FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ward, RE Boudreau, R Caserotti, P Harris, TB Goodpaster, B Cauley, JA Newman, AB Strotmeyer, ES AF Ward, R. E. Boudreau, R. Caserotti, P. Harris, T. B. Goodpaster, B. Cauley, J. A. Newman, A. B. Strotmeyer, E. S. TI SENSORY AND MOTOR PERIPHERAL NERVE FUNCTION PREDICT LONGITUDINAL LOWER-EXTREMITY QUADRICEPS STRENGTH SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ward, R. E.; Boudreau, R.; Goodpaster, B.; Cauley, J. A.; Newman, A. B.; Strotmeyer, E. S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Caserotti, P.] Univ So Denmark, Odense, Denmark. [Harris, T. B.] NIA, Bethesda, MD 20892 USA. RI Strotmeyer, Elsa/F-3015-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 508 EP 508 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203686 ER PT J AU Breslau, ES Bellizzi, K Schonberg, MA AF Breslau, E. S. Bellizzi, K. Schonberg, M. A. TI PREVALENCE OF MAMMOGRAPHY USE IN OLDER WOMEN BY 5-YEAR LIFE EXPECTANCY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Breslau, E. S.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Bellizzi, K.] Univ Connecticut, Storrs, CT USA. [Schonberg, M. A.] Harvard Univ, Sch Med, Boston, MA 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 529 EP 530 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888203785 ER PT J AU Tolea, M Simonsick, EM AF Tolea, M. Simonsick, E. M. TI PERSONALITY CORRELATES OF EXCEPTIONAL HEALTH IN OLDER PARTICIPANTS IN THE BALTIMORE LONGITUDINAL STUDY OF AGING (BLSA) SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Tolea, M.] Univ Missouri, St Louis, MO 63121 USA. [Simonsick, E. M.] NIA, Baltimore, MD 21224 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 559 EP 559 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204056 ER PT J AU Nadkarni, NK Nunley, KA Aizenstein, H Harris, TB Yaffe, K Brach, J Newman, AB Rosano, C AF Nadkarni, N. K. Nunley, K. A. Aizenstein, H. Harris, T. B. Yaffe, K. Brach, J. Newman, A. B. Rosano, C. TI REGIONAL CEREBELLAR GREY MATTER VOLUME, PROCESSING SPEED AND GAIT MEASURES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Nadkarni, N. K.; Nunley, K. A.; Aizenstein, H.; Brach, J.; Newman, A. B.; Rosano, C.] Univ Pittsburgh, Pittsburgh, PA USA. [Harris, T. B.] NIA, Bethesda, MD 20892 USA. [Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Nadkarni, N. K.; Rosano, C.] Pittsburgh Older Amer Independence Ctr, Pittsburgh, PA 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 578 EP 578 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204134 ER PT J AU Tian, Q Erickson, K Simonsick, EM Aizenstein, H Glynn, NW Yaffe, K Newman, AB Rosano, C AF Tian, Q. Erickson, K. Simonsick, E. M. Aizenstein, H. Glynn, N. W. Yaffe, K. Newman, A. B. Rosano, C. TI ASSOCIATION BETWEEN ENDURANCE WALK CAPACITY AND INTEGