IN-VITRO; TISSUE-REPAIR; MOUSE MODEL; ENGRAFTMENT; MICE; COTRANSPLANTATION; PROLIFERATION; SUPPRESSION AB Allogeneic hematopoietic stem cell transplantation (HSCT) is a technologically complicated procedure that represents the only cure for many hematologic malignancies. However, HSCT is often complicated by life-threatening toxicities related to the chemo-radiation conditioning regimen, poor engraftment of donor HSCs, the hyperinflammatory syndrome of graft-versus-host disease (GVHD), infection risks from immunosuppression, and end-organ damage. Bone marrow stromal cells (MSCs), also known as "mesenchymal stromal cells,'' not only play a nurturing role in the hematopoietic microenvironment but also can differentiate into other cell types of mesenchymal origin. MSCs are poorly immunogenic, and they can modulate immunological responses through interactions with a wide range of innate and adaptive immune cells to reduce inflammation. They are easily expanded ex vivo and after infusion, home to sites of injury and inflammation to promote tissue repair. Despite promising early trial results in HSCT with significant responses that have translated into survival benefits, there have been significant barriers to successful commercialization as an off-the-shelf therapy. Current efforts with MSCs in the HSCT setting are geared toward determining the factors determining potency, understanding the precise mechanisms of action in human HSCT, knowing their kinetics and fate, optimizing dose and schedule, incorporating biomarkers as response surrogates, addressing concerns about safety, optimizing clinical trial design, and negotiating the uncharted regulatory landscape for licensable cellular therapy. C1 [Battiwalla, Minoo; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM barrettjj@nhlbi.nih.gov FU Intramural Research Program of the National Heart, Lung, and Blood Institute FX This work was supported in part by the Intramural Research Program of the National Heart, Lung, and Blood Institute. NR 56 TC 7 Z9 7 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3368 EI 1937-3376 J9 TISSUE ENG PART B-RE JI Tissue Eng. Part B-Rev. PD JUN PY 2014 VL 20 IS 3 BP 211 EP 217 DI 10.1089/ten.teb.2013.0566 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AI9JU UT WOS:000337249700005 PM 24410434 ER PT J AU Agarwal, I Glazer, NL Barasch, E Biggs, ML Djousse, L Fitzpatrick, AL Gottdiener, JS Ix, JH Kizer, JR Rimm, EB Siscovick, DS Tracy, RP Zieman, SJ Mukamal, KJ AF Agarwal, Isha Glazer, Nicole L. Barasch, Eddy Biggs, Mary L. Djousse, Luc Fitzpatrick, Annette L. Gottdiener, John S. Ix, Joachim H. Kizer, Jorge R. Rimm, Eric B. Siscovick, David S. Tracy, Russell P. Zieman, Susan J. Mukamal, Kenneth J. TI Fibrosis-Related Biomarkers and Risk of Total and Cause-Specific Mortality The Cardiovascular Health Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE biomarkers; fibrosis; inflammation; mortality ID GROWTH-FACTOR BETA-1; TGF-BETA; DIABETIC-NEPHROPATHY; PULMONARY-FIBROSIS; CARDIAC FIBROSIS; DISEASE; SERUM; INFLAMMATION; PIRFENIDONE; INHIBITION AB Fibrosis has been implicated in diverse diseases of the liver, kidney, lungs, and heart, but its importance as a risk factor for mortality remains unconfirmed. We determined the prospective associations of 2 complementary biomarkers of fibrosis, transforming growth factor-beta (TGF-beta) and procollagen type III N-terminal propeptide (PIIINP), with total and cause-specific mortality risks among community-living older adults in the Cardiovascular Health Study (1996-2010). We measured circulating TGF-beta and PIIINP levels in plasma samples collected in 1996 and ascertained the number of deaths through 2010. Both TGF-beta and PIIINP were associated with elevated risks of total and pulmonary mortality after adjustment for sociodemographic, clinical, and biochemical risk factors. For total mortality, the hazard ratios per doubling of TGF-beta and PIIINP were 1.09 (95% confidence interval (CI): 1.01, 1.17; P = 0.02) and 1.14 (CI: 1.03, 1.27; P = 0.01), respectively. The corresponding hazard ratios for pulmonary mortality were 1.27 (CI: 1.01, 1.60; P = 0.04) for TGF-beta and 1.52 (CI: 1.11, 2.10; P = 0.01) for PIIINP. Associations of TGF-beta and PIIINP with total and pulmonary mortality were strongest among individuals with higher C-reactive protein concentrations (P for interaction < 0.05). Our findings provide some of the first large-scale prospective evidence that circulating biomarkers of fibrosis measured late in life are associated with death. C1 [Agarwal, Isha; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Glazer, Nicole L.] Boston Univ, Dept Med, Boston, MA 02215 USA. [Barasch, Eddy] SUNY Stony Brook, St Francis Hosp, Dept Res & Educ, Roslyn, NY USA. [Biggs, Mary L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Djousse, Luc] Boston Vet Affairs Healthcare Syst, Boston, MA USA. [Fitzpatrick, Annette L.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Gottdiener, John S.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Rimm, Eric B.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Tracy, Russell P.] Univ Vermont, Dept Biochem, Burlington, VT 05405 USA. [Zieman, Susan J.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Agarwal, I (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM Isha_Agarwal@hms.harvard.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung, and Blood Institute [HL118775-01, HL 094555, HL085083, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC 85083, N01HC85086]; National Institute on Aging [AG023629] FX This work was supported by grants HL118775-01, HL 094555, and HL085083 and contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC 85083, and N01HC85086 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by grant AG023629 from the National Institute on Aging. NR 33 TC 9 Z9 9 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2014 VL 179 IS 11 BP 1331 EP 1339 DI 10.1093/aje/kwu067 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI6ZI UT WOS:000337027400008 PM 24771724 ER PT J AU Litzelman, K Witt, WP Gangnon, RE Nieto, FJ Engelman, CD Mailick, MR Skinner, HG AF Litzelman, Kristin Witt, Whitney P. Gangnon, Ronald E. Nieto, F. Javier Engelman, Corinne D. Mailick, Marsha R. Skinner, Halcyon G. TI Association Between Informal Caregiving and Cellular Aging in the Survey of the Health of Wisconsin: The Role of Caregiving Characteristics, Stress, and Strain SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE caregivers; caregiver strain; population-based studies; stress; psychological; Survey of the Health of Wisconsin ID LEUKOCYTE TELOMERE LENGTH; CORONARY-HEART-DISEASE; AGE-RELATED DISEASE; QUALITY-OF-LIFE; CARDIOVASCULAR HEALTH; PHYSICAL HEALTH; RISK-FACTOR; DEVELOPMENTAL-DISABILITIES; LONGITUDINAL FINDINGS; PSYCHOLOGICAL STRESS AB The pathophysiological consequences of caregiving have not been fully elucidated. We evaluated how caregiving, stress, and caregiver strain were associated with shorter relative telomere length (RTL), a marker of cellular aging. Caregivers (n = 240) and some noncaregivers (n = 98) in the 2008-2010 Survey of the Health of Wisconsin, comprising a representative sample of Wisconsin adults aged 21-74 years, reported their sociodemographic, health, and psychological characteristics. RTL was assayed from blood or saliva samples. Median T and S values were used to determine the telomere-to-single copy gene ratio (T/S) for each sample, and log(T/S) was used as the dependent variable in analyses. Multivariable generalized additive models showed that RTL did not differ between caregivers and noncaregivers (difference in log(T/S) = -0.03; P > 0.05), but moderate-to-high levels of stress versus low stress were associated with longer RTL (difference = 0.15; P = 0.04). Among caregivers, more hours per week of care, caring for a young person, and greater strain were associated with shorter RTL (P < 0.05). Caregivers with discordant levels of stress and strain (i.e., low perceived stress/high strain) compared with low stress/low strain had the shortest RTL (difference = -0.24; P = 0.02, P-interaction = 0.13), corresponding to approximately 10-15 additional years of aging. Caregivers with these characteristics may be at increased risk for accelerated aging. Future work is necessary to better elucidate these relationships and develop interventions to improve the long-term health and well-being of caregivers. C1 [Litzelman, Kristin; Witt, Whitney P.; Gangnon, Ronald E.; Nieto, F. Javier; Engelman, Corinne D.; Skinner, Halcyon G.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA. [Gangnon, Ronald E.] Univ Wisconsin, Dept Biostat & Med Informat, Sch Med & Publ Hlth, Madison, WI USA. [Mailick, Marsha R.] Univ Wisconsin, Sch Social Work, Madison, WI 53706 USA. [Mailick, Marsha R.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. RP Litzelman, K (reprint author), NCI, 9609 Med Ctr Dr,MSC 9761,Room 3E620, Bethesda, MD 20892 USA. EM kristin.litzelman@nih.gov FU Wisconsin Partnership Program [233 PRJ56RV]; National Institutes of Health [5UL 1RR025011, RO-1 CA132718]; National Heart, Lung, and Blood Institute [1 RC2 HL101468]; National Institute on Aging [F31 AG 044073]; Center for Demography of Health and Aging at the University of Wisconsin-Madison FX Funding for SHOW was provided by the Wisconsin Partnership Program (grant 233 PRJ56RV), the National Institutes of Health (Clinical and Translational Science Award 5UL 1RR025011), and the National Heart, Lung, and Blood Institute (grant 1 RC2 HL101468). Funding for this study was provided by a training grant from the National Institute on Aging (grant F31 AG 044073; Principal Investigator: Kristin Litzelman) and the Center for Demography of Health and Aging at the University of Wisconsin-Madison, which supported the caregiving component of the SHOW interviews (Principal Investigator: Whitney P. Witt). The assays of telomere length were supported by National Institutes of Health grant RO-1 CA132718. NR 117 TC 9 Z9 9 U1 3 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2014 VL 179 IS 11 BP 1340 EP 1352 DI 10.1093/aje/kwu066 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI6ZI UT WOS:000337027400009 PM 24780842 ER PT J AU Baker, D Park, C Sweeney, C McCormack, L Durkin, M Brenner, R Dabelea, D Entwisle, B AF Baker, Dean Park, Christina Sweeney, Carol McCormack, Lacey Durkin, Maureen Brenner, Ruth Dabelea, Dana Entwisle, Barbara TI Recruitment of Women in the National Children's Study Initial Vanguard Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE birth cohort; children; epidemiology; National Children's Study; population; recruitment; sampling AB The initial Vanguard Study of the National Children's Study was conducted during 2009-2010 in 7 locations in the United States. A goal was to evaluate the feasibility and yield of a household-based sampling design to recruit pregnant women. A multistage area probability sampling design was used to identify study locations (generally, counties) that were subsequently divided into smaller geographical units, termed segments. Between 7 and 18 segments were selected in each location, and dwelling units within segments were listed. A household-based recruitment process was implemented, which included enumeration of households to identify age-eligible women, pregnancy screening to identify pregnant women eligible for immediate enrollment and nonpregnant women for telephone follow-up, and administration of informed consent to eligible women. After a recruitment period of 17-20 months, 67,181 (89%) households were enumerated, which identified 34,172 (88%) age-eligible women to whom the pregnancy screener was administered. Among those who completed the screener, 2,285 women became eligible for enrollment, of whom 1,399 (61%) enrolled. Although response rates were fairly high at initial contact and among pregnant women, the overall yield was lower than anticipated. In particular, telephone follow-up of nonpregnant women was not a practicable strategy for prospective recruitment of newly pregnant women. C1 [Baker, Dean] Univ Calif Irvine, Ctr Occupat & Environm Hlth, Irvine, CA 92617 USA. [Baker, Dean] Univ Calif Irvine, Sch Med, Dept Med, Irvine, CA 92617 USA. [Park, Christina; Brenner, Ruth] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Childrens Study Program Off, Rockville, MD USA. [Sweeney, Carol] Univ Utah, Sch Med, Dept Internal Med, Div Epidemiol, Salt Lake City, UT USA. [McCormack, Lacey] S Dakota State Univ, Coll Educ & Human Sci, Dept Hlth & Nutr Sci, Brookings, SD 57007 USA. [Durkin, Maureen] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. [Durkin, Maureen] Univ Wisconsin, Dept Pediat, Madison, WI USA. [Dabelea, Dana] Univ Colorado, Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Entwisle, Barbara] Univ N Carolina, Carolina Populat Ctr, Coll Arts & Sci, Chapel Hill, NC USA. [Entwisle, Barbara] Univ N Carolina, Dept Sociol, Coll Arts & Sci, Chapel Hill, NC USA. RP Baker, D (reprint author), Univ Calif Irvine, Ctr Occupat & Environm Hlth, Suite 100, Irvine, CA 92617 USA. EM dbaker@uci.edu RI Durkin, Maureen/B-7834-2015; OI Sweeney, Carol/0000-0003-1113-7160 FU National Institutes of Health, Department of Health and Human Services [N01-HD-53414, N01-HD-63416, N01-HD-53410, N01-HD-53415, N01-HD-53396, N01-HD-53413, N01-HD-53411] FX This work was supported by the National Institutes of Health, Department of Health and Human Services, administered by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-53414, N01-HD-63416, N01-HD-53410, N01-HD-53415, N01-HD-53396, N01-HD-53413, and N01-HD-53411). NR 17 TC 11 Z9 11 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2014 VL 179 IS 11 BP 1366 EP 1374 DI 10.1093/aje/kwu062 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI6ZI UT WOS:000337027400011 PM 24793429 ER PT J AU Blumberg, S Enanoria, WTA Lloyd-Smith, JO Lietman, TM Porco, TC AF Blumberg, Seth Enanoria, Wayne T. A. Lloyd-Smith, James O. Lietman, Thomas M. Porco, Travis C. TI Identifying Postelimination Trends for the Introduction and Transmissibility of Measles in the United States SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE disease elimination; effective reproduction number; heterogeneity of transmission; measles; preventable disease; transmissibility; United States; vaccine coverage ID VACCINATION COVERAGE; SIZE DISTRIBUTION; ELIMINATION; OUTBREAKS; POLIOMYELITIS; IMMUNIZATION; POPULATION; VACCINES; DISEASES; CHILDREN AB The continued elimination of measles requires accurate assessment of its epidemiology and a critical evaluation of how its incidence is changing with time. National surveillance of measles in the United States between 2001 and 2011 provides data on the number of measles introductions and the size of the resulting transmission chains. These data allow inference of the effective reproduction number, R-eff, and the probability of an outbreak occurring. Our estimate of 0.52 (95% confidence interval: 0.44, 0.60) for R-eff is smaller than prior results. Our findings are relatively insensitive to the possibility that as few as 75% of cases were detected. Although we confirm that measles remains eliminated, we identify an increasing trend in the number of measles cases with time. We show that this trend is likely attributable to an increase in the number of disease introductions rather than a change in the transmissibility of measles. However, we find that transmissibility may increase substantially if vaccine coverage drops by as little as 1%. Our general approach of characterizing the case burden of measles is applicable to the epidemiologic assessment of other weakly transmitting or vaccine-controlled pathogens that are either at risk of emerging or on the brink of elimination. C1 [Blumberg, Seth; Enanoria, Wayne T. A.; Lietman, Thomas M.; Porco, Travis C.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. [Blumberg, Seth; Lloyd-Smith, James O.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Enanoria, Wayne T. A.] Univ Calif Berkeley, Sch Publ Hlth, Ctr Infect Dis & Emergency Readiness, Berkeley, CA 94720 USA. [Lloyd-Smith, James O.] Univ Calif Los Angeles, Ecol & Evolutionary Biol Dept, Los Angeles, CA USA. [Lietman, Thomas M.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Lietman, Thomas M.; Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Porco, TC (reprint author), Univ Calif San Francisco, Francis I Proctor Fdn, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM travis.porco@ucsf.edu RI Lloyd-Smith, James/K-4080-2012 OI Lloyd-Smith, James/0000-0001-7941-502X FU National Institute of Health Modeling Infectious Disease Agent Study program [NIH NIGMS 1-U01-GM087728]; Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security; National Institutes of Health, Fogarty International Center; National Science Foundation [EF-0928690]; De Logi Chair in Biological Sciences FX This work was supported by the National Institute of Health Modeling Infectious Disease Agent Study program (grant NIH NIGMS 1-U01-GM087728 to T. C. P., T. M. L., W. T. A. E., and S. B.); the Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security (funding to S. B. and J.O.L.-S.); the National Institutes of Health, Fogarty International Center (funding to S. B. and J.O.L.-S.); the National Science Foundation (grant EF-0928690 to J.O.L.-S.); and the De Logi Chair in Biological Sciences (funding to J.O.L.-S.). NR 26 TC 11 Z9 11 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2014 VL 179 IS 11 BP 1375 EP 1382 DI 10.1093/aje/kwu068 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI6ZI UT WOS:000337027400012 PM 24786800 ER PT J AU Adams, KF Harris, TB Kipnis, V AF Adams, Kenneth F. Harris, Tamara B. Kipnis, Victor TI RE: "BODY MASS AND WEIGHT CHANGE IN ADULTS IN RELATION TO MORTALITY RISK" Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 [Adams, Kenneth F.] Minnesota Dept Hlth, Minnesota Canc Surveillance Syst, St Paul, MN 55164 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Kipnis, Victor] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Adams, KF (reprint author), Minnesota Dept Hlth, Minnesota Canc Surveillance Syst, St Paul, MN 55164 USA. EM kenneth.adams@state.mn.us NR 3 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2014 VL 179 IS 11 BP 1403 EP 1404 DI 10.1093/aje/kwu100 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI6ZI UT WOS:000337027400016 PM 24786798 ER PT J AU Ning, L Kurihara, H de Vega, S Ichikawa-Tomikawa, N Xu, Z Nonaka, R Kazuno, S Yamada, Y Miner, JH Arikawa-Hirasawa, E AF Ning, Liang Kurihara, Hidetake de Vega, Susana Ichikawa-Tomikawa, Naoki Xu, Zhuo Nonaka, Risa Kazuno, Saiko Yamada, Yoshihiko Miner, Jeffrey H. Arikawa-Hirasawa, Eri TI Laminin alpha 1 Regulates Age-Related Mesangial Cell Proliferation and Mesangial Matrix Accumulation through the TGF-beta Pathway SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GLOMERULAR-BASEMENT-MEMBRANE; GROWTH-FACTOR-BETA; DIABETIC-NEPHROPATHY; EXTRACELLULAR-MATRIX; TRANSFORMING GROWTH-FACTOR-BETA-1; KIDNEY-DISEASE; IN-VIVO; A-CHAIN; EXPRESSION; RECEPTOR AB Laminin alpha 1 (LAMA1), a subunit of the Laminin-111 basement membrane component, has been implicated in various biological functions in vivo and in vitro. Although LAMA1 is present in kidney, its roles in the kidney are unknown because of early embryonic lethality. Herein, we used a viable conditional knockout mouse model with a deletion of Lama1 in the epiblast Lineage (Lama1(cko)) to study the role of LAMA1 in kidney development and function. Adult Lama1(cko) mice developed focal glomerulosclerosis and proteinuria with age. In addition, mesangial cell proliferation was increased, and the mesangial matrix, which normally contains Laminin-111, was greatly expanded. In vitro, mesangial cells from Lama1(cko) mice exhibited significantly increased proliferation compared with those from controls. This increased proliferation was inhibited by the addition of exogenous LAMA1-containing laminin-111, but not by Laminin-211 or Laminin-511, suggesting a specific role for LAMA1 in regulating mesangial cell behavior. Moreover, the absence of LAMA1 increased transforming growth factor (TGF)-beta 1 induced Smad2 phosphorylation, and inhibitors of TGF-beta 1 receptor I kinase blocked Smad2 phosphorylation in both control and Lama1(cko) mesangial cells, indicating that the increased Smad2 phosphorylation occurred in the absence of LAMA1 via the TGF-beta 1 receptor. These findings suggest that LAMA1 plays a critical role in kidney function and kidney aging by regulating the mesangial cell population and mesangial matrix deposition through TGF-beta/Smad signaling. C1 [Ning, Liang; de Vega, Susana; Ichikawa-Tomikawa, Naoki; Xu, Zhuo; Nonaka, Risa; Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Biomed Res Ctr, Res Inst Dis Old Age, Tokyo 1138421, Japan. [Kurihara, Hidetake] Juntendo Univ, Grad Sch Med, Biomed Res Ctr, Dept Anat & Life Struct, Tokyo 1138421, Japan. [Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Biomed Res Ctr, Dept Neurol, Tokyo 1138421, Japan. [Kazuno, Saiko] Juntendo Univ, Grad Sch Med, Biomed Res Ctr, Div Prote & Biomol Sci, Tokyo 1138421, Japan. [Ichikawa-Tomikawa, Naoki] Fukushima Med Univ, Sch Med, Dept Basic Pathol, Fukushima, Japan. [Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Miner, Jeffrey H.] Washington Univ, Sch Med, Dept Internal Med, Div Renal, St Louis, MO 63110 USA. RP Arikawa-Hirasawa, E (reprint author), Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Bunkyo Ku, 2-1-1 Hongo, Tokyo 1138421, Japan. EM ehirasaw@juntendo.ac.jp FU Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan [24790860]; NIH Intramural Program of the National Institute of Dental and Craniofacial Research; NIH [R01DK078314]; MEXT Supported Program for the Strategic Research Foundation at Private Universities; [17082008]; [2230023] FX Supported by a Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan, Grant-in-Aid for Young Scientists (B) 24790860 (L.N.) and grants 17082008 and 2230023 (E.A.-H.), NIH Intramural Program of the National Institute of Dental and Craniofacial Research grant (Y.Y.), NIH grant R01DK078314 (J.H.M.), and MEXT Supported Program for the Strategic Research Foundation at Private Universities (2011 to 2015). NR 52 TC 9 Z9 10 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 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2014 VL 184 IS 6 BP 1683 EP 1694 DI 10.1016/j.ajpath.2014.02.006 PG 12 WC Pathology SC Pathology GA AI5ZE UT WOS:000336948700007 PM 24720953 ER PT J AU Wang, Y Feng, DC Wang, H Xu, MJ Park, O Li, YM Gao, B AF Wang, Yan Feng, Dechun Wang, Hua Xu, Ming-Jiang Park, Ogyi Li, Yongmei Gao, Bin TI STAT4 Knockout Mice Are More Susceptible to Concanavalin A-Induced T-Cell Hepatitis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; MEDIATED LIVER-INJURY; ISCHEMIA/REPERFUSION INJURY; SERINE PHOSPHORYLATION; IFN-GAMMA; IL-12; INFLAMMATION; ACTIVATION; INTERLEUKIN-12; INVOLVEMENT AB STAT4, which is activated mainly by IL-12, promotes inflammatory responses by inducing Th1 and Th2 cytokines. Recent genome-wide association studies indicate that STAT4 gene variants are associated with risk of various types of liver diseases, but how STAT4 contributes to liver disease pathogenesis remains obscure. In this study, STAT4 activation was detected in liver immune cells from patients with viral hepatitis and autoimmune hepatitis, as well as in a mouse model of concanavaLin A (Con A)-induced hepatitis. Such STAT4 activation was detected mainly in T cells, natural killer T cells, and macrophages and Kupffer cells, and was diminished in I112a/and 11/26/mice. As expected, disruption of the Stat4 gene reduced production of Th1 and Th2 cytokines, but surprisingly exacerbated Con A-induced liver injury. Similarly, disruption of IL12a or 11126 also augmented Con A-induced hepatocellular damage. Further studies showed that hepatic natural killer T (NKT) cells from Con A-treated Stat4(-/-) mice had higher levels of FasL expression and increased cytotoxicity against hepatocytes than those from Con A-treated WT mice. In vitro, blocking FasL attenuated Stat4(-/-) NKT cytotoxicity against hepatocytes. In conclusion, despite up-regulation of proinflammatory cytokines, STAT4 protects against acute T-cell hepatitis, which is mediated by direct or indirect down-regulation of FasL expression on NKT cells. C1 [Wang, Yan; Feng, Dechun; Wang, Hua; Xu, Ming-Jiang; Park, Ogyi; Li, Yongmei; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. [Wang, Yan] Peking Univ, Hosp 1, Dept Infect Dis, Beijing 100871, Peoples R China. RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI Feng, Dechun/Q-5962-2016 FU NIH-National Institute on Alcohol Abuse and Alcoholism; China Scholarship Council; Wu Mengchao Medical Science Foundation; National Natural Science Foundation of China [81300312]; NIH [N01-DK-7-0004/HHSN267200700004C] FX Supported by the intramural program of the NIH-National Institute on Alcohol Abuse and Alcoholism (B.G.), the China Scholarship Council (Y.W.), the Wu Mengchao Medical Science Foundation (Y.W.), and National Natural Science Foundation of China grant 81300312 (Y.W.). The Liver Tissue Cell Distribution System, University of Minnesota, Minneapolis, MN, is supported by NIH contract N01-DK-7-0004/HHSN267200700004C. NR 40 TC 6 Z9 7 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2014 VL 184 IS 6 BP 1785 EP 1794 DI 10.1016/j.ajpath.2014.02.023 PG 10 WC Pathology SC Pathology GA AI5ZE UT WOS:000336948700016 PM 24731448 ER PT J AU Martin, DL Marks, M Galdos-Cardenas, G Gilman, RH Goodhew, B Ferrufino, L Halperin, A Sanchez, G Verastegui, M Escalante, P Naquira, C Levy, MZ Bern, C AF Martin, Diana L. Marks, Morgan Galdos-Cardenas, Gerson Gilman, Robert H. Goodhew, Brook Ferrufino, Lisbeth Halperin, Anthony Sanchez, Gerardo Verastegui, Manuela Escalante, Patricia Naquira, Cesar Levy, Michael Z. Bern, Caryn TI Regional Variation in the Correlation of Antibody and T-Cell Responses to Trypanosoma cruzi SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CHAGAS-DISEASE; GENETIC-VARIABILITY; IMMUNE-RESPONSES; INTERFERON-GAMMA; INFECTION; BLOOD; ARGENTINA; TRANSMISSION; PATHOGENESIS; POPULATIONS AB Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major cause of morbidity and mortality in Central and South America. Geographic variations in the sensitivity of serologic diagnostic assays to T. cruzi may reflect differences in T cruzi exposure. We measured parasite-specific T-cell responses among seropositive individuals in two populations from South America with widely varying antibody titers against T. cruzi. Antibody titers among seropositive individuals were significantly lower in Arequipa, Peru compared with Santa Cruz, Bolivia. Similarly, the proportion of seropositive individuals with positive T-cell responses was lower in Peru than Bolivia, resulting in overall lower frequencies of interferon-gamma (IFN gamma)-secreting cells from Peruvian samples. However, the magnitude of the IFN gamma response was similar among the IFN gamma responders in both locations. These data indicate that immunological discrepancies based on geographic region are reflected in T-cell responses as well as antibody responses. C1 [Martin, Diana L.; Goodhew, Brook] Ctr Dis Control & Prevent, Atlanta, GA 30329 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. [Galdos-Cardenas, Gerson; Ferrufino, Lisbeth] Hosp Univ Japones, Santa Cruz, Bolivia. [Galdos-Cardenas, Gerson; Ferrufino, Lisbeth] Asociac Benef PRISMA, Lima, Peru. [Gilman, Robert H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Naquira, Cesar] Arequipa Minist Hlth, Arequipa, Peru. [Levy, Michael Z.] Univ Penn, Philadelphia, PA 19104 USA. [Sanchez, Gerardo; Verastegui, Manuela] Univ Peruana Cayetano Heredia, Lima, Peru. RP Martin, DL (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, MS D-65,1600 Clifton Rd NE, Atlanta, GA 30329 USA. EM hzx3@cdc.gov; mmarkster@gmail.com; gerson_galdos@yahoo.es; gilmanabob@gmail.com; isd6@cdc.gov; lisbeth_ferrufino@yahoo.es; gjsg2@hotmail.com; mveraste@jhsph.edu; patriciaeem2008@gmail.com; cesar.naquira@gmail.com; rnzlevy@mail.med.upenn.edu; Caryn.Bern2@ucsf.edu FU National Institutes of Health Tropical Medical Research Center [P50 AI074285]; National Institutes of Health Fogarty Scholars Program [R24 TW007988] FX This work was funded by National Institutes of Health Tropical Medical Research Center Grant P50 AI074285 and National Institutes of Health Fogarty Scholars Program Grant R24 TW007988. NR 35 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 2014 VL 90 IS 6 BP 1074 EP 1081 DI 10.4269/ajtmh.13-0391 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AI4FD UT WOS:000336820200016 PM 24710614 ER PT J AU Genkinger, JM Wang, M Li, R Albanes, D Anderson, KE Bernstein, L van den Brandt, PA English, DR Freudenheim, JL Fuchs, CS Gapstur, SM Giles, GG Goldbohm, RA Hakansson, N Horn-Ross, PL Koushik, A Marshall, JR McCullough, ML Miller, AB Robien, K Rohan, TE Schairer, C Silverman, DT Stolzenberg-Solomon, RZ Virtamo, J Willett, WC Wolk, A Ziegler, RG Smith-Warner, SA AF Genkinger, J. M. Wang, M. Li, R. Albanes, D. Anderson, K. E. Bernstein, L. van den Brandt, P. A. English, D. R. Freudenheim, J. L. Fuchs, C. S. Gapstur, S. M. Giles, G. G. Goldbohm, R. A. Hakansson, N. Horn-Ross, P. L. Koushik, A. Marshall, J. R. McCullough, M. L. Miller, A. B. Robien, K. Rohan, T. E. Schairer, C. Silverman, D. T. Stolzenberg-Solomon, R. Z. Virtamo, J. Willett, W. C. Wolk, A. Ziegler, R. G. Smith-Warner, S. A. TI Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies SO ANNALS OF ONCOLOGY LA English DT Review DE pancreatic cancer; dairy products; calcium intake; pooled analysis ID FOOD-FREQUENCY QUESTIONNAIRE; VITAMIN-D STATUS; DIETARY ASSESSMENT; UNITED-STATES; REGRESSION-MODELS; MALE SMOKERS; CALIFORNIA TEACHERS; 25-HYDROXYVITAMIN D; NUTRITIONAL FACTORS; EXOCRINE PANCREAS AB .Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing a parts per thousand yen500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes a parts per thousand yen1300 with < 500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk. C1 [Genkinger, J. M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Wang, M.; Li, R.; Willett, W. C.; Smith-Warner, S. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wang, M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Albanes, D.; Schairer, C.; Silverman, D. T.; Stolzenberg-Solomon, R. Z.; Ziegler, R. G.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Anderson, K. E.] Univ Minnesota, Sch Publ Hlth, Mason Canc Ctr, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Bernstein, L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Bernstein, L.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [van den Brandt, P. A.] Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Epidemiol, Maastricht, Netherlands. [English, D. R.; Giles, G. G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Canc Epidemiol Ctr,Canc Council Victoria, Melbourne, Vic, Australia. [Freudenheim, J. L.; Marshall, J. R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Fuchs, C. S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Fuchs, C. S.; Willett, W. C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Fuchs, C. S.; Willett, W. C.] Harvard Univ, Sch Med, Boston, MA USA. [Gapstur, S. M.; McCullough, M. L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Goldbohm, R. A.] TNO Qual Life, Dept Prevent & Hlth, Leiden, Netherlands. [Hakansson, N.; Wolk, A.] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. [Horn-Ross, P. L.] Canc Prevent Inst Calif, Fremont, CA USA. [Koushik, A.] Univ Montreal, Dept Social & Prevent Med, Montreal, PQ, Canada. [Miller, A. B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Robien, K.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA. [Rohan, T. E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Virtamo, J.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Willett, W. C.; Smith-Warner, S. A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Genkinger, JM (reprint author), Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St, New York, NY 10019 USA. EM jg3081@columbia.edu RI Albanes, Demetrius/B-9749-2015; OI Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188 FU National Institutes of Health [CA55075, CA139578] FX This work was supported by National Institutes of Health grants #CA55075 and #CA139578. NR 87 TC 10 Z9 10 U1 3 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2014 VL 25 IS 6 BP 1106 EP 1115 DI 10.1093/annonc/mdu019 PG 10 WC Oncology SC Oncology GA AI6ZO UT WOS:000337028100005 PM 24631943 ER PT J AU Akilzhanova, A Nurkina, Z Momynaliev, K Ramanculov, E Zhumadilov, Z Rakhypbekov, T Hayashida, N Nakashima, M Takamura, N AF Akilzhanova, Ainur Nurkina, Zhannur Momynaliev, Kuvat Ramanculov, Erlan Zhumadilov, Zhaxibai Rakhypbekov, Tolebay Hayashida, Naomi Nakashima, Masahiro Takamura, Noboru TI Genetic Profile and Determinants of Homocysteine Levels in Kazakhstan Patients with Breast Cancer (vol 33, pg 4049, 2013) SO ANTICANCER RESEARCH LA English DT Correction C1 [Akilzhanova, Ainur; Hayashida, Naomi; Takamura, Noboru] Nagasaki Univ, Grad Sch Biomed Sci, Dept Global Hlth Med & Welf, Nagasaki 852, Japan. [Akilzhanova, Ainur; Nurkina, Zhannur; Zhumadilov, Zhaxibai] Nazarbayev Univ, Ctr Life Sci, Dept Genom & Personalised Med, Astana, Kazakhstan. [Akilzhanova, Ainur; Momynaliev, Kuvat; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan. [Rakhypbekov, Tolebay] Semey State Med Univ, Ctr Oncol, Semey, Kazakhstan. [Nakashima, Masahiro] Nagasaki Univ, Grad Sch Biomed Sci, Dept Tumor & Diagnost Pathol, Nagasaki 852, Japan. RP Akilzhanova, A (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Dept Global Hlth Med & Welf, Nagasaki 852, Japan. NR 1 TC 0 Z9 0 U1 1 U2 7 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 EI 1791-7530 J9 ANTICANCER RES JI Anticancer Res. PD JUN PY 2014 VL 34 IS 6 BP 3231 EP 3231 PG 1 WC Oncology SC Oncology GA AI4ZM UT WOS:000336875200071 ER PT J AU Kessler, DC Taylor, JA Dunson, DB AF Kessler, David C. Taylor, Jack A. Dunson, David B. TI Learning phenotype densities conditional on many interacting predictors SO BIOINFORMATICS LA English DT Article ID DIRICHLET PROCESS MIXTURES; VARIABLE SELECTION; EM ALGORITHM; REGRESSION; MODELS; EXPERTS AB Motivation: Estimating a phenotype distribution conditional on a set of discrete-valued predictors is a commonly encountered task. For example, interest may be in how the density of a quantitative trait varies with single nucleotide polymorphisms and patient characteristics. The subset of important predictors is not usually known in advance. This becomes more challenging with a high-dimensional predictor set when there is the possibility of interaction. Results: We demonstrate a novel non-parametric Bayes method based on a tensor factorization of predictor-dependent weights for Gaussian kernels. The method uses multistage predictor selection for dimension reduction, providing succinct models for the phenotype distribution. The resulting conditional density morphs flexibly with the selected predictors. In a simulation study and an application to molecular epidemiology data, we demonstrate advantages over commonly used methods. C1 [Kessler, David C.] SAS Inst Inc, Adv Analyt Div, Cary, NC 27513 USA. [Taylor, Jack A.] NIEHS, Mol & Genet Epidemiol Sect, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Taylor, Jack A.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Dunson, David B.] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA. RP Kessler, DC (reprint author), SAS Inst Inc, Adv Analyt Div, Cary, NC 27513 USA. EM dave.kessler@gmail.com OI taylor, jack/0000-0001-5303-6398 FU Intramural Research Program of the NIH; National Institute of Environmental Health Sciences [Z01 ES049032, R01ES017240, R01ES017436]; National Institute of Environmental Health Sciences training [T32ES007018] FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, Z01 ES049032. David Kessler's work was partially supported by National Institute of Environmental Health Sciences training grant T32ES007018. David Dunson's work was supported by Award Numbers R01ES017240 and R01ES017436 from the National Institute of Environmental Health Sciences. NR 33 TC 1 Z9 1 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD JUN 1 PY 2014 VL 30 IS 11 BP 1562 EP 1568 DI 10.1093/bioinformatics/btu040 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA AI7CU UT WOS:000337040200010 PM 24501099 ER PT J AU Volkow, ND Tomasi, D Wang, GJ Studentsova, Y Margus, B Crawford, TO AF Volkow, Nora D. Tomasi, Dardo Wang, Gene-Jack Studentsova, Yana Margus, Brad Crawford, Thomas O. TI Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives SO BRAIN LA English DT Article DE cerebellum; globus pallidus; fusiform gyrus; hippocampus; ataxia telangiectasia mutated; ATM ID PARKINSONS-DISEASE; ABNORMALITIES; MOTOR; CONNECTIVITY; STIMULATION; CEREBELLUM; PHENOTYPE; DYSTONIA; BEHAVIOR; ATROPHY AB Ataxia-Telangiectasia (A-T) is a recessive multi-system disorder with prominent cerebellar degeneration. Volkow et al. use PET to reveal widespread changes in brain glucose metabolism in patients with A-T, in addition to the anticipated reduction in cerebellar metabolism. Hyperactivity in the globus pallidus is indicative of basal ganglia involvement in the disorder.Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and F-18-fluorodeoxyglucose to measure brain glucose metabolism (quantified as A mu mol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic rates including hyperactivity in globus pallidus indicative of basal ganglia involvement. Changes in basal ganglia metabolism offer potential insight into targeting strategies for therapeutic deep brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions. C1 [Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana] NIAAA, Rockville, MD 20857 USA. [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. [Margus, Brad] AT Childrens Project, Coconut Creek, FL 33073 USA. [Crawford, Thomas O.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov RI Tomasi, Dardo/J-2127-2015 FU National Institutes of Health's (NIH) Intramural Research Program National Institute on Alcohol Abuse and Alcoholism (NIAAA) [Y1AA3009]; A-T Children's Project FX Research supported by National Institutes of Health's (NIH) Intramural Research Program National Institute on Alcohol Abuse and Alcoholism (NIAAA) #Y1AA3009 and by the A-T Children's Project and carried out at Brookhaven National Laboratory. NR 42 TC 7 Z9 7 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD JUN PY 2014 VL 137 BP 1753 EP 1761 DI 10.1093/brain/awu092 PN 6 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AI6ZU UT WOS:000337028900022 PM 24747834 ER PT J AU Ellis, MW Schlett, CD Millar, EV Wilkins, KJ Crawford, KB Morrison-Rodriguez, SM Pacha, LA Gorwitz, RJ Lanier, JB Tribble, DR AF Ellis, Michael W. Schlett, Carey D. Millar, Eugene V. Wilkins, Kenneth J. Crawford, Katrina B. Morrison-Rodriguez, Stephanie M. Pacha, Laura A. Gorwitz, Rachel J. Lanier, Jeffrey B. Tribble, David R. TI Hygiene Strategies to Prevent Methicillin-Resistant Staphylococcus aureus Skin and Soft Tissue Infections: A Cluster-Randomized Controlled Trial Among High-Risk Military Trainees SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Staphylococcus aureus; methicillin-resistant Staphylococcus aureus (MRSA); skin and soft tissue infection; chlorhexidine; military ID HOUSEHOLD CONTACTS; MARINE RECRUITS; UNITED-STATES; COLONIZATION; EPIDEMIOLOGY; CELLULITIS; CHILDREN; PREVALENCE; CALIFORNIA; MUPIROCIN AB Background. Effective measures are needed to prevent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) in high-risk community settings. The study objective was to evaluate the effect of personal hygiene-based strategies on rates of overall SSTI and MRSA SSTI. Methods. We conducted a prospective, field-based, cluster-randomized trial in US Army Infantry trainees from May 2010 through January 2012. There were 3 study groups with incrementally increased education and hygiene-based interventions: standard (S), enhanced standard (ES), and chlorhexidine (CHG). The primary endpoints were incidence of overall SSTI and MRSA SSTI. Results. The study included 30 209 trainees constituting 540 platoons (168 S, 192 ES, and 180 CHG). A total of 1203 (4%) participants developed SSTI, 316 (26%) due to MRSA. The overall SSTI rate was 4.15 (95% confidence interval [CI], 3.77-4.58) per 100 person-cycles. SSTI rates by study group were 3.48 (95% CI, 2.87-4.22) for S, 4.18 (95% CI, 3.56-4.90) for ES, and 4.71 (95% CI, 4.03-5.50) for CHG. The MRSA SSTI rate per 100 person-cycles for all groups was 1.10 (95% CI,.91-1.32). MRSA SSTI rates by study group were 1.0 (95% CI,.70-1.42) for S, 1.29 (95% CI,.98-1.71) for ES, and 0.97 (95% CI,.70-1.36) for CHG. Conclusions. Personal hygiene and education measures, including once-weekly use of chlorhexidine body wash, did not prevent overall SSTI or MRSA SSTI in a high-risk population of military trainees. C1 [Ellis, Michael W.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Schlett, Carey D.; Millar, Eugene V.; Crawford, Katrina B.; Morrison-Rodriguez, Stephanie M.; Tribble, David R.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Wilkins, Kenneth J.] NIDDK, NIH, Bethesda, MD 20892 USA. [Pacha, Laura A.] US Army Publ Hlth Command, Army Inst Publ Hlth, Aberdeen Proving Ground, MD USA. [Gorwitz, Rachel J.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Lanier, Jeffrey B.] Martin Army Community Hosp, Ft Benning, GA USA. RP Ellis, MW (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM michael.ellis@usuhs.edu FU Infectious Disease Clinical Research Program, a DoD program through the Uniformed Services University of the Health Sciences; National Institute of Allergy and Infectious Diseases, National Institutes of Health [Y1-AI-5072]; CDC, National Center for Emerging and Zoonotic Infectious Diseases, Division of Healthcare Quality Promotion [09FED914272]; DoD Global Emerging Infections Surveillance program [C0366-11-HS] FX The work was supported by the Infectious Disease Clinical Research Program, a DoD program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (Interagency Agreement Y1-AI-5072). Additional funding was provided by CDC, National Center for Emerging and Zoonotic Infectious Diseases, Division of Healthcare Quality Promotion (Interagency Agreement (09FED914272 to M. W. E.), and the DoD Global Emerging Infections Surveillance program (C0366-11-HS to M. W. E.). NR 38 TC 15 Z9 15 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2014 VL 58 IS 11 BP 1540 EP 1548 DI 10.1093/cid/ciu166 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AI7AL UT WOS:000337031200009 PM 24633684 ER PT J AU Chambers, HF Bartlett, JG Bonomo, RA Chiou, C Cosgrove, SE Cross, HR Daum, RS Downing, M Evans, SR Knisely, J Kreiswirth, BN Lautenbach, E Mickley, BS Patel, R Pettigrew, MM Rodvold, KA Spellberg, B Fowler, VG AF Chambers, Henry F. Bartlett, John G. Bonomo, Robert A. Chiou, Christine Cosgrove, Sara E. Cross, Heather R. Daum, Robert S. Downing, Michele Evans, Scott R. Knisely, Jane Kreiswirth, Barry N. Lautenbach, Ebbing Mickley, Brenda S. Patel, Robin Pettigrew, Melinda M. Rodvold, Keith A. Spellberg, Brad Fowler, Vance G., Jr. TI Antibacterial Resistance Leadership Group: Open for Business SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material DE antibacterial resistance; ARLG; Leadership Group; clinical trials; clinical research AB Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance. C1 [Chambers, Henry F.; Downing, Michele] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bartlett, John G.; Cosgrove, Sara E.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Bonomo, Robert A.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Med Serv, Cleveland, OH 44106 USA. [Chiou, Christine; Knisely, Jane] NIH, Div Microbiol & Infect Dis, Inst Allergy & Infect Dis, Bethesda, MD 20892 USA. [Cross, Heather R.; Mickley, Brenda S.; Fowler, Vance G., Jr.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Daum, Robert S.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Evans, Scott R.] Harvard Univ, Dept Biostat, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Kreiswirth, Barry N.] Rutgers State Univ, New Jersey Med Sch, TB Ctr, Publ Hlth Res Inst, Newark, NJ USA. [Lautenbach, Ebbing] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Patel, Robin] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Patel, Robin] Mayo Clin, Dept Med, Rochester, MN USA. [Pettigrew, Melinda M.] Yale Univ, Sch Publ Hlth, Dept Epidemiol, New Haven, CT USA. [Rodvold, Keith A.] Univ Illinois, Coll Pharm, Chicago, IL USA. [Rodvold, Keith A.] Univ Illinois, Coll Med, Chicago, IL USA. [Spellberg, Brad] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Fowler, Vance G., Jr.] Duke Univ, Dept Med, Durham, NC USA. RP Fowler, VG (reprint author), Duke Univ, Med Ctr, Dept Med, Div Infect Dis, Box 102359,Hanes Bldg,Rm 153, Durham, NC 27710 USA. EM fowle003@mc.duke.edu FU NIAID NIH HHS [UM1-AI104681, AI063517-07, AI072219-05, R01 AI063517, R01 AI072219, UM1 AI104681] NR 0 TC 13 Z9 13 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2014 VL 58 IS 11 BP 1571 EP 1576 DI 10.1093/cid/ciu132 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AI7AL UT WOS:000337031200013 PM 24610430 ER PT J AU Echouffo-Tcheugui, JB Prorok, PC AF Echouffo-Tcheugui, Justin B. Prorok, Philip C. TI Considerations in the design of randomized trials to screen for type 2 diabetes SO CLINICAL TRIALS LA English DT Article ID RISK-ASSESSMENT TOOLS; ADDITION-CAMBRIDGE; TASK-FORCE; CANCER; PROSTATE; LUNG; PEOPLE; DEATH; INDIVIDUALS; MORTALITY AB Background Randomized controlled trials (RCTs) are the most robust and valid approach to evaluate screening for diseases. Many in the diabetes research community have advocated sole reliance on RCTs for designing diabetes screening policies. However, the challenges of conducting RCTs of screening for type 2 diabetes may have been underappreciated. Purpose Discuss the key theoretical concepts and practical challenges of designing and conducting RCTs of diabetes screening. Methods Narrative and critical review of the literature pertaining to the theory and practice of designing and conducting RCTs of diabetes screening. Results We present the theoretical basis of a diabetes screening trial, using concepts developed mainly in studies of cancer screening and illustrations from the Cambridge component of the Anglo Danish Dutch Study of Intensive Treatment In peOple with screeN-detected diabetes in primary care (ADDITION-Cambridge), the only extant trial of diabetes screening. We examine design issues, including the appropriate trial question, choice of design, and duration of follow-up, and address aspects of trial implementation, including recruitment, randomization, endpoint determination, sample size requirements, and screening interval. Limitations The limited number of trials of diabetes screening did not permit us to illustrate many of the practical difficulties one encounters when implementing theoretical concepts. Conclusion When diabetes screening trials are planned, we suggest careful consideration to potential areas of practical difficulty, especially the need for particularly large sample sizes and extended follow-up, and the choice of appropriate outcomes and screening intervals. C1 [Echouffo-Tcheugui, Justin B.] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA. [Prorok, Philip C.] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Echouffo-Tcheugui, JB (reprint author), Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM jechouf@emory.edu NR 44 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD JUN PY 2014 VL 11 IS 3 BP 284 EP 291 DI 10.1177/1740774513517062 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI3UX UT WOS:000336791500002 PM 24459176 ER PT J AU Snyder, PJ Ellenberg, SS Cunningham, GR Matsumoto, AM Bhasin, S Barrett-Connor, E Gill, TM Farrar, JT Cella, D Rosen, RC Resnick, SM Swerdloff, RS Cauley, JA Cifelli, D Fluharty, L Pahor, M Ensrud, KE Lewis, CE Molitch, ME Crandall, JP Wang, C Budoff, MJ Wenger, NK Mohler, ER Bild, DE Cook, NL Keaveny, TM Kopperdahl, DL Lee, D Schwartz, AV Storer, TW Ershler, WB Roy, CN Raffel, LJ Romashkan, S Hadley, E AF Snyder, Peter J. Ellenberg, Susan S. Cunningham, Glenn R. Matsumoto, Alvin M. Bhasin, Shalender Barrett-Connor, Elizabeth Gill, Thomas M. Farrar, John T. Cella, David Rosen, Raymond C. Resnick, Susan M. Swerdloff, Ronald S. Cauley, Jane A. Cifelli, Denise Fluharty, Laura Pahor, Marco Ensrud, Kristine E. Lewis, Cora E. Molitch, Mark E. Crandall, Jill P. Wang, Christina Budoff, Matthew J. Wenger, Nanette K. Mohler, Emile R., III Bild, Diane E. Cook, Nakela L. Keaveny, Tony M. Kopperdahl, David L. Lee, David Schwartz, Ann V. Storer, Thomas W. Ershler, William B. Roy, Cindy N. Raffel, Leslie J. Romashkan, Sergei Hadley, Evan TI The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men SO CLINICAL TRIALS LA English DT Article ID LEAN BODY-MASS; BENIGN PROSTATIC HYPERPLASIA; LOW SERUM TESTOSTERONE; BONE-MINERAL DENSITY; OLDER MEN; MUSCLE STRENGTH; TRANSDERMAL TESTOSTERONE; EXOGENOUS TESTOSTERONE; PHYSICAL PERFORMANCE; SEXUAL FUNCTION AB Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation. Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant. Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort. C1 [Snyder, Peter J.] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Ellenberg, Susan S.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Cunningham, Glenn R.] Baylor Coll Med, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA. [Cunningham, Glenn R.] St Lukes Med Ctr, Houston, TX USA. [Matsumoto, Alvin M.] Univ Washington, Sch Med,Dept Vet Affairs Puget Sound Hlth Care Sy, Geriatr Res Educ & Clin Ctr,Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Bhasin, Shalender] Harvard Univ, Sch Med, Brigham & Womens Hosp, Res Program Mens Hlth Aging & Metab, Boston, MA USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Sch Med, Dept Family & Preventat Med, La Jolla, CA 92093 USA. [Gill, Thomas M.] Yale Univ, Sch Med, Div Geriatr Med, New Haven, CT USA. [Farrar, John T.; Cifelli, Denise; Fluharty, Laura] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Rosen, Raymond C.] New England Res Inst, Watertown, MA 02172 USA. [Resnick, Susan M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA. [Swerdloff, Ronald S.; Wang, Christina] Harbor Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst, Div Endocrinol, Torrance, CA USA. [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Pahor, Marco] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Minneapolis VA Hlth Care Syst, Minneapolis, MN 55455 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. [Molitch, Mark E.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. [Crandall, Jill P.] Albert Einstein Coll Med, Div Endocrinol & Geriatr, Bronx, NY 10467 USA. [Budoff, Matthew J.] Harbor Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA USA. [Wenger, Nanette K.] Emory Univ, Sch Med, Div Cardiol, Emory Heart & Vasc Ctr, Atlanta, GA 30322 USA. [Mohler, Emile R., III] Univ Penn, Perelman Sch Med, Div Cardiovasc Dis, Philadelphia, PA 19104 USA. [Mohler, Emile R., III] Univ Penn, Perelman Sch Med, Sect Vasc Med, Philadelphia, PA 19104 USA. [Bild, Diane E.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Cook, Nakela L.] NHLBI, Clin Applicat & Prevent Branch, Div Cardiovasc Sci, Ctr Cardiovasc Outcomes Res, Bethesda, MD 20892 USA. [Keaveny, Tony M.] Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA. [Keaveny, Tony M.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. [Keaveny, Tony M.; Kopperdahl, David L.; Lee, David] ON Diagnost, Berkeley, CA USA. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Storer, Thomas W.] Boston Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA USA. [Ershler, William B.] Inst Adv Studies Aging, Div Hematol Oncol, Falls Church, VA USA. [Roy, Cindy N.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. [Raffel, Leslie J.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Romashkan, Sergei; Hadley, Evan] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. RP Snyder, PJ (reprint author), Univ Penn, Smilow Ctr Translat Res, Div Endocrinol Diabet & Metab, Perelman Sch Med, 3400 Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM pjs@mail.med.upenn.edu RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU National Institute on Aging, National Institutes of Health [U01 AG030644, U01 AG034661, R01 AG37679]; National Heart, Lung and Blood Institute; National Institute of Neurological Diseases and Stroke; National Institute of Child Health and Human Development; National Institute on Aging [R01 AG037679]; AbbVie; Department of Veterans Affairs Puget Sound Health Care System; Midcareer Investigator Award in Patient-Oriented Research from the National Institute on Aging [K24-AG021507]; Academic Leadership Award from the National Institute on Aging [K07AG043587]; Claude D. Pepper Older Americans Independence Center [P30-AG021342]; Intramural Research Program, National Institute on Aging, National Institutes of Health; National Institute for Diabetes, Digestive and Kidney Diseases, National Institutes of Health [DK079626] FX The Testosterone Trials were supported by a grant from the National Institute on Aging, National Institutes of Health (U01 AG030644), supplemented by funds from the National Heart, Lung and Blood Institute, National Institute of Neurological Diseases and Stroke, and National Institute of Child Health and Human Development. The Bone Trial was supported by a grant from the National Institute on Aging (R01 AG037679). The Anemia Trial was supported by a grant from the National Institute on Aging, National Institutes of Health (U01 AG034661) to the Partnership for Anemia Clinical and Translational Trials in the Elderly consortium. AbbVie (formerly Solvay and Abbott Laboratories) generously provided funding, AndroGel, and placebo gel. A. M. M. was supported by the Department of Veterans Affairs Puget Sound Health Care System. T. M. G. was the recipient of a Midcareer Investigator Award in Patient-Oriented Research (K24-AG021507) and is the recipient of an Academic Leadership Award (K07AG043587), both from the National Institute on Aging. The Yale Field Center was partially supported by the Claude D. Pepper Older Americans Independence Center (P30-AG021342). S. M. R. was supported by the Intramural Research Program, National Institute on Aging, National Institutes of Health. C. E. L. was supported by the National Institute for Diabetes, Digestive and Kidney Diseases, National Institutes of Health (DK079626) to the UAB Diabetes Research and Training Center. J.A.C. was supported by the National Institute on Aging, National Institutes of Health (R01 AG37679). NR 46 TC 36 Z9 36 U1 1 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD JUN PY 2014 VL 11 IS 3 BP 362 EP 375 DI 10.1177/1740774514524032 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI3UX UT WOS:000336791500011 PM 24686158 ER PT J AU Baker, SG AF Baker, Stuart G. TI Principal stratification: All-or-none versus partial compliance SO CLINICAL TRIALS LA English DT Letter ID RANDOMIZED-TRIAL; NONCOMPLIANCE; INTENTION; TREAT C1 NCI, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, 9609 Med Ctr Dr 5E638,MSC 9789, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 10 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD JUN PY 2014 VL 11 IS 3 BP 380 EP 381 DI 10.1177/1740774514524650 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI3UX UT WOS:000336791500013 PM 24844842 ER PT J AU Craig, MT McBain, CJ AF Craig, Michael T. McBain, Chris J. TI The emerging role of GABAB receptors as regulators of network dynamics: fast actions from a 'slow' receptor? SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID NEOCORTICAL GABAERGIC NEURONS; PERSISTENT CORTICAL ACTIVITY; DENDRITIC CA2+ SPIKES; PYRAMIDAL NEURONS; NEUROGLIAFORM CELLS; LAYER 1; PREFRONTAL CORTEX; CEREBRAL-CORTEX; DISTINCT ROLES; DENTATE GYRUS AB Convention holds that ionotropic receptors mediate fast neurotransmission and that 'slow' G-protein coupled metabotropic receptors have a secondary, modulatory role in the control of neuronal networks. Here, we discuss recent evidence showing that activation of metabotropic GABA(B) receptors in cortical layer 1 can powerfully inhibit principal cell activity and that their activation can rapidly halt ongoing network activity. Inputs from both within and outwith the cortex converge upon layer 1 where they target various populations of interneurons, including neurogliaform cells. We argue that neurogliaform cells are the main effector of a powerful inhibitory circuit that, acting through GABAB receptors, can be differentially recruited by long-range connections to serve in roles as diverse as conscious perception and memory consolidation. C1 [Craig, Michael T.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA. EM mcbainc@mail.nih.gov RI Craig, Michael/E-7070-2011 OI Craig, Michael/0000-0001-8481-6709 FU Intramural NIH HHS [ZIA HD001205-21] NR 59 TC 14 Z9 14 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 EI 1873-6882 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD JUN PY 2014 VL 26 BP 15 EP 21 DI 10.1016/j.conb.2013.10.002 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AI4IB UT WOS:000336827800004 PM 24650499 ER PT J AU Prussin, C AF Prussin, Calman TI Eosinophilic Gastroenteritis and Related Eosinophilic Disorders SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Eosinophilic gastroenteritis; Eosinophilic gastritis; Eosinophilia; Food allergy; EGID ID PROTEIN-LOSING ENTEROPATHY; FOOD ALLERGY; GASTROINTESTINAL-DISEASE; ELEMENTAL DIET; ESOPHAGITIS; MONTELUKAST; BUDESONIDE; CHILDREN; PATIENT; GLUCOCORTICOSTEROIDS AB Eosinophilic gastroenteritis (EGE) represents one member within the spectrum of diseases collectively referred to as eosinophilic gastrointestinal disorders, which includes eosinophilic esophagitis (EoE), gastritis, enteritis, and colitis. EGE is less common than EoE and involves a different site of disease but otherwise shares many common features with EoE. The clinical manifestations of EGE are protean and can vary from nausea and vomiting to protein-losing enteropathy or even bowel obstruction requiring surgery. Although systemic corticosteroids are an effective treatment for EGE, their use results in substantial corticosteroid toxicity. Accordingly, there is a great need for improved therapies for these patients. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Prussin, C (reprint author), NIAID, Lab Allerg Dis, NIH, 10 Ctr Dr,MSC-1881, Bethesda, MD 20892 USA. EM cprussin@niaid.nih.gov OI Prussin, Calman/0000-0002-3917-3326 FU Intramural NIH HHS [ZIA AI000993-07] NR 55 TC 16 Z9 20 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 EI 1558-1942 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2014 VL 43 IS 2 BP 317 EP + DI 10.1016/j.gtc.2014.02.013 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AI6SJ UT WOS:000337007000012 PM 24813518 ER PT J AU Toke, ER Lorincz, O Csiszovszki, Z Somogyi, E Felfoldi, G Molnar, L Szipocs, R Kolonics, A Malissen, B Lori, F Trocio, J Bakare, N Horkay, F Romani, N Tripp, CH Stoitzner, P Lisziewicz, J AF Toke, E. R. Lorincz, O. Csiszovszki, Z. Somogyi, E. Felfoldi, G. Molnar, L. Szipocs, R. Kolonics, A. Malissen, B. Lori, F. Trocio, J. Bakare, N. Horkay, F. Romani, N. Tripp, C. H. Stoitzner, P. Lisziewicz, J. TI Exploitation of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes SO GENE THERAPY LA English DT Article ID SKIN DENDRITIC CELLS; LINEAR POLYETHYLENIMINE; CANCER VACCINES; ANTIGEN; MOUSE; MACROPINOCYTOSIS; BIODISTRIBUTION; RECEPTOR; IMMUNOTHERAPY; IMMUNIZATION AB There is no clinically available cancer immunotherapy that exploits Langerhans cells (LCs), the epidermal precursors of dendritic cells (DCs) that are the natural agent of antigen delivery. We developed a DNA formulation with a polymer and obtained synthetic 'pathogen-like' nanopartieles that preferentially targeted LCs in epidermal cultures. These nanoparticles applied topically under a patch-elicited robust immune responses in human subjects. To demonstrate the mechanism of action of this novel vaccination strategy in live animals, we assembled a high-resolution two-photon laser scanning-microscope. Nanoparticles applied on the native skin poorly penetrated and poorly induced LC motility. The combination of nanopartitle administration and skin treatment was essential both for efficient loading the vaccine into the epidermis and for potent activation of the LCs to migrate into the lymph nodes. LCs in the epidermis picked up nanoparticles and accumulated them in the nuclear region demonstrating an effective nuclear DNA delivery in vivo. Tissue distribution studies revealed that the majority of the DNA was targeted to the lymph nodes. Preclinical toxicity Of the LC-targeting DNA vaccine was limited to mild and transient local erythema caused by the skin treatment. This novel, clinically proven LC targeting:DNA vaccine platform technology broadens the options On DC-targeting vaccines to generate therapeutic immunity against cancer. C1 [Toke, E. R.; Lorincz, O.; Csiszovszki, Z.; Somogyi, E.; Felfoldi, G.; Molnar, L.; Lisziewicz, J.] Genet Immun Kft, H-1045 Budapest, Hungary. [Szipocs, R.; Kolonics, A.] Wigner RCP HAS, H-1121 Budapest, Hungary. [Szipocs, R.; Kolonics, A.] R&D Ultrafast Lasers Ltd, H-1539 Budapest, Hungary. [Malissen, B.] Aix Marseille Univ, CNRS UMR7280, Ctr Immunol Marseille Luminy, INSERM U1104, Marseille, France. [Lori, F.; Trocio, J.; Bakare, N.] Res Inst Genet & Human Therapy, Bethesda, MD USA. [Horkay, F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD USA. [Romani, N.; Tripp, C. H.; Stoitzner, P.] Med Univ Innsbruck, Dept Dermatol & Venerol, A-6020 Innsbruck, Austria. RP Lisziewicz, J (reprint author), eMMUNITY Inc, 4400 East West Hwy, Bethesda, MD 20814 USA. EM julianna.lisziewicz@emmunityinc.com OI stoitzner, patrizia/0000-0002-8488-6704; Malissen, Bernard/0000-0003-1340-9342 FU NIH [N01-AI-70043]; Hungarian National Office for Research and Technology (FIBERSC2) [TECH-09-A2-2009-0134, DVCLIN01]; Intramural Research Program of the NICHD; NIH; COMET Center ONCOTYROL (Cell Therapy Unit); Austrian Federal Ministries for Transport, Innovation and Technology, and Economics, Family and Youth (via the Austrian Research Promotion Agency / FFG); Standortagentur Tirol FX We thank Drs Michael A Ussery and Hao Zhang (Division of AIDS, NIAID) for their support. The study was supported by NIH (N01-AI-70043) and Hungarian National Office for Research and Technology (FIBERSC2, contract no. TECH-09-A2-2009-0134 and DVCLIN01). FH acknowledges the support of the Intramural Research Program of the NICHD, NIH. CHT was in part supported by the COMET Center ONCOTYROL (Cell Therapy Unit), which is funded by the Austrian Federal Ministries for Transport, Innovation and Technology, and Economics, Family and Youth (via the Austrian Research Promotion Agency / FFG) and the Standortagentur Tirol. NR 44 TC 7 Z9 7 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD JUN PY 2014 VL 21 IS 6 BP 566 EP 574 DI 10.1038/gt.2014.29 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA AI5CU UT WOS:000336883800004 PM 24694539 ER PT J AU Wojcik, GL Thio, CL Kao, WHL Latanich, R Goedert, JJ Mehta, SH Kirk, GD Peter, MG Cox, AL Kims, AY Chungs, RT Thomas, DL Duggal, P AF Wojcik, G. L. Thio, C. L. Kao, W. H. L. Latanich, R. Goedert, J. J. Mehta, S. H. Kirk, G. D. Peter, M. G. Cox, A. L. Kims, A. Y. Chungs, R. T. Thomas, D. L. Duggal, P. TI Admixture analysis of spontaneous hepatitis C virus clearance in individuals of African descent SO GENES AND IMMUNITY LA English DT Article ID GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; INFECTION; IL28B; INFERENCE; ANCESTRY; HOST; MAP AB Hepatitis C virus (HCV) infects an estimated 3% of the global population with the majority of individuals (75-85%) failing to clear the virus without treatment, leading to chronic liver disease. Individuals of African descent have lower rates of clearance compared with individuals of European descent and this is not fully explained by social and environmental factors. This suggests that differences in genetic background may contribute to this difference in clinical outcome following HCV infection. Using 473 individuals and 792 721 single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS), we estimated local African ancestry across the genome. Using admixture mapping and logistic regression, we identified two regions of interest associated with spontaneous clearance of HCV (15q24, 20p12). A genome-wide significant variant was identified on chromosome 15 at the imputed SNP, rs55817928 (P=6.18 x 10(-8)) between the genes SCAPER and RCN. Each additional copy of the African ancestral C allele is associated with 2.4 times the odds of spontaneous clearance. Conditional analysis using this SNP in the logistic regression model explained one-third of the local ancestry association. Additionally, signals of selection in this area suggest positive selection due to some ancestral pathogen or environmental pressure in African, but not in European populations. C1 [Wojcik, G. L.; Kao, W. H. L.; Mehta, S. H.; Kirk, G. D.; Thomas, D. L.; Duggal, P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Thio, C. L.; Kao, W. H. L.; Latanich, R.; Cox, A. L.; Thomas, D. L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Goedert, J. J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Peter, M. G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Kims, A. Y.; Chungs, R. T.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Duggal, P (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6539, Baltimore, MD 21205 USA. EM pduggal@jhsph.edu FU Office of AIDS Research through the Center for Inherited Diseases at Johns Hopkins University; National Institute on Drug Abuse [R01DA013324, DA033541, DA012568, DA04334]; National Institute of Allergy and Infectious Diseases [U19AI088791, AI082630, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; Intramural Research Programs of the National Institutes of Health; Frederick National Laboratory for Cancer Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness Other Communication Disorders; National Center for Research Resources (UCSF-CTSI Grant) [UL1 RR024131]; Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research FX Primary data are available through the central NIH GWAS data repository at the National Center for Biotechnology Information (NCBI), National Library of Medicine (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html). This project was funded in whole or in part by the Office of AIDS Research through the Center for Inherited Diseases at Johns Hopkins University, the National Institute on Drug Abuse (R01DA013324, DA033541, DA012568 and DA04334), the National Institute of Allergy and Infectious Diseases (U19AI088791 and AI082630), and the Frederick National Laboratory for Cancer Research (contract HHSN261200800001E). This research was supported in part by the Intramural Research Programs of the National Institutes of Health and the Frederick National Laboratory for Cancer Research. The WINS is funded by the National Institute of Allergy and Infectious Diseases (U01-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993 and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. NR 29 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2014 VL 15 IS 4 BP 241 EP 246 DI 10.1038/gene.2014.11 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA AI5CT UT WOS:000336883700006 PM 24622687 ER PT J AU Wright, MF Lewis, KL Fisher, TC Hooker, GW Emanuel, TE Biesecker, LG Biesecker, BB AF Wright, Martha F. Lewis, Katie L. Fisher, Tyler C. Hooker, Gillian W. Emanuel, Toby E. Biesecker, Leslie G. Biesecker, Barbara B. TI Preferences for results delivery from exome sequencing/genome sequencing SO GENETICS IN MEDICINE LA English DT Article DE expectations; genome; preferences; results; sequencing ID GENETIC RESEARCH; PARTICIPANTS; EXPECTATIONS; CLINSEQ; RETURN AB Purpose: The aim of this study was to explore the implications of sequencing information and stated preferences for return of results among research participants. Methods: Six focus groups were held with 39 ClinSeq participants. The groups included participants who had received results, those who had not, those affected with cardiovascular disease, and healthy adults. Audio recordings of the sessions were transcribed and coded and analyzed for themes. Results: All participants expressed interest in receiving results that are medically actionable, nonactionable, carrier, and less so variants that cannot be interpreted. Most participants preferred to receive results in person, although several endorsed use of Internet-based resources that they could return to. Participants identified benefits for health management along with satisfying curiosity, Making scientific contributions, and partnering in research. Value was seen in gaining control over health risks. Concerns were distress and/or fear that may result, Some participants were opposed to or ambivalent about learning certain types of results, particularly those having to do with diseases that were incurable or that might have implications for. the health of their children. Conclusion: There was relative enthusiasm about the value of learning sequencing information, yet it was tempered by concern about negative feeling responses and aversion to learning about incurable conditions. C1 [Wright, Martha F.; Lewis, Katie L.; Biesecker, Leslie G.] NHGRI, Genet Dis & Res Branch, NIH, Bethesda, MD 20892 USA. [Fisher, Tyler C.; Hooker, Gillian W.; Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Emanuel, Toby E.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Biesecker, BB (reprint author), NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. EM barbarab@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX The authors thank the focus group moderators, Barbara Rosenthal and Chanza Baytop, and the ClinSeq participants for their time and contributions. This work was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 17 TC 12 Z9 12 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JUN PY 2014 VL 16 IS 6 BP 442 EP 447 DI 10.1038/gim.2013.170 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AI6UF UT WOS:000337011800004 PM 24310310 ER PT J AU Stewart, DR Brems, H Gomes, AG Ruppert, SL Callens, T Williams, J Claes, K Bober, MB Hachen, R Kaban, LB Li, H Lin, A McDonald, M Melancon, S Ortenberg, J Radtke, HB Samson, I Saul, RA Shen, J Siqveland, E Toler, TL van Maarle, M Wallace, M Williams, M Legius, E Messiaen, L AF Stewart, Douglas R. Brems, Hilde Gomes, Alicia G. Ruppert, Sarah L. Callens, Tom Williams, Jennifer Claes, Kathleen Bober, Michael B. Hachen, Rachel Kaban, Leonard B. Li, Hua Lin, Angela McDonald, Marie Melancon, Serge Ortenberg, June Radtke, Heather B. Samson, Ignace Saul, Robert A. Shen, Joseph Siqveland, Elizabeth Toler, Tomi L. van Maarle, Merel Wallace, Margaret Williams, Misti Legius, Eric Messiaen, Ludwine TI Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations, or a distinct disorder SO GENETICS IN MEDICINE LA English DT Article DE cafe-au-lait macule; giant cell lesion; Jaffe-Campanacci syndrome; neurofibromatosis type 1; nonossifying-fibroma ID GIANT-CELL GRANULOMA; OF-THE-LITERATURE; NF1 GENE; ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; MUTATIONAL SPECTRUM; PHENOTYPE; CHERUBISM; DELETIONS; TUMORS; IDENTIFICATION AB Purpose: "Jaffe-Campanacci syndrome" describes the complex of multiple nonossifying fibromas of the long bones, mandibular giant cell lesions, and cafe-au-lait macules in individuals without neurofibromas. We sought to determine whether Jaffe-Campanacci syndrome is a distinct genetic entity or a variant of neurofibromatosis type 1. Methods: We performed germline NF1, SPRED1, and GNAS1 (exon 8) mutation testing on patients with Jaffe-Cainpanacci syndrome of Jaffe-Campanacci syndrome-related features, We also performed somatic NF1 mutation testing on nonossifying fibromas and giant, cell lesions. Results: Pathogenic germline NF1 mutations Were identified 13 of 14 patients with multiple cafe-au-lait macules and niultiple non-ossifying fibromas or giant cell lesions ("classicar Jaffe-Campanacci syndrome); all 13 also fulfilled the National Institues of Health diagnostic criteria for neurofibromatosis type 1. Somatic NFI mutations were detected in two giant cell lesions but not in two nonossifying fibromas. No SPRED1 or GNAS1 (exon 8) mutations were detected in the seven NF1-negative patients with Jaffe-Campanacci syndrome, nonossifying fibromas, or giant cell lesions. Conclusion: In this study, the majority of patients with cafe-au-lait macules and nonossifying fibromas Or giant cell lesions harbored a pathogenic gerinline NF1 mutation,suggesting that many Jaffe-Campanacci syndrome cases may-actually have neurofibromatosis type 1. We provide the first proof of specific somatic second-hit mutations affecting NFI in two giant cell lesions from two unrelated patients, establishing these as neurofibromatosis type 1-associated tumors. C1 [Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol, NIH, Rockville, MD 20850 USA. [Brems, Hilde; Legius, Eric] Univ Louvain, Dept Human Genet, Louvain, Belgium. [Brems, Hilde; Legius, Eric] Leuven Univ Hosp, Ctr Human Genet, Louvain, Belgium. [Gomes, Alicia G.; Callens, Tom; Williams, Jennifer; Messiaen, Ludwine] Univ Alabama Birmingham, Dept Genet, Med Genom Lab, Birmingham, AL USA. [Ruppert, Sarah L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium. [Bober, Michael B.] Alfred I DuPont Hosp Children, Dept Pediat, Div Med Genet, Wilmington, DE USA. [Hachen, Rachel] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Li, Hua; Wallace, Margaret] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Lin, Angela] MassGen Hosp Children, Genet Unit, Boston, MA USA. [McDonald, Marie] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [McDonald, Marie] Duke Univ, Med Ctr, Dept Med Genet, Durham, NC USA. [Melancon, Serge; Ortenberg, June] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Med Genet, Montreal, PQ H3H 1P3, Canada. [Melancon, Serge; Ortenberg, June] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat, Montreal, PQ H3H 1P3, Canada. [Radtke, Heather B.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Samson, Ignace] Univ Hosp Leuven, Dept Orthoped Surg, Louvain, Belgium. [Saul, Robert A.] Greenwood Genet Ctr, Greenwood, SC 29646 USA. [Shen, Joseph] Childrens Hosp Cent Calif, Madera, CA USA. [Siqveland, Elizabeth] Childrens Hosp & Clin Minnesota, Dept Genet, Minneapolis, MN USA. [Toler, Tomi L.] Massachusetts Gen Hosp, Div Med Genet, Boston, MA 02114 USA. [van Maarle, Merel] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Williams, Misti] LewisGale Reg Hlth Syst, Dept Clin Genet, Salem, VA USA. RP Stewart, DR (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol, NIH, Rockville, MD 20850 USA. EM drstewart@mail.nih.gov; lmessiaen@uabmc.edu OI Bober, Michael/0000-0002-6178-1264; Toler, Tomi/0000-0002-1637-8310 FU Medical Genomics Laboratory at the University of Alabama Birmingham; Hayward Foundation (MRW laboratory); Division of Intramural Research of the National Human Genome Research Institute (NHGRI); Division of Cancer Epidemiology and Genetics of the National Cancer Institute's Intramural Research Program; National Cancer Institute, National Institutes of Health; Research Foundation Flanders (FWO) at the KULeuven; Clinical Research Foundation of the University Hospitals Leuven; FWO-Vlaanderen [G057806N] FX This work was supported by internal funds from the Medical Genomics Laboratory at the University of Alabama Birmingham, the Hayward Foundation (MRW laboratory), the Division of Intramural Research of the National Human Genome Research Institute (NHGRI), the Division of Cancer Epidemiology and Genetics of the National Cancer Institute's Intramural Research Program, and in part with federal funds from the National Cancer Institute, National Institutes of Health. H.B. is a postdoctoral researcher of the Research Foundation Flanders (FWO) at the KULeuven. The authors thank Kathleen Freson (Molecular and Vascular Biology, KULeuven) for GNAS1 mutation analysis. E.L. is supported by the Clinical Research Foundation of the University Hospitals Leuven and by a grant from the FWO-Vlaanderen (G057806N). NR 43 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JUN PY 2014 VL 16 IS 6 BP 448 EP 459 DI 10.1038/gim.2013.163 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AI6UF UT WOS:000337011800005 PM 24232412 ER PT J AU Dickinson, D Straub, RE Trampush, J Gao, Y Feng, NP Xie, B Shin, JH Lim, HK Ursini, G Bigos, KL Kolachana, B Hashimoto, R Takeda, M Baum, GL Rujescu, D Callicott, JH Hyde, TM Berman, KF Kleinman, JE Weinberger, DR AF Dickinson, Dwight Straub, Richard E. Trampush, Joeyw. Gao, Yuan Feng, Ningping Xie, Bin Shin, Joo Heon Lim, Hun Ki Ursini, Gianluca Bigos, Kristin L. Kolachana, Bhaskar Hashimoto, Ryota Takeda, Masatoshi Baum, Graham L. Rujescu, Dan Callicott, Joseph H. Hyde, Thomas M. Berman, Karen F. Kleinman, Joel E. Weinberger, Daniel R. TI Differential Effects of Common Variants in SCN2A on General Cognitive Ability, Brain Physiology, and messenger RNA Expression in Schizophrenia Cases and Control Individuals SO JAMA PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; CLINICAL ANTIPSYCHOTIC TRIALS; EFFECTIVENESS CATIE PROJECT; HUMAN INTELLIGENCE; INTELLECTUAL DISABILITY; FUNCTIONAL-CAPACITY; PREFRONTAL CORTEX; GENETIC-VARIATION; RISK; CHILDHOOD AB IMPORTANCE One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation. OBJECTIVE To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals. DESIGN, SETTING, AND PARTICIPANTS Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples. The discovery cohort and unaffected siblings were participants in the National Institute of Mental Health Clinical Brain Disorders Branch schizophrenia genetics studies. Additional schizophrenia cohorts were from psychiatric treatment settings in the United States, Japan, and Germany. The discovery cohort comprised 339 with schizophrenia and 363 community control participants. Follow-up analyses studied 147 unaffected siblings of the schizophrenia cases and independent schizophrenia samples including a total of an additional 668 participants. Imaging analyses included 87 schizophrenia cases and 397 control individuals. Brain tissue samples were available for 64 cases and 61 control individuals. MAIN OUTCOMES AND MEASURES We studied genomewide association with g, by group, in the discovery cohort. We used selected genotypes to test specific associations in unaffected siblings and independent schizophrenia samples. Imaging analyses focused on activation in the prefrontal cortex during working memory. Brain tissue studies yielded messenger RNA expression levels for RefSeq transcripts. RESULTS The schizophrenia discovery cohort showed genomewide-significant association of g with polymorphisms in sodium channel gene SCN2A, accounting for 10.4% of g variance (rs10174400, P = 9.27 x 10(-10)). Control individuals showed a trend for g/genotype association with reversed allelic directionality. The genotype-by-group interaction was also genomewide significant (P = 1.75 x 10(-9)). Siblings showed a genotype association with g parallel to the schizophrenia group and the same interaction pattern. Parallel, but weaker, associations with cognition were found in independent schizophrenia samples. Imaging analyses showed a similar pattern of genotype associations by group and genotype-by-group interaction. Sequencing of RNA in brain revealed reduced expression in 2 of 3 SCN2A alternative transcripts in the patient group, with genotype-by-group interaction, that again paralleled the cognition effects. CONCLUSIONS AND RELEVANCE The findings implicate SCN2A and sodium channel biology in cognitive impairment in schizophrenia cases and unaffected relatives and may facilitate development of cognition-enhancing treatments. C1 [Dickinson, Dwight; Trampush, Joeyw.; Feng, Ningping; Kolachana, Bhaskar; Baum, Graham L.; Callicott, Joseph H.; Hyde, Thomas M.; Berman, Karen F.; Kleinman, Joel E.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Straub, Richard E.; Gao, Yuan; Xie, Bin; Shin, Joo Heon; Lim, Hun Ki; Ursini, Gianluca; Bigos, Kristin L.; Hyde, Thomas M.; Kleinman, Joel E.; Weinberger, Daniel R.] Johns Hopkins Univ Med Campus, Lieber Inst Brain Dev, Baltimore, MD USA. [Ursini, Gianluca] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Psychiat Neurosci Grp, Bari, Italy. [Hashimoto, Ryota; Takeda, Masatoshi] Osaka Univ, United Grad Sch Child Dev, Mol Res Ctr Childrens Mental Dev, Osaka, Japan. [Hashimoto, Ryota; Takeda, Masatoshi] Osaka Univ, Grad Sch Med, Dept Psychiat, Osaka, Japan. [Rujescu, Dan] Univ Munich, Dept Psychiat, D-80539 Munich, Germany. [Rujescu, Dan] Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. RP Weinberger, DR (reprint author), Johns Hopkins Univ, Sch Med, Lieber Inst Brain Dev, 855 NWolfe St, Baltimore, MD 21205 USA. EM drweinberger@libd.org RI Hashimoto, Ryota/P-8572-2014 OI Hashimoto, Ryota/0000-0002-5941-4238 FU Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; Clinical Brain Disorders Branch; Lieber Institute for Brain Development, Baltimore, Maryland FX This work was supported by the Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, as direct funding of the Clinical Brain Disorders Branch (Dr Weinberger, principal investigator) and the Lieber Institute for Brain Development, Baltimore, Maryland. NR 77 TC 8 Z9 9 U1 4 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JUN PY 2014 VL 71 IS 6 BP 647 EP 656 DI 10.1001/jamapsychiatry.2014.157 PG 10 WC Psychiatry SC Psychiatry GA AI5NQ UT WOS:000336915600009 PM 24718902 ER PT J AU Nurnberger, JI Koller, DL Jung, J Edenberg, HJ Foroud, T Guella, I Vawter, MP Kelsoe, JR AF Nurnberger, John I., Jr. Koller, Daniel L. Jung, Jeesun Edenberg, Howard J. Foroud, Tatiana Guella, Ilaria Vawter, Marquis P. Kelsoe, John R. CA Psychiat Genomics Consortium TI Identification of Pathways for Bipolar Disorder A Meta-analysis SO JAMA PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; 7 COMMON DISEASES; PSYCHIATRIC-DISORDERS; CALCIUM; GENES; RISK; SCHIZOPHRENIA; CACNA1C; LITHIUM; SYSTEM AB IMPORTANCE Genome-wide investigations provide systematic information regarding the neurobiology of psychiatric disorders. OBJECTIVE To identify biological pathways that contribute to risk for bipolar disorder (BP) using genes with consistent evidence for association in multiple genome-wide association studies (GWAS). DATA SOURCES Four independent data sets with individual genome-wide data available in July 2011 along with all data sets contributed to the Psychiatric Genomics Consortium Bipolar Group by May 2012. A prior meta-analysis was used as a source for brain gene expression data. STUDY SELECTION The 4 published GWAS were included in the initial sample. All independent BP data sets providing genome-wide data in the Psychiatric Genomics Consortium were included as a replication sample. DATA EXTRACTION AND SYNTHESIS We identified 966 genes that contained 2 or more variants associated with BP at P < .05 in 3 of 4 GWAS data sets (n = 12 127 [5253 cases, 6874 controls]). Simulations using 10 000 replicates of these data sets corrected for gene size and allowed the calculation of an empirical P value for each gene; empirically significant genes were entered into a pathway analysis. Each of these pathways was then tested in the replication sample (n = 8396 [3507 cases, 4889 controls]) using gene set enrichment analysis for single-nucleotide polymorphisms. The 226 genes were also compared with results from a meta-analysis of gene expression in the dorsolateral prefrontal cortex. MAIN OUTCOMES AND MEASURES Empirically significant genes and biological pathways. RESULTS Among 966 genes, 226 were empirically significant (P < .05). Seventeen pathways were overrepresented in analyses of the initial data set. Six of the 17 pathways were associated with BP in both the initial and replication samples: corticotropin-releasing hormone signaling, cardiac beta-adrenergic signaling, phospholipase C signaling, glutamate receptor signaling, endothelin 1 signaling, and cardiac hypertrophy signaling. Among the 226 genes, 9 differed in expression in the dorsolateral prefrontal cortex in patients with BP: CACNA1C, DTNA, FOXP1, GNG2, ITPR2, LSAMP, NPAS3, NCOA2, and NTRK3. CONCLUSIONS AND RELEVANCE Pathways involved in the genetic predisposition to BP include hormonal regulation, calcium channels, second messenger systems, and glutamate signaling. Gene expression studies implicate neuronal development pathways as well. These results tend to reinforce specific hypotheses regarding BP neurobiology and may provide clues for new approaches to treatment and prevention. C1 [Nurnberger, John I., Jr.; Koller, Daniel L.; Edenberg, Howard J.; Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Nurnberger, John I., Jr.; Foroud, Tatiana] Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. [Jung, Jeesun] NIAAA, Neurogenet Lab, Intramural Res Program, Bethesda, MD USA. [Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Guella, Ilaria; Vawter, Marquis P.] Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Funct Genom Lab, Irvine, CA 92717 USA. [Kelsoe, John R.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. [Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, Special Treatment & Evaluat Program, Dept Psychiat, San Diego, CA USA. RP Nurnberger, JI (reprint author), Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, 791 Union Dr, Indianapolis, IN 46202 USA. EM jnurnber@iupui.edu RI Zhang, Peng/N-2920-2014; Collier, David/D-1649-2011; Mattheisen, Manuel/B-4949-2012; Breen, Gerome/A-5540-2010; Melle, Ingrid /B-4858-2011; Ruderfer, Douglas/M-5795-2016; Lohoff, Falk/M-7951-2016; BELLIVIER, FRANK/H-5197-2012; McQuillin, Andrew/C-1623-2008; Schumacher, Johannes/F-4970-2015; OI Zhang, Peng/0000-0003-1182-1392; Collier, David/0000-0003-4087-1559; Mattheisen, Manuel/0000-0002-8442-493X; Breen, Gerome/0000-0003-2053-1792; Melle, Ingrid /0000-0002-9783-548X; Ruderfer, Douglas/0000-0002-2365-386X; McQuillin, Andrew/0000-0003-1567-2240; Bergen, Sarah/0000-0002-5888-0034; Jamain, Stephane/0000-0002-4321-4100; McMahon, Francis/0000-0002-9469-305X; Schumacher, Johannes/0000-0001-9217-6457; Stefansson, Hreinn/0000-0002-9331-6666; Backlund, Lena/0000-0001-9399-5024; Nurnberger, John/0000-0002-7674-1767; lichtenstein, paul/0000-0003-3037-5287; Nothen, Markus/0000-0002-8770-2464; Etain, Bruno/0000-0002-5377-1488; Edenberg, Howard/0000-0003-0344-9690; Thorgeirsson, Thorgeir/0000-0002-5149-7040; McIntosh, Andrew/0000-0002-0198-4588 FU William Lion Penzner Foundation (Department of Psychiatry, University of California, Irvine); National Institute of Mental Health [R01 MH085801, 1 R01 MH094483-01A1]; National Institutes of Health [MH078151, MH081804, MH059567, MH59553, MH080372, 1U54RR025204]; Genetic Association Information Network; National Institute of Mental Health Intramural Research Program; Tzedakah Foundation; American Philosophical Society; Stardust Foundation; National Library of Medicine; Stanley Medical Research Institute; Merck Genome Research Institute; Wellcome Trust; Pritzker Neuropsychiatric Disorders Research Fund LLC; GlaxoSmithKline; Research Council of Norway [167153/V50, 163070/V50, 175345/V50]; South-East Norway Health Authority [123-2004]; European Union (European Network of Bipolar Research Expert Centres) FX This work was supported by the William Lion Penzner Foundation (Department of Psychiatry, University of California, Irvine), grants R01 MH085801 (Dr Vawter) and 1 R01 MH094483-01A1 (Dr Kelsoe) from the National Institute of Mental Health, grants MH078151, MH081804, MH059567 supplement, MH59553, MH080372, and 1U54RR025204 from the National Institutes of Health, the Genetic Association Information Network, National Institute of Mental Health Intramural Research Program, Tzedakah Foundation, American Philosophical Society, Stardust Foundation, National Library of Medicine, Stanley Medical Research Institute, Merck Genome Research Institute, Wellcome Trust, Pritzker Neuropsychiatric Disorders Research Fund LLC, GlaxoSmithKline, and grants for individual studies (see http://www.nature.com/ng/journal/v43/n10/extref/ng.943-S1.pdf for a full list of acknowledgments). The Thematically Organized Psychosis Study was supported by grants 167153/V50, 163070/V50, and 175345/V50 from the Research Council of Norway, grant 123-2004 from the South-East Norway Health Authority, and the European Union (European Network of Bipolar Research Expert Centres). The French sample collection and genotyping were supported by the Centre National de Genotypage, Agence National de la Recherche (ANR NEURO2006, MANAGE_BPAD), Institut National de la Sante et de la Recherche Medicale, Assistance Publique-Hopitaux de Paris, and Fondation FondaMental. NR 40 TC 56 Z9 57 U1 2 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JUN PY 2014 VL 71 IS 6 BP 657 EP 664 DI 10.1001/jamapsychiatry.2014.176 PG 8 WC Psychiatry SC Psychiatry GA AI5NQ UT WOS:000336915600010 PM 24718920 ER PT J AU Rizzo, G Veronese, M Tonietto, M Zanotti-Fregonara, P Turkheimer, FE Bertoldo, A AF Rizzo, Gaia Veronese, Mattia Tonietto, Matteo Zanotti-Fregonara, Paolo Turkheimer, Federico E. Bertoldo, Alessandra TI Kinetic modeling without accounting for the vascular component impairs the quantification of [C-11]PBR28 brain PET data SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE [C-11]PBR28; kinetic modeling; microglia; neuroinflammation; PK11195; TSPO ID POSITRON-EMISSION-TOMOGRAPHY; PROTEIN 18 KDA; VIVO RADIOLIGAND BINDING; TRANSLOCATOR PROTEIN; IN-VIVO; ALZHEIMERS-DISEASE; NEUROINFLAMMATION; MICROGLIA; TSPO; DEPRESSION AB The positron emission tomography radioligand [C-11]PBR28 targets translocator protein (18 kDa) (TSPO) and is a potential marker of neuroinflammation. [C-11]PBR28 binding is commonly quantified using a two-tissue compartment model and an arterial input function. Previous studies with [C-11]-(R)-PK11195 demonstrated a slow irreversible binding component to the TSPO proteins localized in the endothelium of brain vessels, such as venous sinuses and arteries. However, the impact of this component on the quantification of [C-11]PBR28 data has never been investigated. In this work we propose a novel kinetic model for [C-11]PBR28. This model hypothesizes the existence of an additional irreversible component from the blood to the endothelium. The model was tested on a data set of 19 healthy subjects. A simulation was also performed to quantify the error generated by the standard two-tissue compartmental model when the presence of the irreversible component is not taken into account. Our results show that when the vascular component is included in the model the estimates that include the vascular component (2TCM-1K) are more than three-fold smaller, have a higher time stability and are better correlated to brain mRNA TSPO expression than those that do not include the model (2TCM). C1 [Rizzo, Gaia; Tonietto, Matteo; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn, I-35131 Padua, Italy. [Veronese, Mattia; Turkheimer, Federico E.] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London, England. [Zanotti-Fregonara, Paolo] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Zanotti-Fregonara, Paolo] Univ Bordeaux, CNRS, INCIA, UMR 5287, Talence, France. RP Bertoldo, A (reprint author), Univ Padua, Dept Informat Engn, Via G Gradenigo 6-B, I-35131 Padua, Italy. EM bertoldo@dei.unipd.it RI Rizzo, Gaia/A-8697-2013; Turkheimer, Federico/B-9485-2012; Veronese, Mattia/A-6012-2013; OI Rizzo, Gaia/0000-0001-7272-8576; Turkheimer, Federico/0000-0002-3766-3815; Veronese, Mattia/0000-0003-3562-0683; Tonietto, Matteo/0000-0001-9591-5710 FU Intramural Research Program, National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH); Programme Grant 'Quantitative methodologies for Positron Emission Tomography', UK Medical Research Council (MRC) [G1100809/1] FX This work was supported in part by the Intramural Research Program, National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH) and by Programme Grant 'Quantitative methodologies for Positron Emission Tomography', UK Medical Research Council (MRC) No. G1100809/1. NR 32 TC 16 Z9 16 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2014 VL 34 IS 6 BP 1060 EP 1069 DI 10.1038/jcbfm.2014.55 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA AI4JH UT WOS:000336831000017 PM 24667911 ER PT J AU Murphy, E Steenbergen, C AF Murphy, Elizabeth Steenbergen, Charles TI Sex, drugs, and trial design: sex influences the heart and drug responses SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID EXERCISE CAPACITY; CLINICAL STATUS; INHIBITION; SILDENAFIL; FAILURE; HYPERTROPHY; EXPRESSION; PDE5 AB Preclinical studies indicate that the phosphodiesterase 5 (PDE5) inhibitor sildenafil is protective against hypertrophy-induced cardiac remodeling. Despite an initial clinical study demonstrating sildenafil-dependent amelioration of pathological remodeling, the cardioprotective effect of this drug was not significant in a large placebo-controlled clinical trail. In this issue, Sasaki and colleagues reveal that the efficacy of PDE5 inhibition in female mice requires estrogen. Induction of cardiac stress in male and intact female mice resulted in increased activation of protein kinase G (PKG) signaling, which was further enhanced by sildenafil. PKG activity was not enhanced in ovariectomized. (OVX) female mice as a result of cardiac stress, but administration of estrogen restored PKG activation and enhancement by sildenafil. These data highlight the importance of considering sex-specific differences and drug responses in clinical trial design. C1 [Murphy, Elizabeth] NHLBI, NIH, Bethesda, MD 20892 USA. [Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Murphy, E (reprint author), NHLBI, Cardiac Physiol Sect, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM murphy1@mail.nih.gov FU NHLBI NIH HHS [R01 HL039752, ZOI-HL-006059, Z01 HL002065, R01-HL-39752, Z01-HL-002065] NR 14 TC 2 Z9 2 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2014 VL 124 IS 6 BP 2375 EP 2377 DI 10.1172/JCI6262 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI4XC UT WOS:000336868800015 PM 24837428 ER PT J AU Bhadra, R Moretto, MM Castillo, JC Petrovas, C Ferrando-Martinez, S Shokal, U Leal, M Koup, RA Eleftherianos, I Khan, IA AF Bhadra, Rajarshi Moretto, Magali M. Castillo, Julio C. Petrovas, Constantinos Ferrando-Martinez, Sara Shokal, Upasana Leal, Manuel Koup, Richard A. Eleftherianos, Ioannis Khan, Imtiaz A. TI Intrinsic TGF-beta signaling promotes age-dependent CD8(+) T cell polyfunctionality attrition SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID AGING IMMUNE-SYSTEM; GROWTH-FACTOR-BETA; ENCEPHALITOZOON-CUNICULI; HELMINTH COINFECTION; AIDS PATIENTS; IN-VIVO; EFFECTOR; INFECTION; MEMORY; VIRUS AB Advanced age is associated with immune system deficits that result in an increased susceptibility to infectious diseases; however, specific mediators of age-dependent immune dysfunction have not been fully elucidated. Here we demonstrated that aged mice exhibit poor effector CD8(+) T cell polyfunctionality, primarily due to CD8(+) T cell-extrinsic deficits, and that reduced CD8(+) T cell polyfunctionality correlates with increased susceptibility to pathogenic diseases. In aged animals challenged with the parasite Encephalitozoon cuniculi, effector CD8(+) T cell survival and polyfunctionality were suppressed by highly elevated TGF-beta 1. Furthermore, TGF-beta depletion reduced effector CD8(+) T cell apoptosis in both young and aged mice and enhanced effector CD8(+) T cell polyfunctionality in aged mice. Surprisingly, intrinsic blockade of TGF-beta signaling in CD8(+) T cells was sufficient to rescue polyfunctionality in aged animals. Together, these data demonstrate that low levels of TGF-beta 1 promote apoptosis of CD8(+) effector T cells and high TGF-beta 1 levels associated with age result in both CD8(+) T cell apoptosis and an altered transcriptional profile, which correlates with loss of polyfunctionality. Furthermore, elevated TGF-beta levels are observed in the elderly human population and in aged Drosophila, suggesting that TGF-beta represents an evolutionarily conserved negative regulator of the immune response in aging organisms. C1 [Bhadra, Rajarshi; Moretto, Magali M.; Khan, Imtiaz A.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA. [Bhadra, Rajarshi] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. [Castillo, Julio C.; Shokal, Upasana; Eleftherianos, Ioannis] George Washington Univ, Dept Biol Sci, Insect Infect & Immun Lab, Washington, DC 20037 USA. [Petrovas, Constantinos; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Ferrando-Martinez, Sara; Leal, Manuel] Univ Seville, Virgen Rocio Univ Hosp, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville IBiS,Lab Immunovirol,CSIC, Seville, Spain. [Ferrando-Martinez, Sara] Hosp Gen Univ Gregorio Maranon, Lab InmunoBiol Mol, Madrid, Spain. [Ferrando-Martinez, Sara] Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain. [Ferrando-Martinez, Sara] Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid, Spain. RP Khan, IA (reprint author), George Washington Univ, 2300 1 St NW,Ross Hall Room 623, Washington, DC 20037 USA. EM imti56@gwu.edu RI Leal, Manuel/C-8458-2015; IBIS, INMUNOVIROLOGI/O-9246-2015; OI Castillo, Julio/0000-0002-6921-810X FU NIH [AI-096978]; Fondo de Investigaciones Sanitarias [CD 10/00382]; Redes Tematicas de Investigacion en SIDA (ISCIII RETIC) [RD12/0017/0029, RD12/0017/0037]; Proyecto de Excelencia [CTS-6313]; Consejeri de Salud [PI-0278] FX This work was supported by a NIH grant (AI-096978) to I.A. Khan as well as by Fondo de Investigaciones Sanitarias (CD 10/00382), Redes Tematicas de Investigacion en SIDA (ISCIII RETIC RD12/0017/0029 and RD12/0017/0037), Proyecto de Excelencia (CTS-6313), and Consejeri de Salud (PI-0278) to M. Leal and S. Ferrando-Martinez. We thank Louis M. Weiss (Albert Einstein College of Medicine, New York, New York, USA) for critically reading the manuscript. NR 65 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2014 VL 124 IS 6 BP 2441 EP 2455 DI 10.1172/JCI70522 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI4XC UT WOS:000336868800020 PM 24762437 ER PT J AU Sui, YJ Hogg, A Wang, YC Frey, B Yu, HF Xia, Z Venzon, D McKinnon, K Smedley, J Gathuka, M Klinman, D Keele, BF Langermann, S Liu, LD Franchini, G Berzofsky, JA AF Sui, Yongjun Hogg, Alison Wang, Yichuan Frey, Blake Yu, Huifeng Xia, Zheng Venzon, David McKinnon, Katherine Smedley, Jeremy Gathuka, Mercy Klinman, Dennis Keele, Brandon F. Langermann, Sol Liu, Linda Franchini, Genoveffa Berzofsky, Jay A. TI Vaccine-induced myeloid cell population dampens protective immunity to SIV SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CD8(+) T-CELLS; BLOOD MONONUCLEAR-CELLS; SUPPRESSOR-CELLS; ALPHA-GALACTOSYLCERAMIDE; MUCOSAL TRANSMISSION; SIVMAC251 INFECTION; DISEASE PROGRESSION; HIV-1 INFECTION; RHESUS MACAQUES; TUMOR-IMMUNITY AB Vaccines are largely evaluated for their ability to promote adaptive immunity, with little focus on the induction ofnegative immune regulators. Adjuvants facilitate and enhance vaccine-induced immune responses and have been explored for mediating protection against HIV Using a regimen of peptide e priming followed by a modified vaccinia Ankara (MVA) boost in a nonhuman primate model, we found that an SW vaccine incorporating molecular adjuvants mediated partial protection against rectal SIVmac251 challenges. Animals treated with vaccine and multiple adjuvants exhibited a reduced viral load (VL) compared with those treated with vaccine only. Surprisingly, animals treated with adjuvant alone had reduced VLs that were comparable to or better than those of the vaccine-treated group. VL reduction was greatest in animals with the MHC class I allele Mamu-A*01 that were treated with adjuvant only and was largely dependent on CD8(+) T cells. Early VLs correlated with Ki67(+)CCR5(+)CD4(+) T cell frequency, while set-point VL was associated with expansion of a myeloid cell population that was phenotypically similar to myeloid-derived suppressor cells (MDSCs) and that suppressed T cell responses in vitro. MDSC expansion occurred in animals receiving vaccine and was not observed in the adjuvant-only group. Collectively, these results indicate that vaccine-induced MDSCs inhibit protective cellular immunity and suggest that preventing MDSC induction may be critical for effective AIDS vaccination. C1 [Sui, Yongjun; Hogg, Alison; Wang, Yichuan; Frey, Blake; Yu, Huifeng; Xia, Zheng; McKinnon, Katherine; Franchini, Genoveffa; Berzofsky, Jay A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Smedley, Jeremy; Gathuka, Mercy] NCI, Lab Anim Sci Program, NIH, Bethesda, MD 20892 USA. [Klinman, Dennis] NCI, Expt Immunol Lab, NIH, Bethesda, MD 20892 USA. [Keele, Brandon F.] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA. [Langermann, Sol; Liu, Linda] Amplimmune Inc, Gaithersburg, MD USA. RP Sui, YJ (reprint author), NCI, Vaccine Branch, NIH, 41 Medlars Dr, Bethesda, MD 20892 USA. EM suiy@mail.nih.gov; berzofsj@mail.nih.gov OI Smedley, Jeremy/0000-0003-3369-4662 FU NIH [HHSN261200800001E]; NCI; Center for Cancer Research FX We thank E.M. Lee, R. Pal, and S. Omdorff from Advanced Bio-Science Laboratories Inc. for the VL and CD4 assays; D. Watkins (University of Miami) for MHC typing; N. Miller (NIAID) for providing pathogenic SIVmac251 challenge stock; M.R. Anver (NCI) for pathology support; the NIAID tetramer core facility for providing the tetramers; the NIH Nonhuman Primate Reagent Resource for providing anti-CD3 and anti-CD28 antibodies; Lisa Smith for secretarial assistance; and Masaki Terabe (NCI) and Tim Greten (NCI) for helpful discussion. This work was supported by the Intramural Program of the NIH, NCI, Center for Cancer Research and in part by federal funds from the NCI, NIH, under contract HHSN261200800001E. NR 56 TC 15 Z9 16 U1 0 U2 15 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2014 VL 124 IS 6 BP 2538 EP 2549 DI 10.1172/JCI73518 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI4XC UT WOS:000336868800028 PM 24837435 ER PT J AU Yu, WP Zheng, H Lin, W Tajima, A Zhang, Y Zhang, XY Zhang, HW Wu, JH Han, DS Rahman, NA Korach, KS Gao, GF Inoue, I Li, XD AF Yu, Wanpeng Zheng, Han Lin, Wei Tajima, Astushi Zhang, Yong Zhang, Xiaoyan Zhang, Hongwen Wu, Jihua Han, Daishu Rahman, Nafis A. Korach, Kenneth S. Gao, George Fu Inoue, Ituro Li, Xiangdong TI Estrogen promotes Leydig cell engulfment by macrophages in male infertility SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TRANSGENIC MALE-MICE; APOPTOTIC CELLS; PHOSPHOLIPID SCRAMBLASE; TARGETED DISRUPTION; INCREASED EXPOSURE; RECEPTOR-ALPHA; P450 AROMATASE; MOUSE TESTIS; GENE; MEN AB Male infertility accounts for almost half of infertility cases worldwide. A subset of infertile men exhibit reduced testosterone and enhanced levels of estradiol (E2), though it is unclear how increased E2 promotes deterioration of male fertility. Here, we utilized a transgenic mouse strain that overexpresses human CYP19, which encodes aromatase (AROM+ mice), and mice with knockout of Esr1, encoding estrogen receptor alpha (ER alpha KO mice), to analyze interactions between viable Leydig cells (LCs) and testicular macrophages that may lead to male infertility. In AROM+ males, enhanced E2 promoted LC hyperplasia and macrophage activation via ER alpha signaling. E2 stimulated LCs to produce growth arrest-specific 6 (GAS6), which mediates phagocytosis of apoptotic cells by bridging cells with surface exposed phosphatidylserine (PS) to macrophage receptors, including the tyrosine kinases TYRO3, AXL, and MER. Overproduction of E2 increased apoptosis-independent extrusion of PS on LCs, which in turn promoted engulfment by E2/ER alpha-activated macrophages that was mediated by AXL-GAS6-PS interaction. We further confirmed E2-dependant engulfment of LCs by real-time 3D imaging. Furthermore, evaluation of molecular markers in the testes of patients with nonobstructive azoospermia (NOA) revealed enhanced expression of CYP19, GAS6, and AXL, which suggests that the AROM+ mouse model reflects human infertility. Together, these results suggest that GAS6 has a potential as a clinical biomarker and therapeutic target for male infertility. C1 [Yu, Wanpeng; Zheng, Han; Lin, Wei; Zhang, Yong; Li, Xiangdong] China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China. [Tajima, Astushi; Inoue, Ituro] Natl Inst Genet, Div Human Genet, Shizuoka, Japan. [Zhang, Xiaoyan; Han, Daishu] Chinese Acad Med Sci, Peking Union Med Coll, Sch Basic Med, Dept Cell Biol,Inst Basic Med Sci, Beijing 100730, Peoples R China. [Zhang, Hongwen; Wu, Jihua] 306th Hosp PLA, Dept Gen Surg, Beijing, Peoples R China. [Rahman, Nafis A.] Univ Turku, Inst Biomed, Dept Physiol, Turku, Finland. [Korach, Kenneth S.] NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Grp, NIH, Bethesda, MD USA. [Gao, George Fu] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China. RP Li, XD (reprint author), China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China. EM gaof@im.ac.cn; xiangdongli@cau.edu.cn RI Tajima, Atsushi/C-1053-2008; OI Tajima, Atsushi/0000-0001-6808-5491; Korach, Kenneth/0000-0002-7765-418X FU Natural Science Foundation of China [NSFC31071316]; National Science and Technology Major Project [2013ZX10004608]; Ministry of Science/Technology [2009CB941701]; CAU Scientific Fund [2012171034] FX This work was supported by grants from the Natural Science Foundation of China (NSFC31071316), National Science and Technology Major Project (2013ZX10004608), Ministry of Science/Technology (2009CB941701), and the CAU Scientific Fund (no. 2012171034). NR 56 TC 12 Z9 12 U1 1 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2014 VL 124 IS 6 BP 2709 EP 2721 DI 10.1172/JCI59901 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI4XC UT WOS:000336868800041 PM 24762434 ER PT J AU Zhang, YJ Berka, V Song, AR Sun, KQ Wang, W Zhang, WR Ning, C Li, CH Zhang, QB Bogdanov, M Alexander, DC Milburn, MV Ahmed, MH Lin, H Idowu, M Zhang, J Kato, GJ Abdulmalik, OY Zhang, WZ Dowhan, W Kellems, RE Zhang, PM Jin, JP Safo, M Tsai, AL Juneja, HS Xia, Y AF Zhang, Yujin Berka, Vladimir Song, Anren Sun, Kaiqi Wang, Wei Zhang, Weiru Ning, Chen Li, Chonghua Zhang, Qibo Bogdanov, Mikhail Alexander, Danny C. Milburn, Michael V. Ahmed, Mostafa H. Lin, Han Idowu, Modupe Zhang, Jun Kato, Gregory J. Abdulmalik, Osheiza Y. Zhang, Wenzheng Dowhan, William Kellems, Rodney E. Zhang, Pumin Jin, Jianping Safo, Martin Tsai, Ah-Lim Juneja, Harinder S. Xia, Yang TI Elevated sphingosine-1-phosphate promotes sickling and sickle cell disease progression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID 1ST MOLECULAR DISEASE; SPHINGOSINE 1-PHOSPHATE; IN-VITRO; ANGIOGENESIS; MICE; PATHOPHYSIOLOGY; ERYTHROCYTES; HEMOGLOBIN; ANEMIA; BLOOD AB Sphingosine-l-phosphate (SIP) is a bioactive lipid that regulates ulticellular functions through interactions with its receptors on cell surfaces. S1P is enriched and stored in erythrocytes however it is not clear whether alterations in SlP are involved in the prevalent and debilitating hemolytic disorder sickle cell disease (SCD). Here using metabolomic screening we found that SlP is highly elevated in the blood of mice and humans with SCD. In murine models of SCD we demonstrated that elevated erythrocyte sphingosine kinase 1 (SPHK1) underlies sickling and disease progression by increasing SIP levels in the blood. Additionally we observed elevated SPHK1 activity in erythrocytes and increased S1P in blood collected from patients with SCD and demonstrated a direct impact of elevated SPHK1-mediated production of SIP on sickling that was independent of SIP receptor activation in isolated erythrocytes. Together our findings provide insights into erythrocyte pathophysiology revealing that a SPHK1-mediated elevation of SlP contributes to sickling and promotes disease progression and highlight potential therapeutic opportunities for SCD. C1 [Zhang, Yujin; Song, Anren; Sun, Kaiqi; Wang, Wei; Zhang, Weiru; Ning, Chen; Li, Chonghua; Bogdanov, Mikhail; Dowhan, William; Kellems, Rodney E.; Jin, Jianping; Xia, Yang] Univ Texas Hlth Sci Ctr Houston, Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Berka, Vladimir; Idowu, Modupe; Zhang, Wenzheng; Tsai, Ah-Lim; Juneja, Harinder S.] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Houston, TX 77030 USA. [Sun, Kaiqi; Kellems, Rodney E.; Jin, Jianping; Xia, Yang] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA. [Wang, Wei; Zhang, Weiru; Xia, Yang] Cent S Univ, Xiangya Hosp 1, Dept Neurol, Changsha, Hunan, Peoples R China. [Ning, Chen] Cent S Univ, Xiangya Hosp 1, Dept Urol, Changsha, Hunan, Peoples R China. [Zhang, Qibo; Alexander, Danny C.; Milburn, Michael V.] Metabolon Inc, Durham, NC USA. [Ahmed, Mostafa H.; Safo, Martin] Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA USA. [Ahmed, Mostafa H.; Safo, Martin] Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Richmond, VA USA. [Lin, Han; Zhang, Pumin] Baylor Coll Med, Dept Physiol, Houston, TX 77030 USA. [Zhang, Jun] Baylor Coll Med, Dept Hematol Oncol, Houston, TX 77030 USA. [Kato, Gregory J.] NHLBI, Sickle Cell Dis Div, NIH, Bethesda, MD 20892 USA. [Abdulmalik, Osheiza Y.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Xia, Y (reprint author), Univ Texas Med Sch Houston, Dept Biochem & Mol Biol, 6431 Fannin St, Houston, TX 77030 USA. EM yang.xia@uth.tmc.edu RI Kato, Gregory/I-7615-2014; Lin, Han/M-9269-2016 OI Kato, Gregory/0000-0003-4465-3217; Lin, Han/0000-0002-8569-7972 FU NIH [HL119549, DK077748, DK083559, P01HL114457, HL095820]; American Heart Association [10GRNT3760081, 12IRG9150001]; China Scholarship Council [2009637520]; NIH/NHLBI [HL103186] FX This work was supported by NIH grants HL119549 (to Y. Xia), DK077748 (to Y. Xia), DK083559 (to Y. Xia), P01HL114457 (Project 3 to Y. Xia), and HL095820 (to A.-L. Tsai) as well as American Heart Association grants 10GRNT3760081 and 12IRG9150001 (to Y. Xia), China Scholarship Council 2009637520 (to Weiru Zhang), and NIH/NHLBI grant HL103186 (to O.Y. Abdulmalik). NR 35 TC 34 Z9 36 U1 0 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2014 VL 124 IS 6 BP 2750 EP 2761 DI 10.1172/JC174604 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI4XC UT WOS:000336868800044 PM 24837436 ER PT J AU Mulligan, C Fitzgerald, GA Wang, DN Mindell, JA AF Mulligan, Christopher Fitzgerald, Gabriel A. Wang, Da-Neng Mindell, Joseph A. TI Functional characterization of a Na+-dependent dicarboxylate transporter from Vibrio cholerae SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID COUPLED CITRATE TRANSPORTER; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GENOMIC ORGANIZATION; STAPHYLOCOCCUS-AUREUS; ASPARTATE TRANSPORTER; ESCHERICHIA-COLI; SLC13 FAMILY; PYROCOCCUS-HORIKOSHII; INSULIN-RESISTANCE; CRYSTAL-STRUCTURE AB The SLC13 transporter family, whose members play key physiological roles in the regulation of fatty acid synthesis, adiposity, insulin resistance, and other processes, catalyzes the transport of Krebs cycle intermediates and sulfate across the plasma membrane of mammalian cells. SLC13 transporters are part of the divalent anion: Na+ symporter (DASS) family that includes several well-characterized bacterial members. Despite sharing significant sequence similarity, the functional characteristics of DASS family members differ with regard to their substrate and coupling ion dependence. The publication of a high resolution structure of dimer VcINDY, a bacterial DASS family member, provides crucial structural insight into this transporter family. However, marrying this structural insight to the current functional understanding of this family also demands a comprehensive analysis of the transporter's functional properties. To this end, we purified VcINDY, reconstituted it into liposomes, and determined its basic functional characteristics. Our data demonstrate that VcINDY is a high affinity, Na+-dependent transporter with a preference for C-4- and C-5-dicarboxylates. Transport of the model substrate, succinate, is highly pH dependent, consistent with VcINDY strongly preferring the substrate's dianionic form. VcINDY transport is electrogenic with succinate coupled to the transport of three or more Na+ ions. In contrast to succinate, citrate, bound in the VcINDY crystal structure (in an inward-facing conformation), seems to interact only weakly with the transporter in vitro. These transport properties together provide a functional framework for future experimental and computational examinations of the VcINDY transport mechanism. C1 [Mulligan, Christopher; Fitzgerald, Gabriel A.; Mindell, Joseph A.] Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Wang, Da-Neng] NYU, Sch Med, Skirball Inst Biomol Med, Helen L & Martin Kimmel Ctr Biol & Med, New York, NY 10016 USA. [Wang, Da-Neng] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. RP Mindell, JA (reprint author), Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. EM mindellj@ninds.nih.gov OI Fitzgerald, Gabriel/0000-0002-8235-0148; Mindell, Joseph/0000-0002-6952-8247 FU Intramural Research Program of the National Institutes of Health (NIH); National Institute of Neurological Disorders and Stroke; NIH [R01-DK099023, R01-DK073973, R01-GM093825, R01-DA019676, U54-GM095315] FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke, and NIH grants (R01-DK099023, R01-DK073973, R01-GM093825, R01-DA019676, and U54-GM095315). NR 58 TC 15 Z9 15 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 EI 1540-7748 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUN PY 2014 VL 143 IS 6 BP 745 EP 759 DI 10.1085/jgp.201311141 PG 15 WC Physiology SC Physiology GA AI8KM UT WOS:000337162500008 PM 24821967 ER PT J AU Tian, Y Schwieters, CD Opella, SJ Marassi, FM AF Tian, Ye Schwieters, Charles D. Opella, Stanley J. Marassi, Francesca M. TI A practical implicit solvent potential for NMR structure calculation SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Protein structure; Calculation; Implicit solvent; EEFx; XPLOR-NIH; NMR ID MOLECULAR-STRUCTURE DETERMINATION; MAGNETIC-RESONANCE SPECTROSCOPY; PROTEIN-FOLDING THERMODYNAMICS; EFFECTIVE ENERGY FUNCTION; N-TERMINAL DOMAIN; STRUCTURE VALIDATION; STRUCTURE REFINEMENT; PHOSPHOTRANSFERASE SYSTEM; 3-DIMENSIONAL STRUCTURES; CONFORMATIONAL DATABASE AB The benefits of protein structure refinement in water are well documented. However, performing structure refinement with explicit atomic representation of the solvent molecules is computationally expensive and impractical for NMR-restrained structure calculations that start from completely extended polypeptide templates. Here we describe a new implicit solvation potential, EEFx (Effective Energy Function for XPLOR-NIH), for NMR-restrained structure calculations of proteins in XPLOR-NIH. The key components of EEFx are an energy term for solvation energy that works together with other nonbonded energy functions, and a dedicated force field for conformational and nonbonded protein interaction parameters. The initial results obtained with EEFx show that significant improvements in structural quality can be obtained. EEFx is computationally efficient and can be used both to fold and refine structures. Overall, EEFx improves the quality of protein conformation and nonbonded atomic interactions. Moreover, such benefits are accompanied by enhanced structural precision and enhanced structural accuracy, reflected in improved agreement with the cross-validated dipolar coupling data. Finally, implementation of EEFx calculations is straightforward and computationally efficient. Overall, EEFx provides a useful method for the practical calculation of experimental protein structures in a physically realistic environment. (C) 2014 Elsevier Inc. All rights reserved. C1 [Tian, Ye; Marassi, Francesca M.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA. [Tian, Ye; Opella, Stanley J.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. [Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Marassi, FM (reprint author), Sanford Burnham Med Res Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM fmarassi@sbmri.org FU National Institutes of Health [R01 GM100265, P01 AI074805, R21 GM094727, P41 EB002031]; NIH Intramural Research Program of The Center for Information Technology FX This research was supported by Grants from the National Institutes of Health (R01 GM100265; P01 AI074805 and R21 GM094727). It utilized the Resource for Molecular Imaging of Proteins at UCSD, supported by NIH Grant P41 EB002031). CDS was supported by funds from the NIH Intramural Research Program of The Center for Information Technology. NR 75 TC 7 Z9 7 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 EI 1096-0856 J9 J MAGN RESON JI J. Magn. Reson. PD JUN PY 2014 VL 243 BP 54 EP 64 DI 10.1016/j.jmr.2014.03.011 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA AI7ZK UT WOS:000337121300008 PM 24747742 ER PT J AU Thorwarth, A Schnittert-Hubener, S Schrumpf, P Muller, I Jyrch, S Dame, C Biebermann, H Kleinau, G Katchanov, J Schuelke, M Ebert, G Steininger, A Bonnemann, C Brockmann, K Christen, HJ Crock, P deZegher, F Griese, M Hewitt, J Ivarsson, S Hubner, C Kapelari, K Plecko, B Rating, D Stoeva, I Ropers, HH Gruters, A Ullmann, R Krude, H AF Thorwarth, Anne Schnittert-Huebener, Sarah Schrumpf, Pamela Mueller, Ines Jyrch, Sabine Dame, Christof Biebermann, Heike Kleinau, Gunnar Katchanov, Juri Schuelke, Markus Ebert, Grit Steininger, Anne Boennemann, Carsten Brockmann, Knut Christen, Hans-Juergen Crock, Patricia deZegher, Francis Griese, Matthias Hewitt, Jacqueline Ivarsson, Sten Huebner, Christoph Kapelari, Klaus Plecko, Barbara Rating, Dietz Stoeva, Iva Ropers, Hans-Hilger Grueters, Annette Ullmann, Reinhard Krude, Heiko TI Comprehensive genotyping and clinical characterisation reveal 27 novel NKX2-1 mutations and expand the phenotypic spectrum SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID BENIGN HEREDITARY CHOREA; TRANSCRIPTION FACTOR-I; PAPILLARY THYROID-CARCINOMA; ENHANCER-BINDING PROTEIN; EMBRYONIC STEM-CELLS; FUNCTIONAL-CHARACTERIZATION; CONGENITAL HYPOTHYROIDISM; RESPIRATORY-FAILURE; GANGLIONIC EMINENCES; EPITHELIAL-CELLS AB Background NKX2-1 encodes a transcription factor with large impact on the development of brain, lung and thyroid. Germline mutations of NKX2-1 can lead to dysfunction and malformations of these organs. Starting from the largest coherent collection of patients with a suspected phenotype to date, we systematically evaluated frequency, quality and spectrum of phenotypic consequences of NKX2-1 mutations. Methods After identifying mutations by Sanger sequencing and array CGH, we comprehensively reanalysed the phenotype of affected patients and their relatives. We employed electrophoretic mobility shift assay (EMSA) to detect alterations of NKX2-1 DNA binding. Gene expression was monitored by means of in situ hybridisation and compared with the expression level of MBIP, a candidate gene presumably involved in the disorders and closely located in close genomic proximity to NKX2-1. Results Within 101 index patients, we detected 17 point mutations and 10 deletions. Neurological symptoms were the most consistent finding (100%), followed by lung affection (78%) and thyroidal dysfunction (75%). Novel symptoms associated with NKX2-1 mutations comprise abnormal height, bouts of fever and cardiac septum defects. In contrast to previous reports, our data suggest that missense mutations in the homeodomain of NKX2-1 not necessarily modify its DNA binding capacity and that this specific type of mutations may be associated with mild pulmonary phenotypes such as asthma. Two deletions did not include NKX2-1, but MBIP, whose expression spatially and temporarily coincides with NKX2-1 in early murine development. Conclusions The high incidence of NKX2-1 mutations strongly recommends the routine screen for mutations in patients with corresponding symptoms. However, this analysis should not be confined to the exonic sequence alone, but should take advantage of affordable NGS technology to expand the target to adjacent regulatory sequences and the NKX2-1 interactome in order to maximise the yield of this diagnostic effort. C1 [Thorwarth, Anne; Schnittert-Huebener, Sarah; Schrumpf, Pamela; Jyrch, Sabine; Biebermann, Heike; Kleinau, Gunnar; Grueters, Annette; Krude, Heiko] Charite, Inst Expt Pediat Endocrinol, D-13353 Berlin, Germany. [Thorwarth, Anne; Mueller, Ines; Ebert, Grit; Steininger, Anne; Ropers, Hans-Hilger; Ullmann, Reinhard] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Dame, Christof] Charite, Dept Neonatol, D-13353 Berlin, Germany. [Katchanov, Juri] Charite, Dept Neurol, D-13353 Berlin, Germany. [Schuelke, Markus] Charite, Dept Neuropediat, D-13353 Berlin, Germany. [Boennemann, Carsten] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, Bethesda, MD 20892 USA. [Brockmann, Knut] Univ Gottingen, Interdisciplinary Pediat Ctr Children Dev Disabil, Univ Med Ctr, D-37073 Gottingen, Germany. [Christen, Hans-Juergen] Childrens & Youth Hosp Auf der Bult, Dept Neuropediat, Hannover, Germany. [Crock, Patricia] John Hunter Childrens Hosp, Div Pediat Endocrinol & Diabet, Newcastle, NSW, Australia. [deZegher, Francis] Univ Louvain, Dept Woman & Child, Louvain, Belgium. [Griese, Matthias] Univ Munich, Dr von Haunersches Kinderspital, Munich, Germany. [Hewitt, Jacqueline] Royal Childrens Hosp, Div Endocrinol & Diabet, Melbourne, Vic, Australia. [Ivarsson, Sten] Univ Hosp MAS, Dept Clin Sci Pediat Endocrinol, Malmo, Sweden. [Kapelari, Klaus] Med Univ Innsbruck, Dept Pediat & Adolescent Med, A-6020 Innsbruck, Austria. [Plecko, Barbara] Univ Childrens Hosp Zurich, Div Child Neurol, Zurich, Switzerland. [Rating, Dietz] Univ Heidelberg Hosp, Dept Neuropediat, Heidelberg, Germany. [Stoeva, Iva] Med Univ Sofia, Dept Paediat Endocrinol Screening & Funct Endocri, Sofia, Bulgaria. RP Krude, H (reprint author), Charite, Inst Expt Pediat Endocrinol, Augustenburger Pl 1, D-13353 Berlin, Germany. EM ullmann@molgen.mpg.de; ullmann@molgen.mpg.de FU Intramural NIH HHS [Z99 NS999999, ZIA NS003129-02, ZIA NS003129-03, ZIA NS003129-04] NR 86 TC 11 Z9 13 U1 1 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD JUN PY 2014 VL 51 IS 6 BP 375 EP 387 DI 10.1136/jmedgenet-2013-102248 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AI4NE UT WOS:000336841300003 PM 24714694 ER PT J AU Bear, KA Solomon, BD Antonini, S Arnhold, IJP Franca, MM Gerkes, EH Grange, DK Hadley, DW Jaaskelainen, J Paulo, SS Rump, P Stratakis, CA Thompson, EM Willis, M Winder, TL Jorge, AAL Roessler, E Muenke, M AF Bear, Kelly A. Solomon, Benjamin D. Antonini, Sonir Arnhold, Ivo J. P. Franca, Marcela M. Gerkes, Erica H. Grange, Dorothy K. Hadley, Donald W. Jaaskelainen, Jarmo Paulo, Sabrina S. Rump, Patrick Stratakis, Constantine A. Thompson, Elizabeth M. Willis, Mary Winder, Thomas L. Jorge, Alexander A. L. Roessler, Erich Muenke, Maximilian TI Pathogenic mutations in GLI2 cause a specific phenotype that is distinct from holoprosencephaly SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID SONIC-HEDGEHOG; SPECTRUM; HYPOPITUITARISM; INDIVIDUALS; FREQUENCY; VARIANTS; DEFECTS; DISEASE; GENE; ZIC2 AB Background Mutations in GLI2 have been associated with holoprosencephaly (HPE), a neuroanatomic anomaly resulting from incomplete cleavage of the developing forebrain, and an HPE-like phenotype involving pituitary anomalies and polydactyly. Objective To characterise the genotypic and phenotypic findings in individuals with GLI2 variants and clarify clinical findings in individuals with loss-of-function mutations. Methods Through the National Institutes of Health and collaborating centres, similar to 400 individuals with HPE spectrum disorders, endocrine disorders or craniofacial anomalies were screened for GLI2 mutations. Results were combined with all published cases. We compared the clinical and molecular features of individuals with truncating mutations to individuals with variants of unknown significance (defined as not resulting in protein truncation, reported in normal controls and/or deemed unlikely to be pathogenic by functional prediction software). Results 112 individuals with variants in GLI2 were identified, with 43 having truncating mutations. Individuals with truncating mutations were more likely to have both pituitary anomalies and polydactyly versus those with variants of unknown significance (p<0.0001 by Fisher's exact test); only 1 of 43 had frank HPE. These individuals were more likely to have recognised penetrance (polydactyly or pituitary anomalies or both) than those without truncating mutations (p=0.0036 by Fisher's exact test). A common facial phenotype was seen in individuals (with midface hypoplasia, cleft lip/palate and hypotelorism) with truncating mutations. Conclusions Individuals with truncating mutations in GLI2 typically present with pituitary anomalies, polydactyly and subtle facial features rather than HPE. This will be helpful in screening populations for GLI2 mutations and for counselling affected patients. C1 [Bear, Kelly A.; Solomon, Benjamin D.; Hadley, Donald W.; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Bear, Kelly A.] Tripler Army Med Ctr, Dept Pediat, Honolulu, HI 96859 USA. [Solomon, Benjamin D.] Inova Hlth Syst, Inova Translat Med Inst, Div Med Genom, Falls Church, VA USA. [Solomon, Benjamin D.] Inova Hlth Syst, Inova Childrens Hosp, Dept Pediat, Falls Church, VA USA. [Antonini, Sonir; Paulo, Sabrina S.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pediat, Sao Paulo, Brazil. [Arnhold, Ivo J. P.; Franca, Marcela M.] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM 42, Hosp Clin,Fac Med,Disciplina Endocrinol, Sao Paulo, Brazil. [Gerkes, Erica H.; Rump, Patrick] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Grange, Dorothy K.] Washington Univ Schl Mdcn, St Louis, MO USA. [Jaaskelainen, Jarmo] Univ Eastern Finland, Dept Pediat, Kuopio, Finland. [Jaaskelainen, Jarmo] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Thompson, Elizabeth M.] Womens & Childrens Hosp, South Australian Clin Genet Serv, SA Pathol, Adelaide, SA, Australia. [Thompson, Elizabeth M.] Univ Adelaide, Dept Paediat, Adelaide, SA, Australia. [Willis, Mary] Naval Med Ctr, Dept Pediat, San Diego, CA USA. [Winder, Thomas L.] Prevent Genet, Marshfield, WI USA. [Jorge, Alexander A. L.] Univ Sao Paulo, Unidade Endocrinol Genet, LIM 25, Disciplina Endocrinol,Hosp Clin,Fac Med, Sao Paulo, Brazil. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, 35 Convent Dr,Bldg 35,Room 1B 203, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov RI Jorge, Alexander/C-7697-2012; ARNHOLD, IVO/D-2672-2012; Antonini, Sonir /J-5264-2015 OI Jorge, Alexander/0000-0003-2567-7360; FU Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, USA FX This research was supported by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, USA. Pertaining to KAB, the views expressed in this publication are those of the author and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government. Pertaining to MW, the views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense or the United States Government. The authors would like to express their gratitude to the patients and families involved. NR 28 TC 11 Z9 11 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD JUN PY 2014 VL 51 IS 6 BP 413 EP 418 DI 10.1136/jmedgenet-2013-102249 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AI4NE UT WOS:000336841300008 PM 24744436 ER PT J AU Ben-David, U Biran, A Scaffidi, P Herold-Mende, C Boehringer, M Meshorer, E Benvenisty, N AF Ben-David, Uri Biran, Alva Scaffidi, Paola Herold-Mende, Christel Boehringer, Markus Meshorer, Eran Benvenisty, Nissim TI Elimination of undifferentiated cancer cells by pluripotent stem cell inhibitors SO JOURNAL OF MOLECULAR CELL BIOLOGY LA English DT Letter ID THERAPY C1 [Ben-David, Uri; Benvenisty, Nissim] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Stem Cell Unit, IL-91904 Jerusalem, Israel. [Ben-David, Uri; Biran, Alva; Meshorer, Eran; Benvenisty, Nissim] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [Scaffidi, Paola] NCI, NIH, Bethesda, MD 20892 USA. [Scaffidi, Paola] UCL, UCL Canc Inst, London WC1E 6BT, England. [Scaffidi, Paola] Canc Res UK London Res Inst, London WC2A 3LY, England. [Herold-Mende, Christel] Heidelberg Univ, Dept Neurosurg, Div Neurosurg Res, Heidelberg, Germany. [Boehringer, Markus] F Hoffmann La Roche & Cie AG, CH-4070 Basel, Switzerland. RP Meshorer, E (reprint author), Hebrew Univ Jerusalem, Silberman Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. EM meshorer@huji.ac.il; nissimb@cc.huji.ac.il FU Intramural NIH HHS NR 10 TC 4 Z9 4 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1674-2788 EI 1759-4685 J9 J MOL CELL BIOL JI J. Mol. Cell Biol. PD JUN PY 2014 VL 6 IS 3 SI SI BP 267 EP 269 DI 10.1093/jmcb/mju012 PG 3 WC Cell Biology SC Cell Biology GA AI7JR UT WOS:000337065700010 PM 24683201 ER PT J AU Chang, KE Edwards, N Mishra, B Hallett, M Ray-Chaudhury, A AF Chang, Ki-Eun Edwards, Nancy Mishra, Bibhuti Hallett, Mark Ray-Chaudhury, Abhik TI Adult-Onset Alexander Disease in a Paraplegic African-American Male with a Rare D138N Mutation in the GFAP Gene SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [Chang, Ki-Eun] Penn State Coll Med, NIH, Hershey, PA USA. [Edwards, Nancy; Hallett, Mark] NINDS, NIH, Bethesda, MD 20892 USA. [Mishra, Bibhuti] Inova Fairfax Hosp, Falls Church, VA 22042 USA. [Ray-Chaudhury, Abhik] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 59 BP 600 EP 601 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100069 ER PT J AU Curtis, M Mardekian, S Miettinen, M Andrews, E AF Curtis, Mark Mardekian, Stacey Miettinen, Markku Andrews, Edward TI Succinate Dehydrogenase (SDH) Deficiency in Non-familial Pituitary Adenomas SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [Curtis, Mark] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Mardekian, Stacey; Andrews, Edward] Thomas Jefferson Univ Hosp, Dept Pathol, Philadelphia, PA 19107 USA. [Miettinen, Markku] NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 119 BP 616 EP 617 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100126 ER PT J AU Ho, JE Larson, MG Ghorbani, A Cheng, S Coglianese, EE Vasan, RS Wang, TJ AF Ho, Jennifer E. Larson, Martin G. Ghorbani, Anahita Cheng, Susan Coglianese, Erin E. Vasan, Ramachandran S. Wang, Thomas J. TI Long-term Cardiovascular Risks Associated With an Elevated Heart Rate: The Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE cardiovascular disease; epidemiology; heart failure; risk factor ID PACEMAKER IMPLANTATION; MYOCARDIAL-INFARCTION; PHYSICAL-ACTIVITY; PROGNOSTIC-FACTOR; PULSE-RATE; MORTALITY; FAILURE; DISEASE; MEN; ATHEROSCLEROSIS AB Background-Higher heart rate has been associated with an adverse prognosis, but most prior studies focused on individuals with known cardiovascular disease or examined a limited number of outcomes. We sought to examine the association of baseline heart rate with both fatal and nonfatal outcomes during 2 decades of follow-up. Methods and Results-Our study included 4058 Framingham Heart Study participants (mean age 55 years, 56% women). Cox models were performed with multivariable adjustment for clinical risk factors and physical activity. A total of 708 participants developed incident cardiovascular disease (303 heart failure, 343 coronary heart disease, and 216 stroke events), 48 received a permanent pacemaker, and 1186 died. Baseline heart rate was associated with incident cardiovascular disease (hazard ratio [HR] 1.15 per 1 SD [11 bpm] increase in heart rate, 95% CI 1.07 to 1.24, P=0.0002), particularly heart failure (HR 1.32, 95% CI 1.18 to 1.48, P<0.0001). Higher heart rate was also associated with higher all-cause (HR 1.17, 95% CI 1.11 to 1.24, P<0.0001) and cardiovascular mortality (HR 1.18, 95% CI 1.04 to 1.33, P=0.01). Spline analyses did not suggest a lower threshold beyond which the benefit of a lower heart rate abated or increased. In contrast, individuals with a higher heart rate had a lower risk of requiring permanent pacemaker placement (HR 0.55, 95% CI 0.38 to 0.79, P=0.001). Conclusions-Individuals with a higher heart rate are at elevated long-term risk for cardiovascular events, in particular, heart failure, and all-cause death. On the other hand, a higher heart rate is associated with a lower risk of future permanent pacemaker implantation. C1 [Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA. [Ho, Jennifer E.] Boston Univ, Cardiovasc Med Sect, Sch Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. [Ghorbani, Anahita] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Cheng, Susan] Harvard Univ, Sch Med, Dept Med, Div Cardiol,Brigham & Womens Hosp, Boston, MA USA. [Coglianese, Erin E.] Loyola Univ Hlth Syst, Chicago, IL USA. [Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN USA. RP Ho, JE (reprint author), Boston Univ, Med Ctr, 88 East Newton St,C-818, Boston, MA 02118 USA. EM jenho@bu.edu OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institutes of Health [K23-HL116780]; Boston University School of Medicine Department of Medicine; Ellison Foundation FX This work was partially supported by the Framingham Heart Study of the National Heart, Lung, and Blood Institute (contract N01-HC-25195). Dr Ho is supported by National Institutes of Health grant K23-HL116780 and a Boston University School of Medicine Department of Medicine Career Investment Award. Dr Cheng is supported by an award from the Ellison Foundation. NR 37 TC 20 Z9 20 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000668 DI 10.1161/JAHA.113.000668 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI4QB UT WOS:000336848800008 PM 24811610 ER PT J AU McDermott, MM Guralnik, JM Criqui, MH Ferrucci, L Zhao, LH Liu, K Domanchuk, K Spring, B Tian, L Kibbe, M Liao, YH Jones, DL Rejeski, WJ AF McDermott, Mary M. Guralnik, Jack M. Criqui, Michael H. Ferrucci, Luigi Zhao, Lihui Liu, Kiang Domanchuk, Kathryn Spring, Bonnie Tian, Lu Kibbe, Melina Liao, Yihua Jones, Donald Lloyd Rejeski, W. Jack TI Home-Based Walking Exercise in Peripheral Artery Disease: 12-Month Follow-up of the Goals Randomized Trial SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE behavior change; exercise; mobility; peripheral artery disease; physical functioning ID ANKLE BRACHIAL INDEX; INTERMITTENT CLAUDICATION; PHYSICAL-ACTIVITY; FUNCTIONAL PERFORMANCE; DAILY-LIFE; LEG SYMPTOMS; OLDER-ADULTS; REHABILITATION; INTERVENTION; METAANALYSIS AB Background-We studied whether a 6-month group-mediated cognitive behavioral (GMCB) intervention for peripheral artery disease (PAD) participants, which promoted home-based walking exercise, improved 6-minute walk and other outcomes at 12-month follow-up, 6 months after completing the intervention, compared to a control group. Methods and Results-We randomized PAD participants to a GMCB intervention or a control group. During phase I (months 1 to 6), the intervention used group support and self-regulatory skills during weekly on-site meetings to help participants adhere to home-based exercise. The control group received weekly on-site lectures on topics unrelated to exercise. Primary outcomes were measured at the end of phase I. During phase II (months 7 to 12), each group received telephone contact. Compared to controls, participants randomized to the intervention increased their 6-minute walk distance from baseline to 12-month follow-up, (from 355.4 to 381.9 m in the intervention versus 353.1 to 345.6 m in the control group; mean difference=+34.1 m; 95% confidence interval [CI]=+14.6, +53.5; P<0.001) and their Walking Impairment Questionnaire (WIQ) speed score (from 36.1 to 46.5 in the intervention group versus 34.9 to 36.5 in the control group; mean difference =+8.8; 95% CI=+1.6, +16.1; P=0.018). Change in the WIQ distance score was not different between the 2 groups at 12-month follow-up (P=0.139). Conclusions-A weekly on-site GMCB intervention that promoted home-based walking exercise intervention for people with PAD demonstrated continued benefit at 12-month follow-up, 6 months after the GMCB intervention was completed. C1 [McDermott, Mary M.; Domanchuk, Kathryn; Jones, Donald Lloyd] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [McDermott, Mary M.; Zhao, Lihui; Liu, Kiang; Spring, Bonnie; Liao, Yihua; Jones, Donald Lloyd] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Kibbe, Melina] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA. [Tian, Lu] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Kibbe, Melina] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA. [Rejeski, W. Jack] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA. RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU National Heart, Lung and Blood Institute [R01-HL088589, R01-HL107510]; National Institutes on Aging, National Institutes of Health FX Supported by R01-HL088589 and R01-HL107510 from the National Heart, Lung and Blood Institute. Supported, in part, by the Intramural Research Program, National Institutes on Aging, National Institutes of Health. NR 37 TC 21 Z9 22 U1 7 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000711 DI 10.1161/JAHA.113.000711 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI4QB UT WOS:000336848800010 PM 24850615 ER PT J AU Mandell, DT Kristoff, J Gaufin, T Gautam, R Ma, DZ Sandler, N Haret-Richter, G Xu, CL Aamer, H Dufour, J Trichel, A Douek, DC Keele, BF Apetrei, C Pandrea, I AF Mandell, Daniel T. Kristoff, Jan Gaufin, Thaidra Gautam, Rajeev Ma, Dongzhu Sandler, Netanya Haret-Richter, George Xu, Cuiling Aamer, Hadega Dufour, Jason Trichel, Anita Douek, Daniel C. Keele, Brandon F. Apetrei, Cristian Pandrea, Ivona TI Pathogenic Features Associated with Increased Virulence upon Simian Immunodeficiency Virus Cross-Species Transmission from Natural Hosts SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; CD4(+) T-CELLS; IN-VIVO REPLICATION; INFECTED SOOTY MANGABEYS; PRIMARY HIV-1 INFECTION; ACUTE SIV INFECTION; PLASMA VIRAL LOAD; RHESUS MACAQUES; GASTROINTESTINAL-TRACT; PIGTAIL MACAQUES AB While simian immunodeficiency viruses (SIVs) are generally nonpathogenic in their natural hosts, dramatic increases in pathogenicity may occur upon cross-species transmission to new hosts. Deciphering the drivers of these increases in virulence is of major interest for understanding the emergence of new human immunodeficiency viruses (HIVs). We transmitted SIVsab from the sabaeus species of African green monkeys (AGMs) to pigtailed macaques (PTMs). High acute viral replication occurred in all SIVsab-infected PTMs, yet the outcome of chronic infection was highly variable, ranging from rapid progression to controlled infection, which was independent of the dynamics of acute viral replication, CD4(+) T cell depletion, or preinfection levels of microbial translocation. Infection of seven PTMs with plasma collected at necropsy from a rapid-progressor PTM was consistently highly pathogenic, with high acute and chronic viral replication, massive depletion of memory CD4(+) T cells, and disease progression in all PTMs. The plasma inoculum used for the serial passage did not contain adventitious bacterial or viral contaminants. Single-genome amplification showed that this inoculum was significantly more homogenous than the inoculum directly derived from AGMs, pointing to a strain selection in PTMs. In spite of similar peak plasma viral loads between the monkeys in the two passages, immune activation/inflammation levels dramatically increased in PTMs infected with the passaged virus. These results suggest that strain selection and a massive cytokine storm are major factors behind increased pathogenicity of SIV upon serial passage and adaptation of SIVs to new hosts following cross-species transmission. C1 [Mandell, Daniel T.; Gaufin, Thaidra; Gautam, Rajeev; Apetrei, Cristian] TNPRC, Div Microbiol, Covington, LA USA. [Dufour, Jason] TNPRC, Div Vet Med, Covington, LA USA. [Pandrea, Ivona] TNPRC, Div Comparat Pathol, Covington, LA USA. [Kristoff, Jan; Ma, Dongzhu; Haret-Richter, George; Xu, Cuiling; Aamer, Hadega; Apetrei, Cristian; Pandrea, Ivona] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15260 USA. [Sandler, Netanya; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Trichel, Anita] Univ Pittsburgh, Sch Med, Div Lab Anim Resourcese, Pittsburgh, PA USA. [Apetrei, Cristian] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA. [Pandrea, Ivona] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. [Keele, Brandon F.] Leidos Biomed Res Inc, Frederick Natl Lab, AIDS & Canc Virus Program, Frederick, MD USA. RP Pandrea, I (reprint author), Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15260 USA. EM apetreic@pitt.edu; pandrea@pitt.edu RI Haret-Richter, George S/G-3563-2015; OI Utay, Netanya/0000-0002-6407-8670 FU National Institute of Allergy and Infectious Diseases (NIAID) [RO1 AI064066, R01 AI065325, P20 RR020159]; National Center for Research Resources (NCRR) [RO1 RR025781]; National Heart, Lung and Blood Institute [RO1 HL117715]; National Cancer Institute [HHSN261200800001E] FX This work was supported by funds from grants RO1 AI064066 (I. P.) and R01 AI065325 and P20 RR020159 (C. A.) from the National Institute of Allergy and Infectious Diseases (NIAID), RO1 RR025781 (C. A. and I. P.) from the National Center for Research Resources (NCRR), RO1 HL117715 (I. P.) from the National Heart, Lung and Blood Institute, and in part with federal funds from the National Cancer Institute under contract HHSN261200800001E (B.F.K.). NR 76 TC 8 Z9 8 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2014 VL 88 IS 12 BP 6778 EP 6792 DI 10.1128/JVI.03785-13 PG 15 WC Virology SC Virology GA AI5HF UT WOS:000336895600022 PM 24696477 ER PT J AU Chen, ZY Baz, M Lu, J Paskel, M Santos, C Subbarao, K Jin, H Matsuoka, Y AF Chen, Zhongying Baz, Mariana Lu, Janine Paskel, Myeisha Santos, Celia Subbarao, Kanta Jin, Hong Matsuoka, Yumiko TI Development of a High-Yield Live Attenuated H7N9 Influenza Virus Vaccine That Provides Protection against Homologous and Heterologous H7 Wild-Type Viruses in Ferrets SO JOURNAL OF VIROLOGY LA English DT Article ID RECEPTOR-BINDING SPECIFICITY; A VIRUS; HEMAGGLUTININ PROTEIN; BRITISH-COLUMBIA; HUMAN INFECTION; MICE; TRANSMISSION; CONJUNCTIVITIS; CHALLENGE; REPLICATION AB Live attenuated H7N9 influenza vaccine viruses that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the newly emerged wild-type (wt) A/Anhui/1/2013 (H7N9) and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (AA ca) were generated by reverse genetics. The reassortant virus containing the original wt A/Anhui/1/2013 HA and NA sequences replicated poorly in eggs. Multiple variants with amino acid substitutions in the HA head domain that improved viral growth were identified by viral passage in eggs and MDCK cells. The selected vaccine virus containing two amino acid changes (N133D/G198E) in the HA improved viral titer by more than 10-fold (reached a titer of 10(8.6) fluorescent focus units/ml) without affecting viral antigenicity. Introduction of these amino acid changes into an H7N9 PR8 reassortant virus also significantly improved viral titers and HA protein yield in eggs. The H7N9 ca vaccine virus was immunogenic in ferrets. A single dose of vaccine conferred complete protection of ferrets from homologous wt A/Anhui/1/2013 (H7N9) and nearly complete protection from heterologous wt A/Netherlands/219/2003 (H7N7) challenge infection. Therefore, this H7N9 live attenuated influenza vaccine (LAIV) candidate has been selected for vaccine manufacture and clinical evaluation to protect humans from wt H7N9 virus infection. C1 [Chen, Zhongying; Lu, Janine; Jin, Hong] MedImmune LLC, Mountain View, CA 94043 USA. [Baz, Mariana; Paskel, Myeisha; Santos, Celia; Subbarao, Kanta; Matsuoka, Yumiko] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Chen, ZY (reprint author), MedImmune LLC, Mountain View, CA 94043 USA. EM chenz@medimmune.com FU Biomedical Advanced Research and Development Authority of the U.S. Department of Health and Human Services [HHSO100201200012I]; NIAID, NIH FX This study was funded in part by federal funds from Biomedical Advanced Research and Development Authority of the U.S. Department of Health and Human Services under the contract number HHSO100201200012I and by the Intramural Research Program of NIAID, NIH. The work is conducted under a Cooperative Research and Development Agreement between MedImmune and NIAID/NIH. NR 51 TC 20 Z9 21 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2014 VL 88 IS 12 BP 7016 EP 7023 DI 10.1128/JVI.00100-14 PG 8 WC Virology SC Virology GA AI5HF UT WOS:000336895600041 PM 24719414 ER PT J AU Saisawat, P Kohl, S Hilger, AC Hwang, DY Gee, HY Dworschak, GC Tasic, V Pennimpede, T Natarajan, S Sperry, E Matassa, DS Stajic, N Bogdanovic, R de Blaauw, I Marcelis, CLM Wijers, CHW Bartels, E Schmiedeke, E Schmidt, D Marzheuser, S Grasshoff-Derr, S Holland-Cunz, S Ludwig, M Nothen, MM Draaken, M Brosens, E Heij, H Tibboel, D Herrmann, BG Solomon, BD de Klein, A van Rooij, IALM Esposito, F Reutter, HM Hildebrandt, F AF Saisawat, Pawaree Kohl, Stefan Hilger, Alina C. Hwang, Daw-Yang Gee, Heon Yung Dworschak, Gabriel C. Tasic, Velibor Pennimpede, Tracie Natarajan, Sivakumar Sperry, Ethan Matassa, Danilo S. Stajic, Natasa Bogdanovic, Radovan de Blaauw, Ivo Marcelis, Carlo L. M. Wijers, Charlotte H. W. Bartels, Enrika Schmiedeke, Eberhard Schmidt, Dominik Maerzheuser, Stefanie Grasshoff-Derr, Sabine Holland-Cunz, Stefan Ludwig, Michael Noethen, Markus M. Draaken, Markus Brosens, Erwin Heij, Hugo Tibboel, Dick Herrmann, Bernhard G. Solomon, Benjamin D. de Klein, Annelies van Rooij, Iris A. L. M. Esposito, Franca Reutter, Heiko M. Hildebrandt, Friedhelm TI Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association SO KIDNEY INTERNATIONAL LA English DT Article DE genetics and development; genetic renal disease; renal agenesis; renal development; ureteric bud; vesicoureteral reflux ID KIDNEY; HETEROTAXY; DISORDERS AB Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole-exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat-shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle's loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT. C1 [Saisawat, Pawaree; Hilger, Alina C.; Natarajan, Sivakumar; Sperry, Ethan] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Kohl, Stefan; Hwang, Daw-Yang; Gee, Heon Yung; Dworschak, Gabriel C.; Hildebrandt, Friedhelm] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp, Boston, MA USA. [Hilger, Alina C.; Dworschak, Gabriel C.; Bartels, Enrika; Schmidt, Dominik; Noethen, Markus M.; Draaken, Markus; Reutter, Heiko M.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Tasic, Velibor] Univ Childrens Hosp, Dept Pediat Nephrol, Skopje, Macedonia. [Pennimpede, Tracie; Herrmann, Bernhard G.] Max Planck Inst Mol Genet, Dev Genet Dept, D-14195 Berlin, Germany. [Matassa, Danilo S.; Esposito, Franca] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy. [Stajic, Natasa; Bogdanovic, Radovan] Univ Belgrade, Fac Med, Belgrade, Serbia. [Stajic, Natasa; Bogdanovic, Radovan] Inst Mother & Child Healthcare Serbia, Belgrade, Serbia. [de Blaauw, Ivo] Radboud Univ Nijmegen, Med Ctr, Dept Pediat Surg, NL-6525 ED Nijmegen, Netherlands. [Marcelis, Carlo L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Wijers, Charlotte H. W.; van Rooij, Iris A. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands. [Schmiedeke, Eberhard] Hosp Bremen Mitte, Ctr Child & Adolescent Hlth, Dept Pediat Surg & Urol, Bremen, Germany. [Maerzheuser, Stefanie] Charite, Campus Virchow Clin, Dept Pediat Surg, Berlin, Germany. [Grasshoff-Derr, Sabine] Univ Hosp Wurzburg, Dept Pediat Surg, Wurzburg, Germany. [Holland-Cunz, Stefan] Heidelberg Univ, Dept Pediat Surg, Heidelberg, Germany. [Ludwig, Michael] Univ Bonn, Dept Clin Chem & Clin Pharmacol, Bonn, Germany. [Noethen, Markus M.; Draaken, Markus] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. [Brosens, Erwin; Tibboel, Dick] Erasmus MC Sophia, Dept Pediat Surg, Rotterdam, Netherlands. [Brosens, Erwin; de Klein, Annelies] Erasmus MC Sophia, Dept Clin Genet, Rotterdam, Netherlands. [Heij, Hugo] Emma Childrens Hosp, Pediat Surg Ctr Amsterdam, Amsterdam, Netherlands. [Heij, Hugo] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Solomon, Benjamin D.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Reutter, Heiko M.] Univ Bonn, Childrens Hosp, Dept Neonatol, Bonn, Germany. [Hildebrandt, Friedhelm] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Reutter, HM (reprint author), Univ Klinikum Bonn, Biomed Zentrum, Inst Humangenet, Sigmund Freud Str 25, D-53727 Bonn, Germany. EM reutter@uni-bonn.de; friedhelm.hildebrandt@childrens.harvard.edu RI Blaauw, I./L-4203-2015; Marcelis, C.L.M./L-4504-2015; Rooij, van, Iris/A-5705-2014; Matassa, Danilo Swann/K-1596-2016; Esposito, Franca/K-2024-2016; OI Rooij, van, Iris/0000-0002-9519-966X; Matassa, Danilo Swann/0000-0002-4259-9221; Esposito, Franca/0000-0001-9340-6875; Draaken, Markus/0000-0002-4546-0786; Nothen, Markus/0000-0002-8770-2464 FU National Institutes of Health [R01-DK045345, R01-DK088767]; March of Dimes Foundation [6FY11-241]; Division of Intramural Research; National Human Genome Research Institute (NHGRI); National Institutes of Health and Human services; Bundesministerium fur Bildung und Forschung [01GM08107]; BONFOR program of the University of Bonn [O-149.0099, O-149.0096]; Sophia Scientific Research Foundation [SSWO S13/9]; associazione Italiana per la Ricerca sul Cancro (AIRC) [IG13128]; Italian Ministry of Health [GR-2010-2310057] FX We thank the physicians and families for participating in this study, the German self-help organization for people with anorectal malformations (SoMA eV), and all participating physicians, nurses, research assistants, laboratory analysts, and project members of AGORA (Aetiologic research into Genetic and Occupational/Environmental Risk Factors for Anomalies in Children) for their support in building this biobank. FH is an Investigator of the Howard Hughes Medical Institute, a Doris Duke Distinguished Clinical Scientist, and a Frederick GL Huetwell Professor. ACH, GCD, Enrika Bartels, ES, DS, SG-D, SM, SH-C, MMN, ML, HMR, and MD are members of the 'Network for the Systematic Investigation of the Molecular Causes, Clinical Implications and Psychosocial Outcome of Congenital Uro-Rectal Malformations' (CURE-Net). This research was supported by grants from the National Institutes of Health (to FH; R01-DK045345 and R01-DK088767), by the March of Dimes Foundation (6FY11-241), by the Division of Intramural Research, by the National Human Genome Research Institute (NHGRI), by the National Institutes of Health and Human services, by the Bundesministerium fur Bildung und Forschung (grant 01GM08107), by the BONFOR program of the University of Bonn (to Enrika Bartels; grant O-149.0099, and to GCD; grant O-149.0096), by Sophia Scientific Research Foundation (to Enrika Bartels; grant SSWO S13/9), by the associazione Italiana per la Ricerca sul Cancro (AIRC) (to FE; grant IG13128), and by the Italian Ministry of Health (to FE; grant GR-2010-2310057). NR 21 TC 29 Z9 29 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2014 VL 85 IS 6 BP 1310 EP 1317 DI 10.1038/ki.2013.417 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA AI4FG UT WOS:000336820500013 PM 24152966 ER PT J AU Klisovic, RB Blum, W Liu, ZF Xie, ZL Kefauver, C Huynh, L Zwiebel, JA Devine, SM Byrd, JC Grever, MR Chan, KK Marcucci, G AF Klisovic, Rebecca B. Blum, William Liu, Zhongfa Xie, Zhiliang Kefauver, Cheryl Huynh, Lenguyen Zwiebel, James A. Devine, Steven M. Byrd, John C. Grever, Michael R. Chan, Kenneth K. Marcucci, Guido TI Phase I study of GTI-2040, a ribonucleotide reductase antisense, with high dose cytarabine in patients with relapsed/refractory acute myeloid leukemia SO LEUKEMIA & LYMPHOMA LA English DT Article DE Acute myeloid leukemia; antisense therapy; phase I study; GTI-2040; ribonucleotide reductase ID ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; R2 COMPONENT; FLUDARABINE; METABOLISM; CELLS; 5-FLUOROURACIL; COMBINATION; MECHANISMS; RESISTANCE AB We hypothesized that GTI-2040, a 20-mer oligonucleotide complementary to the R2 subunit mRNA of ribonucleotide reductase, combined with high dose cytarabine (HiDAC) would result in enhanced cytotoxicity by favoring Ara-CTP DNA incorporation. In a phase I dose escalation trial, adults (>= 60 years) with refractory or relapsed acute myeloid leukemia (AML) received daily HiDAC plus infusional GTI-2040. Using a novel assay, evidence of intracellular drug accumulation and target R2 down-regulation was observed. GTI-2040/HiDAC can be administered safely. However, with no complete remissions observed, alternative doses and schedules may need to be investigated to achieve clinical activity in older patients with AML. C1 [Klisovic, Rebecca B.; Blum, William; Huynh, Lenguyen; Devine, Steven M.; Byrd, John C.; Grever, Michael R.; Marcucci, Guido] Ohio State Univ, Div Hematol, Dept Med, Columbus, OH 43210 USA. [Liu, Zhongfa; Xie, Zhiliang; Chan, Kenneth K.] Ohio State Univ, Div Pharmaceut, Coll Pharm, Columbus, OH 43210 USA. [Blum, William; Kefauver, Cheryl; Devine, Steven M.; Byrd, John C.; Grever, Michael R.; Chan, Kenneth K.; Marcucci, Guido] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Zwiebel, James A.] NCI, Bethesda, MD 20892 USA. RP Marcucci, G (reprint author), Ohio State Univ, Div Hematol & Oncol, A437A Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM guido.marcucci@osumc.edu FU [NCI U01 CA 076576-10]; [NCI R21 CA 105879] FX This study was supported by NCI U01 CA 076576-10 and NCI R21 CA 105879. NR 29 TC 2 Z9 2 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 2014 VL 55 IS 6 BP 1332 EP 1336 DI 10.3109/10428194.2013.838764 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA AI3FV UT WOS:000336747100019 PM 24015841 ER PT J AU Manasanch, EE Braylan, R Stetler-Stevenson, M Yuan, C Gounden, V Korde, N Tageja, N Bhutani, M Calvo, K Maric, I Roschewski, M Staudt, LM Landgren, O AF Manasanch, Elisabet E. Braylan, Raul Stetler-Stevenson, Maryalice Yuan, Constance Gounden, Verena Korde, Neha Tageja, Nishant Bhutani, Manisha Calvo, Katherine Maric, Irina Roschewski, Mark Staudt, Louis M. Landgren, Ola TI Lack of MYD88 L265P in non-immunoglobulin M lymphoplasmacytic lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Letter ID SOMATIC MUTATION; WALDENSTROMS MACROGLOBULINEMIA; MONOCLONAL GAMMOPATHY; MGUS C1 [Manasanch, Elisabet E.; Korde, Neha; Tageja, Nishant; Bhutani, Manisha; Roschewski, Mark; Landgren, Ola] NCI, Multiple Myeloma Sect, Bethesda, MD 20892 USA. [Staudt, Louis M.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Braylan, Raul; Calvo, Katherine; Maric, Irina] NIH, Hematol Sect, Dept Lab Med, Bethesda, MD 20892 USA. [Stetler-Stevenson, Maryalice; Yuan, Constance] NIH, Flow Cytometry Unit, Pathol Lab, Bethesda, MD 20892 USA. [Gounden, Verena] NIH, Dept Pathol, Bethesda, MD 20892 USA. RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 10 Room 13N240, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov OI Calvo, Katherine/0000-0002-0771-4191 NR 6 TC 7 Z9 7 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 2014 VL 55 IS 6 BP 1402 EP 1403 DI 10.3109/10428194.2013.831091 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA AI3FV UT WOS:000336747100031 PM 23915224 ER PT J AU Peterson, MD Al Snih, S Stoddard, J Mcclain, J Lee, IM AF Peterson, Mark D. Al Snih, Soham Stoddard, Jonathan Mcclain, James Lee, I-Min TI Adiposity and Insufficient MVPA Predict Cardiometabolic Abnormalities in Adults SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE EXERCISE; ACCELEROMETRY; ADIPOSITY; SITTING TIME; INSULIN RESISTANCE ID PHYSICAL-ACTIVITY; SEDENTARY BEHAVIORS; INSULIN-RESISTANCE; SITTING TIME; LIFE-STYLE; MORTALITY; OBESITY; DISEASE; ASSOCIATIONS; WEIGHT AB Objectives: The purpose of this study is to compare the extent to which different combinations of objectively measured sedentary behavior (SB) and physical activity contribute to cardiometabolic health. Design and Methods: A population representative sample of 5268 individuals, ages 20-85 yr, was included from the combined 2003-2006 National Health and Nutrition Examination Survey datasets. Activity categories were created on the combined basis of objectively measured SB and moderate-to-vigorous physical activity (MVPA) tertiles. Cardiometabolic abnormalities included elevated blood pressure, levels of triglycerides, fasting plasma glucose, C-reactive protein, homeostasis model assessment of insulin resistance value, and low HDL cholesterol level. Body mass index and dual-energy x-ray absorptiometry-derived percent body fat and android adiposity were also compared across groups. Predictors for a metabolically abnormal phenotype (>= 3 cardiometabolic abnormalities or insulin resistance) were determined. Results: Adults with the least SB and greatest MVPA exhibited the healthiest cardiometabolic profiles, whereas adults with the greatest SB and lowest MVPA were older and had elevated risk. Time spent in SB was not a predictor of the metabolically abnormal phenotype when MVPA was accounted for. Adults with the highest MVPA across SB tertiles did not differ markedly in prevalence of obesity, adiposity, and/or serum cardiometabolic risk factors; however, less MVPA was associated with substantial elevations of obesity and cardiometabolic risk. Android adiposity (per kilogram) was independently associated with the metabolically abnormal phenotype in both men (odds ratio, 2.36 (95% CI, 1.76-3.17), P < 0.001) and women (odds ratio, 2.00 (95% CI, 1.63-2.45), P < 0.001). Among women, greater SB and less lifestyle moderate activity and MVPA were each independently associated with the metabolically abnormal phenotype, whereas only less MVPA was associated with it in men. Conclusions: MVPA is a strong predictor of cardiometabolic health among adults, independent of time spent in SB. C1 [Peterson, Mark D.; Stoddard, Jonathan] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. [Al Snih, Soham] Univ Texas Med Branch, Dept Internal Med, Div Geriatr, Div Rehabil Sci,Sch Hlth Profess, Galveston, TX 77555 USA. [Mcclain, James] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Lee, I-Min] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. RP Peterson, MD (reprint author), Univ Michigan Hosp & Hlth Syst, Dept Phys Med & Rehabil, 325 E Eisenhower Pkwy,Suite 300, Ann Arbor, MI 48108 USA. EM mdpeterz@med.umich.edu FU U.S. National Institutes of Health [R24 HD065702-03, CA154647]; National Institutes of Health [1KO1-HD074706] FX This study was funded by the U.S. National Institutes of Health: R24 HD065702-03 (M. Peterson and S. Al Snih). Dr. Peterson is funded by the National Institutes of Health (1KO1-HD074706). I-Min Lee was supported in part by grant CA154647 from the U.S. National Institutes of Health. NR 24 TC 4 Z9 4 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 EI 1530-0315 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUN PY 2014 VL 46 IS 6 BP 1133 EP 1139 DI 10.1249/MSS.0000000000000212 PG 7 WC Sport Sciences SC Sport Sciences GA AI6FF UT WOS:000336966200009 PM 24389519 ER PT J AU Antignani, A Sarnovsky, R FitzGerald, DJ AF Antignani, Antonella Sarnovsky, Robert FitzGerald, David J. TI ABT-737 Promotes the Dislocation of ER Luminal Proteins to the Cytosol, Including Pseudomonas Exotoxin SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RECOMBINANT IMMUNOTOXIN; CANCER-CELLS; BCL-2 FAMILY; STRESS; RECEPTOR; COMBINATION; APOPTOSIS; BAK; IMMUNOTHERAPY; CYTOTOXICITY AB Impaired apoptosis is often a key element in tumor development. Therefore, drugs mimicking prosurvival antagonists offer promise as cancer therapeutics. When ABT-737, a BH3-only mimetic, was added to KB3-1 human cervical adenocarcinoma cells, we noted an induction of an endoplasmic reticulum (ER) stress response and the dislocation of ER luminal proteins, including chaperones, to the cell cytosol. Furthermore, when immunotoxin (antibody-toxin chimeric molecule) and ABT-737 combinations were added to cells, there was enhanced toxin-mediated inhibition of protein synthesis, consistent with enhanced translocation of toxin to the cytosol. A similar enhancement was not seen with thapsigargin, suggesting that ER stress alone was not responsible for enhanced translocation. Cytosol preparations from ABT-737-treated but not from thapsigargin-treated cells revealed the presence of greater amounts of processed 37-kDa toxin fragment compared with the addition of immunotoxin alone. As early as 4 hours after the addition of ABT-737 and immunotoxin, there was release of mitochondrial cytochrome c and activation of caspase-3/7 indicating that the combination caused apoptotic cell death. These results were reflected in decreased cellular ATP levels that were noted with combinations of ABT-737 and immunotoxin but not with either agent alone or with combinations of thapsigargin and immunotoxin. We conclude that ABT-737 increases ER permeability, promoting the dislocation of toxin from the ER to the cytosol resulting in early apoptotic cell death. These mechanistic insights suggest why this class of BH3-only mimetic synergizes in a particular way with Pseudomonas exotoxin-based immunotoxins. (C) 2014 AACR. C1 [Antignani, Antonella; Sarnovsky, Robert; FitzGerald, David J.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP FitzGerald, DJ (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5124, Bethesda, MD 20892 USA. EM fitzgerd@helix.nih.gov FU Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute. NR 35 TC 4 Z9 4 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2014 VL 13 IS 6 BP 1655 EP 1663 DI 10.1158/1535-7163.MCT-13-0998 PG 9 WC Oncology SC Oncology GA AI8LX UT WOS:000337168600025 PM 24739394 ER PT J AU Camp, KM Parisi, MA Acosta, PB Berry, GT Bilder, DA Blau, N Bodamer, OA Brosco, JP Brown, CS Burlina, AB Burton, BK Chang, CS Coates, PM Cunningham, AC Dobrowolski, SF Ferguson, JH Franklin, TD Frazier, DM Grange, DK Greene, CL Groft, SC Harding, CO Howell, RR Huntington, KL Hyatt-Knorr, HD Jevaji, IP Levy, HL Lichter-Konecki, U Lindegren, ML Lloyd-Puryear, MA Matalon, K MacDonald, A McPheeters, ML Mitchell, JJ Mofidi, S Moseley, KD Mueller, CM Mulberg, AE Nerurkar, LS Ogata, BN Pariser, AR Prasad, S Pridjian, G Rasmussen, SA Reddy, UM Rohr, FJ Singh, RH Sirrs, SM Stremer, SE Tagle, DA Thompson, SM Urv, TK Utz, JR van Spronsen, F Vockley, J Waisbren, SE Weglicki, LS White, DA Whitley, CB Wilfond, BS Yannicelli, S Young, JM AF Camp, Kathryn M. Parisi, Melissa A. Acosta, Phyllis B. Berry, Gerard. T. Bilder, Deborah A. Blau, Nenad Bodamer, Olaf A. Brosco, Jeffrey P. Brown, Christine S. Burlina, Alberto B. Burton, Barbara K. Chang, Christine S. Coates, Paul M. Cunningham, Amy C. Dobrowolski, Steven F. Ferguson, John H. Franklin, Thomas D. Frazier, Dianne M. Grange, Dorothy K. Greene, Carol L. Groft, Stephen C. Harding, Cary O. Howell, R. Rodney Huntington, Kathleen L. Hyatt-Knorr, Henrietta D. Jevaji, Indira P. Levy, Harvey L. Lichter-Konecki, Uta Lindegren, Mary Lou Lloyd-Puryear, Michele A. Matalon, Kimberlee MacDonald, Anita McPheeters, Melissa L. Mitchell, John J. Mofidi, Shideh Moseley, Kathryn D. Mueller, Christine M. Mulberg, Andrew E. Nerurkar, Lata S. Ogata, Beth N. Pariser, Anne R. Prasad, Suyash Pridjian, Gabriella Rasmussen, Sonja A. Reddy, Uma M. Rohr, Frances J. Singh, Rani H. Sirrs, Sandra M. Stremer, Stephanie E. Tagle, Danilo A. Thompson, Susan M. Urv, Tiina K. Utz, Jeanine R. van Spronsen, Francjan Vockley, Jerry Waisbren, Susan E. Weglicki, Linda S. White, Desiree A. Whitley, Chester B. Wilfond, Benjamin S. Yannicelli, Steven Young, Justin M. TI Phenylketonuria Scientific Review Conference: State of the science and future research needs SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Phenylketonuria; Sapropterin; Hyperphenylalaninemia; Maternal PIN; Large neutral amino acids; Glycomacropeptide ID PHENYLALANINE-HYDROXYLASE DEFICIENCY; NEUTRAL AMINO-ACIDS; DIHYDROPTERIDINE REDUCTASE DEFICIENCY; CONTINUOUSLY TREATED PHENYLKETONURIA; TETRAHYDROBIOPTERIN LOADING TEST; GENOTYPE-PHENOTYPE CORRELATIONS; THERAPEUTIC LIVER REPOPULATION; MATERNAL BLOOD PHENYLALANINE; ENZYME REPLACEMENT THERAPY; TANDEM MASS-SPECTROMETRY AB New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 Rtnol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 [tmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism. C1 [Camp, Kathryn M.; Coates, Paul M.; Lloyd-Puryear, Michele A.] NIH, Off Dietary Supplements, Bethesda, MD 20982 USA. [Parisi, Melissa A.; Reddy, Uma M.; Urv, Tiina K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Acosta, Phyllis B.; Singh, Rani H.] Emory Univ, Atlanta, GA 30033 USA. [Berry, Gerard. T.; Levy, Harvey L.; Waisbren, Susan E.] Harvard Univ, Boston Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Bilder, Deborah A.] Univ Utah, Dept Psychiat, Salt Lake City, UT 84108 USA. [Blau, Nenad] Univ Childrens Hosp, Heidelberg, Germany. [Blau, Nenad] Univ Childrens Hosp, Zurich, Switzerland. [Bodamer, Olaf A.; Howell, R. Rodney] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Brosco, Jeffrey P.] Univ Miami, Mailman Ctr Child Dev, Miami, FL 33101 USA. [Brown, Christine S.; Franklin, Thomas D.] Natl PKU Alliance, Encinitas, CA USA. [Burlina, Alberto B.] Univ Hosp, I-35128 Padua, Italy. [Burton, Barbara K.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Chang, Christine S.] Agcy Healthcare Res & Qual, Rockville, MD 20850 USA. [Cunningham, Amy C.; Pridjian, Gabriella] Tulane Univ, Sch Med, Hayward Genet Ctr, New Orleans, LA 70112 USA. [Dobrowolski, Steven F.; Vockley, Jerry] Univ Pittsburgh, Pittsburgh, PA 15224 USA. [Ferguson, John H.; Groft, Stephen C.; Hyatt-Knorr, Henrietta D.; Nerurkar, Lata S.] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20982 USA. [Frazier, Dianne M.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Grange, Dorothy K.] Washington Univ, St Louis Childrens Hosp, Sch Med, St Louis, MO 63110 USA. [Greene, Carol L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Harding, Cary O.; Huntington, Kathleen L.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Jevaji, Indira P.] NIH, Off Res Womens Hlth, Bethesda, MD 20817 USA. [Lichter-Konecki, Uta] George Washington Univ, Childrens Natl Med Ctr, Washington, DC 20010 USA. [Lindegren, Mary Lou] Vanderbilt Univ, Sch Med, Nashville, TN 37203 USA. [Matalon, Kimberlee] Univ Houston, Houston, TX 77204 USA. [MacDonald, Anita] Birmingham Childrens Hosp, Birmingham B4 6NH, W Midlands, England. [McPheeters, Melissa L.] Inst Med & Publ Hlth, Vanderbilt Evidence Based Practice Ctr, Nashville, TN 37203 USA. [Mitchell, John J.] McGill Univ, Ctr Hlth, Montreal, PQ H3H 1P3, Canada. [Mofidi, Shideh] Maria Fareri Childrens Hosp, Westchester Med Ctr, Valhalla, NY 10595 USA. [Moseley, Kathryn D.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Mueller, Christine M.] US FDA, Off Orphan Prod Dev, Silver Spring, MD 20993 USA. [Mulberg, Andrew E.; Pariser, Anne R.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Ogata, Beth N.] Univ Washington, Seattle, WA 98195 USA. [Prasad, Suyash] BioMarin Pharmaceut Inc, San Rafael, CA 94901 USA. [Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Rohr, Frances J.] Boston Childrens Hosp, Boston, MA 02115 USA. [Sirrs, Sandra M.] Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. [Burlina, Alberto B.] PKU & Allied Disorders Wisconsin, Madison, WI 53705 USA. [Tagle, Danilo A.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Thompson, Susan M.] Childrens Hosp Westrnead, Sydney, NSW 2145, Australia. [Utz, Jeanine R.; Whitley, Chester B.] Univ Minnesota, Minneapolis, MN 55455 USA. [van Spronsen, Francjan] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, NL-9700 AB Groningen, Netherlands. [Weglicki, Linda S.] NINR, NIH, Bethesda, MD 20892 USA. [White, Desiree A.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. [Wilfond, Benjamin S.] Univ Washington, Seattle Childrens Res Inst, Sch Med, Seattle, WA 98101 USA. [Yannicelli, Steven] Nutricia North Amer, Rockville, MD 20850 USA. [Young, Justin M.] Young Face Facial Plast & Reconstruct Surg, Cumming, GA 30041 USA. RP Camp, KM (reprint author), 6100 Execut Blvd, Rockville, MD 20892 USA. EM campkm@od.nih.gov; parisima@mail.nih.gov; pja1933@gmail.com; gerard.berry@childrens.harvard.edu; deborah.bilder@hsc.utah.edu; nenad.blau@med.uni-heidelberg.de; obodamer@med.miami.edu; jbrosco@med.miami.edu; christine.brown@npkua.org; alberto.burlina@unipd.it; bburton@luriechildrens.org; christine.chang@ahrq.hhs.gov; coatesp@od.nih.gov; acunnin@tulane.edu; dobrowolskis@upmc.edu; jferg@helix.nih.gov; tom.franklin@npkua.org; dianne_frazier@med.unc.edu; grange_d@kids.wustl.edu; cgreene@peds.umaryland.edu; stephen.groft@nih.gov; hardingc@ohsu.edu; rhowell@miami.edu; huntingt@ohsu.edu; henrietta.hyatt-knorr@nih.gov; indira.jevaji@cms.hhs.gov; harvey.levy@childrens.harvard.edu; ulichter@cnmc.org; marylou.lindegren@vanderbilt.edu; lloydpuryearma@od.nih.gov; kmatalon@uh.edu; anita.macdonald@bch.nhs.uk; melissa.mcpheeters@vanderbilt.edu; john.mitchell@muhc.mcgill.ca; shideh_mofidi@nymc.edu; kmoseley@usc.edu; christine.mueller@nih.gov; andrew.mulberg@fda.hhs.gov; lnerurkar@gmail.com; bogata@uw.edu; anne.pariser@fda.hhs.gov; sprasad@bmrn.com; pridjian@tulane.edu; skr9@cdc.gov; reddyu@mail.nih.gov; frances.rohr@childrens.harvard.edu; rsingh@emory.edu; sandra.sirrs@vch.ca; sstremer@yahoo.com; danilo.tagle@nih.gov; sue.thompson@health.nsw.gov.au; urvtiin@mail.nih.gov; jutz1@fairview.org; f.j.van.spronsen@umcg.nl; vockleyg@upmc.edu; susan.waisbren@childrens.harvard.edu; weglickils@mail.nih.gov; dawhite@wustl.edu; whitley@umn.edu; benjamin.wilfond@seattlechildrens.org; steven.yannicelli@nutricia.com; jmichaelyoung@yahoo.com OI Berry, Gerard/0000-0001-5299-3313; Vockley, Jerry/0000-0002-8180-6457 NR 336 TC 43 Z9 43 U1 6 U2 74 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUN PY 2014 VL 112 IS 2 BP 87 EP 122 DI 10.1016/j.ymgme.2014.02.013 PG 36 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA AI7KF UT WOS:000337067900002 PM 24667081 ER PT J AU Smith, D Artursson, P Avdeef, A Di, L Ecker, GF Faller, B Houston, JB Kansy, M Kerns, EH Kramer, SD Lennernas, H van de Waterbeemd, H Sugano, K Testa, B AF Smith, Dennis Artursson, Per Avdeef, Alex Di, Li Ecker, Gerhard F. Faller, Bernard Houston, J. Brian Kansy, Manfred Kerns, Edward H. Kramer, Stefanie D. Lennernaes, Hans van de Waterbeemd, Han Sugano, Kiyohiko Testa, Bernard TI Passive Lipoidal Diffusion and Carrier-Mediated Cell Uptake Are Both Important Mechanisms of Membrane Permeation in Drug Disposition SO MOLECULAR PHARMACEUTICS LA English DT Review DE permeation; passive lipoidal diffusion; "carrier-mediated only" concept ID PENETRANT STRUCTURE RELATIONSHIPS; WEAKLY BASIC DRUGS; STRATUM-CORNEUM; EPIDERMAL PERMEABILITY; PHARMACEUTICAL DRUGS; URINARY-EXCRETION; LIPID-MEMBRANES; TRANSPORT; BRAIN; SKIN AB Recently, it has been proposed that drug permeation is essentially carrier-mediated only and that passive lipoidal diffusion is negligible. This opposes the prevailing hypothesis of drug permeation through biological membranes, which integrates the contribution of multiple permeation mechanisms, including both carrier-mediated and passive lipoidal diffusion, depending on the compound's properties, membrane properties, and solution properties. The prevailing hypothesis of drug permeation continues to be successful for application and prediction in drug development. Proponents of the carrier-mediated only concept argue against passive lipoidal diffusion. However, the arguments are not supported by broad pharmaceutics literature. The carrier-mediated only concept lacks substantial supporting evidence and successful applications in drug development. C1 [Artursson, Per; Lennernaes, Hans] Uppsala Univ, Biomed Ctr, Dept Pharm, S-75263 Uppsala, Sweden. [Di, Li] Pfizer Inc, Pharmacokinet Dynam & Metab, Groton, CT 06340 USA. [Ecker, Gerhard F.] Univ Vienna, Dept Med Chem, A-141090 Vienna, Austria. [Faller, Bernard] Novartis Inst Biomed Res, WSJ 350 3 04, CH-4002 Basel, Switzerland. [Houston, J. Brian] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PT, Lancs, England. [Kansy, Manfred] F Hoffmann La Roche, Nonclin Safety Dept, CH-4070 Basel, Switzerland. [Kerns, Edward H.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. [Kramer, Stefanie D.] ETH, Inst Pharmaceut Sci, Zurich, Switzerland. [Sugano, Kiyohiko] Sandwich Labs, Res Formulat, Sandwich CT13 9NJ, Kent, England. [Testa, Bernard] Univ Lausanne Hosp, Dept Pharm, CH-1011 Lausanne, Switzerland. RP Smith, D (reprint author), 4 Maltings, Walmer CT14 7AR, Kent, England. EM professordennis@deltic50.freeserve.co.uk OI Ecker, Gerhard/0000-0003-4209-6883; Kramer, Stefanie D./0000-0002-0426-4340 NR 82 TC 22 Z9 22 U1 7 U2 43 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUN PY 2014 VL 11 IS 6 BP 1727 EP 1738 DI 10.1021/mp400713v PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA AI5XB UT WOS:000336941900001 PM 24724562 ER PT J AU Zhang, B Jia, WH Matsuda, K Kweon, SS Matsuo, K Xiang, YB Shin, AS Jee, SH Kim, DH Cai, QY Long, JR Shi, JJ Wen, WQ Yang, G Zhang, YF Li, C Li, BS Guo, Y Ren, ZF Ji, BT Pan, ZZ Takahashi, A Shin, MH Matsuda, F Gao, YT Oh, JH Kim, S Ahn, YO Chan, AT Chang-Claude, J Slattery, ML Gruber, SB Schumacher, FR Stenzel, SL Casey, G Kim, HR Jeong, JY Park, JW Li, HL Hosono, S Cho, SH Kubo, M Shu, XO Zeng, YX Zheng, W AF Zhang, Ben Jia, Wei-Hua Matsuda, Koichi Kweon, Sun-Seog Matsuo, Keitaro Xiang, Yong-Bing Shin, Aesun Jee, Sun Ha Kim, Dong-Hyun Cai, Qiuyin Long, Jirong Shi, Jiajun Wen, Wanqing Yang, Gong Zhang, Yanfeng Li, Chun Li, Bingshan Guo, Yan Ren, Zefang Ji, Bu-Tian Pan, Zhi-Zhong Takahashi, Atsushi Shin, Min-Ho Matsuda, Fumihiko Gao, Yu-Tang Oh, Jae Hwan Kim, Soriul Ahn, Yoon-Ok Chan, Andrew T. Chang-Claude, Jenny Slattery, Martha L. Gruber, Stephen B. Schumacher, Fredrick R. Stenzel, Stephanie L. Casey, Graham Kim, Hyeong-Rok Jeong, Jin-Young Park, Ji Won Li, Hong-Lan Hosono, Satoyo Cho, Sang-Hee Kubo, Michiaki Shu, Xiao-Ou Zeng, Yi-Xin Zheng, Wei CA Genetics Epidemiology Colorectal C Colorectal Transdisciplinary COREC Colon Canc Family Registry TI Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LYMPHOTOXIN-BETA-RECEPTOR; SUSCEPTIBILITY LOCI; BREAST-CANCER; COLON-CANCER; CELL-GROWTH; EXPRESSION; MUTATIONS; VARIANTS; METAANALYSIS AB Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 x 10(-8) to 9.22 x 10(-21)) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways. C1 [Zhang, Ben; Cai, Qiuyin; Long, Jirong; Shi, Jiajun; Wen, Wanqing; Yang, Gong; Zhang, Yanfeng; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA. [Jia, Wei-Hua; Pan, Zhi-Zhong; Zeng, Yi-Xin] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China. [Matsuda, Koichi] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan. [Kweon, Sun-Seog; Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Kwangju, South Korea. [Kweon, Sun-Seog] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun, South Korea. [Matsuo, Keitaro; Hosono, Satoyo] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 812, Japan. [Xiang, Yong-Bing; Gao, Yu-Tang; Li, Hong-Lan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Shin, Aesun] Natl Canc Ctr, Mol Epidemiol Branch, Goyang Si, South Korea. [Shin, Aesun; Ahn, Yoon-Ok] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Jee, Sun Ha; Kim, Soriul] Yonsei Univ, Grad Sch Publ Hlth, Inst Hlth Promot, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea. [Kim, Dong-Hyun; Jeong, Jin-Young] Hallym Univ, Coll Med, Dept Social & Prevent Med, Okcheon Dong, South Korea. [Li, Chun] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Li, Bingshan] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. [Guo, Yan] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA. [Ren, Zefang] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510275, Guangdong, Peoples R China. [Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Takahashi, Atsushi; Kubo, Michiaki] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan. [Matsuda, Fumihiko] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan. [Oh, Jae Hwan; Park, Ji Won] Natl Canc Ctr, Ctr Colorectal Canc, Goyang Si, South Korea. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Gruber, Stephen B.; Schumacher, Fredrick R.; Stenzel, Stephanie L.; Casey, Graham] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Kim, Hyeong-Rok] Chonnam Natl Univ, Sch Med, Dept Surg, Kwangju, South Korea. [Park, Ji Won] Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea. [Cho, Sang-Hee] Chonnam Natl Univ, Sch Med, Dept Hematooncol, Kwangju, South Korea. RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA. EM wei.zheng@vanderbilt.edu RI Shin, Aesun/E-9145-2014; Gallinger, Steven/E-4575-2013; Hoffmeister, Michael/B-5745-2012; KURY, Sebastien/G-5971-2015; Kubo, Michiaki/N-7947-2015; zhang, yanfeng/E-6971-2016; Brenner, Hermann/B-4627-2017; OI Shin, Aesun/0000-0002-6426-1969; Hoffmeister, Michael/0000-0002-8307-3197; KURY, Sebastien/0000-0001-5497-0465; zhang, yanfeng/0000-0002-3859-3839; Brenner, Hermann/0000-0002-6129-1572; Bezieau, stephane/0000-0003-0095-1319; Matsuda, Koichi/0000-0001-7292-2686; Matsuo, Keitaro/0000-0003-1761-6314 FU US National Institutes of Health (NIH) [R37CA070867, R01CA082729, R01CA124558, R01CA148667, R01CA122364]; Vanderbilt University School of Medicine. Studies; Asia Colorectal Cancer Consortium include the Shanghai Women's Health Study (US NIH) [R37CA070867]; Shanghai Men's Health Study (US NIH) [R01CA082729]; Shanghai Breast and Endometrial Cancer Studies (US NIH) [R01CA064277, R01CA092585]; Shanghai Colorectal Cancer Study 3 (US NIH) [R37CA070867]; Guangzhou Colorectal Cancer Study (National Key Scientific and Technological Project) [2011ZX09307-001-04]; National Basic Research Program [2011CB504303]; Natural Science Foundation of China [81072383]; Japan BioBank Colorectal Cancer Study (grant from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government); Hwasun Cancer Epidemiology Study Colon and Rectum Cancer (HCES-CRC); Korea Center for Disease Control and Prevention; Aichi Colorectal Cancer Study [17015018, 221S0001]; Korea-NCC (National Cancer Center) Colorectal Cancer Study (Basic Science Research Program through-the National Research Foundation of Korea [2010-0010276]; National Cancer Center Korea [0910220]; Korea-Seoul Colorectal Cancer Study; KCPS-II Colorectal Cancer Study (National R&D Program for Cancer Control) [1220180]; Seoul RD Program [10526]; GECCO; CORECT; CCFR; NIH [R01CA048998]; DACHS (German Federal Ministry of Education and Research) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, 01KH0404, 01ER0814]; HPFS (US NIH) [P01CA055075, UM1CA167552, R01137178, P50CA127003]; NHS (US NIH) [R01137178, P50CA127003, P01CA087969]; OFCCR (US NIH) [U01CA074783]; PMH (US NIH) [R01CA076366]; PHS (US NIH) [R01CA042182] FX The authors are solely responsible for the scientific content of this paper. The sponsors of this study had no role in study design, data collection, analysis or interpretation, writing of the report or the decision for submission. We thank all study participants and research staff of all parent studies for their contributions and commitment to this project, R. Courtney for DNA preparation, J. He for data processing and analyses, X. Gun for suggestions on bioinformatics analysis, and M.J. Daly and B.J. Rammer for editing and preparing the manuscript. The work at the Vanderbilt University School of Medicine was supported by US National Institutes of Health (NIH) grants R37CA070867, R01CA082729, R01CA124558, R01CA148667 and R01CA122364, as well as by Ingram Professorship and Research Reward funds from the Vanderbilt University School of Medicine. Studies (grant support) participating in the Asia Colorectal Cancer Consortium include the Shanghai Women's Health Study (US NIH, R37CA070867), the Shanghai Men's Health Study (US NIH, R01CA082729), the Shanghai Breast and Endometrial Cancer Studies (US NIH, R01CA064277 and R01CA092585; contributing only controls), Shanghai Colorectal Cancer Study 3 (US NIH, R37CA070867 and Ingram Professorship funds), the Guangzhou Colorectal Cancer Study (National Key Scientific and Technological Project, 2011ZX09307-001-04; the National Basic Research Program, 2011CB504303, contributing only controls; the Natural Science Foundation of China, 81072383, contributing only controls), the Japan BioBank Colorectal Cancer Study (grant from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government), the Hwasun Cancer Epidemiology Study Colon and Rectum Cancer (HCES-CRC; grants from the Korea Center for Disease Control and Prevention and the Jeonnam Regional Cancer Center), the Aichi Colorectal Cancer Study (Grant-in-Aid for Cancer Research, grant for the Third Term Comprehensive Control Research for Cancer and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, 17015018 and 221S0001), the Korea-NCC (National Cancer Center) Colorectal Cancer Study (Basic Science Research Program through-the National Research Foundation of Korea, 2010-0010276; National Cancer Center Korea, 0910220), the Korea-Seoul Colorectal Cancer Study (none reported) and the KCPS-II Colorectal Cancer Study (National R&D Program for Cancer Control, 1220180; Seoul R&D Program, 10526).; We also thank B. Buecher of ASTERISK; U. Handte-Daub, M. Celik, R. Hettler-Jensen, U. Benscheid and U. Eilber of DACHS; and P. Soule, H. Ranu, I. Devivo, D.J. Hunter, Q. Guo, L. Zhu and H. Zhang of HPFS, NHS and PHS, as well as the following state cancer registries for their help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington and Wyoming. We thank C. Berg and P. Prorok of PLCO; T. Riley of Information Management Services, Inc.; B. O'Brien of Westat, Inc.; B. Kopp and W Shao of SAIC-Frederick; the WHI investigators (see https://www.whi.org/researchers/SitePages/Write%20a%20Paper. aspx) and the GECCO Coordinating Center. Participating studies (grant support) in the GECCO, CORECT and CCFR GWAS meta-analysis are GECCO (US NIH, U01CA137088 and R01CA059045), DALS (US NIH, R01CA048998), DACHS (German Federal Ministry of Education and Research, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1,01KH0404 and 01ER0814), HPFS (US NIH, P01CA055075, UM1CA167552, R01137178 and P50CA127003), NHS (US NIH, R01137178, P50CA127003 and P01CA087969), OFCCR (US NIH, U01CA074783), PMH (US NIH, R01CA076366), PHS (US NIH, R01CA042182), VITAL (US NIH, K05CA154337), WHI (US NIH, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C and 268200764316C) and PLCO (US NIH, Z01CP 010200, U0IHG004446 and U01HG 004438). CORECT is supported by the National Cancer Institute as part of the GAME-ON consortium (US NIH, U19CA148107) with additional support from National Cancer Institute grants (R01CA81488 and P30CA014089), the National Human Genome Research Institute at the US NIH (T32HG000040) and the National Institute of Environmental Health Sciences at the US NIH (T32ES013678). CCFR is supported by the National Cancer Institute, US NIH under RFA CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and principal investigators of the Australasian Colorectal Cancer Family Registry (US NIH, U01CA097735), the Familial Colorectal Neoplasia Collaborative Group (US NIH, U01CA074799) (University of Southern California), the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (US NIH, U01CA074800), the Ontario Registry for Studies of Familial Colorectal Cancer (US NIH, U01CA074783), the Seattle Colorectal Cancer Family Registry (US NIH, U01CA074794) and the University of Hawaii Colorectal Cancer Family Registry (US NIH, U01CA074806). The GWAS work was supported by a National Cancer Institute grant (US NIH, U01CA122839). OFCCR was supported by a GL2 grant from the Ontario Research Fund, Canadian Institutes of Health Research and a Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. T.J. Hudson and B.W. Zanke are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through support from the Ontario Ministry of Economic Development and Innovation. ASTERISK was funded by a Regional Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC).; PLCO data sets were accessed with approval through dbGaP (CGEMS prostate cancer scan, phs000207.v1.p1; CGEMS pancreatic cancer scan, phs000206.v4.p3; and GWAS of Lung Cancer and Smoking, phs000093.v2.p2, which was funded by Z01CP 010200, U01HG004446 and U01HG 004438 from the US NIH). NR 63 TC 63 Z9 68 U1 2 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JUN PY 2014 VL 46 IS 6 BP 533 EP 542 DI 10.1038/ng.2985 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AI4XU UT WOS:000336870700008 PM 24836286 ER PT J AU Kohsaka, S Shukla, N Ameur, N Ito, T Ng, CKY Wang, L Lim, D Marchetti, A Viale, A Pirun, M Socci, ND Qin, LX Sciot, R Bridge, J Singer, S Meyers, P Wexler, LH Barr, FG Dogan, S Fletcher, JA Reis, JS Ladanyi, M AF Kohsaka, Shinji Shukla, Neerav Ameur, Nabahet Ito, Tatsuo Ng, Charlotte K. Y. Wang, Lu Lim, Diana Marchetti, Angela Viale, Agnes Pirun, Mono Socci, Nicholas D. Qin, Li-Xuan Sciot, Raf Bridge, Julia Singer, Samuel Meyers, Paul Wexler, Leonard H. Barr, Frederic G. Dogan, Snjezana Fletcher, Jonathan A. Reis-Filho, Jorge S. Ladanyi, Marc TI A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway mutations SO NATURE GENETICS LA English DT Article ID TUMOR ALVEOLAR RHABDOMYOSARCOMA; SPINDLE-CELL RHABDOMYOSARCOMA; GENOME-WIDE IDENTIFICATION; CHILDRENS ONCOLOGY GROUP; TARGET GENES; SIGNALING PATHWAYS; STEM-CELLS; NEUROBLASTOMA; FUSION; DIFFERENTIATION AB Rhabdomyosarcoma, a cancer of skeletal muscle lineage, is the most common soft-tissue sarcoma in children(1). Major subtypes of rhabdomyosarcoma include alveolar (ARMS) and embryonal (ERMS) tumors(2,3). Whereas ARMS tumors typically contain translocations generating PAX3-FOXO1 or PAX7-FOXO1 fusions that block terminal myogenic differentiation(4-6), no functionally comparable genetic event has been found in ERMS tumors. Here we report the discovery, through whole-exome sequencing, of a recurrent somatic mutation encoding p.Leu122Arg in the myogenic transcription factor MYOD1 in a distinct subset of ERMS tumors with poor outcomes that also often contain mutations altering PI3K-AKT pathway components. Previous mutagenesis studies had shown that MYOD1 with a p.Leu122Arg substitution can block wild-type MYOD1 function and bind to MYC consensus sequences(7), suggesting a possible switch from differentiation to proliferation. Our functional data now confirm this prediction. Thus, MYOD1 p.Leu122Arg defines a subset of rhabdomyosarcomas eligible for high-risk protocols and the development of targeted therapeutics. C1 [Kohsaka, Shinji; Ameur, Nabahet; Ito, Tatsuo; Ng, Charlotte K. Y.; Wang, Lu; Lim, Diana; Marchetti, Angela; Dogan, Snjezana; Reis-Filho, Jorge S.; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Kohsaka, Shinji; Ameur, Nabahet; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Shukla, Neerav; Meyers, Paul; Wexler, Leonard H.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10021 USA. [Pirun, Mono; Socci, Nicholas D.] Mem Sloan Kettering Canc Ctr, Bioinformat Core Facil, New York, NY 10021 USA. [Qin, Li-Xuan] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Sciot, Raf] Univ Hosp Gasthuisberg, Dept Pathol, B-3000 Louvain, Belgium. [Sciot, Raf] Univ Louvain, Louvain, Belgium. [Bridge, Julia] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE USA. [Singer, Samuel] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Barr, Frederic G.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Fletcher, Jonathan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Ladanyi, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. EM laaanyim@mskcc.org OI Meyers, Paul/0000-0001-6146-6101 FU NIH [P01 CA047179]; NCI [P50 CA140146]; National Center for Research Resources (NCRR) Clinical Translational Science Center grant; Virginia and Daniel K. Ludwig Trust for Cancer Research; Yasuda Medical Foundation; HIROKO International Academic Exchange Foundation; Intramural Research Program of the National Cancer Institute; Anbinder Fund; Cancer Center Core [NCI P30 CA008748] FX We thank H. Hosoi (Kyoto Prefectural University of Medicine) and S. Tanaka and M. Tsuda (both at Hokkaido University) for providing cell lines. We also thank T. Akagi and K. Sasai (both at KAN Research Institute, Inc.) for providing the pcx4bleo plasmid. We are also grateful to J. Zhao for technical assistance with microarray analysis, to L. Borsu for assistance with Sequenom analyses and to E. de Stanchina and R. Tieu for the xenograft studies. This work was supported by a generous donation from M.B. Zuckerman (M.L.), by NIH P01 CA047179 (S.S.), by NCI P50 CA140146 (M.L., N.D.S. and S.S.), by a National Center for Research Resources (NCRR) Clinical Translational Science Center grant (M.P. and N.D.S.) and by the Virginia and Daniel K. Ludwig Trust for Cancer Research (J.A.F.). S.K. was supported in part by the Yasuda Medical Foundation and the HIROKO International Academic Exchange Foundation. F.G.B. is supported by the Intramural Research Program of the National Cancer Institute.; The Memorial Sloan Kettering Cancer Center Sequenom facility was supported by the Anbinder Fund, and the Genomics and Bioinformatics Cores are supported by Cancer Center Core grant NCI P30 CA008748. NR 27 TC 29 Z9 29 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JUN PY 2014 VL 46 IS 6 BP 595 EP 600 DI 10.1038/ng.2969 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AI4XU UT WOS:000336870700016 PM 24793135 ER PT J AU Lane, AA Chapuy, B Lin, CY Tivey, T Li, HB Townsend, EC van Bodegom, D Day, TA Wu, SC Liu, HY Yoda, A Alexe, G Schinzel, AC Sullivan, TJ Malinge, S Taylor, JE Stegmaier, K Jaffe, JD Bustin, M te Kronnie, G Izraeli, S Harris, MH Stevenson, KE Neuberg, D Silverman, LB Sallan, SE Bradner, JE Hahn, WC Crispino, JD Pellman, D Weinstock, DM AF Lane, Andrew A. Chapuy, Bjoern Lin, Charles Y. Tivey, Trevor Li, Hubo Townsend, Elizabeth C. van Bodegom, Diederik Day, Tovah A. Wu, Shuo-Chieh Liu, Huiyun Yoda, Akinori Alexe, Gabriela Schinzel, Anna C. Sullivan, Timothy J. Malinge, Sebastien Taylor, Jordan E. Stegmaier, Kimberly Jaffe, Jacob D. Bustin, Michael te Kronnie, Geertruy Izraeli, Shai Harris, Marian H. Stevenson, Kristen E. Neuberg, Donna Silverman, Lewis B. Sallan, Stephen E. Bradner, James E. Hahn, William C. Crispino, John D. Pellman, David Weinstock, David M. TI Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation SO NATURE GENETICS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EMBRYONIC STEM-CELLS; DOWN-SYNDROME; EXPRESSION; CHROMATIN; CRLF2; GENE; TRISOMY-21; MUTATIONS; PROTEINS AB Down syndrome confers a 20-fold increased risk of B cell acute lymphoblastic leukemia (B-ALL)1, and polysomy 21 is most frequent somatic aneuploidy among all B-ALLs(2). Yet the mechanistic links between chromosome 21 triplication and B-ALL remain undefined. Here we show that germline triplication of only 31 genes orthologous to human chromosome 21q22 confers mouse progenitor B cell self renewal in vitro, maturation defects in vivo and B-ALL with either the BCR-ABL fusion protein or CRLF2 with activated JAK2. Chromosome 21q22 triplication suppresses histone H3 Lys27 trimethylation (H3K27me3) in progenitor B cells and B-ALLs, and 'bivalent' genes with both H3K27me3 and H3K4me3 at their promoters in wild-type progenitor B cells are preferentially overexpressed in triplicated cells. Human B-ALLs with polysomy 21 are distinguished by their overexpression of genes marked with H3K27me3 in multiple cell types. Overexpression of HMGN1, a nucleosome remodeling protein encoded on chromosome 21q22 (refs. 3-5), suppresses H3K27me3 and promotes both B cell proliferation in vitro and B-ALL in vivo. C1 [Lane, Andrew A.; Chapuy, Bjoern; Lin, Charles Y.; Tivey, Trevor; Townsend, Elizabeth C.; van Bodegom, Diederik; Day, Tovah A.; Wu, Shuo-Chieh; Liu, Huiyun; Yoda, Akinori; Schinzel, Anna C.; Bradner, James E.; Hahn, William C.; Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Li, Hubo; Alexe, Gabriela; Silverman, Lewis B.; Sallan, Stephen E.; Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Schinzel, Anna C.; Taylor, Jordan E.; Stegmaier, Kimberly; Jaffe, Jacob D.; Hahn, William C.; Weinstock, David M.] Broad Inst, Cambridge, MA USA. [Sullivan, Timothy J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Microarray Core, Boston, MA 02115 USA. [Malinge, Sebastien] Inst Gustave Roussy, INSERM, U985, F-94805 Villejuif, France. [Bustin, Michael] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [te Kronnie, Geertruy] Univ Padua, Dept Pediat, Padua, Italy. [Izraeli, Shai] Chaim Sheba Med Ctr, Dept Pediat Hematooncol, Ramat Gan, Israel. [Izraeli, Shai] Tel Aviv Univ, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. [Harris, Marian H.] Childrens Hosp Boston, Dept Pathol, Boston, MA USA. [Stevenson, Kristen E.; Neuberg, Donna] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Crispino, John D.] Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA. [Pellman, David] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Lane, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM andrew_lane@dfci.harvard.edu; dweinstock@partners.org RI Bustin, Michael/G-6155-2015 OI Crispino, John/0000-0002-8182-8306; FU Conquer Cancer Foundation; Lauri Strauss Leukemia Foundation; Leukemia and Lymphoma Society; Alex Lemonade Stand Foundation; US Department of Defense; Israel Science Foundation; US Israel Binational Foundation; Stellato Fund; US National Institutes of Health/National Cancer Institute [CA15198-01, CA172387-A01] FX We thank N. Kopp and A. Schlauch for technical assistance, M. Busslinger (Research Institute of Molecular Pathology, Vienna) for the Pax5+/- mice and M. Oshimura (Tottori University) for A9 cells carrying human chromosome 21. This research was supported by the Conquer Cancer Foundation (.A.A.L.), the Lauri Strauss Leukemia Foundation (A.A.L.), the Leukemia and Lymphoma Society (A.A.L.), the Alex Lemonade Stand Foundation (A.A.L., H. Li and D.P.), the US Department of Defense (C.Y.L.), the Israel Science Foundation (S.I.), the US Israel Binational Foundation (J.D.C. and S.I.), the Stellato Fund (D.M.W.), US National Institutes of Health/National Cancer Institute R01 awards CA15198-01 and CA172387-A01 (D.M.W.) and a Translational Research Award from the Leukemia and Lymphoma Society (J.D.C. and D.M.W.). NR 31 TC 27 Z9 27 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JUN PY 2014 VL 46 IS 6 BP 618 EP 623 DI 10.1038/ng.2949 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AI4XU UT WOS:000336870700020 PM 24747640 ER PT J AU Rockey, SJ AF Rockey, Sally J. TI Mentorship matters for the biomedical workforce SO NATURE MEDICINE LA English DT Editorial Material AB The mentorship of early-career scientists is necessary to their individual career success and the future of the biomedical research enterprise as a whole. Recently launched NIH programs and tools aim to facilitate this important type of training. C1 NIH, Bethesda, MD 20892 USA. RP Rockey, SJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 OD999999] NR 0 TC 4 Z9 4 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JUN PY 2014 VL 20 IS 6 BP 575 EP 575 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AI7LB UT WOS:000337071000009 PM 24901558 ER PT J AU Cottini, F Hideshima, T Xu, CX Sattler, M Dori, M Agnelli, L ten Hacken, E Bertilaccio, MT Antonini, E Neri, A Ponzoni, M Marcatti, M Richardson, PG Carrasco, R Kimmelman, AC Wong, KK Caigaris-Cappio, F Blandino, G Kuehl, WM Anderson, KC Tonon, G AF Cottini, Francesca Hideshima, Teru Xu, Chunxiao Sattler, Martin Dori, Martina Agnelli, Luca ten Hacken, Elisa Bertilaccio, Maria Teresa Antonini, Elena Neri, Antonino Ponzoni, Maurilio Marcatti, Magda Richardson, Paul G. Carrasco, Ruben Kimmelman, Alec C. Wong, Kwok-Kin Caigaris-Cappio, Federico Blandino, Giovanni Kuehl, W. Michael Anderson, Kenneth C. Tonon, Giovanni TI Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers SO NATURE MEDICINE LA English DT Article ID YES-ASSOCIATED PROTEIN; ABL TYROSINE KINASE; C-ABL; MULTIPLE-MYELOMA; TUMOR-SUPPRESSOR; P73; PATHWAY; PHOSPHORYLATION; TUMORIGENESIS; ACTIVATION AB Oncogene-induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and the mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies, including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53-independent, proapoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway coactivator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1-induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine-threonine kinase, STK4. Notably, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a new synthetic-lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels. C1 [Cottini, Francesca; Hideshima, Teru; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Cottini, Francesca; Dori, Martina; Antonini, Elena; Tonon, Giovanni] Ist Ricovero & Cura Carattere Sci IRCCS San Raffa, Div Mol Oncol, Funct Genom Canc Unit, Milan, Italy. [Xu, Chunxiao; Sattler, Martin; Carrasco, Ruben; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xu, Chunxiao; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Xu, Chunxiao; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Dana Farber Canc Inst, Boston, MA USA. [Agnelli, Luca; Neri, Antonino] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Hematol Unit, Milan, Italy. [ten Hacken, Elisa; Bertilaccio, Maria Teresa; Caigaris-Cappio, Federico] IRCCS San Raffaele Sci Inst, Div Mol Oncol, Lab Lymphoid Malignancies, Milan, Italy. [Ponzoni, Maurilio] IRCCS San Raffaele Sci Inst, Myeloma Unit, Pathol Unit, Milan, Italy. [Marcatti, Magda] IRCCS San Raffaele Sci Inst, Myeloma Unit, Dept Hematol Oncol, Hematol & Bone Marrow Transplantat Unit, Milan, Italy. [Kimmelman, Alec C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Caigaris-Cappio, Federico; Tonon, Giovanni] Univ Vita Salute San Raffaele, Milan, Italy. [Caigaris-Cappio, Federico; Tonon, Giovanni] IRCCS San Raffaele Sci Inst, MAGIC Microenvironm & Genes Canc Blood Interdiv R, Milan, Italy. [Blandino, Giovanni] Italian Natl Canc Inst Regina Elena, Translat Oncogen Unit, Rome, Italy. [Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu; tonon.giovanni@hsr.it OI neri, antonino/0000-0001-9047-5912 FU Fondazione CARIPLO, a Marie Curie International Reintegration Grant; Associazione Raliana per la Ricerca sul Cancro (AIRC); Special Program Molecular Clinical Oncology [9965]; NIH [P50100707, PO-1 78378, RO-1 50947] FX We thank M. Sudol (Mount Sinai School of Medicine) for the eGFP-YAP1 construct, W Hahn (Dana-Farber Cancer Institute) for pLKO.1 shRNA lentiviral vectors and S. Rosen (Northwestern University) and R. Burger (University of Kiel) for MM.1R and INA-6 MM cells. We also thank E. Di Cairano and L. Spagnuolo for immunohistochemical stains, F. Ghini and A.M. Gasparri for technical help, the Dana-Farber Cancer Institute Flow cytometry facility, D. Kufe and F. Bernassola for insightful suggestions, C. Brennan for the bioinformatics analysis and members of the Anderson and Tonon lab for sharing reagents and critical reading of the manuscript. W.M.K. is supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. This work was supported by Fondazione CARIPLO, a Marie Curie International Reintegration Grant and the Associazione Raliana per la Ricerca sul Cancro (AIRC; AIRC Special Program Molecular Clinical Oncology, 5 per milk no. 9980 to A.N. and Investigator Grants and Special Program Molecular Clinical Oncology, 5 per mile no. 9965 to G.T.) (G.T.). K.C.A. is an American Cancer Society Clinical Research Professor and is supported by NIH grants NIH SPORE P50100707, PO-1 78378 and RO-1 50947. NR 38 TC 54 Z9 56 U1 4 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JUN PY 2014 VL 20 IS 6 BP 599 EP 606 DI 10.1038/nm.3562 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AI7LB UT WOS:000337071000021 PM 24813251 ER PT J AU Wang, RX Yu, CR Dambuza, IM Mahdi, RM Dolinska, MB Sergeev, YV Wingfield, PT Kim, SH Egwuagu, CE AF Wang, Ren-Xi Yu, Cheng-Rong Dambuza, Ivy M. Mahdi, Rashid M. Dolinska, Monika B. Sergeev, Yuri V. Wingfield, Paul T. Kim, Sung-Hye Egwuagu, Charles E. TI Interleukin-35 induces regulatory B cells that suppress autoimmune disease SO NATURE MEDICINE LA English DT Article ID T-CELLS; MICE; EXPRESSION; RESPONSES; CYTOKINE; UVEITIS; IL-35; INFLAMMATION; CONTRIBUTES; POPULATION AB Interleukin-10 (IL-10)-producing regulatory B (Bred cells suppress autoimmune disease, and increased numbers of B-reg cells prevent host defense to infection and promote tumor growth and metastasis by converting resting CD4(+) T cells to regulatory T (T-reg) cells. The mechanisms mediating the induction and development of B-reg cells remain unclear. Here we show that IL-35 induces B-reg cells and promotes their conversion to a B-reg subset that produces IL-35 as well as IL-10. Treatment of mice with IL-35 conferred protection from experimental autoimmune uveitis (EAU), and mice lacking IL-35 (p35 knockout (KO) mice) or defective in IL-35 signaling (IL-12R beta 2 KO mice) produced less B-reg cells endogenously or after treatment with IL-35 and developed severe uveitis. Adoptive transfer of B-reg cells induced by recombinant IL-35 suppressed EAU when transferred to mice with established disease, inhibiting pathogenic T helper type 17 (T(H)17) and T(H)1 cells while promoting T-reg cell expansion. In B cells, IL-35 activates STAT1 and STAT3 through the IL-35 receptor comprising the IL-12R beta 2 and IL-27R alpha subunits. As IL-35 also induced the conversion of human B cells into B-reg cells, these findings suggest that IL-35 may be used to induce autologous B-reg and IL-35(+) B-reg cells and treat autoimmune and inflammatory disease. C1 [Wang, Ren-Xi; Yu, Cheng-Rong; Dambuza, Ivy M.; Mahdi, Rashid M.; Kim, Sung-Hye; Egwuagu, Charles E.] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Dolinska, Monika B.; Sergeev, Yuri V.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Wingfield, Paul T.] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov FU NEI; NIH FX The Intramural Research Programs of the NEI and NIH provided funding for this research. We thank H. Young (National Cancer Institute, NIH) and R.R. Caspi and C.-C. Chan (NEI, NIH) for critical reading of the manuscript. We also thank C.-C. Chan for expert analyses of Fundus images and histology sections. In addition, we thank A. O'Hara and C.A. Hunter (University of Pennsylvania) for providing IL-27R alpha KO B cells and R. Villasmil (NEI/NIH FLOW Cytometry Core facility) for cell sorting and FACS analysis. NR 36 TC 134 Z9 148 U1 6 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JUN PY 2014 VL 20 IS 6 BP 633 EP 641 DI 10.1038/nm.3554 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AI7LB UT WOS:000337071000025 PM 24743305 ER PT J AU Cui, GH Jun, SB Jin, X Luo, GX Pham, MD Lovinger, DM Vogel, SS Costa, RM AF Cui, Guohong Jun, Sang Beom Jin, Xin Luo, Guoxiang Pham, Michael D. Lovinger, David M. Vogel, Steven S. Costa, Rui M. TI Deep brain optical measurements of cell type-specific neural activity in behaving mice SO NATURE PROTOCOLS LA English DT Article ID IN-VIVO; ACTIVATION; PROTEIN; MICROSCOPY AB Recent advances in genetically encoded fluorescent sensors enable the monitoring of cellular events from genetically defined groups of neurons in vivo. In this protocol, we describe how to use a time-correlated single-photon counting (TCSPC)-based fiber optics system to measure the intensity, emission spectra and lifetime of fluorescent biosensors expressed in deep brain structures in freely moving mice. When combined with Cre-dependent selective expression of genetically encoded Ca2+ indicators (GECIs), this system can be used to measure the average neural activity from a specific population of cells in mice performing complex behavioral tasks. As an example, we used viral expression of GCaMPs in striatal projection neurons (SPNs) and recorded the fluorescence changes associated with calcium spikes from mice performing a lever-pressing operant task. The whole procedure, consisting of virus injection, behavior training and optical recording, takes 3-4 weeks to complete. With minor adaptations, this protocol can also be applied to recording cellular events from other cell types in deep brain regions, such as dopaminergic neurons in the ventral tegmental area. The simultaneously recorded fluorescence signals and behavior events can be used to explore the relationship between the neural activity of specific brain circuits and behavior. C1 [Cui, Guohong; Jin, Xin; Luo, Guoxiang; Pham, Michael D.; Lovinger, David M.; Costa, Rui M.] NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Bethesda, MD USA. [Jun, Sang Beom] Ewha Womans Univ, Dept Elect Engn, Seoul, South Korea. [Jin, Xin] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA. [Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD USA. [Vogel, Steven S.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. [Costa, Rui M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, Oeiras, Portugal. [Costa, Rui M.] Champalimaud Ctr, Lisbon, Portugal. RP Vogel, SS (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. EM stevevog@mail.nih.gov; ruicosta@fchampalimaud.org OI Vogel, Steven/0000-0002-3005-2667; Costa, Rui/0000-0003-0495-8374 FU US government funding from the Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism; European Research Council [STG 243393]; International Early Career Scientist grant from the Howard Hughes Medical Institute; National Research Foundation of Korea grant [2011-0029485, 2012-0004003]; Smart IT Convergence System Research Center grant from the Korean government (MEST) [SIRC-2011-0031866]; Ellison Medical Foundation grant [AG-NS-0944-12] FX We thank V. Jayaraman, R.A. Kerr, D.S. Kim, L.L. Looger, and K. Svoboda from the GENIE Project, Janelia Farm Research Campus, Howard Hughes Medical Institute for allowing us to use GCaMP6s vectors. We thank L.L. Looger, J. Akerboom and D.S. Kim from the GENIE Project, Janelia Farm Research Campus, Howard Hughes Medical Institute for permission to use GCaMP5G vectors; L.L. Looger and Janelia Farm Research Campus of the Howard Hughes Medical Institute for permission to use GCaMP3 vectors; C.R. Gerfen for gifts of multiple bacterial artificial chromosome transgenic mouse lines; and K. Jalink for gifts of DNA constructs of EPAC (exchange proteins directly activated by cAMP) sensors. This work was supported by US government funding from the Division of Intramural Clinical and Biological Research of the National Institute on Alcohol Abuse and Alcoholism to D.M.L., S.S.V. and R.M.C., by the European Research Council (STG 243393), and by an International Early Career Scientist grant from the Howard Hughes Medical Institute to R.M.C.; by a National Research Foundation of Korea grant (2011-0029485, 2012-0004003) and a Smart IT Convergence System Research Center grant (SIRC-2011-0031866) from the Korean government (MEST) to S.B.J.; and by an Ellison Medical Foundation grant (AG-NS-0944-12) to X. J. NR 20 TC 11 Z9 12 U1 1 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD JUN PY 2014 VL 9 IS 6 BP 1213 EP 1228 DI 10.1038/nprot.2014.080 PG 16 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AI8FS UT WOS:000337145800002 PM 24784819 ER PT J AU Choyke, PL AF Choyke, Peter L. TI Science to Practice: Percutaneous Biopsies in the NIR Future-Will Fluorescence Guide the Way? SO RADIOLOGY LA English DT Editorial Material ID INDOCYANINE GREEN AB Sheth et al present a fascinating glimpse into the future of imaging-guided biopsies. Increasingly, such biopsies are being performed by fusing two or more modalities, such as computed tomography (CT) and ultrasonography (US). To this list should be added optical fluorescence guidance, which will complement all the advances hitherto developed for conventional imaging guidance. Similar progress is being made in the fields of endoscopy and surgery, and it is becoming clearer that optical fluorescence may light the path for many medical procedures in the "NIR," or near-infrared, future. C1 NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B69F, Bethesda, MD 20892 USA. EM pchoyke@nih.gov NR 5 TC 1 Z9 1 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2014 VL 271 IS 3 BP 623 EP 624 DI 10.1148/radiol.14140344 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI5GW UT WOS:000336894600001 PM 24848955 ER PT J AU Sheth, RA Heidari, P Esfahani, SA Wood, BJ Mahmood, U AF Sheth, Rahul A. Heidari, Pedram Esfahani, Shadi A. Wood, Bradford J. Mahmood, Umar TI Interventional Optical Molecular Imaging Guidance during Percutaneous Biopsy SO RADIOLOGY LA English DT Article ID INDOCYANINE GREEN; FLUORESCENCE; ENDOSCOPY AB Purpose: To investigate indocyanine green (ICG) as a molecular beacon for malignant lesions within the liver and evaluate the ability of a developed handheld imaging system to allow measurement of ICG fluorescence within focal hepatic lesions with high target-to-background ratios in a mouse model. Materials and Methods: All animal experiments were approved by the institutional animal care committee. A handheld optical molecular imaging device was constructed to pass through the introducer needle of a standard percutaneous biopsy kit. An ex vivo phantom system was constructed to quantify tissue attenuation properties of ICG in liver parenchyma. Subsequently, intrahepatic colorectal cancer metastases were generated in nude mice, and epifluorescence imaging of ICG, as well as histologic analysis of the explanted livers, was performed at 3 weeks after implantation (n = 6). Epifluorescence imaging with the handheld imaging device was then performed on intrahepatic colorectal metastases after the administration of ICG (n = 15) at 3, 6, and 24 hours after injection. Target-to-background ratios were calculated for each time point. Subsequently, a core biopsy of intrahepatic colorectal metastases was performed by using a standard clinical 18-gauge biopsy needle. Results: There was avid localization of ICG to the focal lesions at all time points. Similarly, fluorescence within the tumors was greater than that within normal liver, as detected with the handheld imaging system (mean target-to-background ratio +/- standard deviation, 3.9 +/- 0.2 at 24 hours). A core biopsy of tumor and normal adjacent liver by using a standard biopsy needle demonstrated a sharp margin of fluorescence intensity at the tumor-liver interface. Conclusion: The custom-designed molecular imaging device, in combination with ICG, readily allowed differentiation between normal and malignant tissue in a murine model of intrahepatic colorectal metastasis. (C) RSNA, 2014 C1 [Sheth, Rahul A.; Heidari, Pedram; Esfahani, Shadi A.; Mahmood, Umar] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA. [Wood, Bradford J.] Ctr Clin, Ctr Intervent Oncol Radiol & Imaging Sci, Bethesda, MD USA. [Wood, Bradford J.] NCI, NIH, Bethesda, MD 20892 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA. EM umah-mood@mgh.harvard.edu FU National Institutes of Health [U01CA084301] FX This research was supported by the National Institutes of Health (grant U01CA084301). NR 14 TC 10 Z9 13 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2014 VL 271 IS 3 BP 770 EP 777 DI 10.1148/radiol.14131880 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI5GW UT WOS:000336894600018 PM 24520946 ER PT J AU Resnik, DB AF Resnik, David B. TI Data Fabrication and Falsification and Empiricist Philosophy of Science SO SCIENCE AND ENGINEERING ETHICS LA English DT Article DE Data fabrication and falsification; Empiricism; Realism; Observation/theory distinction; Ethics; Scientific practice ID RETRACTED ARTICLE. SEE; PG 335; REALISM AB Scientists have rules pertaining to data fabrication and falsification that are enforced with significant punishments, such as loss of funding, termination of employment, or imprisonment. These rules pertain to data that describe observable and unobservable entities. In this commentary I argue that scientists would not adopt rules that impose harsh penalties on researchers for data fabrication or falsification unless they believed that an aim of scientific research is to develop true theories and hypotheses about entities that exist, including unobservable ones. This argument presents a challenge for constructive empiricists, such as van Fraassen. Constructive empiricists need to be able to explain why rules pertaining to data fabrication and falsification do not threaten their philosophy of science. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, 111 Alexander Dr,Mail Drop CU 03,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-05] NR 25 TC 2 Z9 2 U1 3 U2 24 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1353-3452 EI 1471-5546 J9 SCI ENG ETHICS JI Sci. Eng. Ethics PD JUN PY 2014 VL 20 IS 2 BP 423 EP 431 DI 10.1007/s11948-013-9466-z PG 9 WC Ethics; Engineering, Multidisciplinary; History & Philosophy Of Science; Multidisciplinary Sciences; Philosophy SC Social Sciences - Other Topics; Engineering; History & Philosophy of Science; Science & Technology - Other Topics; Philosophy GA AI5KR UT WOS:000336905900010 PM 23982326 ER PT J AU Grabowski, MK Gray, RH Serwadda, D Kigozi, G Gravitt, PE Nalugoda, F Reynolds, SJ Wawer, MJ Watya, S Quinn, TC Tobian, AAR AF Grabowski, Mary K. Gray, Ronald H. Serwadda, David Kigozi, Godfrey Gravitt, Patti E. Nalugoda, Fred Reynolds, Steven J. Wawer, Maria J. Watya, Stephen Quinn, Thomas C. Tobian, Aaron A. R. TI High-risk human papillomavirus viral load and persistence among heterosexual HIV-negative and HIV-positive men SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Article ID FLAT PENILE LESIONS; MALE CIRCUMCISION; NATURAL-HISTORY; CERVICAL-CANCER; KENYAN MEN; INFECTION; CLEARANCE; WOMEN; ACQUISITION; CONCORDANCE AB SObjectives High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men. Methods HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24 months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV. Results HR-HPV genotypes with high viral load (grade: 3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3.11), and HIV-positive men (month 6: adjPRR=1.33, 95% CI 1.06 to 1.67; month 12: adjPRR=1.73, 95% CI 1.18 to 2.54). Long-term persistence of HR-HPV was more frequent among HIV-positive men compared with HIV-negative men (month 24: adjPRR=2.27, 95% CI 1.47 to 3.51). Persistence of newly detected HR-HPV at the 6-month and 12-month visits with high viral load were also more likely to persist to 24 months than HR-HPV with low viral load among HIV-negative men (adjPRR=1.67, 95% CI 0.88 to 3.16). Conclusions HR-HPV genotypes with high viral load are more likely to persist among HIV-negative and HIV-positive men, though persistence was more common among HIV-positive men overall. The results may explain the association between high HR-HPV viral load and HR-HPV transmission. C1 [Grabowski, Mary K.; Gray, Ronald H.; Gravitt, Patti E.; Reynolds, Steven J.; Wawer, Maria J.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. [Gray, Ronald H.; Serwadda, David; Kigozi, Godfrey; Nalugoda, Fred; Reynolds, Steven J.; Wawer, Maria J.; Quinn, Thomas C.; Tobian, Aaron A. R.] Rakai Hlth Sci Program, Entebbe, Uganda. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Gravitt, Patti E.] Perdana Univ, Grad Sch Med, Serdang, Malaysia. [Reynolds, Steven J.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Reynolds, Steven J.; Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21287 USA. [Watya, Stephen] Makerere Univ, Dept Urol, Kampala, Uganda. [Tobian, Aaron A. R.] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA. RP Tobian, AAR (reprint author), Johns Hopkins Univ, Dept Pathol, Carnegie 437,600 N Wolfe St, Baltimore, MD 21287 USA. EM atobian1@jhmi.edu FU National Institutes of Health [UO1AI51171]; Bill and Melinda Gates Foundation [22006.02]; National Institute of Allergy and Infectious Diseases (NIAID), NIH [U01-AI-068613, 3U01-AI075115-03S1, 1K23AI093152-01A1, R01AI087409-01A1]; NIH [1K23AI093152-01A1]; Doris Duke Charitable Foundation Clinician Scientist Development Award [22006.02] FX The trials were funded by the National Institutes of Health (#UO1AI51171) and the Bill and Melinda Gates Foundation (#22006.02). National Institute of Allergy and Infectious Diseases (NIAID), NIH grants U01-AI-068613, 3U01-AI075115-03S1, 1K23AI093152-01A1, R01AI087409-01A1 and the NIAID Intramural Program provided laboratory support. A. A. R. T. was supported by the NIH 1K23AI093152-01A1 and Doris Duke Charitable Foundation Clinician Scientist Development Award (#22006.02). The Fogarty International Center (#5D43TW001508 and #2D43TW000010-19-AITRP) contributed to training. NR 29 TC 10 Z9 10 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 EI 1472-3263 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD JUN PY 2014 VL 90 IS 4 BP 337 EP 343 DI 10.1136/sextrans-2013-051230 PG 7 WC Infectious Diseases SC Infectious Diseases GA AI5HZ UT WOS:000336897700019 PM 24482488 ER PT J AU Viswanathan, S Keating, A Deans, R Hematti, P Prockop, D Stroncek, DF Stacey, G Weiss, DJ Mason, C Rao, MS AF Viswanathan, Sowmya Keating, Armand Deans, Robert Hematti, Peiman Prockop, Darwin Stroncek, David F. Stacey, Glyn Weiss, Dan J. Mason, Christopher Rao, Mahendra S. TI Soliciting Strategies for Developing Cell-Based Reference Materials to Advance Mesenchymal Stromal Cell Research and Clinical Translation SO STEM CELLS AND DEVELOPMENT LA English DT Article ID BONE-MARROW; STEM-CELLS; INTERNATIONAL-SOCIETY; DIFFERENTIATION; FIBROBLASTS; PRECURSORS; STATEMENT; RESPONSES; FRACTION; GROWTH AB The mesenchymal stromal cell (MSC) field continues to rapidly progress with a number of clinical trials initiated and completed, with some reported successes in multiple clinical indications, and a growing number of companies established. The field, nevertheless, faces several challenges. Persistent issues include the definition of a MSC and comparability between MSC preparations. This is because of inherent cell heterogeneity, the absence of markers that are unique to MSCs, and the difficulty in precisely defining them by developmental origin. Differences in the properties of MSCs also depend on the site of tissue harvest, phenotypic and genotypic characteristics of the donor and the isolation, and storage and expansion methods used. These differences may be sufficient to ensure that attributes of the final MSC product could differ in potentially significant ways. Since there are currently no gold standards, we propose using a reference material to establish methods of comparability among MSC preparations. We suggest four possible "ruler scenarios'' and a method for global distribution. We further suggest that critical to establishing a reference material is the need to define protocols for comparing cells. The main purpose of this article is to solicit input in establishing a consensus-based comparison. A comparative approach will be critical to all stages of translation to better clarify mechanisms of MSC actions, define an optimal cell manufacturing process, ensure best practice clinical investigations, extend the use of an MSC product for new indications, protect an MSC product from imitators, and develop uniform reimbursement policies. Importantly, a reference material may enable a consensus on a practical definition of MSCs. C1 [Viswanathan, Sowmya; Keating, Armand] Univ Hlth Network, Cell Therapy Program, Toronto, ON, Canada. [Deans, Robert] Athersys Inc, Regenerat Med, Cleveland, OH USA. [Hematti, Peiman] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Prockop, Darwin] Scott & White Mem Hosp & Clin, Coll Med, Texas A&M Hlth Sci Ctr, Inst Regenerat Med, Temple, TX USA. [Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Stacey, Glyn] NIBSC MHRA, UK Stem Cell Bank, Div Cell Biol & Imaging, S Mimms, Herts, England. [Weiss, Dan J.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA. [Mason, Christopher] UCL, Adv Ctr Biochem Engn, Dept Biochem Engn, London, England. [Rao, Mahendra S.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA. RP Rao, MS (reprint author), NIH, Ctr Regenerat Med, 50 South Dr Suite 1140, Bethesda, MD 20892 USA. EM mahendra.rao@nih.gov FU CCRM; ISCT; Alliance for Regenerative Medicine (ARM); Cell Therapy Catapult; NIH; UK Science & Innovation Network via the British Consulate General in Canada; Office of Science and Technology of the Embassy of France FX The authors would like to acknowledge sponsorship support from CCRM, ISCT, Alliance for Regenerative Medicine (ARM), Cell Therapy Catapult, the NIH, UK Science & Innovation Network via the British Consulate General in Canada, and the Office of Science and Technology of the Embassy of France for a workshop in March 2013 titled "Building Towards a Standard for MSC's: A UK-U.S.-Canada led Workshop,'' which led to the formation of the MSC Reference Materials Working Group. NR 31 TC 33 Z9 36 U1 1 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 EI 1557-8534 J9 STEM CELLS DEV JI Stem Cells Dev. PD JUN 1 PY 2014 VL 23 IS 11 BP 1157 EP 1167 DI 10.1089/scd.2013.0591 PG 11 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA AI6DJ UT WOS:000336959800001 PM 24422625 ER PT J AU Frawley, R DeVito, M Walker, NJ Birnbaum, L White, K Smith, M Maynor, T Recio, L Germolec, D AF Frawley, Rachel DeVito, Michael Walker, Nigel J. Birnbaum, Linda White, Kimber, Jr. Smith, Matthew Maynor, Timothy Recio, Leslie Germolec, Dori TI Relative Potency for Altered Humoral Immunity Induced by Polybrominated and Polychlorinated Dioxins/Furans in Female B6C3F1/N Mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE 2; 3; 7; 8-tetrachlorodibenzo-p-dioxin; chlorinated furans; brominated dioxins; brominated furans; relative potency; IgM antibody forming cell; toxic equivalency factor; TEF ID DIBENZO-P-DIOXINS; TOXIC EQUIVALENCY FACTORS; BIPHENYL CONGENERS; BROMINATED DIOXIN; BILIARY-EXCRETION; C57BL/6J MICE; TCDD-LIKE; RATS; DISAPPEARANCE; SENSITIVITY AB The use of brominated flame retardants and incineration of bromine-containing materials has lead to an increase in polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) in the environment. Measurable amounts of PBDD/Fs have been detected in soil, seafood, and human breast milk and serum. Studies indicate that the relative potencies of some PBDD/Fs based on enzyme induction are equivalent to those of some polychlorinated dibenzo-p-dioxins and dibenzofurans. To assess the humoral immunity relative potencies of PBDD/Fs and compare them to their chlorinated analogs, female B6C3F1/N mice received a single oral exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrabromodibenzofuran (TBDF), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentabromodibenzofuran (1PeBDF), 1,2,3,7,8-pentachlorodibenzofuran (1PeCDF), 2,3,4,7,8-pentabromodibenzofuran (4PeBDF), 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF), 2,3-dibromo-7,8-dichlorodibenzo-p-dioxin (DBDCDD), or 2,3,7-tribromodibenzo-p-dioxin (TriBDD). Inhibition of the immunoglobulin M (IgM) antibody forming cell response was measured 4 days following immunization with sheep red blood cells. The data were fit to a Hill model to estimate the ED50 for inhibition. Expression of xenobiotic metabolizing enzyme (XME) and thyroxine transport protein (Ttr) genes in liver was measured by PCR to assess aryl hydrocarbon-mediated responses. TCDD, TBDF, TCDF, 1PeBDF, 4PeBDF, 4PeCDF, and DBDCDD suppressed the IgM antibody response and Ttr gene expression, and upregulated phase I XME genes. 1PeCDF suppressed the IgM antibody response but only upregulated phase I XME genes; TriBDD had no effect on antibody response. The rank order of potency (ED50) for these chemicals was TCDD > TBDF > 4PeBDF > TCDF/4PeCDF/1PeBDF > 1PeCDF. Whereas TCDD was the most potent compound tested, the brominated analogs were more potent than their chlorinated analogs, suggesting that these compounds should be considered in toxic equivalency factor evaluation and risk assessment. C1 [Frawley, Rachel; DeVito, Michael; Walker, Nigel J.; Birnbaum, Linda; Germolec, Dori] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda] NCI, NIH, Res Triangle Pk, NC 27709 USA. [White, Kimber, Jr.; Smith, Matthew] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23284 USA. [Maynor, Timothy; Recio, Leslie] ILS Inc, Res Triangle Pk, NC 27709 USA. RP Frawley, R (reprint author), NIEHS, NTP, Toxicol Branch, 111 TW Alexander Dr,POB 12233,MD K2-15, Res Triangle Pk, NC 27709 USA. EM frawleyr@niehs.nih.gov RI Walker, Nigel/D-6583-2012; OI Walker, Nigel/0000-0002-9111-6855; Frawley, Rachel/0000-0001-8490-8240 FU National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS); National Cancer Institute; NIEHS Research and Development Contracts [N01-ES-55538, NO1-ES-00005] FX National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) and National Cancer Institute; NIEHS Research and Development Contracts (N01-ES-55538, NO1-ES-00005). NR 38 TC 2 Z9 2 U1 2 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2014 VL 139 IS 2 BP 488 EP 500 DI 10.1093/toxsci/kfu041 PG 13 WC Toxicology SC Toxicology GA AI7MO UT WOS:000337075900019 PM 24713691 ER PT J AU Troisi, R Stephansson, O Jacobsen, J Tretli, S Rensen, HTSO Gissler, M Kaaja, R Ekbom, A Hoover, RN Grotmol, T AF Troisi, Rebecca Stephansson, Olof Jacobsen, Jacob Tretli, Steinar Rensen, Henrik Toft S. O. Gissler, Mika Kaaja, Risto Ekbom, Anders Hoover, Robert N. Grotmol, Tom TI Perinatal characteristics and bone cancer risk in offspring - a Scandinavian population-based study SO ACTA ONCOLOGICA LA English DT Article ID GESTATIONAL HYPERTENSION; EWINGS-SARCOMA; TUMORS; OSTEOSARCOMA; PREECLAMPSIA; CHILDHOOD; REGISTRY; NORWAY; GROWTH; EPIDEMIOLOGY AB Background. We investigated perinatal factors in relation to bone cancer subtypes, osteosarcoma (OS), Ewing Sarcoma (ES) and chondrosarcoma (CS). Materials and methods. All cases in Norway (1970-2009), Sweden (1974-2009) and Denmark (1980-2010) < 43 years were included (n = 914); 10 controls per case were selected from birth registries (which provided information on pregnancies) matched on birth country, sex and birth year (n = 9140). Unconditional logistic regression models including sex and birth year were used to compute relative risk (RR) and 95% confidence intervals (CI). Results. Higher maternal education was associated with a 40% increase in OS risk (95% CI 1-93%). The RR for OS was 3.22 (95% CI 1.37-7.59) comparing offspring of hypertensive mothers with those of mothers with a normotensive pregnancy, and Cesarean section was associated with a 29% risk reduction (95% CI 0-50%). When gestational age, birth weight and birth length were assessed simultaneously, there were no associations with any of the bone tumor subtypes. Conclusion. These results provided little evidence of an important role of pregnancy factors in the etiology of bone cancers. Higher maternal education may be associated with factors, possibly early nutrition or other correlates of socioeconomic status, that increase OS risk in offspring. The elevated OS risk associated with gestational hypertension and reduced risk associated with Cesarean section warrant replication. C1 [Troisi, Rebecca; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Stephansson, Olof; Ekbom, Anders] Karolinska Univ Hosp & Inst, Dept Med, Clin Epidemiol Unit & Ctr, Stockholm, Sweden. [Stephansson, Olof] Karolinska Univ Hosp & Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden. [Jacobsen, Jacob; Rensen, Henrik Toft S. O.] Aarhus Univ, Dept Clin Epidemiol, Aarhus N, Denmark. [Tretli, Steinar; Grotmol, Tom] Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway. [Gissler, Mika] THL Natl Inst Hlth & Welf, Helsinki, Finland. [Gissler, Mika] Nord Sch Publ Hlth, Gothenburg, Sweden. [Kaaja, Risto] Turku Univ, Turku, Finland. RP Troisi, R (reprint author), Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,MSC 9773,9609-7E584, Rockville, MD 20850 USA. EM troisir@mail.nih.gov FU U.S. National Cancer Institute FX This research was funded by the U.S. National Cancer Institute. NR 27 TC 1 Z9 1 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0284-186X EI 1651-226X J9 ACTA ONCOL JI Acta Oncol. PD JUN PY 2014 VL 53 IS 6 BP 830 EP 838 DI 10.3109/0284186X.2013.862594 PG 9 WC Oncology SC Oncology GA AH9ZO UT WOS:000336505600015 PM 24313390 ER PT J AU Bao, W Bowers, K Tobias, DK Olsen, SF Chavarro, J Vaag, A Kiely, M Zhang, CL AF Bao, Wei Bowers, Katherine Tobias, Deirdre K. Olsen, Sjurdur F. Chavarro, Jorge Vaag, Allan Kiely, Michele Zhang, Cuilin TI Prepregnancy low-carbohydrate dietary pattern and risk of gestational diabetes mellitus: a prospective cohort study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CORONARY-HEART-DISEASE; INSULIN-RESISTANCE; IRON INTAKE; PROTEIN; WOMEN; FAT; QUESTIONNAIRE; SCORE; METABOLISM; REGRESSION AB Background: Low-carbohydrate diets (LCDs) have been vastly popular for weight loss. The association between a low-carbohydrate dietary pattern and risk of gestational diabetes mellitus (GDM) remains unknown. Objective: We aimed to prospectively examine the association of 3 prepregnancy low-carbohydrate dietary patterns with risk of GDM. Design: We included 21,411 singleton pregnancies in the Nurses' Health Study II. Prepregnancy LCD scores were calculated from validated food-frequency questionnaires, including an overall LCD score on the basis of intakes of carbohydrate, total protein, and total fat; an animal LCD score on the basis of intakes of carbohydrate, animal protein, and animal fat; and a vegetable LCD score on the basis of intakes of carbohydrate, vegetable protein, and vegetable fat. A higher score reflected a higher intake of fat and protein and a lower intake of carbohydrate, and it indicated closer adherence to a low-carbohydrate dietary pattern. RRs and 95% CIs were estimated by using generalized estimating equations with log-binomial models. Results: We documented 867 incident GDM pregnancies during 10 y follow-up. Multivariable-adjusted RRs (95% CIs) of GDM for comparisons of highest with lowest quartiles were 1.27 (1.06, 1.51) for the overall LCD score (P-trend = 0.03), 1.36 (1.13, 1.64) for the animal LCD score (P-trend = 0.003), and 0.84 (0.69, 1.03) for the vegetable LCD score (P-trend = 0.08). Associations between LCD scores and GDM risk were not significantly modified by age, parity, family history of diabetes, physical activity, or overweight status. Conclusions: A prepregnancy low-carbohydrate dietary pattern with high protein and fat from animal-food sources is positively associated with GDM risk, whereas a prepregnancy low-carbohydrate dietary pattern with high protein and fat from vegetable food sources is not associated with the risk. Women of reproductive age who follow a low-carbohydrate dietary pattern may consider consuming vegetable rather than animal sources of protein and fat to minimize their risk of GDM. C1 [Bao, Wei; Kiely, Michele; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA. [Bowers, Katherine] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [Tobias, Deirdre K.; Chavarro, Jorge] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Tobias, Deirdre K.; Chavarro, Jorge] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Olsen, Sjurdur F.] Statens Serum Inst, Dept Epidemiol Res, Ctr Fetal Programming, DK-2300 Copenhagen, Denmark. [Chavarro, Jorge] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Chavarro, Jorge] Harvard Univ, Sch Med, Boston, MA USA. [Vaag, Allan] Rigshosp, Dept Endocrinol, DK-2100 Copenhagen, Denmark. RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA. EM zhangcu@mail.nih.gov RI Bowers, Katherine/N-5226-2015; OI Bao, Wei/0000-0002-7301-5786 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH [IIHSN275201000020C]; NIH [DK58845, CA50385, P30 DK46200, UM1 CA176726] FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH (contract IIHSN275201000020C). The Nurses' Health Study II was funded by the NIH (research grants DK58845, CA50385, P30 DK46200, and UM1 CA176726). NR 42 TC 17 Z9 18 U1 2 U2 13 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2014 VL 99 IS 6 BP 1378 EP 1384 DI 10.3945/ajcn.113.082966 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AH9NW UT WOS:000336470100010 PM 24717341 ER PT J AU Moy, KA Mondul, AM Zhang, H Weinstein, SJ Wheeler, W Chung, CC Mannisto, S Yu, K Chanock, SJ Albanes, D AF Moy, Kristin A. Mondul, Alison M. Zhang, Han Weinstein, Stephanie J. Wheeler, William Chung, Charles C. Mannisto, Satu Yu, Kai Chanock, Stephen J. Albanes, Demetrius TI Genome-wide association study protein of circulating vitamin D-binding SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID 25-HYDROXYVITAMIN D; PANCREATIC-CANCER; MOLECULAR-CLONING; PROSTATE-CANCER; GC-GLOBULIN; SERUM; RISK; ALBUMIN; FAMILY; METABOLISM AB Background: Vitamin D status may influence a spectrum of health outcomes, including osteoporosis, arthritis, cardiovascular disease, and cancer. Vitamin D-binding protein (DBP) is the primary carrier of vitamin D in the circulation and regulates the bioavailability of 25-hydroxyvitamin D. Epidemiologic studies have shown direct DBP-risk relations and modification by DBP of vitamin D-disease associations. Objective: We aimed to characterize common genetic variants that influence the DBP biochemical phenotype. Design: We conducted a genome-wide association study (GWAS) of 1380 men through linear regression of single-nucleotide polymorphisms (SNPs) in the Illumina HumanHap500/550/610 array on fasting serum DBP, assuming an additive genetic model, with adjustment for age at blood collection. Results: We identified 2 independent SNPs located in the gene encoding DBP, GC, that were highly associated with serum DBP: rs7041 (P = 1.42 X 10(-246)) and rs705117 (P = 4.7 x 10(-91)). For both SNPs, mean serum DBP decreased with increasing copies of the minor allele: mean DBP concentrations (nmol/L) were 7335, 5149, and 3152 for 0, 1, and 2 copies of rs7041 (T), respectively, and 6339, 4280, and 2341, respectively, for rs705117 (G). DBP was also associated with rs12144344 (P = 5.9 x 10(-7)) in ST6GALNAC3. Conclusions: In this GWAS analysis, to our knowledge the first to examine this biochemical phenotype, 2 variants in GC one exonic and one intronic were associated with serum DBP concentrations at the genome-wide level of significance. Understanding the genetic contributions to circulating DBP may provide greater insights into the vitamin D binding, transport, and other functions of DBP and the effect of vitamin D status on health outcomes. The AlphaTocopherol, Beta-Carotene Cancer Prevention clinical trial was registered at clinicaltrials.gov as NCT00342992. C1 [Moy, Kristin A.; Mondul, Alison M.; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Zhang, Han; Yu, Kai] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. [Chung, Charles C.] NCI, Canc Genom Res Lab, NIH, Bethesda, MD 20892 USA. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Wheeler, William] Informat Management Serv Inc, Silver Spring, MD USA. [Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Moy, KA (reprint author), Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, 9609 Med Ctr Dr, Bethesda, MD 20892 USA. EM moyka@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Zhang, Han/K-2118-2016 OI Zhang, Han/0000-0001-7977-9616 FU Intramural Research Program of the National Cancer Institute, NIH, US Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004, HEISN261201000006C, HHSN261200800001E] FX Supported by the Intramural Research Program of the National Cancer Institute, NIH US Public Health Service (grant nos. N01-CN-45165, N01-RC-45035, N01-RC-37004, HEISN261201000006C, and HHSN261200800001E). NR 39 TC 10 Z9 10 U1 0 U2 14 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2014 VL 99 IS 6 BP 1424 EP 1431 DI 10.3945/ajcn.113.080309 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AH9NW UT WOS:000336470100015 PM 24740207 ER PT J AU Siega-Riz, AM Sotres-Alvarez, D Ayala, GX Ginsberg, M Himes, JH Liu, K Loria, CM Mossavar-Rahmani, Y Rock, CL Rodriguez, B Gellman, MD Van Horn, L AF Siega-Riz, Anna Maria Sotres-Alvarez, Daniela Ayala, Guadalupe X. Ginsberg, Mindy Himes, John H. Liu, Kiang Loria, Catherine M. Mossavar-Rahmani, Yasniin Rock, Cheryl L. Rodriguez, Brendaly Gellman, Marc D. Van Horn, Linda TI Food-group and nutrient-density intakes by Hispanic and Latino backgrounds in the Hispanic Community Health Study/Study of Latinos SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID UNITED-STATES; MEXICAN-AMERICANS; SOCIOECONOMIC-STATUS; RECOVERY BIOMARKERS; RISK-FACTORS; US ADULTS; ACCULTURATION; CONSUMPTION; DESIGN; DIET AB Background: Hispanics are a heterogeneous group of individuals with a variation in dietary habits that is reflective of their cultural heritage and country of origin. It is important to identify differences in their dietary habits because it has been well established that nutrition contributes substantially to the burden of preventable diseases and early deaths in the -United States. Objective: We estimated the distribution of usual intakes (of both food groups and nutrients) by Hispanic and Latino backgrounds by using National Cancer Institute methodology. Design: The Hispanic Community Health Study/Study of Latinos is a population-based cohort study that recruited participants who were 18-74 y of age from 4 US cities in 2008-2011 (Miami, Bronx, Chicago, and San Diego). Participants who provided at least one 24-h dietary recall and completed a food propensity questionnaire (n = 13,285) were included in the analyses. Results were adjusted for age, sex, field center, weekend, sequencing, and typical amount of intake. Results: Overall, Cubans (n = 2128) had higher intakes of total energy, macronutrients (including all subtypes of fat), and alcohol than those of other groups. Mexicans (n = 5371) had higher intakes of vitamin C, calcium, and fiber. Lowest intakes of total energy, macronutrients, folate, iron, and calcium were reported by Dominicans (n = 1217), whereas Puerto Ricans (n = 2176) had lowest intakes of vitamin C and fiber. Food-group servings reflected nutrient intakes, 'with Cubans having higher intakes of refined grains, vegetables, red meat, and fats and Dominicans having higher intakes of fruit and poultry, whereas Puerto Ricans had lowest intakes of fruit and vegetables. Central and South Americans (n = 1468 and 925, respectively) were characterized by being second in their reported intakes of fruit and poultry and the highest in fish intake in comparison with other groups. Conclusion: Variations in diet noted in this study, with additional analysis, may help explain diet-related differences in health outcomes observed in Hispanics and Latinos. This trial was registered at clinicaltrials.gov as NCT02060344. C1 [Siega-Riz, Anna Maria] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA. [Siega-Riz, Anna Maria] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27514 USA. [Sotres-Alvarez, Daniela] Univ N Carolina, Gillings Sch Global Publ Hlth, Collaborat Studies Coordinator Ctr, Chapel Hill, NC 27514 USA. [Ayala, Guadalupe X.] San Diego State Univ, Grad Sch Publ Hlth, Div Hlth Promot & Behav Sci, San Diego, CA 92182 USA. [Ginsberg, Mindy; Mossavar-Rahmani, Yasniin] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Himes, John H.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Liu, Kiang] Univ Illinois, Dept Prevent Med, Chicago, IL USA. [Van Horn, Linda] Univ Illinois, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. [Loria, Catherine M.] NHLBI, Epidemiol Branch, Bethesda, MD 20892 USA. [Rock, Cheryl L.] Univ Calif San Diego, Moores Univ Calif, San Diego Canc Ctr, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Rodriguez, Brendaly; Gellman, Marc D.] Univ Miami, Behav Med Res Ctr, Dept Psychol, Miami, FL USA. RP Siega-Riz, AM (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 2105-A McGavran Greenberg Bldg,135 Dauer Dr, Chapel Hill, NC 27514 USA. EM am_siegariz@unc.edu RI DeMarcus, Forrest/O-9190-2016; Sotres-Alvarez, Daniela/O-9085-2016 OI Sotres-Alvarez, Daniela/0000-0002-3226-6140 FU National Heart, Lung, and Blood Institute (NBLBI) [N01-HC65233]; University of Miami [N01-HC65234]; Albert Einstein College of Medicine [N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State University [N01-HC65237]; National Institute on Minority Health and Health Disparities; National Institute on Deafness and Other Communication Disorders; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Neurological Disorders and Stroke; NIH Institution-Office of Dietary Supplements FX The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) was supported by contracts from the 'National Heart, Lung, and Blood Institute (NBLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following institutes, centers, and offices contribute to the HCHS/SOL through a transfer of funds to the NITLBI: the National Institute on Minority Health and Health Disparities, the National Institute on Deafness and Other Communication Disorders, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the NIH Institution-Office of Dietary Supplements. NR 37 TC 17 Z9 17 U1 5 U2 19 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2014 VL 99 IS 6 BP 1487 EP 1498 DI 10.3945/ajcn.113.082685 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AH9NW UT WOS:000336470100022 PM 24760972 ER PT J AU Weaver, CM Dwyer, J Fulgoni, VL King, JC Leveille, GA MacDonald, RS Ordovas, J Schnakenberg, D AF Weaver, Connie M. Dwyer, Johanna Fulgoni, Victor L., III King, Janet C. Leveille, Gilbert A. MacDonald, Ruth S. Ordovas, Jose Schnakenberg, David TI Processed foods: contributions to nutrition(1,2) SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID NUTRIENT-RICH FOODS; DIETARY; RECOMMENDATIONS; TECHNOLOGY; REDUCTION; AMERICANS; SCIENCE; DISEASE; QUALITY; HEALTH AB Both fresh and processed foods make up vital parts of the food supply. Processed food contributes to both food security (ensuring that sufficient food is available) and nutrition security (ensuring that food quality meets human nutrient needs). This ASN scientific statement focuses on one aspect of processed foods: their nutritional impacts. Specifically, this scientific statement 1) provides an introduction to how processed foods contribute to the health of populations, 2) analyzes the contribution of processed foods to "nutrients to encourage" and "constituents to limit" in the American diet as recommended by the Dietary Guidelines for Americans, 3) identifies the responsibilities of various stakeholders in improving the American diet, and 4) reviews emerging technologies and the research needed for a better understanding of the role of processed foods in a healthy diet. Analyses of the NHANES 2003-2008 show that processed foods provide both nutrients to encourage and constituents to limit as specified in the 2010 Dietary Guidelines for Americans. Of the nutrients to encourage, processed foods contributed 55% of dietary fiber, 48% of calcium, 43% of potassium, 34% of vitamin D, 64% of iron,65% of folate, and 46% of vitamin B-12. Of the constituents to limit, processed foods contributed 57% of energy, 52% of saturated fat, 75% of added sugars, and 57% of sodium. Diets are more likely to meet food guidance recommendations if nutrient-dense foods, either processed or not, are selected. Nutrition and food science professionals, the food industry, and other stakeholders can help to improve the diets of Americans by providing a nutritious food supply that is safe, enjoyable, affordable, and sustainable by communicating effectively and accurately with each other and by working together to improve the overall knowledge of consumers. C1 [Weaver, Connie M.] Purdue Univ, Coll Hlth & Human Sci, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Dwyer, Johanna] Tufts Univ, Sch Med, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA. [Dwyer, Johanna] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Dwyer, Johanna; Ordovas, Jose] NIH, Off Dietary Supplements, Bethesda, MD USA. [Fulgoni, Victor L., III] Nutr Impact LLC, Battle Creek, MI USA. [King, Janet C.] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. [King, Janet C.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Leveille, Gilbert A.] Leveillt Associates, Denville, NJ USA. [MacDonald, Ruth S.] Iowa State Univ, Dept Food Sci & Human Nutr, Ames, IA USA. RP Weaver, CM (reprint author), Purdue Univ, Coll Hlth & Human Sci, Dept Nutr Sci, W Lafayette, IN 47907 USA. NR 79 TC 16 Z9 19 U1 3 U2 56 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2014 VL 99 IS 6 BP 1525 EP 1542 DI 10.3945/ajcn.114.089284 PG 18 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AH9NW UT WOS:000336470100030 PM 24760975 ER PT J AU Scheinberg, P Rios, O Scheinberg, P Weinstein, B Wu, CO Young, NS AF Scheinberg, Phillip Rios, Olga Scheinberg, Priscila Weinstein, Barbara Wu, Colin O. Young, Neal S. TI Prolonged cyclosporine administration after antithymocyte globulin delays but does not prevent relapse in severe aplastic anemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID FOLLOW-UP; ASSOCIATION; HORSE AB In severe aplastic anemia, approximately one-third of responders to standard horse antithymocyte globulin (h-ATG) plus cyclosporine (CsA) will relapse. Anecdotal experience has suggested that a gradual CsA taper might avoid relapse, but this practice has not been rigorously assessed prospectively. In 2003, we adopted a strategy to taper CsA beyond 6 months, with the intention to reduce hematologic relapse compared with our extensive historical experience. In total, 102 patients received h-ATG/CsA for 6 months in two sequential clinical protocols: 67 patients (66%) responded and all had the CsA dose tapered per protocol over the subsequent 18 months (total of 2 years). The rate of relapse at 5 years was 33% (95% CI 27-44%), which did not differ from our large historical relapse experience (patients treated before 2003) of 30-40%, in protocols in which CsA was simply discontinued at 6 months. However, time to relapse was prolonged by about 1 year with the longer CsA course. The rates of clonal evolution and overall survival did not differ between the two cohorts. We infer from this large prospective study that CsA taper as implemented delayed but did not prevent relapse. The kinetics of relapse with long course CsA does suggest that a lower long-term dose might be adequate to maintain patients in remission. Am. J. Hematol. 89:571-574, 2014. (c) Published 2014. C1 [Scheinberg, Phillip; Rios, Olga; Scheinberg, Priscila; Weinstein, Barbara; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Scheinberg, Phillip] Hosp Sao Jose, Ctr Oncol, Hematol Serv, Sao Paulo, Brazil. [Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), Rua Martiniano de Carvalho 951, BR-01321001 Sao Paulo, Brazil. EM scheinbp@gmail.com OI Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS [Z99 HL999999] NR 18 TC 2 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 BP 571 EP 574 DI 10.1002/ajh.23692 PG 4 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600203 PM 24971433 ER PT J AU van Beers, EJ Samsel, L Mendelsohn, L Saiyed, R Fertrin, KY Brantner, CA Daniels, MP Nichols, J McCoy, JP Kato, GJ AF van Beers, Eduard J. Samsel, Leigh Mendelsohn, Laurel Saiyed, Rehan Fertrin, Kleber Y. Brantner, Christine A. Daniels, Mathew P. Nichols, James McCoy, J. Philip Kato, Gregory J. TI Imaging flow cytometry for automated detection of hypoxia-induced erythrocyte shape change in sickle cell disease SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID RED-BLOOD-CELLS; INTRACELLULAR POLYMERIZATION; FETAL-HEMOGLOBIN; OXYGEN-TENSION; MICROCIRCULATION; ANEMIA; DEFORMABILITY; PERCENTAGE; DISORDERS; GRADIENTS AB In preclinical and early phase pharmacologic trials in sickle cell disease, the percentage of sickled erythrocytes after deoxygenation, an ex vivo functional sickling assay, has been used as a measure of a patient's disease outcome. We developed a new sickle imaging flow cytometry assay (SIFCA) and investigated its application. To perform the SIFCA, peripheral blood was diluted, deoxygenated (2% oxygen) for 2 hr, fixed, and analyzed using imaging flow cytometry. We developed a software algorithm that correctly classified investigator tagged sickled and normal erythrocyte morphology with a sensitivity of 100% and a specificity of 99.1%. The percentage of sickled cells as measured by SIFCA correlated strongly with the percentage of sickle cell anemia blood in experimentally admixed samples (R=0.98, P0.001), negatively with fetal hemoglobin (HbF) levels (R=-0.558, P=0.027), negatively with pH (R=-0.688, P=0.026), negatively with pretreatment with the antisickling agent, Aes-103 (5-hydroxymethyl-2-furfural) (R=-0.766, P=0.002), and positively with the presence of long intracellular fibers as visualized by transmission electron microscopy (R=0.799, P=0.002). This study shows proof of principle that the automated, operator-independent SIFCA is associated with predictable physiologic and clinical parameters and is altered by the putative antisickling agent, Aes-103. SIFCA is a new method that may be useful in sickle cell drug development. Am. J. Hematol. 89:598-603, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [van Beers, Eduard J.; Samsel, Leigh; Mendelsohn, Laurel; Saiyed, Rehan; Fertrin, Kleber Y.; Brantner, Christine A.; Daniels, Mathew P.; Nichols, James; McCoy, J. Philip; Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Kato, GJ (reprint author), Univ Pittsburgh, Div Hematol Oncol, Dept Med, 200 Lothrop St,BST E1240, Pittsburgh, PA 15261 USA. EM katogj@upmc.edu RI Kato, Gregory/I-7615-2014; Fertrin, Kleber/M-4175-2013; OI Kato, Gregory/0000-0003-4465-3217; Fertrin, Kleber/0000-0003-2637-3297; Brantner, Christine/0000-0001-8172-901X FU Intramural NIH HHS [ZIA HL006013-05]; NHLBI NIH HHS [ZIA HL006013] NR 31 TC 13 Z9 13 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 BP 598 EP 603 DI 10.1002/ajh.23699 PG 6 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600208 PM 24585634 ER PT J AU Soucie, JM Miller, CH Kelly, FM Aschman, D DiMichele, D Konkle, BA Kulkarni, R Monahan, PE AF Soucie, J. Michael Miller, Connie H. Kelly, Fiona M. Aschman, Diane DiMichele, Donna Konkle, Barbara A. Kulkarni, Roshni Monahan, Paul E. CA CDC Inhibitor Surveillance Working TI National surveillance for hemophilia inhibitors in the United States: Summary report of an expert meeting SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID FACTOR-VIII INHIBITORS; NIJMEGEN MODIFICATION; BETHESDA ASSAY; IX INHIBITORS; C INHIBITORS; POPULATION; DIAGNOSIS; KINGDOM AB On March 12, 2012, the Centers for Disease Control and Prevention (CDC) held a meeting of its partners in hemophilia treatment, community-based organizations, industry, and government to review data and discuss implementation issues relevant to planned United States (U.S.) national inhibitor surveillance. Issues discussed included the current status of inhibitor surveillance in the United Kingdom (UK) and the US, the results of a US inhibitor surveillance feasibility study, proposed national surveillance schemes, laboratory testing and reporting issues and potential opportunities for future inhibitor-related research. It was concluded that implementation of a national program of inhibitor surveillance using standardized testing through an established public health registry along with patient and care provider education and targeted research provide the best opportunity to inform efforts to develop and evaluate effective prevention strategies.Am. J. Hematol. 89:621-625, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Soucie, J. Michael; Miller, Connie H.; Kelly, Fiona M.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Div Blood Disorders, Atlanta, GA USA. [Aschman, Diane] Amer Thrombosis & Hemostasis Network, Chicago, IL USA. [DiMichele, Donna] NHLBI, NIH, Bethesda, MD 20892 USA. [Konkle, Barbara A.] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Kulkarni, Roshni] Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. [Monahan, Paul E.] Univ N Carolina, Dept Pediat, Div Hematol Oncol, Chapel Hill, NC USA. RP Soucie, JM (reprint author), Div Blood Disorders, 1600 Clifton Rd,MS E64, Atlanta, GA 30333 USA. EM msoucie@cdc.gov OI Miller, Connie H/0000-0002-3989-7973 FU Intramural CDC HHS [CC999999] NR 15 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 BP 621 EP 625 DI 10.1002/ajh.23704 PG 5 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600212 PM 24616187 ER PT J AU Sorlie, PD Allison, MA Aviles-Santa, ML Cai, JW Daviglus, ML Howard, AG Kaplan, R LaVange, LM Raij, L Schneiderman, N Wassertheil-Smoller, S Talavera, GA AF Sorlie, Paul D. Allison, Matthew A. Aviles-Santa, M. Larissa Cai, Jianwen Daviglus, Martha L. Howard, Annie G. Kaplan, Robert LaVange, Lisa M. Raij, Leopoldo Schneiderman, Neil Wassertheil-Smoller, Sylvia Talavera, Gregory A. TI Prevalence of Hypertension, Awareness, Treatment, and Control in the Hispanic Community Health Study/Study of Latinos SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; epidemiology; Hispanics; hypertension; Latinos; medically uninsured; socioeconomic status ID CARDIOVASCULAR-DISEASE; MEXICAN-AMERICANS; RISK-FACTORS; DESIGN AB BACKGROUND The prevention and control of hypertension is an essential component for reducing the burden of cardiovascular diseases. Here we describe the prevalence of hypertension in diverse Hispanic/Latino background groups and describe the proportion who are aware of their diagnosis, receiving treatment, and having their hypertension under control. METHODS The Hispanic Community Health Study/Study of Latinos is a longitudinal cohort study of 16,415 Hispanics/Latinos, aged 18-74 years from 4 US communities (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA). At baseline (2008-2011) the study collected extensive measurements and completed questionnaires related to research on cardiovascular diseases. Hypertension was defined as measured blood pressure >= 140/90 mm Hg or use of antihypertensive medication. RESULTS The total age-adjusted prevalence of hypertension in this study was 25.5% as compared with 27.4% in non-Hispanic whites in the National Health and Nutrition Examination Survey. Prevalence of hypertension increased with increasing age groups and was highest in Cuban, Puerto Rican, and Dominican background groups. The percent with hypertension who were aware, being treated with medication, or had their hypertension controlled was lower compared with US non-Hispanic whites with hypertension and it was lowest in those without health insurance. CONCLUSIONS These findings indicate a significant deficit in treatment and control of hypertension among Hispanics/Latinos residing in the United States, particularly those without health insurance. Given the relative ease of identification of hypertension and the availability of low-cost medications, enabling better access to diagnostic and treatment services should reduce the burden of hypertension in Hispanic populations. C1 [Sorlie, Paul D.; Aviles-Santa, M. Larissa] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Allison, Matthew A.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Cai, Jianwen; Howard, Annie G.; LaVange, Lisa M.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [Daviglus, Martha L.] Univ Illinois, Inst Minor Hlth Res, Chicago, IL USA. [Kaplan, Robert; Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Raij, Leopoldo] Univ Miami, Miller Sch Med, Renal Hypertens Sect, Miami Vet Affairs Med Ctr,Renal Hypertens Div, Miami, FL 33136 USA. [Raij, Leopoldo] South Florida Vet Affairs Fdn Res & Educ, Miami, FL USA. [Schneiderman, Neil] Univ Miami, Dept Psychol, Miami, FL USA. [Talavera, Gregory A.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. RP Sorlie, PD (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. EM SorlieP@mail.nih.gov OI Allison, Matthew/0000-0003-0777-8272 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233]; University of Miami [N01-HC65234]; Albert Einstein College of Medicine [N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State University [N01-HC65237]; National Institute on Minority Health and Health Disparities; National Institute on Deafness and Other Communication Disorders; National Institute of Dental and Craniofacial Research; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Neurological Disorders and Stroke; National Institutes of Health, Office of Dietary Supplements FX The authors thank the staff and participants of for their important contributions. The study website is http://www.cscc.unc.edu/hchs/. The HCHS/SOL was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following institutes/centers/offices contribute to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, and National Institutes of Health, Office of Dietary Supplements. NR 15 TC 29 Z9 30 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUN PY 2014 VL 27 IS 6 BP 793 EP 800 DI 10.1093/ajh/hpu003 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AI0HO UT WOS:000336527400005 PM 24627442 ER PT J AU Campbell, ANC Nunes, EV Matthews, AG Stitzer, M Miele, GM Polsky, D Turrigiano, E Walters, S McClure, EA Kyle, TL Wahle, A Van Veldhuisen, P Goldman, B Babcock, D Stabile, PQ Winhusen, T Ghitza, UE AF Campbell, Aimee N. C. Nunes, Edward V. Matthews, Abigail G. Stitzer, Maxine Miele, Gloria M. Polsky, Daniel Turrigiano, Eva Walters, Scott McClure, Erin A. Kyle, Tiffany L. Wahle, Aimee Van Veldhuisen, Paul Goldman, Bruce Babcock, Dean Stabile, Patricia Quinn Winhusen, Theresa Ghitza, Udi E. TI Internet-Delivered Treatment for Substance Abuse: A Multisite Randomized Controlled Trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; CLINICAL-TRIALS; DEPENDENT OUTPATIENTS; ALCOHOL-CONSUMPTION; COCAINE DEPENDENCE; ADDICTION; INCENTIVES; NETWORK; CARE; INTERVENTIONS AB Objective: Computer-delivered interventions have the potential to improve access to quality addiction treatment care. The objective of this study was to evaluate the effectiveness of the Therapeutic Education System (TES), an Internet-delivered behavioral intervention that includes motivational incentives, as a clinician-extender in the treatment of substance use disorders. Method: Adult men and women (N=507) entering 10 outpatient addiction treatment programs were randomly assigned to receive 12 weeks of either treatment as usual (N=252) or treatment as usual plus TES, with the intervention substituting for about 2 hours of standard care per week (N=255). TES consists of 62 computerized interactive modules covering skills for achieving and maintaining abstinence, plus prize-based motivational incentives contingent on abstinence and treatment adherence. Treatment as usual consisted of individual and group counseling at the participating programs. The primary outcome measures were abstinence from drugs and heavy drinking (measured by twice-weekly urine drug screens and self-report) and time to dropout from treatment. Results: Compared with patients in the treatment-as-usual group, those in the TES group had a lower dropout rate (hazard ratio=0.72, 95% CI=0.57, 0.92) and a greater abstinence rate (odds ratio=1.62, 95% CI=1.12, 2.35). This effect was more pronounced among patients who had a positive urine drug or breath alcohol screen at study entry (N=228) (odds ratio=2.18, 95% CI=1.30, 3.68). Conclusions: Internet-delivered interventions such as TES have the potential to expand access and improve addiction treatment outcomes. Additional research is needed to assess effectiveness in non-specialty clinical settings and to differentiate the effects of the community reinforcement approach and contingency management components of TES. C1 [Campbell, Aimee N. C.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Dept Psychiat, New York, NY USA. St Lukes Roosevelt Hosp, Dept Psychiat & Behav Hlth, New York, NY USA. EMMES Corp, Rockville, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Ft Worth, TX USA. Med Univ S Carolina, Clin Neurosci Div, Charleston, SC USA. Ctr Drug Free Living, Orlando, FL USA. Zucker Hillside Hosp, North Shore Long Isl Jewish Hlth Syst, Glen Oaks, NY USA. Midtown Community Mental Hlth Ctr, Indianapolis, IN USA. HARBEL Prevent & Recovery Ctr, Baltimore, MD USA. Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA. RP Campbell, ANC (reprint author), New York State Psychiat Inst & Hosp, New York, NY 10032 USA. EM anc2002@columbia.edu OI Winhusen, Theresa/0000-0002-3364-0739 FU National Drug Abuse Treatment Clinical Trials Network, National Institute on Drug Abuse (NIDA) [U10 DA013035, U10 DA015831, U10 DA013034, U10 DA013720, U10 DA013732, U10 DA020024, U10 DA013714, U10 DA015815, K24 DA022412] FX Supported by grants from the National Drug Abuse Treatment Clinical Trials Network, National Institute on Drug Abuse (NIDA): U10 DA013035 (to Dr. Nunes and John Rotrosen), U10 DA015831 (to Kathleen M. Carroll and Roger D. Weiss), U10 DA013034 (Dr. Stitzer and Robert P. Schwartz), U10 DA013720 (to Jose Szapocznik and Lisa R. Metsch), U10 DA013732 (to Eugene C. Somoza), U10 DA020024 (to Madhukar H. Trivedi), U10 DA013714. (to Dennis M. Donovan and John Roll), U10 DA015815 (to James L Sorensen and Dennis McCarty), and K24 DA022412 (to Dr. Nunes). NR 38 TC 31 Z9 31 U1 5 U2 35 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2014 VL 171 IS 6 BP 683 EP 690 DI 10.1176/appi.ajp.2014.13081055 PG 8 WC Psychiatry SC Psychiatry GA AI1TU UT WOS:000336638600016 PM 24700332 ER PT J AU Muftuoglu, Y Sohl, CD Mislak, AC Mitsuya, H Sarafianos, SG Anderson, KS AF Muftuoglu, Yagmur Sohl, Christal D. Mislak, Andrea C. Mitsuya, Hiroaki Sarafianos, Stefan G. Anderson, Karen S. TI Probing the molecular mechanism of action of the HIV-1 reverse transcriptase inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) using pre-steady-state kinetics SO ANTIVIRAL RESEARCH LA English DT Article DE HIV; Reverse transcriptase; Enzyme kinetics; EFdA; Polymerase ID IMMUNODEFICIENCY-VIRUS TYPE-1; MITOCHONDRIAL-DNA POLYMERASE; HOST TOXICITY; 4'-ETHYNYL-2-FLUORO-2'-DEOXYADENOSINE; GAMMA; DISCRIMINATION; NUCLEOTIDE; ENTECAVIR; SUBSTRATE; FIDELITY AB The novel antiretroviral 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a potent nucleoside HIV-1 reverse transcriptase (RT) inhibitor (NRTI). Unlike other FDA-approved NRTIs, EFdA contains a 3'-hydroxyl. Pre-steady-state kinetics showed RT preferred incorporating EFdA-TP over native dATP. Moreover, RT slowly inserted nucleotides past an EFdA-terminated primer, resulting in delayed chain termination with unaffected fidelity. This is distinct from KP1212, another 3'-hydroxyl-containing RT inhibitor considered to promote viral lethal mutagenesis. New mechanistic features of RI inhibition by EFdA are revealed. (C) 2014 Elsevier B.V. All rights reserved. C1 [Muftuoglu, Yagmur; Sohl, Christal D.; Mislak, Andrea C.; Anderson, Karen S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. [Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. [Sarafianos, Stefan G.] Univ Missouri, Sch Med, CS Bond Life Sci Ctr, Columbia, MO 65211 USA. [Sarafianos, Stefan G.] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA. [Sarafianos, Stefan G.] Univ Missouri, Sch Med, Dept Biochem, Columbia, MO 65211 USA. RP Anderson, KS (reprint author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA. EM karen.anderson@yale.edu OI Sarafianos, Stefan G/0000-0002-5840-154X FU NIH [R01 GM049551, F32 GM099289, AI076119, AI099284, AI100890, GM103368] FX This work was supported by NIH grants R01 GM049551 (to K.S.A.), F32 GM099289 (to C.D.S.), and AI076119, AI099284, AI100890, and GM103368 (to S.G.S.). We would like to thank Ligong Wang for the purification of the pol accessory subunit. NR 24 TC 7 Z9 7 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 EI 1872-9096 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2014 VL 106 BP 1 EP 4 DI 10.1016/j.antiviral.2014.03.001 PG 4 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA AI4IA UT WOS:000336827700001 PM 24632447 ER PT J AU Meza, R ten Haaf, K Kong, CY Erdogan, A Black, WC Tammemagi, MC Choi, SE Jeon, J Han, SS Munshi, V van Rosmalen, J Pinsky, P McMahon, PM de Koning, HJ Eric, J Hazelton, WD Plevritis, SK AF Meza, Rafael ten Haaf, Kevin Kong, Chung Yin Erdogan, Ayca Black, William C. Tammemagi, Martin C. Choi, Sung Eun Jeon, Jihyoun Han, Summer S. Munshi, Vidit van Rosmalen, Joost Pinsky, Paul McMahon, Pamela M. de Koning, Harry J. Feuer, Eric J. Hazelton, William D. Plevritis, Sylvia K. TI Comparative Analysis of 5 Lung Cancer Natural History and Screening Models That Reproduce Outcomes of the NLST and PLCO Trials SO CANCER LA English DT Article DE Cancer Intervention and Surveillance Modeling Network (CISNET); comparative modeling analyses; low-dose CT screening; lung cancer screening; cancer natural history models; smoking and lung cancer; simulation model ID MULTISTAGE CARCINOGENESIS; MICROSIMULATION MODELS; POTENTIAL BENEFITS; COLORECTAL-CANCER; UNITED-STATES; MORTALITY; SMOKING; PROSTATE; HEALTH; RISK AB BACKGROUNDThe National Lung Screening Trial (NLST) demonstrated that low-dose computed tomography screening is an effective way of reducing lung cancer (LC) mortality. However, optimal screening strategies have not been determined to date and it is uncertain whether lighter smokers than those examined in the NLST may also benefit from screening. To address these questions, it is necessary to first develop LC natural history models that can reproduce NLST outcomes and simulate screening programs at the population level. METHODSFive independent LC screening models were developed using common inputs and calibration targets derived from the NLST and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Imputation of missing information regarding smoking, histology, and stage of disease for a small percentage of individuals and diagnosed LCs in both trials was performed. Models were calibrated to LC incidence, mortality, or both outcomes simultaneously. RESULTSInitially, all models were calibrated to the NLST and validated against PLCO. Models were found to validate well against individuals in PLCO who would have been eligible for the NLST. However, all models required further calibration to PLCO to adequately capture LC outcomes in PLCO never-smokers and light smokers. Final versions of all models produced incidence and mortality outcomes in the presence and absence of screening that were consistent with both trials. CONCLUSIONSThe authors developed 5 distinct LC screening simulation models based on the evidence in the NLST and PLCO. The results of their analyses demonstrated that the NLST and PLCO have produced consistent results. The resulting models can be important tools to generate additional evidence to determine the effectiveness of lung cancer screening strategies using low-dose computed tomography. Cancer 2014;120:1713-1724. (c) 2014 American Cancer Society. C1 [Meza, Rafael] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [ten Haaf, Kevin; van Rosmalen, Joost; de Koning, Harry J.] Erasmus Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands. [Kong, Chung Yin; Choi, Sung Eun; Munshi, Vidit; McMahon, Pamela M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Kong, Chung Yin; Choi, Sung Eun; Munshi, Vidit; McMahon, Pamela M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Erdogan, Ayca; Han, Summer S.; Plevritis, Sylvia K.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Black, William C.] Dartmouth Coll, Dept Radiol, Geisel Sch Med Dartmouth, Hanover, NH 03755 USA. [Tammemagi, Martin C.] Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada. [Jeon, Jihyoun; Hazelton, William D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98104 USA. [van Rosmalen, Joost] Erasmus Univ, Med Ctr, Dept Biostat, Rotterdam, Netherlands. [Pinsky, Paul] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Meza, R (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM rmeza@umich.edu OI van Rosmalen, Joost/0000-0002-9187-244X FU Agency for Healthcare Research and Quality (AHRQ) [U01-CA152956] FX This report is based on research conducted by the National Cancer Institutes (NCI)'s Cancer Intervention and Surveillance Modeling Network (CISNET) through support from an interagency agreement with the Agency for Healthcare Research and Quality (AHRQ) (administrative supplement to NCI grant U01-CA152956). NR 31 TC 17 Z9 17 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2014 VL 120 IS 11 BP 1713 EP 1724 DI 10.1002/cncr.28623 PG 12 WC Oncology SC Oncology GA AI1OE UT WOS:000336619700021 PM 24577803 ER PT J AU Reid, JM Buhrow, SA Gilbert, JA Jia, L Shoji, M Snyder, JP Ames, MM AF Reid, Joel M. Buhrow, Sarah A. Gilbert, Judith A. Jia, Lee Shoji, Mamoru Snyder, James P. Ames, Matthew M. TI Mouse pharmacokinetics and metabolism of the curcumin analog, 4-piperidinone,3,5-bis[(2-fluorophenyl)methylene]-acetate(3E,5E) (EF-24; NSC 716993) SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE EF-24; Curcumin; LC/MS/MS; Pharmacokinetics; Mouse ID CHEMOPREVENTIVE AGENT CURCUMIN; CANCER-CELLS; IN-VIVO; EF24; ANTICANCER; ANGIOGENESIS; APOPTOSIS; PATHWAY; ENZYME; TISSUE AB Curcumin, a keto-enol constituent of turmeric, has in vitro and in vivo antitumor activity. However, in vivo potency is low due to poor oral absorption. The mono-carbonyl analog, 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone acetate (EF-24, NSC 716993), exhibited broad-spectrum activity in the NCI anticancer cell line screen and potent antiangiogenesis activity in a HUVEC cell migration assay. The purpose of this study was to characterize the preclinical pharmacology of EF-24 in mice. EF-24 plasma stability, protein binding, pharmacokinetics, and metabolism were characterized utilizing an LC/MS/MS assay. An LC/MS/MS assay incorporated protein precipitation with methanol, reverse-phase HPLC separation under gradient elution using an aqueous methanol mobile phase containing 0.1 % formic acid, and positive electrospray ionization detection of the m/z 312 > 149 transition for EF-24. The assay was linear over the range 7.8-1,000 nM. Plasma protein binding was > 98 % with preferential binding to albumin. EF-24 plasma disposition in mice after i.v. administration of a 10 mg/kg dose was best fit to a 3-compartment open model. The terminal elimination half-life and plasma clearance values were 73.6 min and 0.482 L/min/kg, respectively. EF-24 bioavailability was 60 and 35 % after oral and i.p. administration, respectively. NADPH-dependent metabolism of EF-24 loss in liver microsomal preparations yielded several metabolites consistent with EF-24 hydroxylation and reduction. C1 [Reid, Joel M.; Buhrow, Sarah A.; Gilbert, Judith A.; Ames, Matthew M.] Mayo Clin, Div Oncol Res, Dept Oncol, Rochester, MN 55905 USA. [Jia, Lee] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, DCTD, Rockville, MD 20852 USA. [Shoji, Mamoru] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Snyder, James P.] Emory Univ, Dept Chem, Atlanta, GA 30322 USA. [Snyder, James P.] Emory Univ, Mory Inst Drug Dev, Atlanta, GA 30322 USA. RP Reid, JM (reprint author), Mayo Clin, Div Oncol Res, Dept Oncol, 200 First St SW, Rochester, MN 55905 USA. EM reid@mayo.edu FU National Cancer Institute [N01-CM-07105, 5 R21 CA139035-2]; US Department of Defense, Division of US Army [DAMD17-00-1-0241, BC074220] FX MS and JPS are grateful to Dennis Liotta (Emory University) for generous support of preparation of the curcumin analogs. This study was supported by National Cancer Institute Contract N01-CM-07105, US Department of Defense, Division of US Army DAMD17-00-1-0241 (MS and JPS), BC074220 (MS and JPS) and National Cancer Institute 5 R21 CA139035-2 (MS and JPS). NR 28 TC 5 Z9 5 U1 2 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 2014 VL 73 IS 6 BP 1137 EP 1146 DI 10.1007/s00280-014-2447-3 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AH8NV UT WOS:000336395700005 PM 24760417 ER PT J AU Avidan, G Tanzer, M Hadj-Bouziane, F Liu, N Ungerleider, LG Behrmann, M AF Avidan, Galia Tanzer, Michal Hadj-Bouziane, Fadila Liu, Ning Ungerleider, Leslie G. Behrmann, Marlene TI Selective Dissociation Between Core and Extended Regions of the Face Processing Network in Congenital Prosopagnosia SO CEREBRAL CORTEX LA English DT Article DE face processing; functional connectivity; neurodevelopmental disorders; prosopagnosia; ventral visual cortex ID DEVELOPMENTAL PROSOPAGNOSIA; TEMPORAL CORTEX; FUSIFORM GYRUS; FUNCTIONAL CONNECTIVITY; DETAILED EXPLORATION; CORTICAL NETWORK; VISUAL-CORTEX; PERCEPTION; RECOGNITION; SYSTEM AB There is growing consensus that accurate and efficient face recognition is mediated by a neural circuit composed of a posterior "core" and an anterior "extended" set of regions. Here, we characterize the distributed face network in human individuals with congenital prosopagnosia (CP)-a lifelong impairment in face processing-relative to that of matched controls. Using functional magnetic resonance imaging, we first uncover largely normal activation patterns in the posterior core face patches in CP. We also document normal activity of the amygdala (emotion processing) as well as normal or even enhanced functional connectivity between the amygdala and the core regions. Critically, in the same individuals, activation of the anterior temporal cortex (identity processing) is reduced and connectivity between this region and the posterior core regions is disrupted. The dissociation between the neural profiles of the anterior temporal lobe and amygdala was evident both during a task-related face scan and during a resting state scan, in the absence of visual stimulation. Taken together, these findings elucidate selective disruptions in neural circuitry in CP and offer an explanation for the known differential difficulty in identity versus emotional expression recognition in many individuals with CP. C1 [Avidan, Galia; Tanzer, Michal] Ben Gurion Univ Negev, Dept Psychol, IL-84105 Beer Sheva, Israel. [Hadj-Bouziane, Fadila] Lyon Neurosci Res Ctr, CNRS, INSERM, U1028,UMR5292,ImpAct Team, Bron, France. [Liu, Ning; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Behrmann, Marlene] Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. RP Avidan, G (reprint author), Ben Gurion Univ Negev, Dept Psychol, POB 653, IL-84105 Beer Sheva, Israel. EM galiaa@bgu.ac.il RI Avidan, Galia/B-9347-2011; OI Avidan, Galia/0000-0003-2293-3859; Behrmann, Marlene/0000-0002-3814-1015 FU Israeli Science Foundation (ISF) [384/10]; National Institutes of Mental Health [MH54246]; National Science Foundation [NSF BCS0923763, NSF SBE-0542013]; NIMH Intramural Research program FX This research was supported by a grant from the Israeli Science Foundation (ISF, 384/10) to G. A., and from grants from the National Institutes of Mental Health (MH54246), and the National Science Foundation (NSF BCS0923763; NSF SBE-0542013 to the Temporal Dynamics of Learning Center, an NSF Science of Learning Center) to M. B. F.H.-B., N.L., and L. G. U. were supported by the NIMH Intramural Research program. NR 57 TC 54 Z9 54 U1 2 U2 23 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 JUN PY 2014 VL 24 IS 6 BP 1565 EP 1578 DI 10.1093/cercor/bht007 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AI0IG UT WOS:000336529700014 PM 23377287 ER PT J AU Castro, FA Liu, XD Forsti, A Ji, JG Sundquist, J Sundquist, K Koshiol, J Hemminki, K AF Castro, Felipe A. Liu, Xiangdong Forsti, Asta Ji, Jianguang Sundquist, Jan Sundquist, Kristina Koshiol, Jill Hemminki, Kari TI Increased Risk of Hepatobiliary Cancers After Hospitalization for Autoimmune Disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Risk Factor; Cohort; Survival; Hepatocellular Carcinoma ID PRIMARY BILIARY-CIRRHOSIS; POPULATION-BASED COHORT; PRIMARY SCLEROSING CHOLANGITIS; INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; TRACT CANCER; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; PERNICIOUS-ANEMIA; CELIAC-DISEASE AB BACKGROUND & AIMS: Some autoimmune diseases are associated with increased risk of liver cancer. However, there has been no comprehensive evaluation of autoimmune diseases among patients who develop different subtypes of hepatobiliary cancer. We examined the association between autoimmune diseases and cancers of the liver and biliary tract in the Swedish population. METHODS: We analyzed data from national datasets at the Center for Primary Health Care Research (Lund University, Sweden). Data on patients with autoimmune disorders were retrieved from the Swedish Hospital Discharge Register, from 1964 through 2008; 33 diseases were evaluated. Hepatobiliary cancer cases were retrieved from the Swedish Cancer Registry. We calculated standardized incidence ratios (SIRs) and hazard ratios for incident cancers and deaths from hepatobiliary cancers. RESULTS: Among 402,462 patients with autoimmune disorders, 582 were diagnosed with primary liver cancer, 330 with gallbladder cancer, 115 with extrahepatic bile duct cancer, and 43 with ampulla of Vater cancers. We identified 14 autoimmune conditions that were significantly associated with increased risk of primary liver cancer (overall SIR [any autoimmune disease], 2.1; 95% confidence interval [CI], 2.0-2.3), 5 conditions associated with gallbladder cancer (overall SIR, 1.3; 95% CI, 1.1-1.4), and 3 associated with extrahepatic bile duct cancer (overall SIR, 1.6; 95% CI, 1.3-1.9). The autoimmune disorders with the strongest association with primary liver cancer were primary biliary cirrhosis (SIR, 39.5; 95% CI, 28.2-53.8) and autoimmune hepatitis (SIR, 29.0; 95% CI, 9.1-68.2); ulcerative colitis was strongly associated with extrahepatic bile duct cancer (SIR, 5.6; 95% CI, 3.6-8.4). Celiac disease, Crohn's disease, systemic sclerosis, and ulcerative colitis were associated with at least 2 types of cancer. Increased hazard ratios were observed only for patients with biliary tract cancer who had been hospitalized for autoimmune conditions. CONCLUSIONS: In a study of the Swedish population, we identified an increased risk of hepatobiliary cancers among individuals diagnosed with autoimmune disease. Associations among different cancer types indicate that shared immunomodulatory mechanisms determine susceptibility to hepatobiliary cancer. C1 [Castro, Felipe A.; Koshiol, Jill] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Liu, Xiangdong; Forsti, Asta; Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina; Hemminki, Kari] Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden. [Forsti, Asta; Hemminki, Kari] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany. [Sundquist, Jan; Sundquist, Kristina] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP Castro, FA (reprint author), NCI Shady Grove, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr 6-E230, Rockville, MD 20850 USA. EM felipe.castro@nih.gov RI Ji, Jianguang/E-9579-2011 OI Ji, Jianguang/0000-0003-0324-9496 FU Deutsche Krebshilfe, ALF project grant, Lund, Sweden; Swedish Council for Working Life and Social Research; National Institute of Health; National Cancer Institute, Division of Cancer Epidemiology and Genetics, USA FX This work was supported by Deutsche Krebshilfe, ALF project grant, Lund, Sweden and the Swedish Council for Working Life and Social Research. The study was also supported by the Intramural Research Program of the National Institute of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, USA. NR 45 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2014 VL 12 IS 6 BP 1038 EP + DI 10.1016/j.cgh.2013.11.007 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9ZI UT WOS:000336504700026 PM 24246767 ER PT J AU Turnbull, AE Krall, JR Ruhl, AP Curtis, JR Halpern, SD Lau, BM Needham, DM AF Turnbull, Alison E. Krall, Jenna R. Ruhl, A. Parker Curtis, J. Randall Halpern, Scott D. Lau, Bryan M. Needham, Dale M. TI A Scenario-Based, Randomized Trial of Patient Values and Functional Prognosis on Intensivist Intent to Discuss Withdrawing Life Support SO CRITICAL CARE MEDICINE LA English DT Article DE decision making; intensive care; life support care; prognosis; resuscitation orders; withholding treatment ID MORTALITY PROBABILITY-MODELS; IMPROVING PALLIATIVE CARE; MECHANICAL VENTILATION; CHAINED EQUATIONS; FOCUSING ILLUSION; UNIT; PHYSICIANS; ASSOCIATION; IMPUTATION; COMFORT AB Objectives: To evaluate the effect of 1) patient values as expressed by family members and 2) a requirement to document patients' functional prognosis on intensivists' intention to discuss withdrawal of life support in a hypothetical family meeting. Design: A three-armed, randomized trial. Setting: One hundred seventy-nine U.S. hospitals with training programs in critical care accredited by the Accreditation Council for Graduate Medical Education. Subjects: Six hundred thirty intensivists recruited via e-mail invitation from a database of 1,850 eligible academic intensivists. Interventions: Each intensivist was randomized to review 10, online, clinical scenarios with a range of illness severities involving a hypothetical patient (Mrs. X). In control-group scenarios, the patient did not want continued life support without a reasonable chance of independent living. In the first experimental arm, the patient wanted life support regardless of functional outcome. In the second experimental arm, patient values were identical to the control group, but intensivists were required to record the patient's estimated 3-month functional prognosis. Measurements and Main Results: Response to the question: Would you bring up the possibility of withdrawing life support with Mrs. X's family? answered using a five-point Likert scale. There was no effect of patient values on whether intensivists intended to discuss withdrawal of life support (p = 0.81), but intensivists randomized to record functional prognosis were 49% more likely (95% CI, 20-85%) to discuss withdrawal. Conclusions: In this national, scenario-based, randomized trial, patient values had no effect on intensivists' decisions to discuss withdrawal of life support with family. However, requiring intensivists to record patients' estimated 3-month functional outcome substantially increased their intention to discuss withdrawal. C1 [Turnbull, Alison E.; Lau, Bryan M.] Johns Hopkins Univ Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. [Turnbull, Alison E.; Ruhl, A. Parker; Needham, Dale M.] Johns Hopkins Med, Outcomes Crit Illness & Surg OACIS Grp, Baltimore, MD USA. [Turnbull, Alison E.; Ruhl, A. Parker; Needham, Dale M.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. [Krall, Jenna R.] Johns Hopkins Univ Bloomberg, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Ruhl, A. Parker] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Curtis, J. Randall] Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA USA. [Curtis, J. Randall] Univ Washington, Sch Med, Palliat Care Ctr Excellence, Seattle, WA USA. [Halpern, Scott D.] Univ Penn, Perelman Sch Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Perelman Sch Med, Fostering Improvement End Of Life Decis Sci FIELD, Philadelphia, PA 19104 USA. [Needham, Dale M.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD USA. RP Turnbull, AE (reprint author), Johns Hopkins Univ Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. EM turnbull@jhmi.edu FU National Institutes of Health (NIH); National Institute on Aging [T32-AG000247]; Johns Hopkins University Sommer Scholars Program; NIH [T32-AG000247] FX Dr. Turnbull received support for article research from the National Institutes of Health (NIH) (supported by a postdoctoral training grant from the National Institute on Aging, T32-AG000247). Dr. Turnbull is supported by the Johns Hopkins University Sommer Scholars Program. Dr. Krall received grant support from the National Institute on Aging (T32-AG000247) and received support for article research from the NIH (T32-AG000247). The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 37 TC 15 Z9 15 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2014 VL 42 IS 6 BP 1455 EP 1462 DI 10.1097/CCM.0000000000000227 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA AH6UM UT WOS:000336266900031 PM 24584065 ER PT J AU Dimas, AS Lagou, V Barker, A Knowles, JW Magi, R Hivert, MF Benazzo, A Rybin, D Jackson, AU Stringham, HM Song, C Fischer-Rosinsky, A Boesgaard, TW Grarup, N Abbasi, FA Assimes, TL Hao, K Yang, X Lecoeur, C Barroso, I Bonnycastle, LL Bottcher, Y Bumpstead, S Chines, PS Erdos, MR Graessler, J Kovacs, P Morken, MA Narisu, N Payne, F Stancakova, A Swift, AJ Tonjes, A Bornstein, SR Cauchi, S Froguel, P Meyre, D Schwarz, PEH Haring, HU Smith, U Boehnke, M Bergman, RN Collins, FS Mohlke, KL Tuomilehto, J Quertemous, T Lind, L Hansen, T Pedersen, O Walker, M Pfeiffer, AFH Spranger, J Stumvoll, M Meigs, JB Wareham, NJ Kuusisto, J Laakso, M Langenberg, C Dupuis, J Watanabe, RM Florez, JC Ingelsson, E McCarthy, MI Prokopenko, I AF Dimas, Antigone S. Lagou, Vasiliki Barker, Adam Knowles, Joshua W. Maegi, Reedik Hivert, Marie-France Benazzo, Andrea Rybin, Denis Jackson, Anne U. Stringham, Heather M. Song, Ci Fischer-Rosinsky, Antje Boesgaard, Trine Wellov Grarup, Niels Abbasi, Fahim A. Assimes, Themistocles L. Hao, Ke Yang, Xia Lecoeur, Cecile Barroso, Ines Bonnycastle, Lori L. Boettcher, Yvonne Bumpstead, Suzannah Chines, Peter S. Erdos, Michael R. Graessler, Jurgen Kovacs, Peter Morken, Mario A. Narisu, Narisu Payne, Felicity Stancakova, Alena Swift, Amy J. Toenjes, Anke Bornstein, Stefan R. Cauchi, Stephane Froguel, Philippe Meyre, David Schwarz, Peter E. H. Haering, Hans-Ulrich Smith, Ulf Boehnke, Michael Bergman, Richard N. Collins, Francis S. Mohlke, Karen L. Tuomilehto, Jaakko Quertemous, Thomas Lind, Lars Hansen, Torben Pedersen, Oluf Walker, Mark Pfeiffer, Andreas F. H. Spranger, Joachim Stumvoll, Michael Meigs, James B. Wareham, Nicholas J. Kuusisto, Johanna Laakso, Markku Langenberg, Claudia Dupuis, Josee Watanabe, Richard M. Florez, Jose C. Ingelsson, Erik McCarthy, Mark I. Prokopenko, Inga CA MAGIC Investigators TI Impact of Type 2 Diabetes Susceptibility Variants on Quantitative Glycemic Traits Reveals Mechanistic Heterogeneity SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; SCALE ASSOCIATION ANALYSIS; BODY-MASS INDEX; INSULIN SENSITIVITY; PROINSULIN LEVELS; COMMON VARIANT; TCF7L2 GENE; GLUCOSE; GENOME; LOCI AB Patients with established type 2 diabetes display both beta-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF712, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition. C1 [Dimas, Antigone S.; Lagou, Vasiliki; Maegi, Reedik; Ingelsson, Erik; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Dimas, Antigone S.] Biomed Sci Res Ctr, Athens, Greece. [Lagou, Vasiliki; Maegi, Reedik; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Barker, Adam; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England. [Knowles, Joshua W.; Abbasi, Fahim A.; Assimes, Themistocles L.; Quertemous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Knowles, Joshua W.; Abbasi, Fahim A.; Assimes, Themistocles L.; Quertemous, Thomas] Stanford Univ, Sch Med, Cardiovasc Inst, Stanford, CA 94305 USA. [Maegi, Reedik] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Benazzo, Andrea] Univ Ferrara, Dept Biol & Evolut, I-44100 Ferrara, Italy. [Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Jackson, Anne U.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Jackson, Anne U.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Song, Ci; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. [Song, Ci] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Fischer-Rosinsky, Antje; Pfeiffer, Andreas F. H.; Spranger, Joachim] Charite, Dept Endocrinol & Metab, D-13353 Berlin, Germany. [Boesgaard, Trine Wellov] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Grarup, Niels; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Hao, Ke] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA. [Yang, Xia] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA USA. [Lecoeur, Cecile; Cauchi, Stephane; Froguel, Philippe; Meyre, David] Univ Lille 2, Inst Pasteur, Inst Biol, CNRS,UMR8199, Lille, France. [Barroso, Ines; Bumpstead, Suzannah; Payne, Felicity] Wellcome Trust Sanger Inst, Hinxton, England. [Barroso, Ines] Univ Cambridge, Metab Res Labs, Cambridge, England. [Barroso, Ines] Addenbrookes Hosp, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Inst Metab Sci, Cambridge, England. [Bonnycastle, Lori L.; Chines, Peter S.; Erdos, Michael R.; Morken, Mario A.; Narisu, Narisu; Swift, Amy J.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Boettcher, Yvonne; Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Med Ctr, IFB AdiposityDis, D-04109 Leipzig, Germany. [Graessler, Jurgen; Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Div Prevent & Care Diabet, Dept Med 3, Dresden, Germany. [Kovacs, Peter] Interdisciplinary Ctr Clin Res Leipzig, Leipzig, Germany. [Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany. [Froguel, Philippe; Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London, England. [Meyre, David] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Haering, Hans-Ulrich] Univ Tubingen, Dept Internal Med, Div Endocrinol Diabetol Vasc Med Nephrol & Clin C, Tubingen, Germany. [Smith, Ulf] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Lundberg Lab Diabet Res,Ctr Excellence Metab & Ca, Gothenburg, Sweden. [Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Lind, Lars] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden. [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark. [Pedersen, Oluf] Hagedorn Res Inst, Copenhagen, Denmark. [Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, Copenhagen, Denmark. [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Pfeiffer, Andreas F. H.] German Inst Human Nutr, Dept Clin Nutr, Nuthetal, Germany. [Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 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.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [McCarthy, Mark I.] Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England. RP Prokopenko, I (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM rwatanab@usc.edu; jcflorez@partners.org; erik.ingelsson@medsci.uu.se; mark.mccarthy@drl.ox.ac.uk; i.prokopenko@imperial.ac.uk RI Grarup, Niels/K-2807-2015; Prokopenko, Inga/H-3241-2014; Schwarz, Peter/B-5127-2013; OI Grarup, Niels/0000-0001-5526-1070; Prokopenko, Inga/0000-0003-1624-7457; Schwarz, Peter/0000-0001-6317-7880; Magi, Reedik/0000-0002-2964-6011; Song, Ci/0000-0002-0947-9068; Rybin, Denis/0000-0002-3657-4829; Assimes, Themistocles/0000-0003-2349-0009; Payne, Felicity/0000-0003-4228-581X FU European Community [HEALTH-F4-2007-201413, LSHM-CT-2004-512013]; Wellcome Trust [WT098051, 098381]; Cambridge Biomedical Research Centre of the U.K. National Institute for Health Research; Medical Research Council Centre for Obesity and Related Metabolic Diseases; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK-078616]; NIDDK [K24 DK-080140]; Doris Duke Charitable Foundation Clinical Scientist Development Award; NIH [DK-069922, U54 DA021519, DK-062370, DK-072193, RR01066]; National Human Genome Research Institute [1 Z01 HG000024]; Agence Nationale de la Recherche; Conseil Regional Nord-Pas de Calais/Fonds europeen de developpement economique et regional; Academy of Finland [124243]; Clinical Research Group [KFO218/1]; Deutsche Forschungsgemeinschaft (DFG) [SP716/2-1]; German Bundesministerium fur Bildung und Forschung (BMBF); Mallinckrodt General Clinical Research Program, National Center for Research Resources; Swedish Research Council; Swedish Heart-Lung Foundation; Swedish Foundation for Strategic Research; Royal Swedish Academy of Science; Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention; Care; Danish Diabetes Association; Danish Research Council; European Union [QLG1-CT-2001-01252]; AstraZeneca; German Research Council [SF8-1052]; German Diabetes Association; Diabetes Hi Ifs; Forschungsfonds Deutschland; Boehringer Ingelheim Foundation; BMBF [FKZ: 01E01001]; European Commission under the Marie Curie Intra-European Fellowship; European Foundation; National Center for Research Resources, NIH [2 M01 RR000070]; U.S. Public Health Service; American Heart Association Fellow [10FTF3360005] FX The major funding for this meta-analysis was provided through the Seventh Framework Programme of the European Community (FP7/2007-2013), the ENGAGE project, and grant agreement HEALTH-F4-2007-201413. As part of the Ely Study, I.B. was supported by Wellcome Trust grant WT098051, the Cambridge Biomedical Research Centre of the U.K. National Institute for Health Research, and the Medical Research Council Centre for Obesity and Related Metabolic Diseases. The EUGENE2 Study was supported by grant LSHM-CT-2004-512013 from the European Community FP6 EUGENE2. The Framingham Heart Study was conducted in part using data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource project. This work was partially supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195) and its contract with Affymetrix Inc. for genotyping services (contract no. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II), which is funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The Framingham Heart Study was also supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01 DK-078616 to J.B.M., J.D., and J.C.F.; NIDDK grant K24 DK-080140 to J.B.M.; and a Doris Duke Charitable Foundation Clinical Scientist Development Award to J.C.F. Support for the Finland-United States Investigation of NIDDM Genetics was provided by NIH grants DK-069922 (to R.M.W.), U54 DA021519 (to R.M.W.), DK-062370 (to M.B.), and DK-072193 (to K.L.M.). Additional support comes from the National Human Genome Research Institute intramural project number 1 Z01 HG000024 (to F.S.C.). The Metabolisches Syndrom Berlin Potsdam (MESYBEPO) Study was supported by grants from Agence Nationale de la Recherche and Conseil Regional Nord-Pas de Calais/Fonds europeen de developpement economique et regional. Support for the Metabolic Syndrome in Men Study was provided by grant 124243 from the Academy of Finland. In the MESYBEPO Study, J.S. was supported by Clinical Research Group grant KFO218/1, Heisenberg Professorship SP716/2-1 of the Deutsche Forschungsgemeinschaft (DFG), and a research group on molecular nutrition of the German Bundesministerium fur Bildung und Forschung (BMBF). The Partners/Roche Cohort was supported by the Mallinckrodt General Clinical Research Program, National Center for Research Resources, and NIH grant RR01066. In the Prospective Investigation of the Vasculature in Uppsala Seniors and the Uppsala Longitudinal Study of Adult Men, the SNP Technology Platform is supported by Uppsala University, Uppsala University Hospital, and the Swedish Research Council for Infrastructures. El. was supported by grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Foundation for Strategic Research, and the Royal Swedish Academy of Science. The QTL families and UNG92 Study is supported by the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention, and Care, The Danish Diabetes Association, and The Danish Research Council.; The Relationship between Insulin Sensitivity and Cardiovascular Disease Study is supported by European Union grant QLG1-CT-2001-01252 and AstraZeneca. The Sorbs Study was supported by grants from the German Research Council (SF8-1052 "Obesity mechanisms") and the German Diabetes Association and the Diabetes Hi Ifs und Forschungsfonds Deutschland. P.K. is funded by the Boehringer Ingelheim Foundation. The Integrated Research and Treatment Center Adiposity Diseases is supported by BMBF grant FKZ: 01E01001. I.P. and V.L. were partially funded through the Seventh Framework Programme of the European Community (grant FP7/2007-2013) and the ENGAGE project grant agreement HEALTH-F4-2007-201413. R.M. is funded by the European Commission under the Marie Curie Intra-European Fellowship and a European Foundation for the Study of Diabetes New Horizons grant. M.I.M. is supported by Wellcome Trust grant 098381. Sample collection for the Stanford IST Cohort was carried out in part in the Clinical and Translational Research Unit, Stanford University, with funds provided by the National Center for Research Resources, NIH grant 2 M01 RR000070, and the U.S. Public Health Service. J.W.K. is supported by American Heart Association Fellow to Faculty Transition award 10FTF3360005. NR 44 TC 77 Z9 79 U1 4 U2 32 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUN PY 2014 VL 63 IS 6 BP 2158 EP 2171 DI 10.2337/db13-0949 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI1VS UT WOS:000336643900039 PM 24296717 ER PT J AU Vassy, JL Hivert, MF Porneala, B Dauriz, M Florez, JC Dupuis, J Siscovick, DS Fornage, M Rasmussen-Torvik, LJ Bouchard, C Meigs, JB AF Vassy, Jason L. Hivert, Marie-France Porneala, Bianca Dauriz, Marco Florez, Jose C. Dupuis, Josee Siscovick, David S. Fornage, Myriam Rasmussen-Torvik, Laura J. Bouchard, Claude Meigs, James B. TI Polygenic Type 2 Diabetes Prediction at the Limit of Common Variant Detection SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS; DENSITY-LIPOPROTEIN-CHOLESTEROL; LIFE-STYLE INTERVENTION; RISK-FACTORS; AFRICAN-AMERICANS; GLUCOSE-TOLERANCE; RECLASSIFICATION; POPULATION; MELLITUS AB Genome-wide association studies (GWAS) may have reached their limit of detecting common type 2 diabetes (T2D)-associated genetic variation. We evaluated the performance of current polygenic T2D prediction. Using data from the Framingham Offspring (FOS) and the Coronary Artery Risk Development in Young Adults (CARDIA) studies, we tested three hypotheses: 1) a 62-locus genotype risk score (GRS(t)) improves T2D prediction compared with previous less inclusive GRS(t); 2) separate GRS for beta-cell (GRS(beta)) and insulin resistance (GRS(IR)) independently predict T2D; and 3) the relationships between T2D and GRS(t), GRS(beta), or GRS(IR) do not differ between blacks and whites. Among 1,650 young white adults in CARDIA, 820 young black adults in CARDIA, and 3,471 white middle-aged adults in FOS, cumulative T2D incidence was 5.9%, 14.4%, and 12.9%, respectively, over 25 years. The 62-locus GRS(t) was significantly associated with incident T2D in all three groups. In FOS but not CARDIA, the 62-locus GRSt improved the model C statistic (0.698 and 0.726 for models without and with GRS(t), respectively; P < 0.001) but did not materially improve risk reclassification in either study. Results were similar among blacks compared with whites. The GRS(beta) but not GRS(IR) predicted incident T2D among FOS and CARDIA whites. At the end of the era of common variant discovery for T2D, polygenic scores can predict T2D in whites and blacks but do not outperform clinical models. Further optimization of polygenic prediction may require novel analytic methods, including less common as well as functional variants. C1 [Vassy, Jason L.; Hivert, Marie-France; Dauriz, Marco; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA. [Vassy, Jason L.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Hivert, Marie-France] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada. [Porneala, Bianca; Dauriz, Marco; Meigs, James B.] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. [Dauriz, Marco] Univ Verona Med Sch & Hosp Trust Verona, Div Endocrinol & Metab Dis, Dept Med, Verona, Italy. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, 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. [Dupuis, Josee] Boston Univ Sch Publ Hlth, Depat Biostat, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Rasmussen-Torvik, Laura J.] Northwestern Univ Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. [Bouchard, Claude] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA USA. RP Meigs, JB (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM jmeigs@partners.org RI Bouchard, Claude/A-7637-2009; Dauriz, Marco/S-5843-2016 OI Dauriz, Marco/0000-0002-5542-5941 FU National Institutes of Health [R01-DK-078616, K24-DK-080140, U01-HG-006500, L30-DK089597]; National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging; NHLBI [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278] FX This work was supported by National Institutes of Health grants (R01-DK-078616 and K24-DK-080140 to J.B.M. and U01-HG-006500 and L30-DK089597 to J.L.V.). The CARDIA Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging. This manuscript was reviewed by CARDIA personnel for scientific content. The Framingham Heart Study was supported by the NHLBI (contract number N01-HC-25195) and its contract with Affymetrix, Inc., for genotyping services (contract number N02-HL-6-4278). A portion of this research was conducted using the Linux Clusters for Genetic Analysis (LinGA) computing resources at the Boston University Medical Campus. NR 44 TC 44 Z9 44 U1 0 U2 18 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUN PY 2014 VL 63 IS 6 BP 2172 EP 2182 DI 10.2337/db13-1663 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI1VS UT WOS:000336643900040 PM 24520119 ER PT J AU Kuo, I Golin, CE Wang, J Haley, DF Hughes, J Mannheimer, S Justman, J Rompalo, A Frew, PM Adimora, AA Soto-Torres, L Hodder, S AF Kuo, Irene Golin, Carol E. Wang, Jing Haley, Danielle F. Hughes, James Mannheimer, Sharon Justman, Jessica Rompalo, Anne Frew, Paula M. Adimora, Adaora A. Soto-Torres, Lydia Hodder, Sally CA HPTN 064 Study Team TI Substance use patterns and factors associated with changes over time in a cohort of heterosexual women at risk for HIV acquisition in the United States SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Women; Substance use; Opiate use; Cocaine use; Binge drinking; HIV ID NATIONAL EPIDEMIOLOGIC SURVEY; INJECTION-DRUG USERS; AFRICAN-AMERICAN; CRACK COCAINE; YOUNG-ADULTS; CONCURRENT PARTNERSHIPS; SEXUAL PARTNERSHIPS; INTERAGENCY HIV; USE BEHAVIORS; CONDOM USE AB Background: Substance use is associated with HIV sexual risk behaviors, yet few studies have examined substance use patterns longitudinally. We evaluated the types and frequency of substances used over a six-month period among U.S. women at risk for HIV acquisition. Methods: Women reporting unprotected sex with a man in the previous six months and at least one other personal or partner HIV risk characteristic enrolled in a multisite cohort study and completed interviews about substance use at study visits. Prevalence and frequency of substance use at the baseline and six-month visits were compared and correlates of decreased substance use at the six-month visit were assessed. Results: Of 2099 women enrolled, 1882 had substance use data at baseline and six-months. Of these, 76.1% reported using at least one drug or binge drinking in the previous six months; 37.5% were frequent and 38.6% non-frequent substance users. Binge drinking was most frequently reported (63.3%), followed by cocaine (25.0%) and opioids (16.5%). Fifty-five percent of opiate users and 30% of cocaine users reported daily/almost daily use. At the six-month visit, 40.5% reported a decrease in frequency of use. Adjusting for income and type of drug used, poly-substance users were less likely to decrease frequency of use compared to those who only used one substance. Conclusion: A substantial decrease in frequency of substance use over time was observed in this cohort. Poly-substance users were less likely to reduce frequency of use over time, suggesting that specific substance use interventions targeting these users are warranted. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Kuo, Irene] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC 20052 USA. [Golin, Carol E.; Adimora, Adaora A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Golin, Carol E.; Adimora, Adaora A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Wang, Jing; Hughes, James] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Haley, Danielle F.] FHI 360, Durham, NC USA. [Haley, Danielle F.; Frew, Paula M.] Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA USA. [Hughes, James] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Mannheimer, Sharon] Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA. [Mannheimer, Sharon; Justman, Jessica] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Rompalo, Anne] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Frew, Paula M.] Emory Univ, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA. [Soto-Torres, Lydia] NIAID, NIH, Bethesda, MD 20892 USA. [Hodder, Sally] Rutgers, New Jersey Med Sch, Newark, NJ USA. RP Kuo, I (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, 950 New Hampshire Ave NW,5th Floor, Washington, DC 20052 USA. EM ikuo@gwu.edu OI Frew, Paula/0000-0002-3078-9124 FU National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse; National Institute of Mental Health [UM1 AI068619, U01-AI068613, UM1-AI068613]; Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University [5U1AI069466]; University of North Carolina Clinical Trials Unit [AI069423]; University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award [RR 025747]; University of North Carolina Center for AIDS Research [AI050410]; Emory University HIV/AIDS Clinical Trials Unit [5UO1AI069418]; Center for AIDS Research [P30 AI050409]; Clinical and Translational Science Award [UL1 RR025008]; Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit [5UM1 AI069503-07]; Johns Hopkins Adult AIDS Clinical Trial Unit [AI069465]; Johns Hopkins Clinical and Translational Science Award [UL1 RR 25005] FX Nothing declared. Grant support provided by the National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, and National Institute of Mental Health (cooperative agreement no. UM1 AI068619, U01-AI068613, and UM1-AI068613); Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University (5U1AI069466); University of North Carolina Clinical Trials Unit (AI069423); University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award (RR 025747); University of North Carolina Center for AIDS Research (AI050410); Emory University HIV/AIDS Clinical Trials Unit (5UO1AI069418), Center for AIDS Research (P30 AI050409), and Clinical and Translational Science Award (UL1 RR025008); The Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit (5UM1 AI069503-07) and; The Johns Hopkins Adult AIDS Clinical Trial Unit (AI069465) and The Johns Hopkins Clinical and Translational Science Award (UL1 RR 25005). The views expressed herein are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institutes of Health, the HPTN, or its funders. NR 53 TC 3 Z9 3 U1 3 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2014 VL 139 BP 93 EP 99 DI 10.1016/j.drugalcdep.2014.03.007 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AI2SI UT WOS:000336708000013 PM 24698079 ER PT J AU Keyes, KM Shmulewitz, D Greenstein, E McLaughlin, KA Wall, M Aharonovich, E Weizman, A Frisch, A Spivak, B Grant, BF Hasin, D AF Keyes, Katherine M. Shmulewitz, Dvora Greenstein, Eliana McLaughlin, Katie A. Wall, Melanie Aharonovich, Efrat Weizman, Abraham Frisch, Amos Spivak, Baruch Grant, Bridget F. Hasin, Deborah TI Exposure to the Lebanon War of 2006 and effects on alcohol use disorders: The moderating role of childhood maltreatment (vol 134, pg 296, 2014) SO DRUG AND ALCOHOL DEPENDENCE LA English DT Correction C1 [Keyes, Katherine M.; Hasin, Deborah] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Shmulewitz, Dvora; Greenstein, Eliana; Aharonovich, Efrat; Hasin, Deborah] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Shmulewitz, Dvora; Greenstein, Eliana; Aharonovich, Efrat; Hasin, Deborah] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [McLaughlin, Katie A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Gen Pediat, Boston, MA 02115 USA. [Wall, Melanie] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA. [Weizman, Abraham; Frisch, Amos; Spivak, Baruch] Tel Aviv Univ, Sackler Fac Med, Felsenstein Med Res Ctr, IL-69978 Tel Aviv, Israel. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Keyes, KM (reprint author), Columbia Univ, Dept Epidemiol, 722 West 168th St,Suite 503, New York, NY 10032 USA. EM kmk2104@columbia.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2014 VL 139 BP 182 EP 182 DI 10.1016/j.drugalcdep.2014.03.019 PG 1 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AI2SI UT WOS:000336708000027 ER PT J AU Lowe, JR Duncan, AF Bann, CM Fuller, J Hintz, SR Das, A Higgins, RD Watterberg, KL AF Lowe, Jean R. Duncan, Andrea Freeman Bann, Carla M. Fuller, Janell Hintz, Susan R. Das, Abhik Higgins, Rosemary D. Watterberg, Kristi L. CA Eunice Kennedy Shriver Natl Inst C TI Early working memory as a racially and ethnically neutral measure of outcome in extremely preterm children at 18-22 months (vol 89, pg 1055, 2013) SO EARLY HUMAN DEVELOPMENT LA English DT Correction C1 [Lowe, Jean R.; Duncan, Andrea Freeman; Fuller, Janell; Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Bann, Carla M.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Hintz, Susan R.] Stanford Univ, Palo Alto, CA 94304 USA. [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Lowe, JR (reprint author), Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. EM jrlowe@unm.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-3782 EI 1872-6232 J9 EARLY HUM DEV JI Early Hum. Dev. PD JUN PY 2014 VL 90 IS 6 BP 319 EP 319 DI 10.1016/j.earlhumdev.2014.03.004 PG 1 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA AI2UW UT WOS:000336714600009 ER PT J AU Parra, GI Green, KY AF Parra, Gabriel I. Green, Kim Y. TI Sequential Gastroenteritis Episodes Caused by 2 Norovirus Genotypes SO EMERGING INFECTIOUS DISEASES LA English DT Article AB We investigated sequential episodes of acute norovirus gastroenteritis in a young child within an 11-month period. The infections were caused by 2 distinct genotypes (GII.4 and GII.6). Failure to achieve cross-protective immunity was linked to absence of an enduring and cross-reactive mucosal immune response, a critical consideration for vaccine design. C1 [Parra, Gabriel I.; Green, Kim Y.] NIH, Bethesda, MD 20892 USA. RP Parra, GI (reprint author), NIAID, Infect Dis Lab, Caliciviruses Sect, NIH, Room 6318,Bldg 50,50 South Dr, Bethesda, MD 20892 USA. EM parrag@niaid.nih.gov; kgreen@niaid.nih.gov OI Parra, Gabriel/0000-0002-1102-4740 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 15 TC 12 Z9 12 U1 0 U2 11 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 EI 1080-6059 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUN PY 2014 VL 20 IS 6 BP 1016 EP 1018 DI 10.3201/eid2006.131627 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AI0SZ UT WOS:000336561600014 PM 24857806 ER PT J AU Abrams, JA Appelman, HD Beer, DG Berry, LD Chak, A Falk, GW Fitzgerald, RC Ginsberg, GG Grady, WM Joshi, BP Lynch, JP Markowitz, S Richmond, ES Rustgi, AK Seibel, EJ Shaheen, NJ Shyr, Y Umar, A Wang, KK Wang, TC Wang, TD Yassin, R AF Abrams, Julian A. Appelman, Henry D. Beer, David G. Berry, Lynne D. Chak, Amitabh Falk, Gary W. Fitzgerald, Rebecca C. Ginsberg, Gregory G. Grady, William M. Joshi, Bishnu P. Lynch, John P. Markowitz, Sanford Richmond, Ellen S. Rustgi, Anil K. Seibel, Eric J. Shaheen, Nicholas J. Shyr, Yu Umar, Asad Wang, Kenneth K. Wang, Timothy C. Wang, Thomas D. Yassin, Rihab TI Barrett's Esophagus Translational Research Network (BETRNet): The Pivotal Role of Multi-institutional Collaboration in Esophageal Adenocarcinoma Research SO GASTROENTEROLOGY LA English DT Editorial Material C1 [Abrams, Julian A.; Wang, Timothy C.] Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY 10027 USA. [Appelman, Henry D.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Beer, David G.] Univ Michigan, Thorac Surg Sect, Ann Arbor, MI 48109 USA. [Berry, Lynne D.] Vanderbilt Univ, Sch Med, Ctr Quantitat Sci, Nashville, TN 37212 USA. [Chak, Amitabh] Case Western Reserve Univ, Div Gastroenterol, Cleveland, OH 44106 USA. [Falk, Gary W.; Ginsberg, Gregory G.; Lynch, John P.; Rustgi, Anil K.] Univ Penn, Div Gastroenterol, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Fitzgerald, Rebecca C.] Hutchison MRC Res Ctr, MRC Canc Unit, Cambridge, England. [Grady, William M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Sch Med, Seattle, WA 98195 USA. [Grady, William M.] Univ Washington, Sch Med, Div Gastroenterol, Seattle, WA 98195 USA. [Joshi, Bishnu P.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Markowitz, Sanford] Case Western Reserve Univ, Div Hematol Oncol, Cleveland, OH 44106 USA. [Markowitz, Sanford] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Richmond, Ellen S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Seibel, Eric J.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Shaheen, Nicholas J.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Shyr, Yu] Vanderbilt Univ, Sch Med, Ctr Quantitat Sci, Nashville, TN 37212 USA. [Umar, Asad] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Wang, Kenneth K.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Wang, Thomas D.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Yassin, Rihab] NCI, Div Canc Biol, Bethesda, MD 20892 USA. RP Abrams, JA (reprint author), Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY 10027 USA. OI Falk, Gary/0000-0002-7143-1436 FU Department of Health [NIHR-RP-02-12-011]; Medical Research Council [MC_UU_12022/2, MC_U105365007]; NCATS NIH HHS [U18 TR000536]; NCI NIH HHS [U54 CA163004, U01 CA152756, U54 CA163060, U01CA182940, P50 CA095103, U54 CA163059, U01CA152756, U01 CA182940, U01 CA163056]; NIH HHS [K26 OD012097] NR 5 TC 2 Z9 2 U1 0 U2 2 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2014 VL 146 IS 7 BP 1586 EP 1590 DI 10.1053/j.gastro.2014.04.014 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9YD UT WOS:000336500900007 PM 24768332 ER PT J AU Erlinger, S Arias, IM Dhumeaux, D AF Erlinger, Serge Arias, Irwin M. Dhumeaux, Daniel TI Inherited Disorders of Bilirubin Transport and Conjugation: New Insights Into Molecular Mechanisms and Consequences SO GASTROENTEROLOGY LA English DT Article DE Crigler-Najjar Syndrome; Hepatic Storage Disease; Glucuronosyl Transferase; Bile Secretion; Kernicterus ID CRIGLER-NAJJAR-SYNDROME; DUBIN-JOHNSON-SYNDROME; ORGANIC-ANION TRANSPORT; SYNDROME TYPE-I; GLUCURONOSYLTRANSFERASE 1A1 UGT1A1; ORTHOTOPIC LIVER-TRANSPLANTATION; RESISTANCE-ASSOCIATED PROTEIN-2; CANALICULAR MEMBRANE-VESICLES; SPORADIC COLORECTAL-CANCER; MUTANT TR RATS AB Inherited disorders of bilirubin metabolism might reduce bilirubin uptake by hepatocytes, bilirubin conjugation, or secretion of bilirubin into bile. Reductions in uptake could increase levels of unconjugated or conjugated bilirubin (Rotor syndrome). Defects in bilirubin conjugation could increase levels of unconjugated bilirubin; the effects can be benign and frequent (Gilbert syndrome) or rare but severe, increasing the risk of bilirubin encephalopathy (Crigler-Najjar syndrome). Impairment of bilirubin secretion leads to accumulation of conjugated bilirubin (Dubin-Johnson syndrome). We review the genetic causes and pathophysiology of disorders of bilirubin transport and conjugation as well as clinical and therapeutic aspects. We also discuss the possible mechanisms by which hyperbilirubinemia protects against cardiovascular disease and the metabolic syndrome and the effects of specific genetic variants on drug metabolism and cancer development. C1 [Erlinger, Serge] Univ Paris 07, Paris, France. [Arias, Irwin M.] NIH, Bethesda, MD 20892 USA. [Dhumeaux, Daniel] Univ Paris Est, Hop Henri Mondor, Creteil, France. RP Erlinger, S (reprint author), 1422 Route Mauvares, F-13840 Rognes, France. EM serge.erlinger@gmail.com NR 135 TC 22 Z9 23 U1 5 U2 25 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2014 VL 146 IS 7 BP 1625 EP 1638 DI 10.1053/j.gastro.2014.03.047 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9YD UT WOS:000336500900018 PM 24704527 ER PT J AU Keenan, BP Saenger, Y Kafrouni, MI Leubner, A Lauer, P Maitra, A Rucki, AA Gunderson, AJ Coussens, LM Brockstedt, DG Dubensky, TW Hassan, R Armstrong, TD Jaffee, EM AF Keenan, Bridget P. Saenger, Yvonne Kafrouni, Michel I. Leubner, Ashley Lauer, Peter Maitra, Anirban Rucki, Agnieszka A. Gunderson, Andrew J. Coussens, Lisa M. Brockstedt, Dirk G. Dubensky, Thomas W., Jr. Hassan, Raffit Armstrong, Todd D. Jaffee, Elizabeth M. TI A Listeria Vaccine and Depletion of T-Regulatory Cells Activate Immunity Against Early Stage Pancreatic Intraepithelial Neoplasms and Prolong Survival of Mice SO GASTROENTEROLOGY LA English DT Article DE Pancreatic Cancer; Listeria Vaccine; Tumor Microenvironment; Immunity ID DUCTAL ADENOCARCINOMA; ONCOGENIC KRAS; ADOPTIVE TRANSFER; SUPPRESSOR-CELLS; MOUSE MODEL; TC17 CELLS; CANCER; IMMUNOTHERAPY; MONOCYTOGENES; TUMORS AB BACKGROUND & AIMS: Premalignant lesions and early stage tumors contain immunosuppressive microenvironments that create barriers for cancer vaccines. Kras(G12D/+);Trp53(R172H/+); Pdx-1-Cre (KPC) mice, which express an activated form of Kras in pancreatic tissues, develop pancreatic intraepithelial neoplasms (PanIN) that progress to pancreatic ductal adenocarcinoma (PDA). We used these mice to study immune suppression in PDA. METHODS: We immunized KPC and Kras(G12D/+); Pdx-1-Cre mice with attenuated intracellular Listeria monocytogenes (which induces CD4(+) and CD8(+) T-cell immunity) engineered to express Kras(G12D) (LM-Kras). The vaccine was given alone or in sequence with an anti-CD25 antibody (PC61) and cyclophosphamide to deplete T-regulatory (Treg) cells. Survival times were measured; pancreatic and spleen tissues were collected and analyzed by histologic, flow cytometry, and immunohistochemical analyses. RESULTS: Interferon gamma-mediated, CD8(+) T-cell responses were observed in KPC and Kras(G12D/+); Pdx-1-Cre mice given LM-Kras, but not in unvaccinated mice. Administration of LM-Kras to KPC mice 4-6 weeks old (with early stage PanINs), depleted of Treg cells, significantly prolonged survival and reduced PanIN progression (median survival, 265 days), compared with unvaccinated mice (median survival, 150 days; P = .002), mice given only LM-Kras (median survival, 150 days; P = .050), and unvaccinated mice depleted of Treg cells (median survival, 170 days; P = .048). In 8- to 12-week-old mice (with late-stage PanINs), LM-Kras, alone or in combination with Treg cell depletion, did not increase survival time or slow PanIN progression. The combination of LM-Kras and Treg cell depletion reduced numbers of Foxp3(+)CD4(+) T cells in pancreatic lymph nodes, increased numbers of CD4(+) T cells that secrete interleukin 17 and interferon gamma, and caused CD11b(+)Gr1(+) cells in the pancreas to acquire an immunostimulatory phenotype. CONCLUSIONS: Immunization of KPC mice with Listeria monocytogenes engineered to express Kras(G12D), along with depletion of Treg cells, reduces progression of early stage, but not late-stage, PanINs. This approach increases infiltration of the lesion with inflammatory cells. It might be possible to design immunotherapies against premalignant pancreatic lesions to slow or prevent progression to PDA. C1 [Keenan, Bridget P.; Kafrouni, Michel I.; Leubner, Ashley; Rucki, Agnieszka A.; Armstrong, Todd D.; Jaffee, Elizabeth M.] Johns Hopkins, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA. [Keenan, Bridget P.; Kafrouni, Michel I.; Leubner, Ashley; Rucki, Agnieszka A.; Armstrong, Todd D.; Jaffee, Elizabeth M.] Johns Hopkins, Skip Viragh Ctr Clin Pancreat Canc Res, Baltimore, MD 21231 USA. [Keenan, Bridget P.; Kafrouni, Michel I.; Leubner, Ashley; Rucki, Agnieszka A.; Armstrong, Todd D.; Jaffee, Elizabeth M.] Johns Hopkins, Sol Goldman Pancreat Canc Ctr, Baltimore, MD 21231 USA. [Keenan, Bridget P.] Johns Hopkins Univ, Sch Med, Grad Program Immunol, Baltimore, MD USA. [Saenger, Yvonne] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Oncol, New York, NY USA. [Saenger, Yvonne] Mt Sinai Sch Med, Dept Dermatol, New York, NY USA. [Lauer, Peter; Brockstedt, Dirk G.; Dubensky, Thomas W., Jr.] Aduro BioTech Inc, Berkeley, CA USA. [Maitra, Anirban] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Maitra, Anirban] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA. [Gunderson, Andrew J.; Coussens, Lisa M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Cell & Dev Biol, Portland, OR 97201 USA. [Hassan, Raffit] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Jaffee, EM (reprint author), Johns Hopkins, Sidney Kimmel Canc Ctr, 1650 Orleans St, Baltimore, MD 21231 USA. EM ejaffee@jhmi.edu FU National Cancer Institute, National Institutes of Health [P50CA062924, R01CA122081, U19CA113341]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX Supported by grants from the National Cancer Institute, National Institutes of Health (P50CA062924, R01CA122081, and U19CA113341 to E.M.J.), and supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 48 TC 25 Z9 26 U1 0 U2 15 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2014 VL 146 IS 7 BP 1784 EP + DI 10.1053/j.gastro.2014.02.055 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9YD UT WOS:000336500900032 PM 24607504 ER PT J AU Koerner, JF Coleman, CN Murrain-Hill, P FitzGerald, DJ Sullivan, JM AF Koerner, John F. Coleman, C. Norman Murrain-Hill, Paula FitzGerald, Denis J. Sullivan, Julie M. TI THE MEDICAL DECISION MODEL AND DECISION MAKER TOOLS FOR MANAGEMENT OF RADIOLOGICAL AND NUCLEAR INCIDENTS SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT Conrad-Global Conference on Radiation Topics-Preparedness, Response, Protection and Research CY MAY 13-16, 2013 CL Munich, GERMANY DE accidents; nuclear; accidents; power reactor; emergencies; radiological; risk communication AB Effective decision making during a rapidly evolving emergency such as a radiological or nuclear incident requires timely interim decisions and communications from onsite decision makers while further data processing, consultation, and review are ongoing by reachback experts. The authors have recently proposed a medical decision model for use during a radiological or nuclear disaster, which is similar in concept to that used in medical care, especially when delay in action can have disastrous effects. For decision makers to function most effectively during a complex response, they require access to onsite subject matter experts who can provide information, recommendations, and participate in public communication efforts. However, in the time before this expertise is available or during the planning phase, just-in-time tools are essential that provide critical overview of the subject matter written specifically for the decision makers. Recognizing the complexity of the science, risk assessment, and multitude of potential response assets that will be required after a nuclear incident, the Office of the Assistant Secretary for Preparedness and Response, in collaboration with other government and non-government experts, has prepared a practical guide for decision makers. This paper illustrates how the medical decision model process could facilitate onsite decision making that includes using the deliberative reachback process from science and policy experts and describes the tools now available to facilitate timely and effective incident management. C1 [Koerner, John F.; Coleman, C. Norman; Murrain-Hill, Paula; FitzGerald, Denis J.; Sullivan, Julie M.] US Dept HHS, Off Assistant Secretary Preparedness & Response, Off Emergency Management, Washington, DC 20201 USA. [Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Sullivan, Julie M.] AAAS Sci & Technol Policy, Washington, DC USA. RP Koerner, JF (reprint author), US Dept HHS, Off Assistant Secretary Preparedness & Response, Off Emergency Management, Washington, DC 20201 USA. EM john.koerner@hhs.gov NR 7 TC 5 Z9 5 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUN PY 2014 VL 106 IS 6 BP 645 EP 651 DI 10.1097/HP.0000000000000053 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA AH9YG UT WOS:000336501300004 PM 24776895 ER PT J AU Macri, V Mahida, SN Zhang, ML Sinner, MF Dolmatova, EV Tucker, NR McLellan, M Shea, MA Milan, DJ Lunetta, KL Benjamin, EJ Ellinor, PT AF Macri, Vincenzo Mahida, Saagar N. Zhang, Michael L. Sinner, Moritz F. Dolmatova, Elena V. Tucker, Nathan R. McLellan, Micheal Shea, Marisa A. Milan, David J. Lunetta, Kathryn L. Benjamin, Emelia J. Ellinor, Patrick T. TI A novel trafficking-defective HCN4 mutation is associated with early-onset atrial fibrillation SO HEART RHYTHM LA English DT Article DE HCN4; Mutation; Atrial fibrillation; Electrophysiology ID FUNCTIONAL EXPRESSION; SINUS BRADYCARDIA; PACEMAKER CHANNEL; DOMAIN; HAPLOINSUFFICIENCY; DYSFUNCTION; TERMINUS; GENES AB BACKGROUND Atrial fibrillation (AF) is the most common arrhythmia, and a recent genome-wide association study identified the hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) as a novel AF susceptibility locus. HCN4 encodes for the cardiac pacemaker channel, and HCN4 mutations are associated with familial sinus bradycardia and AF. OBJECTIVE The purpose of this study was to determine whether novel variants in the coding region of HCN4 contribute to the susceptibility for AF. METHODS We sequenced the coding region of HCN4 for novel variants from 527 cases with early-onset AF from the Massachusetts General Hospital AF Study and 443 referents from the Framingham Heart Study. We used site-directed mutagenesis, cellular electrophysiology, immunocytochemistry, and confocal microscopy to functionally characterize novel variants. RESULTS We found the frequency of novel coding HCN4 variants was 2-fold greater for individuals with AF (7 variants) compared to the referents (3 variants). We determined that of the 7 novel HCN4 variants in our AF cases, 1 (p.Pro257Ser, located in the amino-terminus adjacent to the first transmembrane spanning domain) did not traffic to cell membrane, whereas the remaining 6 were not functionally different from wild type. In addition, the 3 novel variants in our referents did not alter function compared to wild-type. Coexpression studies showed that the p.Pro257Ser mutant channel failed to colocalize with the wild-type HCN4 channel on the cell membrane. CONCLUSION Our findings are consistent with HCN4 haploinsufficiency as the likely mechanism for early-onset AF in the p. Pro257Ser carrier. C1 [Macri, Vincenzo; Mahida, Saagar N.; Zhang, Michael L.; Sinner, Moritz F.; Dolmatova, Elena V.; Tucker, Nathan R.; McLellan, Micheal; Milan, David J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Macri, Vincenzo; Mahida, Saagar N.; Dolmatova, Elena V.; Tucker, Nathan R.; Milan, David J.; Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA USA. [Sinner, Moritz F.] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Shea, Marisa A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. RP Ellinor, PT (reprint author), Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM ellinor@mgh.harvard.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health [1RO1HL104156, 1K2411L105780, 1RO1HL092577]; Established Investigator Award from the American Heart Association [13EIA14220013]; National Heart, Lung, and Blood Institute [T32HL007208]; Heart Rhythm Society (The Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology) FX Drs. Macri and Mahida contributed equally to this manuscript. The current work was funded by National Institutes of Health Grants 1RO1HL104156 and 1K2411L105780 to Dr. Elinor and Grant 1RO1HL092577 to Drs. Benjamin and Elinor. Dr. Ellinor is supported by an Established Investigator Award from the American Heart Association (13EIA14220013). Dr. Tucker was supported by award number T32HL007208 from the National Heart, Lung, and Blood Institute. Dr. Macri is supported by the Heart Rhythm Society (The Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology). NR 25 TC 9 Z9 9 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD JUN PY 2014 VL 11 IS 6 BP 1055 EP 1062 DI 10.1016/j.hrthm.2014.03.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH8NU UT WOS:000336395600021 PM 24607718 ER PT J AU Yudkin, D Hayward, BE Aladjem, MI Kumari, D Usdin, K AF Yudkin, Dmitry Hayward, Bruce E. Aladjem, Mirit I. Kumari, Daman Usdin, Karen TI Chromosome fragility and the abnormal replication of the FMR1 locus in fragile X syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID DNA-REPLICATION; CGG-REPEAT; TRINUCLEOTIDE REPEATS; DELAYED REPLICATION; MENTAL-RETARDATION; POLYMERASE-DELTA; CALF THYMUS; SITE; GENE; EXPANSION AB Fragile X Syndrome (FXS) is a learning disability seen in individuals who have > 200 CGGaEuro cent CCG repeats in the 5' untranslated region of the X-linked FMR1 gene. Such alleles are associated with a fragile site, FRAXA, a gap or constriction in the chromosome that is coincident with the repeat and is induced by folate stress or thymidylate synthase inhibitors like fluorodeoxyuridine (FdU). The molecular basis of the chromosome fragility is unknown. Previous work has suggested that the stable intrastrand structures formed by the repeat may be responsible, perhaps via their ability to block DNA synthesis. We have examined the replication dynamics of normal and FXS cells with and without FdU. We show here that an intrinsic problem with DNA replication exists in the FMR1 gene of individuals with FXS even in the absence of FdU. Our data suggest a model for chromosome fragility in FXS in which the repeat impairs replication from an origin of replication (ORI) immediately adjacent to the repeat. The fact that the replication problem occurs even in the absence of FdU suggests that this phenomenon may have in vivo consequences, including perhaps accounting for the loss of the X chromosome containing the fragile site that causes Turner syndrome (45, X0) in female carriers of such alleles. Our data on FRAXA may also be germane for the other FdU-inducible fragile sites in humans, that we show here share many common features with FRAXA. C1 [Yudkin, Dmitry; Hayward, Bruce E.; Kumari, Daman; Usdin, Karen] NIDDK, Sect Gene Struct & Dis, Lab Cell & Mol Biol, Bethesda, MD 20892 USA. [Aladjem, Mirit I.] NCI, DNA Replicat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Yudkin, Dmitry] Inst Mol & Cellular Biol SB RAS, Dept Genom Divers & Evolut, Novosibirsk 630090, Russia. RP Usdin, K (reprint author), NIH, Bldg 8,Room 2A19,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. EM ku@helix.nih.gov RI Yudkin, Dmitry/N-6135-2015; Aladjem, Mirit/G-2169-2010 OI Yudkin, Dmitry/0000-0002-8940-9173; Aladjem, Mirit/0000-0002-1875-3110 FU National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health; Center for Cancer Research, National Cancer Institute, National Institutes of Health; Russian Foundation for Basic Research FX This work was supported by a grant from the intramural program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health to K U.; from the Center for Cancer Research, National Cancer Institute, National Institutes of Health to M.A. and from the Russian Foundation for Basic Research to D.Y. NR 57 TC 14 Z9 14 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2014 VL 23 IS 11 BP 2940 EP 2952 DI 10.1093/hmg/ddu006 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AH9ST UT WOS:000336483200012 PM 24419320 ER PT J AU Moayyeri, A Hsu, YH Karasik, D Estrada, K Xiao, SM Nielson, C Srikanth, P Giroux, S Wilson, SG Zheng, HF Smith, AV Pye, SR Leo, PJ Teumer, A Hwang, JY Ohlsson, C McGuigan, F Minster, RL Hayward, C Olmos, JM Lyytikainen, LP Lewis, JR Swart, KMA Masi, L Oldmeadow, C Holliday, EG Cheng, SL van Schoor, NM Harvey, NC Kruk, M Fabiola Del Greco, M Igl, W Trummer, O Grigoriou, E Luben, R Liu, CT Zhou, YH Oei, L Medina-Gomez, C Zmuda, J Tranah, G Brown, SJ Williams, FM Soranzo, N Jakobsdottir, J Siggeirsdottir, K Holliday, KL Hannemann, A Go, MJ Garcia, M Polasek, O Laaksonen, M Zhu, K Enneman, AW McEvoy, M Peel, R Sham, PC Jaworski, M Johansson, A Hicks, AA Pludowski, P Scott, R Dhonukshe-Rutten, RAM van der Velde, N Kahonen, M Viikari, JS Sievanen, H Raitakari, OT Gonzalez-Macias, J Hernandez, JL Mellstroom, D Ljunggren, O Cho, YS Volker, U Nauck, M Homuth, G Volzke, H Haring, R Brown, MA McCloskey, E Nicholson, GC Eastell, R Eisman, JA Jones, G Reid, IR Dennison, EM Wark, J Boonen, S Vanderschueren, D Wu, FCW Aspelund, T Richards, JB Bauer, D Hofman, A Khaw, KT Dedoussis, G Obermayer-Pietsch, B Gyllensten, U Pramstaller, PP Lorenc, RS Cooper, C Kung, AWC Lips, P Alen, M Attia, J Brandi, ML de Groot, LCPGM Lehtimaki, T Riancho, JA Campbell, H Liu, YM Harris, TB Akesson, K Karlsson, M Lee, JY Wallaschofski, H Duncan, EL O'Neill, TW Gudnason, V Spector, TD Rousseau, F Orwoll, E Cummings, SR Wareham, NJ Rivadeneira, F Uitterlinden, AG Prince, RL Kiel, DP Reeve, J Kaptoge, SK AF Moayyeri, Alireza Hsu, Yi-Hsiang Karasik, David Estrada, Karol Xiao, Su-Mei Nielson, Carrie Srikanth, Priya Giroux, Sylvie Wilson, Scott G. Zheng, Hou-Feng Smith, Albert V. Pye, Stephen R. Leo, Paul J. Teumer, Alexander Hwang, Joo-Yeon Ohlsson, Claes McGuigan, Fiona Minster, Ryan L. Hayward, Caroline Olmos, Jose M. Lyytikaeinen, Leo-Pekka Lewis, Joshua R. Swart, Karin M. A. Masi, Laura Oldmeadow, Chris Holliday, Elizabeth G. Cheng, Sulin van Schoor, Natasja M. Harvey, Nicholas C. Kruk, Marcin Fabiola Del Greco, M. Igl, Wilmar Trummer, Olivia Grigoriou, Efi Luben, Robert Liu, Ching-Ti Zhou, Yanhua Oei, Ling Medina-Gomez, Carolina Zmuda, Joseph Tranah, Greg Brown, Suzanne J. Williams, Frances M. Soranzo, Nicole Jakobsdottir, Johanna Siggeirsdottir, Kristin Holliday, Kate L. Hannemann, Anke Go, Min Jin Garcia, Melissa Polasek, Ozren Laaksonen, Marika Zhu, Kun Enneman, Anke W. McEvoy, Mark Peel, Roseanne Sham, Pak Chung Jaworski, Maciej Johansson, Asa Hicks, Andrew A. Pludowski, Pawel Scott, Rodney Dhonukshe-Rutten, Rosalie A. M. van der Velde, Nathalie Kaehoenen, Mika Viikari, Jorma S. Sievaenen, Harri Raitakari, Olli T. Gonzalez-Macias, Jesus Hernandez, Jose L. Mellstroem, Dan Ljunggren, Oesten Cho, Yoon Shin Voelker, Uwe Nauck, Matthias Homuth, Georg Voelzke, Henry Haring, Robin Brown, Matthew A. McCloskey, Eugene Nicholson, Geoffrey C. Eastell, Richard Eisman, John A. Jones, Graeme Reid, Ian R. Dennison, Elaine M. Wark, John Boonen, Steven Vanderschueren, Dirk Wu, Frederick C. W. Aspelund, Thor Richards, J. Brent Bauer, Doug Hofman, Albert Khaw, Kay-Tee Dedoussis, George Obermayer-Pietsch, Barbara Gyllensten, Ulf Pramstaller, Peter P. Lorenc, Roman S. Cooper, Cyrus Kung, Annie Wai Chee Lips, Paul Alen, Markku Attia, John Luisa Brandi, Maria de Groot, Lisette C. P. G. M. Lehtimaeki, Terho Riancho, Jose A. Campbell, Harry Liu, Yongmei Harris, Tamara B. Akesson, Kristina Karlsson, Magnus Lee, Jong-Young Wallaschofski, Henri Duncan, Emma L. O'Neill, Terence W. Gudnason, Vilmundur Spector, Timothy D. Rousseau, Francois Orwoll, Eric Cummings, Steven R. Wareham, Nick J. Rivadeneira, Fernando Uitterlinden, Andre G. Prince, Richard L. Kiel, Douglas P. Reeve, Jonathan Kaptoge, Stephen K. TI Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium SO HUMAN MOLECULAR GENETICS LA English DT Article ID X-RAY ABSORPTIOMETRY; QUANTITATIVE ULTRASOUND; MINERAL DENSITY; OSTEOPOROSIS; FRACTURE; RISK; DENSITOMETRY; PHENOTYPES; CALCANEUS; WOMEN AB Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology. C1 [Moayyeri, Alireza; Luben, Robert; Khaw, Kay-Tee; Reeve, Jonathan; Kaptoge, Stephen K.] Univ Cambridge, Dept Publ Hlth Primary Care, Cambridge CB1 8RN, England. [Moayyeri, Alireza; Wilson, Scott G.; Williams, Frances M.; Richards, J. Brent; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA. [Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Enneman, Anke W.; van der Velde, Nathalie; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Estrada, Karol] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit,Dept Med, Boston, MA USA. [Estrada, Karol] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Netherlands Consortium Healthy Aging NCHA, Netherlands Genom Initiat NGI, Leiden, Netherlands. [Xiao, Su-Mei; Kung, Annie Wai Chee] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Xiao, Su-Mei; Kung, Annie Wai Chee] Univ Hong Kong, Res Ctr Heart Brain Hormone & Healthy Aging, Hong Kong, Hong Kong, Peoples R China. [Sham, Pak Chung] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Sham, Pak Chung] Univ Hong Kong, Ctr Reprod Dev & Growth, Hong Kong, Hong Kong, Peoples R China. [Nielson, Carrie; Srikanth, Priya] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Orwoll, Eric] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. [Giroux, Sylvie; Rousseau, Francois] HSFA, Ctr Rech CHU Quebec, Quebec City, PQ, Canada. [Wilson, Scott G.; Lewis, Joshua R.; Zhu, Kun; Prince, Richard L.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Wilson, Scott G.; Lewis, Joshua R.; Brown, Suzanne J.; Zhu, Kun; Prince, Richard L.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA 6000, Australia. [Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Med, Montreal, PQ, Canada. [Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Human Genet, Montreal, PQ, Canada. [Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Epidemiol, Montreal, PQ, Canada. [Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Biostat, Montreal, PQ, Canada. [Smith, Albert V.; Jakobsdottir, Johanna; Siggeirsdottir, Kristin; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Siggeirsdottir, Kristin; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Pye, Stephen R.; Holliday, Kate L.; O'Neill, Terence W.] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester M13 9WL, Lancs, England. [Wu, Frederick C. W.] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Androl Res Unit,Dev & Regenerat Biomed Res Grp, Manchester M13 9WL, Lancs, England. [Leo, Paul J.; Brown, Matthew A.; Duncan, Emma L.] Univ Queensland, Diamantina Inst, Human Genet Grp, Brisbane, Qld, Australia. [Teumer, Alexander; Voelker, Uwe; Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany. [Hannemann, Anke; Nauck, Matthias; Haring, Robin; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany. [Hannemann, Anke; Nauck, Matthias; Haring, Robin; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Lab Med, Greifswald, Germany. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Hwang, Joo-Yeon; Go, Min Jin; Lee, Jong-Young] NIH, Ctr Genome Sci, Chungcheongbuk, South Korea. [Ohlsson, Claes; Mellstroem, Dan] Univ Gothenburg, Ctr Bone & Arthrit Res, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden. [McGuigan, Fiona; Akesson, Kristina; Karlsson, Magnus] Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci, Malmo, Sweden. [Karlsson, Magnus] Lund Univ, Dept Orthopaed, Malmo, Sweden. [Minster, Ryan L.] Univ Pittsburgh, Dept Human Genet, Pitsburgh, PA USA. [Zmuda, Joseph] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pitsburgh, PA USA. [Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Univ Cantabria, Dept Med, E-39005 Santander, Spain. [Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Hosp Univ Marques Valdecilla, Dept Internal Med, Santander, Spain. [Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Inst Formac & Invest Marques Valdecilla IFIMAV, Santander, Spain. [Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Univ Tampere, Dept Clin Chem, Sch Med, FIN-33101 Tampere, Finland. [Kaehoenen, Mika] Univ Tampere, Dept Clin Physiol, Sch Med, FIN-33101 Tampere, Finland. [Swart, Karin M. A.; van Schoor, Natasja M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Lips, Paul] Vrije Univ Amsterdam, Med Ctr, Dept Endocrinol, Amsterdam, Netherlands. [Lips, Paul] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Masi, Laura] Univ Florence, Metab Bone Dis Unit AOUC, Florence, Italy. [Luisa Brandi, Maria] Univ Florence, Dept Surg & Translat Med, Florence, Italy. [Oldmeadow, Chris; Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Scott, Rodney; Attia, John] Univ Newcastle, John Hunter Hosp, Newcastle, NSW 2300, Australia. [Oldmeadow, Chris; Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Scott, Rodney; Attia, John] Hunter Med Res Inst, Newcastle, NSW, Australia. [Cheng, Sulin] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland. [Harvey, Nicholas C.; Dennison, Elaine M.; Cooper, Cyrus] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Kruk, Marcin; Jaworski, Maciej; Pludowski, Pawel; Lorenc, Roman S.] Childrens Mem Hlth Inst, Dept Biochem Radioimmunol & Expt Med, Warsaw, Poland. [Fabiola Del Greco, M.; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Fabiola Del Greco, M.; Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany. [Igl, Wilmar; Johansson, Asa; Gyllensten, Ulf] SciLifeLab, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Ljunggren, Oesten] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Trummer, Olivia; Obermayer-Pietsch, Barbara] Med Univ Graz, Div Endocrinol & Metab, Dept Internal Med, Graz, Austria. [Grigoriou, Efi; Dedoussis, George] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. [Liu, Ching-Ti; Zhou, Yanhua] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Tranah, Greg; Bauer, Doug; Cummings, Steven R.] Univ Calif San Francisco, San Francisco Coordinating Ctr, Calif Pacif Med Ctr Res Inst, San Francisco, CA 94143 USA. [Tranah, Greg; Bauer, Doug; Cummings, Steven R.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Soranzo, Nicole] Wellcome Trust Res Labs, Sanger Inst, Cambridge, England. [Garcia, Melissa; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Polasek, Ozren] Univ Split, Sch Med, Dept Publ Hlth, Split, Croatia. [Laaksonen, Marika] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland. [Dhonukshe-Rutten, Rosalie A. M.; de Groot, Lisette C. P. G. M.] Wageningen Univ, Dept Human Nutr, NL-6700 AP Wageningen, Netherlands. [van der Velde, Nathalie] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Sect Geriatr, NL-1105 AZ Amsterdam, Netherlands. [Kaehoenen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Viikari, Jorma S.] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Viikari, Jorma S.] Univ Turku, Dept Med, Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Sievaenen, Harri] UKK Inst Hlth Promot Res, Tampere, Finland. [Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea. [McCloskey, Eugene] Univ Sheffield, Natl Inst Hlth & Res NIHR, Musculoskeletal Biomed Res Unit, Sheffield, S Yorkshire, England. [McCloskey, Eugene; Eastell, Richard] Univ Sheffield, Acad Unit Bone Metab, Metab Bone Ctr, Sheffield, S Yorkshire, England. [Nicholson, Geoffrey C.] Univ Queensland, Rural Clin Sch, Toowoomba, Qld, Australia. [Eisman, John A.] Garvan Inst Med Res, Clin Translat & Adv Educ & Osteoporosis & Bone Bi, Sydney, NSW, Australia. [Eisman, John A.] Univ New S Wales, Dept ofMedicine, Kensington, NSW 2033, Australia. [Eisman, John A.] Univ Notre Dame, Sch Med Sydney, Sydney, NSW, Australia. [Eisman, John A.] St Vincents Hosp, Dept Endocrinol, Sydney, NSW 2010, Australia. [Jones, Graeme] Univ Tasmania, Menzies Res Inst, Hobart, Tas, Australia. [Reid, Ian R.] Univ Auckland, Auckland 1, New Zealand. [Wark, John] Royal Melbourne Hosp, Dept Clin Sci, Melbourne, Vic, Australia. [Boonen, Steven] Katholieke Univ Leuven, Div Geriatr Med, Leuven, Belgium. [Boonen, Steven] Katholieke Univ Leuven, Ctr Metab Bone Dis, Leuven, Belgium. [Vanderschueren, Dirk] Katholieke Univ Leuven, Dept Androl & Endocrinol, Leuven, Belgium. [Cooper, Cyrus; Reeve, Jonathan] Univ Oxford, NIHR Musculoskeletal Biomed Res Unit, Inst Musculoskeletal Sci, Oxford, England. [Alen, Markku] Oulu Univ Hosp, Dept Rehabil Med, Oulu, Finland. [Alen, Markku] Inst Hlth Sci, Oulu, Finland. [Campbell, Harry] Ctr Populat Hlth Sci, Sch Med, Edinburgh, Midlothian, Scotland. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC USA. [Duncan, Emma L.] Royal Brisbane & Womens Hosp, Dept Endocrinol, Brisbane, Qld, Australia. [Rousseau, Francois] Univ Laval, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ, Canada. [Rousseau, Francois] Univ Laval, APOGEE Net, CanGeneTest Network Genet Hlth Serv & Policy, Quebec City, PQ, Canada. [Wareham, Nick J.] Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Reeve, Jonathan; Kaptoge, Stephen K.] Strangeways Res Lab, Cambridge CB1 4RN, England. RP Kaptoge, SK (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England. EM stephen@srl.cam.ac.uk RI Lyytikainen, Leo-Pekka/C-8544-2016; Oei, Ling/E-8163-2013; Smith, Albert/K-5150-2015; Pye, Stephen/D-9236-2011; Hayward, Caroline/M-8818-2016; Hicks, Andrew/E-9518-2017; Polasek, Ozren/B-6002-2011; Rivadeneira, Fernando/O-5385-2015; Duncan, Emma/L-1224-2013; Aspelund, Thor/C-5983-2008; Pramstaller, Peter/C-2357-2008; Nicholson, Geoffrey/F-1901-2010; Leo, Paul/B-3470-2011; Lewis, Joshua/D-5077-2013; Moayyeri, Alireza/N-3332-2014; Reeve, Jonathan/C-7551-2012; Gudnason, Vilmundur/K-6885-2015 OI Johansson, Asa/0000-0002-2915-4498; Brown, Matthew A/0000-0003-0538-8211; de Groot, Lisette /0000-0003-2778-2789; Luben, Robert/0000-0002-5088-6343; Soranzo, Nicole/0000-0003-1095-3852; Karasik, David/0000-0002-8826-0530; Medina-Gomez, Carolina/0000-0001-7999-5538; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Oei, Ling/0000-0003-3523-458X; Smith, Albert/0000-0003-1942-5845; Pye, Stephen/0000-0002-7263-2897; Hayward, Caroline/0000-0002-9405-9550; Hicks, Andrew/0000-0001-6320-0411; van der Velde, Nathalie/0000-0002-6477-6209; Kiel, Douglas/0000-0001-8474-0310; Williams, Frances/0000-0002-2998-2744; Polasek, Ozren/0000-0002-5765-1862; Rivadeneira, Fernando/0000-0001-9435-9441; Duncan, Emma/0000-0002-8143-4403; Aspelund, Thor/0000-0002-7998-5433; Nicholson, Geoffrey/0000-0002-0152-1153; Leo, Paul/0000-0001-8325-4134; Lewis, Joshua/0000-0003-1003-8443; Moayyeri, Alireza/0000-0002-9143-2161; Reeve, Jonathan/0000-0002-4364-2682; Gudnason, Vilmundur/0000-0001-5696-0084 FU European Commission [HEALTH-F2-2008-201865-GEFOS] FX This research and the Genetic Factors for Osteoporosis (GEFOS) consortium have been funded by the European Commission (HEALTH-F2-2008-201865-GEFOS). Several other sources of funding and people have supported work in the contributing cohorts as acknowledged in Supplementary Material, Table S2. NR 43 TC 27 Z9 28 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2014 VL 23 IS 11 BP 3054 EP 3068 DI 10.1093/hmg/ddt675 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AH9ST UT WOS:000336483200021 PM 24430505 ER PT J AU Nguyen, TA Menendez, D Resnick, MA Anderson, CW AF Nguyen, Thuy-Ai Menendez, Daniel Resnick, Michael A. Anderson, Carl W. TI Mutant TP53 Posttranslational Modifications: Challenges and Opportunities SO HUMAN MUTATION LA English DT Review DE TP53; p53; phosphorylation; acetylation; methylation; ubiquitylation; transcription ID DNA-DAMAGE RESPONSE; TUMOR-SUPPRESSOR PROTEIN; WILD-TYPE P53; PROSTATE-CANCER CELLS; PROLYL ISOMERASE PIN1; LI-FRAUMENI-SYNDROME; POLO-LIKE KINASES; FUNCTIONS IN-VIVO; TETRAMERIZATION DOMAIN; IONIZING-RADIATION AB The wild-type (WT) human p53 (TP53) tumor suppressor can be posttranslationally modified at over 60 of its 393 residues. These modifications contribute to changes in TP53 stability and in its activity as a transcription factor in response to a wide variety of intrinsic and extrinsic stresses in part through regulation of protein-protein and protein-DNA interactions. The TP53 gene frequently is mutated in cancers, and in contrast to most other tumor suppressors, the mutations are mostly missense often resulting in the accumulation of mutant (MUT) protein, which may have novel or altered functions. Most MUT TP53s can be posttranslationally modified at the same residues as in WT TP53. Strikingly, however, codons for modified residues are rarely mutated in human tumors, suggesting that TP53 modifications are not essential for tumor suppression activity. Nevertheless, these modifications might alter MUT TP53 activity and contribute to a gain-of-function leading to increased metastasis and tumor progression. Furthermore, many of the signal transduction pathways that result in TP53 modifications are altered or disrupted in cancers. Understanding the signaling pathways that result in TP53 modification and the functions of these modifications in both WT TP53 and its many MUT forms may contribute to more effective cancer therapies. C1 [Nguyen, Thuy-Ai; Menendez, Daniel; Resnick, Michael A.; Anderson, Carl W.] NIEHS, Mol Genet Lab, Chromosome Stabil Sect, Res Triangle Pk, NC 27709 USA. [Anderson, Carl W.] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA. RP Anderson, CW (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. EM cwa@bnl.gov FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX We thank K. Bebenek for assistance with structural representations of PTM residues, and D. W. Meek (University of Dundee) and K. Sakaguchi (Hokkaido University) for comments and suggestions. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 179 TC 15 Z9 16 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD JUN PY 2014 VL 35 IS 6 SI SI BP 738 EP 755 DI 10.1002/humu.22506 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA AI1NX UT WOS:000336618900010 PM 24395704 ER PT J AU Ouimet, MC Brown, TG Guo, F Klauer, SG Simons-Morton, BG Fang, YJ Lee, SE Gianoulakis, C Dingus, TA AF Ouimet, Marie Claude Brown, Thomas G. Guo, Feng Klauer, Sheila G. Simons-Morton, Bruce G. Fang, Youjia Lee, Suzanne E. Gianoulakis, Christina Dingus, Thomas A. TI Higher Crash and Near-Crash Rates in Teenaged Drivers With Lower Cortisol Response An 18-Month Longitudinal, Naturalistic Study SO JAMA PEDIATRICS LA English DT Article ID DELINQUENT MALE-ADOLESCENTS; PITUITARY-ADRENAL AXIS; LOW SALIVARY CORTISOL; VIOLENT OFFENDERS; RISK-TAKING; EXTERNALIZING BEHAVIOR; NOVICE DRIVERS; EARLY RELAPSE; AGGRESSION; BOYS AB IMPORTANCE Road traffic crashes are one of the leading causes of injury and death among teenagers worldwide. Better understanding of the individual pathways to driving risk may lead to better-targeted intervention in this vulnerable group. OBJECTIVE To examine the relationship between cortisol, a neurobiological marker of stress regulation linked to risky behavior, and driving risk. DESIGN, SETTING, AND PARTICIPANTS The Naturalistic Teenage Driving Study was designed to continuously monitor the driving behavior of teenagers by instrumenting vehicles with kinematic sensors, cameras, and a global positioning system. During 2006-2008, a community sample of 42 newly licensed 16-year-old volunteer participants in the United States was recruited and driving behavior monitored. It was hypothesized in teenagers that higher cortisol response to stress is associated with (1) lower crash and near-crash (CNC) rates during their first 18 months of licensure and (2) faster reduction in CNC rates over time. MAIN OUTCOMES AND MEASURES Participants' cortisol response during a stress-inducing task was assessed at baseline, followed by measurement of their involvement in CNCs and driving exposure during their first 18 months of licensure. Mixed-effect Poisson longitudinal regression models were used to examine the association between baseline cortisol response and CNC rates during the follow-up period. RESULTS Participants with a higher baseline cortisol response had lower CNC rates during the follow-up period (exponential of the regression coefficient, 0.93; 95% CI, 0.88-0.98) and faster decrease in CNC rates over time (exponential of the regression coefficient, 0.98; 95%, CI, 0.96-0.99). CONCLUSIONS AND RELEVANCE Cortisol is a neurobiological marker associated with teenaged-driving risk. As in other problem-behavior fields, identification of an objective marker of teenaged-driving risk promises the development of more personalized intervention approaches. C1 [Ouimet, Marie Claude] Univ Sherbrooke, Fac Med & Hlth Sci, Longueuil, PQ J4K 0A8, Canada. [Ouimet, Marie Claude; Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Brown, Thomas G.; Gianoulakis, Christina] McGill Univ, Res Ctr, Douglas Hosp, Montreal, PQ, Canada. [Guo, Feng; Klauer, Sheila G.; Lee, Suzanne E.; Dingus, Thomas A.] Virginia Tech, Transportat Inst, Blacksburg, VA USA. [Guo, Feng; Fang, Youjia] Virginia Tech, Dept Stat, Blacksburg, VA USA. RP Ouimet, MC (reprint author), Univ Sherbrooke, Fac Med & Hlth Sci, 150 Charles Le Moyne Pl,Ste 200, Longueuil, PQ J4K 0A8, Canada. EM marie.claude.ouimet@usherbrooke.ca OI Simons-Morton, Bruce/0000-0003-1099-6617 FU National Institutes of Health [N01-HD-5-3405]; National Highway Traffic Safety Administration; Quebec Health Research Fund (Fonds de recherche du Quebec-Sante) FX This research was supported by the Intramural Research Program of the National Institutes of Health (grant N01-HD-5-3405) and by the National Highway Traffic Safety Administration. Cortisol sampling kits and analyses were provided by the Douglas Hospital Research Centre. Dr Ouimet was supported through a career grant from the Quebec Health Research Fund (Fonds de recherche du Quebec-Sante). NR 50 TC 8 Z9 8 U1 1 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD JUN PY 2014 VL 168 IS 6 BP 517 EP 522 DI 10.1001/jamapediatrics.2013.5387 PG 6 WC Pediatrics SC Pediatrics GA AI4MZ UT WOS:000336840800009 PM 24710522 ER PT J AU Bousquet, J Gern, JE Martinez, FD Anto, JM Johnson, CC Holt, PG Lemanske, RF Le Souef, PN Tepper, RS von Mutius, ERM Arshad, SH Bacharier, LB Becker, A Belanger, K Bergstrom, A Bernstein, DI Cabana, MD Carroll, KN Castro, M Cooper, PJ Gillman, MW Gold, DR Henderson, J Heinrich, J Hong, SJ Jackson, DJ Keil, T Kozyrskyj, AL Carlsen, KCL Miller, RL Momas, I Morgan, WJ Noel, P Ownby, DR Pinart, M Ryan, PH Schwaninger, JM Sears, MR Simpson, A Smit, HA Stern, DA Subbarao, P Valenta, R Wang, XB Weiss, ST Wood, R Wright, AL Wright, RJ Togias, A Gergen, PJ AF Bousquet, Jean Gern, James E. Martinez, Fernando D. Anto, Josep M. Johnson, Christine C. Holt, Patrick G. Lemanske, Robert F., Jr. Le Souef, Peter N. Tepper, Robert S. von Mutius, Erika R. M. Arshad, S. Hasan Bacharier, Leonard B. Becker, Allan Belanger, Kathleen Bergstrom, Anna Bernstein, David I. Cabana, Michael D. Carroll, Kecia N. Castro, Mario Cooper, Philip J. Gillman, Matthew W. Gold, Diane R. Henderson, John Heinrich, Joachim Hong, Soo-Jong Jackson, Daniel J. Keil, Thomas Kozyrskyj, Anita L. Carlsen, Karin C. Lodrup Miller, Rachel L. Momas, Isabelle Morgan, Wayne J. Noel, Patricia Ownby, Dennis R. Pinart, Mariona Ryan, Patrick H. Schwaninger, Julie M. Sears, Malcolm R. Simpson, Angela Smit, Henriette A. Stern, Debra A. Subbarao, Padmaja Valenta, Rudolf Wang, Xiaobin Weiss, Scott T. Wood, Robert Wright, Anne L. Wright, Rosalind J. Togias, Alkis Gergen, Peter J. TI Birth cohorts in asthma and allergic diseases: Report of a NIAID/NHLBI/MeDALL joint workshop SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allergy; asthma; birth cohorts; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Disease (NIAID); Mechanisms of the Development of Allergy (MeDALL) ID EXHALED NITRIC-OXIDE; WHEEZING RHINOVIRUS ILLNESSES; 1ST 6 YEARS; LUNG-FUNCTION; YOUNG-CHILDREN; EARLY-LIFE; AIRWAY RESPONSIVENESS; PRESCHOOL-CHILDREN; CHILDHOOD ASTHMA; ATOPIC DISEASES AB Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts. C1 [Bousquet, Jean] Univ Hosp, Montpellier, France. [Bousquet, Jean] INSERM, U1018, Villejuif, France. [Gern, James E.; Lemanske, Robert F., Jr.; Jackson, Daniel J.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Martinez, Fernando D.; Stern, Debra A.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA. [Anto, Josep M.; Pinart, Mariona] CREAL, Barcelona, Spain. [Anto, Josep M.; Pinart, Mariona] IMIM Hosp del Mar Res Inst, Barcelona, Spain. [Anto, Josep M.; Pinart, Mariona] CIBERESP, Barcelona, Spain. [Anto, Josep M.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain. [Johnson, Christine C.] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA. [Holt, Patrick G.] Univ Western Australia, Telethon Inst Child Hlth Res, Brisbane, Qld, Australia. [Holt, Patrick G.] Univ Queensland, Queensland Childrens Med Res Inst, Brisbane, Qld, Australia. [Le Souef, Peter N.] Univ Western Australia, Princess Margaret Hosp Children, Sch Paediat & Child Hlth, Perth, WA 6009, Australia. [Tepper, Robert S.] Indiana Univ Sch Med, James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. [von Mutius, Erika R. M.] Univ Munich, Dr von Hauner Childrens Hosp, D-81377 Munich, Germany. [Arshad, S. Hasan] Univ Southampton, Fac Med, Isle Of Wight, England. [Arshad, S. Hasan] David Hide Asthma & Allergy Res Ctr, Isle Of Wight, England. [Bacharier, Leonard B.] Washington Univ, St Louis, MO 63130 USA. [Bacharier, Leonard B.] St Louis Childrens Hosp, St Louis, MO USA. [Becker, Allan] Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada. [Belanger, Kathleen] Yale Univ, Sch Publ Hlth, Sch Med, Ctr Perinatal Pediat & Environm Epidemiol, New Haven, CT USA. [Bergstrom, Anna] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Bernstein, David I.] Univ Cincinnati, Coll Med, Div Immunol Allergy & Rheumatol, Cincinnati, OH 45221 USA. [Cabana, Michael D.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [Cabana, Michael D.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Carroll, Kecia N.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. [Castro, Mario] Washington Univ, Sch Med, Div Pulm & Crit Care Med, St Louis, MO 63130 USA. [Cooper, Philip J.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Cooper, Philip J.] Pontificia Univ Catolica Ecuador, Escuela Biol, Quito, Ecuador. [Gillman, Matthew W.] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Gold, Diane R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA. [Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Henderson, John] Univ Bristol, Sch Social & Community Med, Bristol BS8 1TH, Avon, England. [Heinrich, Joachim] German Ctr Environm Hlth, Helmholtz Zentrum, Inst Epidemiol 1, Munich, Germany. [Hong, Soo-Jong] Univ Ulsan, Coll Med, Asan Med Ctr,Dept Pediat, Res Ctr Standardizat Allerg Dis,Childhood Asthma, Seoul, South Korea. [Keil, Thomas] Charite, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany. [Keil, Thomas] Univ Wurzburg, Inst Clin Epidemiol & Biometry, Wurzburg, Germany. [Kozyrskyj, Anita L.] Univ Alberta, Dept Pediat, Fac Med & Dent, Edmonton, AB, Canada. [Carlsen, Karin C. Lodrup] Oslo Univ Hosp, Oslo, Norway. [Carlsen, Karin C. Lodrup] Univ Oslo, N-0316 Oslo, Norway. [Miller, Rachel L.] Columbia Univ, Dept Med, Div Pulm Allergy & Critcare Med, New York, NY USA. [Momas, Isabelle] Paris Descartes Univ, Dept Publ Hlth & Biostat, Paris, France. [Momas, Isabelle] Paris Municipal Dept Social Act Childhood & Hlth, Paris, France. [Miller, Rachel L.] Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA. [Noel, Patricia] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. [Ownby, Dennis R.] Georgia Regents Univ, Augusta, GA USA. [Ryan, Patrick H.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA. [Schwaninger, Julie M.; Togias, Alkis; Gergen, Peter J.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Sears, Malcolm R.] McMaster Univ, AstraZeneca Chair Resp Epidemiol, Dept Med, Hamilton, ON L8S 4L8, Canada. [Simpson, Angela] Univ Manchester, Manchester Acad Hlth Sci Ctr, Ctr Resp & Allergy, Inst Inflammat & Repair, Manchester M13 9PL, Lancs, England. [Simpson, Angela] Univ Hosp South Manchester, Manchester, Lancs, England. [Smit, Henriette A.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Subbarao, Padmaja] Univ Toronto, Dept Pediat, Toronto, ON M5S 1A1, Canada. [Valenta, Rudolf] Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Dept Pathophysiol & Allergy Res, Div Immunopathol, Vienna, Austria. [Wang, Xiaobin] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Weiss, Scott T.] Harvard Univ, Sch Med, Dept Med, Channing Div Network Med, Boston, MA USA. [Wood, Robert] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Wright, Anne L.] Univ Arizona, Coll Med, Arizona Resp Ctr, Tucson, AZ USA. [Wright, Anne L.] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ USA. [Wright, Rosalind J.] Icahn Sch Med, Dept Pediat, Mt Sinai, NY USA. [Wright, Rosalind J.] Icahn Sch Med, Mindich Child Hlth & Dev Inst, Mt Sinai, NY USA. RP Bousquet, J (reprint author), Ctr Hosp Montpellier, F-34295 Montpellier 05, France. EM jean.bousquet@inserm.fr RI Ryan, Patrick /L-7062-2015; Pinart, Mariona/L-1931-2015; Anto, J/H-2676-2014; Holt, Patrick/H-1548-2011; OI Pinart, Mariona/0000-0002-8223-1325; Anto, J/0000-0002-4736-8529; Holt, Patrick/0000-0003-1193-0935; Simpson, Angela/0000-0003-2733-6666; von Mutius, Erika/0000-0002-8893-4515 FU MeDALL (Mechanisms of the Development of Allergy, EU) [261357]; Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases; Division of Lung Diseases, National Heart, Lung, and Blood Institute FX Supported by MeDALL (Mechanisms of the Development of Allergy, EU FP7 Grant agreement no. 261357). The workshop was supported in part by funds from the Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, and the Division of Lung Diseases, National Heart, Lung, and Blood Institute. NR 94 TC 33 Z9 33 U1 0 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2014 VL 133 IS 6 BP 1535 EP 1546 DI 10.1016/j.jaci.2014.01.018 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA AI2FI UT WOS:000336672500004 PM 24636091 ER PT J AU Moore, WC Hastie, AT Li, XN Li, HS Busse, WW Jarjour, NN Wenzel, SE Peters, SP Meyers, DA Bleecker, ER AF Moore, Wendy C. Hastie, Annette T. Li, Xingnan Li, Huashi Busse, William W. Jarjour, Nizar N. Wenzel, Sally E. Peters, Stephen P. Meyers, Deborah A. Bleecker, Eugene R. CA Natl Heart Lung Blood Inst Severe TI Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Severe Asthma Research Program; severe asthma; sputum; eosinophils; neutrophils; phenotype; cluster analysis ID RANDOMIZED CONTROLLED-TRIAL; AIRWAY INFLAMMATION; REFRACTORY ASTHMA; EOSINOPHIL COUNTS; RESEARCH-PROGRAM; DOUBLE-BLIND; CORTICOSTEROIDS; CLARITHROMYCIN; EXACERBATIONS; PREVENTION AB Background: Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (>= 2%) and neutrophil (>= 40%) percentages had characteristics of very severe asthma. Objective: To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. Methods: Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis. Results: Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment. Conclusion: This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation. C1 [Moore, Wendy C.; Hastie, Annette T.; Li, Xingnan; Li, Huashi; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA. [Moore, Wendy C.; Hastie, Annette T.; Li, Xingnan; Li, Huashi; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.] Sect Pulm Crit Care Allergy & Immunol Dis, Winston Salem, NC USA. [Busse, William W.; Jarjour, Nizar N.] Univ Wisconsin, Sch Med & Publ Hlth, Allergy Pulm & Crit Care Div, Madison, WI 53706 USA. [Wenzel, Sally E.] Univ Pittsburgh, Sch Med Pulm Allergy & Crit Care Med, Bethesda, MD USA. [Natl Heart Lung Blood Inst Severe] NHLBI, Severe Asthma Res Program, Bethesda, MD 20892 USA. RP Moore, WC (reprint author), Wake Forest Sch Med, Dept Med, Ctr Genom & Personalized Med Res, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM wmoore@wakehealth.edu FU National Heart, Lung, and Blood Institute (NHLBI); [HL69116]; [HL69167]; [HL69174]; [UL1RR025011] FX The Severe Asthma Research Program (SARP) is a multicenter asthma research group funded by the National Heart, Lung, and Blood Institute (NHLBI) and consisting of the following universities (principal investigators): Brigham & Women's Hospital-Elliot Israel; Cleveland Clinic-Serpil C. Erzurum; Emory University-Anne M. Fitzpatrick; Imperial College School of Medicine-Kian F. Chung; University of Pittsburgh-Sally E. Wenzel; University of Texas-Medical Branch-William J. Calhoun; University of Virginia-Benjamin Gaston, W. Gerald Teague; University of Wisconsin-William W. Busse; Wake Forest University-Eugene R. Bleecker; Washington University in St Louis-Mario Castro; Data Coordinating Center-Douglas Curran-Everett; NHLBI-Patricia Noel, Robert Smith.; Supported by grants HL69116, HL69167, HL69174, and UL1RR025011. NR 33 TC 79 Z9 80 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2014 VL 133 IS 6 BP 1557 EP + DI 10.1016/j.jaci.2013.10.011 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA AI2FI UT WOS:000336672500006 PM 24332216 ER PT J AU Jing, H Zhang, Q Zhang, Y Hill, BJ Dove, CG Gelfand, EW Atkinson, TP Uzel, G Matthews, HF Mustillo, PJ Lewis, DB Kavadas, FD Hanson, IC Kumar, AR Geha, RS Douek, DC Holland, SM Freeman, AF Su, HC AF Jing, Huie Zhang, Qian Zhang, Yu Hill, Brenna J. Dove, Christopher G. Gelfand, Erwin W. Atkinson, T. Prescott Uzel, Gulbu Matthews, Helen F. Mustillo, Peter J. Lewis, David B. Kavadas, Fotini D. Hanson, I. Celine Kumar, Ashish R. Geha, Raif S. Douek, Daniel C. Holland, Steven M. Freeman, Alexandra F. Su, Helen C. TI Somatic reversion in dedicator of cytokinesis 8 immunodeficiency modulates disease phenotype SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Dedicator of cytokinesis 8; reversion; somatic repair; recombination; gene conversion; intragenic single crossover; T cell; natural killer cell; allergy; immunodeficiency ID HYPER-IGE SYNDROME; STEM-CELL TRANSPLANTATION; DOCK8 DEFICIENCY; MUTATIONS; KINETICS; SURVIVAL; MEMORY; RECOMBINATION; MOSAICISM; HUMANS AB Background: Autosomal recessive loss-of-function mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency characterized by atopy, recurrent infections, and cancer susceptibility. A genotype-phenotype explanation for the variable disease expression is lacking. Objective: We investigated whether reversions contributed to the variable disease expression. Methods: Patients followed at the National Institutes of Health's Clinical Center were studied. We performed detailed genetic analyses and intracellular flow cytometry to detect DOCK8 protein expression within lymphocyte subsets. Results: We identified 17 of 34 DOCK8-deficient patients who had germline mutations with variable degrees of reversion caused by somatic repair. Somatic repair of the DOCK8 mutations resulted from second-site mutation, original-site mutation, gene conversion, and intragenic crossover. Higher degrees of reversion were associated with recombination-mediated repair. DOCK8 expression was restored primarily within antigen-experienced T cells or natural killer cells but less so in naive T or B cells. Several patients exhibited multiple different repair events. Patients who had reversions were older and had less severe allergic disease, although infection susceptibility persisted. No patients were cured without hematopoietic cell transplantation. Conclusions: In patients with DOCK8 deficiency, only certain combinations of germline mutations supported secondary somatic repair. Those patients had an ameliorated disease course with longer survival but still had fatal complications or required hematopoietic cell transplantation. These observations support the concept that some DOCK8-immunodeficient patients have mutable mosaic genomes that can modulate disease phenotype over time. C1 [Jing, Huie; Zhang, Qian; Zhang, Yu; Dove, Christopher G.; Su, Helen C.] NIAID, Lab Host Def, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Uzel, Gulbu; Holland, Steven M.; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Hill, Brenna J.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Gelfand, Erwin W.] Natl Jewish Hlth, Div Cell Biol, Dept Pediat, Div Allergy & Immunol, Denver, CO USA. [Atkinson, T. Prescott] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Mustillo, Peter J.] Nationwide Childrens Hosp, Div Infect Dis & Immunol, Columbus, OH USA. [Lewis, David B.] Stanford Univ, Div Immunol Allergy & Rheumatol, Dept Pediat, Stanford, CA 94305 USA. [Kavadas, Fotini D.] Alberta Childrens Prov Gen Hosp, Dept Pediat, Sect Clin Immunol & Allergy, Calgary, AB, Canada. [Kavadas, Fotini D.] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Hanson, I. Celine] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Allergy & Immunol, Houston, TX 77030 USA. [Kumar, Ashish R.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immune Deficiency, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA. [Kumar, Ashish R.] Univ Cincinnati, Cincinnati, OH 45221 USA. [Geha, Raif S.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Geha, Raif S.] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [Geha, Raif S.] Harvard Univ, Sch Med, Boston, MA USA. RP Su, HC (reprint author), NIAID, Lab Host Def, Div Intramural Res, NIH, Bldg 10CRC,Rm 5W3940,10CRC Ctr Dr,MSC 1456, Bethesda, MD 20892 USA. EM hsu@niaid.nih.gov RI Su, Helen/H-9541-2015; OI Su, Helen/0000-0002-5582-9110; Zhang, Qian/0000-0002-9040-3289 FU Intramural Research Program; Vaccine Research Center of the National Institutes of Health, National Institute of Allergy and Infectious Diseases FX Supported by the Intramural Research Program and the Vaccine Research Center of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 28 TC 25 Z9 25 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2014 VL 133 IS 6 BP 1667 EP 1675 DI 10.1016/j.jaci.2014.03.025 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA AI2FI UT WOS:000336672500020 PM 24797421 ER PT J AU Buckner, CM Moir, S Kardava, L Ho, J Santich, BH Kim, LJY Funk, EK Nelson, AK Winckler, B Chairez, CL Theobald-Whiting, NL Anaya-O'Brien, S Alimchandani, M Quezado, MM Yao, MD Kovacs, JA Chun, TW Fauci, AS Malech, HL De Ravin, SS AF Buckner, Clarisa M. Moir, Susan Kardava, Lela Ho, Jason Santich, Brian H. Kim, Leo Jin Young Funk, Emily K. Nelson, Amy K. Winckler, Britanny Chairez, Cheryl L. Theobald-Whiting, Narda L. Anaya-O'Brien, Sandra Alimchandani, Meghna Quezado, Martha M. Yao, Michael D. Kovacs, Joseph A. Chun, Tae-Wook Fauci, Anthony S. Malech, Harry L. De Ravin, Suk See TI CXCR4/IgG-expressing plasma cells are associated with human gastrointestinal tissue inflammation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Plasma cells; primary and infectious immunodeficiencies; gastrointestinal inflammation; inflammatory bowel disease; homing receptors ID ULCERATIVE-COLITIS; IMMUNOGLOBULIN-A; ANTIRETROVIRAL THERAPY; MONOCLONAL-ANTIBODIES; IMMUNE ACTIVATION; HIV-1 INFECTION; SECRETING CELLS; CROHNS-DISEASE; MUCOSAL; EXPRESSION AB Background: We previously reported abnormalities in circulating B cells in patients with chronic granulomatous disease (CGD) and those with HIV infection. Gastrointestinal complications are common to both diseases and likely involve perturbation of immune cells, including plasma cells (PCs). IgA is the most abundant immunoglobulin in the human body, with roles in protection and maintenance of intestinal homeostasis. IgA is produced primarily by PCs residing in mucosal tissues that are also thought to circulate in the blood. Objective: We sought to characterize and compare PCs in patients with infectious (HIV) and noninfectious (CGD and Crohn disease) diseases that have been associated with intestinal inflammation. Methods: Phenotypic and transcriptional analyses were performed on cells isolated from the blood and colon. Results: IgA-secreting CCR10-expressing PCs predominated in the guts of healthy subjects, whereas in patients with HIV, CGD, and Crohn disease, there was a significant increase in the proportion of IgG-secreting PCs. Where intestinal inflammation was present, IgG-secreting PCs expressed reduced levels of CCR10 and increased levels of CXCR4. The intensity of CXCR4 expression correlated with the frequency of IgG-expressing PCs and the frequency of CXCR4(+)/IgG(+) PCs was associated with the severity of intestinal inflammatory disease yet distinct from PCs and plasmablasts circulating in the blood. Conclusions: These findings suggest that regardless of the underlying disease, the presence of CXCR4(+)/IgG(+) PCs in the gut is a strong yet localized indicator of intestinal inflammation. Furthermore, our findings suggest that CXCR4(+)/IgG(+) PCs might play a role in immune cell homeostasis during inflammatory processes of the gut. C1 [Buckner, Clarisa M.; Moir, Susan; Kardava, Lela; Ho, Jason; Santich, Brian H.; Kim, Leo Jin Young; Funk, Emily K.; Nelson, Amy K.; Chairez, Cheryl L.; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. [Winckler, Britanny; Theobald-Whiting, Narda L.; Anaya-O'Brien, Sandra; Yao, Michael D.; Malech, Harry L.; De Ravin, Suk See] NIAID, Host Def Lab, Bethesda, MD 20892 USA. [Alimchandani, Meghna; Quezado, Martha M.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Kovacs, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,6A02, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov; sderavin@niaid.nih.gov OI Malech, Harry/0000-0001-5874-5775 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX Supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 33 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2014 VL 133 IS 6 BP 1676 EP + DI 10.1016/j.jaci.2013.10.050 PG 15 WC Allergy; Immunology SC Allergy; Immunology GA AI2FI UT WOS:000336672500021 PM 24373354 ER PT J AU Szefler, SJ Chmiel, JF Fitzpatrick, AM Giacoia, G Green, TP Jackson, DJ Nielsen, HC Phipatanakul, W Raissy, HH AF Szefler, Stanley J. Chmiel, James F. Fitzpatrick, Anne M. Giacoia, George Green, Thomas P. Jackson, Daniel J. Nielsen, Heber C. Phipatanakul, Wanda Raissy, Hengameh H. TI Test for Respiratory and Asthma Control in Kids (TRACK): A validated control tool for preschool-aged children Reply SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID QUESTIONNAIRE C1 [Szefler, Stanley J.] Natl Jewish Hlth, Dept Pediat & Pharmacol, Denver, CO 80206 USA. [Szefler, Stanley J.] Univ Colorado Sch Med, Denver, CO USA. [Chmiel, James F.] Univ Hosp Rainbow Babies & Childrens Hosp, Cleveland, OH USA. [Chmiel, James F.] Case Western Reserve Univ Sch Med, Cleveland, OH USA. [Fitzpatrick, Anne M.] Emory Univ Dept Pediat, Atlanta, GA USA. [Fitzpatrick, Anne M.] Childrens Healthcare Atlanta Ctr Dev Lung Biol, Atlanta, GA USA. [Giacoia, George] Natl Inst Child Hlth & Dev, Bethesda, MD USA. [Green, Thomas P.] Northwestern Univ Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA. [Jackson, Daniel J.] Univ Wisconsin Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA. [Nielsen, Heber C.] Tufts Univ Sch Med, Tufts Med Ctr, Floating Hosp Children, Boston, MA USA. [Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA USA. [Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Raissy, Hengameh H.] Univ New Mexico Sch Med, Dept Pediat, Albuquerque, NM USA. RP Szefler, SJ (reprint author), Natl Jewish Hlth, Dept Pediat & Pharmacol, Denver, CO 80206 USA. EM Stanley.szefler@childrenscolorado.or FU NCATS NIH HHS [UL1 TR000041] NR 7 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 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2014 VL 133 IS 6 BP 1776 EP 1777 DI 10.1016/j.jaci.2014.03.013 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA AI2FI UT WOS:000336672500040 PM 24786239 ER PT J AU Kirklin, JK Naftel, DC Pagani, FD Kormos, RL Stevenson, LW Blume, ED Miller, MA Baldwin, JT Young, JB AF Kirklin, James K. Naftel, David C. Pagani, Francis D. Kormos, Robert L. Stevenson, Lynne W. Blume, Elizabeth D. Miller, Marissa A. Baldwin, J. Timothy Young, James B. TI Sixth INTERMACS annual report: A 10,000-patient database SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE mechanical support; ventricular assist device; INTERMACS; advanced heart failure; destination therapy ID CIRCULATORY SUPPORT; DESTINATION THERAPY AB The sixth annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 8 years of patient enrollment. The analysis is based on data from >10,000 patients and updates demographics, survival, adverse events and risk factors. Among patients with continuous-flow pumps, actuarial survival continues to be 80% at 1 year and 70% at 2 years. The report features a comparison of two eras of continuous-flow durable devices in the USA in terms of device strategy, patient profiles, adverse event burden, survival and quality of life. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Kirklin, James K.; Naftel, David C.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Pagani, Francis D.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Kormos, Robert L.] Univ Pittsburgh, Presbyterian Univ Hosp, Med Ctr, Dept Surg, Pittsburgh, PA USA. [Stevenson, Lynne W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Blume, Elizabeth D.] Boston Childrens Hosp, Dept Pediat, Boston, MA USA. [Miller, Marissa A.; Baldwin, J. Timothy] Natl Heart Lung & Blood Inst, Div Cardiovasc Dis, Adv Technol & Surg Branch, Bethesda, MD USA. [Young, James B.] Cleveland Clin, Fdn Lerner Coll Med, Dept Med, Cleveland, OH 44106 USA. RP Kirklin, JK (reprint author), Univ Alabama Birmingham, Dept Surg, Div Cardiovasc Surg, 760 Tinsley Harrison Towers, Birmingham, AL 35294 USA. EM jkirklin@uab.edu FU NHLBI [HHSN2682011000250] FX This analysis and the INTERMACS device database are funded by a contract grant from the NHLBI (HHSN2682011000250). NR 7 TC 359 Z9 362 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JUN PY 2014 VL 33 IS 6 BP 555 EP 564 DI 10.1016/j.healun.2014.04.010 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AI1TG UT WOS:000336637100001 PM 24856259 ER PT J AU Dang, HT Budhu, A Wang, XW AF Dang, Hien T. Budhu, Anuradha Wang, Xin W. TI The origin of cancer stem cells SO JOURNAL OF HEPATOLOGY LA English DT Article DE Hepatocellular carcinoma; Cancer stem cells; Hepatocarcinogenesis; IL-6; HCC progenitor cells; Foci altered hepatocytes ID HEPATOCELLULAR-CARCINOMA; LIVER-CANCER; MICROENVIRONMENT AB Hepatocellular carcinoma (HCC) is a slowly developing malignancy postulated to evolve from premalignant lesions in chronically damaged livers. However, it was never established that premalignant lesions actually contain tumor progenitors that give rise to cancer. Here, we describe the isolation and characterization of HCC progenitor cells (HcPCs) from different mouse HCC models. Unlike fully malignant HCC, HcPCs give rise to cancer only when introduced into a liver undergoing chronic damage and compensatory proliferation. Although HcPCs exhibit a similar transcriptomic profile to bipotential hepatobiliary progenitors, the latter do not give rise to tumors. Cells resembling HcPCs reside within dysplastic lesions that appear several months before HCC nodules. Unlike early hepatocarcinogenesis, which depends on paracrine IL-6 production by inflammatory cells, due to upregulation of LIN28 expression, HcPCs had acquired autocrine IL-6 signaling that stimulates their in vivo growth and malignant progression. This may be a general mechanism that drives other IL-6-producing malignancies. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Dang, Hien T.; Budhu, Anuradha; Wang, Xin W.] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 NR 9 TC 3 Z9 3 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD JUN PY 2014 VL 60 IS 6 BP 1304 EP 1305 DI 10.1016/j.cell.2013.09.031 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9BO UT WOS:000336434300026 PM 24631602 ER PT J AU Han, H Noureddin, M Witthaus, M Park, YJ Hoofnagle, JH Liang, TJ Rotman, Y AF Han, Hwalih Noureddin, Mazen Witthaus, Michael Park, Yoon J. Hoofnagle, Jay H. Liang, T. Jake Rotman, Yaron TI Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype (vol 59, pg 957, 2013) SO JOURNAL OF HEPATOLOGY LA English DT Correction C1 [Han, Hwalih; Noureddin, Mazen; Witthaus, Michael; Park, Yoon J.; Hoofnagle, Jay H.; Liang, T. Jake; Rotman, Yaron] Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bethesda, MD USA. RP Rotman, Y (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9C434,MSC 1800, Bethesda, MD 20892 USA. EM rotmany@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD JUN PY 2014 VL 60 IS 6 BP 1334 EP 1335 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9BO UT WOS:000336434300037 PM 25467605 ER PT J AU Graham, BS AF Graham, Barney S. TI Protecting the Family to Protect the Child: Vaccination Strategy Guided by RSV Transmission Dynamics SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID RESPIRATORY SYNCYTIAL VIRUS; INFECTIONS; MORTALITY; DISEASE; INFANTS C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3017,Bldg 40,Rm 2502, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU Intramural NIH HHS NR 11 TC 11 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2014 VL 209 IS 11 BP 1679 EP 1681 DI 10.1093/infdis/jiu075 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AH9TP UT WOS:000336485900001 PM 24523511 ER PT J AU Meissner, EG Bon, D Prokunina-Olsson, L Tang, W Masur, H O'Brien, TR Herrmann, E Kottilil, S Osinusi, A AF Meissner, Eric G. Bon, Dimitra Prokunina-Olsson, Ludmila Tang, Wei Masur, Henry O'Brien, Thomas R. Herrmann, Eva Kottilil, Shyamasundaran Osinusi, Anuoluwapo TI IFNL4-Delta G Genotype Is Associated With Slower Viral Clearance in Hepatitis C, Genotype-1 Patients Treated With Sofosbuvir and Ribavirin SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE viral kinetics; pharmacokinetics; IL28B; IFNL4; haplotype; SVR; hepatitis C virus; DAA therapy; relapse ID INFECTION; HCV; VIRUS; KINETICS; THERAPY AB Response to pegylated interferon-alpha and ribavirin (IFN-alpha/RBV) treatment for chronic hepatitis C virus (HCV) infection is influenced by host genetic factors, but their role for IFN-alpha-free, direct-acting antiviral (DAA) regimens is unclear. An exonic deletion allele (IFNL4-Delta G) bolsters the established association with IFN-alpha/RBV therapy treatment outcome of another IFNL4 variant, rs12979860, which is located upstream of IFNL3 (IL28B). We report that in patients treated with the DAA sofosbuvir along with RBV, IFNL4-Delta G is associated with slower early viral decay, due to slower loss of free virus (P = .039) and decreased drug efficacy (P = .048), suggesting functional relevance of IFN-lambda 4 in IFN-alpha-free DAA therapies. C1 [Meissner, Eric G.; Kottilil, Shyamasundaran; Osinusi, Anuoluwapo] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Bon, Dimitra; Herrmann, Eva] Goethe Univ Frankfurt, Inst Biostat & Math Modeling, Frankfurt, Germany. [Prokunina-Olsson, Ludmila; Tang, Wei] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Osinusi, Anuoluwapo] Sci Applicat Int Corp Frederick Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick, MD USA. [Osinusi, Anuoluwapo] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. RP Meissner, EG (reprint author), 10 Ctr Dr,Bldg 10 Room 11N204, Bethesda, MD 20892 USA. EM eric.meissner@nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health Clinical Center; Division of Cancer Epidemiology and Genetics of the National Cancer Institute; National Institute of Allergy and Infectious Diseases; German Research Foundation (DFG) by the clinical research unit [KFO 129] FX This work was supported in part, with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E, the National Institutes of Health Clinical Center, and the Division of Cancer Epidemiology and Genetics of the National Cancer Institute. This research was supported, in part, by the intramural program of the National Institute of Allergy and Infectious Diseases. The study was also supported, in part, by the German Research Foundation (DFG) by the clinical research unit KFO 129. NR 15 TC 41 Z9 41 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2014 VL 209 IS 11 BP 1700 EP 1704 DI 10.1093/infdis/jit827 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AH9TP UT WOS:000336485900005 PM 24367041 ER PT J AU Preston, MD Assefa, SA Ocholla, H Sutherland, CJ Borrmann, S Nzila, A Michon, P Hien, TT Bousema, T Drakeley, CJ Zongo, I Ouedraogo, JB Djimde, AA Doumbo, OK Nosten, F Fairhurst, RM Conway, DJ Roper, C Clark, TG AF Preston, Mark D. Assefa, Samuel A. Ocholla, Harold Sutherland, Colin J. Borrmann, Steffen Nzila, Alexis Michon, Pascal Tran Tinh Hien Bousema, Teun Drakeley, Christopher J. Zongo, Issaka Ouedraogo, Jean-Bosco Djimde, Abdoulaye A. Doumbo, Ogobara K. Nosten, Francois Fairhurst, Rick M. Conway, David J. Roper, Cally Clark, Taane G. TI PlasmoView: A Web-based Resource to Visualise Global Plasmodium falciparum Genomic Variation SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Plasmodium falciparum; malaria; genomics; drug resistance; vaccine targets; visualization ID CHLOROQUINE RESISTANCE; ARTEMISININ RESISTANCE; MITOCHONDRIAL-DNA; GENETIC DIVERSITY; WESTERN CAMBODIA; MALARIA; MUTATIONS; ORIGIN; POPULATIONS; VARIANTS AB Malaria is a global public health challenge, with drug resistance a major barrier to disease control and elimination. To meet the urgent need for better treatments and vaccines, a deeper knowledge of Plasmodium biology and malaria epidemiology is required. An improved understanding of the genomic variation of malaria parasites, especially the most virulent Plasmodium falciparum (Pf) species, has the potential to yield new insights in these areas. High-throughput sequencing and genotyping is generating large amounts of genomic data across multiple parasite populations. The resulting ability to identify informative variants, particularly single-nucleotide polymorphisms (SNPs), will lead to the discovery of intra- and inter-population differences and thus enable the development of genetic barcodes for diagnostic assays and clinical studies. Knowledge of genetic variability underlying drug resistance and other differential phenotypes will also facilitate the identification of novel mutations and contribute to surveillance and stratified medicine applications. The PlasmoView interactive web-browsing tool enables the research community to visualise genomic variation and annotation (eg, biological function) in a geographic setting. The first release contains over 600 000 high-quality SNPs in 631 Pf isolates from laboratory strains and four malaria-endemic regions (West Africa, East Africa, Southeast Asia and Oceania). C1 [Preston, Mark D.; Assefa, Samuel A.; Sutherland, Colin J.; Bousema, Teun; Drakeley, Christopher J.; Conway, David J.; Roper, Cally; Clark, Taane G.] LSHTM, Dept Pathogen Mol Biol, London WC1E 7HT, England. [Ocholla, Harold] Malawi Liverpool Wellcome Trust Clin Res Programm, Blantyre 3, Malawi. [Ocholla, Harold] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Borrmann, Steffen; Nzila, Alexis] KEMRI Wellcome Trust Res Programme, Kilifi, Kenya. [Borrmann, Steffen] Heidelberg Univ, Sch Med, Dept Infect Dis, D-69120 Heidelberg, Germany. [Nzila, Alexis] King Fahd Univ Petr & Minerals, Dhahran 31262, Saudi Arabia. [Michon, Pascal] Papua New Guinea Inst Med Res, Madang, Papua N Guinea. [Tran Tinh Hien] Hosp Trop Dis, Oxford Univ Clin Res Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam. [Zongo, Issaka; Ouedraogo, Jean-Bosco] Inst Rech Sci St, Bobo Dioulasso 01, Burkina Faso. [Djimde, Abdoulaye A.; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali. [Djimde, Abdoulaye A.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. [Nosten, Francois] Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand. [Nosten, Francois] Univ Oxford, Ctr Trop Med, Oxford OX3 7LJ, England. [Nosten, Francois] Shoklo Malaria Res Unit, Mae Sot Tak 63110, Thailand. [Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Preston, MD (reprint author), LSHTM, Dept Pathogen Mol Biol, Keppel St, London WC1E 7HT, England. EM mark.preston@lshtm.ac.uk RI Roper, Cally/K-2989-2013; Bousema, Teun/N-3574-2014; Preston, Mark/P-1429-2015; OI Roper, Cally/0000-0002-6545-309X; Preston, Mark/0000-0002-6506-3104; Borrmann, Steffen/0000-0001-9189-4393; Conway, David/0000-0002-8711-3037; Nosten, Francois/0000-0002-7951-0745 FU Medical Research Council, UK [MR/J005398/1]; Malaria Capacity Development Consortium (HO Wellcome Trust) [WT084289MA]; National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA FX This work was supported by the Medical Research Council, UK (MDP and TGC MR/J005398/1) the Malaria Capacity Development Consortium (HO Wellcome Trust Grant WT084289MA) and the Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA (RMF). NR 34 TC 12 Z9 12 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2014 VL 209 IS 11 BP 1808 EP 1815 DI 10.1093/infdis/jit812 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AH9TP UT WOS:000336485900018 PM 24338354 ER PT J AU Reedy, J Krebs-Smith, SM Miller, PE Liese, AD Kahle, LL Park, Y Subar, AF AF Reedy, Jill Krebs-Smith, Susan M. Miller, Paige E. Liese, Angela D. Kahle, Lisa L. Park, Yikyung Subar, Amy F. TI Higher Diet Quality Is Associated with Decreased Risk of All-Cause, Cardiovascular Disease, and Cancer Mortality among Older Adults SO JOURNAL OF NUTRITION LA English DT Article ID MAJOR CHRONIC DISEASE; HEALTHY EATING INDEX; FOOD-FREQUENCY QUESTIONNAIRE; GUIDELINES-FOR-AMERICANS; RETIRED-PERSONS DIET; LIFE-STYLE FACTORS; MEDITERRANEAN DIET; 10-YEAR MORTALITY; NATIONAL-INSTITUTES; ALCOHOL-CONSUMPTION AB Increased attention in dietary research and guidance has been focused on dietary patterns, rather than on single nutrients or food groups, because dietary components are consumed in combination and correlated with one another. However, the collective body of research on the topic has been hampered by the lack of consistency in methods used. We examined the relationships between 4 indices the Healthy Eating Index-2010 (HEI-2010), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) and all-cause, cardiovascular disease (CVD), and cancer mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124-item food-frequency questionnaire were used to calculate scores; adjusted HRs and 95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and 29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were associated with a 12-28% decreased risk of all-cause, CVD, and cancer mortality. Specifically, comparing the highest with the lowest quintile scores, adjusted HRs for all-cause mortality for men were as follows: HEI-2010 HR: 0.78(95% Cl: 0.76, 0.80), AHEI-2010 HR: 0.76(95% Cl: 0.74, 0.78), aMED HR: 0 77 (95% Cl: 0.75, 0.79), and DASH HR: 0.83 (95% Cl: 0.80, 0.85); for women, these were HEI-2010 HR: 0.77 (95% Cl: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76 (95% Cl: 0.73, 0.79), and DASH HR: 0.78 (95% Cl: 0.75, 0.81). Similarly, high adherence on each index was protective for CVD and cancer mortality examined separately. These findings indicate that multiple scores reflect core tenets of a healthy diet that may lower the risk of mortality outcomes, including federal guidance as operationalized in the HEI-2010, Harvard's Healthy Eating Plate as captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized aMED, and the DASH Eating Plan as included in the DASH score. C1 [Reedy, Jill; Krebs-Smith, Susan M.; Subar, Amy F.] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Park, Yikyung] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Miller, Paige E.] Exponent, Chicago, IL USA. [Liese, Angela D.] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Kahle, Lisa L.] Informat Management Serv Inc, Calverton, MD USA. RP Reedy, J (reprint author), NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM reedyj@mail.nih.gov OI Park, Yikyung/0000-0002-6281-489X NR 46 TC 82 Z9 82 U1 2 U2 35 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD JUN PY 2014 VL 144 IS 6 BP 881 EP 889 DI 10.3945/jn.113.189407 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AH9LZ UT WOS:000336465200014 PM 24572039 ER PT J AU Beydoun, MA Gamaldo, AA Beydoun, HA Tanaka, T Tucker, KL Talegawkar, SA Ferrucci, L Zonderman, AB AF Beydoun, May A. Gamaldo, Alyssa A. Beydoun, Hind A. Tanaka, Toshiko Tucker, Katherine L. Talegawkar, Sameera A. Ferrucci, Luigi Zonderman, Alan B. TI Caffeine and Alcohol Intakes and Overall Nutrient Adequacy Are Associated with Longitudinal Cognitive Performance among US Adults SO JOURNAL OF NUTRITION LA English DT Article ID OLDER CHINESE ADULTS; MEDITERRANEAN DIET; RISK-FACTORS; MIDDLE-AGE; EPIDEMIOLOGIC EVIDENCE; COFFEE CONSUMPTION; JAPANESE-AMERICANS; CIGARETTE-SMOKING; ALZHEIMER-DISEASE; COMMUNITY SAMPLE AB Among modifiable lifestyle factor's, diet may affect cognitive health. Cross-sectional and longitudinal associations may exist between dietary exposures [e.g., caffeine (mg/d), alcohol (g/d), and nutrient adequacy] and cognitive performance and change over time. This was a prospective cohort study, the Baltimore Longitudinal Study of Aging (n = 628-1305 persons depending on the cognitive outcome; similar to 2 visits/person). Outcomes included 10 cognitive scores, spanning various domains of cognition. Caffeine and alcohol intakes and a nutrient adequacy score (NAS) were estimated from 7-d food diaries. Among key findings, caffeine intake was associated with better baseline global cognition among participants with a baseline age (Age(base)) of y. A higher NAS was associated with better baseline global cognition performance (overall, women, Age(base) <70 y), better baseline verbal memory (immediate and delayed recall, Age(base) >= 70 y), and slower rate of decline or faster improvement in the attention domain (women). For an Age(base) of <70 y, alcohol consumption was associated with slower improvement on letter fluency and global cognition over time. Conversely, for an Age(base) of >= 70y and among women, alcohol intake was related to better baseline attention and working memory. In sum, patterns of diet and cognition associations indicate stratum-specific associations by sex and baseline age. The general observed trend was that of putative beneficial effects of caffeine intake and nutrient adequacy on domains of global cognition, verbal memory, and attention, and mixed effects of alcohol on domains of letter fluency, attention, and working memory. Further longitudinal studies conducted on larger samples of adults are needed to determine whether dietary factors individually or in combination are modifiers of cognitive trajectories among adults. C1 [Beydoun, May A.; Gamaldo, Alyssa A.; Tanaka, Toshiko; Ferrucci, Luigi; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Gamaldo, Alyssa A.] Univ S Florida, Sch Aging Studies, Tampa, FL USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. [Tucker, Katherine L.] Univ Massachusetts, Lowell, MA USA. [Talegawkar, Sameera A.] Johns Hopkins Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD USA. RP Beydoun, MA (reprint author), NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM baydounm@mail.nih.gov OI Tucker, Katherine/0000-0001-7640-662X; Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging, Intramural Research Program (NIA/NIH/IRP) FX Supported entirely by the National Institute on Aging, Intramural Research Program (NIA/NIH/IRP). NR 94 TC 4 Z9 4 U1 3 U2 21 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD JUN PY 2014 VL 144 IS 6 BP 890 EP 901 DI 10.3945/jn.113.189027 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AH9LZ UT WOS:000336465200015 PM 24744319 ER PT J AU Richard, SA Black, RE Gilman, RH Guerrant, RL Kang, G Lanata, CF Molbak, K Rasmussen, ZA Sack, RB Valentiner-Branth, P Checkley, W AF Richard, Stephanie A. Black, Robert E. Gilman, Robert H. Guerrant, Richard L. Kang, Gagandeep Lanata, Claudio F. Molbak, Kare Rasmussen, Zeba A. Sack, R. Bradley Valentiner-Branth, Palle Checkley, William CA Childhood Malnutr Infection TI Catch-Up Growth Occurs after Diarrhea in Early Childhood SO JOURNAL OF NUTRITION LA English DT Article ID RURAL BANGLADESH; LINEAR GROWTH; PERUVIAN CHILDREN; GUINEA-BISSAU; RISK-FACTORS; MALNUTRITION; DISEASE; MORBIDITY; COMMUNITY; INFANTS AB Diarrhea and linear growth faltering continue to burden low-income countries and are among the most important contributors to poor health during early childhood. Diarrhea is thought to adversely affect linear growth, but catch-up growth can occur if no additional insults are experienced. We sought to characterize catch-up growth in relation to diarrhea burden in a multisite dataset of 1007 children. Using longitudinal anthropometry and diarrheal surveillance data from 7 cohort studies in 4 countries, we examined the relation between diarrhea prevalence and growth in 3- to 6-mo periods using linear mixed-effect models. Growth during each period was calculated as a function of age using linear splines. We incorporated the longitudinal prevalence of diarrhea in both current and previous periods into the model. Diarrhea during the current period was associated with slower linear and ponderal growth. Faster (catch-up) growth in length was observed in children with no diarrhea in age groups immediately after an age group in which diarrhea was experienced [age group >6-12 mo: 0.03 mm/mo for each percentage diarrhea prevalence in the previous period (95% Cl: 0.007, 0.06) relative to 11.3 mm/mo mean growth rate; age group >12-18 mo: 0.04 mm/mo (95% Cl: 0.02, 0.06) relative to 8.9 mm/mo mean growth rate; age group >18-24 mo: 0.04 mm/mo (95% Cl: 0.003, 0.09) relative to 7.9 mm/mo mean growth rate]. The associations were stronger in boys than in girls when separate models were run. Similar results were observed when weight was the outcome variable. When diarrheal episodes are followed by diarrhea-free periods in the first 2 y of life, catch-up growth is observed that may allow children to regain their original trajectories. The finding of a greater effect of diarrhea on linear growth in boys than in girls was unexpected and requires additional study. Diarrhea burdens are high throughout the first 2 y of life in these study sites, therefore reducing the likelihood of catch-up growth. Extending diarrhea-free periods may increase the likelihood of catch-up growth and decrease the prevalence of stunting. C1 [Richard, Stephanie A.; Black, Robert E.; Gilman, Robert H.; Checkley, William] Johns Hopkins Univ, Program Global Dis Epidemiol & Control, Dept Int Hlth, Bloomberg Sch Publ Heath, Baltimore, MD 21218 USA. [Richard, Stephanie A.; Rasmussen, Zeba A.; Sack, R. Bradley] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Guerrant, Richard L.] Univ Virginia, Sch Med, Ctr Global Hlth, Charlottesville, VA 22908 USA. [Kang, Gagandeep] Christian Med Coll & Hosp, Dept Gastrointestinal Sci, Vellore, Tamil Nadu, India. [Lanata, Claudio F.] Inst Invest Nutr, Lima, Peru. [Molbak, Kare; Valentiner-Branth, Palle] Statens Serum Inst, Div Epidemiol, DK-2300 Copenhagen, Denmark. RP Checkley, W (reprint author), Johns Hopkins Univ, Program Global Dis Epidemiol & Control, Dept Int Hlth, Bloomberg Sch Publ Heath, Baltimore, MD 21218 USA. EM wcheckl1@jhmi.edu OI Moore, Sean/0000-0003-1150-6632; Kang, Gagandeep/0000-0002-3656-564X; Fischer, Thea Kolsen/0000-0003-4812-980X FU Bill and Melinda Gates Foundation; Consequences for Child Health and Development (MAL-ED); National Heart, Lung, and Blood Institute/NIH [R00HL096955] FX S.A.R. and W.C. were supported in part by the Bill and Melinda Gates Foundation project The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED). S.A.R. was a Sommer Scholar in the Department of International Health while conducting this work. W.C was supported by Pathway to Independence Award R00HL096955 from the National Heart, Lung, and Blood Institute/NIH. NR 44 TC 11 Z9 11 U1 1 U2 13 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD JUN PY 2014 VL 144 IS 6 BP 965 EP 971 DI 10.3945/jn.113.187161 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AH9LZ UT WOS:000336465200025 PM 24699805 ER PT J AU Shurin, SB Castle, VP AF Shurin, Susan B. Castle, Valerie P. TI United States Biomedical Research Impacting Child Health and the Growth of the National Institutes of Health Funding to Pediatric Departments and Children's Hospitals SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 [Shurin, Susan B.] NHLBI, NIH, Bethesda, MD 20892 USA. [Castle, Valerie P.] Univ Michigan Hlth Syst, Mott Childrens Hosp, Dept Pediat, Ann Arbor, MI USA. RP Shurin, SB (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2014 VL 164 IS 6 BP 1248 EP + DI 10.1016/j.jpeds.2014.03.026 PG 3 WC Pediatrics SC Pediatrics GA AH9YX UT WOS:000336503200001 PM 24855924 ER PT J AU Wren, TAL Kalkwarf, HJ Zemel, BS Lappe, JM Oberfield, S Shepherd, JA Winer, KK Gilsanz, V AF Wren, Tishya A. L. Kalkwarf, Heidi J. Zemel, Babette S. Lappe, Joan M. Oberfield, Sharon Shepherd, John A. Winer, Karen K. Gilsanz, Vicente CA Bone Mineral Density Childhood TI Longitudinal Tracking of Dual-Energy X-ray Absorptiometry Bone Measures Over 6 Years in Children and Adolescents: Persistence of Low Bone Mass to Maturity SO JOURNAL OF PEDIATRICS LA English DT Article ID MINERAL DENSITY; CHILDHOOD; PUBERTY; GROWTH; BLACK; AGE; ACCUMULATION; OSTEOPOROSIS; MATURATION; DAUGHTERS AB Objectives Early assessment of bone mass may be useful for predicting future osteoporosis risk if bone measures "track" during growth. This prospective longitudinal multicenter study examined tracking of bone measures in children and adolescents over 6 years to sexual and skeletal maturity. Study design A total of 240 healthy male and 293 healthy female patients, ages 6-17 years, underwent yearly evaluations of height, weight, body mass index, skeletal age, Tanner stage, and dual-energy x-ray absorptiometry (DXA) bone measurements of the whole body, spine, hip, and forearm for 6 years. All subjects were sexually and skeletally mature at final follow-up. Correlation was performed between baseline and 6-year follow-up measures, and change in DXA Z-scores was examined for subjects who had baseline Z < -1.5. Results DXA Z-scores (r = 0.66-0.87) had similar tracking to anthropometric measures (r = 0.64-0.74). Tracking was stronger for bone mineral density compared with bone mineral content and for girls compared with boys. Tracking was weakest during mid-to late puberty but improved when Z-scores were adjusted for height. Almost all subjects with baseline Z < -1.5 had final Z-scores below average, with the majority remaining less than -1.0. Conclusions Bone status during childhood is a strong predictor of bone status in young adulthood, when peak bone mass is achieved. This suggests that bone mass measurements in children and adolescents may be useful for early identification of individuals at risk for osteoporosis later in life. C1 [Wren, Tishya A. L.; Gilsanz, Vicente] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Kalkwarf, Heidi J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Zemel, Babette S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Lappe, Joan M.] Creighton Univ, Omaha, NE 68178 USA. [Oberfield, Sharon] Columbia Univ, New York, NY USA. [Shepherd, John A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Winer, Karen K.] NICHHD, Bethesda, MD 20892 USA. RP Wren, TAL (reprint author), Childrens Hosp Los Angeles, 4650 Sunset Blvd,MS 69, Los Angeles, CA 90027 USA. EM twren@chla.usc.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [NO1-HD-1-3228, NO1-HD-1-3329, NO1-HD-1-3330, NO1-HD-1-3331, NO1-HD-1-3332, NO1-HD-1-3333]; National Center for Research Resources [UL1 RR026314, UL1RR024134] FX Supported by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NO1-HD-1-3228, NO1-HD-1-3329, NO1-HD-1-3330, NO1-HD-1-3331, NO1-HD-1-3332, and NO1-HD-1-3333) and the National Center for Research Resources (UL1 RR026314 and UL1RR024134). The authors declare no conflicts of interest. NR 29 TC 20 Z9 20 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2014 VL 164 IS 6 BP 1280 EP + DI 10.1016/j.jpeds.2013.12.040 PG 8 WC Pediatrics SC Pediatrics GA AH9YX UT WOS:000336503200011 PM 24485819 ER PT J AU DeMauro, SB D'Agostino, JA Bann, C Bernbaum, J Gerdes, M Bell, EF Carlo, WA D'Angio, CT Das, A Higgins, R Hintz, SR Laptook, AR Natarajan, G Nelin, L Poindexter, BB Sanchez, PJ Shankaran, S Stoll, BJ Truog, W Van Meurs, KP Vohr, B Walsh, MC Kirpalani, H AF DeMauro, Sara B. D'Agostino, Jo Ann Bann, Carla Bernbaum, Judy Gerdes, Marsha Bell, Edward F. Carlo, Waldemar A. D'Angio, Carl T. Das, Abhik Higgins, Rosemary Hintz, Susan R. Laptook, Abbot R. Natarajan, Girija Nelin, Leif Poindexter, Brenda B. Sanchez, Pablo J. Shankaran, Seetha Stoll, Barbara J. Truog, William Van Meurs, Krisa P. Vohr, Betty Walsh, Michele C. Kirpalani, Haresh CA Eunice Kennedy Shriver Natl Inst TI Developmental Outcomes of Very Preterm Infants with Tracheostomies SO JOURNAL OF PEDIATRICS LA English DT Article ID LOW-BIRTH-WEIGHT; BRONCHOPULMONARY DYSPLASIA; NEURODEVELOPMENTAL OUTCOMES; PEDIATRIC TRACHEOSTOMIES; PHYSIOLOGICAL DEFINITION; MECHANICAL VENTILATION; EMOTIONAL ASSESSMENT; CAFFEINE THERAPY; CURRENT TRENDS; CHILDREN AB Objectives To evaluate the neurodevelopmental outcomes of very preterm (<30 weeks) infants who underwent tracheostomy. Study design Retrospective cohort study from 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network over 10 years (2001-2011). Infants who survived to at least 36 weeks (N = 8683), including 304 infants with tracheostomies, were studied. Primary outcome was death or neurodevelopmental impairment (NDI; a composite of >= 1 of developmental delay, neurologic impairment, profound hearing loss, severe visual impairment) at a corrected age of 18-22 months. Outcomes were compared using multiple logistic regression. We assessed the impact of timing by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. Results Tracheostomies were associated with all neonatal morbidities examined and with most adverse neurodevelopmental outcomes. Death or NDI occurred in 83% of infants with tracheostomies and 40% of those without (OR adjusted for center 7.0, 95% CI 5.2-9.5). After adjustment for potential confounders, odds of death or NDI remained higher (OR 3.3, 95% CI 2.4-4.6), but odds of death alone were lower (OR 0.4, 95% CI 0.3-0.7) among infants with tracheostomies. Death or NDI was lower in infants who received their tracheostomies before, rather than after, 120 days of life (aOR 0.5, 95% CI 0.3-0.9). Conclusions Tracheostomy in preterm infants is associated with adverse developmental outcomes and cannot mitigate the significant risk associated with many complications of prematurity. These data may inform counseling about tracheostomy in this vulnerable population. C1 [DeMauro, Sara B.; D'Agostino, Jo Ann; Bernbaum, Judy; Gerdes, Marsha; Kirpalani, Haresh] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [DeMauro, Sara B.; Bernbaum, Judy; Gerdes, Marsha; Kirpalani, Haresh] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. [Bann, Carla; D'Angio, Carl T.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Das, Abhik] Univ Rochester, Dept Pediat, Rochester, NY USA. [Higgins, Rosemary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Neonatal Res Network, Rockville, MD USA. [Hintz, Susan R.; Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. [Laptook, Abbot R.; Vohr, Betty] Brown Univ, Dept Pediat, Providence, RI 02912 USA. [Natarajan, Girija; Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Nelin, Leif] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Nelin, Leif] Nationwide Childrens Hosp, Columbus, OH USA. [Poindexter, Brenda B.] Indiana Univ, Dept Pediat, Indianapolis, IN 46204 USA. [Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA. [Truog, William] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA. [Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. RP DeMauro, SB (reprint author), Childrens Hosp Philadelphia, 34th St & Civ Ctr Blvd,2nd Floor Main, Philadelphia, PA 19104 USA. EM DeMauro@email.chop.edu FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) for the Neonatal Research Network; Generic Database Study; Candidiasis Study; Cord Clamping Study; Delivery Room CPAP Study; Early Blood Pressure pilot study; PCV-7 Study; Phototherapy Trial; Preemie aEEG pilot study; Preemie iNO Trial; SUPPORT trial FX Supported by grants from the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) for the Neonatal Research Network, including for the Generic Database Study, Candidiasis Study, Cord Clamping Study, Delivery Room CPAP Study, Early Blood Pressure pilot study, PCV-7 Study, Phototherapy Trial, Preemie aEEG pilot study, Preemie iNO Trial, and SUPPORT trial. Data collected at participating sites of the NICHD Neonatal Research Network were transmitted to RTI International, the data coordinating center for the network, which stored, managed, and analyzed the data for this study. The authors declare no conflicts of interest. NR 47 TC 15 Z9 15 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2014 VL 164 IS 6 BP 1303 EP + DI 10.1016/j.jpeds.2013.12.014 PG 10 WC Pediatrics SC Pediatrics GA AH9YX UT WOS:000336503200016 PM 24472229 ER PT J AU Diaz, SD Smith, LM LaGasse, LL Derauf, C Newman, E Shah, R Arria, A Huestis, MA Della Grotta, S Dansereau, LM Neal, C Lester, BM AF Diaz, Sabrina D. Smith, Lynne M. LaGasse, Linda L. Derauf, Chris Newman, Elana Shah, Rizwan Arria, Amelia Huestis, Marilyn A. Della Grotta, Sheri Dansereau, Lynne M. Neal, Charles Lester, Barry M. TI Effects of Prenatal Methamphetamine Exposure on Behavioral and Cognitive Findings at 7.5 Years of Age SO JOURNAL OF PEDIATRICS LA English DT Article ID MATERNAL LIFE-STYLE; PHYSICALLY ABUSED-CHILDREN; INFANT DEVELOPMENT; PSYCHOSOCIAL CHARACTERISTICS; INTRAUTERINE GROWTH; COCAINE EXPOSURE; PREGNANCY; OUTCOMES; ENVIRONMENT; AMPHETAMINE AB Objective To examine child behavioral and cognitive outcomes after prenatal exposure to methamphetamine. Study design We enrolled 412 mother-infant pairs (204 methamphetamine-exposed and 208 unexposed matched comparisons) in the Infant Development, Environment, and Lifestyle study. The 151 children exposed to methamphetamine and 147 comparisons who attended the 7.5-year visit were included. Exposure was determined by maternal self-report and/or positive meconium toxicology. Maternal interviews assessed behavioral and cognitive outcomes using the Conners' Parent Rating Scale-Revised: Short Form. Results After adjusting for covariates, children exposed to methamphetamine had significantly higher cognitive problems subscale scores than comparisons and were 2.8 times more likely to have cognitive problems scores that were above average on the Conners' Parent Rating Scale-Revised: Short Form. No association between prenatal methamphetamine exposure and behavioral problems, measured by the oppositional, hyperactivity, and attention-deficit/hyperactivity disorder index subscales, were found. Conclusions Prenatal methamphetamine exposure was associated with increased cognitive problems, which may affect academic achievement and lead to increased negative behavioral outcomes. C1 [Diaz, Sabrina D.; Smith, Lynne M.] Univ Calif Los Angeles, Harbor UCLA Med Ctr, LA Inst Biomed, Los Angeles, CA USA. [Diaz, Sabrina D.; Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [LaGasse, Linda L.; Della Grotta, Sheri; Dansereau, Lynne M.; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, Warren Alpert Med Sch, Providence, RI USA. [Derauf, Chris] Mayo Clin, Rochester, MN USA. [Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA. [Shah, Rizwan] Blank Hosp Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA. [Arria, Amelia] Univ Maryland, Sch Publ Hlth, Ctr Young Adult Hlth & Dev, College Pk, MD 20742 USA. [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Neal, Charles] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Smith, LM (reprint author), Harbor UCLA Med Ctr, 1124 W Carson St,RB-1, Torrance, CA 90502 USA. EM smith@labiomed.org OI Arria, Amelia/0000-0002-6360-9265 FU National Institute on Drug Abuse [R01DA014918]; National Center on Research Resources [UL1TR000124, U54RR026136] FX Supported by the National Institute on Drug Abuse (R01DA014918) and the National Center on Research Resources (UL1TR000124 and U54RR026136). The authors declare no conflicts of interest. NR 38 TC 6 Z9 6 U1 2 U2 16 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2014 VL 164 IS 6 BP 1333 EP 1338 DI 10.1016/j.jpeds.2014.01.053 PG 6 WC Pediatrics SC Pediatrics GA AH9YX UT WOS:000336503200022 PM 24630350 ER PT J AU James, A Hoang, U Seagroatt, V Clacey, J Goldacre, M Leibenluft, E AF James, Anthony Hoang, Uy Seagroatt, Valerie Clacey, Joe Goldacre, Michael Leibenluft, Ellen TI A Comparison of American and English Hospital Discharge Rates for Pediatric Bipolar Disorder, 2000 to 2010 SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE pediatric; bipolar disorder; hospital discharge rates ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SEVERE MOOD DYSREGULATION; FOLLOW-UP; NATIONAL TRENDS; I DISORDER; CHILDREN; MANIA; ADOLESCENTS; YOUTH; PREVALENCE AB Objective: Controversy exists over the diagnosis and prevalence of pediatric bipolar disorder (PBD). Although several small surveys suggest that the rate of the PBD diagnosis in clinical settings is higher in the United States than in other countries, no comprehensive cross-national comparisons of clinical practice have been performed. Here, we used longitudinal national datasets from 2000 to 2010 to compare US and English hospital discharge rates for PBD in patients aged 1 to 19 years. Method: We used the English National Health Service (NHS) Hospital Episode Statistics (RES) dataset and the United States National Hospital Discharge Survey (NHDS) to compare US and English discharge rates for PBD (bipolar I disorder [BP-I], bipolar II disorder [BP-II], bipolar disorder not otherwise specified [BP-NOS], and cyclothymia). We also conducted cross-national comparisons for all other psychiatric diagnoses in youth and for adults with bipolar disorder (BD). Results: There was a 72.1-fold difference in discharge rates for PBD in youth between the United States and England (United States, 100.9 per 100,000 population, 95% confidence interval = 98.1-103.8, versus England, 1.4 per 100,000 population, 95% CI = 1.4-1.5). After controlling for cross-national differences in length of stay, discharge rates for PBD remained 12.5 times higher in the United States than in England. For all other child psychiatric diagnoses, the discharge rate was 3.9-fold higher, and for adults with BD 7.2-fold higher, in the United States than in England. Conclusion: The disparity between US and English discharge rates for PBD is markedly greater than the disparity for child psychiatric discharge rates overall and for adult rates of BD. This suggests that the difference in discharge rates for PBD may be due to differing diagnostic practices for PBD in the United States versus in England. C1 [James, Anthony] Univ Oxford, Oxford OX3 7JX, England. [James, Anthony; Clacey, Joe] Warneford Hosp, Oxford OX3 7JX, England. [Hoang, Uy; Seagroatt, Valerie; Goldacre, Michael] Univ Oxford, Nuffield Dept Populat Hlth, Oxford OX3 7JX, England. [Leibenluft, Ellen] NIMH, Bethesda, MD 20892 USA. RP James, A (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. EM anthony.james@psych.ox.ac.uk FU English National Institute for Health Research FX The English National Institute for Health Research funds the Unit of Health Care Epidemiology to undertake research using the English national dataset. NR 43 TC 11 Z9 11 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2014 VL 53 IS 6 BP 614 EP 624 DI 10.1016/j.jaac.2014.02.008 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AI0SO UT WOS:000336560400005 PM 24839880 ER PT J AU Pan, PM Salum, GA Gadelha, A Moriyama, T Cogo-Moreira, H Graeff-Martins, AS Rosario, MC Polanczyk, GV Brietzke, E Rohde, LA Stringaris, A Goodman, R Leibenluft, E Bressan, RA AF Pan, Pedro Mario Salum, Giovanni Abrahao Gadelha, Ary Moriyama, Tais Cogo-Moreira, Hugo Graeff-Martins, Ana Soledade Rosario, Maria Conceicao Polanczyk, Guilherme Vanoni Brietzke, Elisa Rohde, Luis Augusto Stringaris, Argyris Goodman, Robert Leibenluft, Ellen Bressan, Rodrigo Affonseca TI Manic Symptoms in Youth: Dimensions, Latent Classes, and Associations With Parental Psychopathology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE mania; bipolar; latent; family history; factor analysis ID DIFFICULTIES QUESTIONNAIRE SDQ; BIPOLAR SPECTRUM DISORDERS; PSYCHIATRIC-DISORDERS; COMMUNITY SAMPLE; ADOLESCENTS; CHILDREN; STRENGTHS; VALIDATION; PHENOMENOLOGY; METAANALYSIS AB Objective: The purpose of the study was to define the latent structure of parent-reported manic symptoms and their association with functional impairment and familial risk in a community sample of Brazilian children. Method: We screened for manic symptoms in a community sample of 2,512 children 6 to 12 years of age. Parents of children with "episodes of going abnormally high" completed a detailed mania section (n = 479; 19.1%). Confirmatory factor analysis (CFA) tested a solution with "Under-Control (UC)" and "Exuberant (EX)" dimensions, investigating the severity (threshold) and factor loading of each symptom. We also used latent class analysis (LCA) to evaluate the latent categorical structure of manic symptoms. Associations of these latent constructs with psychiatric comorbidity, psychosocial impairment, and family history of psychopathology were tested. Results: The 2-dimensional model fit the data well. Only the UC dimension was associated with psychiatric morbidity, psychosocial impairment, and a family history of mania, depression, or suicide attempts. Both UC and EX items discriminated subjects with "episodes of going abnormally high," but EX items lay at the mild end of the severity spectrum, whereas UC items lay at the severe end. The LCA yielded a small group of children with high levels of manic symptoms and a distinct profile of psychiatric comorbidity and impairment ("high-symptom group"). Conclusion: In a large, community-based sample, we found a 2-dimensional latent structure for parent-reported manic symptoms in youth, and demonstrated familial associations between the UC dimension and affective disorders. Both UC and EX items are clinically useful, but their contributions vary with symptom severity. C1 [Pan, Pedro Mario; Gadelha, Ary; Moriyama, Tais; Cogo-Moreira, Hugo; Rosario, Maria Conceicao; Brietzke, Elisa; Bressan, Rodrigo Affonseca] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Salum, Giovanni Abrahao; Rohde, Luis Augusto] Univ Fed Rio Grande do Sul, BR-90046900 Porto Alegre, RS, Brazil. [Graeff-Martins, Ana Soledade; Polanczyk, Guilherme Vanoni] Univ Sao Paulo, BR-05508 Sao Paulo, Brazil. [Stringaris, Argyris; Goodman, Robert] Kings Coll London, London WC2R 2LS, England. [Leibenluft, Ellen] NIMH, Bethesda, MD USA. RP Pan, PM (reprint author), LINC Edificio Pesquisas 2,Rua Pedro Toledo,669, BR-04039032 Sao Paulo, Brazil. EM pedro.pan@unifesp.br RI Rohde, Luis Augusto/A-6426-2008; Bressan, Rodrigo/E-9178-2010; Graeff-Martins, Ana Soledade/K-1974-2012; Salum, Giovanni/A-7849-2010; Polanczyk, Guilherme/C-2345-2012; Cogo-Moreira, Hugo/E-4602-2011; Pan, Pedro/I-5167-2013; OI Rohde, Luis Augusto/0000-0002-4552-4188; Bressan, Rodrigo/0000-0002-0868-4449; Salum, Giovanni/0000-0002-7537-7289; Polanczyk, Guilherme/0000-0003-2311-3289; Cogo-Moreira, Hugo/0000-0001-9411-9237; Pan, Pedro/0000-0002-1943-6520; Gadelha, Ary/0000-0002-0993-8017 FU National Council for Scientific and Technological Development (CNPq); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Sao Paulo Research Foundation (FAPESP) FX This work was supported by the following Brazilian government agencies: The National Council for Scientific and Technological Development (CNPq); the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), and the Sao Paulo Research Foundation (FAPESP). NR 41 TC 1 Z9 1 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2014 VL 53 IS 6 BP 625 EP 634 DI 10.1016/j.jaac.2014.03.003 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AI0SO UT WOS:000336560400006 PM 24839881 ER PT J AU Wang, YJ Abu-Asab, MS Yu, CR Tang, ZS Shen, DF Tuo, JS Li, XR Chan, CC AF Wang, Yujuan Abu-Asab, Manes S. Yu, Cheng-Rong Tang, Zhongshu Shen, Defen Tuo, Jingsheng Li, Xuri Chan, Chi-Chao TI Platelet-derived growth factor (PDGF)-C inhibits neuroretinal apoptosis in a mu rifle model of focal retinal degeneration SO LABORATORY INVESTIGATION LA English DT Article DE age-related macular degeneration; apoptosis; neuroprotection; platelet-derived growth factor-C; retina ID TISSUE-PLASMINOGEN ACTIVATOR; ANTI-VEGF TREATMENT; MACULAR DEGENERATION; PDGF-C; PHOTORECEPTOR DEGENERATION; PIGMENT EPITHELIUM; ALPHA-RECEPTOR; BLOOD-VESSELS; BETA-RECEPTOR; HUMAN RPE AB Platelet-derived growth factor (PDGF)-C is a member of the PDGF family and is critical for neuronal survival in the central nervous system. We studied the possible survival and antiapoptotic effects of PDGF-C on focal retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)] (DKO rd8) background mice, a model for progressive and focal retinal degeneration. We found no difference in transcript and protein expression of PDGF-C in the retina between DKO rd8 mice and wild type (WT, C57BL/6N). Recombinant PDGF-CC protein (500 ng/eye) was injected intravitreally into the right eye of DKO rd8 mice with phosphate-buffered saline as controls into the left eye. The retinal effects of PDGF-C were assessed by fundoscopy, ocular histopathology, A2E levels, apoptotic molecule analysis, and direct flat mount retinal vascular labeling. We found that the PDGF-CC-treated eyes showed slower progression or attenuation of the focal retinal lesions, lesser photoreceptor and retinal pigment epithelial degeneration resulting in better-preserved photoreceptor structure. Lower expression of apoptotic molecules was detected in the PDGF-CC-treated eyes than in controls. In addition, no retinal neovascularization was observed after PDGF-CC treatment. Our results demonstrate that PDGF-C potently ameliorates photoreceptor degeneration via the suppression of apoptotic pathways without inducing retinal angiogenesis. The protective effects of PDGF-C suggest a novel alternative approach for potential age-related retinal degeneration treatment. C1 [Wang, Yujuan; Shen, Defen; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Yujuan; Tang, Zhongshu; Li, Xuri] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China. [Abu-Asab, Manes S.; Chan, Chi-Chao] NEI, Histopathol Core, NIH, Bethesda, MD 20892 USA. [Yu, Cheng-Rong] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI wang, yujuan/C-8428-2016 FU National Eye Institute Intramural Research Program FX The National Eye Institute Intramural Research Program supported the study. NR 61 TC 2 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JUN PY 2014 VL 94 IS 6 BP 674 EP 682 DI 10.1038/labinvest.2014.60 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA AI0TI UT WOS:000336562500008 PM 24709779 ER PT J AU Li, GW Zhang, P Wang, JP An, YL Gong, QH Gregg, EW Yang, WY Zhang, B Shuai, Y Hong, J Engelgau, MM Li, H Roglic, G Hu, Y Bennett, PH AF Li, Guangwei Zhang, Ping Wang, Jinping An, Yali Gong, Qiuhong Gregg, Edward W. Yang, Wenying Zhang, Bo Shuai, Ying Hong, Jing Engelgau, Michael M. Li, Hui Roglic, Gojka Hu, Yinghua Bennett, Peter H. TI Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; FASTING GLUCOSE; ADULT DEATHS; METFORMIN; MELLITUS; PROGRAM; IMPACT; CHINA; RISK; METAANALYSIS AB Background Lifestyle interventions among people with impaired glucose tolerance reduce the incidence of diabetes, but their effect on all-cause and cardiovascular disease mortality is unclear. We assessed the long-term effect of lifestyle intervention on long-term outcomes among adults with impaired glucose tolerance who participated in the Da Qing Diabetes Prevention Study. Methods The study was a cluster randomised trial in which 33 clinics in Da Qing, China-serving 577 adults with impaired glucose tolerance-were randomised (1: 1: 1: 1) to a control group or lifestyle intervention groups (diet or exercise or both). Patients were enrolled in 1986 and the intervention phase lasted for 6 years. In 2009, we followed up participants to assess the primary outcomes of cardiovascular mortality, all-cause mortality, and incidence of diabetes in the intention-to-treat population. Findings Of the 577 patients, 439 were assigned to the intervention group and 138 were assigned to the control group (one refused baseline examination). 542 (94%) of 576 participants had complete data for mortality and 568 (99%) contributed data to the analysis. 174 participants died during the 23 years of follow-up (121 in the intervention group vs 53 in the control group). Cumulative incidence of cardiovascular disease mortality was 11.9% (95% CI 8.8-15.0) in the intervention group versus 19.6% (12.9-26.3) in the control group (hazard ratio [HR] 0.59, 95% CI 0.36-0 96; p=0.033). All-cause mortality was 28.1% (95% CI 23.9-32 4) versus 38.4% (30.3-46.5; HR 0 71, 95% CI 0.51-0.99; p=0.049). Incidence of diabetes was 72.6% (68.4-76.8) versus 89.9% (84.9-94.9; HR 0.55, 95% CI 0.40-0.76; p=0.001). Interpretation A 6-year lifestyle intervention programme for Chinese people with impaired glucose tolerance can reduce incidence of cardiovascular and all-cause mortality and diabetes. These findings emphasise the long-term clinical benefits of lifestyle intervention for patients with impaired glucose tolerance and provide further justification for adoption of lifestyle interventions as public health measures to control the consequences of diabetes. C1 [Li, Guangwei; Yang, Wenying; Zhang, Bo; Shuai, Ying; Hong, Jing] China Japan Friendship Hosp, Dept Endocrinol, Beijing, Peoples R China. [Li, Guangwei; An, Yali; Gong, Qiuhong] Natl Ctr Cardiol, Ctr Endocrinol & Cardiovasc Dis, Beijing, Peoples R China. [Li, Guangwei; An, Yali; Gong, Qiuhong] Fuwai Hosp, Beijing, Peoples R China. [Zhang, Ping; Gregg, Edward W.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA 30341 USA. [Engelgau, Michael M.] Ctr Dis Control & Prevent, Ctr Global Hlth, Atlanta, GA 30341 USA. [Wang, Jinping; Li, Hui; Hu, Yinghua] Da Qing First Hosp, Dept Cardiol, Da Qing, Peoples R China. [Roglic, Gojka] WHO, Dept Management Noncommunicable Dis, CH-1211 Geneva, Switzerland. [Bennett, Peter H.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. RP Li, GW (reprint author), Dept Endocrinol, 167 Beilishi Rd, Beijing 100037, Peoples R China. EM guangwei_li@medmail.com.cn; pzhang@cdc.gov FU CDC/WHO [U58/CCU424123-01-02]; China-Japan Friendship Hospital FX Supported by CDC/WHO Cooperative Agreement No. U58/CCU424123-01-02 and the China-Japan Friendship Hospital. We thank the participants in the original Da Qing Diabetes Prevention Study and their proxies who contributed to the follow-up study. We also thank Lingzhi Kong, China Ministry of Health, the leadership at the China-Japan Friendship Hospital, Da Qing First Hospital, the Da Qing City Health Bureau, and the Beijing and West Pacific Regional Office of WHO for their general support. We thank Xilin Yang (Tianjin Medical University), Yang Yang (National Center of Cardiology and Fuwai Hospital, China), and Ted Thompson (Centers for Disease Control and Prevention, USA) for statistical advice. Our special thanks go to the late Prof Xiaoren Pan as this study would not have been possible without his leadership in the design and implementation of the original Da Qing Diabetes Prevention Study. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official positions of the Centers for Disease Control and Prevention, the National Institute of Diabetes and Digestive and Kidney Diseases, or WHO. NR 33 TC 128 Z9 138 U1 11 U2 41 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD JUN PY 2014 VL 2 IS 6 BP 474 EP 480 DI 10.1016/S2213-8587(14)70057-9 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI2YE UT WOS:000336724300024 PM 24731674 ER PT J AU Amaratunga, C Witkowski, B Khim, N Menard, D Fairhurst, RM AF Amaratunga, Chanaki Witkowski, Benoit Khim, Nimol Menard, Didier Fairhurst, Rick M. TI Artemisinin resistance in Plasmodium falciparum SO LANCET INFECTIOUS DISEASES LA English DT Letter ID MALARIA C1 [Amaratunga, Chanaki; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Witkowski, Benoit; Khim, Nimol; Menard, Didier] Inst Pasteur Cambodge, Malaria Mol Epidemiol Unit, Phnom Penh, Cambodia. RP Amaratunga, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM rfairhurst@niaid.nih.gov FU Intramural NIH HHS [Z01 AI001000-01] NR 3 TC 22 Z9 22 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JUN PY 2014 VL 14 IS 6 BP 449 EP 450 DI 10.1016/S1473-3099(14)70777-7 PG 2 WC Infectious Diseases SC Infectious Diseases GA AH8UW UT WOS:000336414700010 PM 24849722 ER PT J AU Herrick, JA Lederman, RJ Sullivan, B Powers, JH Palmore, TN AF Herrick, Jesica A. Lederman, Robert J. Sullivan, Brigit Powers, John H. Palmore, Tara N. TI Brucella arteritis: clinical manifestations, treatment, and prognosis SO LANCET INFECTIOUS DISEASES LA English DT Article ID ABDOMINAL AORTIC-ANEURYSM; MYCOTIC-ANEURYSM; SURGICAL-TREATMENT; ROOT ABSCESS; ENDOCARDITIS; DOXYCYCLINE; MELITENSIS; INFECTION; PSEUDOANEURYSM; METAANALYSIS AB Brucellosis is the most common bacterial zoonosis, and causes a considerable burden of disease in endemic countries. Cardiovascular involvement is the main cause of mortality due to infection with Brucella spp, and most commonly manifests as endocarditis, peripheral and cerebrovascular aneurysms, or arterial and venous thromboses. We report a case of brucellosis presenting as bacteraemia and aortic endarteritis 18 years after the last known exposure to risk factors for brucella infection. The patient was treated with doxycycline, rifampicin, and gentamicin, and underwent surgical repair of a penetrating aortic ulcer, with a good clinical recovery. We review the signs and symptoms, diagnostic approach, prognosis, and treatment of brucella arteritis. We draw attention to the absence of consensus about the optimum therapy for vascular brucellosis, and the urgent need for additional studies and renewed scientific interest in this major pathogen. C1 [Herrick, Jesica A.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. [Palmore, Tara N.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Powers, John H.] NIAID, Sci Applicat Int Corp Support Collaborat Clin Res, Bethesda, MD 20892 USA. [Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA. [Sullivan, Brigit] NIH, Off Res Serv, Bethesda, MD 20892 USA. [Powers, John H.] George Washington Univ, Sch Med, Washington, DC USA. RP Herrick, JA (reprint author), Univ Illinois, Dept Med, Sect Infect Dis Immunol & Int Med, 808 South Wood St MC 735, Chicago, IL 60612 USA. EM christe5@uic.edu OI lederman, robert/0000-0003-1202-6673 FU federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health [HHSN261200800001E]; National Cancer Institute, National Institutes of Health; Collaborative Clinical Research Branch, Clinical Research Directorate/CMRP; SAIC-Frederick FX We thank the Fellows Editorial Board of the NIH for their valuable assistance with editing of this Grand Round. JP is supported by the Collaborative Clinical Research Branch, Clinical Research Directorate/CMRP, SAIC-Frederick. This project was supported by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily represent the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government. NR 64 TC 6 Z9 7 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JUN PY 2014 VL 14 IS 6 BP 520 EP 526 DI 10.1016/S1473-3099(13)70270-6 PG 7 WC Infectious Diseases SC Infectious Diseases GA AH8UW UT WOS:000336414700023 PM 24480149 ER PT J AU Boada, M Antunez, C Ramirez-Lorca, R DeStefano, AL Gonzalez-Perez, A Gayan, J Lopez-Arrieta, J Ikram, MA Hernandez, I Marin, J Galan, JJ Bis, JC Mauleon, A Rosende-Roca, M Moreno-Rey, C Gudnasson, V Moron, FJ Velasco, J Carrasco, JM Alegret, M Espinosa, A Vinyes, G Lafuente, A Vargas, L Fitzpatrick, AL Launer, LJ Saez, ME Vazquez, E Becker, JT Lopez, OL Serrano-Rios, M Tarraga, L van Duijn, CM Real, LM Seshadri, S Ruiz, A AF Boada, M. Antunez, C. Ramirez-Lorca, R. DeStefano, A. L. Gonzalez-Perez, A. Gayan, J. Lopez-Arrieta, J. Ikram, M. A. Hernandez, I. Marin, J. Galan, J. J. Bis, J. C. Mauleon, A. Rosende-Roca, M. Moreno-Rey, C. Gudnasson, V. Moron, F. J. Velasco, J. Carrasco, J. M. Alegret, M. Espinosa, A. Vinyes, G. Lafuente, A. Vargas, L. Fitzpatrick, A. L. Launer, L. J. Saez, M. E. Vazquez, E. Becker, J. T. Lopez, O. L. Serrano-Rios, M. Tarraga, L. van Duijn, C. M. Real, L. M. Seshadri, S. Ruiz, A. CA Alzheimer's Dis Neuroimaging Initi TI ATP5H/KCTD2 locus is associated with Alzheimer's disease risk SO MOLECULAR PSYCHIATRY LA English DT Article DE Alzheimer's disease; genomics; GWAS; molecular epidemiology; SNP ID GENOME-WIDE ASSOCIATION; LATE-ONSET ALZHEIMERS; IDENTIFIES VARIANTS; COMMON VARIANTS; GENE; VISUALIZATION; POPULATION; EXPRESSION; CARRIERS; MODIFY AB To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 x 10(-6) were genotyped in an independent Stage III sample (the Fundacio ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H + transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)= 1.58, P= 2.6 X 10(-7) in discovery and OR 1.43, P= 0.004 in Fundacio ACE data set; combined OR= 1.53, P= 4.7 X 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation. C1 [Boada, M.; Hernandez, I.; Mauleon, A.; Rosende-Roca, M.; Alegret, M.; Espinosa, A.; Vinyes, G.; Lafuente, A.; Vargas, L.; Tarraga, L.; Ruiz, A.] Fdn ACE, Memory Clin, Inst Catala Neurociencies Aplicades, Barcelona 08029, Spain. [Boada, M.] Univ Autonoma Barcelona VHIR UAB, Hosp Univ Vall dHebron Inst Recerca, E-08193 Barcelona, Spain. [Antunez, C.; Marin, J.] Univ Hosp Virgen de la Arrixaca, Dementia Unit, Murcia, Spain. [Ramirez-Lorca, R.; Gonzalez-Perez, A.; Gayan, J.; Galan, J. J.; Moreno-Rey, C.; Moron, F. J.; Velasco, J.; Carrasco, J. M.; Saez, M. E.; Vazquez, E.; Real, L. M.; Ruiz, A.] Neocodex, Dept Struct Genom, Seville, Spain. [DeStefano, A. L.; Seshadri, S.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [DeStefano, A. L.; Seshadri, S.] Boston Univ, Sch Med, Dept Biostat, Boston, MA USA. [Lopez-Arrieta, J.] Univ Hosp La Paz Cantoblanco, Memory Unit, Madrid, Spain. [Ikram, M. A.; van Duijn, C. M.] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. A.; van Duijn, C. M.] Netherlands Consortium Hlth Aging, Leiden, Netherlands. [Bis, J. C.; Fitzpatrick, A. L.] Univ Washington, Dept Med, Seattle, WA USA. [Gudnasson, V.] Kopavogur Univ Iceland, Icelandic Heart Assoc, Kopavogur, Iceland. [Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Washington, DC USA. [Becker, J. T.; Lopez, O. L.] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Neurol, Pittsburgh, PA USA. [Becker, J. T.] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Psychiat, Pittsburgh, PA USA. [Becker, J. T.] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Psychol, Pittsburgh, PA USA. [Serrano-Rios, M.] Hosp Clin San Carlos, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain. [Seshadri, S.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Ruiz, A (reprint author), Fdn ACE, CSO Cap Recerca, Inst Catala Neurociencies Aplicades, Marques Sentmenat 57, Barcelona 08029, Spain. EM aruiz@fundacioace.com RI Reposo, Ramirez-Lorca/D-7907-2014; Real, Luis M/K-9646-2014; Gonzalez-Perez, Antonio/A-5247-2010; IBIS, INFECCIOSAS HU/C-1271-2016; IBIS, TERAPIA CELULA/P-3297-2015; OI Real, Luis M/0000-0003-4932-7429; Gonzalez-Perez, Antonio/0000-0001-9771-5982; Ikram, Mohammad Arfan/0000-0003-0372-8585 FU Fundacion Alzheimur (Murcia); Ministerio de Educacion y Ciencia [PCT-010000-2007-18, DEX-580000-2008-4]; Corporacion Tecnologica de Andalucia [08/211]; Agencia IDEA [841318]; Diabetes Research Laboratory, Biomedical Research Foundation; CIBER de Diabetes y Enfermedades Metabolicas Asociadas; Alzheimer's Disease Neuroimaging Initiative (ADNI); National Institutes of Health Grant [U01 AG024904]; National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering; Abbott; Janssen Alzheimer Immunotherapy Research Development; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC; Novartis Pharmaceuticals Corporation; Pfizer Inc; NIH [P30 AG010129, K01 AG030514]; Dana Foundation; Fundacio ACE collaborates with CIBERNED; Alzheimer's Association; Alzheimer's Drug Discovery Foundation FX We thank the patients and controls who participated in this project. This work has been partially funded by the Fundacion Alzheimur (Murcia), the Ministerio de Educacion y Ciencia (PCT-010000-2007-18), (DEX-580000-2008-4; Gobierno de Espana), Corporacion Tecnologica de Andalucia (08/211) and Agencia IDEA (841318) (Consejeria de Innovacion, Junta de Andalucia). The Diabetes Research Laboratory, Biomedical Research Foundation. University Hospital Clinico San Carlos has been supported by CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM); CIBERDEM is an ISCIII Project. We are indebted to Trinitat Port-Carbo ' and her family who are supporting Fundacio ' ACE research programs. We also are indebted to TGEN investigators who provided a free access to genotype data to other researchers via Coriell Biorepositories. The genotypic and associated phenotypic data used in the study, 'Multi-Site Collaborative Study for Genotype-Phenotype Associations in Alzheimer's Disease (GenADA)' were provided by the GlaxoSmithKline, R& D Limited. The data sets used for analyses described in this manuscript were obtained from dbGaP through dbGaP accession number phs000219. v1. p1. Funding support for the ` Genetic Consortium for Late Onset Alzheimer's Disease' was provided through the Division of Neuroscience, NIA. The Genetic Consortium for Late Onset Alzheimer's Disease includes a genome-wide association study funded as part of the Division of Neuroscience, NIA. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by Genetic Consortium for Late Onset Alzheimer's Disease. The data sets used for analyses described in this manuscript were obtained from dbGaP through dbGaP accession number phs000168. v1. p1. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (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; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Amorfix Life Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N. V.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions 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, CA, USA. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles, CA, USA. This research was also supported by NIH Grants P30 AG010129, K01 AG030514 and the Dana Foundation. Fundacio ACE collaborates with CIBERNED.; The following have contributed to the papers as collaborators: Alejandro Romo, Irene Blanca, Susana Ruiz, Mar Buendia, Fuensanta Noguera-Perea, Emma Rodriguez-Noriega, Evaristo Fernandez-Aranda, Agustina Legaz-Garcia, Laura Vivancos-Moreau, America Morera, Marina Guitart, Susana Lara, Martirio Antequera-Torres, Salvadora Manzanares, Sandra Castano, Blanca Garcia, Begona Martinez-Herrada, Sergi Valero. NR 43 TC 16 Z9 16 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2014 VL 19 IS 6 BP 682 EP 687 DI 10.1038/mp.2013.86 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AI2BZ UT WOS:000336663100010 PM 23857120 ER PT J AU Kasza, KA Bansal-Travers, M O'Connor, RJ Compton, WM Kettermann, A Borek, N Fong, GT Cummings, KM Hyland, AJ AF Kasza, Karin A. Bansal-Travers, Maansi O'Connor, Richard J. Compton, Wilson M. Kettermann, Anna Borek, Nicolette Fong, Geoffrey T. Cummings, K. Michael Hyland, Andrew J. TI Cigarette Smokers' Use of Unconventional Tobacco Products and Associations With Quitting Activity: Findings From the ITC-4 U.S. Cohort SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID 4 COUNTRY SURVEY; SMOKELESS TOBACCO; SMOKING-CESSATION; ELECTRONIC CIGARETTES; DELIVERY-SYSTEMS; POLYTOBACCO USE; PATTERNS; SNUS; INITIATION; REDUCTION AB The purpose of this study was to evaluate the prevalence and correlates of use of nicotine-containing tobacco products such as cigars, pipe tobacco, and cigarettes that promise less exposure to toxins; e-cigarettes; and smokeless tobacco products among a cohort of conventional cigarette smokers followed over the past decade. We also evaluated associations between use of such products and cigarette quitting. Participants were 6,110 adult smokers in the United States, who were interviewed as part of the International Tobacco Control Four Country Survey between 2002 and 2011. Respondents reported their concurrent use of other smoked tobacco products (including cigars, pipe tobacco, and cigarillos), smokeless tobacco products (including chewing tobacco, snus, and snuff), unconventional cigarettes (including Omni, Accord, and Eclipse), and electronic cigarettes. Prevalence and correlates of use and associations between use and cigarette quitting were assessed using regression analyses via generalized estimating equations. Most cigarette smokers did not use unconventional tobacco products, although use of any of these products started to rise at the end of the study period (2011). For each type of tobacco product evaluated, use was most prevalent among those aged 18-24 years. Smokers who did use unconventional tobacco products did not experience a clear cessation advantage. During the past decade, relatively few cigarette smokers reported also using other tobacco products. Those that did use such products were no more likely to stop using conventional cigarettes compared with those who did not use such products. C1 [Kasza, Karin A.] Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. [Bansal-Travers, Maansi; O'Connor, Richard J.; Hyland, Andrew J.] Roswell Pk Canc Inst, Dept Hlth Behav, Buffalo, NY 14263 USA. [Compton, Wilson M.] NIDA, NIH, Bethesda, MD 20892 USA. [Kettermann, Anna; Borek, Nicolette] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. [Fong, Geoffrey T.] Univ Waterloo, Dept Psychol, Waterloo, CA USA. [Fong, Geoffrey T.] Ontario Inst Canc Res, Toronto, ON, Canada. [Cummings, K. Michael] Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Kasza, KA (reprint author), Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. EM karin.kasza@roswellpark.org RI Fong, Geoffrey/H-2810-2014; O'Connor, Richard/A-6961-2009 OI Fong, Geoffrey/0000-0001-9098-6472; FU Federal funds from the National Institute on Drug Abuse; National Institutes of Health; U.S. Food and Drug Administration, Department of Health and Human Services [HHSN271201100027C]; U.S. National Cancer Institute [P50 CA111326, P01 CA138389, R01 CA100362, R01 CA125116]; Canadian Institutes of Health Research [57897, 79551, 115016]; National Health and Medical Research Council of Australia [265903, 450110, 1005922]; Cancer Research UK [C312/A3726, C312/A6465, C312/A11039]; Robert Wood Johnson Foundation [045734]; Canadian Tobacco Control Research Initiative [014578]; Ontario Institute for Cancer Research; Canadian Cancer Society Research Institute FX This study was supported by Federal funds from the National Institute on Drug Abuse, National Institutes of Health, and the U.S. Food and Drug Administration, Department of Health and Human Services, under Contract No. HHSN271201100027C. The ITC Four Country Survey has been funded by the U.S. National Cancer Institute (P50 CA111326, P01 CA138389, R01 CA100362, R01 CA125116), Canadian Institutes of Health Research (57897, 79551, and 115016), National Health and Medical Research Council of Australia (265903, 450110, and 1005922), Cancer Research UK (C312/A3726, C312/A6465, and C312/A11039), Robert Wood Johnson Foundation (045734), and Canadian Tobacco Control Research Initiative (014578). Geoffrey T. Fong is supported by a Senior Investigator Award from the Ontario Institute for Cancer Research and a Prevention Scientist Award from the Canadian Cancer Society Research Institute. The roles of Wilson Compton, Nicolette Borek, and Anna Kettermann on this article are solely as collaborators on HHSN271201100027C, with no involvement in any other cited projects. NR 46 TC 13 Z9 13 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUN PY 2014 VL 16 IS 6 BP 672 EP 681 DI 10.1093/ntr/ntt212 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA AH9UX UT WOS:000336491000006 PM 24376276 ER PT J AU Sutin, AR English, D Evans, MK Zonderman, AB AF Sutin, Angelina R. English, Devin Evans, Michele K. Zonderman, Alan B. TI Perceived Sex Discrimination Amplifies the Effect of Antagonism on Cigarette Smoking SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID RACIAL-DISCRIMINATION; NICOTINE WITHDRAWAL; PERSONALITY-TRAITS; 5-FACTOR MODEL; MENTAL-HEALTH; UNITED-STATES; LIFE; DEPRESSION; PREDICTION; HOSTILITY AB Compared to men, the decline in smoking during the past few decades has been slower for women, and smoking-related morbidity and mortality has increased substantially. Identifying sex-specific risk factors will inform more targeted intervention/prevention efforts. The purpose of this research is to examine the interactive effect of psychological (trait antagonism) and social (perceived sex discrimination) factors on current cigarette smoking and whether these effects differ by sex. Participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS; N = 454) and participants in the Health and Retirement Study (HRS; N = 8,155) completed measures of antagonism, perceived sex discrimination, and reported whether they smoked currently. Logistic regressions were used to predict smoking from antagonism, discrimination, and their interaction. Antagonism was associated with an increased risk of smoking. For women, there was an interaction between antagonism and discrimination: among women who perceived sex discrimination, every standard deviation increase in antagonism was associated with a 2.5 increased risk of current smoking in HANDLS (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.46-4.39) and an almost 1.5 increased risk in HRS (OR = 1.43, 95% CI = 1.18-1.73). This interaction was not significant for men in either sample. In 2 independent samples, perceived sex discrimination amplified the effect of antagonism on cigarette smoking for women but not men. A hostile disposition and a perceived hostile social environment have a synergistic effect on current cigarette smoking for women. C1 [Sutin, Angelina R.] Florida State Univ, Coll Med, Dept Behav Sci & Social Med, Tallahassee, FL 32306 USA. [English, Devin] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA. RP Sutin, AR (reprint author), Florida State Univ, Coll Med, Dept Behav Sci & Social Med, 1115 W Call St, Tallahassee, FL 32306 USA. EM angelina.sutin@med.fsu.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health; National Institute on Aging [NIA U01AG009740] FX This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. The Health and Retirement Study is sponsored by the National Institute on Aging (NIA U01AG009740) and is conducted by the University of Michigan. NR 48 TC 0 Z9 0 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUN PY 2014 VL 16 IS 6 BP 794 EP 799 DI 10.1093/ntr/ntt222 PG 6 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA AH9UX UT WOS:000336491000020 PM 24477195 ER PT J AU Persoskie, A Mao, QN Chou, WYS Hesse, BW Zhao, XQ Yu, GM Li, YH Xu, ZH Song, MJ Nie, XQ Kim, P Kreps, GL AF Persoskie, Alexander Mao, Qunan Chou, Wen-Ying Sylvia Hesse, Bradford W. Zhao, Xiaoquan Yu, Guoming Li, Yinghua Xu, Zihao Song, Meijie Nie, Xueqiong Kim, Paula Kreps, Gary L. TI Absolute and Comparative Cancer Risk Perceptions Among Smokers in Two Cities in China SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID UNREALISTIC OPTIMISM; SMOKING-CESSATION; CIGARETTE SMOKERS; HEALTH; MORTALITY; IMPLEMENTATION; PREVALENCE; BELIEFS; DISEASE; BIAS AB Introduction: Knowledge about health effects of smoking motivates quit attempts and sustained abstinence among smokers and also predicts greater acceptance of tobacco control efforts such as cigarette taxes and public smoking bans. We examined whether smokers in China, the world's largest consumer of cigarettes, recognized their heightened personal risk of cancer relative to nonsmokers. Methods: A sample of Chinese people (N = 2,517; 555 current smokers) from 2 cities (Beijing and Hefei) estimated their personal risk of developing cancer, both in absolute terms (overall likelihood) and in comparative terms (relative to similarly aged people). Results: Controlling for demographics, smokers judged themselves to be at significantly lower risk of cancer than did nonsmokers on the comparative measure. No significant difference emerged between smokers and nonsmokers in absolute estimates. Conclusions: Smokers in China did not recognize their heightened personal risk of cancer, possibly reflecting ineffective warning labels on cigarette packs, a positive affective climate associated with smoking in China, and beliefs that downplay personal vulnerability among smokers (e. g., I don't smoke enough to increase my cancer risk; I smoke high-quality cigarettes that won't cause cancer). C1 [Persoskie, Alexander; Chou, Wen-Ying Sylvia; Hesse, Bradford W.] NCI, Behav Res Program, Bethesda, MD 20892 USA. [Mao, Qunan; Li, Yinghua; Nie, Xueqiong] Minist Hlth, Chinese Ctr Hlth Educ, Beijing, Peoples R China. [Zhao, Xiaoquan; Kim, Paula; Kreps, Gary L.] George Mason Univ, Dept Commun, Fairfax, VA 22030 USA. [Yu, Guoming; Xu, Zihao; Song, Meijie] Renmin Univ, Sch Journalism & Commun, Beijing, Peoples R China. RP Persoskie, A (reprint author), NCI, Behav Res Program, 9609 Med Ctr Dr,Room 3E204, Bethesda, MD 20892 USA. EM persoskieai@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 FU Chinese Center for Health Education, Ministry of Health, China FX This work was funded by the Chinese Center for Health Education, Ministry of Health, China. NR 41 TC 2 Z9 2 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUN PY 2014 VL 16 IS 6 BP 899 EP 903 DI 10.1093/ntr/ntu028 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA AH9UX UT WOS:000336491000037 PM 24668289 ER PT J AU White, A AF White, Amina TI Responding to Prenatal Disclosure of Past Sexual Abuse SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MATERNITY CARE; PREVALENCE; HISTORY; TRAUMA AB The American College of Obstetricians and Gynecologists recommends that physicians elicit a sexual abuse and rape trauma history for every patient, yet, in practice, physicians still may struggle to understand how best to obtain this history and what clinical obligations arise when a physician inquires and a woman discloses a remote history of childhood or adult sexual trauma during the course of her prenatal care. This commentary offers a practical strategy for responding to sexual trauma disclosure by developing a tailored obstetric care plan for avoiding retraumatization in labor. In this way, obstetricians may avoid causing harm and begin to meet the unique obstetric and psychological needs of sexual trauma survivors during pregnancy and delivery. C1 NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP White, A (reprint author), NIH, Ctr Clin, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM amina.white@nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 11 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2014 VL 123 IS 6 SI SI BP 1344 EP 1347 DI 10.1097/AOG.0000000000000266 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AI4BF UT WOS:000336809600028 PM 24807334 ER PT J AU Pang, ALY Title, AC Rennert, OM AF Pang, Alan Lap-Yin Title, Alexandra C. Rennert, Owen M. TI Modulation of microRNA expression in human lung cancer cells by the G9a histone methyltransferase inhibitor BIX01294 SO ONCOLOGY LETTERS LA English DT Article DE G9a methyltransferase; microRNA; lung cancer; H1299; BIX01294 ID TUMOR-SUPPRESSOR; DNA METHYLATION; DOWN-REGULATION; EPIGENETIC REGULATION; INDUCE APOPTOSIS; GENE; INVASION; TARGETS; AMPLIFICATION; CARCINOMA AB MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of their target genes at the post-transcriptional level. In cancer cells, miRNAs, depending on the biological functions of their target genes, may have a tumor-promoting or -suppressing effect. Treatment of cancer cells with inhibitors of DNA methylation and/or histone deacetylation modulates the expression level of miRNAs, which provides evidence for epigenetic regulation of miRNA expression. The consequences of inhibition of histone methyltransferase on miRNA expression, however, have not been thoroughly investigated. The present study examined the expression pattern of miRNAs in the non-small cell lung cancer cell line, H1299 with or without treatment of BIX01294, a potent chemical inhibitor of G9a methyltransferase that catalyzes the mono-and di-methylation of the lysine 9 residue of histone H3. By coupling microarray analysis with quantitative real-time polymerase chain reaction analysis, two miRNAs were identified that showed consistent downregulation following BIX01294 treatment. The results indicate that histone H3 methylation regulates miRNA expression in lung cancer cells, which may provide additional insight for future chemical treatment of lung cancer. C1 [Pang, Alan Lap-Yin; Title, Alexandra C.; Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, Bethesda, MD 20892 USA. RP Pang, ALY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, 49 Convent Dr,Room 2C08,MSC 4429, Bethesda, MD 20892 USA. EM alypang@yahoo.com FU Intramural Research Program of Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA FX The authors are supported by the Intramural Research Program of Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA. NR 47 TC 1 Z9 1 U1 1 U2 10 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 EI 1792-1082 J9 ONCOL LETT JI Oncol. Lett. PD JUN PY 2014 VL 7 IS 6 BP 1819 EP 1825 DI 10.3892/ol.2014.2034 PG 7 WC Oncology SC Oncology GA AI0QY UT WOS:000336555200013 ER PT J AU Wright, SE Rewers-Felicins, KA Quinlin, I Chowdhury, NI Ahmed, J Eldridge, PW Srivastava, SK Pastan, I AF Wright, Stephen E. Rewers-Felicins, Kathleen A. Quinlin, Imelda Chowdhury, Nazrul I. Ahmed, Jewel Eldridge, Paul W. Srivastava, Sanjay K. Pastan, Ira TI TGF alpha-PE38 enhances cytotoxic T-lymphocyte killing of breast cancer cells SO ONCOLOGY LETTERS LA English DT Article DE TGF alpha-PE38; cytotoxic T lymphocyte; cancer; breast; mucin-1 ID BLOOD MONONUCLEAR-CELLS; EPIDERMAL-GROWTH-FACTOR; PSEUDOMONAS EXOTOXIN; FACTOR-ALPHA; TUMOR-CELLS; VIABILITY; ASSAY; ADENOCARCINOMAS; XTT AB The aim of the present study was to determine whether the combination of two modalities of immunotherapy, targeting two different tumor antigens, may be feasible and non-toxic, yet enhance the killing of a human breast cancer cell line. The first modality was tumor growth factor alpha-Pseudomonas exotoxin 38 (TGF alpha-PE38), which specifically targets and kills tumor cells that express the epidermal growth factor receptor. The second modality was mucin-1 (MUC1)-specific cytotoxic T lymphocytes (CTLs), generated by MUC1 stimulation of peripheral blood mononuclear cells, to target the human breast cancer cell line, MCF7. TGF alpha-PE38 exhibited specific lysis of the MCF7 cells in a concentration- and time-dependent manner. TGF alpha-PE38 did not kill the normal hematopoietic stem cells or CTLs. Furthermore, TGF alpha-PE38 was not inhibitory for the growth or differentiation of the normal human hematopoietic stem cells into erythroid and myeloid colonies. In addition, TGF alpha-PE38 did not inhibit the killing function of CTLs, either when preincubated or co-incubated with CTLs. Finally, therapeutic enhancement was observed, in that TGF alpha-PE38 and CTLs were additive in the specific lysis of the MCF7 cells. These two modalities of immunotherapy may be beneficial for humans with breast cancer with or without other therapies, including autologous hematopoietic stem cell transplantation, specifically for purging cancer cells from hematopoietic stem cells prior to transplantation. C1 [Wright, Stephen E.; Rewers-Felicins, Kathleen A.; Quinlin, Imelda; Chowdhury, Nazrul I.; Ahmed, Jewel] Texas Tech Univ, Hlth Sci Ctr, Womens Hlth Res Inst, Dept Internal Med, Amarillo, TX 79106 USA. [Wright, Stephen E.] Texas Tech Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Sch Med, Amarillo, TX 79106 USA. [Wright, Stephen E.; Srivastava, Sanjay K.] Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Sch Pharm, Amarillo, TX 79106 USA. [Wright, Stephen E.; Eldridge, Paul W.] Harrington Canc Ctr, Amarillo, TX 79106 USA. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wright, SE (reprint author), Texas Tech Univ, Hlth Sci Ctr, Womens Hlth Res Inst, Dept Internal Med, 1400 Wallace Blvd, Amarillo, TX 79106 USA. EM stephen.wright@ttuhsc.edu FU VA medical research funds [0006]; Harrington Research Foundation (Amarillo, TX, USA); Women's Health Research Institute; Texas Tech University Health Sciences Center (Amarillo, TX, USA); Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX The authors are grateful to the Coffee Memorial Blood Center (Amarillo, TX, USA) and the Harrington Cancer Center (Amarillo, TX, USA) for the PBMCs, and to those mentioned in the text for materials and/or services. Gigi O'Connell participated in the initial phase of the studies. This study was supported in part by VA medical research funds (no. 0006), the Harrington Research Foundation (Amarillo, TX, USA), the Women's Health Research Institute, Texas Tech University Health Sciences Center (Amarillo, TX, USA) and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 23 TC 0 Z9 0 U1 1 U2 2 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 EI 1792-1082 J9 ONCOL LETT JI Oncol. Lett. PD JUN PY 2014 VL 7 IS 6 BP 2113 EP 2117 DI 10.3892/ol.2014.1969 PG 5 WC Oncology SC Oncology GA AI0QY UT WOS:000336555200073 ER PT J AU Wang, Z Niu, G Chen, XY AF Wang, Zhe Niu, Gang Chen, Xiaoyuan TI Polymeric Materials for Theranostic Applications SO PHARMACEUTICAL RESEARCH LA English DT Review DE drug delivery; imaging; nanoparticle; polymer; theranostics ID IRON-OXIDE NANOPARTICLES; POLYPEPTIDE-DOXORUBICIN CONJUGATE; MAGNETIC-RESONANCE ANGIOGRAPHY; TARGETED DRUG-DELIVERY; MRI CONTRAST AGENTS; IN-VIVO; QUANTUM-DOT; POLY(L-GLUTAMIC ACID); GOLD NANOPARTICLES; CARBON NANOTUBES AB Nanotechnology has continuously contributed to the fast development of diagnostic and therapeutic agents. Theranostic nanomedicine has encompassed the ongoing efforts on concurrent molecular imaging of biomarkers, delivery of therapeutic agents, and monitoring of therapy response. Among these formulations, polymer-based theranostic agents hold great promise for the construction of multifunctional agents for translational medicine. In this article, we reviewed the state-of-the-art polymeric nanoparticles, from preparation to application, as potential theranostic agents for diagnosis and therapy. We summarized several major polymer formulas, including polymeric conjugate complexes, nanospheres, micelles, and dendrimers for integrated molecular imaging and therapeutic applications. C1 [Wang, Zhe; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bldg 31,1C22, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov FU Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX This work was supported by the Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 177 TC 24 Z9 24 U1 6 U2 140 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 EI 1573-904X J9 PHARM RES-DORDR JI Pharm. Res. PD JUN PY 2014 VL 31 IS 6 BP 1358 EP 1376 DI 10.1007/s11095-013-1103-7 PG 19 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA AI3FK UT WOS:000336745800002 PM 23765400 ER PT J AU Xing, RJ Liu, G Zhu, JH Hou, YL Chen, XY AF Xing, Ruijun Liu, Gang Zhu, Jinghan Hou, Yanglong Chen, Xiaoyuan TI Functional Magnetic Nanoparticles for Non-Viral Gene Delivery and MR Imaging SO PHARMACEUTICAL RESEARCH LA English DT Review DE gene delivery; gene therapy; magnetic nanoparticles (MNPs); magnetic resonance imaging (MRI) ID IRON-OXIDE NANOPARTICLES; SMALL INTERFERING RNA; LOW-MOLECULAR-WEIGHT; IN-VIVO; DRUG-DELIVERY; PAMAM DENDRIMERS; BIOMEDICAL APPLICATIONS; SURFACE MODIFICATION; DNA DELIVERY; TRANSFECTION EFFICIENCY AB Gene therapy is becoming a promising strategy to treat various kinds of genetic and acquired diseases. However, the development of safe, efficient, and targetable gene delivery systems remains a major challenge in gene therapy. The unique material characteristics of magnetic nanoparticles (MNPs), including high surface area, facile surface modification, controllable size, and excellent magnetic properties, make them promising candidates for gene delivery. The engineered MNPs with modifiable functional surfaces and bioactive cores can result in several advantageous diagnostic and therapeutic properties including enhanced magnetic resonance imaging (MRI) signal intensity, long permeation and retention in the circulatory system, specific delivery of therapeutic genes to target sites. In this review, the updated research on the preparation and surface modification of MNPs for gene delivery is summarized. C1 [Xing, Ruijun; Zhu, Jinghan; Hou, Yanglong] Peking Univ, Dept Mat Sci & Engn, Coll Engn, Beijing 100871, Peoples R China. [Liu, Gang] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361102, Peoples R China. [Liu, Gang] North Sichuan Med Coll, Sichuan Key Lab Med Imaging, Nanchong 637007, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. RP Hou, YL (reprint author), Peking Univ, Dept Mat Sci & Engn, Coll Engn, Beijing 100871, Peoples R China. EM gangliu.cmitm@xmu.edu.cn; hou@pku.edu.cn RI Hou, Yanglong/B-8688-2012 FU Major State Basic Research Development Program of China (973 Program) [2010-CB934601, 2013CB733802]; National Nature Science of Foundation of China (NSFC) [81101101, 51273165, 51125001, 51172005]; National Natural Science Foundation of China [51250110078]; Fundamental Research Funds for the Central Universities [2013121039]; Chinese Ministry of Education [212149] FX This work was supported by the Major State Basic Research Development Program of China (973 Program) (2010-CB934601, 2013CB733802); the National Nature Science of Foundation of China (NSFC) (81101101, 51273165, 51125001, 51172005); the Research Fellowship for International Young Scientists of the National Natural Science Foundation of China (51250110078); Fundamental Research Funds for the Central Universities (2013121039); and the Key Project of Chinese Ministry of Education (212149). NR 119 TC 8 Z9 8 U1 3 U2 72 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 EI 1573-904X J9 PHARM RES-DORDR JI Pharm. Res. PD JUN PY 2014 VL 31 IS 6 BP 1377 EP 1389 DI 10.1007/s11095-013-1205-2 PG 13 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA AI3FK UT WOS:000336745800003 PM 24065595 ER PT J AU Ramos, E Doumatey, A Elkahloun, AG Shriner, D Huang, H Chen, G Zhou, J McLeod, H Adeyemo, A Rotimi, CN AF Ramos, E. Doumatey, A. Elkahloun, A. G. Shriner, D. Huang, H. Chen, G. Zhou, J. McLeod, H. Adeyemo, A. Rotimi, C. N. TI Pharmacogenomics, ancestry and clinical decision making for global populations SO PHARMACOGENOMICS JOURNAL LA English DT Article DE ADME; clinical decision making; global populations; pharmacogenomics ID NATURAL-SELECTION; GENOMIC MEDICINE; WARFARIN; EIGENANALYSIS; POLYMORPHISMS; ASSOCIATION; GENOTYPES; CYP2C19; DISEASE; SIGNALS AB Pharmacogenomically relevant markers of drug response and adverse drug reactions are known to vary in frequency across populations. We examined minor allele frequencies (MAFs), genetic diversity (F-ST) and population structure of 1156 genetic variants (including 42 clinically actionable variants) in 212 genes involved in drug absorption, distribution, metabolism and excretion (ADME) in 19 populations (n=1478). There was wide population differentiation in these ADME variants, reflected in the range of mean MAF (Delta MAF) and F-ST. The largest mean Delta MAF was observed in African ancestry populations (0.10) and the smallest mean AMAF in East Asian ancestry populations (0.04). MAFs ranged widely, for example, from 0.93 for single-nucleotide polymorphism (SNP) rs9923231, which influences warfarin dosing to 0.01 for SNP rs3918290 associated with capecitabine metabolism. ADME genetic variants show marked variation between and within continental groupings of populations. Enlarging the scope of pharmacogenomics research to include multiple global populations can improve the evidence base for clinical translation to benefit all peoples. C1 [Ramos, E.; Doumatey, A.; Shriner, D.; Huang, H.; Chen, G.; Zhou, J.; Adeyemo, A.; Rotimi, C. N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Elkahloun, A. G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [McLeod, H.] Univ N Carolina, Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC USA. RP Ramos, E (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. EM ramose@mail.nih.gov OI Adeyemo, Adebowale/0000-0002-3105-3231 FU National Institutes of Health [S06GM008016-320107, S06GM008016-380111]; former National Center for Research Resources [2M01RR010284]; National Institutes of Health; Intramural Research Program of the Center for Research on Genomics and Global Health; National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Center for Information Technology; Office of the Director at the National Institutes of Health [Z01HG200362] FX The informatics expertise of Kevin Long, University of North Carolina, Chapel Hill is greatly appreciated. The study was supported by National Institutes of Health grants S06GM008016-320107 to CNR and S06GM008016-380111 to AA. HUFS participants were enrolled at the Howard University General Clinical Research Center, which is supported by grant 2M01RR010284 from the former National Center for Research Resources, National Institutes of Health. This research was supported in part by the Intramural Research Program of the Center for Research on Genomics and Global Health. The Center for Research on Genomics and Global Health is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology and the Office of the Director at the National Institutes of Health (Z01HG200362). NR 27 TC 14 Z9 14 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD JUN PY 2014 VL 14 IS 3 BP 217 EP 222 DI 10.1038/tpj.2013.24 PG 6 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA AI0SK UT WOS:000336560000003 PM 23835662 ER PT J AU McCracken, JT Badashova, KK Posey, DJ Aman, MG Scahill, L Tierney, E Arnold, LE Vitiello, B Whelan, F Chuang, SZ Davies, M Shah, B McDougle, CJ Nurmi, EL AF McCracken, J. T. Badashova, K. K. Posey, D. J. Aman, M. G. Scahill, L. Tierney, E. Arnold, L. E. Vitiello, B. Whelan, F. Chuang, S. Z. Davies, M. Shah, B. McDougle, C. J. Nurmi, E. L. TI Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders SO PHARMACOGENOMICS JOURNAL LA English DT Article DE autism spectrum disorders; dopamine; genetics; hyperactivity; methylphenidate ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; DOPAMINE TRANSPORTER GENOTYPE; ABERRANT BEHAVIOR CHECKLIST; ADHD CHILDREN; DOSE-RESPONSE; RECEPTOR GENE; SCHIZOPHRENIC CHILDREN; GENOME BROWSER; ASSOCIATION AB Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P< 0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability. C1 [McCracken, J. T.; Badashova, K. K.; Whelan, F.; Shah, B.; Nurmi, E. L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci, Los Angeles, CA 90024 USA. [Posey, D. J.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychiat, Columbus, OH 43210 USA. [Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychol, Columbus, OH 43210 USA. [Scahill, L.] Yale Univ, Child Study Ctr, New Haven, CT USA. [Tierney, E.] Johns Hopkins Univ, Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA. [Vitiello, B.] NIMH, NIH, Bethesda, MD 20892 USA. [Chuang, S. Z.; Davies, M.] Columbia Univ, Dept Psychiat, New York, NY USA. [McDougle, C. J.] Massachusetts Gen Hosp, Lurie Autism Ctr, Dept Psychiat, Boston, MA 02114 USA. RP McCracken, JT (reprint author), UCLA NPI Semel Inst, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM jmccracken@mednet.ucla.edu RI Nurmi, Erika/P-4627-2014; OI Nurmi, Erika/0000-0003-4893-8957; Scahill, Lawrence/0000-0001-5073-1707 FU NIMH [N01 MH-70070, N01 MH-70009, N01 MH-70001, N01 MH 80011, MH-01805, MH094613, T32MH073517, MH-68627]; NIH Division of Research Resources General Clinical Research Center [M01 RR-00750, M01 RR-00052, M01 RR-00034, M01 RR-06022]; Korczak Foundation FX The RUPP Autism Network comprises the following investigators listed by role and study site: Ohio State University: principal investigator Michael G Amen, PhD, co-investigators L Eugene Arnold, MEd, MD, Yaser Ramadan, MD, Andrea Witwer, MA, Ronald Lindsay, MD and Patricia Nash, MD; University of California at Los Angeles: principal investigator James T McCracken, MD, co-investigators Bhavik Shah, MD, James Mc Gough, MD, Pegeen Cronin, PhD, Lisa Lee, BA; Indiana University: principal investigator Christopher J McDougle, MD, co-investigators David Posey, MD, Naomi Swiezy, PhD, Arlene Kohn, BA; Yale University: principal investigator Lawrence Scahill, MSN, PhD, co-investigators Andres Martin, MD, Kathleen Koenig, MSN, Fred Volkmar, MD, Deirdre Carroll, MSN, Allison Lancor, BS; Kennedy Krieger Institute: principal investigator Elaine Tierney, MD, co-investigators Jaswinder Ghuman, MD, Nilda Gonzalez, MD, Marco Grados, MD; National Institute of Mental Health: principal investigator Benedetto Vitiello, MD, co-investigator Louise Ritz, MBA; statisticians: Shirley Z Chuang, MS, Mark Davies, MPH, of Columbia University; data management: James Robinson, MEd, Don McMahon, MS, Nathan Kline Institute. Research supported by NIMH contracts N01 MH-70070 (principal investigator: Dr McCracken), N01 MH-70009 (principal investigator: Dr Scahill), N01 MH-70001 (principal investigator: Dr McDougle), and N01 MH 80011 (principal investigator: Dr Amen); by NIH Division of Research Resources General Clinical Research Center grants M01 RR-00750 (to Indiana University), M01 RR-00052 (to John Hopkins University), M01 RR-00034 (to Ohio University) and M01 RR-06022 (to Yale University); by NIMH grants MH-01805 (to Dr McCracken) NIMH grants MH094613 and T32MH073517 (Dr Nurmi) and MH-68627 (to Dr Posey); and by funding from the Korczak Foundation (to Dr Scahill). The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the National Institute of Mental Health, the National Institutes of Health, or the Department of Health and Human Services. NR 67 TC 11 Z9 12 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD JUN PY 2014 VL 14 IS 3 BP 295 EP 302 DI 10.1038/tpj.2013.23 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA AI0SK UT WOS:000336560000014 PM 23856854 ER PT J AU Holman, DM Berkowitz, Z Guy, GP Hartman, AM Perna, FM AF Holman, Dawn M. Berkowitz, Zahava Guy, Gery P., Jr. Hartman, Anne M. Perna, Frank M. TI The association between demographic and behavioral characteristics and sunburn among U.S. adults - National Health Interview Survey, 2010 SO PREVENTIVE MEDICINE LA English DT Article DE Sunburn; Skin neoplasms; Primary prevention; Health behavior; Adult ID SKIN-CANCER RISK; CUTANEOUS MALIGNANT-MELANOMA; UNITED-STATES; SUN PROTECTION; WOMEN; METAANALYSIS; POPULATION; PREVALENCE; PREVENTION; SUNSCREEN AB Objective. To examine the association between demographic and behavioral characteristics and sunburn among U.S. adults. Method We used 2010 National Health Interview Survey data (N = 24,970) to conduct multivariable logistic regressions examining associations with having 1 or more sunburns in the past year and having 4 or more sunburns in the past year. Results. Overall, 37.1% of adults experienced sunburn in the past year. The adjusted prevalence of sunburn was particularly common among adults aged 18-29 years (52.0%), those who repeatedly burn or freckle after 2 weeks in the sun (45.9%), whites (443%), indoor tanners (44.1%), those with a family history of melanoma (43.9%), and those who are US-born (39.5%). Physical activity, alcohol consumption, and overweight/obesity were positively associated with sunburn (all P < 0.001); sun protection behaviors were not significantly associated with sunburn (P = 0.35). Among those who were sunburned in the past year, 12.1% experienced 4 or more sunburns. Conclusion. Sunburn is common, particularly among younger adults, those with a more sun-sensitive skin type, whites, those with a family history of melanoma, the highly physically active, and indoor tanners. Efforts are needed to facilitate sun-safety during outdoor recreation, improve the consistency of sun protection practices, and prevent sunburn, particularly among these subgroups. Published by Elsevier Inc. C1 [Holman, Dawn M.; Berkowitz, Zahava; Guy, Gery P., Jr.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30341 USA. [Hartman, Anne M.; Perna, Frank M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Holman, DM (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Highway,NE Chamblee Bldg 107,MS F76, Atlanta, GA 30341 USA. EM dholman@cdc.gov; zab3@cdc.gov; irm2@cdc.gov; hartmana@mail.nih.gov; pernafm@mail.nih.gov FU Intramural CDC HHS [CC999999] NR 39 TC 22 Z9 22 U1 4 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD JUN PY 2014 VL 63 BP 6 EP 12 DI 10.1016/j.ypmed.2014.02.018 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AI0TM UT WOS:000336562900002 PM 24589442 ER PT J AU Ursano, RJ Colpe, LJ Heeringa, SG Kessler, RC Schoenbaum, M Stein, MB AF Ursano, Robert J. Colpe, Lisa J. Heeringa, Steven G. Kessler, Ronald C. Schoenbaum, Michael Stein, Murray B. CA Army STARRS Collaborators TI The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID ADOLESCENT SUICIDE; PROPENSITY SCORE; VETERANS; BEHAVIOR; AFGHANISTAN; MILITARY; IRAQ; CARE; MEN AB Importance/Objective: Although the suicide rate in the U.S. Army has traditionally been below age-gender matched civilian rates, it has climbed steadily since the beginning of the Iraq and Afghanistan conflicts and since 2008 has exceeded the demographically matched civilian rate. The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multicomponent epidemiological and neurobiological study designed to generate actionable evidence-based recommendations to reduce Army suicides and increase knowledge about risk and resilience factors for suicidality and its psychopathological correlates. This paper presents an overview of the Army STARRS component study designs and of recent findings. Design/Setting/Participants/Intervention: Army STARRS includes six main component studies: (1) the Historical Administrative Data Study (HADS) of Army and Department of Defense (DoD) administrative data systems (including records of suicidal behaviors) for all soldiers on active duty 2004-2009 aimed at finding administrative record predictors of suicides; (2) retrospective case-control studies of fatal and nonfatal suicidal behaviors (each planned to have n = 150 cases and n = 300 controls); (3) a study of new soldiers (n = 50,765 completed surveys) assessed just before beginning basic combat training (BCT) with self-administered questionnaires (SAQ), neurocognitive tests, and blood samples; (4) a cross-sectional study of approximately 35,000 (completed SAQs) soldiers representative of all other (i.e., exclusive of BCT) active duty soldiers; (5) a pre-post deployment study (with blood samples) of soldiers in brigade combat teams about to deploy to Afghanistan (n = 9,421 completed baseline surveys), with sub-samples assessed again one, three, and nine months after returning from deployment; and (6) a pilot study to follow-up SAQ respondents transitioning to civilian life. Army/DoD administrative data are being linked prospectively to the large-scale survey samples to examine predictors of subsequent suicidality and related mental health outcomes. Main outcome measures: Measures (self-report and administratively recorded) of suicidal behaviors and their psychopathological correlates. Results: Component study cooperation rates are comparatively high. Sample biases are relatively small. Inefficiencies introduced into parameter estimates by using nonresponse adjustment weights and time-space clustering are small. Initial findings show that the suicide death rate, which rose over 2004-2009, increased for those deployed, those never deployed, and those previously deployed. Analyses of administrative records show that those deployed or previously deployed were at greater suicide risk. Receiving a waiver to enter the Army was not associated with increased risk. However, being demoted in the past two years was associated with increased risk. Time in current deployment, length of time since return from most recent deployment, total number of deployments, and time interval between most recent deployments (known as dwell time) were not associated with suicide risk. Initial analyses of survey data show that 13.9% of currently active non-deployed regular Army soldiers considered suicide at some point in their lifetime, while 5.3% had made a suicide plan, and 2.4% had attempted suicide. Importantly, 47-60% of these outcomes first occurred prior to enlistment. Prior mental disorders, in particular major depression and intermittent explosive disorder, were the strongest predictors of these self-reported suicidal behaviors. Most onsets of plans-attempts among ideators (58.3-63.3%) occurred within the year of onset of ideation. About 25.1% of non-deployed U.S. Army personnel met 30-day criteria for a DSM-IV anxiety, mood, disruptive behavior, or substance disorder (15.0% an internalizing disorder; 18.4% an externalizing disorder) and 11.1% for multiple disorders. Importantly, three-fourths of these disorders had pre-enlistment onsets. Conclusions: Integration across component studies creates strengths going well beyond those in conventional applications of the same individual study designs. These design features create a strong methodological foundation from which Army STARRS can pursue its substantive research goals. The early findings reported here illustrate the importance of the study and its approach as a model of studying rare events particularly of national security concern. Continuing analyses of the data will inform suicide prevention for the U.S. Army. C1 [Ursano, Robert J.] Uniformed Serv Univ Sch Med, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD USA. [Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA. [Heeringa, Steven G.] Univ Michigan Inst Social Res, Ann Arbor, MI USA. [Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA USA. RP Ursano, RJ (reprint author), USUHS, Dept Psychiat, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM robert.ursano@usuhs.edu FU Eli Lilly Company; EPI-Q; GlaxoSmithKline; Ortho-McNeil Janssen Scientific Affairs; Sanofi-Aventis Groupe; Shire U.S., Inc.; Walgreens Co.; Janssen; Department of the Army; U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIH/NIMH) [U01MH087981] FX Financial Disclosure: In the past five years, Dr. Kessler has been a consultant for Eli Lilly & Company, Glaxo, Inc., Integrated Benefits Institute, Ortho-McNeil Janssen Scientific Affairs, Pfizer Inc., Sanofi-Aventis Groupe, Shire U.S. Inc., and Transcept Pharmaceuticals Inc. and has served on advisory boards for Johnson & Johnson. He has had research support for his epidemiological studies over this time period from Eli Lilly & Company, EPI-Q, GlaxoSmithKline, Ortho-McNeil Janssen Scientific Affairs, Sanofi-Aventis Groupe, Shire U.S., Inc., and Walgreens Co. Dr. Kessler owns a 25% share in DataStat, Inc. Dr. Stein has in the last three years been a consultant for Healthcare Management Technologies and had research support for pharmacological imaging studies from Janssen. The remaining authors report nothing to disclose.; Funding/Support: Army STARRS was sponsored by the Department of the Army and funded under cooperative agreement number U01MH087981 with the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIH/NIMH). The contents are solely the responsibility of the authors and do not necessarily represent the views of the Department of Health and Human Services, NIMH, the Department of the Army, or the Department of Defense. NR 35 TC 39 Z9 39 U1 3 U2 23 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD SUM PY 2014 VL 77 IS 2 BP 107 EP 119 PG 13 WC Psychiatry SC Psychiatry GA AI1VD UT WOS:000336642400001 PM 24865195 ER PT J AU Wang, HR Wang, XH Archer, TK Zwaka, TP Cooney, AJ AF Wang, Hongran Wang, Xiaohong Archer, Trevor K. Zwaka, Thomas P. Cooney, Austin J. TI GCNF-Dependent Activation of Cyclin D1 Expression via Repression of Mir302a During ESC Differentiation SO STEM CELLS LA English DT Article DE Cyclin D1; GCNF; microRNA; Mir302; ESCs ID CELL NUCLEAR FACTOR; EMBRYONIC STEM-CELLS; RECEPTOR GCNF; BINDING; PROTEIN; OCT4; PLURIPOTENCY; PROGENITORS; TRANSITION; INHIBITION AB Cyclin D1 plays an important role in the regulation of cellular proliferation and its expression is activated during gastrulation in the mouse; however, it remains unknown how cyclin D1 expression is regulated during early embryonic development. Here, we define the role of germ cell nuclear factor (GCNF) in the activation of cyclin D1 expression during embryonic stem cell (ESC) differentiation as a model of early development. During our study of GCNF knockout (GCNF(-/-)) ESC, we discovered that loss of GCNF leads to the repression of cyclin D1 activation during ESC differentiation. This was determined to be an indirect effect of deregulation Mir302a, which is a cyclin D1 suppressor via binding to the 3'UTR of cyclin D1 mRNA. Moreover, we showed that Mir302 is a target gene of GCNF that inhibits Mir302 expression by binding to a DR0 element within its promoter. Inhibition of Mir302a using Mir302 inhibitor during differentiation of GCNF(-/-) ESCs restored cyclin D1 expression. Similarly over-expression of GCNF during differentiation of GCNF(-/-) ESCs rescued the inhibition of Mir302a expression and the activation of cyclin D1. These results reveal that GCNF plays a key role in regulating activation of cyclin D1 expression via inhibition of Mir302a. C1 [Wang, Hongran; Wang, Xiaohong; Cooney, Austin J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Wang, Hongran; Wang, Xiaohong; Cooney, Austin J.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. [Wang, Xiaohong] Texas Heart Inst, Stem Cell Ctr, Houston, TX 77025 USA. [Archer, Trevor K.] NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Zwaka, Thomas P.] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Med, Black Family Stem Cell Inst, New York, NY USA. RP Cooney, AJ (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM acooney@bcm.edu FU NIH [P01 GM081627] FX This work was supported by a Grant NIH P01 GM081627 to A.J.C. NR 41 TC 2 Z9 2 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PD JUN PY 2014 VL 32 IS 6 BP 1527 EP 1537 DI 10.1002/stem.1689 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AI3EE UT WOS:000336741700017 PM 24578347 ER PT J AU Robertson, DJ Lieberman, DA Winawer, SJ Ahnen, DJ Baron, JA Schatzkin, A Cross, AJ Zauber, AG Church, TR Lance, P Greenberg, ER Martinez, ME AF Robertson, Douglas J. Lieberman, David A. Winawer, Sidney J. Ahnen, Dennis J. Baron, John A. Schatzkin, Arthur Cross, Amanda J. Zauber, Ann G. Church, Timothy R. Lance, Peter Greenberg, E. Robert Martinez, Maria Elena TI Colorectal cancers soon after colonoscopy: a pooled multicohort analysis SO GUT LA English DT Article ID FECAL OCCULT-BLOOD; SOCIETY TASK-FORCE; SCREENING COLONOSCOPY; ANTIOXIDANT VITAMINS; ASYMPTOMATIC ADULTS; ADENOMATOUS POLYPS; RANDOMIZED-TRIAL; INCREASED RISK; SURVEILLANCE; POLYPECTOMY AB Objective Some individuals are diagnosed with colorectal cancer (CRC) despite recent colonoscopy. We examined individuals under colonoscopic surveillance for colonic adenomas to assess possible reasons for diagnosing cancer after a recent colonoscopy with complete removal of any identified polyps. Design Primary data were pooled from eight large (>800 patients) North American studies in which participants with adenoma(s) had a baseline colonoscopy (with intent to remove all visualised lesions) and were followed with subsequent colonoscopy. We used an algorithm based on the time from previous colonoscopy and the presence, size and histology of adenomas detected at prior exam to assign interval cancers as likely being new, missed, incompletely resected (while previously an adenoma) or due to failed biopsy detection. Results 9167 participants (mean age 62) were included in the analyses, with a median follow-up of 47.2 months. Invasive cancer was diagnosed in 58 patients (0.6%) during follow-up (1.71 per 1000 person-years follow-up). Most cancers (78%) were early stage (I or II); however, 9 (16%) resulted in death from CRC. We classified 30 cancers (52%) as probable missed lesions, 11 (19%) as possibly related to incomplete resection of an earlier, non-invasive lesion and 14 (24%) as probable new lesions. The cancer diagnosis may have been delayed in three cases (5%) because of failed biopsy detection. Conclusions Despite recent colonoscopy with intent to remove all neoplasia, CRC will occasionally be diagnosed. These cancers primarily seem to represent lesions that were missed or incompletely removed at the prior colonoscopy and might be avoided by increased emphasis on identifying and completely removing all neoplastic lesions at colonoscopy. C1 [Robertson, Douglas J.] Dept Vet Affairs Med Ctr, White River Jct, VT USA. [Robertson, Douglas J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Robertson, Douglas J.] Dartmouth Inst, Hanover, NH USA. [Lieberman, David A.] Dept Vet Affairs Med Ctr, Portland, OR USA. [Winawer, Sidney J.; Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ahnen, Dennis J.] Univ Colorado, Dept Vet Affairs Med Ctr, Denver, CO 80202 USA. [Ahnen, Dennis J.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Baron, John A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Schatzkin, Arthur; Cross, Amanda J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA. [Lance, Peter; Martinez, Maria Elena] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Lance, Peter; Martinez, Maria Elena] Univ Arizona, Mel & Enid Zuckerman Arizona Coll Publ Hlth, Tucson, AZ USA. [Lance, Peter] Univ Arizona, Dept Med, Tucson, AZ USA. [Greenberg, E. Robert] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Robertson, DJ (reprint author), VA Med Ctr, 215 N Main St,Sect Gastroenterol 111E, White River Jct, VT 05009 USA. EM douglas.robertson@va.gov RI Lance, Peter/I-2196-2014; OI Lance, Peter/0000-0003-2944-1881; Church, Timothy R./0000-0003-3292-5035 FU Public Health Service from the National Cancer Institute [CA-41108, CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005, CA26852]; Cooperative Studies Program, Department of Veterans Affairs; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Career Development Award FX This work was supported by Public Health Service grants CA-41108, CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005 and CA26852 from the National Cancer Institute. Funding for the Veteran's Affairs Study was supported by the Cooperative Studies Program, Department of Veterans Affairs. Dr Robertson's work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development Career Development Award. NR 57 TC 79 Z9 81 U1 0 U2 10 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JUN PY 2014 VL 63 IS 6 BP 949 EP 956 DI 10.1136/gutjnl-2012-303796 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AG4AB UT WOS:000335360000014 PM 23793224 ER PT J AU Naluyima, P Eller, MA Laeyendecker, O Quinn, TC Serwadda, D Sewankambo, NK Gray, RH Michael, NL Wabwire-Mangen, F Robb, ML Sandberg, JK AF Naluyima, Prossy Eller, Michael A. Laeyendecker, Oliver Quinn, Thomas C. Serwadda, David Sewankambo, Nelson K. Gray, Ronald H. Michael, Nelson L. Wabwire-Mangen, Fred Robb, Merlin L. Sandberg, Johan K. TI Impaired natural killer cell responses are associated with loss of the highly activated NKG2AR CD57 R CD56 dim subset in HIV-1 subtype D infection in Uganda SO AIDS LA English DT Article DE AIDS; CD57; HIV-1; immune activation; natural killer cells; NKG2A; subtype D ID VIRUS TYPE-1 INFECTION; KIR3DL1(+) NK CELLS; DENDRITIC CELLS; INNATE IMMUNITY; RAKAI DISTRICT; T-CELLS; HLA-B; EXPRESSION; DIVERSITY; PATTERNS AB Objective:Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and function in Ugandans with chronic untreated HIV-1 subtype D infection in comparison to uninfected community matched controls.Methods:Cryopreserved peripheral blood mononuclear cells (PBMCs) from 42 HIV-infected individuals and 28 HIV-negative controls were analysed using eight-colour flow cytometry. NK cell surface expression of CD16, CD56, CD57, HLA-DR and NKG2A were used to investigate activation, maturation and differentiation status. NK cell function was evaluated by measuring interferon-gamma (IFN) production in response to K562 cells, or interleukin (IL)-12 and IL-18.Results:CD56(dim) NK cells from HIV-infected individuals produced less IFN in response to IL-12 and IL-18 than did CD56(dim) NK cells from uninfected controls. Infected individuals had lower levels of CD56(dim) NK cells coexpressing the differentiation markers NKG2A and CD57 than controls. In addition, their NKG2A(+)CD57(+) CD56(dim) NK cells displayed elevated activation levels as assessed by HLA-DR expression. Cytokine-induced IFN production correlated directly with coexpression of CD57 and NKG2A on CD56(dim) NK cells.Conclusion:HIV-1 subtype D infection is associated with impaired NK cell responsiveness to cytokines, decline of the NKG2A(+)CD57(+) CD56(dim) NK cell subset, as well as elevated activation in this subset. These alterations within the NK cell compartment may contribute to immunopathogenesis of HIV-1 subtype D infection in Ugandans. C1 [Naluyima, Prossy; Wabwire-Mangen, Fred] Makerere Univ Walter Reed Project, Kampala, Uganda. [Naluyima, Prossy; Sandberg, Johan K.] Karolinska Univ Hosp Huddinge, Karolinska Inst, Ctr Infect Med, Dept Med, S-14186 Stockholm, Sweden. [Eller, Michael A.; Michael, Nelson L.; Robb, Merlin L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Eller, Michael A.; Robb, Merlin L.] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA. [Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Div Intramural Res, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Serwadda, David; Wabwire-Mangen, Fred] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Kampala, Uganda. [Serwadda, David; Sewankambo, Nelson K.] Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda. [Sewankambo, Nelson K.] Makerere Univ, Coll Hlth Sci, Fac Med, Kampala, Uganda. [Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Sandberg, JK (reprint author), Karolinska Univ Hosp Huddinge, Karolinska Inst, Ctr Infect Med, Dept Med, F59, S-14186 Stockholm, Sweden. EM johan.sandberg@ki.se FU Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; U.S. Department of Defense; National Institute of Allergy and Infectious Diseases (NIAID) [R01 AI34826, R01 AI34265]; National Institute of Child and Health Development [5P30HD06826]; Fogarty Foundation [5D43TW00010]; Swedish Research Council; Swedish Cancer Society; Stockholm County Council; Karolinska Institutet; Division of Intramural Research, NIAID, NIH FX Primary support was provided by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense. Data collection was supported, in part, by grants R01 AI34826 and R01 AI34265 from the National Institute of Allergy and Infectious Diseases (NIAID); grant 5P30HD06826 from the National Institute of Child and Health Development; grant 5D43TW00010 from the Fogarty Foundation. Additional support was provided by the Swedish Research Council, the Swedish Cancer Society, the Stockholm County Council, Karolinska Institutet and the Division of Intramural Research, NIAID, NIH. NR 39 TC 4 Z9 4 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 1 PY 2014 VL 28 IS 9 BP 1273 EP 1278 DI 10.1097/QAD.0000000000000286 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AH2SX UT WOS:000335972500004 PM 24959961 ER PT J AU Kapetanovic, S Dass-Brailsford, P Nora, D Talisman, N AF Kapetanovic, Suad Dass-Brailsford, Priscilla Nora, Diana Talisman, Nicholas TI Mental Health of HIV-Seropositive Women During Pregnancy and Postpartum Period: A Comprehensive Literature Review SO AIDS AND BEHAVIOR LA English DT Review DE HIV; Pregnancy; Mental health; Perinatal depression; Women ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTIMATE PARTNER VIOLENCE; QUALITY-OF-LIFE; DEPRESSIVE SYMPTOMS; POSITIVE WOMEN; INFECTED WOMEN; SOUTH-AFRICA; PRENATAL DEPRESSION; EMOTIONAL DISTRESS; SUBSTANCE USE AB With growing numbers of HIV-seropositive (HIV+) women of child-bearing age and increased access to effective clinical protocols for preventing mother-to-child transmission (MTCT) of HIV, mental health-related factors have become increasingly relevant due to their potential to affect the women's quality of life, obstetric outcomes and risk of MTCT. This review synthesizes evidence from 53 peer-reviewed publications examining mental health-related variables in pregnant and postpartum HIV+ women. The presentation of results is organized by the level of socioeconomic resources in the countries where studies were conducted (i.e., high-, middle-, and low-income countries). It is concluded that psychiatric symptoms, particularly depression, and mental health vulnerabilities (e.g., inadequate coping skills) are widespread among pregnant HIV+ women globally and have a potential to affect psychological well-being, quality of life and salient clinical outcomes. The current body of evidence provides rationale for developing and evaluating clinical and structural interventions aimed at improving mental health outcomes and their clinical correlates in pregnant HIV+ women. C1 [Kapetanovic, Suad; Nora, Diana] NIMH, NIH, Bethesda, MD 20892 USA. [Kapetanovic, Suad] NIMH, Off Clin Director, Bethesda, MD 20892 USA. [Dass-Brailsford, Priscilla] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. [Talisman, Nicholas] Georgetown Univ, Sch Med, Washington, DC USA. RP Kapetanovic, S (reprint author), NIMH, Off Clin Director, 10 CRC,Room 6-5340,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. EM suad.kapetanovic@nih.gov FU Intramural NIH HHS [Z99 MH999999]; NIAID NIH HHS [P30 AI087714, P30AI087714] NR 72 TC 10 Z9 10 U1 0 U2 16 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JUN PY 2014 VL 18 IS 6 BP 1152 EP 1173 DI 10.1007/s10461-014-0728-9 PG 22 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AH5YF UT WOS:000336206400019 PM 24584458 ER PT J AU Prizment, AE Yatsuya, H Lutsey, PL Lubin, JH Woodward, M Folsom, AR Huxley, RR AF Prizment, Anna E. Yatsuya, Hiroshi Lutsey, Pamela L. Lubin, Jay H. Woodward, Mark Folsom, Aaron R. Huxley, Rachel R. TI Smoking Behavior and Lung Cancer in a Biracial Cohort The Atherosclerosis Risk in Communities Study SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID UNITED-STATES; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; CIGARETTE-SMOKING; INTERVAL ESTIMATION; MENTHOL CIGARETTES; WHITE SMOKERS; CARCINOMA; CESSATION; WOMEN AB Background: In the U.S., the incidence of lung cancer varies by race, with rates being highest among black men. There are marked differences in smoking behavior between blacks and whites, but little is known regarding how these differences contribute to the racial disparities in lung cancer. Purpose: To compare the lung cancer risk associated with smoking in 14,610 blacks and whites in the prospective cohort Atherosclerosis Risk in Communities study. Methods: Smoking characteristics were ascertained at baseline and three follow-up visits in 1990-1992, 1993-1995, and 1996-1998 (response rates were 93%, 86%, and 80%, respectively), as well as from annual telephone interviews. Data Were analyzed in the fall of 2012. Multivariable-adjusted proportional hazards models were used to calculate hazard ratios and 95% CIs for lung cancer. Results: Over 20 years of follow-up (1987-2006), 470 incident cases of lung cancer occurred. Lung cancer incident rates were highest in black men and lowest in black women. However, there was no evidence to support racial differences in the associations of smoking status, intensity, or age at initiation with lung cancer risk (all p(interaction) >= 0.25). The hazard ratio for those who started smoking at age <= 12 versus >22 years was 3.03 (95% CI =1.62, 5.67). Prolonged smoking cessation ( >= 10 years) was associated with a decrease in lung cancer risk, with equivalent benefits in whites and blacks, 84% and 74%, respectively (P-interaction=0.25). Conclusions: Smoking confers similar lung cancer risk in blacks and whites. (C) 2014 American Journal of Preventive Medicine C1 [Prizment, Anna E.; Lutsey, Pamela L.; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Yatsuya, Hiroshi] Fujita Hlth Univ, Sch Med, Dept Publ Hlth, Toyoake, Aichi 47011, Japan. [Lubin, Jay H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Huxley, Rachel R.] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia. RP Prizment, AE (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 South Second St,Suite 300, Minneapolis, MN 55454 USA. EM prizm001@umn.edu RI Huxley, Rachel/J-4638-2013; Woodward, Mark/D-8492-2015; Huxley, Rachel/C-7032-2013 OI Huxley, Rachel/0000-0002-2705-6616; Huxley, Rachel/0000-0002-2705-6616 FU Intramural NIH HHS; NCATS NIH HHS [KL2 TR000113]; NCI NIH HHS [T32 CA132670, T32CA132670, U01 CA164975, U01 CA164975-01]; NCRR NIH HHS [UL1 RR025005, UL1RR025005]; NHLBI NIH HHS [HHSN268201100006C, HHSN268201100005C, HHSN268201100005G, HHSN268201100005I, HHSN268201100007C, HHSN268201100007I, HHSN268201100008C, HHSN268201100008I, HHSN268201100009C, HHSN268201100009I, HHSN268201100010C, HHSN268201100011C, HHSN268201100011I, HHSN268201100012C] NR 41 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2014 VL 46 IS 6 BP 624 EP 632 DI 10.1016/j.amepre.2014.01.017 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA AH5SC UT WOS:000336190400010 PM 24842739 ER PT J AU Wira, CR Veronese, F AF Wira, Charles R. Veronese, Fulvia TI Hormone Regulation of the Mucosal Environment in the Reproductive Tract and the Prevention of HIV Infection SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Letter C1 [Wira, Charles R.] Geisel Sch Med Dartmouth, Dept Physiol & Neurobiol, Lebanon, NH 03756 USA. [Veronese, Fulvia] NIAID, Prevent Sci Program, DAIDS, NIH,DHHS, Bethesda, MD 20892 USA. RP Wira, CR (reprint author), Geisel Sch Med Dartmouth, Dept Physiol & Neurobiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Charles.R.Wira@Dartmouth.edu; veronesf@niaid.nih.gov FU NIAID NIH HHS [R01 AI102838] NR 1 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JUN PY 2014 VL 71 IS 6 SI SI BP 487 EP 489 DI 10.1111/aji.12269 PG 3 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA AH1YK UT WOS:000335917600001 PM 24832616 ER PT J AU Barreto-de-Souza, V Arakelyan, A Margolis, L Vanpouille, C AF Barreto-de-Souza, Victor Arakelyan, Anush Margolis, Leonid Vanpouille, Christophe TI HIV-1 Vaginal Transmission: Cell- Free or Cell- Associated Virus? SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Review DE Cell; HIV-1; mucosa; semen; transmission ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN LYMPHOID-TISSUE; SEXUALLY-TRANSMITTED-DISEASES; ACTIVE ANTIRETROVIRAL THERAPY; FEMALE REPRODUCTIVE-TRACT; GENITAL EPITHELIAL-CELLS; TROJAN HORSE LEUKOCYTES; MATURE DENDRITIC CELLS; CD4(+) T-CELLS; IN-VITRO AB The vast majority of new HIV infections in male-to-female transmission occurs through semen, where HIV-1 is present in two different forms: as free and as cell-associated virus. In the female lower genital tract, semen mixes with female genital secretions that contain various factors, some of which facilitate or inhibit HIV-1 transmission. Next, HIV-1 crosses the genital epithelia, reaches the regional lymph nodes, and disseminates through the female host. Cervico-vaginal mucosa contains multiple barriers, resulting in a low probability of vaginal transmission. However, in some cases, HIV-1 is able to break these barriers. Although the exact mechanisms of how these barriers function remain unclear, their levels of efficiency against cell-free and cell-associated HIV-1 are different, and both cell-free and cell-associated virions seem to use different strategies to overcome these barriers. Understanding the basic mechanisms of HIV-1 vaginal transmission is required for the development of new antiviral strategies to contain HIV-1 epidemics. C1 [Barreto-de-Souza, Victor; Arakelyan, Anush; Margolis, Leonid; Vanpouille, Christophe] NICHHD, Sect Intercellular Interact, Program Phys Biol, Bethesda, MD 20892 USA. RP Margolis, L (reprint author), NICHHD, Program Phys Biol, Bldg 10,Room 9D58,10 Ctr Dr,MSC 1855, Bethesda, MD 20892 USA. EM margolis@helix.nih.gov FU NICHD; Brazilian Ministry of Education/CAPES; Brazilian Ministry of Science and Technology/CNPq FX This work was supported by the NICHD intramural program. VBS was partially supported by fellowships from the Brazilian Ministry of Education/CAPES and the Brazilian Ministry of Science and Technology/CNPq. We are also grateful to Dr. Jean-Charles Grivel for his critical review of the manuscript and helpful suggestions. NR 139 TC 7 Z9 7 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JUN PY 2014 VL 71 IS 6 SI SI BP 589 EP 599 DI 10.1111/aji.12240 PG 11 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA AH1YK UT WOS:000335917600013 PM 24730358 ER PT J AU Mestecky, J Wei, Q Alexander, R Raska, M Novak, J Moldoveanu, Z AF Mestecky, Jiri Wei, Qing Alexander, Rashada Raska, Milan Novak, Jan Moldoveanu, Zina TI Humoral Immune Responses to HIV in the Mucosal Secretions and Sera of HIV- Infected SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Review DE Antibody responses; human immunodeficiency virus; mucosal immunity; secretory IgA and IgG ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENITAL-TRACT; NEUTRALIZING ANTIBODIES; IGA ANTIBODIES; 1-INFECTED INDIVIDUALS; ENVELOPE-GLYCOPROTEIN; EXTERNAL SECRETIONS; MONOCLONAL-ANTIBODY; IMMUNOGLOBULIN-G; IN-VITRO AB Although sera and all external secretions contain antibodies to human immunodeficiency virus (HIV), their levels, specificity, isotypes, and relevant effector functions display a great degree of variability. Antibodies that bind HIV antigens and neutralize the virus are predominantly associated with the IgG isotype in sera and in all external secretions, even where total levels of IgG are much lower than those of IgA. Rectal fluid that contains high IgA, but low IgG levels, displayed low neutralizing activity independent of antibodies. Therefore, external secretions should be evaluated before and after selective depletion of Ig. At the systemic level, HIV-specific IgA may interfere with the effector functions of IgG, as suggested by recent studies of individuals systemically immunized with an experimental HIV vaccine. Although HIV-specific IgG and IgA antibodies may exhibit their protective activities at mucosal surfaces through interference with viral entry and local neutralization at the systemic level, such antibodies may display discordant effector functions. C1 [Mestecky, Jiri; Wei, Qing; Alexander, Rashada; Raska, Milan; Novak, Jan; Moldoveanu, Zina] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Mestecky, Jiri] Charles Univ Prague, Fac Med, Inst Microbiol & Immunol, Prague, Czech Republic. [Alexander, Rashada] NIH, Off Director, Bethesda, MD 20892 USA. [Raska, Milan] Palacky Univ, Fac Med, Dept Immunol, CR-77147 Olomouc, Czech Republic. RP Mestecky, J (reprint author), Univ Alabama Birmingham, BBRB 757,845 19th St South, Birmingham, AL 35294 USA. EM mestecky@uab.edu FU NIH-NIAID [PO1 AI083027, R21 AI083613]; University of Alabama at Birmingham (UAB) School of Medicine; UAB Immunology, Autoimmunity, and Transplantation Strategic Planning; UAB CFAR [P30 AI027767] FX This work was supported by grants from NIH-NIAID (PO1 AI083027; R21 AI083613), a Pilot Grant from the University of Alabama at Birmingham (UAB) School of Medicine, a grant from UAB Immunology, Autoimmunity, and Transplantation Strategic Planning and a Developmental Grant from UAB CFAR (P30 AI027767). NR 69 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JUN PY 2014 VL 71 IS 6 SI SI BP 600 EP 607 DI 10.1111/aji.12203 PG 8 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA AH1YK UT WOS:000335917600014 PM 24494997 ER PT J AU Aladjem, MI Fu, HQ AF Aladjem, Mirit I. Fu, Haiqing TI A new light on DNA replication from the inactive X chromosome SO BIOESSAYS LA English DT Article DE cell cycle; chromatin; DNA replication; epigenetics; inactive X chromosome ID HBO1 HISTONE ACETYLASE; ALLELE-SPECIFIC REPLICATION; BETA-GLOBIN LOCUS; MAMMALIAN-CELLS; ASYNCHRONOUS REPLICATION; TRANSCRIPTION-FACTOR; DELAYED REPLICATION; GENE-EXPRESSION; S-PHASE; ORIGIN AB While large portions of the mammalian genome are known to replicate sequentially in a distinct, tissue-specific order, recent studies suggest that the inactive X chromosome is duplicated rapidly via random, synchronous DNA synthesis at numerous adjacent regions. The rapid duplication of the inactive X chromosome was observed in high-resolution studies visualizing DNA replication patterns in the nucleus, and by allele-specific DNA sequencing studies measuring the extent of DNA synthesis. These studies conclude that inactive X chromosomes complete replication earlier than previously thought and suggest that the strict order of DNA replication detected in the majority of genomic regions is not preserved in non-transcribed, silent chromatin. These observations alter current concepts about the regulation of DNA replication in non-transcribed portions of the genome in general and in the inactive X-chromosome in particular. C1 [Aladjem, Mirit I.; Fu, Haiqing] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Aladjem, MI (reprint author), NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM aladjemm@mail.nih.gov RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU CCR; National Cancer Institute; National Institutes of Health FX We thank Drs. Eric Bouhassira, Carl Schildkraut and Mathew Thayer for helpful discussions and Owen Smith for critical reading of the manuscript. We apologize to colleagues whose work could not be cited directly due to space limitations. Studies at our lab are supported by the intramural program of the CCR, National Cancer Institute, National Institutes of Health. NR 84 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 EI 1521-1878 J9 BIOESSAYS JI Bioessays PD JUN PY 2014 VL 36 IS 6 BP 591 EP 597 DI 10.1002/bies.201400021 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA AI0IH UT WOS:000336529800011 PM 24706495 ER PT J AU Yanik, GA Horowitz, MM Weisdorf, DJ Logan, BR Ho, VT Soiffer, RJ Carter, SL Wu, J Wingard, JR Difronzo, NL Ferrara, JL Giralt, S Madtes, DK Drexler, R White, ES Cooke, KR AF Yanik, Gregory A. Horowitz, Mary M. Weisdorf, Daniel J. Logan, Brent R. Ho, Vincent T. Soiffer, Robert J. Carter, Shelly L. Wu, Juan Wingard, John R. Difronzo, Nancy L. Ferrara, James L. Giralt, Sergio Madtes, David K. Drexler, Rebecca White, Eric S. Cooke, Kenneth R. TI Randomized, Double-Blind, Placebo-Controlled Trial of Soluble Tumor Necrosis Factor Receptor: Enbrel (Etanercept) for the Treatment of Idiopathic Pneumonia Syndrome after Allogeneic Stem Cell Transplantation: Blood and Marrow Transplant Clinical Trials Network Protocol SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Bone marrow transplantation; IPS; TNF; Pneumonia; Pulmonary ID LUNG INJURY; RISK AB Idiopathic pneumonia syndromes (IPS) is a diffuse, noninfectious lung injury that occurs acutely after allogeneic hematopoietic cell transplantation (HCT). JPS-related mortality has been historically high (>50%) despite treatment with systemic corticosteroids and supportive care measures. We have now examined the role of tumor necrosis factor inhibition in a randomized, double-blind, placebo-controlled trial of corticosteroids with etanercept or placebo. Thirty-four subjects (>= 18 years) with IPS after HCT were randomized to receive methylprednisolone (2 mg/kg/day) plus etanercept (0.4 mg/kg twice weekly X 4 weeks; n = 16) or placebo (n = 18). No active infections and a pathogen-negative bronchoscopy were required at study entry. Response (alive, with complete discontinuation of supplemental oxygen support) and overall survival were examined. This study, originally planned to accrue 120 patients, was terminated prematurely due to slow accrual. In the limited number of patients examined, there were no differences in response rates at day 28 of study. Ten of 16 patients (62.5% [95%,confidence interval {CI}, 35.4% to 84.8%]) receiving etanercept and 12 of 18 patients (66.7% [95% CI, 41,0% to 86.7%]) receiving placebo met the day 28 response definition (P = 1.00). The median survival was 170 days (95% CI, 11 to 362) with etanercept versus 64 days (95% CI, 26 to 209) with placebo (P = .51). Among responders, the-median time to discontinuation of supplemental oxygen was 9 days (etanercept) versus 7 days (placebo). Therapy was well tolerated, With 1 toxicity-related death froth infectious pneumonia in the placebo arm. The treatment of IPS with corticosteroids in adult HCT recipients was associated with high early response rates (>60%) compared with historical reports, with poor overall survival. The addition of etanercept did not lead to further increases in response, although the sample size of this truncated trial preclude a definitive conclusion. (C) 2014 Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation. C1 [Yanik, Gregory A.; Ferrara, James L.] Univ Michigan, Blood & Marrow Transplant Program, Med Ctr, Dept Pediat & Internal Med, Ann Arbor, MI 48109 USA. [Horowitz, Mary M.; Logan, Brent R.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Weisdorf, Daniel J.] Univ Minnesota, Dept Internal Med, Blood & Marrow Transplantat Program, Minneapolis, MN USA. [Ho, Vincent T.; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. [Carter, Shelly L.; Wu, Juan] EMMES Corp, Rockville, MD USA. [Wingard, John R.] Univ Florida, Dept Med, Gainesville, FL USA. [Difronzo, Nancy L.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. [Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Dept Stem Cell Transplantat, New York, NY 10021 USA. [Madtes, David K.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA. [Madtes, David K.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Drexler, Rebecca] Natl Marrow Donor Program, Minneapolis, MN USA. [Drexler, Rebecca] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [White, Eric S.] Univ Michigan, Med Ctr, Dept Internal Med Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Cooke, Kenneth R.] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Canc Ctr, Baltimore, MD 21205 USA. RP Yanik, GA (reprint author), Univ Michigan, Blood & Marrow Transplant Program, Med Ctr, 5310 Canc Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM gyanik@umich.edu FU National Heart, Lung, and Blood Institute [U10HL069294]; Leukemia and Lymphoma Society; Burroughs Welcome Fund; National Cancer Institute FX Support for this study was provided by grant U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute, The Leukemia and Lymphoma Society (to K.R.C.), and the Burroughs Welcome Fund (to K.R.C.). Immunex Corporation, a wholly owned subsidiary of Amgen Inc., provided study drug and central pharmacy support for the trial. NR 17 TC 13 Z9 13 U1 0 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2014 VL 20 IS 6 BP 858 EP 864 DI 10.1016/j.bbmt.2014.02.026 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AH8WH UT WOS:000336418400019 PM 24607553 ER PT J AU Koethe, Y Mannes, AJ Wood, BJ AF Koethe, Yilun Mannes, Andrew J. Wood, Bradford J. TI Image-guided Nerve Cryoablation for Post-thoracotomy Pain Syndrome SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Cryoablation; Clinical practice; Pain management; Spine/nervous system; Experimental IR ID FEASIBILITY; ABLATION; ACCURACY; FUSION; TUMORS AB Chronic post-thoracotomy pain syndrome (PTPS) can cause significant patient distress and is frequently difficult to manage. Percutaneous intercostal nerve (ICN) cryoablation by palpation of surface landmarks can be risky, as inaccurate probe placement can lead to hemo- or pneumothorax. Experience with image-guided ICN cryoablation with treatment planning and device navigation is limited. A patient with intractable PTPS was treated with ICN cryoablation under cone-beam computed tomography guidance with software-assisted needle trajectory planning and ablation zone simulation. This procedure provided the patient similar to 8 weeks of relief. This case demonstrated that ICN cryoablation is feasible under image guidance with device navigation and ablation simulation and may result in a few months of pain relief in cases of intractable PTPS. C1 [Koethe, Yilun; Wood, Bradford J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Koethe, Yilun] Duke Univ, Sch Med, Durham, NC 27710 USA. [Mannes, Andrew J.] NIH, Perioperat Med Clin Ctr, Bethesda, MD 20892 USA. RP Koethe, Y (reprint author), NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,MSC 1182,Bldg 10, Bethesda, MD 20892 USA. EM yilun.koethe@gmail.com; bwood@cc.nih.gov OI Mannes, Andrew/0000-0001-5834-5667 FU [ZIA BC 011242-03CCRO] FX The authors wish to thank Dr. Nadine Abi-Jaoudeh for contributing the images used in this publication. Grant #No. ZIA BC 011242-03CCRO NR 14 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 EI 1432-086X J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JUN PY 2014 VL 37 IS 3 BP 843 EP 846 DI 10.1007/s00270-013-0718-8 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AH7RM UT WOS:000336331300041 PM 23954965 ER PT J AU Amalou, H Wood, BJ AF Amalou, Hayet Wood, Bradford J. TI Beware Catheter Breakdown During Alcohol Sclerosis of Lymphoceles SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter ID POSTOPERATIVE LYMPHOCELES; RENAL-TRANSPLANTATION; SCLEROTHERAPY; MANAGEMENT C1 [Amalou, Hayet; Wood, Bradford J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol Radiol & Imaging Sci, MSC 1182,10 Ctr Dr, Bethesda, MD 20892 USA. EM bwood@nih.gov FU Intramural NIH HHS NR 5 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 EI 1432-086X J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JUN PY 2014 VL 37 IS 3 BP 850 EP 851 DI 10.1007/s00270-013-0774-0 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AH7RM UT WOS:000336331300043 PM 24190637 ER PT J AU Solier, S Pommier, Y AF Solier, Stephanie Pommier, Yves TI The nuclear gamma-H2AX apoptotic ring: implications for cancers and autoimmune diseases SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Chromatin; Epigenetics; Biomarkers ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; DNA-DAMAGE RESPONSE; DEPENDENT PROTEIN-KINASE; PROGRAMMED CELL-DEATH; ATM ACTIVATION; CHROMOSOME CONDENSATION; CYCLE PHASE; SERINE 139; S-PHASE AB Apoptosis is a fundamental process for metazoan development. It is also relevant to the pathophysiology of immune diseases and cancers and to the outcome of cancer chemotherapies, as well as being a target for cancer therapies. Apoptosis involves intrinsic pathways typically initiated by DNA damaging agents and engaging mitochondria, and extrinsic pathways typically initiated by "death receptors" and their ligands TRAIL and TNF at the cell surface. Recently, we discovered the apoptotic ring, which microscopically looks like a nuclear annular staining early in apoptosis. This ring is, in three-dimensional space, a thick intranuclear shell consisting of epigenetic modifications including histone H2AX and DNA damage response (DDR) proteins. It excludes the DNA repair factors usually associated with gamma-H2AX in the DDR nuclear foci. Here, we summarize our knowledge of the apoptotic ring, and discuss its biological and pathophysiological relevance, as well as its value as a potential pharmacodynamic biomarker for anticancer therapies. C1 [Solier, Stephanie; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU NCI Intramural Program, Center for Cancer Research, NIH FX We wish to thank our close laboratory colleagues for their commitment to gamma-H2AX basic research: Dr. William Bonner, Dr. Christophe Redon, Dr. James H. Doroshow, and Dr. Kurt W. Kohn. We also wish to thank our NCI colleagues from the DCTD, PADIS, for the development of gamma-H2AX pharmacodynamics biomarker assays: Dr. James H. Doroshow, Dr. Joseph E. Tomaszewski, Dr. Raph E. Parchment, and Dr. Robert Kinders. Our studies are supported by the NCI Intramural Program, Center for Cancer Research, NIH. NR 68 TC 16 Z9 16 U1 1 U2 10 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X EI 1420-9071 J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUN PY 2014 VL 71 IS 12 BP 2289 EP 2297 DI 10.1007/s00018-013-1555-2 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH8SJ UT WOS:000336408200007 PM 24448903 ER PT J AU Case, ED Chong, A Wehrly, TD Hansen, B Child, R Hwang, S Virgin, HW Celli, J AF Case, Elizabeth Di Russo Chong, Audrey Wehrly, Tara D. Hansen, Bryan Child, Robert Hwang, Seungmin Virgin, Herbert W. Celli, Jean TI The Francisella O-antigen mediates survival in the macrophage cytosol via autophagy avoidance SO CELLULAR MICROBIOLOGY LA English DT Article ID LIPID-A; TULARENSIS; LIPOPOLYSACCHARIDE; REPLICATION; ESCAPE; RECOGNITION; MUTANTS; PATHOGENICITY; STRAINS; ATG5 AB Autophagy is a key innate immune response to intracellular parasites that promotes their delivery to degradative lysosomes following detection in the cytosol or within damaged vacuoles. Like Listeria and Shigella, which use specific mechanisms to avoid autophagic detection and capture, the bacterial pathogen Francisella tularensis proliferates within the cytosol of macrophages without demonstrable control by autophagy. To examine how Francisella evades autophagy, we screened a library of F.tularensis subsp. tularensisSchu S4 HimarFT transposon mutants in GFP-LC3-expressing murine macrophages by microscopy for clones localized within autophagic vacuoles after phagosomal escape. Eleven clones showed autophagic capture at 6h post-infection, whose HimarFT insertions clustered to fourgenetic loci involved in lipopolysaccharidic and capsular O-antigen biosynthesis. Consistent with the HimarFT mutants, in-frame deletion mutants of two representative loci, FTT1236 and FTT1448c (manC), lacking both LPS and capsular O-antigen, underwent phagosomal escape but were cleared from the host cytosol. Unlike wild-type Francisella, the O-antigen deletion mutants were ubiquitinated, and recruited the autophagy adaptor p62/SQSTM1 and LC3 prior to cytosolic clearance. Autophagy-deficient macrophages partially supported replication of both mutants, indicating that O-antigen-lacking Francisella are controlled by autophagy. These data demonstrate the intracellular protective role of this bacterial surface polysaccharide against autophagy. C1 [Case, Elizabeth Di Russo; Chong, Audrey; Wehrly, Tara D.; Child, Robert; Celli, Jean] NIAID, Lab Intracellular Parasites, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Hansen, Bryan] NIAID, Electron Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Hwang, Seungmin; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Hwang, Seungmin; Virgin, Herbert W.] Washington Univ, Sch Med, Midwest Reg Ctr Excellence Biodef & Emerging Infe, St Louis, MO 63110 USA. RP Celli, J (reprint author), Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA. EM jcelli@vetmed.wsu.edu OI Hwang, Seungmin/0000-0003-0846-5462; Case, Elizabeth/0000-0002-9129-3894 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases; NIAID [U54 AI057160] FX We thank members of the lab for their assistance with generating the Francisella-HimarFT insertion library, Michael Apicella for the monoclonal 11B7 antibody against Francisella capsule, helpful suggestions and critical reading of the manuscript, Thomas Zahrt for the pHimarH3, Jacques Peschon and Ed Miao for pBMN-Z-v-mycMC29, and Leigh Knodler for critical reading of the manuscript. We also thank Stephanie Lathrop and Olivia Steele-Mortimer for providing human peripheral blood monocytes. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases and by NIAID Grant U54 AI057160 to H.W. Virgin. The authors declare that they have no conflict of interest. NR 37 TC 20 Z9 20 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-5814 EI 1462-5822 J9 CELL MICROBIOL JI Cell Microbiol. PD JUN PY 2014 VL 16 IS 6 BP 862 EP 877 DI 10.1111/cmi.12246 PG 16 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA AH2DF UT WOS:000335930200006 PM 24286610 ER PT J AU Den Linger, CS Meropol, NJ Li, T Lewis, NL Engstrom, PF Weiner, LM Cheng, JD Alpaugh, RK Cooper, H Wright, JJ Cohen, SJ AF Den Linger, Crystal S. Meropol, Neal J. Li, Tianyu Lewis, Nancy L. Engstrom, Paul F. Weiner, Louis M. Cheng, Jonathan D. Alpaugh, R. Katherine Cooper, Harry Wright, John J. Cohen, Steven J. TI A Phase II Trial of the Proteasome Inhibitor Bortezomib in Patients With Advanced Biliary Tract Cancers SO CLINICAL COLORECTAL CANCER LA English DT Article DE Biliary tract cancers; Bortezomib; Cholangiocarcinoma; Proteosome inhibition ID HUMAN CHOLANGIOCARCINOMA CELLS; DIAGNOSED MULTIPLE-MYELOMA; SINGLE-AGENT GEMCITABINE; INTRAHEPATIC CHOLANGIOCARCINOMA; GALLBLADDER CARCINOMA; P27(KIP1) EXPRESSION; PLUS DEXAMETHASONE; HISTOLOGIC TYPES; SURVIVAL RATES; KAPPA-B AB Therapeutic options in advanced biliary tract cancers are limited. We evaluated bortezomib in 20 patients with advanced biliary tract cancers in a single-arm phase H study. Although no objective responses were seen, 9 patients achieved stable disease with encouraging median time to progression and survival rates, suggesting that evaluation of bortezomib in combination with other therapies is warranted in this disease. Background: Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest that proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers. Patients and Methods: Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0 to 2 previous therapies received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 of a 21-day cycle. The primary end point was objective response rate. A Simon 2-stage design was used (null response rate of < 5% and response rate of >= 20% of interest). Results: Twenty patients enrolled (bile duct/gallbladder cancer [14/6] and previous treatments 0/1/2 [10/6/3]). The trial was discontinued early because of lack of confirmed partial responses. No unanticipated adverse events were noted. There was 1 unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% confidence interval [CI], 0.7-77.6 months). Median survival was 9 months (95% CI, 4.6-18.5 months). The 6-month and 1-year survival rates were 70% and 38%, respectively. There was no difference in survival based on primary disease site. Conclusion: Single-agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered.(C) 2014 Elsevier Inc. All rights reserved. C1 [Den Linger, Crystal S.; Engstrom, Paul F.; Cheng, Jonathan D.; Alpaugh, R. Katherine; Cohen, Steven J.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Meropol, Neal J.] Case Western Reserve Univ, Univ Hosp, Case Med Ctr, Case Comprehens Canc Ctr,Seidman Canc Ctr,Div Hem, Cleveland, OH 44106 USA. [Li, Tianyu] Fox Chase Canc Ctr, Dept Biostat, Philadelphia, PA 19111 USA. [Lewis, Nancy L.] Thomas Jefferson Univ Hosp, Dept Med Oncol, Philadelphia, PA 19107 USA. [Weiner, Louis M.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. [Cooper, Harry] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. [Wright, John J.] Natl Canc Inst, Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD USA. RP Den Linger, CS (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM crystal.denlinger@fccc.edu FU National Cancer Institute [P30 CA006927]; Cancer Therapy Evaluation Program NCI [6135] FX This study was supported by the National Cancer Institute P30 CA006927 (Fisher) and the Cancer Therapy Evaluation Program NCI # 6135 (SJC). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. NR 48 TC 4 Z9 4 U1 0 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 EI 1938-0674 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD JUN PY 2014 VL 13 IS 2 BP 81 EP 86 DI 10.1016/j.clcc.2013.12.005 PG 6 WC Oncology SC Oncology GA AH5UO UT WOS:000336196800002 PM 24512954 ER PT J AU Huang, J Nair, SG Mahoney, MR Nelson, GD Shields, AF Chan, E Goldberg, RM Gill, S Kahlenberg, MS Quesenberry, JT Thibodeau, SN Smyrk, TC Grothey, A Sinicrope, FA Webb, TA Farr, GH Pockaj, BA Berenberg, JL Mooney, M Sargent, DJ Alberts, SR AF Huang, Jocelin Nair, Suresh G. Mahoney, Michelle R. Nelson, Garth D. Shields, Anthony F. Chan, Emily Goldberg, Richard M. Gill, Sharlene Kahlenberg, Morton S. Quesenberry, James T. Thibodeau, Stephen N. Smyrk, Thomas C. Grothey, Axel Sinicrope, Frank A. Webb, Thomas A. Farr, Gist H., Jr. Pockaj, Barbara A. Berenberg, Jeffrey L. Mooney, Margaret Sargent, Daniel J. Alberts, Steven R. CA Alliance Clinical Trials Oncology TI Comparison of FOLFIRI With or Without Cetuximab in Patients With Resected Stage III Colon Cancer; NCCTG (Alliance) Intergroup Trial N0147 SO CLINICAL COLORECTAL CANCER LA English DT Article DE Adjuvant therapy; Disease free survival; Overall survival; Response rate ID METASTATIC COLORECTAL-CANCER; 1ST-LINE TREATMENT; ADJUVANT TREATMENT; RANDOMIZED-TRIAL; FLUOROURACIL; LEUCOVORIN; CHEMOTHERAPY; IRINOTECAN; KRAS; OXALIPLATIN AB In the randomized phase III trial N0147 for resected colon cancer, the early trial versions included treatment arms of FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) with and without cetuximab, in addition to FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) with and without cetuximab. In the small group receiving FOLFIRI plus cetuximab evidence of possible benefit was noted. However, pending results of a randomized trial, FOLFIRI plus cetuximab should not be considered as an option for adjuvant therapy. Background: Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomized phase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRI-containing arms were discontinued. We report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab. Patients and Methods: After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity. Results: One hundred and six patients received FOLFIRI and 40 received FOLFIRI plus cetuximab. Median follow-up was 5.95 years (range, 0.1-7.0 years). The addition of cetuximab showed a trend toward improved DFS (hazard ratio [HR], 0.53; 95% CI, 0.26-1.1; P = .09) and OS (HR, 0.45; 95% CI, 0.17-1.16; P = .10) in the overall group, regardless of KRAS status, and in patients with wild type KRAS. Grade >= 3 nonhematologic adverse effects were significantly increased in the cetuximab versus FOLFIRI-alone arm (68% vs. 46%; P = .02). Adjuvant FOLFIRI resulted in a 3-year DFS less than that expected for FOLFOX. Conclusion: In this small randomized subset of patients with resected stage III colon cancer, the addition of cetuximab to FOLFIRI was associated with a nonsignificant trend toward improved DFS and OS. Nevertheless, considering the limitations of this analysis, FOLFOX without the addition of a biologic agent remains the standard of care for adjuvant therapy in resected stage Ill colon cancer. (C) 2014 Elsevier Inc. All rights reserved. C1 [Huang, Jocelin; Thibodeau, Stephen N.; Smyrk, Thomas C.; Grothey, Axel; Sinicrope, Frank A.; Alberts, Steven R.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA. [Nair, Suresh G.] Lehigh Valley Hosp, Allentown, PA USA. [Mahoney, Michelle R.; Nelson, Garth D.; Sargent, Daniel J.] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN 55905 USA. [Shields, Anthony F.] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Chan, Emily] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA. [Goldberg, Richard M.] Ohio State Univ, Wexner Med Ctr, Dept Oncol, Columbus, OH 43210 USA. [Gill, Sharlene] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Kahlenberg, Morton S.] Surg Oncol Assoc South Texas, San Antonio, TX USA. [Quesenberry, James T.] Siouxland Hematol Oncol Assoc, Sioux City, IA USA. [Webb, Thomas A.] Illinois Oncol Res Assoc Community Clin Oncol Pro, Peoria, IL USA. [Farr, Gist H., Jr.] Ochsner Community Clin Oncol Program, New Orleans, LA USA. [Pockaj, Barbara A.] Mayo Clin Arizona, Scottsdale, AZ USA. [Berenberg, Jeffrey L.] Univ Hawaii, Ctr Canc, Community Clin Oncol Program, Honolulu, HI 96822 USA. [Mooney, Margaret] Natl Canc Inst, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Clin Invest Branch, Bethesda, MD USA. RP Alberts, SR (reprint author), Mayo Clin, Div Med Oncol, Go-10,200 First St SW, Rochester, MN 55905 USA. EM alberts.steven@mayo.edu OI Sargent, Daniel/0000-0002-2684-4741 FU NCCTG; Mayo Clinic; Public Health Service from NCI - Department of Health and Human Services [CA-25224, CA-37404, CA-35103, CA-35113, CA-35272, CA-114740, CA-32102, CA-14028, CA49957, CA21115, CA31946, CAl2027, CA37377]; Canadian Cancer Society Research Institute [021039, 015469]; US NCI [CA077202] FX This study was conducted as a collaborative trial of the NCCTG, Mayo Clinic, and was supported in part by Public Health Service grants CA-25224, CA-37404, CA-35103, CA-35113, CA-35272, CA-114740, CA-32102, CA-14028, CA49957, CA21115, CA31946, CAl2027, CA37377 from the NCI, Department of Health and Human Services. National Cancer Institute of Canada Clinical Trials Group participation in this trial was supported by funding received from the Canadian Cancer Society Research Institute (Grant #021039 and #015469) and the US NCI (Grant #CA077202). The content is solely the responsibility of the authors and does not necessarily represent the views of the NCI or the National Institutes of Health. NR 18 TC 15 Z9 17 U1 0 U2 5 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 EI 1938-0674 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD JUN PY 2014 VL 13 IS 2 BP 100 EP 109 DI 10.1016/j.clcc.2013.12.002 PG 10 WC Oncology SC Oncology GA AH5UO UT WOS:000336196800005 PM 24512953 ER PT J AU Keller, SP Fessler, HE AF Keller, Steven P. Fessler, Henry E. TI Monitoring of oesophageal pressure SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE respiratory monitoring; dead space; volumetric capnography; mechanical ventilation ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; TRANSPULMONARY PRESSURE; PLEURAL PRESSURE; MECHANICS; EXCHANGE; BALLOONS; SUPINE AB Purpose of review Volumetric capnography (VCap) measures the kinetics of carbon dioxide (CO2) elimination on a breath-by-breath basis. A volumetric capnogram contains extensive physiological information about metabolic production, circulatory transport and CO2 elimination within the lungs. VCap is also the best clinical tool to measure dead spaces allowing a detailed analysis of the functional components of each tidal volume, thereby providing clinically useful hints about the lung's efficiency of gas exchange. Difficulties in its bedside measurement, oversimplifications of its interpretation along with prevailing misconceptions regarding dead space analysis have, however, limited its adoption as a routine tool for monitoring mechanically ventilated patients. Recent findings Improvements in CO2 measuring technologies and more advanced algorithms for faster and more accurate analysis of volumetric capnograms have increased our physiological understanding and thus the clinical usefulness of VCap. The recently validated VCap-based method for estimating alveolar partial pressure of CO2 provided a breakthrough for a fully noninvasive breath-by-breath measurement of physiological dead space. Recent advances in VCap and our improved understanding of its clinical implications may help in overcoming the known limitations and reluctances to include expired CO2 kinetics and dead space analysis in routine bedside monitoring. It is about time to start using this powerful monitoring tool to support decision making in the intensive care environment. C1 [Keller, Steven P.] NIH, Dept Crit Care, Bethesda, MD 20892 USA. [Keller, Steven P.; Fessler, Henry E.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. RP Fessler, HE (reprint author), Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, 1830 E Monument St,5th Floor, Baltimore, MD 21205 USA. EM hfessler@jhmi.ed NR 29 TC 5 Z9 7 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5295 EI 1531-7072 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD JUN PY 2014 VL 20 IS 3 BP 340 EP 346 DI 10.1097/MCC.0000000000000095 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA AH2TK UT WOS:000335973800017 PM 24751808 ER PT J AU Clark, NA Mumford, SL Segars, JH AF Clark, Natalie A. Mumford, Sunni L. Segars, James H. TI Reproductive impact of MRI-guided focused ultrasound surgery for fibroids: a systematic review of the evidence SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Review DE fertility; fibroids; HIFU; MRgFUS; pregnancy ID UTERINE FIBROIDS; PREGNANCY; ABLATION; MRGFUS; LEIOMYOMAS; HYPERINTENSE; IMPROVEMENT; PREDICTORS; EXPERIENCE; EFFICACY AB Purpose of reviewMagnetic-resonance-guided focused ultrasound surgery (MRgFUS) is a minimally invasive technique for the treatment of uterine fibroids. The purpose of this review is to highlight the impact of MRgFUS on fertility and reproductive outcomes.Recent findingsThe role of MRgFUS in the treatment of fibroids has been evolving since its introduction in 2004. Several new devices and techniques including location-specific treatment, volumetric therapy, and vessel-targeted therapy have been introduced over the last few years. Several case series report uncomplicated pregnancy following MRgFUS; however, results of the ongoing studies will further elucidate the utility of MRgFUS in patients planning future fertility. A systematic review of the literature was completed and studies that reported quality of life at baseline and after 6 months were included in a meta-analysis.SummaryMRgFUS represents a minimally invasive treatment for uterine fibroids that is able to improve the quality of life and fibroid size with durability. It is possible that MRgFUS could be the treatment of choice for patients desiring future fertility; however, further investigation is needed. C1 [Clark, Natalie A.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. [Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA. [Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Segars, JH (reprint author), CRC, Bldg 10,Room 1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov FU Intramural Research Program of Reproductive and Adult Endocrinology, NICHD, NIH [ZIA HD-008737-12]; Division of Intramural Population Health Research, NICHD, NIH FX This research was supported, in part, by the Intramural Research Program of Reproductive and Adult Endocrinology, NICHD, NIH (ZIA HD-008737-12) and the Division of Intramural Population Health Research, NICHD, NIH. NR 50 TC 13 Z9 14 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X EI 1473-656X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD JUN PY 2014 VL 26 IS 3 BP 151 EP 161 DI 10.1097/GCO.0000000000000070 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA AH1PF UT WOS:000335892600005 PM 24751998 ER PT J AU Tan, IS Ramamurthi, KS AF Tan, Irene S. Ramamurthi, Kumaran S. TI Spore formation in Bacillus subtilis SO ENVIRONMENTAL MICROBIOLOGY REPORTS LA English DT Review ID DEVELOPMENTAL TRANSCRIPTION FACTOR; PENICILLIN-BINDING PROTEINS; BACTERIAL ENDOSPORE FORMATION; CELL-SPECIFIC TRANSCRIPTION; ACID-SOLUBLE PROTEINS; HEAT-RESISTANCE; SUBCELLULAR-LOCALIZATION; MORPHOGENETIC PROTEIN; SPORULATION PROTEIN; HISTIDINE KINASE AB Although prokaryotes ordinarily undergo binary fission to produce two identical daughter cells, some are able to undergo alternative developmental pathways that produce daughter cells of distinct cell morphology and fate. One such example is a developmental programme called sporulation in the bacterium Bacillus subtilis, which occurs under conditions of environmental stress. Sporulation has long been used as a model system to help elucidate basic processes of developmental biology including transcription regulation, intercellular signalling, membrane remodelling, protein localization and cell fate determination. This review highlights some of the recent work that has been done to further understand prokaryotic cell differentiation during sporulation and its potential applications. C1 [Tan, Irene S.; Ramamurthi, Kumaran S.] NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. [Tan, Irene S.] Johns Hopkins Univ, NIH, Grad Partnerships Program, Baltimore, MD 21218 USA. RP Ramamurthi, KS (reprint author), NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. EM ramamurthiks@mail.nih.gov RI Ramamurthi, Kumaran/P-3516-2015 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research FX We thank P. Eswaramoorthy for comments on the manuscript. This work was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and Center for Cancer Research. NR 157 TC 40 Z9 42 U1 12 U2 85 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1758-2229 J9 ENV MICROBIOL REP JI Environ. Microbiol. Rep. PD JUN PY 2014 VL 6 IS 3 BP 212 EP 225 DI 10.1111/1758-2229.12130 PG 14 WC Environmental Sciences; Microbiology SC Environmental Sciences & Ecology; Microbiology GA AG9VQ UT WOS:000335768400002 PM 24983526 ER PT J AU Williams, TH Mendelson, TC AF Williams, Tory H. Mendelson, Tamra C. TI Quantifying Reproductive Barriers in a Sympatric Pair of Darter Species SO EVOLUTIONARY BIOLOGY LA English DT Review DE Behavioral isolation; Coloration; Etheostoma; Reproductive barrier; Sexual selection; Speciation ID SEXUAL SELECTION; PERCIDAE ETHEOSTOMATINAE; BEHAVIORAL ISOLATION; MALE COLORATION; VISUAL SIGNALS; SPECIATION; DIVERSIFICATION; EVOLUTION; PATTERNS; GENUS AB Quantifying and comparing the strengths of different reproductive barriers between diverging lineages is especially useful for determining the evolutionary mechanisms driving speciation. Etheostoma barrenense and Etheostoma zonale are closely related sympatric species of darters that are sexually dimorphic and exhibit clear differences in male nuptial coloration. Prior studies demonstrated that these species exhibit complete behavioral isolation, and that both intraspecific and interspecific variation in male coloration play a role in female choice, all consistent with speciation by sexual selection on male nuptial color. Remaining unclear, however, is whether behavioral isolation is the strongest reproductive barrier between these species or, alternatively, whether additional reproductive barriers are equally strong, which could implicate mechanisms other than sexual selection in speciation. Here, we compare the relative strengths of multiple reproductive barriers between the two focal species, measuring: (1) ecological isolation, (2) gametic incompatibility, (3) hybrid inviability, (4) conspecific sperm precedence, and comparing these measures to a previously estimated strength of behavioral isolation. We find that behavioral isolation is the strongest reproductive barrier measured to date and suggest it may be the only barrier that has evolved to completion. This result provides additional empirical evidence for speciation driven by sexual selection and provides insight into the maintenance of sympatric species in nature. C1 [Williams, Tory H.] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Mendelson, Tamra C.] Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA. RP Williams, TH (reprint author), NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. EM tory.williams@nih.gov FU National Science Foundation [DEB-0718987, IOS-0919271] FX We thank J.M. Gumm and M. D. Martin for help during fish capture and ecological data collection, P.J. Ciccotto for aid in fish care, and C. F. O'Rourke for assistance with microsatellite protocols. We thank our anonymous reviewers for their time and suggestions. The authors have no conflict of interest regarding this work. This research was partially funded by National Science Foundation grants DEB-0718987 and IOS-0919271 to TCM. NR 34 TC 4 Z9 4 U1 3 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0071-3260 EI 1934-2845 J9 EVOL BIOL JI Evol. Biol. PD JUN PY 2014 VL 41 IS 2 BP 212 EP 220 DI 10.1007/s11692-013-9259-y PG 9 WC Evolutionary Biology SC Evolutionary Biology GA AH7QG UT WOS:000336327800004 ER PT J AU Kaplan, R Bush, D Bonnefond, M Bandettini, PA Barnes, GR Doeller, CF Burgess, N AF Kaplan, Raphael Bush, Daniel Bonnefond, Mathilde Bandettini, Peter A. Barnes, Gareth R. Doeller, Christian F. Burgess, Neil TI Medial prefrontal theta phase coupling during spatial memory retrieval SO HIPPOCAMPUS LA English DT Article DE hippocampus; mPFC; MTL; MEG; oscillations ID FRONTAL-MIDLINE THETA; HIPPOCAMPAL THETA; GAMMA OSCILLATIONS; WORKING-MEMORY; EPISODIC MEMORY; TEMPORAL-LOBE; NEURONAL OSCILLATIONS; DECISION-MAKING; BEHAVING RAT; FREQUENCY AB Memory retrieval is believed to involve a disparate network of areas, including medial prefrontal and medial temporal cortices, but the mechanisms underlying their coordination remain elusive. One suggestion is that oscillatory coherence mediates inter-regional communication, implicating theta phase and theta-gamma phase-amplitude coupling in mnemonic function across species. To examine this hypothesis, we used non-invasive whole-head magnetoencephalography (MEG) as participants retrieved the location of objects encountered within a virtual environment. We demonstrate that, when participants are cued with the image of an object whose location they must subsequently navigate to, there is a significant increase in 4-8 Hz theta power in medial prefrontal cortex (mPFC), and the phase of this oscillation is coupled both with ongoing theta phase in the medial temporal lobe (MTL) and perceptually induced 65-85 Hz gamma amplitude in medial parietal cortex. These results suggest that theta phase coupling between mPFC and MTL and theta-gamma phase-amplitude coupling between mPFC and neocortical regions may play a role in human spatial memory retrieval. (c) 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc. C1 [Kaplan, Raphael] NIMH, NIMH UCL Joint Neurosci Grad Partnership Program, Bethesda, MD 20892 USA. [Kaplan, Raphael; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Kaplan, Raphael; Bush, Daniel; Burgess, Neil] UCL, Inst Cognit Neurosci, London WC1N 3AR, England. [Kaplan, Raphael; Bush, Daniel; Barnes, Gareth R.; Burgess, Neil] UCL, Inst Neurol, London WC1N 1PJ, England. [Bonnefond, Mathilde; Doeller, Christian F.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behaviour, NL-6500 HB Nijmegen, Netherlands. RP Kaplan, R (reprint author), Wellcome Trust Ctr Neuroimaging, 12 Queen Sq, London WC1N 3BG, England. EM raphael.kaplan.09@ucl.ac.uk; n.burgess@ucl.ac.uk RI Burgess, Neil/B-2420-2009; OI Burgess, Neil/0000-0003-0646-6584; Kaplan, Raphael/0000-0002-5023-1566 FU European Research Council; MRC UK; National Institute of Mental Health; Wellcome Trust; National Institutes of Health Graduate Partnership Program; MRC UK MEG Partnership FX Grant sponsors: European Research Council; MRC UK; National Institute of Mental Health; Wellcome Trust; National Institutes of Health Graduate Partnership Program; MRC UK MEG Partnership. NR 93 TC 19 Z9 19 U1 1 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1050-9631 EI 1098-1063 J9 HIPPOCAMPUS JI Hippocampus PD JUN PY 2014 VL 24 IS 6 BP 656 EP 665 DI 10.1002/hipo.22255 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AH2IY UT WOS:000335945900005 PM 24497013 ER PT J AU Tu, WZ Eckert, GJ Hannon, TS Liu, H Pratt, LM Wagner, MA DiMeglio, LA Jung, J Pratt, JH AF Tu, Wanzhu Eckert, George J. Hannon, Tamara S. Liu, Hai Pratt, Linda M. Wagner, Mary Anne DiMeglio, Linda A. Jung, Jeesun Pratt, J. Howard TI Racial Differences in Sensitivity of Blood Pressure to Aldosterone SO HYPERTENSION LA English DT Article DE aldosterone; blood pressure; child; continental population groups; renin; sodium ID LEFT-VENTRICULAR MASS; HYPERTENSION; BLACKS; HYPERALDOSTERONISM; ASSOCIATION; MECHANISMS; DIAGNOSIS; CHILDREN; HEART AB Blacks in comparison with whites are at risk for a more serious form of hypertension with high rates of complications. Greater sodium retention is thought to underlie the blood pressure (BP)-determining physiology of blacks, but specific mechanisms have not been identified. In a prospective observational study of BP, 226 black children and 314 white children (mean age, 10.6 years) were enrolled initially. Assessments were repeated in 85 blacks and 136 whites after reaching adulthood (mean age, 31 years). The relationship of BP to plasma aldosterone concentration in the context of the prevailing level of plasma renin activity was studied in blacks and whites. In a secondary interventional study, 9-alpha fludrocortisone was administered for 2 weeks to healthy adult blacks and whites to simulate hyperaldosteronism. BP responses in the 2 race groups were then compared. Although black children had lower levels of plasma renin activity and plasma aldosterone, their BP was positively associated with the plasma aldosterone concentration, an effect that increased as plasma renin activity decreased (P=0.004). Data from black adults yielded similar results. No similar relationship was observed in whites. In the interventional study, 9-alpha fludrocortisone increased BP in blacks but not in whites. In conclusion, aldosterone sensitivity is a significant determinant of BP in young blacks. Although its role in establishing the risk of hypertension is not known, it could be as relevant as the actual level of aldosterone. C1 [Tu, Wanzhu; Eckert, George J.; Liu, Hai; Pratt, Linda M.] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 USA. [Hannon, Tamara S.; DiMeglio, Linda A.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. [Wagner, Mary Anne; Pratt, J. Howard] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Jung, Jeesun] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Tu, Wanzhu] Indiana Univ Sch Med, Regenstrief Inst, Indianapolis, IN 46202 USA. [Wagner, Mary Anne; Pratt, J. Howard] VA Med Ctr, Indianapolis, IN USA. [Jung, Jeesun] NIAAA, Bethesda, MD USA. RP Pratt, JH (reprint author), 541 Clin Dr,CL 365a, Indianapolis, IN 46202 USA. EM johpratt@iu.edu OI DiMeglio, Linda/0000-0002-8033-6078 FU National Institutes of Health [RO1-HL095086, RO1-HL 35795]; Department of Veterans Affairs Merit Review Award FX Funded by the National Institutes of Health (RO1-HL095086 and RO1-HL 35795) and by a Department of Veterans Affairs Merit Review Award. NR 28 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUN PY 2014 VL 63 IS 6 BP 1212 EP 1218 DI 10.1161/HYPERTENSIONAHA.113.02989 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AG5XL UT WOS:000335491900156 PM 24711519 ER PT J AU Tabet, F Lee, S Torres, LC Levin, M Drummond, GR Remaley, A Rye, KA Vickers, K Sobey, CG AF Tabet, F. Lee, S. Torres, Cuesta L. Levin, M. Drummond, G. R. Remaley, A. Rye, K. A. Vickers, K. Sobey, C. G. TI TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL CIRCUITRY IN THE BRAIN AFTER TRANSIENT AND PERMANENT ISCHEMIA SO HYPERTENSION LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the High-Blood-Pressure-Research-Council-of-Australia (HBPRCA) / 39th Annual Scientific Meeting of the Australian-Atherosclerosis-Society (AAS) CY DEC 05-07, 2013 CL Melbourne, AUSTRALIA SP High Blood Pressure Res Council Australia, Australian Atherosclerosis Soc C1 [Tabet, F.; Torres, Cuesta L.; Rye, K. A.] Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia. [Lee, S.; Drummond, G. R.; Sobey, C. G.] Monash Univ, Dept Pharmacol, Clayton, Vic 3168, Australia. [Levin, M.; Remaley, A.; Vickers, K.] NIH, Bethesda, MD 20892 USA. [Vickers, K.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUN PY 2014 VL 63 IS 6 BP E157 EP E158 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AG5XL UT WOS:000335491900076 ER PT J AU Chen, G Wang, XW Severo, MS Sakhon, OS Sohail, M Brown, LJ Sircar, M Snyder, GA Sundberg, EJ Ulland, TK Olivier, AK Andersen, JF Zhou, Y Shi, GP Sutterwala, FS Kotsyfakis, M Pedra, JHF AF Chen, Gang Wang, Xiaowei Severo, Maiara S. Sakhon, Olivia S. Sohail, Mohammad Brown, Lindsey J. Sircar, Mayukh Snyder, Greg A. Sundberg, Eric J. Ulland, Tyler K. Olivier, Alicia K. Andersen, John F. Zhou, Yi Shi, Guo-Ping Sutterwala, Fayyaz S. Kotsyfakis, Michail Pedra, Joao H. F. TI The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated Inflammation during Anaplasma phagocytophilum Infection SO INFECTION AND IMMUNITY LA English DT Article ID GRANULOCYTIC EHRLICHIOSIS AGENT; PERIPHERAL-BLOOD LEUKOCYTES; TUMOR-NECROSIS-FACTOR; CATHEPSIN-L ACTIVITY; IXODES-SCAPULARIS; NLRP3 INFLAMMASOME; NALP3 INFLAMMASOME; GLAND EXTRACTS; MESSENGER-RNA; CUTTING EDGE AB Saliva from arthropod vectors facilitates blood feeding by altering host inflammation. Whether arthropod saliva counters inflammasome signaling, a protein scaffold that regulates the activity of caspase-1 and cleavage of interleukin-1 beta (IL-1 beta) and IL-18 into mature molecules, remains elusive. In this study, we provide evidence that a tick salivary protein, sialostatin L2, inhibits inflammasome formation during pathogen infection. We show that sialostatin L2 targets caspase-1 activity during host stimulation with the rickettsial agent Anaplasma phagocytophilum. A. phagocytophilum causes macrophage activation and hemophagocytic syndrome features. The effect of sialostatin L2 in macrophages was not due to direct caspase-1 enzymatic inhibition, and it did not rely on nuclear factor kappa B or cathepsin L signaling. Reactive oxygen species from NADPH oxidase and the Loop2 domain of sialostatin L2 were important for the regulatory process. Altogether, our data expand the knowledge of immunoregulatory pathways of tick salivary proteins and unveil an important finding in inflammasome biology. C1 [Chen, Gang; Severo, Maiara S.; Sakhon, Olivia S.; Sohail, Mohammad; Pedra, Joao H. F.] Univ Calif Riverside, Ctr Dis Vector Res, Riverside, CA 92521 USA. [Chen, Gang; Severo, Maiara S.; Sakhon, Olivia S.; Sohail, Mohammad; Pedra, Joao H. F.] Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA. [Wang, Xiaowei; Brown, Lindsey J.; Sircar, Mayukh; Pedra, Joao H. F.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Snyder, Greg A.] Univ Maryland, Sch Med, Dept Med, Inst Human Virol, Baltimore, MD 21201 USA. [Sundberg, Eric J.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Inst Human Virol,Dept Med, Baltimore, MD 21201 USA. [Ulland, Tyler K.; Sutterwala, Fayyaz S.] Univ Iowa, Dept Internal Med, Inflammat Program, Iowa City, IA 52242 USA. [Ulland, Tyler K.; Sutterwala, Fayyaz S.] Univ Iowa, Dept Internal Med, Div Infect Dis, Iowa City, IA 52242 USA. [Olivier, Alicia K.] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. [Andersen, John F.] NIAID, Lab Malaria & Vector Res, Rockville, MD USA. [Zhou, Yi; Shi, Guo-Ping] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02115 USA. [Kotsyfakis, Michail] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic. RP Pedra, JHF (reprint author), Univ Calif Riverside, Ctr Dis Vector Res, Riverside, CA 92521 USA. EM jpedra@som.umaryland.edu RI Kotsyfakis, Michail/G-9525-2014; OI Kotsyfakis, Michail/0000-0002-7526-1876; Severo, Maiara/0000-0001-5972-0035; Pedra, Joao/0000-0001-8740-2667; Ulland, Tyler/0000-0002-6507-4989 FU Centers for Disease Control and Prevention [K01 CK000101]; National Institutes of Health [R01 AI093653]; University of California; University of Maryland, Baltimore School of Medicine; American Association of University Women FX This work was supported by the Centers for Disease Control and Prevention (grant K01 CK000101), the National Institutes of Health (grant R01 AI093653), an initial complement provided by the University of California, start-up funds provided by the University of Maryland, Baltimore School of Medicine, and an international fellowship from the American Association of University Women. NR 55 TC 8 Z9 9 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2014 VL 82 IS 6 BP 2553 EP 2564 DI 10.1128/IAI.01679-14 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA AH8HN UT WOS:000336378100040 PM 24686067 ER PT J AU Truog, RD Miller, FG AF Truog, Robert D. Miller, Franklin G. TI Defining death: the importance of scientific candor and transparency SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID BRAIN-DEATH C1 [Truog, Robert D.] Boston Childrens Hosp, Div Crit Care Med, Boston, MA 02115 USA. [Truog, Robert D.] Harvard Univ, Ctr Bioeth, Sch Med, Boston, MA 02115 USA. [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Truog, RD (reprint author), Boston Childrens Hosp, Div Crit Care Med, Boston, MA 02115 USA. EM Robert.Truog@childrens.harvard.edu NR 11 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD JUN PY 2014 VL 40 IS 6 BP 885 EP 887 DI 10.1007/s00134-014-3301-0 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA AH6ZJ UT WOS:000336281100014 PM 24807081 ER PT J AU Lee, SY Chen, SL Chang, YH Chen, SH Chu, CH Huang, SY Tzeng, NS Wang, CL Wang, LJ Lee, IH Yeh, TL Yang, YK Hong, JS Lu, RB AF Lee, Sheng-Yu Chen, Shiou-Lan Chang, Yun-Hsuan Chen, Shih-Heng Chu, Chun-Hsieh Huang, San-Yuan Tzeng, Nian-Sheng Wang, Chen-Lin Wang, Liang-Jen Lee, I. Hui Yeh, Tzung Lieh Yang, Yen Kuang Hong, Jau-Shyong Lu, Ru-Band TI Genotype variant associated with add-on memantine in bipolar II disorder (vol 17, pg 189, 2014) SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Correction C1 [Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsieh; Wang, Chen-Lin; Lee, I. Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Tainan 70101, Taiwan. [Chang, Yun-Hsuan; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Inst Allied Hlth Sci, Tainan 70101, Taiwan. [Huang, San-Yuan; Tzeng, Nian-Sheng] Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Psychiat, Taipei, Taiwan. [Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Inst Behav Med, Tainan 70101, Taiwan. [Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Addit Res Ctr, Tainan 70101, Taiwan. [Wang, Liang-Jen] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan. [Wang, Liang-Jen] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan. [Hong, Jau-Shyong] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. RP Lee, SY (reprint author), Natl Cheng Kung Univ, Dept Psychiat, Tainan 70101, Taiwan. NR 1 TC 0 Z9 0 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2014 VL 17 IS 6 BP 979 EP 979 DI 10.1017/S1461145714000091 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AG6DI UT WOS:000335508300014 ER PT J AU Ziai, WC Tuhrim, S Lane, K McBee, N Lees, K Dawson, J Butcher, K Vespa, P Wright, DW Keyl, PM Mendelow, AD Kase, C Wijman, C Lapointe, M John, S Thompson, R Thompson, C Mayo, S Reilly, P Janis, S Awad, I Hanley, DF AF Ziai, Wendy C. Tuhrim, Stanley Lane, Karen McBee, Nichol Lees, Kennedy Dawson, Jesse Butcher, Kenneth Vespa, Paul Wright, David W. Keyl, Penelope M. Mendelow, A. David Kase, Carlos Wijman, Christine Lapointe, Marc John, Sayona Thompson, Richard Thompson, Carol Mayo, Steven Reilly, Pat Janis, Scott Awad, Issam Hanley, Daniel F. CA CLEAR III Investigators TI A multicenter, randomized, double-blinded, placebo-controlled phase III study of Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III) SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE intracerebral haemorrhage; protocols; thrombolysis; stroke; randomized clinical trial ID SPONTANEOUS INTRACEREBRAL HEMORRHAGE; BLOOD-CLOT; PLASMINOGEN-ACTIVATOR; FIBRINOLYTIC THERAPY; CEREBROSPINAL-FLUID; CANINE MODEL; UROKINASE; HYDROCEPHALUS; SAFETY; TRIAL AB Background In adults, intraventricular thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) facilitates resolution of intraventricular haemorrhage (IVH), reduces intracranial pressure, decreases duration of cerebrospinal fluid diversion, and may ameliorate direct neural injury. We hypothesize that patients with small parenchymal haematoma volumes (<30 cc) and relatively large IVH causing acute obstructive hydrocephalus would have improved clinical outcomes when given injections of low-dose rtPA to accelerate lysis and evacuation of IVH compared with placebo. Methods The Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage III trial is an investigator-initiated, phase III, randomized, multicenter, double-blind, placebo-controlled study comparing the use of external ventricular drainage (EVD) combined with intraventricular injection of rtPA to EVD plus intraventricular injection of normal saline (placebo) for the treatment of IVH. Patients with known symptom onset within 24 h of the computed tomography scan confirmed IVH and third or fourth ventricle obstruction, with or without supratentorial intracerebral haemorrhage volume <30 cc, who require EVD are screened with a computed tomography scan at least six hours after EVD placement and, if necessary, at consecutive 12-h intervals until stabilization of any intracranial bleeding has been established. Patients who meet clinical and imaging criteria (no ongoing coagulopathy and no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly) will be randomized to either intraventricular rtPA or placebo. Results The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 180 days. Clinical secondary outcomes include additional modified Rankin Scale dichotomizations at 180 days (0-4 vs. 5-6), ordinal modified Rankin Scale (0-6), mortality and safety events at 30 days, mortality at 180 days, functional status measures, type and intensity of intensive care unit management, rate and extent of ventricular blood clot removal, and quality of life measures. C1 [Ziai, Wendy C.] Johns Hopkins Univ, Sch Med, Dept Neurol, Div Neurosci Crit Care,Johns Hopkins Hosp, Baltimore, MD 21205 USA. [Tuhrim, Stanley] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Lane, Karen; McBee, Nichol; Keyl, Penelope M.; Hanley, Daniel F.] Johns Hopkins Univ, Sch Med, Div Brain Injury Outcomes, Baltimore, MD USA. [Lees, Kennedy; Dawson, Jesse] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Butcher, Kenneth] Univ Alberta, Div Neurol, Edmonton, AB, Canada. [Vespa, Paul] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA. [Wright, David W.] Emory Univ, Sch Med, Grady Mem Hosp, Dept Emergency Neurosci, Atlanta, GA USA. [Mendelow, A. David] Newscastle Gen Hosp, Dept Neurosurg, Newcastle Upon Tyne, Tyne & Wear, England. [Kase, Carlos] Boston Med Ctr, Dept Neurol, Boston, MA USA. [Wijman, Christine] Stanford Med, Dept Neurol & Neurol Sci, Stanford, CA USA. [Lapointe, Marc] Med Univ S Carolina, Coll Pharm, Charleston, SC 29425 USA. [John, Sayona] Rush Univ, Med Ctr, Dept Neurol, Chicago, IL 60612 USA. [Thompson, Richard; Thompson, Carol] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Mayo, Steven] Emissary Int LLC, Austin, TX USA. [Reilly, Pat] Genentech Inc, San Francisco, CA 94080 USA. [Janis, Scott] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Awad, Issam] Univ Chicago, Pritzker Sch Med, Neurosurg Sect, Chicago, IL 60637 USA. [Awad, Issam] Univ Chicago, Pritzker Sch Med, Neurovasc Surg Program, Chicago, IL 60637 USA. RP Ziai, WC (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, 600 Wolf St, Baltimore, MD 21231 USA. EM weziai@jhmi.edu RI Wright, David/F-1209-2013 OI Wright, David/0000-0002-7145-9105 FU NIH/NINDS [5U01 NS062851, RO1NS046309]; Eleanor Naylor Dana Charitable Trust [272-2007]; Jeffry and Harriet Legum Endowment; Genentech, Inc. FX Funding: The CLEAR III trial is supported by a grant (NIH/NINDS 5U01 NS062851 to Dr Hanley). Drs Wendy Ziai and Stanley Tuhrim, Karen Lane, Nichol McBee, Drs Issam Awad, Kennedy Lees, Jesse Dawson, Kenneth Butcher, Paul Vespa, Penelope Keyl, A. David Mendelow, Carlos Kase, Christine Wijman, Marc Lapointe, Sayona John, Richard Thompson, Carol Thompson, and Steven Mayo receive funding from the same grant (NIH/NINDS 5U01 NS062851 to Dr Daniel F. Hanley). Dr Hanley is also supported by grants RO1NS046309 from the NIH/NINDS, grant 272-2007 from the Eleanor Naylor Dana Charitable Trust, the Jeffry and Harriet Legum Endowment, and materials grants from Genentech, Inc. NR 37 TC 33 Z9 36 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 EI 1747-4949 J9 INT J STROKE JI Int. J. Stroke PD JUN PY 2014 VL 9 IS 4 BP 536 EP 542 DI 10.1111/ijs.12097 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AG8JP UT WOS:000335664900029 PM 24033910 ER PT J AU Farber, CR Reich, A Barnes, AM Becerra, P Rauch, F Cabral, WA Bae, A Quinlan, A Glorieux, FH Clemens, TL Marini, JC AF Farber, Charles R. Reich, Adi Barnes, Aileen M. Becerra, Patricia Rauch, Frank Cabral, Wayne A. Bae, Alison Quinlan, Aaron Glorieux, Francis H. Clemens, Thomas L. Marini, Joan C. TI A Novel IFITM5 Mutation in Severe Atypical Osteogenesis Imperfecta Type VI Impairs Osteoblast Production of Pigment Epithelium-Derived Factor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE IFITM5; BRIL; SERPINF1; PEDF; OSTEOGENESIS IMPERFECTA; OI ID INTEGRATIVE GENOMICS VIEWER; BRITTLE BONE-DISEASE; I COLLAGEN; HYPERPLASTIC CALLUS; NETWORK ANALYSIS; SEQUENCING DATA; PEDF; MINERALIZATION; ASSOCIATION; EXPRESSION AB Osteogenesis imperfecta (OI) types V and VI are caused, respectively, by a unique dominant mutation in IFITM5, encoding BRIL, a transmembrane ifitm-like protein most strongly expressed in the skeletal system, and recessive null mutations in SERPINF1, encoding pigment epithelium-derived factor (PEDF). We identified a 25-year-old woman with severe OI whose dermal fibroblasts and cultured osteoblasts displayed minimal secretion of PEDF, but whose serum PEDF level was in the normal range. SERPINF1 sequences were normal despite bone histomorphometry consistent with type VI OI and elevated childhood serum alkaline phosphatase. We performed exome sequencing on the proband, both parents, and an unaffected sibling. IFITM5 emerged as the candidate gene from bioinformatics analysis, and was corroborated by membership in a murine bone co-expression network module containing all currently known OI genes. The de novo IFITM5 mutation was confirmed in one allele of the proband, resulting in a p.S40L substitution in the intracellular domain of BRIL but was absent in unaffected family members. IFITM5 expression was normal in proband fibroblasts and osteoblasts, and BRIL protein level was similar to control in differentiated proband osteoblasts on Western blot and in permeabilized mutant osteoblasts by microscopy. In contrast, SERPINF1 expression was decreased in proband osteoblasts; PEDF was barely detectable in conditioned media of proband cells. Expression and secretion of type I collagen was similarly decreased in proband osteoblasts; the expression pattern of several osteoblast markers largely overlapped reported values from cells with a primary PEDF defect. In contrast, osteoblasts from a typical case of type V OI, with an activating mutation at the 5'-terminus of BRIL, have increased SERPINF1 expression and PEDF secretion during osteoblast differentiation. Together, these data suggest that BRIL and PEDF have a relationship that connects the genes for types V and VI OI and their roles in bone mineralization. (c) 2014 American Society for Bone and Mineral Research. C1 [Farber, Charles R.; Quinlan, Aaron] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Farber, Charles R.; Quinlan, Aaron] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Farber, Charles R.; Quinlan, Aaron] Univ Virginia, Dept Biochem, Charlottesville, VA 22908 USA. [Farber, Charles R.; Quinlan, Aaron] Univ Virginia, Dept Mol Genet, Charlottesville, VA USA. [Reich, Adi; Barnes, Aileen M.; Cabral, Wayne A.; Bae, Alison; Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. [Becerra, Patricia] NEI, Sect Prot Struct & Funct, LRCMB, NIH, Bethesda, MD 20892 USA. [Rauch, Frank; Glorieux, Francis H.] Shriners Hosp Children, Montreal, PQ, Canada. [Rauch, Frank; Glorieux, Francis H.] McGill Univ, Montreal, PQ, Canada. [Clemens, Thomas L.] Johns Hopkins Sch Med, Dept Orthopaed Surg, Baltimore, MD USA. [Clemens, Thomas L.] Baltimore VA Med Ctr, Baltimore, MD USA. RP Marini, JC (reprint author), NICHD, Bone & Extracellular Matrix Branch, NIH, Bldg 10 Room 10D39,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov OI Quinlan, Aaron/0000-0003-1756-0859; Farber, Charles/0000-0002-6748-4711 FU NICHD; NEI [RO1-AR057759, RO1-AR049410]; VA Merit Review; Shriners Hospital of North America; Chercheur-Boursier Clinicien program of the Fonds de Recherche du Quebec-Sante; VA Senior Career Scientist Award FX We thank the proband and her family for their dedicated long-term support of OI research. We are grateful to Prof Pierre Moffatt for communication of unpublished results on BRIL structure in the cell membrane. We thank the NICHD Microscopy and Imaging Core in which the confocal microscopy was conducted. This work was supported by NICHD (JCM) and NEI (PB) intramural funding, extramural RO1-AR057759 (CRF), RO1-AR049410 (TLC), a VA Merit Review (TLC), and Shriners Hospital of North America (FR and FHG). FR received salary support from the Chercheur-Boursier Clinicien program of the Fonds de Recherche du Quebec-Sante. TLC is also supported by a VA Senior Career Scientist Award. NR 52 TC 12 Z9 13 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2014 VL 29 IS 6 BP 1402 EP 1411 DI 10.1002/jbmr.2173 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AH3DJ UT WOS:000336001500013 PM 24519609 ER PT J AU Lee, SY Chen, SL Chang, YH Chen, PS Huang, SY Tzeng, NS Wang, YS Wang, LJ Lee, IH Wang, TY Yeh, TL Yang, YK Hong, JS Lu, RB AF Lee, Sheng-Yu Chen, Shiou-Lan Chang, Yun-Hsuan Chen, Po See Huang, San-Yuan Tzeng, Nian-Sheng Wang, Yu-Shan Wang, Liang-Jen Lee, I. Hui Wang, Tzu-Yun Yeh, Tzung Lieh Yang, Yen Kuang Hong, Jau-Shyong Lu, Ru-Band TI The Effects of Add-On Low-Dose Memantine on Cytokine Levels in Bipolar II Depression A 12-Week Double- Blind, Randomized Controlled Trial SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE bipolar II depression; memantine; treatment; cytokines ID NMDA RECEPTOR ANTAGONISTS; DOUBLE-BLIND; ALCOHOL DEPENDENCE; AFFECTIVE-DISORDER; LITHIUM TREATMENT; MAJOR DEPRESSION; RATING-SCALE; HYPOMANIA; BRAIN; MOOD AB Memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist with a mood-stabilizing effect, and an association between bipolar disorder and proinflammatory cytokine levels have been reported. Whether adding-on memantine would reduce cytokine levels and is more effective than valproic acid (VPA) alone in bipolar II disorder was investigated. A randomized, double-blind, controlled, 12-week study was conducted. Patients undergoing regular VPA treatments were randomly assigned to a group: VPA + memantine (5 mg/d) (n = 106) or VPA + placebo (n = 108). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response. Symptom severity, plasma tumor necrosis factor (TNF-), interleukin 6 (IL-6), IL-8, and IL-1 levels were examined during weeks 0, 1, 2, 4, 8, and 12. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Tumor necrosis factor levels were significantly lower in the VPA + memantine group than in the VPA + placebo group (P = 0.013). Posttreatment HDRS and YMRS scores decreased significantly in both groups, but not significant, nor was the other between-group cytokine level difference pretreatment and posttreatment. The HDRS score changes were significantly associated with IL-6 (P = 0.012) and IL-1 (P = 0.005) level changes and changes in YMRS score changes with TNF- (P = 0.005) level changes. Treating bipolar II depression with VPA + memantine may improve the plasma TNF- level. However, adding-on memantine may not improve clinical symptoms or cytokine levels other than TNF-. Clinical symptoms may be correlated with certain cytokines. C1 [Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Po See; Lee, I. Hui; Wang, Tzu-Yun; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Dept Psychiat, Tainan 70428, Taiwan. [Chen, Shiou-Lan; Wang, Yu-Shan; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Inst Behav Med, Tainan 70428, Taiwan. [Chang, Yun-Hsuan; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Inst Allied Hlth Sci, Tainan 70428, Taiwan. [Huang, San-Yuan; Tzeng, Nian-Sheng] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. [Wang, Liang-Jen] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan. [Wang, Liang-Jen] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan. [Wang, Tzu-Yun] Tainan Hosp, Dept Hlth Execut Yuan, Dept Psychiat, Tainan, Taiwan. [Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70101, Taiwan. [Hong, Jau-Shyong] NIH NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC USA. RP Lu, RB (reprint author), Natl Cheng Kung Univ, Coll Med & Hosp, Addict Ctr, Inst Behav Med,Dept Psychiat, 138 Sheng Li Rd, Tainan 70428, Taiwan. EM rblu@mail.ncku.edu.tw FU Taiwan National Science Council [NSC98-2314-B-006-022-MY3, NSC100-2314-B-006-048-MY3]; Taiwan Department of Health [DOH 95-TD-M-113-055]; Taiwan National Health Research Institute [NHRI-EX-97-9738NI]; National Cheng Kung University Project for Promoting Academic Excellence and Developing World Class Research Centers FX This work was supported in part by grant NSC98-2314-B-006-022-MY3 (to R.-B.L.) and NSC100-2314-B-006-048-MY3 (to S.-Y.L.) from the Taiwan National Science Council, grant DOH 95-TD-M-113-055 (to R.-B.L.) from the Taiwan Department of Health, grant NHRI-EX-97-9738NI (to R.-B.L.) from the Taiwan National Health Research Institute, and the National Cheng Kung University Project for Promoting Academic Excellence and Developing World Class Research Centers. NR 65 TC 7 Z9 7 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2014 VL 34 IS 3 BP 337 EP 343 DI 10.1097/JCP.0000000000000109 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AH3AR UT WOS:000335994100012 PM 24717258 ER PT J AU Ferguson, GM Desir, C Bornstein, MH AF Ferguson, Gail M. Desir, Charlene Bornstein, Marc H. TI "Ayiti Cheri": Cultural Orientation of Early Adolescents in Rural Haiti SO JOURNAL OF EARLY ADOLESCENCE LA English DT Article DE cultural maintenance; globalization; remote acculturation; family obligations; Caribbean ID ACCULTURATION; IDENTITY AB Adolescents are an emerging population in Haiti, particularly after the deadly 2010 earthquake. The steady penetration of U.S. culture into this poor, disaster-prone country begs the question, Do today's adolescents possess a similar fondness for their home country, culture, and traditional family values as did Haitians of old? Or are they more oriented toward U.S. culture? Early adolescents (N = 105, 52% female, M = 12.87 years, SD = .86) in rural Haiti reported their cultural orientation toward Haitian culture and U.S. culture as well as their family obligations beliefs. Findings revealed high Haitian orientation, very high family obligations (boys especially), and very low U.S. orientation, although adolescents who interacted more frequently with U.S. tourists and those who consumed more U.S. fast food had higher U.S. culture orientation. Despite severe challenges, rural Haitian early adolescents demonstrate remarkable allegiance to their home country, culture, and traditional family values. C1 [Ferguson, Gail M.] Univ Illinois, Urbana, IL 61801 USA. [Ferguson, Gail M.] Univ Illinois, Ctr Latin Amer & Caribbean Studies, Urbana, IL 61801 USA. [Desir, Charlene] Novasoutheastern Univ, North Miami Beach, FL USA. [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Ferguson, GM (reprint author), Univ Illinois, Doris Kelley Christopher Hall,MC-081, Urbana, IL 61801 USA. EM gmfergus@illinois.edu NR 28 TC 0 Z9 0 U1 5 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-4316 EI 1552-5449 J9 J EARLY ADOLESCENCE JI J. Early Adolesc. PD JUN PY 2014 VL 34 IS 5 BP 621 EP 637 DI 10.1177/0272431613503214 PG 17 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA AH6UC UT WOS:000336265600004 ER PT J AU Brooks-Russell, A Farhat, T Haynie, D Simons-Morton, B AF Brooks-Russell, Ashley Farhat, Tilda Haynie, Denise Simons-Morton, Bruce TI Trends in Substance Use Among 6th-to 10th-Grade Students From 1998 to 2010: Findings From a National Probability Study SO JOURNAL OF EARLY ADOLESCENCE LA English DT Article DE adolescent tobacco use; adolescent alcohol use; substance use trends; national prevalence of substance use ID DRINKING; SMOKING; ONSET AB Of the handful of national studies tracking trends in adolescent substance use in the United States, only the Health Behavior in School-Aged Children (HBSC) study collects data from 6th through 10th graders. The purpose of this study was to examine trends from 1998 to 2010 (four time points) in the prevalence of tobacco, alcohol, and marijuana use among 6th through 10th graders. Differences in trends by grade, gender, and race/ethnicity were examined for each substance use behavior, with a primary focus on trends for sixth and seventh graders. Overall, there were significant declines in tobacco, alcohol, and marijuana use from 1998 to 2010. The declines were largest for the younger grades, which suggest promise for future declines among high school students as these cohorts age into high school. C1 [Brooks-Russell, Ashley; Farhat, Tilda; Haynie, Denise; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Brooks-Russell, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd Room 7B13, Bethesda, MD 20892 USA. EM ashley.russell@nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 FU Intramural NIH HHS [ZIA HD002525-18] NR 14 TC 4 Z9 4 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-4316 EI 1552-5449 J9 J EARLY ADOLESCENCE JI J. Early Adolesc. PD JUN PY 2014 VL 34 IS 5 BP 667 EP 680 DI 10.1177/0272431613501409 PG 14 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA AH6UC UT WOS:000336265600006 PM 26949282 ER PT J AU Goveas, JS Espeland, MA Hogan, PE Tindle, HA Shih, RA Kotchen, JM Robinson, JG Barnes, DE Resnick, SM AF Goveas, Joseph S. Espeland, Mark A. Hogan, Patricia E. Tindle, Hilary A. Shih, Regina A. Kotchen, Jane M. Robinson, Jennifer G. Barnes, Deborah E. Resnick, Susan M. TI Depressive Symptoms and Longitudinal Changes in Cognition: Women's Health Initiative Study of Cognitive Aging SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE depression; cognitive decline; vascular risk factors; cardiovascular disease; women; dementia; depressive symptoms ID LATE-LIFE DEPRESSION; APOLIPOPROTEIN-E GENOTYPE; PRIMARY-CARE PATIENTS; GERIATRIC DEPRESSION; VASCULAR DEPRESSION; POSTMENOPAUSAL WOMEN; ALZHEIMER-DISEASE; IMPAIRMENT; DEMENTIA; RISK AB Elevated depressive symptoms (DS) are associated with incident mild cognitive impairment and probable dementia in postmenopausal women. We examined the association of elevated DS with domain-specific cognitive changes and the moderating role of cardiovascular risk factor severity and cardiovascular disease (CVD). A total of 2221 elderly women who participated in the Women's Health Initiative Study of Cognitive Aging were separated into those with (N = 204) and without (N = 2017) elevated DS. The DS and multidomain cognitive outcomes were measured annually for an average follow-up of 5.04 years. Women with elevated DS showed baseline multidomain cognitive deficits but longitudinal declines in global cognition only. Persistent DS was related to greater global cognition, verbal knowledge and fluency, and memory declines. Significant DS-CVD interactions were observed cross-sectionally (but not longitudinally) for figural memory and fine motor speed. Future studies should investigate the role of nonvascular mechanisms linking DS and cognitive decline. C1 [Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. [Espeland, Mark A.; Hogan, Patricia E.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Tindle, Hilary A.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Shih, Regina A.] RAND Corp, Arlington, VA USA. [Kotchen, Jane M.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Kotchen, Jane M.] Med Coll Wisconsin, Clin & Translat Sci Inst, Milwaukee, WI 53226 USA. [Robinson, Jennifer G.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat & Epidemiol, San Francisco, CA 94143 USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Barnes, Deborah E.] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA. [Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Goveas, JS (reprint author), Med Coll Wisconsin, Dept Psychiat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM jgoveas@mcw.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; Department of Health and Human Services; National Institute on Aging [NO1-AG-1-2106]; Intramural Research Program, National Institute on Aging; National Institutes of Health; Alzheimer's Association [NIRG-11-204070]; Extendicare Foundation; Brain & Behavior Research Foundation (NARSAD); Wyeth Pharmaceuticals; Brain and Behavior Research Foundation (previously NARSAD) young investigator award FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The WHI Study of Cognitive Aging (WHISCA) was supported by the Department of Health and Human Services and the National Institute on Aging (NO1-AG-1-2106). SMR is supported by the Intramural Research Program, National Institute on Aging, and National Institutes of Health. JSG is supported by the Alzheimer's Association New Investigator NIRG-11-204070 and Extendicare Foundation, and previously by Brain & Behavior Research Foundation (NARSAD) young investigator, and Research for a Healthier Tomorrow, a Component of the Advancing a Healthier Wisconsin Endowment at MCW. The Women's Health Initiative Memory Study was funded in part by Wyeth Pharmaceuticals as an ancillary study to the WHI. DB's contributions were supported in part by Brain and Behavior Research Foundation (previously NARSAD) young investigator award. NR 46 TC 11 Z9 11 U1 3 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 EI 1552-5708 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUN PY 2014 VL 27 IS 2 BP 94 EP 102 DI 10.1177/0891988714522697 PG 9 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA AH6DG UT WOS:000336220300004 PM 24584465 ER PT J AU Villarroel, VA Okiyama, N Tsuji, G Linton, JT Katz, SI AF Villarroel, Vadim A. Okiyama, Naoko Tsuji, Gaku Linton, Jay T. Katz, Stephen I. TI CXCR3-Mediated Skin Homing of Autoreactive CD8 T Cells Is a Key Determinant in Murine Graft-Versus-Host Disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; ALLOGRAFT-REJECTION; CHEMOKINE RECEPTORS; ALOPECIA-AREATA; CXCR3; EXPRESSION; INFILTRATION; RECRUITMENT; MIGRATION; CXCL10 AB The pathomechanisms underlying the development of cutaneous graft-versus-host disease (GVHD) are incompletely defined. We previously reported that K14-mOVA mice expressing membrane ovalbumin (mOVA), driven by the keratin 14 (K14) promoter, developed GVHD-like mucocutaneous disease and weight loss following transfer of OVA-specific, CD8(+) OT-I T cells. In this study, we demonstrate that early in the course of disease, the kinetics of epidermal expression of C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10, interferon-gamma-inducible chemokines that bind the C-X-C motif chemokine receptor 3 (CXCR3) receptor, coincides with CXCR3 expression by OT-I cells in secondary lymphoid organs. Recruitment of OT-I cells into the skin began by day 5 with progressive accumulation through day 13 post transfer. Transfer of CXCR3-knockout (CXCR3KO) OT-I cells into K14-mOVA mice resulted in strikingly attenuated skin disease. CXCR3KO OT-I cells retained full activation and effector function, but preferentially accumulated in the spleen, in contrast to wild-type (WT) OT-I cells that accumulated in skin-draining lymph nodes. Moreover, OT-I cells accounted for a significantly reduced percentage of skin-infiltrating lymphocytes in mice receiving CXCR3KO OT-I cells compared with WT OT-I cells. These results identify CXCR3 as being critical to the skin-selective effector T-cell recruitment underlying autoreactive GVHD, suggesting CXCR3 as a potential target in the treatment of GVHD and related skin diseases. C1 [Villarroel, Vadim A.; Okiyama, Naoko; Tsuji, Gaku; Linton, Jay T.; Katz, Stephen I.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM katzs@od.niams.nih.gov NR 35 TC 8 Z9 8 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 2014 VL 134 IS 6 BP 1552 EP 1560 DI 10.1038/jid.2014.2 PG 9 WC Dermatology SC Dermatology GA AH5TJ UT WOS:000336193700013 PM 24390137 ER PT J AU Turkbey, B Merino, MJ Gallardo, EC Shah, V Aras, O Bernardo, M Mena, E Daar, D Rastinehad, AR Linehan, WM Wood, BJ Pinto, PA Choyke, PL AF Turkbey, Baris Merino, Maria J. Gallardo, Elma Carvajal Shah, Vijay Aras, Omer Bernardo, Marcelino Mena, Esther Daar, Dagane Rastinehad, Ardeshir R. Linehan, W. Marston Wood, Bradford J. Pinto, Peter A. Choyke, Peter L. TI Comparison of Endorectal Coil and Nonendorectal Coil T2W and Diffusion-Weighted MRI at 3 Tesla for Localizing Prostate Cancer: Correlation With Whole-Mount Histopathology SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE prostate cancer; surface coil; endorectal coil; MRI; 3 Tesla ID PHASED-ARRAY COIL; STAGING ACCURACY; IMAGE QUALITY; 1.5 T; LOCALIZATION AB PurposeTo compare utility of T2-weighted (T2W) MRI and diffusion-weighted MRI (DWI-MRI) obtained with and without an endorectal coil at 3 Tesla (T) for localizing prostate cancer. Materials and MethodsThis Institutional Review Board-approved study included 20 patients (median prostate-specific antigen, 8.4 ng/mL). Patients underwent consecutive prostate MRIs at 3T, first with a surface coil alone, then with combination of surface, endorectal coils (dual coil) followed by robotic assisted radical prostatectomy. Lesions were mapped at time of acquisition on dual-coil T2W, DWI-MRI. To avoid bias, 6 months later nonendorectal coil T2W, DWI-MRI were mapped. Both MRI evaluations were performed by two readers blinded to pathology with differences resolved by consensus. A lesion-based correlation with whole-mount histopathology was performed. ResultsAt histopathology 51 cancer foci were present ranging in size from 2 to 60 mm. The sensitivity of the endorectal dual-coil, nonendorectal coil MRIs were 0.76, 0.45, respectively. PPVs for endorectal dual-coil, nonendorectal coil MRI were 0.80, 0.64, respectively. Mean size of detected lesions with nonendorectal coil MRI were larger than those detected by dual-coil MRI (22 mm versus 17.4 mm). ConclusionDual-coil prostate MRI detected more cancer foci than nonendorectal coil MRI. While nonendorectal coil MRI is an attractive alternative, physicians performing prostate MRI should be aware of its limitations. J. Magn. Reson. Imaging 2014;39:1443-1448. (c) 2013 Wiley Periodicals, Inc. C1 [Turkbey, Baris; Aras, Omer; Bernardo, Marcelino; Mena, Esther; Daar, Dagane; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Gallardo, Elma Carvajal; Wood, Bradford J.] NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA. [Gallardo, Elma Carvajal; Wood, Bradford J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Gallardo, Elma Carvajal] UMC Utrecht, Image Sci Inst, Utrecht, Netherlands. [Shah, Vijay] VirtualScopics, Rochester, NY USA. [Bernardo, Marcelino] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Rastinehad, Ardeshir R.; Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM pchoyke@mail.nih.gov RI Shah, Vijay/D-4083-2014 OI Shah, Vijay/0000-0003-3856-156X FU Intramural NIH HHS [Z01 BC010655-03, ZIA BC010655-08] NR 20 TC 52 Z9 52 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 EI 1522-2586 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2014 VL 39 IS 6 BP 1443 EP 1448 DI 10.1002/jmri.24317 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG5LM UT WOS:000335460500014 PM 24243824 ER PT J AU Mattmiller, SA Carlson, BA Gandy, JC Sordillo, LM AF Mattmiller, Sarah A. Carlson, Bradley A. Gandy, Jeff C. Sordillo, Lorraine M. TI Reduced macrophage selenoprotein expression alters oxidized lipid metabolite biosynthesis from arachidonic and linoleic acid SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Selenium; Selenoproteins; Macrophage; Oxylipids; Eicosanoids ID AORTIC ENDOTHELIAL-CELLS; FACTOR-KAPPA-B; PROLIFERATOR-ACTIVATED RECEPTOR; SELENIUM DEFICIENCY; GENE-EXPRESSION; FATTY-ACIDS; EICOSANOID BIOSYNTHESIS; OXIDATIVE STRESS; IMMUNE FUNCTION; UP-REGULATION AB Uncontrolled inflammation is an underlying etiology for multiple diseases and macrophages orchestrate inflammation largely through the production of oxidized fatty acids known as oxylipids. Previous studies showed that selenium (Se) status altered the expression of oxylipids and magnitude of inflammatory responses. Although selenoproteins are thought to mediate many of the biological effects of Se, the direct effect of selenoproteins on the production of oxylipids is unknown. Therefore, the role of decreased selenoprotein activity in modulating the production of biologically active oxylipids from macrophages was investigated. Thioglycollate-elicited peritoneal macrophages were collected from wild-type and myeloid-cell-specific selenoprotein knockout mice to analyze oxylipid production by liquid chromatography/mass spectrometry as well as oxylipid biosynthetic enzyme and inflammatory marker gene expression by quantitative real-time polymerase chain reaction. Decreased selenoprotein activity resulted in the accumulation of reactive oxygen species, enhanced cyclooxygenase and lipoxygenase expression and decreased oxylipids with known anti-inflammatory properties such as arachidonic acid-derived lipoxin A(4) (LXA(4)) and linoleic acid-derived 9-oxo-octadecadienoic acid (9-oxoODE). Treating RAW 264.7 macrophages with LXA(4) or 9-oxoODE diminished oxidant-induced macrophage inflammatory response as indicated by decreased production of TNF alpha. The results show for the first time that selenoproteins are important for the balanced biosynthesis of pro- and anti-inflammatory oxylipids during inflammation. A better understanding of the Se-dependent control mechanisms governing oxylipid biosynthesis may uncover nutritional intervention strategies to counteract the harmful effects of uncontrolled inflammation due to oxylipids. (C) 2014 Elsevier Inc. All rights reserved. C1 [Mattmiller, Sarah A.; Gandy, Jeff C.; Sordillo, Lorraine M.] Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. [Carlson, Bradley A.] NCI, Mol Biol Selenium Sect, Mouse Canc Genet Program, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Sordillo, LM (reprint author), Michigan State Univ, Coll Vet Med, 748 Wilson Rd,G300 Vet Med Ctr, E Lansing, MI 48824 USA. EM Sordillo@msu.edu FU AFRI Animal Health competitive grant from the USDA National Institute of Food and Agriculture [2011-67015-30179]; Pre-Doctoral Fellowship from the USDA National Institute of Food and Agriculture [2012-67011-19944] FX This study was supported by grants from AFRI Animal Health competitive grant (no. 2011-67015-30179) and for a Pre-Doctoral Fellowship (grant no. 2012-67011-19944), both from the USDA National Institute of Food and Agriculture. NR 41 TC 6 Z9 7 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 EI 1873-4847 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JUN PY 2014 VL 25 IS 6 BP 647 EP 654 DI 10.1016/j.jnutbio.2014.02.005 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA AH8AD UT WOS:000336355600008 PM 24746836 ER PT J AU Murai, J Zhang, YP Morris, J Ji, JP Takeda, S Doroshow, JH Pommier, Y AF Murai, Junko Zhang, Yiping Morris, Joel Ji, Jiuping Takeda, Shunichi Doroshow, James H. Pommier, Yves TI Rationale for Poly(ADP-ribose) Polymerase (PARP) Inhibitors in Combination Therapy with Camptothecins or Temozolomide Based on PARP Trapping versus Catalytic Inhibition SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DNA TOPOISOMERASE-I; CANCER CELL-LINES; HOMOLOGOUS RECOMBINATION; VERTEBRATE CELLS; DRUG-COMBINATION; MAMMALIAN-CELLS; STRAND BREAKS; L1210 CELLS; REPAIR; DAMAGE AB We recently showed that poly(ADP-ribose) polymerase (PARP) inhibitors exert their cytotoxicity primarily by trapping PARP-DNA complexes in addition to their NAD(+)-competitive catalytic inhibitory mechanism. PARP trapping is drug-specific, with olaparib exhibiting a greater ability than veliparib, whereas both compounds are potent catalytic PARP inhibitors. Here, we evaluated the combination of olaparib or veliparib with therapeutically relevant DNA-targeted drugs, including the topoisomerase I inhibitor camptothecin, the alkylating agent temozolomide, the cross-linking agent cisplatin, and the topoisomerase II inhibitor etoposide at the cellular and molecular levels. We determined PARP-DNA trapping and catalytic PARP inhibition in genetically modified chicken lymphoma DT40, human prostate DU145, and glioblastoma SF295 cancer cells. For camptothecin, both PARP inhibitors showed highly synergistic effects due to catalytic PARP inhibition, indicating the value of combining either veliparib or olaparib with topoisomerase I inhibitors. On the other hand, for temozolomide, PARP trapping was critical in addition to catalytic inhibition, consistent with the fact that olaparib was more effective than veliparib in combination with temozolomide. For cisplatin and etoposide, olaparib only showed no or a weak combination effect, which is consistent with the lack of involvement of PARP in the repair of cisplatin-and etoposide-induced lesions. Hence, we conclude that catalytic PARP inhibitors are highly effective in combination with camptothecins, whereas PARP inhibitors capable of PARP trapping are more effective with temozolomide. Our study provides insights in combination treatment rationales for different PARP inhibitors. C1 [Murai, Junko; Doroshow, James H.; Pommier, Yves] NCI, Dev Therapeut Branch, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Zhang, Yiping; Ji, Jiuping] NCI, Natl Clin Target Validat Lab, NIH, Bethesda, MD 20892 USA. [Morris, Joel; Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Murai, Junko; Takeda, Shunichi] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto, Japan. RP Pommier, Y (reprint author), NCI, Dev Therapeut Branch, Mol Pharmacol Lab, Ctr Canc Res,NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU John Mung program (Kyoto University); Kyoto University Foundation; Intramural Research Program of the National Institutes of Health [National Cancer Institute]; Center for Cancer Research [Z01 BC 006150]; Japan Society for the Promotion of Science KAKENHI program [25740016]; National Institutes of Health National Cancer Institute [HHSN261200800001E] FX J.M. is a recipient of fellowships from the John Mung program (Kyoto University) and the Kyoto University Foundation. This work was supported by the Intramural Research Program of the National Institutes of Health [National Cancer Institute]; and the Center for Cancer Research [Grant Z01 BC 006150]. J.M. was supported by Japan Society for the Promotion of Science KAKENHI program [Grant 25740016]. J.J. was supported by the National Institutes of Health National Cancer Institute [Contract no. HHSN261200800001E]. NR 44 TC 51 Z9 51 U1 2 U2 13 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2014 VL 349 IS 3 BP 408 EP 416 DI 10.1124/jpet.113.210146 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH5GJ UT WOS:000336156200005 PM 24650937 ER PT J AU Pichard, DC Hensley, JR Williams, E Apolo, AB Klion, AD DiGiovanna, JJ AF Pichard, Dominique C. Hensley, Jennifer R. Williams, Esther Apolo, Andrea B. Klion, Amy D. DiGiovanna, John J. TI Rapid development of migratory, linear, and serpiginous lesions in association with immunosuppression SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material ID STRONGYLOIDES-STERCORALIS HYPERINFECTION; CUTANEOUS LARVA MIGRANS; PREVENTION; CURRENS C1 [Pichard, Dominique C.; Hensley, Jennifer R.] Georgetown Univ Hosp, Dept Dermatol, Washington, DC 20007 USA. [Williams, Esther] NIH, Ctr Clin, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA. [Apolo, Andrea B.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Klion, Amy D.] NIAID, Eosinophil Pathol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [DiGiovanna, John J.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP DiGiovanna, JJ (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res,NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM jdg@nih.gov OI Klion, Amy/0000-0002-4986-5326 FU Intramural NIH HHS [Z99 CA999999, ZIA BC004517-37] NR 17 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUN PY 2014 VL 70 IS 6 BP 1130 EP 1134 DI 10.1016/j.jaad.2013.11.036 PG 5 WC Dermatology SC Dermatology GA AH3NJ UT WOS:000336030400034 PM 24831316 ER PT J AU Dave, J Ahlman, MA Lockshin, BN Bluemke, DA Mehta, NN AF Dave, Jenny Ahlman, Mark A. Lockshin, Benjamin N. Bluemke, David A. Mehta, Nehal N. TI Vascular inflammation in psoriasis localizes to the arterial wall using a novel imaging technique SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID POSITRON-EMISSION-TOMOGRAPHY; PET/CT C1 [Dave, Jenny; Mehta, Nehal N.] NHLBI, Bethesda, MD 20892 USA. [Ahlman, Mark A.; Bluemke, David A.] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Lockshin, Benjamin N.] DermAssociates PC, Silver Spring, MD USA. RP Mehta, NN (reprint author), NIH, Bldg 10,CRC 5-5140, Bethesda, MD 20892 USA. EM nehal.mehta@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU Intramural NIH HHS [Z99 HL999999]; NHLBI NIH HHS [HL-Z-000000] NR 7 TC 9 Z9 9 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUN PY 2014 VL 70 IS 6 BP 1137 EP 1138 DI 10.1016/j.jaad.2013.12.043 PG 3 WC Dermatology SC Dermatology GA AH3NJ UT WOS:000336030400037 PM 24641984 ER PT J AU Schwartz, SM Lu, MM Ohye, RG Hill, KD Atz, AM Naim, MY Williams, IA Goldberg, CS Lewis, A Pigula, F Manning, P Pizarro, C Chai, P McCandless, R Dunbar-Masterson, C Kaltman, JR Kanter, K Sleeper, LA Schonbeck, JV Ghanayem, N AF Schwartz, Steven M. Lu, Minmin Ohye, Richard G. Hill, Kevin D. Atz, Andrew M. Naim, Maryam Y. Williams, Ismee A. Goldberg, Caren S. Lewis, Alan Pigula, Frank Manning, Peter Pizarro, Christian Chai, Paul McCandless, Rachel Dunbar-Masterson, Carolyn Kaltman, Jonathan R. Kanter, Kirk Sleeper, Lynn A. Schonbeck, Julie V. Ghanayem, Nancy CA Pediat Heart Network Investigators TI Risk factors for prolonged length of stay after the stage 2 procedure in the single-ventricle reconstruction trial SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID LEFT-HEART SYNDROME; BIDIRECTIONAL CAVOPULMONARY SHUNT; PULMONARY-ARTERY CONDUIT; BLALOCK-TAUSSIG SHUNT; HEMI-FONTAN PROCEDURE; NORWOOD PROCEDURE; CARDIOPULMONARY BYPASS; GLENN OPERATION; OUTCOMES; PALLIATION AB Background: The single-ventricle reconstruction trial randomized patients with single right ventricle lesions to a modified Blalock-Taussig or right ventricle-to-pulmonary artery shunt at the Norwood. This analysis describes outcomes at the stage 2 procedure and factors associated with a longer hospital length of stay (LOS). Methods: We examined the association of shunt type with stage 2 hospital outcomes. Cox regression and bootstrapping were used to evaluate risk factors for longer LOS. We also examined characteristics associated with in-hospital death. Results: There were 393 subjects in the analytic cohort. Median stage 2 procedure hospital LOS (8 days; interquartile range [IQR], 6-14 days), hospital mortality (4.3%), transplantation (0.8%), median ventilator time (2 days; IQR, 1-3 days), median intensive care unit LOS (4 days; IQR, 3-7 days), number of additional cardiac procedures or complications, and serious adverse events did not differ by shunt type. Longer LOS was associated (R-2 = 0.26) with center, longer post-Norwood LOS (hazard ratio [HR], 1.93 per log day; P <.001), nonelective timing of the stage 2 procedure (HR, 1.78; P <.001), and pulmonary artery (PA) stenosis (HR, 1.56; P <.001). By univariate analysis, nonelective stage 2 (65% vs 32%; P = .009), moderate or greater atrioventricular valve (AVV) regurgitation (75% vs 24%; P <.001), and AVV repair (53% vs 9%; P <.001) were among the risk factors associated with in-hospital death. Conclusions: Norwood LOS, PA stenoses, and nonelective stage 2 procedure, but not shunt type, are independently associated with longer LOS. Nonelective stage 2 procedure, moderate or greater AVV regurgitation, and need for AVV repair are among the risk factors for death. C1 [Schwartz, Steven M.] Hosp Sick Children, Dept Crit Care Med, Div Cardiac Crit Care Med, Toronto, ON M5G 1X8, Canada. [Schwartz, Steven M.] Hosp Sick Children, Dept Crit Care Med, Div Cardiol, Toronto, ON M5G 1X8, Canada. [Schwartz, Steven M.] Hosp Sick Children, Dept Paediat, Toronto, ON M5G 1X8, Canada. [Lu, Minmin; Sleeper, Lynn A.; Schonbeck, Julie V.] New England Res Inst, Watertown, MA 02172 USA. [Ohye, Richard G.] Univ Michigan, Sch Med, Dept Cardiac Surg, Div Pediat Cardiovasc Surg, Ann Arbor, MI USA. [Goldberg, Caren S.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Div Pediat Cardiol, Ann Arbor, MI USA. [Hill, Kevin D.] Duke Univ, Dept Pediat, Div Cardiol, Durham, NC 27706 USA. [Atz, Andrew M.] Med Univ S Carolina, Dept Pediat, Div Pediat Cardiol, Charleston, SC 29425 USA. [Naim, Maryam Y.] Childrens Hosp Philadelphia, Dept Anesthesia & Crit Care, Div Crit Care Med, Philadelphia, PA 19104 USA. [Williams, Ismee A.] Columbia Univ, Dept Pediat, Div Pediat Cardiol, New York, NY 10027 USA. [Lewis, Alan] Univ Calif Los Angeles, Dept Pediat, Div Cardiol, Los Angeles, CA 90024 USA. [Pigula, Frank] Childrens Hosp, Dept Cardiac Surg, Boston, MA 02115 USA. [Dunbar-Masterson, Carolyn] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Manning, Peter] Cincinnati Childrens Hosp Med Ctr, Dept Surg, Div Cardiovasc Surg, Cincinnati, OH 45229 USA. [Pizarro, Christian] Alfred I duPont Hosp Children, Dept Surg, Div Pediat Cardiothorac Surg, Wilmington, DE USA. [Chai, Paul] All Childrens Hosp, Div Cardiovasc Surg, Tampa, FL USA. [McCandless, Rachel] Primary Childrens Med Ctr, Dept Pediat, Div Pediat Cardiol, Salt Lake City, UT 84103 USA. [Kaltman, Jonathan R.] NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Kanter, Kirk] Emory Univ, Dept Surg, Div Cardiothorac Surg, Atlanta, GA 30322 USA. [Ghanayem, Nancy] Childrens Hosp Wisconsin, Dept Pediat, Div Crit Care Med, Milwaukee, WI 53201 USA. RP Schwartz, SM (reprint author), Hosp Sick Children, Dept Crit Care Med, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM steven.schwartz@sickkids.ca FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057, HL109781, HL109737] FX This study was supported by U01 grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288, HL085057, HL109781, and HL109737). This work is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. NR 30 TC 4 Z9 5 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 2014 VL 147 IS 6 BP 1791 EP U134 DI 10.1016/j.jtcvs.2013.07.063 PG 12 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AH9HF UT WOS:000336452000022 PM 24075564 ER PT J AU Rastinehad, AR Turkbey, B Salami, SS Yaskiv, O George, AK Fakhoury, M Beecher, K Vira, MA Kavoussi, LR Siegel, DN Villani, R Ben-Levi, E AF Rastinehad, Ardeshir R. Turkbey, Baris Salami, Simpa S. Yaskiv, Oksana George, Arvin K. Fakhoury, Mathew Beecher, Karin Vira, Manish A. Kavoussi, Louis R. Siegel, David N. Villani, Robert Ben-Levi, Eran TI Improving Detection of Clinically Significant Prostate Cancer: Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Guided Prostate Biopsy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; biopsy; magnetic resonance imaging; ultrasonography ID ACTIVE SURVEILLANCE; NEGATIVE BIOPSIES; MORTALITY; ACCURACY; MEN AB Purpose: Given the limitations of prostate specific antigen and standard biopsies for detecting prostate cancer, we evaluated the cancer detection rate and external validity of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system used at the National Institutes of Health. Materials and Methods: We performed a phase III trial of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system with participants enrolled between 2012 and 2013. A total of 153 men consented to the study and underwent 3 Tesla multiparametric magnetic resonance imaging with an endorectal coil for clinical suspicion of prostate cancer. Lesions were classified as low or moderate/high risk for prostate cancer. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and standard 12-core prostate biopsy were performed and 105 men were eligible for analysis. Results: Mean patient age was 65.8 years and mean prostate specific antigen was 9.5 ng/ml. The overall cancer detection rate was 62.9% (66 of 105 patients). The cancer detection rate in those with moderate/high risk on imaging was 72.3% (47 of 65) vs 47.5% (19 of 40) in those classified as low risk for prostate cancer (p < 0.05). Mean tumor core length was 4.6 and 3.7 mm for fusion biopsy and standard 12-core biopsy, respectively (p < 0.05). Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detected prostate cancer that was missed by standard 12-core biopsy in 14.3% of cases (15 of 105), of which 86.7% (13 of 15) were clinically significant. This biopsy upgraded 23.5% of cancers (4 of 17) deemed clinically insignificant on 12-core biopsy to clinically significant prostate cancer necessitating treatment. Conclusions: Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy can improve prostate cancer detection. The results of this trial support the external validity of this platform and may be the next step in the evolution of prostate cancer management. C1 [Rastinehad, Ardeshir R.] Hofstra North Shore Jewish Sch Med, Arthur Smith Inst Urol, New Hyde Pk, NY 11040 USA. Hofstra North Shore Jewish Sch Med, Dept Radiol, New Hyde Pk, NY 11040 USA. Hofstra North Shore Jewish Sch Med, Dept Intervent Radiol & Pathol, New Hyde Pk, NY 11040 USA. [Turkbey, Baris] NIH, Mol Imaging Program, Bethesda, MD 20892 USA. RP Rastinehad, AR (reprint author), Hofstra North Shore Jewish Sch Med, Arthur Smith Inst Urol, 450 Lakeville Rd,Suite M-41, New Hyde Pk, NY 11040 USA. EM arastine@nshs.edu NR 20 TC 70 Z9 71 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD JUN PY 2014 VL 191 IS 6 BP 1749 EP 1754 DI 10.1016/j.juro.2013.12.007 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AI0IS UT WOS:000336531100028 PM 24333515 ER PT J AU Fwu, CW Eggers, PW Kirkali, Z McVary, KT Burrows, PK Kusek, JW AF Fwu, Chyng-Wen Eggers, Paul W. Kirkali, Ziya McVary, Kevin T. Burrows, Pamela K. Kusek, John W. TI Change in Sexual Function in Men with Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Associated with Long-Term Treatment with Doxazosin, Finasteride and Combined Therapy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; lower urinary tract symptoms; sexual dysfunction; physiological; doxazosin; finasteride ID REAL-LIFE PRACTICE; COMBINATION THERAPY; MEDICAL THERAPY; OLMSTED COUNTY; HEALTH-STATUS; DYSFUNCTION; TRIAL; EFFICACY; DUTASTERIDE; CANCER AB Purpose: We examined the effects of doxazosin, finasteride and combined therapy in men with lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function, as assessed by the Brief Male Sexual Function Inventory during 4 years. Materials and Methods: The MTOPS (Medical Therapy of Prostatic Symptoms) study was a multicenter, randomized, double-blind, placebo controlled clinical trial with a primary outcome of time to benign prostatic hyperplasia progression. Change in sexual function was a secondary outcome. We analyzed the records of 2,783 men enrolled in the study who completed the inventory at baseline and at least once during followup. Results: In men enrolled in MTOPS sexual function decreased with time. Men assigned to finasteride and combined therapy experienced overall statistically significant but slight worsening of ejaculatory function compared with men on placebo. Men assigned to combined therapy also experienced significant worsening in erectile function and sexual problem assessment. There was no significant difference in changes in any inventory domain in men assigned to doxazosin alone compared to placebo. Conclusions: This study significantly extends understanding of the effects of long-term treatment with these drugs on sexual function in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. Treatment with finasteride or combined therapy was associated with worsening sexual function while treatment with doxazosin alone was associated with minimal negative impact, if any. Physicians should discuss with their patients the possible long-term effects of these drugs for lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function. C1 [Fwu, Chyng-Wen] Social & Sci Syst Inc, Silver Spring, MD 20910 USA. [Eggers, Paul W.; Kirkali, Ziya; Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. [Burrows, Pamela K.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [McVary, Kevin T.] So Illinois Univ, Sch Med, Div Urol, Springfield, IL USA. RP Fwu, CW (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cfwu@s-3.com FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [HHSN 276201200161U]; NIDDK (MTOPS) FX Supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Contract HHSN 276201200161U (CWF) and NIDDK (MTOPS). NR 30 TC 15 Z9 15 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD JUN PY 2014 VL 191 IS 6 BP 1828 EP 1834 DI 10.1016/j.juro.2013.12.014 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AI0IS UT WOS:000336531100074 PM 24342143 ER PT J AU Duyn, JH AF Duyn, Jeff H. TI Frequency Shifts in the Myelin Water Compartment SO MAGNETIC RESONANCE IN MEDICINE LA English DT Letter ID MAGNETIC-SUSCEPTIBILITY; WHITE-MATTER; BRAIN; ORIENTATION; MRI; ANISOTROPY; MEMBRANES; SHEATH; NERVE C1 NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Duyn, JH (reprint author), NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bldg 10,Room B1D118,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jhd@helix.nih.gov FU Intramural NIH HHS [ZIA NS002990-14] NR 23 TC 5 Z9 5 U1 1 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUN PY 2014 VL 71 IS 6 BP 1953 EP 1955 DI 10.1002/mrm.24983 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH6SL UT WOS:000336260900001 PM 24700549 ER PT J AU Gamache, B Leist, SR Bard, AD Logan, DW Carpanini, SM AF Gamache, Benjamin Leist, Sarah R. Bard, Andrew Daniel Logan, Darren W. Carpanini, Sarah M. TI 27th International Mammalian Genome Conference meeting report SO MAMMALIAN GENOME LA English DT Article C1 [Gamache, Benjamin] NCI, NIH, Bethesda, MD 20892 USA. [Leist, Sarah R.] Helmholtz Ctr Infect Res, Dept Infect Genet, Braunschweig, Germany. [Bard, Andrew Daniel; Logan, Darren W.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Bard, Andrew Daniel] Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England. [Carpanini, Sarah M.] Univ Edinburgh, Div Neurobiol, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland. RP Carpanini, SM (reprint author), Univ Edinburgh, Div Neurobiol, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland. EM sarah.carpanini@roslin.ed.ac.uk OI Logan, Darren /0000-0003-1545-5510 FU NHGRI [2R13HG0002394]; NICHD at NIH; Mouse News Letter Ltd; COST Action SYSGENET FX The IMGS wishes to thank the organising committee for arranging this fantastic conference; Elena de la Casa Esperon, Lluis Montoliu, Fernando Pardo-Manuel de Villena and Jesus Perez-Losada. The IMGS also wishes to thank the Secretariat comprising David Beier (President), Teresa Gunn (Vice-President), David Threadgill (Past President), Klaus Schughart, Linda Siracusa, Sarah Carpanini, Piero Carninci, Steven Munger, Elena de la Casa Esperon, Jiri Forejt and Darren Logan for their service. The society is also indebted to Darla Miller. The meeting was supported by The Jackson Laboratory, Taconic, Disease Models and Mechanisms, PLOS Genetics, GeneSeek and MMRRC. Funding for scholarship awards was made available through 2R13HG0002394 from NHGRI and NICHD at NIH and from Mouse News Letter Ltd, and through the COST Action SYSGENET. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 EI 1432-1777 J9 MAMM GENOME JI Mamm. Genome PD JUN PY 2014 VL 25 IS 5-6 BP 195 EP 201 DI 10.1007/s00335-014-9513-3 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA AH8LD UT WOS:000336388400002 PM 24752582 ER PT J AU Sacktor, N Nakasujja, N Redd, AD Manucci, J Laeyendecker, O Wendel, SK Porcella, SF Martens, C Bruno, D Skolasky, RL Okonkwo, OC Robertson, K Musisi, S Katabira, E Quinn, TC AF Sacktor, Ned Nakasujja, Noeline Redd, Andrew D. Manucci, Jordyn Laeyendecker, Oliver Wendel, Sarah K. Porcella, Stephen F. Martens, Craig Bruno, Daniel Skolasky, Richard L. Okonkwo, Ozioma C. Robertson, Kevin Musisi, Seggane Katabira, Elly Quinn, Thomas C. TI HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda SO METABOLIC BRAIN DISEASE LA English DT Article DE HIV; Dementia; Subtype; Uganda; Clade ID SUB-SAHARAN AFRICA; DISEASE PROGRESSION; NEUROPSYCHOLOGICAL PERFORMANCE; COGNITIVE IMPAIRMENT; RAKAI; SUPERINFECTION; RECEPTORS; INFECTION; CHILDREN; COHORT AB HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count > 150 cells/mu L and < 250 cells/mu L). The study enrolled 117 antiretroviral na < ve HIV+ individuals in Kampala, Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. 41 % of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count = 233 cells/mu L). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results. C1 [Sacktor, Ned] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA. [Skolasky, Richard L.] Johns Hopkins Univ, Sch Med, Dept Orthoped Surg, Baltimore, MD USA. [Manucci, Jordyn; Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Nakasujja, Noeline; Musisi, Seggane] Dept Psychiat, Kampala, Uganda. [Katabira, Elly] Makerere Univ, Dept Med, Kampala, Uganda. [Redd, Andrew D.; Manucci, Jordyn; Laeyendecker, Oliver; Wendel, Sarah K.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Porcella, Stephen F.; Martens, Craig; Bruno, Daniel] NIAID, Genom Unit, Res Technol Branch, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT USA. [Okonkwo, Ozioma C.] Univ Wisconsin, Dept Med, Madison, WI USA. [Robertson, Kevin] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. RP Sacktor, N (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol, 301 Bldg,Suite 2100,4940 Eastern Ave, Baltimore, MD 21224 USA. EM sacktor@jhmi.edu OI Laeyendecker, Oliver/0000-0002-6429-4760; Skolasky, Richard/0000-0002-2598-4427 FU National Institute of Mental Health at the National Institutes of Health [MH083465]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the National Institute of Mental Health at the National Institutes of Health (Grant number MH083465). Funding also was provided in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 29 TC 4 Z9 4 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 EI 1573-7365 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD JUN PY 2014 VL 29 IS 2 SI SI BP 261 EP 268 DI 10.1007/s11011-014-9498-3 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AH7SU UT WOS:000336335200007 PM 24515303 ER PT J AU Ciucci, T Bosselut, R AF Ciucci, Thomas Bosselut, Remy TI A ROG(ue) in charge of the (natural) killers SO NATURE IMMUNOLOGY LA English DT Editorial Material ID REPRESSOR; CELLS; DIFFERENTIATION; REGULATORS; EXPRESSION; EFFECTORS; LINEAGE; FAMILY; GATA AB Natural killer (NK) cells are innate lymphocytes that exhibit many features of adaptive immunity, such as long-lived memory. This can now be extended to the transcriptional circuits that control the proliferation of NK cells and lymphocytes. C1 [Ciucci, Thomas; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ciucci, T (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM remy@helix.nih.gov NR 12 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD JUN PY 2014 VL 15 IS 6 BP 531 EP 532 PG 2 WC Immunology SC Immunology GA AH8WQ UT WOS:000336419300007 PM 24840990 ER PT J AU Lee, JH Halperin-Sheinfeld, M Baatar, D Mughal, MR Tae, HJ Kim, JW Carter, A Lustig, A Snir, O Lavie, G Okun, E Mattson, MP Sredni, B Taub, DD AF Lee, Jun-Ho Halperin-Sheinfeld, Meital Baatar, Dolgar Mughal, Mohamed R. Tae, Hyun-Jin Kim, Jie-Wan Carter, Arnell Lustig, Ana Snir, Omri Lavie, Gad Okun, Eitan Mattson, Mark P. Sredni, Benjamin Taub, Dennis D. TI Tellurium Compound AS101 Ameliorates Experimental Autoimmune Encephalomyelitis by VLA-4 Inhibition and Suppression of Monocyte and T Cell Infiltration into the CNS SO NEUROMOLECULAR MEDICINE LA English DT Article DE Inflammation; Integrin; Macrophages; Multiple sclerosis; Spinal cord; VLA-4 ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; CANCER-PATIENTS; IMMUNOMODULATOR AS101; DEMYELINATING DISEASE; ADHESION MOLECULE-1; DENDRITIC CELLS; ANIMAL-MODELS; LEWIS RATS AB Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) involving demyelinating and neurodegenerative processes. Several of the major pathological CNS alterations and behavioral deficits of MS are recapitulated in the experimental autoimmune encephalitis (EAE) mouse model in which the disease process is induced by administration of myelin peptides. Development of EAE requires infiltration of inflammatory cytokine-generating monocytes and macrophages, and auto-reactive T cells, into the CNS. Very late antigen-4 (VLA-4, alpha 4 beta 1) is an integrin molecule that plays a role in inflammatory responses by facilitating the migration of leukocytes across the blood-brain barrier during inflammatory disease, and antibodies against VLA-4 exhibit therapeutic efficacy in mouse and monkey MS models. Here, we report that the tellurium compound AS101 (ammonium trichloro (dioxoethylene-o,o') tellurate) ameliorates EAE by inhibiting monocyte and T cell infiltration into the CNS. CD49d is an alpha subunit of the VLA-4 (alpha 4 beta 1) integrin. During the peak stage of EAE, AS101 treatment effectively ameliorated the disease process by reducing the number of CD49d(+) inflammatory monocyte/macrophage cells in the spinal cord. AS101 treatment markedly reduced the pro-inflammatory cytokine levels, while increasing anti-inflammatory cytokine levels. In contrast, AS101 treatment did not affect the peripheral populations of CD11b(+) monocytes and macrophages. AS101 treatment reduced the infiltration of CD4(+) and CD49(+)/VLA4 T cells. In addition, treatment of T cells from MS patients with AS101 resulted in apoptosis, while such treatment did not affect T cells from healthy donors. These results suggest that AS101 reduces accumulation of leukocytes in the CNS by inhibiting the activity of the VLA-4 integrin and provide a rationale for the potential use of Tellurium IV compounds for the treatment of MS. C1 [Lee, Jun-Ho; Baatar, Dolgar; Tae, Hyun-Jin; Kim, Jie-Wan; Carter, Arnell; Lustig, Ana; Taub, Dennis D.] NIA, Lab Cell Biol & Immunol, Intramural Res Program, Baltimore, MD 21224 USA. [Lee, Jun-Ho; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA. [Halperin-Sheinfeld, Meital; Snir, Omri; Okun, Eitan; Sredni, Benjamin] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel. [Snir, Omri; Lavie, Gad] Chaim Sheba Med Ctr, Ctr Blood Transfus, IL-52621 Tel Hashomer, Israel. [Snir, Omri; Lavie, Gad] Chaim Sheba Med Ctr, Multiple Sclerosis Ctr, IL-52621 Tel Hashomer, Israel. [Mattson, Mark P.] Johns Hopkins Univ Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Taub, DD (reprint author), NIA, Lab Cell Biol & Immunol, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov; srednib@mail.biu.ac.il; taubd@grc.nia.nih.gov FU National Institute on Aging FX This research was supported in part by the Intramural Research Program of the National Institute on Aging. NR 60 TC 4 Z9 4 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PD JUN PY 2014 VL 16 IS 2 BP 292 EP 307 DI 10.1007/s12017-013-8277-3 PG 16 WC Neurosciences SC Neurosciences & Neurology GA AH6EW UT WOS:000336224500005 PM 24272426 ER PT J AU Byun, NE Grannan, M Bubser, M Barry, RL Thompson, A Rosanelli, J Gowrishankar, R Kelm, ND Damon, S Bridges, TM Melancon, BJ Tarr, JC Brogan, JT Avison, MJ Deutch, AY Wess, J Wood, MR Lindsley, CW Gore, JC Conn, PJ Jones, CK AF Byun, Nellie E. Grannan, Michael Bubser, Michael Barry, Robert L. Thompson, Analisa Rosanelli, John Gowrishankar, Raajaram Kelm, Nathaniel D. Damon, Stephen Bridges, Thomas M. Melancon, Bruce J. Tarr, James C. Brogan, John T. Avison, Malcolm J. Deutch, Ariel Y. Wess, Juergen Wood, Michael R. Lindsley, Craig W. Gore, John C. Conn, P. Jeffrey Jones, Carrie K. TI Antipsychotic Drug-Like Effects of the Selective M-4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator VU0152100 SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE M-4; muscarinic; antipsychotic; allosteric; phMRI; VU0152100 ID IN-VIVO VALIDATION; AGONIST XANOMELINE; KNOCKOUT MICE; CHOLINERGIC INTERNEURONS; FUNCTIONAL CONNECTIVITY; PREPULSE INHIBITION; PHARMACOLOGICAL MRI; PREFRONTAL CORTEX; OREXIN NEURONS; DOPAMINE AB Accumulating evidence suggests that selective M-4 muscarinic acetylcholine receptor (mAChR) activators may offer a novel strategy for the treatment of psychosis. However, previous efforts to develop selective M-4 activators were unsuccessful because of the lack of M-4 mAChR subtype specificity and off-target muscarinic adverse effects. We recently developed VU0152100, a highly selective M-4 positive allosteric modulator (PAM) that exerts central effects after systemic administration. We now report that VU01521 00 dose-dependently reverses amphetamine-induced hyperlocomotion in rats and wild-type mice, but not in M-4 KO mice. VU0152100 also blocks amphetamine-induced disruption of the acquisition of contextual fear conditioning and prepulse inhibition of the acoustic startle reflex. These effects were observed at doses that do not produce catalepsy or peripheral adverse effects associated with non-selective mAChR agonists. To further understand the effects of selective potentiation of M-4 on region-specific brain activation, VU0152100 alone and in combination with amphetamine were evaluated using pharmacologic magnetic resonance imaging (phMRI). Key neural substrates of M-4-mediated modulation of the amphetamine response included the nucleus accumbens (NAS), caudate-putamen (CP), hippocampus, and medial thalamus. Functional connectivity analysis of phMRI data, specifically assessing correlations in activation between regions, revealed several brain networks involved in the M4 modulation of amphetamine-induced brain activation, including the NAS and retrosplenial cortex with motor cortex, hippocampus, and medial thalamus. Using in vivo microdialysis, we found that VU0152100 reversed amphetamine-induced increases in extracellular dopamine levels in NAS and CP. The present data are consistent with an antipsychotic drug-like profile of activity for VU0152100. Taken together, these data support the development of selective M-4 PAMs as a new approach to the treatment of psychosis and cognitive impairments associated with psychiatric disorders such as schizophrenia. C1 [Byun, Nellie E.; Grannan, Michael; Bubser, Michael; Thompson, Analisa; Rosanelli, John; Bridges, Thomas M.; Melancon, Bruce J.; Tarr, James C.; Brogan, John T.; Wood, Michael R.; Lindsley, Craig W.; Conn, P. Jeffrey; Jones, Carrie K.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Byun, Nellie E.; Grannan, Michael; Bubser, Michael; Thompson, Analisa; Bridges, Thomas M.; Brogan, John T.; Avison, Malcolm J.; Deutch, Ariel Y.; Lindsley, Craig W.; Conn, P. Jeffrey; Jones, Carrie K.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Byun, Nellie E.; Barry, Robert L.; Kelm, Nathaniel D.; Damon, Stephen; Avison, Malcolm J.; Gore, John C.] Vanderbilt Univ, Med Ctr, Vanderbilt Univ Inst Imaging Sci, Nashville, TN 37232 USA. [Barry, Robert L.; Avison, Malcolm J.] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA. [Gowrishankar, Raajaram] Vanderbilt Univ, Grad Program Neurosci, Nashville, TN 37232 USA. [Gowrishankar, Raajaram] Vanderbilt Univ, Vanderbilt Brain Inst, Nashville, TN 37232 USA. [Gowrishankar, Raajaram] Vanderbilt Univ, Vanderbilt Int Scholars Program, Nashville, TN 37232 USA. [Kelm, Nathaniel D.; Gore, John C.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37232 USA. [Bridges, Thomas M.; Brogan, John T.; Wood, Michael R.; Lindsley, Craig W.] Vanderbilt Univ, Med Ctr, Dept Chem, Nashville, TN 37232 USA. [Deutch, Ariel Y.] Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN 37232 USA. [Wess, Juergen] Natl Inst Diabet & Digest & Kidney Dis, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA. RP Jones, CK (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, 418B Preston Res Bldg, Nashville, TN 37232 USA. EM carrie.jones@vanderbilt.edu OI Bubser, Michael/0000-0002-0583-5248 FU NovoNordisk; NIH; Bristol Myers Squibb; Johnson Johnson; AstraZeneca; Michael J Fox Foundation; Thome Foundation; US National Institutes of Health [MH077298]; Eli Lilly; Barrus Foundation FX Dr Avison receives funding from NovoNordisk and received funding through NIH. Dr Conn received research support from Bristol Myers Squibb, Johnson & Johnson, and AstraZeneca, the Michael J Fox Foundation, the Thome Foundation and NIH and is an inventor on filed patent applications protecting M4 PAMs for the treatment of schizophrenia. Dr Deutch is supported in part by the US National Institutes of Health (MH077298) and by the Michael J Fox Foundation. He has served as a consultant for Eli Lilly, for which he has received honoraria and travel support. In addition, he has received compensation for editorial board responsibilities on Neuropsychopharmacology (ACNP). He has received travel support to attend meetings of Medical and Scientific Board of the National Parkinson Foundation. Dr Gore received funding from Astra Zeneca and the NIH. Dr Jones received research support from Bristol Myers Squibb, Johnson & Johnson, and AstraZeneca. Dr Jones also received funding through the Michael J Fox Foundation, the Barrus Foundation, and NIH. Dr Lindsley received compensation as a consultant for AbbVie Pharmaceuticals and research support from AstraZeneca, Johnson & Johnson, and Bristol Myers Squibb. Dr Lindsley also received funding through the Michael J Fox Foundation and NIH and is an inventor on filed patent applications protecting M4 PAMs for the treatment of schizophrenia. The remaining authors declare no conflict of interest. NR 70 TC 24 Z9 24 U1 2 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2014 VL 39 IS 7 BP 1578 EP 1593 DI 10.1038/npp.2014.2 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AH4OG UT WOS:000336107300004 PM 24442096 ER PT J AU Kramar, CP Chefer, VI Wise, RA Medina, JH Barbano, MF AF Kramar, Cecilia P. Chefer, Vladimir I. Wise, Roy A. Medina, Jorge H. Flavia Barbano, M. TI Dopamine in the Dorsal Hippocampus Impairs the Late Consolidation of Cocaine-Associated Memory SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE memory persistence; memory consolidation; hippocampus; dopamine; cocaine; conditioned behavior ID LONG-TERM-MEMORY; CONDITIONED PLACE PREFERENCE; VENTRAL TEGMENTAL AREA; MOLECULAR-MECHANISMS; NUCLEUS-ACCUMBENS; ADENYLYL-CYCLASE; LITHIUM-CHLORIDE; DRUG-ADDICTION; REWARD; GLUTAMATE AB Cocaine is thought to be addictive because it elevates dopamine levels in the striatum, reinforcing drug-seeking habits. Cocaine also elevates dopamine levels in the hippocampus, a structure involved in contextual conditioning as well as in reward function. Hippocampal dopamine promotes the late phase of consolidation of an aversive step-down avoidance memory. Here, we examined the role of hippocampal dopamine function in the persistence of the conditioned increase in preference for a cocaine-associated compartment. Blocking dorsal hippocampal DI -type receptors (D1Rs) but not D2-type receptors (D2Rs) 12 h after a single training trial extended persistence of the normally short-lived memory; conversely, a general and a specific phospholipase C-coupled DIR agonist (but not a D2R or adenylyl cyclase-coupled DIR agonist) decreased the persistence of the normally long-lived memory established by three-trial training. These effects of DI agents were opposite to those previously established in a step-down avoidance task, and were here also found to be opposite to those in a lithium chloride-conditioned avoidance task. After returning to normal following cocaine injection, dopamine levels in the dorsal hippocampus were found elevated again at the time when dopamine antagonists and agonists were effective: between 13 and 17 h after cocaine injection. These findings confirm that, long after the making of a cocaine place association, hippocampal activity modulates memory consolidation for that association via a dopamine dependent mechanism. They suggest a dynamic role for dorsal hippocampal dopamine in this late-phase memory consolidation and, unexpectedly, differential roles for late consolidation of memories for places that induce approach or withdrawal because of a drug association. C1 [Kramar, Cecilia P.; Medina, Jorge H.; Flavia Barbano, M.] Univ Buenos Aires, Fac Med, Inst Biol Celular & Neurociencias CONICET UBA, Buenos Aires, DF, Argentina. [Chefer, Vladimir I.; Wise, Roy A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Medina, Jorge H.] Univ Buenos Aires, Fac Med, Dept Fisiol, RA-1425 Buenos Aires, DF, Argentina. RP Barbano, MF (reprint author), NIDA, Intramural Res Program, Neuronal Networks Sect, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM maria.barbano@nih.gov FU CONICET, Argentina; CONICET, UBA, Foncyt [PICT 2010-1169, PICT 2011-1941]; Intramural Research Program of the National Institute on Drug Abuse (NIDA/NIH) FX We gratefully acknowledge Dr Gustavo Murer and Verardo y Cia. laboratory for their kind donation of quinpirole and cocaine hydrochloride, respectively. We thank Catherine Schweppe, Fernando Garagoli, Eduardo Gigante, and Carolina Gonzalez for excellent technical help. CP Kramar was supported by a doctoral fellowship from CONICET, Argentina. This work was supported by CONICET, UBA, Foncyt (Grants PICT 2010-1169 to Dr Medina and PICT 2011-1941 to Dr Barbano) and by the Intramural Research Program of the National Institute on Drug Abuse (NIDA/NIH). NR 41 TC 6 Z9 7 U1 2 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2014 VL 39 IS 7 BP 1645 EP 1653 DI 10.1038/npp.2014.11 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AH4OG UT WOS:000336107300010 PM 24442095 ER PT J AU Rose, EJ Salmeron, BJ Ross, TJ Waltz, J Schweitzer, JB McClure, SM Stein, EA AF Rose, Emma Jane Salmeron, Betty Jo Ross, Thomas J. Waltz, James Schweitzer, Julie B. McClure, Samuel M. Stein, Elliot A. TI Temporal Difference Error Prediction Signal Dysregulation in Cocaine Dependence SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cocaine dependence; temporal difference error prediction; reward; motivation; fMRI ID STATE FUNCTIONAL CONNECTIVITY; EVENT-RELATED FMRI; PREFRONTAL CORTEX; HUMAN BRAIN; DOPAMINE RELEASE; DORSAL STRIATUM; DRUG-ADDICTION; EMISSION-TOMOGRAPHY; NEURAL RESPONSES; DECISION-MAKING AB Cocaine dependence impacts drug-related, dopamine-dependent reward processing, yet its influence on non-drug reward processing is unclear. Here, we investigated cocaine-mediated effects on reward learning using a natural food reinforcer. Cocaine-dependent subjects (N =14) and healthy controls (N-= 14) learned to associate a visual cue with a juice reward. In subsequent functional imaging sessions they were exposed to trials where juice was received as learned, withheld (negative temporal difference error (NTDE)), or received unexpectedly (positive temporal difference error (PTDE)). Subjects were scanned twice in sessions that were identical, except that cocaine-dependent participants received cocaine or saline 10 min before task onset In the insula, precentral and postcentral gyri NTDE signals were greater, and PTDE-related function was reduced in cocaine-dependent subjects. Compared with healthy controls, in the cocaine-dependent group PTDE signals were also reduced in medial frontal gyrus and reward-related function, irrespective of predictability, was reduced in the putamen. Group differences in error-related activity were predicted by the time as last selfadministered cocaine use, but TDE function was not influenced by acute cocaine. Thus, cocaine dependence seems to engender increased responsiveness to unexpected negative outcomes and reduced sensitivity to positive events in dopaminergic reward regions. Although it remains to be established if these effects are a consequence of or antecedent to cocaine dependence, they likely have implications for the high-cocaine use recidivism rates by contributing to the drive to consume cocaine, perhaps via influence on dopamine-related reward computations. The fact that these effects do not acquiesce to acute cocaine administration might factor in binge-related escalated consumption. C1 [Rose, Emma Jane; Salmeron, Betty Jo; Ross, Thomas J.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD USA. [Waltz, James] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Schweitzer, Julie B.] Univ Calif Davis, Sch Med, MIND Inst, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. [McClure, Samuel M.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Rose, EJ (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Ctr Translat Res Advers Neurodev & Subst Abuse, 4th Floor,110 S Paca St, Baltimore, MD 21201 USA. EM ejrose@rti.org RI Rose, Emma/A-9960-2010; Salmeron, Betty Jo/M-1793-2016; OI Rose, Emma/0000-0001-5365-4794; Salmeron, Betty Jo/0000-0003-1699-9333; Ross, Thomas/0000-0002-7745-3572 FU Intramural Research Program of the National Institute on Drug Abuse (NIDA) FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), We gratefully acknowledge Kimberley Slater for her invaluable support and assistance in running this study. We thank Loretta Spurgeon, Eliscia Smith, NIDA-IRP nursing and recruitment staff, and the individuals who volunteered their time to participate. NR 68 TC 6 Z9 7 U1 3 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2014 VL 39 IS 7 BP 1732 EP 1742 DI 10.1038/npp.2014.21 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA AH4OG UT WOS:000336107300019 PM 24569319 ER PT J AU Takakura, A Tessler, HH Goldstein, DA Guex-Crosier, Y Chan, CC Brown, DM Thorne, JE Wang, R Cunningham, ET AF Takakura, Ako Tessler, Howard H. Goldstein, Debra A. Guex-Crosier, Yan Chan, Chi-Chao Brown, Diane M. Thorne, Jennifer E. Wang, Robert Cunningham, Emmett T., Jr. TI Viral Retinitis following Intraocular or Periocular Corticosteroid Administration: A Case Series and Comprehensive Review of the Literature SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Acute retinal necrosis; corticosteroid; cytomegalovirus; herpes virus; injection; retinitis ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; ACUTE RETINAL NECROSIS; CYTOMEGALOVIRUS RETINITIS; IMMUNOCOMPETENT PATIENT; CMV RETINITIS; INJECTION; UVEITIS; AIDS; IMPLANT AB Purpose: To describe viral retinitis following intravitreal and periocular corticosteroid administration. Methods: Retrospective case series and comprehensive literature review. Results: We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25-13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%). Conclusions: Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy. C1 [Takakura, Ako; Cunningham, Emmett T., Jr.] Calif Pacific Med Ctr, Dept Ophthalmol, San Francisco, CA USA. [Tessler, Howard H.] Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA. [Goldstein, Debra A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Guex-Crosier, Yan; Chan, Chi-Chao] Univ Lausanne, Jules Gonin Eye Hosp, Lausanne, Switzerland. [Brown, Diane M.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Thorne, Jennifer E.] Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA. [Wang, Robert] Texas Retina Associates, Dallas, TX USA. [Cunningham, Emmett T., Jr.] Stanford Univ, Dept Ophthalmol, Sch Med, Stanford, CA 94305 USA. [Cunningham, Emmett T., Jr.] UCSF, Francis I Proctor Fdn, San Francisco, CA USA. RP Cunningham, ET (reprint author), West Coast Retina Med Grp Inc, 1445 Bush St, San Francisco, CA 94109 USA. EM emmett_cunningham@yahoo.com FU Pacific Vision Foundation; Retina Foundation FX Supported in part by the Pacific Vision Foundation and the Retina Foundation. NR 28 TC 9 Z9 9 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0927-3948 EI 1744-5078 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD JUN PY 2014 VL 22 IS 3 BP 175 EP 182 DI 10.3109/09273948.2013.866256 PG 8 WC Ophthalmology SC Ophthalmology GA AH8ZR UT WOS:000336428300003 PM 24655372 ER PT J AU Weiss, B Widemann, BC Wolters, P Dombi, E Vinks, AA Cantor, A Korf, B Perentesis, J Gutmann, DH Schorry, E Packer, R Fisher, MJ AF Weiss, Brian Widemann, Brigitte C. Wolters, Pamela Dombi, Eva Vinks, Alexander A. Cantor, Alan Korf, Bruce Perentesis, John Gutmann, David H. Schorry, Elizabeth Packer, Roger Fisher, Michael J. TI Sirolimus for Non-Progressive NF1-Associated Plexiform Neurofibromas: An NF Clinical Trials Consortium Phase II Study SO PEDIATRIC BLOOD & CANCER LA English DT Article DE clinical trials; mTOR; neurofibromatosis; new agents; solid; tumors ID VISUAL ANALOG SCALE; QUALITY-OF-LIFE; MAMMALIAN TARGET; CANCER-THERAPY; FUNCTIONAL ASSESSMENT; PAIN QUESTIONNAIRE; RAPAMYCIN PATHWAY; PEDIATRIC PAIN; RELIABILITY; POPULATION AB BackgroundPatients with Neurofibromatosis Type 1 (NF1) have an increased risk of developing tumors of the central and peripheral nervous system, including plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among the most debilitating complications of NF1. There are no standard treatment options for PN other than surgery, which is often difficult due to the extensive growth and invasion of surrounding tissues. Mammalian Target of Rapamcyin (mTOR) acts as a master switch of cellular catabolism and anabolism and controls protein translation, angiogenesis, cell motility, and proliferation. The NF1 tumor suppressor, neurofibromin, regulates the mTOR pathway activity. Sirolimus is a macrolide antibiotic that inhibits mTOR activity. ProcedureWe conducted a 2-stratum phase II clinical trial. In stratum 2, we sought to determine whether the mTOR inhibitor sirolimus in subjects with NF1 results in objective radiographic responses in inoperable PNs in the absence of documented radiographic progression at trial entry. ResultsNo subjects had better than stable disease by the end of six courses. However, the children's self-report responses on health-related quality of life questionnaires indicated a significant improvement in the mean scores of the Emotional and School domains from baseline to 6 months of sirolimus. ConclusionsThis study efficiently documented that sirolimus does not cause shrinkage of non-progressive PNs, and thus should not be considered as a treatment option for these tumors. This study also supports the inclusion of patient-reported outcome measures in clinical trials to assess areas of benefit that are not addressed by the medical outcomes. Pediatr Blood Cancer 2014;61:982-986. (c) 2013 Wiley Periodicals, Inc. C1 [Weiss, Brian; Perentesis, John] Cincinnati Childrens Hosp Med Ctr, Div Oncol, Cincinnati, OH 45229 USA. [Widemann, Brigitte C.; Wolters, Pamela; Dombi, Eva] NCI, Dept Pediat Oncol, Bethesda, MD 20892 USA. [Vinks, Alexander A.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. [Cantor, Alan; Korf, Bruce] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. [Gutmann, David H.] Washington Univ, Dept Neurol, St Louis, MO USA. [Schorry, Elizabeth] Cincinnati Childrens Hosp Med Ctr, Dept Genet, Cincinnati, OH 45229 USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Fisher, Michael J.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. RP Weiss, B (reprint author), Div Hematol Oncol, MLC 7015,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM brian.weiss@cchmc.org FU Neurofibromatosis Clinical Trials Award [W81XWH-05-1-0615] FX Grant sponsor: Neurofibromatosis Clinical Trials Award for FY2007; Grant number: W81XWH-05-1-0615 NR 39 TC 16 Z9 17 U1 3 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2014 VL 61 IS 6 BP 982 EP 986 DI 10.1002/pbc.24873 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AE9IC UT WOS:000334320100008 PM 24851266 ER PT J AU Lee, B Lee, M Lefevre, M Kim, HR AF Lee, Bonggi Lee, Minsup Lefevre, Michael Kim, Hyeung-Rak TI Anthocyanins Inhibit Lipogenesis During Adipocyte Differentiation of 3T3-L1 Preadipocytes SO PLANT FOODS FOR HUMAN NUTRITION LA English DT Article DE Anthocyanins; Lipogenesis; Adipocytes ID FATTY-ACID SYNTHASE; ISOLATED RAT ADIPOCYTES; LIVER X-RECEPTORS; GENE-EXPRESSION; MICE; INSULIN; CELLS; ADIPOGENESIS; PERSPECTIVES; METABOLISM AB Anthocyanins have been shown to suppress body weight and fat mass in animal studies. However, the effect of anthocyanins on the process of lipid accumulation during adipocyte differentiation is not fully understood and the lipogenic transcription factors regulated by anthocyanins have not been identified. We investigated the effects of anthocyanins on lipogenesis pathways during adipocyte differentiation in 3T3-L1 cells. Anthocyanins reduced triglyceride (TG) accumulation in a dose-dependent manner during adipocyte differentiation. Accumulation of TG was rapidly reversed by anthocyanin withdrawal. Anthocyanins markedly reduced gene and protein expression levels of lipogenic transcription factors such as liver X receptor alpha, sterol regulatory element-binding protein-1c, peroxisome proliferators-activated receptor-gamma, and CCAAT enhancer-binding protein-alpha. In addition, the target gene and protein expression of these lipogenic transcription factors such as fatty acid synthase, stearoyl-CoA desaturase-1, and acetyl-CoA carboxylase alpha were markedly suppressed by anthocyanins. Thus, anthocyanins suppress lipid accumulation in adipocytes due to broad inhibition of the transcription factors regulating lipogenesis. This may partially explain the mechanism by which anthocyanins exert their anti-obesity effect. C1 [Lee, Bonggi; Lee, Minsup; Kim, Hyeung-Rak] Pukyong Natl Univ, Dept Food Sci & Nutr, Pusan 608737, South Korea. [Lee, Bonggi] NICHHD, NIH, Bethesda, MD 20892 USA. [Lefevre, Michael] Utah State Univ, Ctr Adv Nutr, Logan, UT 84322 USA. RP Kim, HR (reprint author), Pukyong Natl Univ, Dept Food Sci & Nutr, 45 Yongso Ro, Pusan 608737, South Korea. EM hrkim@pknu.ac.kr RI Lefevre, Michael/B-5030-2014 OI Lefevre, Michael/0000-0002-2046-3593 FU Pukyong National University Research Abroad Fund [C-D-2013-0915] FX This work was supported by Pukyong National University Research Abroad Fund in 2013 (C-D-2013-0915). NR 34 TC 6 Z9 7 U1 2 U2 25 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0921-9668 EI 1573-9104 J9 PLANT FOOD HUM NUTR JI Plant Food Hum. Nutr. PD JUN PY 2014 VL 69 IS 2 BP 137 EP 141 DI 10.1007/s11130-014-0407-z PG 5 WC Plant Sciences; Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Plant Sciences; Chemistry; Food Science & Technology; Nutrition & Dietetics GA AH8NC UT WOS:000336393700008 PM 24682657 ER PT J AU Brotman, MA Tseng, WL Olsavsky, AK Fromm, SJ Muhrer, EJ Rutenberg, JG Deveney, CM Adleman, NE Zarate, CA Pine, DS Leibenluft, E AF Brotman, M. A. Tseng, W. -L. Olsavsky, A. K. Fromm, S. J. Muhrer, E. J. Rutenberg, J. G. Deveney, C. M. Adleman, N. E. Zarate, C. A., Jr. Pine, D. S. Leibenluft, E. TI Fronto-limbic-striatal dysfunction in pediatric and adult patients with bipolar disorder: impact of face emotion and attentional demands SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Attention; bipolar disorder; face emotion; fronto-limbic-striatal dysfunction; imaging; pediatric ID ANTERIOR CINGULATE CORTEX; SEVERE MOOD DYSREGULATION; FACIAL AFFECT RECOGNITION; DEPRESSION RATING-SCALE; AMYGDALA ACTIVATION; PREFRONTAL CORTEX; QUANTITATIVE METAANALYSIS; FUNCTIONAL CONNECTIVITY; FMRI; CHILDREN AB Background Research in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age. Method During functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing. Results Pediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces. Conclusions Findings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands. C1 [Brotman, M. A.; Tseng, W. -L.; Fromm, S. J.; Muhrer, E. J.; Rutenberg, J. G.; Deveney, C. M.; Adleman, N. E.; Pine, D. S.; Leibenluft, E.] NIMH, Emot & Dev Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Olsavsky, A. K.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Zarate, C. A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brotman, MA (reprint author), Bldg 10,Room B1D43C,10 Ctr Dr, Bethesda, MD 20892 USA. EM brotmanm@mail.nih.gov RI Brotman, Melissa/H-7409-2013 FU Intramural Research Program of the National Institute of Mental Health (NIMH), National Institutes of Health (NIH) FX Funding for this study was provided by the Intramural Research Program of the National Institute of Mental Health (NIMH), National Institutes of Health (NIH). We thank the staff of the Emotion and Development and Experimental Therapeutics and Pathophysiology Branches at NIMH and the patients and their parents for their participation. NR 77 TC 8 Z9 8 U1 2 U2 16 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD JUN PY 2014 VL 44 IS 8 BP 1639 EP 1651 DI 10.1017/S003329171300202X PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AG6DG UT WOS:000335508100010 PM 23930595 ER PT J AU Rhebergen, D van der Steenstraten, IM Sunderland, M de Graaf, R ten Have, M Lamers, F Penninx, BWJH Andrews, G AF Rhebergen, D. van der Steenstraten, I. M. Sunderland, M. de Graaf, R. ten Have, M. Lamers, F. Penninx, B. W. J. H. Andrews, G. TI An examination of generalized anxiety disorder and dysthymic disorder by latent class analysis SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Dysthymia; generalized anxiety disorder; latent class analysis; nosology ID INTERNATIONAL DIAGNOSTIC INTERVIEW; NATIONAL-COMORBIDITY-SURVEY; DEPRESSIVE SYMPTOMATOLOGY IDS; WORLD-HEALTH-ORGANIZATION; COMMON MENTAL-DISORDERS; PSYCHOMETRIC PROPERTIES; SURVEY REPLICATION; MAJOR DEPRESSION; INVENTORY; CIDI AB Background The nosological status of generalized anxiety disorder (GAD) versus dysthymic disorder (DD) has been questioned. The aim of this study was to examine qualitative differences within (co-morbid) GAD and DD symptomatology. Method Latent class analysis was applied to anxious and depressive symptomatology of respondents from three population-based studies (2007 Australian National Survey of Mental Health and Wellbeing; National Comorbidity Survey Replication; and Netherlands Mental Health Survey and Incidence Study-2; together known as the Triple study) and respondents from a multi-site naturalistic cohort [Netherlands Study of Depression and Anxiety (NESDA)]. Sociodemographics and clinical characteristics of each class were examined. Results A three-class (Triple study) and two-class (NESDA) model best fitted the data, reflecting mainly different levels of severity of symptoms. In the Triple study, no division into a predominantly GAD or DD co-morbidity subtype emerged. Likewise, in spite of the presence of pure GAD and DD cases in the NESDA sample, latent class analysis did not identify specific anxiety or depressive profiles in the NESDA study. Next, sociodemographics and clinical characteristics of each class were examined. Classes only differed in levels of severity. Conclusions The absence of qualitative differences in anxious or depressive symptomatology in empirically derived classes questions the differentiation between GAD and DD. C1 [Rhebergen, D.; van der Steenstraten, I. M.; Penninx, B. W. J. H.] VU Univ Med Ctr Amsterdam, Dept Psychiat, Amsterdam, Netherlands. [Rhebergen, D.; van der Steenstraten, I. M.; Penninx, B. W. J. H.] VU Univ Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Rhebergen, D.; Penninx, B. W. J. H.] GGZ inGeest, Amsterdam, Netherlands. [Sunderland, M.; Andrews, G.] Univ New S Wales, CRUfAD, Sydney, NSW, Australia. [de Graaf, R.; ten Have, M.] Netherlands Inst Mental Hlth & Addict, Utrecht, Netherlands. [Lamers, F.] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. RP Rhebergen, D (reprint author), VU Univ Med Ctr Amsterdam, Amsterdam, Netherlands. EM d.rhebergen@ggzingeest.nl OI Sunderland, Matthew/0000-0001-8452-364X FU Australian Department of Health and Ageing; Ministry of Health, Welfare and Sport; Geestkracht program of the Netherlands Organization for Health Research and Development (ZonMw) [10-000-1002]; VU University Medical Center; GGZ inGeest; Arkin; Leiden University Medical Center; GGZ Rivierduinen; University Medical Center Groningen; Lentis; GGZ Friesland; GGZ Drenthe; IQ Healthcare; Netherlands Institute for Health Services Research (NIVEL); Netherlands Institute of Mental Health and Addiction; Dr Catharine van Tussenbroek Fonds; National Health and Medical Research Council (NHMRC) Capacity Building Grant [568940]; Netherlands Organization for Scientific Research (NWO) FX We greatly acknowledge the National Comorbidity Survey Replication for releasing a public use version of their dataset. The 2007 Australian National Survey of Mental Health and Wellbeing was funded by the Australian Department of Health and Ageing and conducted by the Australian Bureau of Statistics. NEMESIS-2 is conducted by the Netherlands Institute of Mental Health and Addiction (Trimbos Institute) in Utrecht with financial support from the Ministry of Health, Welfare and Sport. The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (ZonMw, grant no. 10-000-1002) and is supported by participating universities and mental health care organizations [VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, IQ Healthcare, Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction]. D. R. was supported by a grant from the Dr Catharine van Tussenbroek Fonds. M. S. was supported by a National Health and Medical Research Council (NHMRC) Capacity Building Grant (no.568940). F. L. was supported by a Rubicon Fellowship from the Netherlands Organization for Scientific Research (NWO). NR 46 TC 1 Z9 1 U1 4 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD JUN PY 2014 VL 44 IS 8 BP 1701 EP 1712 DI 10.1017/S0033291713002225 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AG6DG UT WOS:000335508100015 PM 24020863 ER PT J AU Dunbar-Jacob, J McCloskey, DJ Weglicki, LS Grady, PA AF Dunbar-Jacob, Jacqueline McCloskey, Donna Jo Weglicki, Linda S. Grady, Patricia A. TI The Contributions and Challenges of NINR Centers: Perspectives of Directors SO RESEARCH IN NURSING & HEALTH LA English DT Editorial Material DE Nursing research; research productivity; research centers; interprofessional research; research mentoring ID TRANSLATIONAL SCIENCE C1 [Dunbar-Jacob, Jacqueline] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [McCloskey, Donna Jo; Weglicki, Linda S.; Grady, Patricia A.] NINR, NIH, Bethesda, MD 20892 USA. RP Dunbar-Jacob, J (reprint author), Univ Pittsburgh, Sch Nursing, 3500 Victoria St,Room 350, Pittsburgh, PA 15261 USA. EM dunbar@pitt.edu NR 10 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-6891 EI 1098-240X J9 RES NURS HEALTH JI Res. Nurs. Health PD JUN PY 2014 VL 37 IS 3 BP 174 EP 181 DI 10.1002/nur.21598 PG 8 WC Nursing SC Nursing GA AH2PF UT WOS:000335962700002 PM 24797436 ER PT J AU Bloodworth, RF Ward, KD Relyea, GE Cashion, AK AF Bloodworth, Robin F. Ward, Kenneth D. Relyea, George E. Cashion, Ann K. TI Food Availability as a Determinant of Weight Gain Among Renal Transplant Recipients SO RESEARCH IN NURSING & HEALTH LA English DT Article DE food availability; obesity; BMI; renal transplant; post-transplant weight gain ID KIDNEY-TRANSPLANTATION; OBESITY; IMMUNOSUPPRESSION; ENVIRONMENTS; THERAPY; RISK AB Excessive weight gain is common after renal transplantation, but it is unknown whether environmental factors, such as food availability, contribute to this important clinical problem. We evaluated the effects of food availability (fast food restaurants, convenience stores, and grocery stores within 1, 2, and 3 mile buffers of transplant recipients' residences) on body mass index (BMI) change during the first year post-transplant. Participants (n=299) resided in Memphis, Tennessee. BMI increased by 1.42 units (p<.001) corresponding to an average weight gain of 9.25lbs (5.43%) during the first year post-transplant. The number of grocery stores within 1 mile of recipient's residence was associated with an increase in BMI (p<.05), but fast food restaurants and convenience stores were not significantly associated with BMI change. (c) 2014 Wiley Periodicals, Inc. C1 [Bloodworth, Robin F.] Univ Maryland, Dept Hlth Serv Adm, College Pk, MD 20742 USA. [Bloodworth, Robin F.] Univ Memphis, Sch Publ Hlth, Memphis, TN 38152 USA. [Bloodworth, Robin F.] Univ Tennessee, Ctr Hlth Sci, Coll Nursing, Memphis, TN 38163 USA. [Ward, Kenneth D.] Univ Memphis, Sch Publ Hlth, Div Social & Behav Sci, Memphis, TN 38152 USA. [Relyea, George E.] Univ Memphis, Sch Publ Hlth, Dept Epidemiol & Biostat, Memphis, TN 38152 USA. [Cashion, Ann K.] NINR, NIH, Bethesda, MD 20892 USA. RP Bloodworth, RF (reprint author), Univ Maryland, Dept Hlth Serv Adm, 1222 Sch Publ Hlth Bldg, College Pk, MD 20742 USA. EM rbloodwo@umd.edu FU Intramural NIH HHS [Z99 NR999999] NR 24 TC 5 Z9 5 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-6891 EI 1098-240X J9 RES NURS HEALTH JI Res. Nurs. Health PD JUN PY 2014 VL 37 IS 3 BP 253 EP 259 DI 10.1002/nur.21599 PG 7 WC Nursing SC Nursing GA AH2PF UT WOS:000335962700011 PM 24805885 ER PT J AU Albert, PS Shih, JH AF Albert, Paul S. Shih, Joanna H. TI Modelling batched Gaussian longitudinal weight data in mice subject to informative dropout SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article DE Missing data; pattern mixture models; repeated measures; shared random parameter models ID TO-EVENT DATA; LIKELIHOOD APPROACH; SURVIVAL-DATA; LINEAR-MODEL; JOINT; ALGORITHMS; TIMES AB Modelling longitudinal data subject to informative dropout is an active area in statistical research. This article focuses on modelling such longitudinal data when the outcome at each follow-up time is collected in batches rather than individually collected. The problem occurred in a study that compared the weight of mice over time between a control and a treatment group, where animal weight was measured in batches of five animals per cage. We develop both a shared parameter and a pattern mixture modelling approach for accounting for potentially informative dropout due to an animal's death. Our methodology suggests that animals receiving the treatment have a lower weight in mid-life, and have a slower decline in weight in the later period of life. Our simulations suggest that both the shared random parameter and pattern mixture modelling approaches work well under a correctly specified model. However, the pattern mixture model is more robust against model misspecification than the shared random parameter model, but the shared random parameter model parameters have a more direct interpretation than those of the pattern mixture modelling approach. C1 [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. EM albertp@mail.nih.gov FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank two referees for their constructive comments which lead to a substantially improved manuscript. We thank Dr John Mitchell and Dr John Cook for collaborations which has led to the development of this methodology. We also thank them for allowing us access to the data and for reviewing the manuscript. This research was supported in part by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development. We thank the Center for Information Technology, NIH, for providing access to the high-performance computational capabilities of the Biowulf cluster computer system. NR 23 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 EI 1477-0334 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD JUN PY 2014 VL 23 IS 3 BP 203 EP 217 DI 10.1177/0962280210397886 PG 15 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA AH7SZ UT WOS:000336335800001 PM 21300625 ER PT J AU Phipps, KM Devlin, M AF Phipps, Karl M. Devlin, Mark TI Dr. Mark Devlin SO TRIBOLOGY & LUBRICATION TECHNOLOGY LA English DT Editorial Material C1 [Devlin, Mark] Afton Chem Corp, Richmond, VA USA. [Devlin, Mark] NIH, Bethesda, MD 20892 USA. EM mark.devlin@aftonchemical.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC TRIBOLOGISTS & LUBRICATION ENGINEERS PI PARK RIDGE PA 840 BUSSE HIGHWAY, PARK RIDGE, IL 60068 USA SN 1545-858X J9 TRIBOL LUBR TECHNOL JI Tribol. Lubr. Technol. PD JUN PY 2014 VL 70 IS 6 BP 20 EP 23 PG 4 WC Engineering, Mechanical SC Engineering GA AH8BY UT WOS:000336360300006 ER PT J AU Pan, WL Wong, JH Fang, EF Chan, YS Ng, TB Cheung, RCF AF Pan, Wen Liang Wong, Jack Ho Fang, Evandro Fei Chan, Yau Sang Ng, Tzi Bun Cheung, Randy Chi Fai TI Preferential cytotoxicity of the type I ribosome inactivating protein alpha-momorcharin on human nasopharyngeal carcinoma cells under normoxia and hypoxia SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE alpha-Momorcharin; Unfolded protein response; Ribosome inactivating protein; Nasopharyngeal carcinoma; Hypoxic tumors ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-CELLS; INDUCIBLE FACTOR-1; CYCLIN D1; ACTIVATION; SURVIVAL; CANCER; STRESS; RADIOTHERAPY; APOPTOSIS AB All primary nasopharyngeal carcinoma (NPC) tumors contain hypoxic regions which are implicated in decreased local control and increased distant metastases, as well as resistance to chemotherapy in advanced NPC patients. One of the promising therapeutic approaches for NPC is to use drugs that can target hypoxic factors in tumors. In the present investigation, the type I ribosome inactivating protein alpha-momorcharin (alpha-MMC), isolated from seeds of the bitter gourd Momordica charantia, reduced cell viability and inhibited clonogenic formation of human NPC CNE2 and HONE1 cells under normoxia and cobalt chloride-induced hypoxia. By comparison, alpha-MMC exhibited only slight cytotoxicity on human nasopharyngeal epithelial NP69 cells under normoxia. Interestingly, alpha-MMC suppressed the expression levels of hypoxia-inducible factor 1-alpha (HIF1 alpha) and vascular endothelial growth factor (VEGF) in hypoxic NPC, as well as the growth of human umbilical vein endothelial cells. Further study disclosed that alpha-MMC targeted endoplasmic reticulum and down-regulated unfolded protein response (UPR) in NPC cells. Moreover, alpha-MMC induced apoptosis in NPC cells in a dose- and time-dependent manner. It initiated mitochondrial- and death receptor-mediated apoptotic signaling in CNE2 cells, but there was hardly any effect on HONE1 cells. In addition, alpha-MMC brought about G0/G1 phase cell cycle arrest in CNE2 cells and S phase arrest in HONE1 cells. Collectively, alpha-MMC preferentially exhibited inhibitory effect on normoxic and hypoxic NPC cells partly by blocking survival signaling (e.g. HIFI alpha, VEGF and UPR), and triggering apoptotic pathways mediated by mitochondria or death receptor. These observations indicate the potential utility of alpha-MMC for prophylaxis and therapy of NPC. (C) 2014 Elsevier Inc. All rights reserved. C1 [Pan, Wen Liang; Wong, Jack Ho; Chan, Yau Sang; Ng, Tzi Bun; Cheung, Randy Chi Fai] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. [Fang, Evandro Fei] NIA, NIH, Baltimore, MD 21224 USA. RP Ng, TB (reprint author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. EM tzibunng@cuhk.edu.hk FU Intramural Research Program of the NIH, National Institute on Aging [Z01-AG000723-02] FX EFF is supported by the Intramural Research Program (Grant number: Z01-AG000723-02) of the NIH, National Institute on Aging. NR 53 TC 11 Z9 13 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 1 PY 2014 VL 89 IS 3 BP 329 EP 339 DI 10.1016/j.bcp.2014.03.004 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH3GZ UT WOS:000336013000004 PM 24637239 ER PT J AU Spruiell, K Jones, DZ Cullen, JM Awumey, EM Gonzalez, FJ Gyamfi, MA AF Spruiell, Krisstonia Jones, Dominique Z. Cullen, John M. Awumey, Emmanuel M. Gonzalez, Frank J. Gyamfi, Maxwell A. TI Role of human pregnane X receptor in high fat diet-induced obesity in pre-menopausal female mice SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Obesity; High-fat diet; Pregnane X receptor; Nuclear receptors; Type 2 diabetes; Females ID UNCOUPLING PROTEIN GENE; BROWN ADIPOSE-TISSUE; ESTROGEN-RECEPTOR; INSULIN-RESISTANCE; BODY-FAT; NUCLEAR RECEPTOR; GLUCOSE-HOMEOSTASIS; DIABETES-MELLITUS; CROSS-TALK; ANDROSTANE RECEPTOR AB Obesity is a complex metabolic disorder that is more prevalent among women. Until now, the only relevant rodent models of diet-induced obesity were via the use of ovariectomized ("postmenopausal") females. However, recent reports suggest that the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to obesity. Therefore, we compared the roles of mouse and human PXRs in diet-induced obesity between wild type (WT) and PXR-humanized (hPXR) transgenic female mice fed either control or high-fat diets (HFD) for 16 weeks. HFD-fed hPXR mice gained weight more rapidly than controls, exhibited hyperinsulinemia, and impaired glucose tolerance. Fundamental differences were observed between control-fed hPXR and WT females: hPXR mice possessed reduced estrogen receptor alpha (ER alpha) but enhanced uncoupling protein 1 (UCP1) protein expression in white adipose tissue (WAT); increased protein expression of the hepatic cytochrome P450 3A11 (CYP3A11) and key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, and increased total cholesterol. Interestingly, HFD ingestion induced both UCP1 and glucokinase protein expression in WT mice, but inhibited these enzymes in hPXR females. Unlike WT mice, CYP3A1 l protein, serum 17 beta-estradiol levels, and WAT ERa expression were unaffected by HFD in hPXR females. Together, these studies indicate that the hPXR gene promotes obesity and metabolic syndrome by dysregulating lipid and glucose homeostasis while inhibiting UCP1 expression. Furthermore, our studies indicate that the human PXR suppresses the protective role of estrogen in metabolic disorders. Finally, these data identify PXR-humanized mice as a promising in vivo research model for studying obesity and diabetes in women. Published by Elsevier Inc. C1 [Spruiell, Krisstonia; Jones, Dominique Z.; Awumey, Emmanuel M.; Gyamfi, Maxwell A.] N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Cardiovasc & Metab Dis Res Program, Durham, NC 27707 USA. [Spruiell, Krisstonia; Awumey, Emmanuel M.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. [Cullen, John M.] N Carolina State Univ, North Carolina Coll Vet Med, Raleigh, NC 27607 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gyamfi, MA (reprint author), N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Cardiovasc & Metab Dis Res Program, 700 George St, Durham, NC 27707 USA. EM mgyamfi@nccu.edu FU National Institutes of Health (NIH) [U54 AA019765, SC1 HL099139, P20 MD000175, RO1 HL064761, R25HL059868]; National Cancer Institute Intramural Research Program, NIH FX The authors are grateful to Drs. Thomas Pazdernik and Susan T. Yeyeodu for critical reading of the manuscript. This work was supported by the National Institutes of Health (NIH) grants U54 AA019765, SC1 HL099139, P20 MD000175, RO1 HL064761, and R25HL059868 and the National Cancer Institute Intramural Research Program, NIH. NR 101 TC 9 Z9 10 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 1 PY 2014 VL 89 IS 3 BP 399 EP 412 DI 10.1016/j.bcp.2014.03.019 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH3GZ UT WOS:000336013000010 PM 24721462 ER PT J AU Lissek, S Kaczkurkin, AN Rabin, S Geraci, M Pine, DS Grillon, C AF Lissek, Shmuel Kaczkurkin, Antonia N. Rabin, Stephanie Geraci, Marilla Pine, Daniel S. Grillon, Christian TI Generalized Anxiety Disorder Is Associated With Overgeneralization of Classically Conditioned Fear SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Behavioral-and-Cognitive-Therapies CY NOV, 2012 CL National Harbor, MD SP Assoc Behav & Cognit Therapies DE Fear conditioning; fear-potentiated startle; generalized; anxiety disorder; interpretation bias; pathophysiology; stimulus generalization ID STIMULUS-GENERALIZATION; DISCRIMINATION; CORTEX; MODEL; RATS; VALIDATION; LESIONS AB Background: Meta-analytic results of fear-conditioning studies in the anxiety disorders implicate generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of anxiety pathology. Due to the absence of conditioning studies assessing generalization in generalized anxiety disorder (GAD), results of this meta-analysis do not reveal whether such generalization abnormalities also apply to GAD. The current study fills this gap by behaviorally and psychophysiologically assessing levels of conditioned fear generalization across adults with and without GAD. Methods: Twenty-two patients with a DSM-IV-Text Revision diagnosis of GAD and 26 healthy comparison subjects were recruited and tested. The employed generalization paradigm consisted of quasi-randomly presented rings of gradually increasing size, with extreme sizes serving as conditioned danger cues (CS+) and conditioned safety cues. The rings of intermediary size served as generalization stimuli, creating a continuum of similarity between CS+ and conditioned safety cues across which to assess response slopes, referred to as generalization gradients. Primary outcome variables included slopes for fear-potentiated startle (electromyography) and self-reported risk ratings. Results: Behavioral and psychophysiological findings demonstrated overgeneralization of conditioned fear among patients with GAD. Specifically, generalization gradients were abnormally shallow among GAD patients, reflecting less degradation of the conditioned fear response as the presented stimulus differentiated from the CS+. Conclusions: Overgeneralization of conditioned fear to safe encounters resembling feared situations may contribute importantly to the psychopathology of GAD by proliferating anxiety cues in the individual's environment that are then capable of evoking and maintaining anxiety and worry associated with GAD. C1 [Lissek, Shmuel; Geraci, Marilla; Pine, Daniel S.; Grillon, Christian] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. [Lissek, Shmuel; Kaczkurkin, Antonia N.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Rabin, Stephanie] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. RP Lissek, S (reprint author), Univ Minnesota, Dept Psychol, Elliott Hall,75 East River Rd, Minneapolis, MN 55455 USA. EM smlissek@umn.edu OI Rabin, Stephanie/0000-0002-8282-0867 FU Intramural NIH HHS; NIMH NIH HHS [K99 MH080130, R00 MH080130] NR 23 TC 56 Z9 59 U1 8 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2014 VL 75 IS 11 BP 909 EP 915 DI 10.1016/j.biopsych.2013.07.025 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AH1SX UT WOS:000335902400014 PM 24001473 ER PT J AU Thompson, PM Stein, JL Medland, SE Hibar, DP Vasquez, AA Renteria, ME Toro, R Jahanshad, N Schumann, G Franke, B Wright, MJ Martin, NG Agartz, I Alda, M Alhusaini, S Almasy, L Almeida, J Alpert, K Andreasen, NC Andreassen, OA Apostolova, LG Appel, K Armstrong, NJ Aribisala, B Bastin, ME Bauer, M Bearden, CE Bergmann, O Binder, EB Blangero, J Bockholt, HJ Boen, E Bois, C Boomsma, DI Booth, T Bowman, IJ Bralten, J Brouwer, RM Brunner, HG Brohawn, DG Buckner, RL Buitelaar, J Bulayeva, K Bustillo, JR Calhoun, VD Cannon, DM Cantor, RM Carless, MA Caseras, X Cavalleri, GL Chakravarty, MM Chang, KD Ching, CRK Christoforou, A Cichon, S Clark, VP Conrod, P Coppola, G Crespo-Facorro, B Curran, JE Czisch, M Deary, IJ de Geus, EJC den Braber, A Delvecchio, G Depondt, C de Haan, L de Zubicaray, GI Dima, D Dimitrova, R Djurovic, S Dong, HW Donohoe, G Duggirala, R Dyer, TD Ehrlich, S Ekman, CJ Elvsashagen, T Emsell, L Erk, S Espeseth, T Fagerness, J Fears, S Fedko, I Fernandez, G Fisher, SE Foroud, T Fox, PT Francks, C Frangou, S Frey, EM Frodl, T Frouin, V Garavan, H Giddaluru, S Glahn, DC Godlewska, B Goldstein, RZ Gollub, RL Grabe, HJ Grimm, O Gruber, O Guadalupe, T Gur, RE Gur, RC Goring, H Hagenaars, S Hajek, T Hall, GB Hall, J Hardy, J Hartman, CA Hass, J Hatton, SN Haukvik, UK Hegenscheid, K Heinz, A Hickie, IB Ho, BC Hoehn, D Hoekstra, PJ Hollinshead, M Holmes, AJ Homuth, G Hoogman, M Hong, LE Hosten, N Hottenga, JJ Pol, HEH Hwang, KS Jack, CR Jenkinson, M Johnston, C Jonsson, E Kahn, R Kasperaviciute, D Kelly, S Kim, S Kochunov, P Koenders, L Kramer, B Kwok, JBJ Lagopoulos, J Laje, G Landen, M Landman, BA Lauriello, J Lawrie, SM Lee, PH Le Hellard, S Lemaitre, H Leonardo, CD Li, CS Liberg, B Liewald, DC Liu, XM Lopez, LM Loth, E Lourdusamy, A Luciano, M Macciardi, F Machielsen, MWJ MacQueen, GM Malt, UF Mandl, R Manoach, DS Martinot, JL Matarin, M Mather, KA Mattheisen, M Mattingsdal, M Meyer-Lindenberg, A McDonald, C McIntosh, AM McMahon, FJ McMahon, KL Meisenzahl, E Melle, I Milaneschi, Y Mohnke, S Montgomery, GW Morris, DW Moses, EK Mueller, BA Munoz Maniega, S Muhleisen, T Muller-Myhsok, B Mwangi, B Nauck, M Nho, K Nichols, TE Nilsson, LG Nugent, AC Nyberg, L Olvera, RL Oosterlaan, J Ophoff, RA Pandolfo, M Papalampropoulou-Tsiridou, M Papmeyer, M Paus, T Pausova, Z Pearlson, GD Penninx, BW Peterson, CP Pfennig, A Phillips, M Pike, GB Poline, JB Potkin, SG Putz, B Ramasamy, A Rasmussen, J Rietschel, M Rijpkema, M Risacher, SL Roffman, JL Roiz-Santianez, R Romanczuk-Seiferth, N Rose, EJ Royle, NA Rujescu, D Ryten, M Sachdev, PS Salami, A Satterthwaite, TD Savitz, J Saykin, AJ Scanlon, C Schmaal, L Schnack, HG Schork, AJ Schulz, SC Schur, R Seidman, L Shen, L Shoemaker, JM Simmons, A Sisodiya, SM Smith, C Smoller, JW Soares, JC Sponheim, SR Sprooten, E Starr, JM Steen, VM Strakowski, S Strike, L Sussmann, J Samann, PG Teumer, A Toga, AW Tordesillas-Gutierrez, D Trabzuni, D Trost, S Turner, J Van den Heuvel, M Van der Wee, NJ van Eijk, K van Erp, TGM van Haren, NEM Van 't Ent, D van Tol, MJ Hernandez, MCV Veltman, DJ Versace, A Volzke, H Walker, R Walter, H Wang, L Wardlaw, JM Weale, ME Weiner, MW Wen, W Westlye, LT Whalley, HC Whelan, CD White, T Winkler, AM Wittfeld, K Woldehawariat, G Wolf, C Zilles, D Zwiers, MP Thalamuthu, A Schofield, PR Freimer, NB Lawrence, NS Drevets, W AF Thompson, Paul M. Stein, Jason L. Medland, Sarah E. Hibar, Derrek P. Vasquez, Alejandro Arias Renteria, Miguel E. Toro, Roberto Jahanshad, Neda Schumann, Gunter Franke, Barbara Wright, Margaret J. Martin, Nicholas G. Agartz, Ingrid Alda, Martin Alhusaini, Saud Almasy, Laura Almeida, Jorge Alpert, Kathryn Andreasen, Nancy C. Andreassen, Ole A. Apostolova, Liana G. Appel, Katja Armstrong, Nicola J. Aribisala, Benjamin Bastin, Mark E. Bauer, Michael Bearden, Carrie E. Bergmann, Orjan Binder, Elisabeth B. Blangero, John Bockholt, Henry J. Boen, Erlend Bois, Catherine Boomsma, Dorret I. Booth, Tom Bowman, Ian J. Bralten, Janita Brouwer, Rachel M. Brunner, Han G. Brohawn, David G. Buckner, Randy L. Buitelaar, Jan Bulayeva, Kazima Bustillo, Juan R. Calhoun, Vince D. Cannon, Dara M. Cantor, Rita M. Carless, Melanie A. Caseras, Xavier Cavalleri, Gianpiero L. Chakravarty, M. Mallar Chang, Kiki D. Ching, Christopher R. K. Christoforou, Andrea Cichon, Sven Clark, Vincent P. Conrod, Patricia Coppola, Giovanni Crespo-Facorro, Benedicto Curran, Joanne E. Czisch, Michael Deary, Ian J. de Geus, Eco J. C. den Braber, Anouk Delvecchio, Giuseppe Depondt, Chantal de Haan, Lieuwe de Zubicaray, Greig I. Dima, Danai Dimitrova, Rali Djurovic, Srdjan Dong, Hongwei Donohoe, Gary Duggirala, Ravindranath Dyer, Thomas D. Ehrlich, Stefan Ekman, Carl Johan Elvsashagen, Torbjorn Emsell, Louise Erk, Susanne Espeseth, Thomas Fagerness, Jesen Fears, Scott Fedko, Iryna Fernandez, Guillen Fisher, Simon E. Foroud, Tatiana Fox, Peter T. Francks, Clyde Frangou, Sophia Frey, Eva Maria Frodl, Thomas Frouin, Vincent Garavan, Hugh Giddaluru, Sudheer Glahn, David C. Godlewska, Beata Goldstein, Rita Z. Gollub, Randy L. Grabe, Hans J. Grimm, Oliver Gruber, Oliver Guadalupe, Tulio Gur, Raquel E. Gur, Ruben C. Goering, Harald H. H. Hagenaars, Saskia Hajek, Tomas Hall, Geoffrey B. Hall, Jeremy Hardy, John Hartman, Catharina A. Hass, Johanna Hatton, Sean N. Haukvik, Unn K. Hegenscheid, Katrin Heinz, Andreas Hickie, Ian B. Ho, Beng-Choon Hoehn, David Hoekstra, Pieter J. Hollinshead, Marisa Holmes, Avram J. Homuth, Georg Hoogman, Martine Hong, L. Elliot Hosten, Norbert Hottenga, Jouke-Jan Pol, Hilleke E. Hulshoff Hwang, Kristy S. Jack, Clifford R., Jr. Jenkinson, Mark Johnston, Caroline Joensson, Erik G. Kahn, Rene S. Kasperaviciute, Dalia Kelly, Sinead Kim, Sungeun Kochunov, Peter Koenders, Laura Kraemer, Bernd Kwok, John B. J. Lagopoulos, Jim Laje, Gonzalo Landen, Mikael Landman, Bennett A. Lauriello, John Lawrie, Stephen M. Lee, Phil H. Le Hellard, Stephanie Lemaitre, Herve Leonardo, Cassandra D. Li, Chiang-shan Liberg, Benny Liewald, David C. Liu, Xinmin Lopez, Lorna M. Loth, Eva Lourdusamy, Anbarasu Luciano, Michelle Macciardi, Fabio Machielsen, Marise W. J. MacQueen, Glenda M. Malt, Ulrik F. Mandl, Rene Manoach, Dara S. Martinot, Jean-Luc Matarin, Mar Mather, Karen A. Mattheisen, Manuel Mattingsdal, Morten Meyer-Lindenberg, Andreas McDonald, Colm McIntosh, Andrew M. McMahon, Francis J. McMahon, Katie L. Meisenzahl, Eva Melle, Ingrid Milaneschi, Yuri Mohnke, Sebastian Montgomery, Grant W. Morris, Derek W. Moses, Eric K. Mueller, Bryon A. Munoz Maniega, Susana Muehleisen, Thomas W. Mueller-Myhsok, Bertram Mwangi, Benson Nauck, Matthias Nho, Kwangsik Nichols, Thomas E. Nilsson, Lars-Goeran Nugent, Allison C. Nyberg, Lars Olvera, Rene L. Oosterlaan, Jaap Ophoff, Roel A. Pandolfo, Massimo Papalampropoulou-Tsiridou, Melina Papmeyer, Martina Paus, Tomas Pausova, Zdenka Pearlson, Godfrey D. Penninx, Brenda W. Peterson, Charles P. Pfennig, Andrea Phillips, Mary Pike, G. Bruce Poline, Jean-Baptiste Potkin, Steven G. Puetz, Benno Ramasamy, Adaikalavan Rasmussen, Jerod Rietschel, Marcella Rijpkema, Mark Risacher, Shannon L. Roffman, Joshua L. Roiz-Santianez, Roberto Romanczuk-Seiferth, Nina Rose, Emma J. Royle, Natalie A. Rujescu, Dan Ryten, Mina Sachdev, Perminder S. Salami, Alireza Satterthwaite, Theodore D. Savitz, Jonathan Saykin, Andrew J. Scanlon, Cathy Schmaal, Lianne Schnack, Hugo G. Schork, Andrew J. Schulz, S. Charles Schuer, Remmelt Seidman, Larry Shen, Li Shoemaker, Jody M. Simmons, Andrew Sisodiya, Sanjay M. Smith, Colin Smoller, Jordan W. Soares, Jair C. Sponheim, Scott R. Sprooten, Emma Starr, John M. Steen, Vidar M. Strakowski, Stephen Strike, Lachlan Sussmann, Jessika Saemann, Philipp G. Teumer, Alexander Toga, Arthur W. Tordesillas-Gutierrez, Diana Trabzuni, Daniah Trost, Sarah Turner, Jessica Van den Heuvel, Martijn van der Wee, Nic J. van Eijk, Kristel van Erp, Theo G. M. van Haren, Neeltje E. M. van 't Ent, Dennis van Tol, Marie-Jose Hernandez, Maria C. Valdes Veltman, Dick J. Versace, Amelia Voelzke, Henry Walker, Robert Walter, Henrik Wang, Lei Wardlaw, Joanna M. Weale, Michael E. Weiner, Michael W. Wen, Wei Westlye, Lars T. Whalley, Heather C. Whelan, Christopher D. White, Tonya Winkler, Anderson M. Wittfeld, Katharina Woldehawariat, Girma Wolf, Christiane Zilles, David Zwiers, Marcel P. Thalamuthu, Anbupalam Schofield, Peter R. Freimer, Nelson B. Lawrence, Natalia S. Drevets, Wayne CA Alzheimer's Dis Neuroimaging EPIGEN Consortium IMAGEN Consortium Saguenay Youth Study SYS Grp TI The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Genetics; MRI; GWAS; Consortium; Meta-analysis; Multi-site ID GENOME-WIDE ASSOCIATION; CORTICAL SURFACE-AREA; WHITE-MATTER MICROSTRUCTURE; MULTIVARIATE PARALLEL ICA; TENSOR-BASED MORPHOMETRY; QUANTITATIVE TRAIT LOCI; VOXEL-BASED MORPHOMETRY; HUMAN BRAIN STRUCTURE; DISEASE RISK VARIANT; BODY-MASS INDEX AB The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. C1 [Thompson, Paul M.; Hibar, Derrek P.; Jahanshad, Neda; Bowman, Ian J.; Ching, Christopher R. K.; Dong, Hongwei; Leonardo, Cassandra D.; Toga, Arthur W.] Univ So Calif, Imaging Genet Ctr, Inst Neuroimaging & Informat, Keck Sch Med, Los Angeles, CA 90033 USA. [Montgomery, Grant W.; Strike, Lachlan] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia. [Lee, Phil H.; Smoller, Jordan W.] Broad Inst Harvard & MIT, Boston, MA USA. [Vasquez, Alejandro Arias; Franke, Barbara; Bralten, Janita; Brunner, Han G.; Hoogman, Martine] Radboud Univ Nijmegen Med Ctr, Dept Human Genet, Nijmegen, Netherlands. [Vasquez, Alejandro Arias; Franke, Barbara; Bralten, Janita; Buitelaar, Jan; Fisher, Simon E.; Francks, Clyde; Rijpkema, Mark; Zwiers, Marcel P.] Radboud Univ Nijmegen Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands. [Toro, Roberto] Inst Pasteur, Human Genet & Cognit Funct, Paris, France. [Toro, Roberto] Inst Pasteur, CNRS URA Genes Synapses & Cognit 2182, Paris, France. [Toro, Roberto] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Glahn, David C.] Hartford Hosp, Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT 06115 USA. [Glahn, David C.; Li, Chiang-shan; Pearlson, Godfrey D.; Winkler, Anderson M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Appel, Katja; Grabe, Hans J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany. [Andreassen, Ole A.; Christoforou, Andrea; Djurovic, Srdjan; Espeseth, Thomas; Giddaluru, Sudheer; Haukvik, Unn K.; Le Hellard, Stephanie; Mattingsdal, Morten; Melle, Ingrid; Steen, Vidar M.; Westlye, Lars T.] Univ Oslo, NORMENT, KG Jebsen Ctr Psychosis Res, Oslo Univ Hosp, Oslo, Norway. [Andreassen, Ole A.; Christoforou, Andrea; Djurovic, Srdjan; Espeseth, Thomas; Giddaluru, Sudheer; Haukvik, Unn K.; Le Hellard, Stephanie; Mattingsdal, Morten; Melle, Ingrid; Steen, Vidar M.; Westlye, Lars T.] Univ Oslo, Inst Clin Med, Oslo, Norway. [Alhusaini, Saud; Cavalleri, Gianpiero L.; Whelan, Christopher D.] Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin 2, Ireland. [Almasy, Laura; Blangero, John; Carless, Melanie A.; Curran, Joanne E.; Duggirala, Ravindranath; Dyer, Thomas D.; Goering, Harald H. H.; Moses, Eric K.; Peterson, Charles P.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Andreasen, Nancy C.; Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Apostolova, Liana G.; Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Aribisala, Benjamin; Bastin, Mark E.; Booth, Tom; Deary, Ian J.; Liewald, David C.; Lopez, Lorna M.; Luciano, Michelle; Munoz Maniega, Susana; Royle, Natalie A.; Starr, John M.; Hernandez, Maria C. Valdes; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Aribisala, Benjamin; Munoz Maniega, Susana; Wardlaw, Joanna M.] Scottish Imaging Network, St Andrews, Fife, Scotland. [Aribisala, Benjamin; Bastin, Mark E.; Munoz Maniega, Susana; Royle, Natalie A.; Hernandez, Maria C. Valdes; Wardlaw, Joanna M.] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland. [Binder, Elisabeth B.; Czisch, Michael; Hoehn, David; Mueller-Myhsok, Bertram; Puetz, Benno; Saemann, Philipp G.; Wolf, Christiane] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Calhoun, Vince D.; Shoemaker, Jody M.; Turner, Jessica] Mind Res Network, Albuquerque, NM USA. [Boomsma, Dorret I.; de Geus, Eco J. C.; den Braber, Anouk; Fedko, Iryna; Hottenga, Jouke-Jan; van 't Ent, Dennis] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Bralten, Janita; Fernandez, Guillen] Radboud Univ Nijmegen Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands. [Brouwer, Rachel M.; Pol, Hilleke E. Hulshoff; Kahn, Rene S.; Mandl, Rene; Ophoff, Roel A.; Schnack, Hugo G.; Schuer, Remmelt; Van den Heuvel, Martijn; van Haren, Neeltje E. M.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [Buckner, Randy L.; Fagerness, Jesen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Buitelaar, Jan] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. [Bulayeva, Kazima] Russian Acad Sci, NI Vavilov Inst Gen Genet, Moscow 119991, Russia. [Bustillo, Juan R.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Cannon, Dara M.; Donohoe, Gary; Emsell, Louise; McDonald, Colm; Scanlon, Cathy] Natl Univ Ireland Galway, Clin Neuroimaging Lab, Galway, Ireland. [Cantor, Rita M.; Fears, Scott; Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. [Chakravarty, M. Mallar] Ctr Addict & Mental Hlth, Kimel Family Translat Imaging Genet Lab, Toronto, ON, Canada. [Christoforou, Andrea; Le Hellard, Stephanie; Steen, Vidar M.] Univ Bergen, Dept Clin Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway. [Giddaluru, Sudheer] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, N-5021 Bergen, Norway. [Muehleisen, Thomas W.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany. [Cichon, Sven; Muehleisen, Thomas W.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Cichon, Sven; Muehleisen, Thomas W.] Forschungszentrum Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany. [Cichon, Sven] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland. [Crespo-Facorro, Benedicto; Roiz-Santianez, Roberto; Tordesillas-Gutierrez, Diana] Univ Cantabria, Sch Med, Dept Psychiat, Marques de Valdecilla Univ Hosp,IFIMAV, E-39005 Santander, Spain. [Crespo-Facorro, Benedicto; Roiz-Santianez, Roberto; Tordesillas-Gutierrez, Diana] Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain. [Lopez, Lorna M.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Depondt, Chantal; Pandolfo, Massimo] Univ Libre Bruxelles, Dept Neurol, Hop Erasme, B-1070 Brussels, Belgium. [de Zubicaray, Greig I.] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. [Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway. [Donohoe, Gary; Kelly, Sinead; Morris, Derek W.] Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dept Psychiat, Inst Mol Med, Dublin 2, Ireland. [Donohoe, Gary; Kelly, Sinead; Morris, Derek W.] Univ Dublin Trinity Coll, Inst Neurosci, Dublin 2, Ireland. [Ehrlich, Stefan; Gollub, Randy L.; Hollinshead, Marisa; Holmes, Avram J.; Manoach, Dara S.] Massachusetts Gen Hosp, MGH HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ehrlich, Stefan; Hass, Johanna] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Univ Hosp CG Carus, Dresden, Germany. [Erk, Susanne; Heinz, Andreas; Mohnke, Sebastian; Romanczuk-Seiferth, Nina; Walter, Henrik] Charite, Dept Psychiat & Psychotherapy, Charite Campus Mitte, D-13353 Berlin, Germany. [Espeseth, Thomas; Westlye, Lars T.] Univ Oslo, Dept Psychol, Oslo, Norway. [Fisher, Simon E.; Francks, Clyde; Guadalupe, Tulio] Max Planck Inst Psycholinguist, NL-6500 AH Nijmegen, Netherlands. [Fox, Peter T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Ctr, San Antonio, TX USA. [Frouin, Vincent] CEA, Neurospin, Paris, France. [Gollub, Randy L.; Holmes, Avram J.; Lee, Phil H.; Manoach, Dara S.; Roffman, Joshua L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Grabe, Hans J.; Wittfeld, Katharina] Ernst Moritz Arndt Univ Greifswald, German Ctr Neurodegenerat Dis DZNE, Greifswald, Germany. [Grimm, Oliver; Meyer-Lindenberg, Andreas; Rietschel, Marcella] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany. [Gruber, Oliver; Kraemer, Bernd; Trost, Sarah; Zilles, David] Univ Gottingen, Ctr Translat Res Syst Neurosci & Psychiat, Dept Psychiat, Gottingen, Germany. [Bois, Catherine; Dimitrova, Rali; Hagenaars, Saskia; Hall, Geoffrey B.; Lawrie, Stephen M.; McIntosh, Andrew M.; Papalampropoulou-Tsiridou, Melina; Papmeyer, Martina; Sussmann, Jessika; Whalley, Heather C.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland. [Hardy, John; Ryten, Mina; Trabzuni, Daniah] UCL Inst, Dept Mol Neurosci, London, England. [Hegenscheid, Katrin; Hosten, Norbert] Ernst Moritz Arndt Univ Greifswald, Dept Diagnost Radiol & Neuroradiol, Greifswald, Germany. [Hartman, Catharina A.; Hoekstra, Pieter J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Homuth, Georg; Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Johnston, Caroline] South London & Maudsley Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res Biomed Res, Ctr Mental Hlth, London, England. [Johnston, Caroline] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Agartz, Ingrid; Ekman, Carl Johan; Joensson, Erik G.; Liberg, Benny] Karolinska Hosp & Inst, Dept Clin Neurosci, Stockholm, Sweden. [Kasperaviciute, Dalia; Matarin, Mar; Sisodiya, Sanjay M.] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London, England. [Shen, Li] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Saykin, Andrew J.; Shen, Li] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Neuroimaging, Indianapolis, IN 46202 USA. [Hong, L. Elliot; Kochunov, Peter] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Brohawn, David G.; Fagerness, Jesen; Lee, Phil H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Liu, Xinmin; McMahon, Francis J.; Woldehawariat, Girma] NIMH, Mood & Anxiety Disorders Sect, Human Genet Branch, Intramural Res Program,NIH,US Dept HHS, Bethesda, MD 20892 USA. [Liu, Xinmin] Columbia Univ Med Ctr, Taub Inst Res Alzheimer Dis & Aging Brain, New York, NY USA. [Schumann, Gunter; Delvecchio, Giuseppe; Dima, Danai; Loth, Eva] Kings Coll London, Inst Psychiat, MRC SGDP Ctr, London WC2R 2LS, England. [Macciardi, Fabio; Potkin, Steven G.; Rasmussen, Jerod; van Erp, Theo G. M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Mather, Karen A.; Sachdev, Perminder S.; Wen, Wei] Univ New South Wales Med, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Mattheisen, Manuel] Aarhus Univ, Dept Biomed, Aarhus, Denmark. [Mattheisen, Manuel] Univ Bonn, Dept Genom Math, Bonn, Germany. [Mattingsdal, Morten] Sorlandet Hosp HF, Res Unit, Kristiansand, Norway. [McMahon, Katie L.] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia. [Meisenzahl, Eva] Univ Munich, Munich, Germany. [Penninx, Brenda W.; Schmaal, Lianne; Veltman, Dick J.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat & Neurosci, Amsterdam, Netherlands. [Moses, Eric K.] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia. [Mueller, Bryon A.; Schulz, S. Charles; Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Med Ctr, Minneapolis, MN 55455 USA. [Nilsson, Lars-Goeran] Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden. [Nyberg, Lars; Salami, Alireza] Umea Univ, Umea Ctr Funct Brain Imaging UFBI, Umea, Sweden. [Olvera, Rene L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Paus, Tomas] Univ Toronto, Rotman Res Inst, Toronto, ON, Canada. [Pausova, Zdenka] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [van der Wee, Nic J.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [van der Wee, Nic J.] Leiden Univ, Med Ctr, Leiden Inst Brain & Cognit, Leiden, Netherlands. [Ramasamy, Adaikalavan; Ryten, Mina; Weale, Michael E.] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England. [Sachdev, Perminder S.] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia. [Savitz, Jonathan] Laureate Inst Brain Res, Tulsa, OK USA. [Foroud, Tatiana; Saykin, Andrew J.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Seidman, Larry] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Simmons, Andrew] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London WC2R 2LS, England. [Simmons, Andrew] Kings Coll London, NIHR Biomed Res Ctr Mental Hlth, South London & Maudsley NHS Trust, London WC2R 2LS, England. [Simmons, Andrew] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Sponheim, Scott R.] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [van Tol, Marie-Jose] Univ Groningen, Univ Med Ctr Groningen, Behav & Cognit Neurosci Neuroimaging Ctr, NL-9713 AV Groningen, Netherlands. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [White, Tonya] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Rijpkema, Mark; Zwiers, Marcel P.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands. [Jenkinson, Mark; Winkler, Anderson M.] Univ Oxford, Oxford Ctr Funct MRI Brain FMRIB, Oxford, England. [Kwok, John B. J.; Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW, Australia. [Kwok, John B. J.; Schofield, Peter R.] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia. [Buckner, Randy L.; Hollinshead, Marisa; Holmes, Avram J.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Hatton, Sean N.; Hickie, Ian B.; Lagopoulos, Jim] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Walker, Robert] Univ Edinburgh, Ctr Regenerat Med, Edinburgh, Midlothian, Scotland. [Bastin, Mark E.; Smith, Colin] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland. [de Haan, Lieuwe; Koenders, Laura; Machielsen, Marise W. J.] UvA, Acad Psychiat Ctr, AMC, Dept Early Psychosis, Amsterdam, Netherlands. [Boomsma, Dorret I.; de Geus, Eco J. C.; Milaneschi, Yuri; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands. [Schork, Andrew J.] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA USA. [Haukvik, Unn K.] Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway. [Oosterlaan, Jaap] Vrije Univ Amsterdam, Dept Clin Neuropsychol, Amsterdam, Netherlands. [Ramasamy, Adaikalavan] UCL Inst Neurol, Reta Lila Weston Inst, London, England. [Ramasamy, Adaikalavan] UCL Inst Neurol, Dept Mol Neurosci, London, England. [Alhusaini, Saud] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. [Almeida, Jorge; Phillips, Mary; Versace, Amelia] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Alda, Martin; Hajek, Tomas] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. [Godlewska, Beata] Univ Oxford, Dept Psychiat, Oxford, England. [Mwangi, Benson; Soares, Jair C.] Univ Texas Med Sch, Dept Psychiat & Behav Sci, Houston, TX USA. [Mwangi, Benson] UT Med Sch, Dept Psychiat, Univ Texas Ctr Excellence Mood Disorders, Houston, TX USA. [Bearden, Carrie E.; Coppola, Giovanni; Fears, Scott] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Bearden, Carrie E.; Coppola, Giovanni; Fears, Scott] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA. [Milaneschi, Yuri] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Walter, Henrik] Humboldt Univ, Berlin Sch Mind & Brain, D-10099 Berlin, Germany. [Bauer, Michael; Pfennig, Andrea] Carl Gustav Carus Univ Hosp, Dept Psychiat & Psychotherapy, Dresden, Germany. [Grabe, Hans J.] Helios Hosp Stralsund, Dept Psychiat & Psychotherapy, Stralsund, Germany. [Seidman, Larry] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Almeida, Jorge] Brown Univ, Dept Psychiat, Providence, RI 02912 USA. [Frangou, Sophia] Mt Sinai Sch Med, Psychosis Res Unit, New York, NY USA. [Strakowski, Stephen] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [Gur, Raquel E.; Gur, Ruben C.; Satterthwaite, Theodore D.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Gur, Ruben C.] Philadelphia Vet Adm Med Ctr, Philadelphia, PA USA. [Frey, Eva Maria; Frodl, Thomas] Univ Regensburg, Dept Psychiat & Psychotherapy, D-93053 Regensburg, Germany. [Frodl, Thomas] Univ Dublin, Trinity Coll, Dept Psychiat & Psychotherapy, Dublin, Germany. [Nilsson, Lars-Goeran] Univ Dublin, Trinity Coll, Dept Psychiat & Psychotherapy, Dublin, Germany. [Turner, Jessica] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Turner, Jessica] Georgia State Univ, Neurosci Inst, Atlanta, GA 30303 USA. [Hall, Geoffrey B.] McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON, Canada. [Clark, Vincent P.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Boen, Erlend; Elvsashagen, Torbjorn; Malt, Ulrik F.] Oslo Univ Hosp, Dept Psychosomat Med, Oslo, Norway. [Agartz, Ingrid; Bergmann, Orjan; Boen, Erlend; Elvsashagen, Torbjorn; Malt, Ulrik F.] Univ Oslo, Inst Clin Med, Oslo, Norway. [Risacher, Shannon L.] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. [Pike, G. Bruce] Univ Calgary, Dept Radiol, Calgary, AB, Canada. [Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England. [Nichols, Thomas E.] Univ Warwick, Warwick Mfg Grp, Coventry CV4 7AL, W Midlands, England. [Alpert, Kathryn; Wang, Lei] Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Alpert, Kathryn; Wang, Lei] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [Landman, Bennett A.] Vanderbilt Univ, Nashville, TN 37235 USA. [Nugent, Allison C.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Landen, Mikael] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Landen, Mikael] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Chakravarty, M. Mallar] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON, Canada. [Savitz, Jonathan] Univ Tulsa, Fac Community Med, Tulsa, OK 74104 USA. [Laje, Gonzalo] Maryland Inst Neurosci & Dev MIND, Chevy Chase, MD USA. [MacQueen, Glenda M.] Univ Calgary, Hotchkiss Brain Inst, Mathison Ctr Mental Hlth Res & Educ, Calgary, AB, Canada. [Mueller-Myhsok, Bertram] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Caseras, Xavier] Cardiff Univ, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. [Hall, Jeremy] Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF10 3AX, S Glam, Wales. [Kwok, John B. J.] Univ New S Wales, Sch Med Sci, Kensington, NSW 2033, Australia. [Hwang, Kristy S.] Oakland Univ, William Beaumont Sch Med, Rochester, MI 48063 USA. [Conrod, Patricia] CHU St Justine Univ Hosp Res Ctr, Montreal, PQ, Canada. [Conrod, Patricia] Kings Coll London, Kings Hlth Partners, Addict Dept, London WC2R 2LS, England. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Lemaitre, Herve; Martinot, Jean-Luc] Paris Descartes Univ, Univ Paris 11, INSERM, CEA,Fac Med,Res Unit 1000,SHFJ Orsay,Maison de So, Paris, France. [Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [van Eijk, Kristel] Univ Med Ctr Utrecht, Rudolf Magnus Inst, Dept Psychiat, Utrecht, Netherlands. [Armstrong, Nicola J.] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia. [Lourdusamy, Anbarasu] Univ Nottingham, Sch Med, Nottingham, England. [Chang, Kiki D.] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. [Salami, Alireza] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden. [Salami, Alireza] Stockholm Univ, S-10691 Stockholm, Sweden. [Poline, Jean-Baptiste] Univ Calif Berkeley, Brain Imaging Ctr, Hellen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Lauriello, John] Univ Missouri, Dept Psychiat, Columbia, MO 65201 USA. [Pearlson, Godfrey D.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Pearlson, Godfrey D.] Yale Univ, Dept Neurobiol, Sch Med, New Haven, CT USA. [Jack, Clifford R., Jr.] Mayo Clin, Rochester, MN USA. [Rose, Emma J.] RTI Int, Transdisciplinary & Translat Prevent Program, Baltimore, MD USA. [Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY USA. [Rujescu, Dan] Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany. [Bockholt, Henry J.] Adv Biomed Informat Grp Llc, Iowa City, IA USA. [Stein, Jason L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90095 USA. [Medland, Sarah E.; Renteria, Miguel E.; Wright, Margaret J.; Martin, Nicholas G.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Macciardi, Fabio] Univ Milan, Dept Pharmacol & Biomol Sci, I-20122 Milan, Italy. [Steen, Vidar M.] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr E Martens Res Grp Biol Psychiat, N-5021 Bergen, Norway. [Garavan, Hugh] UHC Univ Vermont, Dept Psychiat, Burlington, VT USA. [Thalamuthu, Anbupalam] UNSW, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Freimer, Nelson B.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA. [Lawrence, Natalia S.] Univ Exeter, Sch Psychol, Exeter, Devon, England. [Drevets, Wayne] Johnson & Johnson Inc, Janssen Res & Dev, Titusville, NJ 08560 USA. RP Thompson, PM (reprint author), Univ So Calif, Imaging Genet Ctr, Inst Neuroimaging & Informat, Keck Sch Med, 2001 N Soto St, Los Angeles, CA 90033 USA. EM pthomp@usc.edu; wdrevets@its.jnj.com RI Winkler, Anderson/P-7773-2016; Luciano, Michelle/F-7277-2010; Meyer-Lindenberg, Andreas/H-1076-2011; Clark, Vincent/B-3343-2010; Almeida, Jorge/O-5185-2014; Montgomery, Grant/B-7148-2008; Mattheisen, Manuel/B-4949-2012; Wright, Margaret/A-4560-2016; Arias Vasquez, Alejandro/E-4762-2012; McMahon, Katie/C-6440-2009; Macciardi, Fabio/N-3768-2014; Frodl, Thomas/D-8118-2012; Li, Chiang-Shan/J-2813-2016; Matarin, Mar/F-1771-2016; Melle, Ingrid /B-4858-2011; Karen, Mather/O-9795-2016; Putz, Benno/P-2630-2016; Nyberg, Lars/C-2514-2009; Weale, Michael/F-2587-2010; de Zubicaray, Greig/B-1763-2008; Walter, Henrik/O-2612-2013; Bralten, Janita/D-4647-2011; Hoogman, Martine/G-8958-2015; Roiz-Santianez, Roberto/H-6462-2015; Tordesillas-Gutierrez, Diana/H-6893-2015; Turner, Jessica/H-7282-2015; Rijpkema, Mark/D-1974-2010; Zwiers, Marcel/D-2968-2009; Alda, Martin/F-5812-2010; Cavalleri, Gianpiero/A-6632-2010; Rose, Emma/A-9960-2010; Brunner, Han/C-9928-2013; Hoekstra, Pieter/O-4396-2014; Savitz, Jonathan/C-3088-2009; Fox, Peter/B-4725-2010; Fisher, Simon/E-9130-2012; Ho, Beng-Choon/D-6959-2011; Lourdusamy, Anbarasu/P-6606-2014; Franke, Barbara/D-4836-2009; Ramasamy, Adaikalavan/G-2632-2010; Medland, Sarah/C-7630-2013; Jack, Clifford/F-2508-2010; Laje, Gonzalo/L-2654-2014; Hardy, John/C-2451-2009; McDonald, Colm/C-1430-2009; Dima, Danai/H-4342-2014; Hulshoff Pol, Hilleke/B-4795-2014; Munoz Maniega, Susana/I-8730-2014; Fernandez, Guillen/B-3771-2009; Simmons, Andrew/B-8848-2008; Pike, Bruce/K-5562-2014; Binder, Elisabeth/K-8905-2014; Delvecchio, Giuseppe/J-7721-2016; Trabzuni, Daniah/C-4034-2012; OI Winkler, Anderson/0000-0002-4169-9781; Luciano, Michelle/0000-0003-0935-7682; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Clark, Vincent/0000-0002-9151-2102; Almeida, Jorge/0000-0002-1213-1986; Bulayeva, Kazima/0000-0003-4830-5383; Lemaitre, Herve/0000-0002-5952-076X; Toro, Roberto/0000-0002-6671-858X; van den Heuvel, Martijn/0000-0003-1570-1195; Romanczuk-Seiferth, Nina/0000-0002-6931-269X; Whelan, Christopher/0000-0003-0308-5583; Montgomery, Grant/0000-0002-4140-8139; Mattheisen, Manuel/0000-0002-8442-493X; Wright, Margaret/0000-0001-7133-4970; Arias Vasquez, Alejandro/0000-0002-4786-0169; McMahon, Katie/0000-0002-6357-615X; Macciardi, Fabio/0000-0003-0537-4266; Li, Chiang-Shan/0000-0002-9393-1212; Matarin, Mar/0000-0002-4717-5735; Melle, Ingrid /0000-0002-9783-548X; Karen, Mather/0000-0003-4143-8941; Putz, Benno/0000-0002-2208-209X; Nyberg, Lars/0000-0002-3367-1746; Weale, Michael/0000-0003-4593-1186; de Zubicaray, Greig/0000-0003-4506-0579; Hoogman, Martine/0000-0002-1261-7628; Roiz-Santianez, Roberto/0000-0002-5176-2983; Tordesillas-Gutierrez, Diana/0000-0003-1458-3932; Turner, Jessica/0000-0003-0076-8434; Rijpkema, Mark/0000-0002-8495-4703; Zwiers, Marcel/0000-0001-5483-2935; Alda, Martin/0000-0001-9544-3944; Rose, Emma/0000-0001-5365-4794; Savitz, Jonathan/0000-0001-8143-182X; Fox, Peter/0000-0002-0465-2028; Fisher, Simon/0000-0002-3132-1996; Ho, Beng-Choon/0000-0003-3976-1555; Franke, Barbara/0000-0003-4375-6572; Ramasamy, Adaikalavan/0000-0002-7598-2892; Medland, Sarah/0000-0003-1382-380X; Jack, Clifford/0000-0001-7916-622X; Laje, Gonzalo/0000-0003-2763-3329; Dima, Danai/0000-0002-2598-0952; Hulshoff Pol, Hilleke/0000-0002-2038-5281; Munoz Maniega, Susana/0000-0001-5185-6384; Fernandez, Guillen/0000-0002-5522-0604; Simmons, Andrew/0000-0003-2306-5811; Pike, Bruce/0000-0001-8924-683X; Delvecchio, Giuseppe/0000-0003-4750-1980; Jenkinson, Mark/0000-0001-6043-0166; Gollub, Randy L./0000-0002-9434-4044; McMahon, Francis/0000-0002-9469-305X; Cannon, Dara/0000-0001-7378-3411; Agartz, Ingrid/0000-0002-9839-5391; Kwok, John/0000-0001-9574-6195; Lourdusamy, Anbarasu/0000-0002-1978-6301; Morris, Derek/0000-0002-3413-570X; Andreassen, Ole A./0000-0002-4461-3568; Martin, Nicholas/0000-0003-4069-8020; McIntosh, Andrew/0000-0002-0198-4588; Cavalleri, Gianpiero/0000-0002-9802-0506; Nugent, Allison/0000-0003-2569-2480; Lawrence, Natalia/0000-0003-1969-6637; Donohoe, Gary/0000-0003-3037-7426; Sachdev, Perminder/0000-0002-9595-3220; Mwangi, Benson/0000-0002-1717-4395; Shen, Li/0000-0002-5443-0503; Schur, Remmelt/0000-0002-2840-2592; Hatton, Sean/0000-0002-9149-8726; Westlye, Lars T./0000-0001-8644-956X; de Geus, Eco/0000-0001-6022-2666; Emsell, Louise/0000-0003-0011-4158; Potkin, Steven/0000-0003-1028-1013; Trabzuni, Daniah/0000-0003-4826-9570; Stein, Jason/0000-0003-4829-0513; Frodl, Thomas/0000-0002-8113-6959; Caseras, Xavier/0000-0002-8490-6891; Jonsson, Erik/0000-0001-8368-6332 FU Biotechnology and Biological Sciences Research Council [BB/F019394/1]; Medical Research Council [G0600429, G0700704, G0701120, G0802462, G0901254, G1001245, MR/J006742/1, MR/K01417X/1, MR/K026992/1, MR/L010305/1, MR/L016400/1]; NCATS NIH HHS [UL1 TR001108]; NIA NIH HHS [P50 AG005134, P30 AG010133, R01 AG019771, R01 AG040770, U01 AG024904, U19 AG010483, U24 AG021886]; NIBIB NIH HHS [P41 EB015922, R01 EB005846, R01 EB015611, U54 EB020403]; NIMH NIH HHS [K01 MH099232, K99 MH101367]; NLM NIH HHS [K99 LM011384, R00 LM011384, R01 LM011360]; Parkinson's UK [G-0907]; Wellcome Trust [100309, 104036] NR 195 TC 84 Z9 85 U1 10 U2 83 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2014 VL 8 IS 2 SI SI BP 153 EP 182 DI 10.1007/s11682-013-9269-5 PG 30 WC Neuroimaging SC Neurosciences & Neurology GA AG9UP UT WOS:000335765700003 PM 24399358 ER PT J AU Kutsenko, A de Gonzalez, AB Curtis, RE Rajaraman, P AF Kutsenko, Alina de Gonzalez, Amy Berrington Curtis, Rochelle E. Rajaraman, Preetha TI Risk of second benign brain tumors among cancer survivors in the surveillance, epidemiology, and end results program SO CANCER CAUSES & CONTROL LA English DT Article DE Meningioma; Radiotherapy; SEER; Brain neoplasm; Second primary neoplasm ID CENTRAL-NERVOUS-SYSTEM; ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; CHILDHOOD-CANCER; MALIGNANT NEOPLASMS; GENETIC-STRUCTURE; UNITED-STATES; FOLLOW-UP; MENINGIOMA; ASSOCIATION AB To assess risk of developing a second benign brain tumor in a nationwide population of cancer survivors. We evaluated the risk of developing second benign brain tumors among 2,038,074 1-year minimum cancer survivors compared to expected risk in the general population between 1973 and 2007 in nine population-based cancer registries in the NCI's surveillance, epidemiology, and end results program. Excess risk was estimated using standardized incidence ratios (SIRs) for all second benign brain tumors and specifically for second meningiomas and acoustic neuromas diagnosed during 2004-2008. 1,025 patients were diagnosed with a second primary benign brain tumor, of which second meningiomas composed the majority (n = 745). Statistically significant increases in risk of developing a second meningioma compared to the general population were observed following first cancers of the brain [SIR = 19.82; 95 % confidence interval (CI) 13.88-27.44], other central nervous system (CNS) (SIR = 9.54; CI 3.10-22.27), thyroid (SIR = 2.05; CI 1.47-2.79), prostate (SIR = 1.21; CI 1.02-1.43), and acute lymphocytic leukemia (ALL) (SIR = 42.4; CI 23.18-71.13). Statistically significant decreases in risk were observed following first cancers of the uterine corpus (SIR = 0.63; CI 0.42-0.91) and colon (SIR = 0.56; CI 0.37-0.82). Differences in risk between patients initially treated with radiotherapy versus non-irradiated patients were statistically significant for second meningioma after primary cancers of the brain (p (Het) < 0.001) and ALL (p (Het) = 0.02). No statistically significant increased risks were detected for second acoustic neuromas (n = 114) following any first primary tumor. Risk of second benign brain tumors, particularly meningioma, is increased following first primary cancers of the brain/CNS, thyroid, prostate, and ALL. Radiation exposure likely contributes to these excess risks. C1 [Kutsenko, Alina; de Gonzalez, Amy Berrington; Curtis, Rochelle E.; Rajaraman, Preetha] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Kutsenko, A (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,MSC 9778, Bethesda, MD 20892 USA. EM alk2022@med.cornell.edu; berringtona@mail.nih.gov; rcurtis@mail.nih.gov; rajarama@mail.nih.gov NR 36 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2014 VL 25 IS 6 BP 659 EP 668 DI 10.1007/s10552-014-0367-5 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA AH3LA UT WOS:000336023600002 PM 24682745 ER PT J AU Colloca, L Grillon, C AF Colloca, Luana Grillon, Christian TI Understanding Placebo and Nocebo Responses for Pain Management SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Brain Imaging; Cannabinoids; Conditioning; Dopamine; Expectation; Genetics; Interpersonal interactions; Learning; Psychological traits; Opioids; Social observation; Oxytocin ID DISPOSITIONAL OPTIMISM; SOCIAL-BEHAVIOR; OPIOID ACTIVITY; SPINAL-CORD; ANALGESIA; ACTIVATION; MECHANISMS; SYSTEM; EXPECTATION; PERSONALITY AB Placebo analgesia makes individuals experience relief of their pain simply by virtue of the anticipation of a benefit. A reduction of pain can occur also when placebos follow the administration of active and effective painkillers. In fact, studies indicate that placebos mimic the action of active treatments and promote the endogenous release of opioids in both humans and animals. Finally, social support and observational learning also lead to analgesic effects. Thus, different psychological factors and situations induce expectations of analgesia facilitating the activation of the top-down systems for pain control along with the release of endogenous mediators crucially involved in placebo-induced benefits. Recent scientific investigation in the field of brain imaging is opening new avenues to understanding the cognitive mechanisms and neurobiological substrates of expectation-induced pain modulation. Gaining deeper knowledge of top-down mechanisms of pain modulation has enormous implications for personalizing and optimizing pain management. C1 [Colloca, Luana; Grillon, Christian] NIMH, NIH, Bethesda, MD 20892 USA. [Colloca, Luana] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Colloca, L (reprint author), NIH, Ctr Clin, Bldg 10,Room 1C154, Bethesda, MD 20892 USA. EM luana.colloca@nih.gov OI Colloca, Luana/0000-0002-6503-4709 FU NIMH; NCCAM [11-M-0104, NCT:01328561] FX This research was funded by intramural NIMH and NCCAM (11-M-0104; NCT:01328561). The authors thank Catherine M. Bushnell for helpful comments on this article. NR 68 TC 7 Z9 7 U1 2 U2 41 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 EI 1534-3081 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD JUN PY 2014 VL 18 IS 6 AR 419 DI 10.1007/s11916-014-0419-2 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA AG8QF UT WOS:000335682600004 PM 24771206 ER PT J AU Andrulis, M Bauerle, T Goldschmidt, H Delorme, S Landgren, O Schirmacher, P Hillengass, J AF Andrulis, Mindaugas Baeuerle, Tobias Goldschmidt, Hartmut Delorme, Stefan Landgren, Ola Schirmacher, Peter Hillengass, Jens TI Infiltration patterns in monoclonal plasma cell disorders: correlation of magnetic resonance imaging with matched bone marrow histology SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Paraproteinemias; Multiple myeloma; Plasma cells; Magnetic resonance imaging; Bone marrow; Histology ID UNDETERMINED SIGNIFICANCE MGUS; MULTIPLE-MYELOMA; WHOLE-BODY; PROGNOSTIC-SIGNIFICANCE; GAMMOPATHY; MRI; CLASSIFICATION; SURVIVAL; DISEASE; SALMON AB Objectives: To investigate how plasma cell infiltration patterns detected by MRI match the plasma cell distribution in bone marrow biopsy. Methods: We assessed 50 patients with monoclonal plasma cell disorders of all clinical stages. MRI infiltration pattern was compared with matched BM histology from the same anatomic region. Results: MRI revealed a minimal (n = 11, 22%), focal (n = 5,10%), diffuse (n = 14, 28%) and mixed (n= 20,40%) infiltration pattern. Diffuse MRI pattern was predominant in smoldering myeloma patients whereas the MRI patterns with "focal component" (i.e. focal and mixed) were most common in symptomatic myeloma (p < 0.01). In histology an interstitial (n = 13, 26%), nodular (n = 23,46%) and packed marrow (n = 14, 28%) was found respectively. All three histological types of infiltration were observed in patients with diffuse and mixed MRI patterns. Minimal MRI pattern was found in all MGUS patients and was associated with an interstitial BM infiltration. In two patients with minimal MRI pattern an extensive micro-nodular BM infiltration was found in histology. Conclusions: Infiltration patterns in MRI represent different histological growth patterns of plasma cells, but the MRI resolution is not sufficient to visualize micro-nodular aggregates of plasma cells. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Andrulis, Mindaugas; Schirmacher, Peter] Heidelberg Univ, Inst Pathol, D-69120 Heidelberg, Germany. [Baeuerle, Tobias] Univ Hamburg, Dept Diagnost & Intervent Radiol, Hamburg, Germany. [Goldschmidt, Hartmut; Hillengass, Jens] Heidelberg Univ, Dept Hematol & Oncol, D-69120 Heidelberg, Germany. [Delorme, Stefan; Hillengass, Jens] German Canc Res Ctr, Dept Radiol, Heidelberg, Germany. [Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, Bethesda, MD 20892 USA. RP Hillengass, J (reprint author), Heidelberg Univ, Dept Hematol & Oncol, Neuenheimer Feld 410D, D-69120 Heidelberg, Germany. EM jens.hillengass@med.uni-heidelberg.de OI Delorme, Stefan/0000-0002-1000-2582 FU International Myeloma Foundation; German Research Foundation FX This work was supported by grants from the International Myeloma Foundation and from the German Research Foundation: grant for "initiation of bilateral cooperation" and Transregio 79. NR 23 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X EI 1872-7727 J9 EUR J RADIOL JI Eur. J. Radiol. PD JUN PY 2014 VL 83 IS 6 BP 970 EP 974 DI 10.1016/j.ejrad.2014.03.005 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH1UJ UT WOS:000335906400016 PM 24725673 ER PT J AU Wang, LL Cummings, RD Smith, DF Huflejt, M Campbell, CT Gildersleeve, JC Gerlach, JQ Kilcoyne, M Joshi, L Serna, S Reichardt, NC Pera, NP Pieters, RJ Eng, W Mahal, LK AF Wang, Linlin Cummings, Richard D. Smith, David F. Huflejt, Margaret Campbell, Christopher T. Gildersleeve, Jeffrey C. Gerlach, Jared Q. Kilcoyne, Michelle Joshi, Lokesh Serna, Sonia Reichardt, Niels-Christian Pera, Nuria Parera Pieters, Roland J. Eng, William Mahal, Lara K. TI Cross-platform comparison of glycan microarray formats SO GLYCOBIOLOGY LA English DT Article DE comparison; glycan microarray; lectin; presentation ID WHEAT-GERM-AGGLUTININ; CARBOHYDRATE-PROTEIN INTERACTIONS; LECTIN MICROARRAY; BINDING-PROTEINS; CELL-BINDING; ARRAY DATA; SURFACE; RECOGNITION; DENSITY; SPECIFICITIES AB Carbohydrates participate in almost every aspect of biology from protein sorting to modulating cell differentiation and cell-cell interactions. To date, the majority of data gathered on glycan expression has been obtained via analysis with either anti-glycan antibodies or lectins. A detailed understanding of the specificities of these reagents is critical to the analysis of carbohydrates in biological systems. Glycan microarrays are increasingly used to determine the binding specificity of glycan-binding proteins (GBPs). In this study, six different glycan microarray platforms with different modes of glycan presentation were compared using five well-known lectins; concanavalin A, Helix pomatia agglutinin, Maackia amurensis lectin I, Sambucus nigra agglutinin and wheat germ agglutinin. A new method (universal threshold) was developed to facilitate systematic comparisons across distinct array platforms. The strongest binders of each lectin were identified using the universal threshold across all platforms while identification of weaker binders was influenced by platform-specific factors including presentation of determinants, array composition and self-reported thresholding methods. This work compiles a rich dataset for comparative analysis of glycan array platforms and has important implications for the implementation of microarrays in the characterization of GBPs. C1 [Wang, Linlin; Eng, William; Mahal, Lara K.] NYU, Dept Chem, Biomed Chem Inst, New York, NY 10003 USA. [Cummings, Richard D.; Smith, David F.] Emory Univ, Dept Biochem, Glyc Ctr, Sch Med, Atlanta, GA 30322 USA. [Huflejt, Margaret] NYU, Div Thorac Surg & Thorac Oncol, Dept Cardiothorac Surg, Sch Med, New York, NY 10016 USA. [Campbell, Christopher T.; Gildersleeve, Jeffrey C.] NCI, Chem Biol Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Gerlach, Jared Q.; Kilcoyne, Michelle; Joshi, Lokesh] Natl Univ Ireland Galway, Glycosci Grp, Natl Ctr Biomed Engn Sci, Galway, Ireland. [Serna, Sonia; Reichardt, Niels-Christian] CICbiomaGUNE, Biofunct Nanomat Unit, San Sebastian 20009, Spain. [Pera, Nuria Parera; Pieters, Roland J.] Univ Utrecht, Dept Med Chem & Chem Biol, Utrecht Inst Pharmaceut Sci, NL-3508 TB Utrecht, Netherlands. RP Mahal, LK (reprint author), NYU, Dept Chem, Biomed Chem Inst, 100 Washington Sq East,Room 1001, New York, NY 10003 USA. EM lkmahal@nyu.edu RI Serna, Sonia/K-5795-2014; Gildersleeve, Jeffrey/N-3392-2014; biomaGUNE, CIC/J-9136-2014; Pieters, Roland/A-9254-2008; Gerlach, Jared/K-2698-2013; OI Serna, Sonia/0000-0002-2085-4412; biomaGUNE, CIC/0000-0001-7690-0660; Pieters, Roland/0000-0003-4723-3584; Gerlach, Jared/0000-0001-7343-7201; Kilcoyne, Michelle/0000-0002-8870-1308 FU NIH [GM62116, GM098791]; National Center for Functional Glycomics [P41-GM103694]; National Cancer Institute, National Institutes of Health; Consortium for Functional Glycomics (Scripps Research Institute) [GM62116]; Pharmacology Research Associate Training (PRAT) program of the NIGMS; Science Foundation Ireland [08/SRC/B1393]; European Union [260600]; Ministerio de Ciencia e Innovacion [CTQ2008-04444/BQA, CTQ2011-27874]; Government of the Basque Country; Etortek grant; European Union; Dutch Technology Foundation STW; applied science division of NWO; Ministry of Economic Affairs; National Institutes of Health [5 U54 GM062116-09]; MacCracken Fellowship (NYU) FX R.D.C. and D.F.S.: The Protein-Glycan Interaction Resource (Core H) of the Consortium for Functional Glycomics is supported by NIH Grants GM62116 GM098791 and the National Center for Functional Glycomics P41-GM103694. J.C.G.: This work was supported in part by the intramural research program of the National Cancer Institute, National Institutes of Health and the Consortium for Functional Glycomics (GM62116; The Scripps Research Institute). C. T. C. received fellowship support through the Pharmacology Research Associate Training (PRAT) program of the NIGMS. L.J.: This work was supported by Science Foundation Ireland (grant 08/SRC/B1393) in support of the Alimentary Glycoscience Research Cluster (AGRC) and the European Union FP7 program (grant 260600) in support of GlycoHIT. N.C.R.: This work was supported by Ministerio de Ciencia e Innovacion, projects CTQ2008-04444/BQA and CTQ2011-27874, Government of the Basque Country, Etortek grant and the European Union, ITN-EuroGlycoArrays grant is gratefully acknowledged. R.J.P.: This work was supported by the Dutch Technology Foundation STW, applied science division of NWO and the Technology Program of the Ministry of Economic Affairs. L. K. M.: This work was supported by the National Institutes of Health Grant No. 5 U54 GM062116-09. L. W. was supported by a MacCracken Fellowship (NYU). NR 55 TC 36 Z9 36 U1 2 U2 47 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD JUN PY 2014 VL 24 IS 6 BP 507 EP 517 DI 10.1093/glycob/cwu019 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH2CO UT WOS:000335928500004 PM 24658466 ER PT J AU Beare, PA Sandoz, KM Larson, CL Howe, D Kronmiller, B Heinzen, RA AF Beare, Paul A. Sandoz, Kelsi M. Larson, Charles L. Howe, Dale Kronmiller, Brent Heinzen, Robert A. TI Essential Role for the Response Regulator PmrA in Coxiella burnetii Type 4B Secretion and Colonization of Mammalian Host Cells SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LEGIONELLA-PNEUMOPHILA; SIGNAL-TRANSDUCTION; HUMAN MACROPHAGES; INTRACELLULAR MULTIPLICATION; ACANTHAMOEBA-CASTELLANII; VESICULAR TRAFFICKING; ESCHERICHIA-COLI; EUKARYOTIC CELLS; EFFECTOR PROTEIN; SYSTEM AB Successful host cell colonization by the Q fever pathogen, Coxiella burnetii, requires translocation of effector proteins into the host cytosol by a Dot/Icm type 4B secretion system (T4BSS). In Legionella pneumophila, the two-component system ( TCS) PmrAB regulates the Dot/Icm T4BSS and several additional physiological processes associated with pathogenesis. Because PmrA consensus regulatory elements are associated with some dot/icm and substrate genes, a similar role for PmrA in regulation of the C. burnetii T4BSS has been proposed. Here, we constructed a C. burnetii pmrA deletion mutant to directly probe PmrA-mediated gene regulation. Compared to wild-type bacteria, C. burnetii Delta pmrA exhibited severe intracellular growth defects that coincided with failed secretion of effector proteins. Luciferase gene reporter assays demonstrated PmrA-dependent expression of 5 of 7 dot/icm operons and 9 of 11 effector-encoding genes with a predicted upstream PmrA regulatory element. Mutational analysis verified consensus sequence nucleotides required for PmrA-directed transcription. RNA sequencing and whole bacterial cell mass spectrometry of wild-type C. burnetii and the Delta pmrA mutant uncovered new components of the PmrA regulon, including several genes lacking PmrA motifs that encoded Dot/Icm substrates. Collectively, our results indicate that the PmrAB TCS is a critical virulence factor that regulates C. burnetii Dot/Icm secretion. The presence of PmrA-responsive genes lacking PmrA regulatory elements also suggests that the PmrAB TCS controls expression of regulatory systems associated with the production of additional C. burnetii proteins involved in host cell parasitism. C1 [Beare, Paul A.; Sandoz, Kelsi M.; Larson, Charles L.; Howe, Dale; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Kronmiller, Brent] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural Research Program of the National Institutes of Health; National Institute of Allergy and Infectious Diseases FX We thank Renee Olano of the Research Technologies Branch, National Institute of Allergy and Infectious Diseases, for mass spectrometry.; This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 76 TC 9 Z9 9 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 2014 VL 196 IS 11 BP 1925 EP 1940 DI 10.1128/JB.01532-14 PG 16 WC Microbiology SC Microbiology GA AH1VM UT WOS:000335909500002 PM 24610709 ER PT J AU Machado, ES Krauss, MR Megazzini, K Coutinho, CM Kreitchmann, R Melo, VH Pilotto, JH Ceriotto, M Hofer, CB Siberry, GK Watts, DH AF Machado, Elizabeth Stankiewicz Krauss, Margot R. Megazzini, Karen Coutinho, Conrado Milani Kreitchmann, Regis Melo, Victor Hugo Pilotto, Jose Henrique Ceriotto, Mariana Hofer, Cristina B. Siberry, George K. Watts, D. Heather CA NICHD Int Site Dev Initiative NISD TI Hypertension, preeclampsia and eclampsia among HIV-infected pregnant women from Latin America and Caribbean countries SO JOURNAL OF INFECTION LA English DT Article DE HIV-infected women; Pregnancy; Hypertensive disorders ID ACTIVE ANTIRETROVIRAL THERAPY; INCREASED RISK; BLOOD-VOLUME; INFANTS; METAANALYSIS; ZIDOVUDINE; OUTCOMES; WEIGHT; CITY; AIDS AB Objectives: To evaluate the incidence of and risk factors for hypertensive disorders in a cohort of HIV-infected pregnant women. Methods: Hypertensive disorders ( HD) including preeclampsia/eclampsia (PE/E) and pregnancy induced hypertension, and risk factors were evaluated in a cohort of HIV-infected pregnant women from Latin America and the Caribbean enrolled between 2002 and 2009. Only pregnant women enrolled for the first time in the study and delivered at >= 20 weeks gestation were analyzed. Results: HD were diagnosed in 73 (4.8%, 95% CI: 3.8%-6.0%) of 1513 patients; 35 (47.9%) had PE/E. HD was significantly increased among women with a gestational age-adjusted body mass index (gBMI) >= 25 kg/m(2) (OR = 3.1; 95% CI: 1.9-5.0), hemoglobin (Hg) >= 11 g/dL at delivery (OR = 2.1; 95% CI: 1.2-3.6) and age >= 35 years (OR = 1.8; 95% CI: 1.1-3.2). PE/E was increased among women with a gBMI >= 25 kg/m(2) (OR = 3.0; 95% CI: 1.5-6.0)and Hg >= 11 g/dL at delivery (OR = 2.8; 95% CI: 1.2-6.5). A previous history of PE/E increased the risk of PE/E 6.7 fold (95% CI: 1.8-25.5). HAART before conception was associated with PE/E (OR = 2.3; 95% CI: 1.1-4.9). Conclusions: HIV-infected women, with a previous history of PE/E, a gBMI >= 25 kg/m(2), Hg at delivery >= 11 g/dL and in use of HAART before conception are at an increased risk of developing PE/E during pregnancy. (C) 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved. C1 [Machado, Elizabeth Stankiewicz; Hofer, Cristina B.] Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira, Rio De Janeiro, Brazil. [Krauss, Margot R.; Megazzini, Karen] WESTAT Corp, Rockville, MD 20850 USA. [Coutinho, Conrado Milani] Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, BR-05508 Sao Paulo, Brazil. [Kreitchmann, Regis] Irmandade Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, Brazil. [Melo, Victor Hugo] Univ Fed Minas Gerais, Fac Med, Belo Horizonte, MG, Brazil. [Pilotto, Jose Henrique] Fiocruz IOC, Lab AIDS & Imunol Mol, Rio De Janeiro, Brazil. [Pilotto, Jose Henrique] Hosp Geral Nova Iguacu, Rio De Janeiro, Brazil. [Ceriotto, Mariana] Dr Cecilia Grierson Hosp, Infect Dis Unit, Buenos Aires, MD, Argentina. [Siberry, George K.; Watts, D. Heather] NICHD, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA. RP Machado, ES (reprint author), IPPMG UFRJ, Serv Prenatal, Av Bruno Lobo 50,Cidade Univ, BR-21941912 Rio De Janeiro, RJ, Brazil. EM emachado@infolink.com.br FU Eunice Kennedy ShriverNational Institute of Child Health and Human Development, Bethesda, Maryland, USA (NICHD) [N01-HD-3-3345]; NICHD [HHSN267200800001C, N01-HD-8-0001] FX Supported by Eunice Kennedy ShriverNational Institute of Child Health and Human Development, Bethesda, Maryland, USA (NICHD) Contract # N01-HD-3-3345 (2002-2007) and by NICHD Contract # HHSN267200800001C (NICHD Control #: N01-HD-8-0001) (2007-2012). NICHD was involved in all aspects of study design, data analysis and interpretation, and manuscript writing/ editing. NR 46 TC 5 Z9 5 U1 0 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD JUN PY 2014 VL 68 IS 6 BP 572 EP 580 DI 10.1016/j.jinf.2013.12.018 PG 9 WC Infectious Diseases SC Infectious Diseases GA AG9XL UT WOS:000335773200008 PM 24462561 ER PT J AU Alonso, WJ McCormick, BJJ Schuck-Paim, C AF Alonso, Wladimir J. McCormick, Benjamin J. J. Schuck-Paim, Cynthia TI Influenza and specific humidity in French Guiana: When analytical simplicity is golden SO JOURNAL OF INFECTION LA English DT Letter C1 [Alonso, Wladimir J.; McCormick, Benjamin J. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Schuck-Paim, Cynthia] Origem Sci, BR-03337 Sao Paulo, Brazil. RP Alonso, WJ (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr,Bldg 16, Bethesda, MD 20892 USA. EM alonsow@mail.nih.gov NR 6 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD JUN PY 2014 VL 68 IS 6 BP 604 EP 605 DI 10.1016/j.jinf.2014.02.002 PG 3 WC Infectious Diseases SC Infectious Diseases GA AG9XL UT WOS:000335773200012 PM 24513392 ER PT J AU Mahamat, A Viboud, C AF Mahamat, A. Viboud, C. TI Influenza and specific humidity in French Guiana: When analytical simplicity is golden Response SO JOURNAL OF INFECTION LA English DT Letter ID SEASONALITY; EPIDEMICS C1 [Mahamat, A.] Cayenne Gen Hosp, Infect Dis & Trop Med Unit, Cayenne, French Guiana. [Mahamat, A.] Univ Antilles Guyane, EA 3595, Cayenne, French Guiana. [Viboud, C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Mahamat, A (reprint author), CH Andree Rosemon, Unite Malad Infect & Trop, Ave Flamboyants, Cayenne 97306, French Guiana. EM mahamataba@gmail.com NR 14 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 EI 1532-2742 J9 J INFECTION JI J. Infect. PD JUN PY 2014 VL 68 IS 6 BP 605 EP 606 DI 10.1016/j.jinf.2014.02.004 PG 3 WC Infectious Diseases SC Infectious Diseases GA AG9XL UT WOS:000335773200013 PM 24530373 ER PT J AU Schulz, KS Liu, XQ Klupp, BG Granzow, H Cohen, JI Mettenleiter, TC AF Schulz, Katharina S. Liu, XueQiao Klupp, Barbara G. Granzow, Harald Cohen, Jeffrey I. Mettenleiter, Thomas C. TI Pseudorabies Virus pUL46 Induces Activation of ERK1/2 and Regulates Herpesvirus-Induced Nuclear Envelope Breakdown SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-CYCLE PROGRESSION; TEGUMENT PROTEIN US2; FAMILY KINASE LCK; DELETION MUTANTS; GENE-PRODUCT; MAP KINASES; TYPE-1 UL46; SIMPLEX; PHOSPHORYLATION; EGRESS AB Herpesvirus capsid morphogenesis occurs in the nucleus, while final maturation takes place in the cytosol, requiring translocation of capsids through the nuclear envelope. The nuclear egress complex, consisting of homologs of herpes simplex virus pUL31 and pUL34, is required for efficient nuclear egress via primary envelopment and de-envelopment. Recently, we described an alternative mode of nuclear escape by fragmentation of the nuclear envelope induced by replication-competent pUL31 and pUL34 deletion mutants of the alphaherpesvirus pseudorabies virus (PrV), which had been selected by serial passaging in cell culture. Both passaged viruses carry congruent mutations in seven genes, including UL46, which encodes one of the major tegument proteins. Herpesvirus pUL46 homologs have recently been shown to activate the PI3K-Akt and ERK1/2 signaling pathways, which are involved in regulation of mitosis and apoptosis. Since in uninfected cells fragmentation of the nuclear envelope occurs during mitosis and apoptosis, we analyzed whether pUL46 of PrV is involved in signaling events impairing the integrity of the nuclear envelope. We show here that PrV pUL46 is able to induce phosphorylation of ERK1/2 and, thus, expression of ERK1/2 target genes but fails to activate the PI3K-Akt pathway. Deletion of UL46 from PrV-Delta UL34Pass and PrV-Delta UL31Pass or replacement by wild-type UL46 resulted in enhanced nuclear envelope breakdown, indicating that the mutations in pUL46 may limit the extent of NEBD. Thus, although pUL46 induces ERK1/2 phosphorylation, controlling the integrity of the nuclear envelope is independent of the ERK1/2 signaling pathway. C1 [Schulz, Katharina S.; Klupp, Barbara G.; Mettenleiter, Thomas C.] Friedrich Loeffler Inst, Inst Mol Biol, Greifswald, Germany. [Granzow, Harald] Friedrich Loeffler Inst, Inst Infectol, Greifswald, Germany. [Liu, XueQiao; Cohen, Jeffrey I.] NIH, Med Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA. RP Mettenleiter, TC (reprint author), Friedrich Loeffler Inst, Inst Mol Biol, Greifswald, Germany. EM thomas.mettenleiter@fli.bund.de FU Deutsche Forschungsgemeinschaft [DFG Me 854/12-1]; intramural research program of the National Institute of Allergy and Infectious Diseases FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG Me 854/12-1) and the intramural research program of the National Institute of Allergy and Infectious Diseases. NR 42 TC 4 Z9 4 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2014 VL 88 IS 11 BP 6003 EP 6011 DI 10.1128/JVI.00501-14 PG 9 WC Virology SC Virology GA AH2SB UT WOS:000335970300010 PM 24623429 ER PT J AU Grohman, JK Gorelick, RJ Kottegoda, S Allbritton, NL Rein, A Weeks, KM AF Grohman, Jacob K. Gorelick, Robert J. Kottegoda, Sumith Allbritton, Nancy L. Rein, Alan Weeks, Kevin M. TI An Immature Retroviral RNA Genome Resembles a Kinetically Trapped Intermediate State SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE-LEUKEMIA-VIRUS; SELECTIVE 2'-HYDROXYL ACYLATION; SINGLE NUCLEOTIDE RESOLUTION; PRIMER EXTENSION SHAPE; SECONDARY STRUCTURE; HIV-1 VIRIONS; VIRAL-RNA; WILD-TYPE; GAG; DIMERIZATION AB Retroviral virions initially assemble in an immature form that differs from that of the mature infectious particle. The RNA genomes in both immature and infectious particles are dimers, and interactions between the RNA dimer and the viral Gag protein ensure selective packaging into nascent immature virions. We used high-sensitivity selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) to obtain nucleotide-resolution structural information from scarce, femtomole quantities of Moloney murine leukemia virus (MuLV) RNA inside authentic virions and from viral RNA extracted from immature (protease-minus) virions. Our secondary structure model of the dimerization and packaging domain indicated that a stable intermolecular duplex known as PAL2, previously shown to be present in mature infectious MuLV particles, was sequestered in an alternate stem-loop structure inside immature virions. The intermediate state corresponded closely to a late-folding intermediate that we detected in time-resolved studies of the free MuLV RNA, suggesting that the immature RNA structure reflects trapping of the intermediate folding state by interactions in the immature virion. We propose models for the RNA-protein interactions that trap the RNA in the immature state and for the conformational rearrangement that occurs during maturation of virion particles. C1 [Grohman, Jacob K.; Kottegoda, Sumith; Allbritton, Nancy L.; Weeks, Kevin M.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Gorelick, Robert J.] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA. [Allbritton, Nancy L.] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC USA. [Allbritton, Nancy L.] N Carolina State Univ, Raleigh, NC 27695 USA. [Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. RP Weeks, KM (reprint author), Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. EM weeks@unc.edu FU U. S. National Institutes of Health [GM064803] FX This work was supported by a grant from the U. S. National Institutes of Health (GM064803 to K.M.W.); in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (A. R.); and under contract number HHSN261200800001E with Leidos Biomedical Research, Inc. (R.J.G.). NR 40 TC 5 Z9 5 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2014 VL 88 IS 11 BP 6061 EP 6068 DI 10.1128/JVI.03277-13 PG 8 WC Virology SC Virology GA AH2SB UT WOS:000335970300015 PM 24623442 ER PT J AU Walsh, KB Teijaro, JR Brock, LG Fremgen, DM Collins, PL Rosen, H Oldstone, MBA AF Walsh, Kevin B. Teijaro, John R. Brock, Linda G. Fremgen, Daniel M. Collins, Peter L. Rosen, Hugh Oldstone, Michael B. A. TI Animal Model of Respiratory Syncytial Virus: CD8(+) T Cells Cause a Cytokine Storm That Is Chemically Tractable by Sphingosine-1-Phosphate 1 Receptor Agonist Therapy SO JOURNAL OF VIROLOGY LA English DT Article ID PNEUMONIA VIRUS; INFLUENZA-VIRUS; MICE; INFECTION; ANALOG; RESPONSES; DISEASE; FTY720; INNATE; INJURY AB The cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory response driven by cytokine and immune cell components. The cytokine storm during influenza virus infection, whereby the amplified innate immune response is primarily responsible for pulmonary damage, has been well characterized. Now we describe a novel event where virus-specific T cells induce a cytokine storm. The paramyxovirus pneumonia virus of mice (PVM) is a model of human respiratory syncytial virus (hRSV). Unexpectedly, when C57BL/6 mice were infected with PVM, the innate inflammatory response was undetectable until day 5 postinfection, at which time CD8(+) T cells infiltrated into the lung, initiating a cytokine storm by their production of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Administration of an immunomodulatory sphingosine-1-phosphate (S1P) receptor 1 (S1P1R) agonist significantly inhibited PVM-elicited cytokine storm by blunting the PVM-specific CD8(+) T cell response, resulting in diminished pulmonary disease and enhanced survival. C1 [Walsh, Kevin B.; Teijaro, John R.; Fremgen, Daniel M.; Oldstone, Michael B. A.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Brock, Linda G.; Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Rosen, Hugh] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA. RP Oldstone, MBA (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM hrosen@scripps.edu; mbaobo@scripps.edu FU USPHS [AI074564, AI009484, AI055509, MH084512]; NIH training [NS041219, AI007244, AI007364]; American Heart Association [11POST7430106]; Intramural Program of NIAID, NIH FX This work was supported in part by USPHS grants AI074564 (to M.B.A.O., H.R., K.B.W., and J.R.T.), AI009484 (to M.B.A.O.), AI055509 (to H.R.), and MH084512 (to H.R.), NIH training grants NS041219 (to K.B.W.), AI007244 (to K.B.W.), and AI007364 (to J.R.T.), and American Heart Association grant 11POST7430106 (to J.R.T.). L.G.B. and P.L.C. were supported by the Intramural Program of NIAID, NIH. NR 41 TC 13 Z9 13 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2014 VL 88 IS 11 BP 6281 EP 6293 DI 10.1128/JVI.00464-14 PG 13 WC Virology SC Virology GA AH2SB UT WOS:000335970300035 PM 24672024 ER PT J AU Le Nouen, C Hillyer, P Brock, LG Winter, CC Rabin, RL Collins, PL Buchholz, UJ AF Le Nouen, Cyril Hillyer, Philippa Brock, Linda G. Winter, Christine C. Rabin, Ronald L. Collins, Peter L. Buchholz, Ursula J. TI Human Metapneumovirus SH and G Glycoproteins Inhibit Macropinocytosis-Mediated Entry into Human Dendritic Cells and Reduce CD4(+) T Cell Activation SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNOSUPPRESSION IN-VITRO; RESPIRATORY-TRACT DISEASE; VIRAL GLYCOPROTEINS; FLOW-CYTOMETRY; VIRUS ENTRY; ADULTS; INFECTION; CHILDREN; SURFACE; MEMORY AB Human metapneumovirus (HMPV) is a major etiologic agent of respiratory disease worldwide. HMPV reinfections are common in healthy adults and children, suggesting that the protective immune response to HMPV is incomplete and short-lived. We used gene-deletion viruses to evaluate the role of the attachment G and small hydrophobic SH glycoproteins on virus uptake by primary human monocyte-derived dendritic cells (MDDC) in vitro and on subsequent MDDC maturation and activation of autologous T cells. HMPV with deletion of G and SH (Delta SHG) exhibited increased infectivity but had little effect on MDDC maturation. However, MDDC stimulated with Delta SHG induced increased proliferation of autologous Th1-polarized CD4(+) T cells. This effect was independent of virus replication. Increased T cell proliferation was strictly dependent on contact between virus-stimulated MDDC and CD4(+) T cells. Confocal microscopy revealed that deletion of SH and G was associated with an increased number of immunological synapses between memory CD4(+) T cells and virus-stimulated MDDC. Uptake of HMPV by MDDC was found to be primarily by macropinocytosis. Uptake of wild-type (WT) virus was reduced compared to that of Delta SHG, indicative of inhibition by the SH and G glycoproteins. In addition, DC-SIGN-mediated endocytosis provided a minor alternative pathway that depended on SH and/or G and thus operated only for WT. Altogether, our results show that SH and G glycoproteins reduce the ability of HMPV to be internalized by MDDC, resulting in a reduced ability of the HMPV-stimulated MDDC to activate CD4(+) T cells. This study describes a previously unknown mechanism of virus immune evasion. C1 [Le Nouen, Cyril; Brock, Linda G.; Winter, Christine C.; Collins, Peter L.; Buchholz, Ursula J.] NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Hillyer, Philippa; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Le Nouen, C (reprint author), NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lenouenc@niaid.nih.gov FU Intramural Research Program of the NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 9 Z9 9 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JUN PY 2014 VL 88 IS 11 BP 6453 EP 6469 DI 10.1128/JVI.03261-13 PG 17 WC Virology SC Virology GA AH2SB UT WOS:000335970300050 PM 24672038 ER PT J AU Kreimer, AR AF Kreimer, Aimee R. TI Prospects for prevention of HPV-driven oropharynx cancer SO ORAL ONCOLOGY LA English DT Article DE Prevention; Human papillomavirus; HPV; Oropharyngeal cancer ID HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS-CELL CARCINOMA; YOUNG-WOMEN; INTRAEPITHELIAL NEOPLASIA; VACCINATION COVERAGE; UNITED-STATES; COSTA-RICA; TRIAL; MEN; PREVALENCE AB Prevention of HPV-associated cancers can take two forms-one through prevention of infection via prophylactic HPV vaccination, and one through interruption of disease progression through early identification (i.e.: screening) and treatment. Primary prevention via vaccination seems promising, as a proof-of-principal study demonstrated high vaccine efficacy against one-time detection of oral HPV16/18 infection. In addition to the direct benefit of vaccination, indirect protection from reduced genital HPV infection should also reduce oral HPV exposure at the individual level. Yet, for the current unvaccinated cohorts who will bear the burden of non-cervical HPV-associated cancers for the foreseeable future, no secondary prevention opportunities exist, as the field has not yet validated any screening methods for non-cervical HPV associated cancers. Serum HPV16 E6 antibody data suggest that this test might one day be able to detect many of the at-risk patients prior to tumor development. For any biomarker that proves valid and reliable, transitioning into clinical practice will require additional research focused on (1) diagnostics, (2) effective intervention, and (3) observed reductions in cancer mortality. (C) 2013 The Author. Published by Elsevier Ltd. All rights reserved. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Kreimer, AR (reprint author), NCI, NIH, 9609 Med Ctr Dr,RM 6-E104,MSC 9767, Bethesda, MD 20892 USA. EM kreimera@mail.nih.gov RI Kreimer, Aimee/H-1687-2015 FU Intramural NIH HHS [ZIA CP010209-01] NR 41 TC 18 Z9 18 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD JUN PY 2014 VL 50 IS 6 BP 555 EP 559 DI 10.1016/j.oraloncolgy.2013.06.007 PG 5 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA AH1NY UT WOS:000335889000005 PM 23876626 ER PT J AU Klinger, R Colloca, L Bingel, U Flor, H AF Klinger, Regine Colloca, Luana Bingel, Ulrike Flor, Herta TI Placebo analgesia: Clinical applications SO PAIN LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; IRRITABLE-BOWEL-SYNDROME; LOW-BACK-PAIN; MECHANISMS; EXPECTATIONS; RESPONSES; EFFICACY; DISEASE C1 [Klinger, Regine] Univ Hamburg, Dept Psychol, Psychotherapeut Univ Outpatient Clin Behav Therap, D-20146 Hamburg, Germany. [Colloca, Luana] NIMH, NCCAM, Bethesda, MD 20892 USA. [Colloca, Luana] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Bingel, Ulrike] Univ Duisburg Essen, Univ Hosp Essen, Dept Neurol, Essen, Germany. [Flor, Herta] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Health, Dept Cognit & Clin Neurosci, D-68159 Mannheim, Germany. RP Klinger, R (reprint author), Univ Hamburg, Dept Psychol, Psychotherapeut Univ Outpatient Clin Behav Therap, Von Melle Pk 5, D-20146 Hamburg, Germany. EM rklinger@uni-hamburg.de OI Colloca, Luana/0000-0002-6503-4709; Flor, Herta/0000-0003-4809-5398 FU National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Mental Health (NIMH); Deutsche Forschungsgemeinschaft [FOR 1328/1, Kl 1350/3-1, Fl 156/33-1, BI 789/2-1]; Federal Ministry of Education and Research [01GQ0808] FX This research was funded by an intramural grant from the National Center for Complementary and Alternative Medicine (NCCAM) and National Institute of Mental Health (NIMH) (L.C.), and grants by the Deutsche Forschungsgemeinschaft (FOR 1328/1) to R.K. (Kl 1350/3-1), H.F. (Fl 156/33-1), and U.B. (BI 789/2-1), and the Federal Ministry of Education and Research (01GQ0808) (U.B.). NR 41 TC 20 Z9 21 U1 4 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JUN PY 2014 VL 155 IS 6 BP 1055 EP 1058 DI 10.1016/j.pain.2013.12.007 PG 4 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA AH1SY UT WOS:000335902500005 PM 24333780 ER PT J AU Yeung, STA Colagiuri, B Lovibond, PF Colloca, L AF Yeung, Siu Tsin Au Colagiuri, Ben Lovibond, Peter F. Colloca, Luana TI Partial reinforcement, extinction, and placebo analgesia SO PAIN LA English DT Article DE Conditioning; Expectancy; Extinction; Pain; Partial reinforcement; Placebo effect ID IRRITABLE-BOWEL-SYNDROME; DOSE REDUCTION; EXPECTANCY; MECHANISMS; EXPERIENCE; RESPONSES; NALOXONE; NOCEBO AB Numerous studies indicate that placebo analgesia can be established via conditioning procedures. However, these studies have exclusively involved conditioning under continuous reinforcement. Thus, it is currently unknown whether placebo analgesia can be established under partial reinforcement and how durable any such effect would be. We tested this possibility using electrocutaneous pain in healthy volunteers. Sixty undergraduates received placebo treatment (activation of a sham electrode) under the guise of an analgesic trial. The participants were randomly allocated to different conditioning schedules, namely continuous reinforcement (CRF), partial reinforcement (PRF), or control (no conditioning). Conditioning was achieved by surreptitiously reducing pain intensity during training when the placebo was activated compared with when it was inactive. For the CRF group, the placebo was always followed by a surreptitious reduction in pain during training. For the PRF group, the placebo was followed by a reduction in pain stimulation on 62.5% of trials only. In the test phase, pain stimulation was equivalent across placebo and no placebo trials. Both CRF and PRF produced placebo analgesia, with the magnitude of initial analgesia being larger after CRF. However, although the placebo analgesia established under CRF extinguished during test phase, the placebo analgesia established under PRF did not. These findings indicate that PRF can induce placebo analgesia and that these effects are more resistant to extinction than those established via CRF. PRF may therefore reflect a novel way of enhancing clinical outcomes via the placebo effect. (C) 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Yeung, Siu Tsin Au; Colagiuri, Ben] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia. [Colagiuri, Ben; Lovibond, Peter F.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia. [Colloca, Luana] NIMH, Bethesda, MD USA. [Colloca, Luana] NCCAM, NIH, Bethesda, MD USA. RP Colagiuri, B (reprint author), Univ Sydney, Sch Psychol, A18, Sydney, NSW 2006, Australia. EM ben.colagiuri@sydney.edu.au OI Colloca, Luana/0000-0002-6503-4709; Lovibond, Peter/0000-0003-2146-9054 FU Intramural Research Program of the National Institute of Mental Health; National Center for Complementary and Alternative Medicine FX The authors thank Professor Justin Harris, University of Sydney, for his useful advice on the current project. Dr. Luana Colloca is supported by the Intramural Research Program of the National Institute of Mental Health and National Center for Complementary and Alternative Medicine. NR 44 TC 7 Z9 7 U1 0 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JUN PY 2014 VL 155 IS 6 BP 1110 EP 1117 DI 10.1016/j.pain.2014.02.022 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA AH1SY UT WOS:000335902500012 ER PT J AU Forsythe, LP Arora, N Alfano, CM Weaver, KE Hamilton, AS Aziz, N Rowland, JH AF Forsythe, Laura P. Arora, Neeraj K. Alfano, Catherine M. Weaver, Kathryn E. Hamilton, Ann S. Aziz, Noreen Rowland, Julia H. TI Role of oncologists and primary care physicians in providing follow-up care to non-Hodgkin lymphoma survivors within 5 years of diagnosis: a population-based study SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Cancer; Non-Hodgkin lymphoma; Survivor; Follow-up care; Patient-centered ID QUALITY-OF-LIFE; CANCER SURVIVORS; BREAST-CANCER; OUTCOMES RESEARCH; PATIENT; ADULT; EXPECTATIONS; SYMPTOMS; RISK AB The growing population of non-Hodgkin lymphoma (NHL) survivors living longer with high physical and psychological treatment burden, in combination with the projected shortage of medical professionals, necessitates redesigning cancer follow-up care. This study examined follow-up care patterns, factors associated with follow-up care, and attitudes towards follow-up care among NHL survivors. We surveyed survivors of aggressive NHL 2 to 5 years post-diagnosis (N = 363) using a population-based sample from the Los Angeles County Surveillance Epidemiology and End Results registry. Most survivors (82 %) received cancer-related follow-up care in the past year from an oncologist. History of recurrence, more comorbidities, more symptoms, and a shorter survivor-oncologist relationship were associated with high-frequency care with the oncologist [(a parts per thousand yen5 visits in the past year), p < 0.05]. Many survivors followed up by oncologists (71 %) also saw a primary care provider (PCP) and 47 % also saw both a PCP and other specialists. Factors associated with seeing a PCP in addition to an oncologist included more symptoms, more health information needs, no history of recurrence, perceived excellent quality of cancer follow-up care, and fewer visits with the oncologist (p < 0.05). Survivors generally reported high reassurance from, and low negative anticipation towards, follow-up care. The high proportion of NHL survivors receiving care from multiple physicians, and the sizable proportion (similar to 30 %) who have not recently seen a PCP, suggests that coordinating care across specialties is critical to ensure comprehensive, non-duplicative care. Understanding factors associated with cancer-related follow-up is a first step towards more effective, efficient, patient-centered care. C1 [Forsythe, Laura P.] PCORI, Washington, DC 20036 USA. [Forsythe, Laura P.; Alfano, Catherine M.; Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH DHHS, Bethesda, MD 20892 USA. [Forsythe, Laura P.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH DHHS, Bethesda, MD 20892 USA. [Arora, Neeraj K.] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH DHHS, Bethesda, MD 20892 USA. [Weaver, Kathryn E.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Social Sci & Hlth Policy, Winston Salem, NC USA. [Hamilton, Ann S.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Aziz, Noreen] NINR, Off Extramural Programs, Bethesda, MD 20892 USA. RP Forsythe, LP (reprint author), PCORI, 1828 L St,NW,Suite 900, Washington, DC 20036 USA. EM lforsythe@pcori.org FU California Department of Health Services [103885]; National Cancer Institute Surveillance, Epidemiology, and End Results Program [N01-PC-35139, N02-PC-15105]; Centers for Disease Control and Prevention [U55/CCR921930-02] FX This study was supported in part by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; by National Cancer Institute Surveillance, Epidemiology, and End Results Program Contract No. N01-PC-35139 awarded to the University of Southern California and Contract No. N02-PC-15105 awarded to the Public Health Institute; and by Centers for Disease Control and Prevention National Program of Cancer Registries Agreement No. U55/CCR921930-02 awarded to the Public Health Institute. Selected findings from this manuscript were presented in abstract form at the Annual Meeting of the American Society of Clinical Oncology in June 2001 in Chicago, IL. NR 39 TC 3 Z9 3 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD JUN PY 2014 VL 22 IS 6 BP 1509 EP 1517 DI 10.1007/s00520-013-2113-z PG 9 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA AG9YC UT WOS:000335775000009 PM 24414999 ER PT J AU Madeo, AC Tercyak, KP Tarini, BA McBride, CM AF Madeo, Anne C. Tercyak, Kenneth P. Tarini, Beth A. McBride, Colleen M. TI Effects of Undergoing Multiplex Genetic Susceptibility Testing on Parent Attitudes towards Testing Their Children SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Genetic Predisposition to Disease; Genetic Testing/Psychology; Health Knowledge; Attitudes; Practice; Parents; Psychology ID RISK INFORMATION; PEDIATRICS; BEHAVIORS AB Parents may pursue common disease risk information about themselves via multiplex genetic susceptibility testing (MGST) for their children. To prospectively assess whether parents who received MGST disclosed their test results to their child, intended to change the child's health habits, or have the child tested. Eighty parents who opted for free MGST completed an online survey about a child in their household before undergoing MGST and a follow-up telephone survey 3 months after receiving results. Few parents (21 %) disclosed results to the child. Undergoing MGST was unrelated to intentions to change the child's health habits but did increase parental willingness to test the child. Greater willingness to test a child was associated with positive attitudes toward pediatric genetic testing and intentions to change the child's health habits. The experience of receiving MGST had little impact on parents' perceptions or behaviors related to their minor child. C1 [Madeo, Anne C.; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. [Tarini, Beth A.] Univ Michigan, Dept Pediat, Child Hlth Evaluat & Res CHEAR Unit, Ann Arbor, MI 48109 USA. [Madeo, Anne C.] George E Whalen Dept Vet Affairs Med Ctr, Genom Med Serv, Salt Lake City, UT 84148 USA. RP Madeo, AC (reprint author), George E Whalen Dept Vet Affairs Med Ctr, Genom Med Serv, 500 Foothill Dr,151Z, Salt Lake City, UT 84148 USA. EM acmadeo@gmail.com FU Intramural NIH HHS [ZIA HG200344-07]; NCI NIH HHS [R01 CA137625, R01CA137625, U19CA079689, U19 CA079689]; NHGRI NIH HHS [K18 HG006754, HHSN268200782096C, K18HG006754]; NICHD NIH HHS [K23 HD057994, K23HD057994] NR 18 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD JUN PY 2014 VL 47 IS 3 BP 388 EP 394 DI 10.1007/s12160-013-9553-z PG 7 WC Psychology, Multidisciplinary SC Psychology GA AG8EV UT WOS:000335652500016 PM 24338635 ER PT J AU Shepperd, JA Novell, CA O'Neill, SC Docherty, SL Sanderson, SC McBride, CM Lipkus, IM AF Shepperd, James A. Novell, Corinne A. O'Neill, Suzanne C. Docherty, Sharron L. Sanderson, Saskia C. McBride, Colleen M. Lipkus, Isaac M. TI Contemplating Genetic Feedback Regarding Lung Cancer Susceptibility SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Lung cancer; Genes; Expectations; Consistency theory; Self-enhancement theory ID S-TRANSFERASE M1; SELF-ENHANCEMENT; RISK; SMOKING; POLYMORPHISMS; INDIVIDUALS; INVOLVEMENT; MUTATIONS; RESPONSES; SMOKERS AB We examined three theoretical models (self-enhancement theory, consistency theory, and a combined model) for understanding how expectations and test result favorability influence smokers' desire for a retest following hypothetical genetic test results. College smokers (N = 128) read a brochure describing a biomarker for lung cancer (the GSTM1 gene) then reported whether they thought they had the gene (indicating lower lung cancer risk) or were missing the gene (indicating higher lung cancer risk). Participants then reported whether they would get retested if they received favorable GSTM1 results versus unfavorable GSTM1 results. Participants were most likely to want a retest, suggesting rejection of the results, if they expected favorable news yet received unfavorable news. The findings supported the combined model such that smokers expressed greatest interest in a retest when they imagined genetic risk feedback that challenges both enhancement and consistency motives. C1 [Shepperd, James A.; Novell, Corinne A.] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [O'Neill, Suzanne C.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Docherty, Sharron L.; Lipkus, Isaac M.] Duke Univ, Sch Nursing, Durham, NC USA. [Sanderson, Saskia C.] Icahn Sch Med Mt Sinai, New York, NY USA. [McBride, Colleen M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. RP Shepperd, JA (reprint author), Univ Florida, Dept Psychol, POB 112250, Gainesville, FL 32611 USA. EM shepperd@ufl.edu FU NCI NIH HHS [R01 CA121922-01A2, R01 CA121922] NR 30 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD JUN PY 2014 VL 47 IS 3 BP 395 EP 403 DI 10.1007/s12160-013-9561-z PG 9 WC Psychology, Multidisciplinary SC Psychology GA AG8EV UT WOS:000335652500017 PM 24222509 ER PT J AU Napolitano, C Johnson, WE Sanderson, J O'Brien, SJ Hoelzel, AR Freer, R Dunstone, N Ritland, K Ritland, CE Poulin, E AF Napolitano, Constanza Johnson, Warren E. Sanderson, Jim O'Brien, Stephen J. Hoelzel, A. Rus Freer, Rachel Dunstone, Nigel Ritland, Kermit Ritland, Carol E. Poulin, Elie TI Phylogeography and population history of Leopardus guigna, the smallest American felid SO CONSERVATION GENETICS LA English DT Article DE Leopardus guigna; Felid; Phylogeography; Demographic history; Dispersal barriers ID SOUTHERN SOUTH-AMERICA; QUATERNARY CLIMATE-CHANGE; CHILEAN LAKE DISTRICT; OLIGORYZOMYS-LONGICAUDATUS RODENTIA; LAST GLACIAL MAXIMUM; DNA CONTROL REGION; MITOCHONDRIAL-DNA; GENETIC-STRUCTURE; ONCIFELIS-GUIGNA; POSTGLACIAL RECOLONIZATION AB The guigna (Leopardus guigna) is the smallest and most-restricted New World cat species, inhabiting only around 160,000 km(2) of temperate rain forests in southern South America and is currently threatened by habitat loss, fragmentation and human persecution. We investigated phylogeographic patterns of genetic diversity, demographic history and barriers to gene flow with 116 individuals sampled across the species geographic range by analyzing 1,798 base pairs of the mtDNA (496 bp HVSI region, 720 bp NADH-5 gene, 364 bp from 16S gene and 218 bp from ATP-8 gene) and 15 microsatellite loci. Mitochondrial DNA data revealed a clear phylogeographic pattern with moderate separation between northern and southern Chilean populations supporting recognized subspecific partitions based on morphology. A recent demographic expansion was inferred for the southern-most group (San Rafael Lake), presumably due to the complete coverage of this area during the last glacial period, 28000-16000 years BP. Geographical barriers such as the Andes Mountains and the Chacao Channel have partially restricted historic and more-recent gene flow and the Chilo, Island population has diverged genetically since being separated from the mainland 7000 years BP. This is the first study of the genetic structure of this threatened species throughout its whole geographic range. C1 [Napolitano, Constanza; Poulin, Elie] Univ Chile, Lab Ecol Mol, Santiago, Chile. [Napolitano, Constanza; Poulin, Elie] Univ Chile, Inst Ecol & Biodiversidad, Dept Ciencias Ecol, Fac Ciencias, Santiago, Chile. [Johnson, Warren E.] NCI, Lab Genom Div, Frederick, MD 21701 USA. [Sanderson, Jim] Small Wild Cat Conservat Fdn, Campbell, CA USA. [O'Brien, Stephen J.] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg 199034, Russia. [Hoelzel, A. Rus; Freer, Rachel; Dunstone, Nigel] Univ Durham, Sch Biol & Biomed Sci, Durham, England. [Freer, Rachel] FPCR Environm & Design Ltd, Derby, England. [Dunstone, Nigel] Nat Hist New Zealand, Dunedin, Otago, New Zealand. [Ritland, Kermit; Ritland, Carol E.] Univ British Columbia, Dept Forest & Conservat Sci, Vancouver, BC V6T 1Z4, Canada. RP Napolitano, C (reprint author), Univ Chile, Lab Ecol Mol, Las Palmeras 3425, Santiago, Chile. EM cnapolit@uchile.cl RI Poulin, Elie/C-2654-2012; Johnson, Warren/D-4149-2016; OI Poulin, Elie/0000-0001-7736-0969; Johnson, Warren/0000-0002-5954-186X; O'Brien, Stephen J./0000-0001-7353-8301 FU Instituto de Ecologia y Biodiversidad (IEB, Facultad de Ciencias, Universidad de Chile) [ICM P05-002]; Emerging Leaders in The Americas Program (ELAP, Canadian Bureau for International Education, Government of Canada); CONICYT, Chile; Instituto de Ecologia y Biodiversidad (Facultad de Ciencias, Universidad de Chile); Panthera Kaplan Awards Program (Panthera Foundation, New York, USA); Scott Neotropical Fund Award (Cleveland Metroparks Zoo & the Cleveland Zoological Society, Cleveland, USA); Eric York Scholarship (Felidae Conservation Fund, California, USA); Intramural Research Program of the NCI, NIH FX Guignas were captured with permission from the Agriculture and Livestock Service (SAG) in Chile, capture permit numbers 814/13-Feb-2008, 109/9-Jan-2009, 1220/22-Feb-2010 and 1708/26-Mar-2010. Samples were obtained in Argentina with permission from the National Parks Administration (APN), permit number 1002/8-May-2009. Samples were imported with permission from the Agriculture and Livestock Service (SAG) in Chile, permit number 30/09. C.N. acknowledges support from the doctoral fellowship ICM P05-002 from the Instituto de Ecologia y Biodiversidad (IEB, Facultad de Ciencias, Universidad de Chile), the Emerging Leaders in The Americas Program (ELAP, Canadian Bureau for International Education, Government of Canada) and Becas Chile para pasantias doctorales 2010 (CONICYT, Chile). This study was funded by the Instituto de Ecologia y Biodiversidad (Facultad de Ciencias, Universidad de Chile), Panthera Kaplan Awards Program (Panthera Foundation, New York, USA), Scott Neotropical Fund Award (Cleveland Metroparks Zoo & the Cleveland Zoological Society, Cleveland, USA) and the Eric York Scholarship (Felidae Conservation Fund, California, USA). This research was supported in part by the Intramural Research Program of the NCI, NIH. We wish to thank Benito Gonzalez, Emma Elgueta, Milton Gallardo (Universidad Austral), Jaime Rau (Universidad de Los Lagos), Oscar Skewes (Universidad de Concepcion), Barbara Zentilli (CODEFF), Denise Donoso, Nicolas Galvez, Felipe Hernandez, Elke Schuttler, Cristian Bonacic, Martin Monteverde (Centro de Ecologia Aplicada del Neuquen-Argentina), Jose Luis Brito (Museo Municipal de Ciencias Naturales y Arqueologia de San Antonio), Juan Carlos Torres (Museo de Historia Natural Santiago), Jose Yanez (Museo de Historia Natural Santiago), Osvaldo Rojas (Museo de Historia Natural Calama), Fernando Soto (Museo de Historia Natural de Valparaiso), Elvira Solar (Museo de Zoologia Universidad de Concepcion), Franklin Troncoso (Museo de Historia Natural de Concepcion), Luis Villanueva (SAG VII Region), Cecilia Gonzalez (SAG RM), David Flores (Museo de Ciencias Naturales Bernardino Rivadavia-Argentina), Diego Verzi (Museo de La Plata-Argentina), Manuel Valdes (Parque Tantauco), Bernardita Silva, Lito Quezada, Maximiliano Sepulveda, Javier Cabello, Alejandro Bravo (Universidad Austral), Jorge Valenzuela (CECPAN), Andres Charrier, Juan Luis Celis, Buin Zoo and Fidel Ovidio Castro (Banco de Recursos Geneticos, Facultad de Ciencias Veterinarias, Universidad de Concepcion, Campus Chillan) for generous collaboration with samples for this study. We specially thank Magdalena Bennett for map elaboration. We thank Sylvain Faugeron and Juliana Vianna de Abreu for help with molecular markers. Special thanks to Jennifer Hetz, Monica Mora, Valentina Sanchez, Tatiana Vuskovic, Veronica Sole, Rousset Palou, Yuri Zuniga and Juan Vidal for assisting in the capture of guignas. We thank Raleigh International for logistical support in collection of samples at San Rafael Lake. We thank Parque Ahuenco, especially to Alberto Carvacho, for kindly letting us work in their lands. We thank the Sindicato de Pescadores Mar Adentro from Chepu, especially to Carlos Villarroel, for their kind help during field work. We thank Parque Tantauco, especially to Alan Bannister, for their kind support and for letting us work in their lands. We thank the Senda Darwin Foundation, Ines Hanning from Caulin, and many other local land owners in Chiloe Island who kindly let us work in their lands. NR 154 TC 4 Z9 4 U1 2 U2 47 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1566-0621 EI 1572-9737 J9 CONSERV GENET JI Conserv. Genet. PD JUN PY 2014 VL 15 IS 3 BP 631 EP 653 DI 10.1007/s10592-014-0566-3 PG 23 WC Biodiversity Conservation; Genetics & Heredity SC Biodiversity & Conservation; Genetics & Heredity GA AG8MB UT WOS:000335671500011 ER PT J AU Shui, IM Lindstrom, S Kibel, AS Berndt, SI Campa, D Gerke, T Penney, KL Albanes, D Berg, C Bueno-de-Mesquita, HB Chanock, S Crawford, ED Diver, WR Gapstur, SM Gaziano, JM Giles, GG Henderson, B Hoover, R Johansson, M Le Marchand, L Ma, J Navarro, C Overvad, K Schumacher, FR Severi, G Siddiq, A Stampfer, M Stevens, VL Travis, RC Trichopoulos, D Vineis, P Mucci, LA Yeager, M Giovannucci, E Kraft, P AF Shui, Irene M. Lindstroem, Sara Kibel, Adam S. Berndt, Sonja I. Campa, Daniele Gerke, Travis Penney, Kathryn L. Albanes, Demetrius Berg, Christine Bueno-de-Mesquita, H. Bas Chanock, Stephen Crawford, E. David Diver, W. Ryan Gapstur, Susan M. Gaziano, J. Michael Giles, Graham G. Henderson, Brian Hoover, Robert Johansson, Mattias Le Marchand, Loic Ma, Jing Navarro, Carmen Overvad, Kim Schumacher, Fredrick R. Severi, Gianluca Siddiq, Afshan Stampfer, Meir Stevens, Victoria L. Travis, Ruth C. Trichopoulos, Dimitrios Vineis, Paolo Mucci, Lorelei A. Yeager, Meredith Giovannucci, Edward Kraft, Peter TI Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium SO EUROPEAN UROLOGY LA English DT Article DE Prostate cancer; Risk single nucleotide polymorphisms; Prostate cancer mortality; Genetic epidemiology ID GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; MORTALITY; LOCI; SUSCEPTIBILITY; DISEASE; DEATH; 8Q24; MEN AB Background: Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM). Objective: To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM. Design, setting, and participants: We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred. Outcome measurements and statistical analysis: The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls. Results and limitations: Among the cases, we found that 8 of the 47 SNPs were significantly associated (p < 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p < 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only. Conclusions: Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa. Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Shui, Irene M.; Lindstroem, Sara; Gerke, Travis; Penney, Kathryn L.; Gaziano, J. Michael; Ma, Jing; Stampfer, Meir; Trichopoulos, Dimitrios; Mucci, Lorelei A.; Giovannucci, Edward; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kibel, Adam S.] Brigham & Womens Hosp, Dept Surg, Div Urol, Boston, MA 02115 USA. [Kibel, Adam S.; Penney, Kathryn L.; Ma, Jing; Stampfer, Meir] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Berndt, Sonja I.; Albanes, Demetrius; Chanock, Stephen; Hoover, Robert; Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Campa, Daniele] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany. [Penney, Kathryn L.; Ma, Jing; Stampfer, Meir] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Berg, Christine] Johns Hopkins Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Chanock, Stephen; Yeager, Meredith] Frederick Natl Lab Canc Res, Canc Genom Res Lab, Gaithersburg, MD USA. [Crawford, E. David] Univ Colorado, Denver, CO 80202 USA. [Diver, W. Ryan; Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Gaziano, J. Michael] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia. [Henderson, Brian; Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France. [Johansson, Mattias] Umea Univ, Dept Biobank Res, Umea, Sweden. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Navarro, Carmen] Murcia Reg Hlth Author, Dept Epidemiol, Murcia, Spain. [Navarro, Carmen] Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain. [Overvad, Kim] Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark. [Severi, Gianluca] HuGeF Fdn, Turin, Italy. [Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London, England. [Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece. [Bueno-de-Mesquita, H. Bas; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England. RP Shui, IM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM ishui@hsph.harvard.edu RI Albanes, Demetrius/B-9749-2015; Campa, Daniele/K-1617-2016; OI Campa, Daniele/0000-0003-3220-9944; Giles, Graham/0000-0003-4946-9099 FU NIH NCI [U19 CA148537-01]; American Cancer Society; NCI [5U01CA098710]; Danish Cancer Society; Hellenic Health Foundation; Health Research Fund; regional government of Andalucia; regional government of Asturias; regional government of Basque Country; regional government of Murcia [6236]; Navarra; ISCIII RETIC (Spain) [RD06/0020]; intramural program of the Division of Cancer Epidemiology and Genetics, NCI; Cancer Council Victoria FX This work was supported by the NIH NCI (cooperative agreement U19 CA148537-01). The maintenance of the Cancer Prevention Study II is supported by the American Cancer Society, and genotyping of the CPS-II samples was supported by a grant from the NCI (5U01CA098710). The Danish study Diet, Cancer and Health was funded by the Danish Cancer Society. EPIC-Greece was supported through the Hellenic Health Foundation. EPIC-Spain was supported by Health Research Fund; the regional governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236), and Navarra; and ISCIII RETIC (RD06/0020; Spain). PLCO was supported by the intramural program of the Division of Cancer Epidemiology and Genetics, NCI. The Melbourne Collaborative Cohort Study recruitment was funded and its follow-up supported by Cancer Council Victoria. NR 29 TC 17 Z9 17 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD JUN PY 2014 VL 65 IS 6 BP 1069 EP 1075 DI 10.1016/j.eururo.2013.12.058 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AG4JV UT WOS:000335386700025 PM 24411283 ER PT J AU Ward, MM Guthrie, LC Alba, M AF Ward, Michael M. Guthrie, Lori C. Alba, Maria TI Dependence of the minimal clinically important improvement on the baseline value is a consequence of floor and ceiling effects and not different expectations by patients SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Minimal clinically important difference; Responsiveness; Ceiling effect; Floor effect; Outcome measures; Rheumatoid arthritis ID LOW-BACK-PAIN; VISUAL ANALOG SCALE; QUALITY-OF-LIFE; HEALTH-STATUS MEASURES; RHEUMATOID-ARTHRITIS; REPORTED OUTCOMES; INTENSITY; QUESTIONNAIRE; MEANINGFUL; SENSITIVITY AB Objective: Estimates of minimal clinically important improvements (MCIIs) are larger among patients with higher values at baseline, suggesting that these patients require larger changes to appreciate improvements. We examined if baseline dependency of MCIIs was associated with specific patients across three measures, or was owing to floor and ceiling effects. Study Design and Setting: We prospectively examined 250 outpatients with active rheumatoid arthritis (RA). We used an anchor-based approach to estimate MCIIs for three measures of RA activity (patient global assessment, swollen joint count, and walking time). We examined if the same patients constituted the baseline subgroups with high MOTs across measures. Results: The MCIIs were greater for those with higher baseline values of all three measures. At the ceiling, there was little opportunity to improve, and judgments were unrelated to measured changes. At midrange, improvements were balanced by worsenings, including some judged as improvements. At the floor, improvements were not similarly balanced. Patients in subgroups with high MCII for patient global assessment were not also predominantly in subgroups with high MCII for the swollen joint count or walking time, and vice versa. Conclusion: Variation in MCII by baseline values is because of floor and ceiling effects rather than expectations of particular patients. Published by Elsevier Inc. C1 [Ward, Michael M.; Guthrie, Lori C.; Alba, Maria] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov OI Alba, Maria/0000-0002-2131-6325 FU Intramural Research Program, National Institute of Arthritis; Musculoskeletal and Skin Diseases, National Institutes of Health; U.S. Public Health Service grant [AR45177] FX This study was supported by the Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and U.S. Public Health Service grant AR45177. NR 36 TC 5 Z9 5 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 2014 VL 67 IS 6 BP 689 EP 696 DI 10.1016/j.jclinepi.2013.10.025 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AG7PL UT WOS:000335610000013 PM 24556220 ER PT J AU Ungerleider, LG Galkin, TW Desimone, R Gattass, R AF Ungerleider, Leslie G. Galkin, Thelma W. Desimone, Robert Gattass, Ricardo TI Subcortical Projections of Area V2 in the Macaque SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID SUPERIOR TEMPORAL SULCUS; MONKEY VISUAL-CORTEX; OLD-WORLD MONKEYS; RHESUS-MONKEY; CEBUS MONKEY; CORTICAL PROJECTIONS; INFERIOR PULVINAR; STRIATE CORTEX; MACACA-MULATTA; NEUROCHEMICAL SUBDIVISIONS AB To investigate the subcortical efferent connections of visual area V2, we injected tritiated amino acids under electrophysiological control into 15 V2 sites in 14 macaques. The injection sites included the fovea representation as well as representations ranging from central to far peripheral eccentricities in both the upper and lower visual fields. The results indicated that V2 projects topographically to different portions of the inferior and lateral pulvinar and to the superficial and intermediate layers of the superior colliculus. Within the pulvinar, the V2 projections terminated in fields P1, P2, and P4, with the strongest projection being in P2. Central visual field injections in V2 labeled projection zones in P1 and P2, whereas peripheral field injections labeled P1, P2, and P4. No projections were found in P3. Both central and peripheral field injections in V2 projected topographically to the superficial and intermediate layers of the superior colliculus. Projections from V2 to the pulvinar and the superior colliculus constituted cortical-subcortical loops through which circuits serving spatial attention are activated. C1 [Ungerleider, Leslie G.; Galkin, Thelma W.] NIH, Bethesda, MD 20892 USA. [Desimone, Robert] MIT, Cambridge, MA 02139 USA. [Gattass, Ricardo] Univ Fed Rio de Janeiro, BR-21941 Rio De Janeiro, Brazil. RP Ungerleider, LG (reprint author), Lab Brain & Cognit, NIMH Bldg 10,Room 4C104,10 Ctr Dr, Bethesda, MD 20892 USA. EM ungerlel@mail.nih.gov FU CNPq; FAPERJ; [EY017292] FX We thank Charles G. Gross for his support during several phases of this work, Juliana Soares for her valuable comments on the manuscript, and John N. Sewell III and Joanna Lawrence for their skillful technical assistance. The injections into V2 were made at the Laboratory of Professor Charles Gross in Princeton, in the late 1970s. L. G. U., R. D., and R. G. planned the experiment and placed the injections, and T. W. G. plotted the data. R. G., R. D., and L. G. U. reviewed the data, prepared the illustrations, and wrote the manuscript. R. D. was supported by EY017292, and R. G. was supported by CNPq and FAPERJ. NR 80 TC 4 Z9 4 U1 0 U2 3 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUN PY 2014 VL 26 IS 6 SI SI BP 1220 EP 1233 DI 10.1162/jocn_a_00571 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AG6CM UT WOS:000335506100004 PM 24456395 ER PT J AU De Pisapia, N Serra, M Rigo, P Jager, J Papinutto, N Esposito, G Venuti, P Bornstein, MH AF De Pisapia, Nicola Serra, Mauro Rigo, Paola Jager, Justin Papinutto, Nico Esposito, Gianluca Venuti, Paola Bornstein, Marc H. TI Interpersonal Competence in Young Adulthood and Right Laterality in White Matter SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID DIFFUSION TENSOR TRACTOGRAPHY; MIRROR NEURON SYSTEM; RIGHT-HEMISPHERE; HUMAN BRAIN; SOCIAL COGNITION; EMOTIONAL INTELLIGENCE; LEARNING-DISABILITIES; CONFLICT-RESOLUTION; SPATIAL STATISTICS; CHILDHOOD AB The right hemisphere of the human brain is known to be involved in processes underlying emotion and social cognition. Clinical neuropsychology investigations and brain lesion studies have linked a number of personality and social disorders to abnormal white matter (WM) integrity in the right hemisphere. Here, we tested the hypothesis that interpersonal competencies are associated with integrity of WM tracts in the right hemisphere of healthy young adults. Thirty-one participants underwent diffusion tensor imaging scanning. Fractional anisotropy was used to quantify water diffusion. After the scanning session, participants completed the Adolescent Interpersonal Competence Questionnaire. Fractional anisotropy was subsequently correlated with Adolescent Interpersonal Competence Questionnaire scores using tract-based spatial statistics. Higher interpersonal competencies are related to higher WM integrity in several major tracts of the right hemisphere, in specific the uncinate fasciculus, the cingulum, the forceps minor, the infero-fronto occipital fasciculus, the inferior longitudinal fasciculus, and the superior longitudinal fasciculus. These results provide the first direct analysis of the neuroanatomical basis of interpersonal competencies and young adult self-reported skills in social contexts. C1 [De Pisapia, Nicola; Serra, Mauro; Rigo, Paola; Esposito, Gianluca; Venuti, Paola] Univ Trento, Rovereto, TN, Italy. [Jager, Justin] Arizona State Univ, Tempe, AZ 85287 USA. [Papinutto, Nico] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Esposito, Gianluca] RIKEN Brain Sci Inst, Saitama, Japan. [Bornstein, Marc H.] NIH, US Dept HHS, Bethesda, MD 20892 USA. RP De Pisapia, N (reprint author), Univ Trento, Dept Psychol & Cognit Sci, Rovereto, TN, Italy. EM nicola.depisapia@unitn.it OI De Pisapia, Nicola/0000-0002-1089-8841 FU Intramural Research Program of the NIH, NICHD; Center for Mind/Brain Sciences of the University of Trento (Italy); Department of Psychology and Cognitive Science of the University of Trento (Italy) FX This research was supported by the Intramural Research Program of the NIH, NICHD, by the Center for Mind/Brain Sciences of the University of Trento (Italy), and by the Department of Psychology and Cognitive Science of the University of Trento (Italy). For Charles G. Gross with admiration and affection in equal measure. NR 88 TC 5 Z9 5 U1 2 U2 10 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUN PY 2014 VL 26 IS 6 SI SI BP 1257 EP 1265 DI 10.1162/jocn_a_00534 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AG6CM UT WOS:000335506100006 PM 24345175 ER PT J AU Liu, JT Fan, WW Liu, MH Lin, XD Wang, YB Wang, F Chen, XY Cao, F Liang, JM AF Liu, Junting Fan, Weiwei Liu, Muhan Lin, Xiuduan Wang, Yabin Wang, Fu Chen, Xiaoyuan Cao, Feng Liang, Jimin TI Spatial Vascular Volume Fraction Imaging for Quantitative Assessment of Angiogenesis SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Angiogenesis; Mesenchymal stem cells; SVVF; Quantitative assessment; Hybrid micro-CTA/BLT ID MESENCHYMAL STEM-CELLS; IN-VIVO; BIOLUMINESCENCE TOMOGRAPHY; STROMAL CELLS; BONE-MARROW; MICE; PERFUSION; ISCHEMIA; PROLIFERATION; REGENERATION AB The purpose of this study is to set up a quantitative imaging strategy for therapeutic angiogenesis and monitoring the spatial distribution and survival of the transplanted mesenchymal stem cells (MSCs) in vivo simultaneously. Mouse adipose-derived MSCs (AD-MSCs) were isolated from firefly luciferase and enhanced green fluorescent protein positive transgenic mice, and implanted intramuscularly into hindlimbs of C57BL/6 mice. Serial spatial vascular volume fraction (SVVF) imaging was performed to quantitatively assess angiogenesis by calculating the spatially explicit vascular volume. The hybrid microcomputed tomography angiography/bioluminescence tomography (micro-CTA/BLT) was used to track the fate of AD-MSCs in vivo. Laser Doppler perfusion imaging (LDPI) was used to evaluate blood perfusion. Ex vivo conventional methods were performed to cross-validate the therapeutic angiogenesis. There was a linear correlation relation between the cell number and Fluc/Fluc protein signal intensity in AD-MSCs via BLT. LDPI showed improved perfusion rate in mice treated with cytotherapy, compared to control mice. Furthermore, angiogenesis assessed by SVVF was 10.67 +/- 0.41 %, 13.99 +/- 0.28 %, and 23.50 +/- 1.23 % on days 7, 14, and 28 post-transplantation of AD-MSCs, respectively. Vascular densities of the longitudinally monitored ischemic hindlimbs were significantly higher than those at early time points and controls, which was also confirmed by vascular corrosion casting, scanning electron microscopic imaging, and histological analysis. Hybrid high-resolution micro-CTA/BLT enabled monitoring and quantitative assessment of cytotherapeutically induced angiogenesis in vivo. C1 [Liu, Junting; Liu, Muhan; Lin, Xiuduan; Wang, Fu; Liang, Jimin] Xidian Univ, Sch Life Sci & Technol, Xian 710071, Peoples R China. [Fan, Weiwei; Wang, Yabin; Cao, Feng] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiol, Xian 710032, Peoples R China. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Cao, F (reprint author), Fourth Mil Med Univ, Xijing Hosp, Dept Cardiol, 127 West Changle Rd, Xian 710032, Peoples R China. EM wind8828@gmail.com; jiminliang@gmail.com RI Liu, Junting/F-3550-2010; Liang, Jimin/B-5394-2014; OI Liu, Junting/0000-0002-2099-0190; Wang, Fu/0000-0001-9222-0833 FU National Basic Research and Development Program of China (973 program) [2011CB707702, 2013CB733802]; National Nature Science Foundation of China [81227901, 81090270, 81090272, 81090274, 31371006]; Ministry of Science and Technology of China (863 program) [2012AA02A603]; National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX We would like to thank Dr. Robert Gillies from Moffitt Cancer Center and Research Institute for scientific insight. This work was supported in part by the National Basic Research and Development Program of China (973 program nos. 2011CB707702 and 2013CB733802), the National Nature Science Foundation of China (81227901, 81090270, 81090272, 81090274, and 31371006), the Ministry of Science and Technology of China (863 program 2012AA02A603), and the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 35 TC 1 Z9 1 U1 0 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JUN PY 2014 VL 16 IS 3 BP 362 EP 371 DI 10.1007/s11307-013-0694-z PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG9JH UT WOS:000335734900008 PM 24158404 ER PT J AU Peterson, LM Kurland, BF Schubert, EK Link, JM Gadi, VK Specht, JM Eary, JF Porter, P Shankar, LK Mankoff, DA Linden, HM AF Peterson, Lanell M. Kurland, Brenda F. Schubert, Erin K. Link, Jeanne M. Gadi, V. K. Specht, Jennifer M. Eary, Janet F. Porter, Peggy Shankar, Lalitha K. Mankoff, David A. Linden, Hannah M. TI A Phase 2 Study of 16 alpha-[F-18]-fluoro-17 beta-estradiol Positron Emission Tomography (FES-PET) as a Marker of Hormone Sensitivity in Metastatic Breast Cancer (MBC) SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE FES-PET; FDG-PET; Metastatic breast cancer; ER expression; Endocrine therapy; Response ID ESTROGEN-RECEPTOR STATUS; FDG-PET; SYSTEMIC THERAPY; AFRICAN-AMERICAN; SOLID TUMORS; EXPRESSION; WOMEN; F-18-FLUOROESTRADIOL; FLUOROESTRADIOL; SURVIVAL AB 16 alpha-[F-18]-fluoro-17 beta-estradiol positron emission tomography (FES-PET) quantifies estrogen receptor (ER) expression in tumors and may provide diagnostic benefit. Women with newly diagnosed metastatic breast cancer (MBC) from an ER-positive primary tumor were imaged before starting endocrine therapy. FES uptake was evaluated qualitatively and quantitatively, and associated with response and with ER expression. Nineteen patients underwent FES imaging. Fifteen had a biopsy of a metastasis and 15 were evaluable for response. Five patients had quantitatively low FES uptake, six had at least one site of qualitatively FES-negative disease. All patients with an ER-negative biopsy had both low uptake and at least one site of FES-negative disease. Of response-evaluable patients, 2/2 with low FES standard uptake value tumors had progressive disease within 6 months, as did 2/3 with qualitatively FES-negative tumors. Low/absent FES uptake correlates with lack of ER expression. FES-positron emission tomography can help identify patients with endocrine resistant disease and safely measures ER in MBC. C1 [Peterson, Lanell M.; Schubert, Erin K.; Gadi, V. K.; Specht, Jennifer M.; Mankoff, David A.; Linden, Hannah M.] Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Kurland, Brenda F.; Gadi, V. K.; Specht, Jennifer M.; Porter, Peggy; Linden, Hannah M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Kurland, Brenda F.] Univ Pittsburgh, Pittsburgh, PA USA. [Schubert, Erin K.; Mankoff, David A.] Univ Penn, Philadelphia, PA 19104 USA. [Link, Jeanne M.; Eary, Janet F.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Shankar, Lalitha K.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA. RP Peterson, LM (reprint author), Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA. EM lanell@uw.edu OI Specht, Jennifer/0000-0003-1484-2113 FU NCI [N01-CM-37008, 8052]; UPCI Biostatistics Shared Resource [P30CA047904] FX The authors would like to thank Eunice How, the radiochemistry staff, nuclear medicine technologists, and physicists in the UW Department of Radiology as well as the staff of the Fred Hutchinson Breast Cancer Research Center Cancer Biology lab. This study was sponsored by the NCI Phase I and II Cancer Imaging Program (Contract #N01-CM-37008, Protocol 8052) and was supported by the UPCI Biostatistics Shared Resource (P30CA047904). NR 35 TC 25 Z9 25 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JUN PY 2014 VL 16 IS 3 BP 431 EP 440 DI 10.1007/s11307-013-0699-7 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG9JH UT WOS:000335734900015 PM 24170452 ER PT J AU Zhang, W Yan, ZF Gao, JH Sun, L Huang, XY Liu, Z Yu, SY Cao, CJ Zuo, LJ Chen, ZJ Hu, Y Wang, F Hong, JS Wang, XM AF Zhang, Wei Yan, Zhao-fen Gao, Jun-hua Sun, Li Huang, Xi-yan Liu, Zhuo Yu, Shu-yang Cao, Chen-Jie Zuo, Li-jun Chen, Ze-Jie Hu, Yang Wang, Fang Hong, Jau-shyong Wang, Xiao-min TI Role and Mechanism of Microglial Activation in Iron-Induced Selective and Progressive Dopaminergic Neurodegeneration SO MOLECULAR NEUROBIOLOGY LA English DT Article DE Dopaminergic neurodegeneration; Iron; Microglial activation; Neuroinflammation; beta-nicotinamide adenine dinucleotide phosphate oxidase 2; Parkinson's disease; Mechanism ID PROTEIN-KINASE-C; PARKINSONS-DISEASE; NADPH OXIDASE; OXIDATIVE STRESS; ALPHA-SYNUCLEIN; HUMAN MONOCYTES; LEWY BODIES; CELL-DEATH; METABOLISM; BRAIN AB Parkinson's disease (PD) patients have excessive iron depositions in substantia nigra (SN). Neuroinflammation characterized by microglial activation is pivotal for dopaminergic neurodegeneration in PD. However, the role and mechanism of microglial activation in iron-induced dopaminergic neurodegeneration in SN remain unclear yet. This study aimed to investigate the role and mechanism of microglial beta-nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) activation in iron-induced selective and progressive dopaminergic neurodegeneration. Multiple primary midbrain cultures from rat, NOX2(+/+) and NOX2(-/-) mice were used. Dopaminergic neurons, total neurons, and microglia were visualized by immunostainings. Cell viability was measured by MTT assay. Superoxide (O-2(center dot-)) and intracellular reactive oxygen species (iROS) were determined by measuring SOD-inhibitable reduction of tetrazolium salt WST-1 and DCFH-DA assay. mRNA and protein were detected by real-time PCR and Western blot. Iron induces selective and progressive dopaminergic neurotoxicity in rat neuron-microglia-astroglia cultures and microglial activation potentiates the neurotoxicity. Activated microglia produce a magnitude of O-2(center dot-) and iROS, and display morphological alteration. NOX2 inhibitor diphenylene iodonium protects against iron-elicited dopaminergic neurotoxicity through decreasing microglial O-2(center dot-) generation, and NOX2(-/-) mice are resistant to the neurotoxicity by reducing microglial O-2(center dot-) production, indicating that iron-elicited dopaminergic neurotoxicity is dependent of NOX2, a O-2(center dot-)-generating enzyme. NOX2 activation is indicated by the increased mRNA and protein levels of subunits P47 and gp91. Molecules relevant to NOX2 activation include PKC-sigma, P38, ERK1/2, JNK, and NF-KBP65 as their mRNA and protein levels are enhanced by NOX2 activation. Iron causes selective and progressive dopaminergic neurodegeneration, and microglial NOX2 activation potentiates the neurotoxicity. PKC-sigma, P38, ERK1/2, JNK, and NF-KBP65 are the potential molecules relevant to microglial NOX2 activation. C1 [Zhang, Wei; Yan, Zhao-fen; Gao, Jun-hua; Sun, Li; Huang, Xi-yan; Liu, Zhuo; Yu, Shu-yang; Cao, Chen-Jie; Zuo, Li-jun; Chen, Ze-Jie; Hu, Yang; Wang, Fang] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing 100050, Peoples R China. [Zhang, Wei] Beijing Inst Brain Disorders, Parkinsons Dis Ctr, Beijing 100053, Peoples R China. [Zhang, Wei] Beijing Key Lab Parkinsons Dis, Beijing 100053, Peoples R China. [Hong, Jau-shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Wang, Xiao-min] Capital Med Univ, Dept Physiol, Beijing 100069, Peoples R China. [Wang, Xiao-min] Capital Med Univ, Dept Neurobiol, Beijing 100069, Peoples R China. [Wang, Xiao-min] Minist Educ, Key Lab Neurodegenerat Disorders, Beijing 100069, Peoples R China. [Wang, Xiao-min] Beijing Inst Brain Disorders, Beijing 100069, Peoples R China. RP Zhang, W (reprint author), Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing 100050, Peoples R China. EM ttyyzw@163.com FU National Basic Research Program of China [2011CB504100]; National Natural Science Foundation of China [81071015, 30770745, 81030062]; Natural Science Foundation of Beijing, China [7082032]; High Level Technical Personnel Training Project of Beijing Health System, China [2009-3-26]; Excel lent Personnel Training Project of Beijing, China [20071D0300400076]; Capital Clinical Characteristic Application Research Project [Z121107001012161]; Important National Science and Technology Specific Project [2011ZX09102-003-01]; Beijing Natural Science Foundation [kz200910025001]; Basic-Clinical Research Cooperation Funding of Capital Medical University [10JL49] FX This work is supported by the National Basic Research Program of China (2011CB504100); the National Natural Science Foundation of China (81071015, 30770745, and 81030062), the Natural Science Foundation of Beijing, China (7082032), High Level Technical Personnel Training Project of Beijing Health System, China (2009-3-26), Excel lent Personnel Training Project of Beijing, China (20071D0300400076), Capital Clinical Characteristic Application Research (Z121107001012161), Important National Science and Technology Specific Projects ( 2011ZX09102-003-01), Key Project of Beijing Natural Science Foundation (kz200910025001), and Basic-Clinical Research Cooperation Funding of Capital Medical University (10JL49). We thank Dr. Yang Du for her efforts of editing the manuscript. NR 58 TC 13 Z9 14 U1 2 U2 13 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 EI 1559-1182 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD JUN PY 2014 VL 49 IS 3 BP 1153 EP 1165 DI 10.1007/s12035-013-8586-4 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AG8KE UT WOS:000335666500004 PM 24277523 ER PT J AU Choi, K Forster, JL AF Choi, Kelvin Forster, Jean L. TI Context on Use Is Needed Before Public Health Recommendations Are Made About E-Cigarettes Response SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Letter C1 [Choi, Kelvin] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, Bethesda, MD USA. [Forster, Jean L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Choi, K (reprint author), Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, Bethesda, MD USA. RI Choi, Kelvin/H-1544-2015 NR 5 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2014 VL 46 IS 6 BP E58 EP E59 DI 10.1016/j.amepre.2014.02.013 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA V43UN UT WOS:000209706400004 PM 24842747 ER PT J AU Renvoise, B Chang, J Singh, R Yonekawa, S FitzGibbon, EJ Mankodi, A Vanderver, A Schindler, AB Toro, C Gahl, WA Mahuran, DJ Blackstone, C Pierson, TM AF Renvoise, Benoit Chang, Jaerak Singh, Rajat Yonekawa, Sayuri FitzGibbon, Edmond J. Mankodi, Ami Vanderver, Adeline Schindler, Alice B. Toro, Camilo Gahl, William A. Mahuran, Don J. Blackstone, Craig Pierson, Tyler Mark TI Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11 SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article AB Objective: Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to earlyonset parkinsonism. Methods: We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes. Results: Fibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent. Interpretation: Emerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26-/- mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction. C1 [Renvoise, Benoit; Chang, Jaerak; Singh, Rajat; Mankodi, Ami; Schindler, Alice B.; Blackstone, Craig; Pierson, Tyler Mark] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Yonekawa, Sayuri; Mahuran, Don J.] Hosp Sick Children, Res Inst, Toronto, ON, Canada. [Yonekawa, Sayuri; Mahuran, Don J.] Univ Toronto, Toronto, ON, Canada. [FitzGibbon, Edmond J.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. [Vanderver, Adeline] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Toro, Camilo; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Toro, Camilo; Gahl, William A.] NIH, Undiagnosed Dis Program, Off Rare Dis Res, Bethesda, MD 20892 USA. [Toro, Camilo; Gahl, William A.] NHGRI, Bethesda, MD 20892 USA. [Pierson, Tyler Mark] Cedars Sinai Med Ctr, Dept Pediat, 8700 Beverly Blvd,ASHP 8401, Los Angeles, CA 90048 USA. [Pierson, Tyler Mark] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA. [Pierson, Tyler Mark] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA. RP Pierson, TM (reprint author), Cedars Sinai Med Ctr, Dept Pediat, 8700 Beverly Blvd,ASHP 8401, Los Angeles, CA 90048 USA. EM tyler.pierson@cshs.org FU Intramural NIH HHS [Z01 NS002992-06, Z01 NS002992-07] NR 32 TC 15 Z9 15 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD JUN PY 2014 VL 1 IS 6 BP 379 EP 389 DI 10.1002/acn3.64 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V45KI UT WOS:000209815100001 PM 24999486 ER PT J AU Adeyemo, MA McDuffie, JR Brady, S Condarco, TA Garcia, RM Hubbard, VS Yanovski, JA AF Adeyemo, Mopelola Adetola McDuffie, Jennifer R. Brady, Sheila Condarco, Tania Andrea Garcia, Rubi Maricela Hubbard, Van S. Yanovski, Jack A. TI Effect of Orlistat on Ratings of Fat-Containing Foods Among Obese Adolescents SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Adeyemo, Mopelola Adetola; Garcia, Rubi Maricela; Yanovski, Jack A.] NIH, Bethesda, MD 20892 USA. [McDuffie, Jennifer R.; Brady, Sheila; Condarco, Tania Andrea] NICHD, NIH, Bethesda, MD USA. [Hubbard, Van S.] NIH, DNRC, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0938 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103170 ER PT J AU Agarwal, N Iyer, D Oplt, T Shenoy, A Schubert, U Kopp, JB Balasubramanyam, A AF Agarwal, Neeti Iyer, Dinakar Oplt, Toni Shenoy, Akhil Schubert, Ulrich Kopp, Jeffrey B. Balasubramanyam, Ashok TI Mechanism of HIV-Associated Hepatic Steatosis: Role of HIV-1 Accessory Protein Vpr, Pparalpha and Lxralpha SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Agarwal, Neeti; Iyer, Dinakar; Oplt, Toni; Shenoy, Akhil; Balasubramanyam, Ashok] Baylor Coll Med, Houston, TX 77030 USA. [Schubert, Ulrich] Univ Erlangen Nurnberg, Erlangen, Germany. [Kopp, Jeffrey B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR21-2 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102266 ER PT J AU Allison, MB Patterson, CM Krashes, M Lowell, BB Olson, DP Myers, MG AF Allison, Margaret B. Patterson, Christa M. Krashes, Michael Lowell, Bradford Barr Olson, David P. Myers, Martin Grosvenor TI Translational Profiling Reveals the Transcriptome of Hypothalamic Leptin Receptor Neurons and Its Regulation By Leptin SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Allison, Margaret B.; Patterson, Christa M.; Olson, David P.; Myers, Martin Grosvenor] Univ Michigan, Ann Arbor, MI 48109 USA. [Krashes, Michael] NIDDK, NIH, Bethesda, MD 20892 USA. [Lowell, Bradford Barr] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR45-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103151 ER PT J AU Alwazeer, MR Olutoye, O Margolin, JF Castro, E Williams, J Quezado, MM Lodish, MB Stratakis, CA Balazs, AE AF Alwazeer, Mouhammad Rateb Olutoye, Oluyinka Margolin, Judith F. Castro, Eumenia Williams, Jennifer Quezado, Martha M. Lodish, Maya Beth Stratakis, Constantine A. Balazs, Andrea Erika TI Cushing Syndrome Secondary to Bronchial Carcinoid Tumor in a 14-Year- Old Female: Challenges in Diagnosis and Treatment SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Alwazeer, Mouhammad Rateb] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Olutoye, Oluyinka; Margolin, Judith F.; Castro, Eumenia; Williams, Jennifer; Balazs, Andrea Erika] Baylor Coll Med, Houston, TX 77030 USA. [Quezado, Martha M.] NCI, Bethesda, MD 20892 USA. [Lodish, Maya Beth; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0136 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103280 ER PT J AU Arduc, A Yavuz, S Linderman, JD Smith, S Eliseeva, E Neumann, SE Celi, FS AF Arduc, Ayse Yavuz, Sahzene Linderman, Joyce D. Smith, Sheila Eliseeva, Elena Neumann, Susanne E. Celi, Francesco S. TI Impaired Thyrotroph Dynamics during Thyroid Hormone Withdrawal in a Patient with Differentiated Thyroid Cancer and Underlying Graves' Disease SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Arduc, Ayse] NIDDKD, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD 20892 USA. [Yavuz, Sahzene] Univ Florida, Gainesville, FL 32611 USA. [Linderman, Joyce D.; Smith, Sheila] NIDDK, Diabet Endocrinol Obes Branch, NIH, Bethesda, MD 20892 USA. [Eliseeva, Elena; Neumann, Susanne E.] NIDDK, NIH, Bethesda, MD 20892 USA. [Celi, Francesco S.] Virginia Commonwealth Univ, Richmond, VA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0497 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108237 ER PT J AU Bernhardt, ML Williams, CJ AF Bernhardt, Miranda L. Williams, Carmen J. TI Normal Fertilization Is Observed in Oocyte-Specific Stiml Knockout Mice SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Bernhardt, Miranda L.; Williams, Carmen J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0055 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109314 ER PT J AU Beuschlein, F Fassnacht, M Assie, G Calebiro, D Stratakis, CA Osswald, A Ronchi, CL Wielanda, T Sbiera, S Faucz, FR Schaak, K Schmittfull, A Schwarzmayr, T Barreau, O Vezzosi, D Rizk-Rabbin, M Zabel, U Szarek, E Salpea, P Forlino, A Vetro, A Zuffardi, O Kisker, C Diener, S Meitinger, T Lohse, M Reincke, M Bertherat, JY Strom, TM Allolio, B AF Beuschlein, Felix Fassnacht, Martin Assie, Guillaume Calebiro, Davide Stratakis, Constantine A. Osswald, Andrea Ronchi, Cristina Lucia Wielanda, Thomas Sbiera, Silviu Faucz, Fabio Rueda Schaak, Kathrin Schmittfull, Anett Schwarzmayr, Thomas Barreau, Olivia Vezzosi, Delphine Rizk-Rabbin, Marthe Zabel, Ulrike Szarek, Eva Salpea, Paraskevi Forlino, Antonella Vetro, Annalisa Zuffardi, Orsetta Kisker, Caroline Diener, Susanne Meitinger, Thomas Lohse, Martin Reincke, Martin Bertherat, Jerome Yves Strom, Tim M. Allolio, Bruno TI Constitutive Activation of Prkaca in Adrenal Cushing's Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Beuschlein, Felix; Reincke, Martin] Univ Munich, Munich, Germany. [Fassnacht, Martin; Calebiro, Davide; Lohse, Martin; Allolio, Bruno] Univ Wurzburg, Wurzburg, Germany. [Assie, Guillaume; Bertherat, Jerome Yves] Inst Cochin, CNRS, Unite Mixte Rech 8104, INSERM,Unite 1016, Paris, France. [Stratakis, Constantine A.; Faucz, Fabio Rueda; Szarek, Eva; Salpea, Paraskevi] NIH, Bethesda, MD 20892 USA. [Osswald, Andrea] Med Klin & Poliklin IV, Munich, Germany. [Ronchi, Cristina Lucia] Univ Hosp Wuerzburg, Wurzburg, Germany. [Wielanda, Thomas; Diener, Susanne; Meitinger, Thomas; Strom, Tim M.] Helmholtz Zentrum Munchen, Inst Human Genet, Munich, Germany. [Sbiera, Silviu; Schaak, Kathrin] Ludwig Maximilians Univ Munchen, Med Klin & Poliklin 4, Munich, Germany. [Schmittfull, Anett; Schwarzmayr, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany. [Barreau, Olivia] Paris Descartes Univ, Inst Cochin, CNRS 8104, Inserm,U1016, Paris, France. [Vezzosi, Delphine] Hosp Rangueil, Toulouse, France. [Rizk-Rabbin, Marthe] CNRS, UMR 8104, INSERM, U1016, Paris, France. [Zabel, Ulrike] Univ Wurzburg, Inst Pharmacol & Toxicol, Wurzburg, Germany. [Forlino, Antonella; Vetro, Annalisa; Zuffardi, Orsetta] Univ Pavia, Pavia, Italy. [Kisker, Caroline] Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, Wurzburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR14-3 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102237 ER PT J AU Beverly, BEJ Lambright, C Furr, J Sampson, H Travlos, G Foster, PM McIntyre, B Wilson, V Gray, LE AF Beverly, Brandiese E. J. Lambright, Christy Furr, Johnathan Sampson, Hunter Travlos, Gregory Foster, Paul M. McIntyre, Barry Wilson, Vickie Gray, L. Earl TI Simvastatin and Dipentyl Phthalate Display Different Modes of Action but Exhibit Dose Additive Effects on Fetal Testicular Testosterone Production in Sprague Dawley Rats SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Beverly, Brandiese E. J.; Lambright, Christy; Furr, Johnathan; Sampson, Hunter; Wilson, Vickie; Gray, L. Earl] US EPA, Washington, DC 20460 USA. [Travlos, Gregory; Foster, Paul M.; McIntyre, Barry] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR18-4 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100158 ER PT J AU Bram, Z Louiset, E Ragazzon, B Renouf, S Risk-Rabin, M Libe, R Young, J Vantyghem, MC Martinez, A Stratakis, CA Bertherat, JY Lefebvre, H AF Bram, Zakariae Louiset, Estelle Ragazzon, Bruno Renouf, Sylvie Risk-Rabin, Marthe Libe, Rossella Young, Jacques Vantyghem, Marie-Christine Martinez, Antoine Stratakis, Constantine A. Bertherat, Jerome Yves Lefebvre, Herve TI Role of Sp1 in cAMP-Dependent Transcriptional Regulation of the Serotonergic Signaling Pathway in Primary Pigmented Nodular Adrenal Disease (PPNAD) Tissues Associated with Cushing's Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Bram, Zakariae; Louiset, Estelle; Renouf, Sylvie] Univ Rouen, Inst Biomed Res & Innovat, U982, INSERM, Mont St Aignan, France. [Ragazzon, Bruno; Libe, Rossella; Bertherat, Jerome Yves] CNRS, UMR 8104, Inst Cochin, INSERM,Unite 1016, Paris, France. [Risk-Rabin, Marthe] Univ Paris 05, Cochin Inst, U1016, INSERM, Paris, France. [Young, Jacques] Univ Paris 11, Dept Endocrinol, Bicetre Hosp, INSERM,U693, Le Kremlin Bicetre, France. [Vantyghem, Marie-Christine] Univ Lille 2, INSERM, Lille Reg Univ Hosp, Dept Endocrinol,U859, Lille, France. [Martinez, Antoine] Clermont Univ, CNRS, UMR6247, INSERM,U931,Gred, Aubiere, France. [Stratakis, Constantine A.] NICHHD, NIH, Bethesda, MA USA. [Lefebvre, Herve] Univ Hosp Rouen, Inst Biomed Res & Innovat, Rouen, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0774 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103095 ER PT J AU Bram, Z Wils, J Ragazzon, B Risk-Rabin, M Libe, R Young, J Vantyghem, MC Martinez, A Stratakis, CA Bertherat, JY Lefebvre, H Louiset, E AF Bram, Zakariae Wils, Julien Ragazzon, Bruno Risk-Rabin, Marthe Libe, Rossella Young, Jacques Vantyghem, Marie-Christine Martinez, Antoine Stratakis, Constantine A. Bertherat, Jerome Yves Lefebvre, Herve Louiset, Estelle TI beta-Estradiol (E2) Stimulates Cortisol Secretion in Primary Pigmented Nodular Adrenal Disease: An Explanation for the Increased Frequency of Cushing's Syndrome in Female Patients with Carney Complex SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Bram, Zakariae; Wils, Julien; Louiset, Estelle] Univ Rouen, Inst Biomed Res & Innovat, INSERM, U982, Mont St Aignan, France. [Ragazzon, Bruno; Libe, Rossella; Bertherat, Jerome Yves] Inst Cochin, CNRS, INSERM, Unite 1016,Unite Mixte Rech 8104, Paris, France. [Risk-Rabin, Marthe] Univ Paris V, Cochin Inst, INSERM, U1016, Paris, France. [Young, Jacques] Univ Paris Sud, Dept Endocrinol, Bicetre Hosp, INSERM,U693, Le Kremlin Bicetre, France. [Vantyghem, Marie-Christine] Lille2 Univ, INSERM, U859, Dept Endocrinol,Lille Reg Univ Hosp, Lille, France. [Martinez, Antoine] Clermont Univ, Gred, INSERM, U931,CNRS,UMR6247, Aubiere, France. [Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Lefebvre, Herve] Univ Hosp Rouen, Inst Biomed Res & Innovat, Rouen, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR14-2 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102227 ER PT J AU Brand, MR Milford, E Pelch, K Bromfield, J Nagel, SC AF Brand, Mayah Rose Milford, Emily Pelch, Katie Bromfield, John Nagel, Susan Carol TI Perinatal Exposure to Xenoestrogens Alters Adult Mammary Gland Histoarchitecture in the Mouse SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Brand, Mayah Rose; Bromfield, John] Univ Missouri, Columbia, MO USA. [Milford, Emily] Univer Missouri Columbia, Columbia, MO USA. [Pelch, Katie] NIEHS, Res Triangle Pk, NC 27709 USA. [Nagel, Susan Carol] Univ MO Columbia, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0366 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100185 ER PT J AU Cauley, JA Fluharty, L Ellenberg, S Gill, TM Ensrud, KE Barrett-Connor, EL Cifelli, D Cunningham, GR Matsumoto, AM Bhasin, S Pahor, M Farrar, JT Cella, D Rosen, RC Resnick, SM Swerdloff, RS Lewis, CE Molitch, ME Crandall, JP Stephens, A Wang, C Romashkan, S Hadley, E Snyder, PJ AF Cauley, Jane A. Fluharty, Laura Ellenberg, Susan Gill, Thomas M. Ensrud, Kristine E. Barrett-Connor, Elizabeth Louise Cifelli, Denise Cunningham, Glenn R. Matsumoto, Alvin M. Bhasin, Shalender Pahor, Marco Farrar, John T. Cella, David Rosen, Raymond C. Resnick, Susan M. Swerdloff, Ronald S. Lewis, Cora E. Molitch, Mark E. Crandall, Jill P. Stephens, Alisa Wang, Christina Romashkan, Sergei Hadley, Evan Snyder, Peter J. TI Screening and Recruitment for the Testosterone Trials (TTrials) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Cauley, Jane A.] Univ Pittsburgh, Pittsburgh, PA USA. [Fluharty, Laura; Cifelli, Denise] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ellenberg, Susan] Univ Penn, Sch Me, Philadelphia, PA 19104 USA. [Gill, Thomas M.] Yale Sch Med, New Haven, CT USA. [Ensrud, Kristine E.] Univ Minnesota, Minneapolis, MN USA. [Barrett-Connor, Elizabeth Louise] Univ Calif San Diego, La Jolla, CA 92093 USA. [Cunningham, Glenn R.] Baylor Coll Med, Houston, TX 77030 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Sys, Seattle, WA USA. [Bhasin, Shalender] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Pahor, Marco] Univ Florida, Gainesville, FL USA. [Farrar, John T.; Stephens, Alisa] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Cella, David] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. [Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA. [Resnick, Susan M.; Romashkan, Sergei; Hadley, Evan] NIA, Baltimore, MD 21224 USA. [Swerdloff, Ronald S.; Wang, Christina] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Swerdloff, Ronald S.; Wang, Christina] Los Angeles Biomed Res Inst, Torrance, CA USA. [Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA. [Molitch, Mark E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Snyder, Peter J.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0096 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107212 ER PT J AU Cedars, MI Mumford, S Steiner, AZ Casson, PR Coutifaris, C Diamond, MP Christman, GM Schlaff, WD Alvero, R Huang, H Santoro, N Eisenberg, E Legro, RS Zhang, HP AF Cedars, Marcelle Ivonne Mumford, Sunni Steiner, Anne Z. Casson, Peter Raymond Coutifaris, Christos Diamond, Michael P. Christman, Gregory M. Schlaff, Wlliam D. Alvero, Ruben Huang, Hao Santoro, Nanette Eisenberg, Esther Legro, Richard S. Zhang, Heping CA Reproductive Med Network TI Impact of AMH Level on Chances for Ovulation in Pregnancy in Polycystic Ovary Syndrome II, a Multi-Center Randomized Clinical Trial SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Cedars, Marcelle Ivonne] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mumford, Sunni] NICHD, NIH, Bethesda, MD USA. [Steiner, Anne Z.] Univ N Carolina, Chapel Hill, NC USA. [Casson, Peter Raymond] Univ Vermont, Burlington, VT USA. [Coutifaris, Christos] Hosp Univ PA, Philadelphia, PA USA. [Diamond, Michael P.] Wayne State Univ, Grosse Pointe Shores, MI USA. [Christman, Gregory M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Schlaff, Wlliam D.] Jefferson Univ, Philadelphia, PA USA. [Alvero, Ruben; Santoro, Nanette] Univ Colorado Denver, Aurora, CO USA. [Huang, Hao] Yale Univ, Sch Med, New Haven, CT USA. [Eisenberg, Esther] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Legro, Richard S.] Penn State Univ, Hershey, PA USA. [Zhang, Heping] Yale Univ, New Haven, CT USA. [Reproductive Med Network] NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR04-4 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104220 ER PT J AU Chia, CW Egan, JM AF Chia, Chee Wei Egan, Josephine Mary TI Fungiform Papillae Density Is Associated with Age and Markers of Glucose Metabolism in the Baltimore Longitudinal Study of Aging SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Chia, Chee Wei; Egan, Josephine Mary] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-1005 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106307 ER PT J AU Christensen, JD Lungu, AO Cochran, E Collins, MT Gafni, RI Reynolds, JC Gorden, P Brown, RJ AF Christensen, John D. Lungu, Andreea O. Cochran, Elaine Collins, Michael T. Gafni, Rachel I. Reynolds, James C. Gorden, Phillip Brown, Rebecca J. TI Increased Bone Mineral Content in Patients with Congenital Generalized Lipodystrophy Is Unaffected By Metreleptin Replacement Therapy SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Christensen, John D.; Cochran, Elaine; Gorden, Phillip; Brown, Rebecca J.] NIDDK, NIH, Bethesda, MD USA. [Lungu, Andreea O.] Joslin Diabet Ctr, Brookline, MA USA. [Collins, Michael T.; Gafni, Rachel I.] NIDCR, NIH, Bethesda, MD USA. [Reynolds, James C.] NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR43-6 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105097 ER PT J AU Chrysostomou, P Lodish, MB Turkbey, E Stratakis, CA AF Chrysostomou, Paola Lodish, Maya Beth Turkbey, Evrim Stratakis, Constantine A. TI Use of 3-Dimensional Volumetric Modeling of Adrenal Gland Size in Patients with Primary Pigmented Nodular Adrenocortical Disease SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Chrysostomou, Paola] NICHD, NIH, Bethesda, MD USA. [Lodish, Maya Beth; Turkbey, Evrim; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0775 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103106 ER PT J AU Condarco, TA McDuffie, JR Brady, S Adeyemo, MA Garcia, RM Reynolds, J Hubbard, VS Calis, KA Yanovski, JA AF Condarco, Tania Andrea McDuffie, Jennifer R. Brady, Sheila Adeyemo, Mopelola Adetola Garcia, Rubi Maricela Reynolds, James Hubbard, Van S. Calis, Karim Anton Yanovski, Jack A. TI Differences in Bone Turnover Markers and Bone Mineral Density in African-American and Caucasian Adolescents Taking Orlistat SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Condarco, Tania Andrea; McDuffie, Jennifer R.; Brady, Sheila] NICHD, NIH, Bethesda, MD USA. [Adeyemo, Mopelola Adetola; Garcia, Rubi Maricela; Yanovski, Jack A.] NIH, Bethesda, MD 20892 USA. [Reynolds, James; Calis, Karim Anton] NIH, CC, Bethesda, MD 20892 USA. [Hubbard, Van S.] NIH, DNRC, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0163 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104047 ER PT J AU Correa, RR Lysikatos-Lyssikatos, C Belyayskaya, E Stratakis, CA AF Correa, Ricardo Rafael Lysikatos-Lyssikatos, Charalampos Belyayskaya, Elena Stratakis, Constantine A. TI Atypical Presentation of a Ganglioneuroma SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Correa, Ricardo Rafael] NIH, Rockville, MD USA. [Lysikatos-Lyssikatos, Charalampos; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Belyayskaya, Elena] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0753 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105165 ER PT J AU Cunningham, GR Rosen, RC Wang, C Stephens, A Ellenberg, S Matsumoto, AM Bhasin, S Molitch, ME Farrar, JT Cella, D Gill, TM Barrett-Connor, EL Cauley, JA Cifelli, D Crandall, JP Ensrud, KE Fluharty, L Hadley, E Lewis, CE Pahor, M Resnick, SM Romashkan, S Swerdloff, RS Snyder, PJ AF Cunningham, Glenn R. Rosen, Raymond C. Wang, Christina Stephens, Alisa Ellenberg, Susan Matsumoto, Alvin M. Bhasin, Shalender Molitch, Mark E. Farrar, John T. Cella, David Gill, Thomas M. Barrett-Connor, Elizabeth Louise Cauley, Jane A. Cifelli, Denise Crandall, Jill P. Ensrud, Kristine E. Fluharty, Laura Hadley, Evan Lewis, Cora E. Pahor, Marco Resnick, Susan M. Romashkan, Sergei Swerdloff, Ronald S. Snyder, Peter J. TI Free Testosterone but Not Total Testosterone or Estradiol Is Associated with Sexual Function in Symptomatic Older Hypogonadal Men in the Sexual Function Trial of the Testosterone Trials SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Cunningham, Glenn R.] Baylor Coll Med, Houston, TX 77030 USA. [Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA. [Wang, Christina] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Wang, Christina; Swerdloff, Ronald S.] Los Angeles Biomed Res Inst, Torrance, CA USA. [Stephens, Alisa; Ellenberg, Susan; Farrar, John T.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Bhasin, Shalender] Brigham & Womens Hosp, Boston, MA 02115 USA. [Molitch, Mark E.; Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gill, Thomas M.] Yale Sch Med, New Haven, CT USA. [Barrett-Connor, Elizabeth Louise] Univ CA San Diego, La Jolla, CA USA. [Cauley, Jane A.] Univ Pittsburgh, Pittsburgh, PA USA. [Cifelli, Denise; Fluharty, Laura] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Ensrud, Kristine E.] Univ Minnesota, Minneapolis, MN USA. [Hadley, Evan; Romashkan, Sergei] NIA, Bethesda, MD 20892 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA. [Pahor, Marco] Univ Florida, Gainesville, FL USA. [Resnick, Susan M.] NIA, Baltimore, MD 21224 USA. [Swerdloff, Ronald S.] Harbor Univ Calif Med Ctr, Torrance, CA USA. [Snyder, Peter J.] Univ PA, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0084 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107199 ER PT J AU Del Rivero, J Madan, R Marx, SJ AF Del Rivero, Jaydira Madan, Ritu Marx, Stephen J. TI Uterine Leiomyomas Associated with Multiple Endocrine Neoplasia Type 1 SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Del Rivero, Jaydira] NICHHD, NIH, Bethesda, MD 20892 USA. [Madan, Ritu] NIH, Bethesda, MD 20892 USA. [Marx, Stephen J.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0315 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108079 ER PT J AU Del Rivero, J Zhuang, ZP Yang, CZ Prchal, JT Lechan, RM Tischler, AS Fojo, T Taieb, D Popovic, V Lorenzo, F Young, JA Nambuba, J Adams, KT Jochmanova, I Merino, M Stratakis, CA Kebebew, E Pacak, K AF Del Rivero, Jaydira Zhuang, Zhengping Yang, Chunzhang Prchal, Josef T. Lechan, Ronald M. Tischler, Arthur S. Fojo, Tito Taieb, David Popovic, Vera Lorenzo, Felipe Young, James A. Nambuba, Joan Adams, Karen T. Jochmanova, Ivana Merino, Maria Stratakis, Constantine A. Kebebew, Electron Pacak, Karel TI The NIH Experience of Seven Somatic HIF2A Patients Presenting with Multiple Paragangliomas and/or Duodenal Somatostatinomas Associated with Polycythemia SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Del Rivero, Jaydira; Nambuba, Joan; Adams, Karen T.; Jochmanova, Ivana; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Zhuang, Zhengping; Yang, Chunzhang] NINDS, NIH, Bethesda, MD 20892 USA. [Prchal, Josef T.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Prchal, Josef T.] VAH, Salt Lake City, UT USA. [Lechan, Ronald M.] Tufts Med Ctr, Boston, MA USA. [Tischler, Arthur S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Fojo, Tito; Merino, Maria; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA. [Taieb, David] CHU Timone, Marseille 05, France. [Popovic, Vera] Clin Ctr Serbia, Belgrade, Serbia. [Lorenzo, Felipe] Univ Utah Hlth Sci, Salt Lake City, UT USA. [Young, James A.] Rocky Mt Canc Ctr, Denver, CO USA. [Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0767 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103016 ER PT J AU Del Rivero, J Zhuang, ZP Yang, CZ Prchal, JT Lechan, RM Tischler, AS Fojo, T Taieb, D Popovic, V Lorenzo, F Young, JA Nambuba, J Adams, KT Jochmanova, I Merino, M Stratakis, CA Kebebew, E Pacak, K AF Del Rivero, Jaydira Zhuang, Zhengping Yang, Chunzhang Prchal, Josef T. Lechan, Ronald M. Tischler, Arthur S. Fojo, Tito Taieb, David Popovic, Vera Lorenzo, Felipe Young, James A. Nambuba, Joan Adams, Karen T. Jochmanova, Ivana Merino, Maria Stratakis, Constantine A. Kebebew, Electron Pacak, Karel TI The NIH Experience of Seven Somatic HIF2A Patients Presenting with Multiple Paragangliomas and/or Duodenal Somatostatinomas Associated with Polycythemia SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Del Rivero, Jaydira; Nambuba, Joan; Adams, Karen T.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Zhuang, Zhengping; Yang, Chunzhang] NINDS, NIH, Bethesda, MD 20892 USA. [Prchal, Josef T.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Prchal, Josef T.] VAH, Salt Lake City, UT USA. [Lechan, Ronald M.] Tufts Med Ctr, Boston, MA USA. [Tischler, Arthur S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Fojo, Tito] NCI, NIH, Bethesda, MD 20892 USA. [Taieb, David] CHU Timone, Marseille 05, France. [Popovic, Vera] Clin Ctr Serbia, Belgrade, Serbia. [Lorenzo, Felipe] Univ Utah Hlth Sci, Salt Lake City, UT USA. [Young, James A.] Rocky Mt Canc Ctr, Denver, CO USA. [Jochmanova, Ivana] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Merino, Maria; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP35-4 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102005 ER PT J AU Delaney, A Lalonde, FM Blumenthal, JD Clasen, LS Hicks, RL Denker, AH Giedd, JN Crowley, WF Balasubramanian, R AF Delaney, Angela Lalonde, Francois M. Blumenthal, Jonathan D. Clasen, Liv S. Hicks, Rebecca L. Denker, Alexander H. Giedd, Jay N. Crowley, William F. Balasubramanian, Ravikumar TI Delayed Sex Hormone Exposure during Puberty Is Associated with Differences in Brain Cortical Thickness, Spatial Ability, and Recognition Memory SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Delaney, Angela; Lalonde, Francois M.; Blumenthal, Jonathan D.; Clasen, Liv S.; Hicks, Rebecca L.; Denker, Alexander H.; Giedd, Jay N.] NIH, Bethesda, MD 20892 USA. [Crowley, William F.; Balasubramanian, Ravikumar] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR11-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104109 ER PT J AU Deng, Q Aguilera, G AF Deng, Qiong Aguilera, Greti TI Leucine Repeat 687 to 690 of the Glucocorticoid Receptor (GR) Is Essential for Ligand Binding and GR Interaction with Heat Shock Protein 90 (HSP90) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Deng, Qiong; Aguilera, Greti] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0432 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109297 ER PT J AU Deng, Q Aguilera, G AF Deng, Qiong Aguilera, Greti TI Rapid Glucocorticoid Feedback Inhibition of ACTH Secretion Involves Ligand-Dependent Membrane Association of Glucocorticoid Receptors and Inhibition of Src Phosphorylation SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Deng, Qiong; Aguilera, Greti] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR48-6 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102042 ER PT J AU Desai, SS Modali, SD Parekh, VI Agarwal, SK AF Desai, Shruti S. Modali, Sita D. Parekh, Vaishali I. Agarwal, Sunita K. TI Inhibitory Effect of LiCl Treatment on Pancreatic Islet beta-Cell Tumorigenesis in the Mouse Model of Multiple Endocrine Neoplasia Type 1 SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Desai, Shruti S.; Modali, Sita D.; Parekh, Vaishali I.; Agarwal, Sunita K.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0305 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108068 ER PT J AU Dogan, BA Arduc, A Tuna, MM Imga, NN Isik, S Berker, D Guler, S AF Dogan, Bercem Aycicek Arduc, Ayse Tuna, Mazhar Muslum Imga, Narin Nasiroglu Isik, Serhat Berker, Dilek Guler, Serdar TI Evaluation of Atherosclerosis after Cessation of Cabergoline Therapy in Patients with Prolactinoma: Preliminary Results of a Prospective Cohort Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Dogan, Bercem Aycicek; Tuna, Mazhar Muslum; Imga, Narin Nasiroglu; Berker, Dilek] Ankara Numune Training & Res Hosp, Ankara, Turkey. [Arduc, Ayse] NIDDK, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD 20892 USA. [Isik, Serhat] Ankara Numune Training & Res Hosp, Ankara, Turkey. [Guler, Serdar] Hitit Univ, Fac Med, Corum, Turkey. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0622 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101058 ER PT J AU El-Maouche, D Kaufmann, M Gafni, RI Jones, G Collins, MT AF El-Maouche, Diala Kaufmann, Martin Gafni, Rachel I. Jones, Glenville Collins, Michael T. TI FGF23-Mediated Vitamin D Metabolism in Tumor-Induced Osteomalacia SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [El-Maouche, Diala] NIH, Bethesda, MD 20892 USA. [Kaufmann, Martin; Jones, Glenville] Queens Univ, Kingston, ON, Canada. [Gafni, Rachel I.; Collins, Michael T.] NIDCR, NIH, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR43-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105093 ER PT J AU Escajadillo, T Segars, JH Sewer, MB AF Escajadillo, Tamara Segars, James Hugh Sewer, Marion B. TI Silencing a-Kinase Anchoring Protein Impairs cAMP Signaling and Steroid Hormone Biosynthesis in the Adrenal Cortex SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Escajadillo, Tamara] Calif State Univ Dominguez Hills, Carson, CA 90747 USA. [Segars, James Hugh] NIH, Potomac, MD USA. [Sewer, Marion B.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0410 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102238 ER PT J AU Estrada, A Venkatesan, A Wolfgang, CL Guthrie, L Fishman, EK Kamei, I Ali, SZ Goggins, M Hruban, RH Maitra, A Gafni, RI Lennon, AM Collins, MT AF Estrada, Andrea Venkatesan, Aradhana Wolfgang, Christopher L. Guthrie, Lori Fishman, Elliot K. Kamei, Ihab Ali, Syed Z. Goggins, Michael Hruban, Ralph H. Maitra, Anirban Gafni, Rachel I. Lennon, Anne Marie Collins, Michael T. TI Pancreatic Pathology in Mccune Albright Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Estrada, Andrea] NICHHD, NIH, Bethesda, MD 20892 USA. [Venkatesan, Aradhana; Gafni, Rachel I.] NIH, Bethesda, MD 20892 USA. [Wolfgang, Christopher L.; Fishman, Elliot K.; Kamei, Ihab; Ali, Syed Z.; Goggins, Michael; Hruban, Ralph H.; Lennon, Anne Marie] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Guthrie, Lori] NIH, Bethesda, MD 20892 USA. [Maitra, Anirban] MD Anderson, Bethesda, MD USA. [Collins, Michael T.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0314 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108077 ER PT J AU Faucz, FR Berthon, AS Zilbermint, M Assie, G Lodish, MB Szarek, E Trivellin, G Sinaii, N Libe, R Espiard, S Drougat, L Ragazzon, B Feldman, B Bertherat, JY Stratakis, CA AF Faucz, Fabio Rueda Berthon, Annabel Sophie Zilbermint, Mihail Assie, Guillaume Lodish, Maya Beth Szarek, Eva Trivellin, Giampaolo Sinaii, Ninet Libe, Rossella Espiard, Stephanie Drougat, Ludivine Ragazzon, Bruno Feldman, Benjamin Bertherat, Jerome Yves Stratakis, Constantine A. TI Functional Investigation of a New Aimah Suppressor Gene, ARMC5 Using Animal Models SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Faucz, Fabio Rueda; Berthon, Annabel Sophie; Zilbermint, Mihail; Lodish, Maya Beth; Szarek, Eva; Trivellin, Giampaolo; Sinaii, Ninet; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Assie, Guillaume; Espiard, Stephanie; Drougat, Ludivine; Ragazzon, Bruno; Bertherat, Jerome Yves] Inst Cochin, CNRS, UMR 8104, INSERM Unite 1016, Paris, France. [Libe, Rossella] Inst Cochin, Paris, France. [Feldman, Benjamin] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0817 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102197 ER PT J AU Feelders, RA Sharma, ST Elgarf, R Ouwerkerk, R Gharib, AM Abd-Elmoniem, KZ Nieman, LK AF Feelders, Richard A. Sharma, Susmeeta T. Elgarf, Reham Ouwerkerk, Ronald Gharib, Ahmed M. Abd-Elmoniem, Khaled Z. Nieman, Lynnette K. TI Noninvasive Assessment of the Coronary Artery Vessel Wall in Cushing's Syndrome Using 3-T Magnetic Resonance Imaging: Evidence for Increased Atherosclerosis Compared to Risk-Matched Controls SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Feelders, Richard A.] Erasmus MC, Rotterdam, Netherlands. [Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Elgarf, Reham; Ouwerkerk, Ronald; Gharib, Ahmed M.; Abd-Elmoniem, Khaled Z.; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0660 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101282 ER PT J AU Fliedner, SMJ Shankavaram, U Elkahloun, A Lehnert, H Pacak, K AF Fliedner, Stephanie M. J. Shankavaram, Uma Elkahloun, Abdel Lehnert, Hendrik Pacak, Karel TI Characteristic Expression Signature of Hypoxia Inducible Factor 2 Alpha Mutation-Related Paragangliomas SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Fliedner, Stephanie M. J.; Lehnert, Hendrik] Univ Med Ctr Schleswig Holstein, Lubeck, Germany. [Shankavaram, Uma] NCI, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel] NHGRI, NIH, Bethesda, MD 20892 USA. [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA LBSU-0820 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100026 ER PT J AU Fortin, J Boehm, U Deng, CX Treier, M Bernard, DJ AF Fortin, Jerome Boehm, Ulrich Deng, Chuxia Treier, Mathias Bernard, Daniel J. TI Follicle-Stimulating Hormone Synthesis and Fertility Require the Independent and Complementary Activities of SMAD4 and FOXL2 in Gonadotropes SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Fortin, Jerome; Bernard, Daniel J.] McGill Univ, Montreal, PQ, Canada. [Boehm, Ulrich] Univ Saarland, Sch Med, Homburg, Germany. [Deng, Chuxia] NIH, Bethesda, MD 20892 USA. [Treier, Mathias] Max Delbruck Ctr Mol Med, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR30-6 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101193 ER PT J AU Gourgari, E Lodish, MB Keil, M Sinai, N Turkbey, E Lyssikatos, C Khurana, D Crutchfield, C Nesterova, MV Sierra, MD Xekouki, P Backlund, P Yergey, A Ten, SB Dobs, AS Stratakis, CA AF Gourgari, Evgenia Lodish, Maya Beth Keil, Margaret Sinai, Ninet Turkbey, Evrim Lyssikatos, Charalampos Khurana, Divya Crutchfield, Chris Nesterova, Maria V. Sierra, Maria De La Luz Xekouki, Paraskevi Backlund, Peter Yergey, Al Ten, Svetlana B. Dobs, Adrian Sandra Stratakis, Constantine A. TI Micronodular Adrenal Hyperplasia: A New Mechanism for Hyperandrogenism in Women with Polycystic Ovarian Syndrome (PCOS) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Gourgari, Evgenia] Georgetown Univ Hosp, Washington, DC 20007 USA. [Lodish, Maya Beth; Keil, Margaret; Turkbey, Evrim; Lyssikatos, Charalampos; Nesterova, Maria V.; Sierra, Maria De La Luz; Xekouki, Paraskevi; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA. [Sinai, Ninet] NICHD, Rockville, MD USA. [Khurana, Divya] MMC, Hicksville, NY USA. [Crutchfield, Chris] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Backlund, Peter] NICHD, Bethesda, MD USA. [Yergey, Al] NICHD, NIH, Rockville, MD USA. [Ten, Svetlana B.] Maimonides Hosp, Brooklyn, NY 11219 USA. [Dobs, Adrian Sandra] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0087 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109277 ER PT J AU Hein, AC Vatish, M Kino, T Grammatopoulos, D DeCherney, AH AF Hein, Anna Caroline Vatish, Manu Kino, Tomoshige Grammatopoulos, Dimitris DeCherney, Alan H. TI Novel Role of the Enzyme 11 beta-Hydroxysteroid Dehydrogenase Type 2 (11 beta-HSD2) on Trophoblast Biology SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Hein, Anna Caroline; Kino, Tomoshige] NICHD, NIH, Bethesda, MD USA. [Vatish, Manu] Univ Oxford, Oxford, England. [Grammatopoulos, Dimitris] Univ Warwick, Biomed Res Inst, Coventry, W Midlands, England. [DeCherney, Alan H.] NIH, Potomac, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0076 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105012 ER PT J AU Hernandez-Ramirez, LC Gabrovska, P Denes, J Trivellin, G Radian, S Tilley, D Ferrau, F Akkers, SA Grossman, AB Gadelha, M Korbonits, M AF Hernandez-Ramirez, Laura C. Gabrovska, Plamena Denes, Judit Trivellin, Giampaolo Radian, Serban Tilley, Daniel Ferrau, Francesco Akkers, Scott Alexander Grossman, Ashley B. Gadelha, MA'nica Korbonits, Marta CA Int FIPA Consortium TI Pituitary Adenomas Harboring AIP Mutations Exhibit Phenotype-Genotype Correlation, but No Association with the Germline FGFR4 G388R Variant or Somatic GNAS1 Mutations SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Hernandez-Ramirez, Laura C.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England. [Gabrovska, Plamena] Queen Mary Univ London, William Harvey Res Inst, London, England. [Denes, Judit; Radian, Serban; Tilley, Daniel; Ferrau, Francesco; Korbonits, Marta; Int FIPA Consortium] Queen Mary Univ London, Barts & London Sch Med, London, England. [Trivellin, Giampaolo] NIH, Bethesda, MD 20892 USA. [Akkers, Scott Alexander] St Bartholomews Hosp, London, England. [Grossman, Ashley B.] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Gadelha, MA'nica] Univ Fed Rio de Janeiro, Clementino Fraga Filho Univ Hosp, Rio De Janeiro, Brazil. RI Radian, Serban/C-3559-2011 OI Radian, Serban/0000-0002-6488-4242 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR09-3 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102034 ER PT J AU Ho, TP Hattenbach, J Linderman, JD Smith, S Simchowitz, L Celi, FS AF Ho, Thanh P. Hattenbach, Jacob Linderman, Joyce D. Smith, Sheila Simchowitz, Louis Celi, Francesco S. TI Effects of Inflammation and Adiposity on Bone Density in Non-Elderly Adults SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Ho, Thanh P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hattenbach, Jacob; Linderman, Joyce D.; Smith, Sheila; Simchowitz, Louis] NIH, Bethesda, MD 20892 USA. [Celi, Francesco S.] Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0273 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105272 ER PT J AU Ho, T Ranganath, K Kablan, A Chen, M Weinstein, LS AF Ho, Thuy Ranganath, Khushi Kablan, Ahmed Chen, Min Weinstein, Lee S. TI Pancreatic alpha Cell-Specific Gsa Deficiency Promotes alpha and beta Cell Growth SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Ho, Thuy; Ranganath, Khushi; Kablan, Ahmed; Chen, Min; Weinstein, Lee S.] NIDDK, NIH, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0949 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106150 ER PT J AU Huang, CCJ Forrest, D AF Huang, Chen-Che Jeff Forrest, Douglas TI Thyroid Hormone Receptor beta 1-Mediated Adrenal Remodeling SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Huang, Chen-Che Jeff; Forrest, Douglas] NIDDKD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0471 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108186 ER PT J AU Jewell, C Murphy, L Cannon, C Garantziotis, S Cidlowski, JA AF Jewell, Christine Murphy, Lisa Cannon, Crystal Garantziotis, Stavros Cidlowski, John A. TI The Role of Glucocorticoid Receptor N363S Single Nucleotide Polymorphism in Receptor Function and Metabolic Disease SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Jewell, Christine; Murphy, Lisa; Cannon, Crystal; Garantziotis, Stavros; Cidlowski, John A.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0803 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104074 ER PT J AU Jha, S Nair, G Patel, J Bhatia, A Parseghian, SA Albert, SG AF Jha, Smita Nair, Gopakumar Patel, Jaymin Bhatia, Ashmeet Parseghian, Shant A. Albert, Stewart Gary TI Exploring the Benefits of Early Endocrinology Consultation for Diabetic Ketoacidosis in a Community Hospital Setting SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Jha, Smita] NIH, Bethesda, MD 20892 USA. [Nair, Gopakumar] Brockton Hosp, Brockton, MA USA. [Patel, Jaymin; Bhatia, Ashmeet] North Shore Med Ctr, Miami, FL USA. [Parseghian, Shant A.] NSPG, Winchester, MA USA. [Albert, Stewart Gary] St Louis Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0984 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106271 ER PT J AU Kantorovich, V Arai, AE Martucci, VL Adams, KT Reynolds, JC Pacak, K AF Kantorovich, Vitaly Arai, Andrew E. Martucci, Victoria L. Adams, Karen T. Reynolds, James C. Pacak, Karel TI Functional and Structural Cardiac Abnormalities in Patients with Metastatic Pheochromocytomas and Paragangliomas SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Kantorovich, Vitaly] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Arai, Andrew E.] NHLBI, Bethesda, MD 20892 USA. [Martucci, Victoria L.; Adams, Karen T.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Reynolds, James C.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0769 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103038 ER PT J AU Kantorovich, V Arai, AE Martucci, VL Adams, KT Reynolds, JC Pacak, K AF Kantorovich, Vitaly Arai, Andrew E. Martucci, Victoria L. Adams, Karen T. Reynolds, James C. Pacak, Karel TI Functional and Structural Cardiac Abnormalities in Patients with Metastatic Pheochromocytomas and Pa ragangliomas SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Kantorovich, Vitaly] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Arai, Andrew E.] NHLBI, Bethesda, MD 20892 USA. [Martucci, Victoria L.; Adams, Karen T.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Reynolds, James C.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP27-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100159 ER EF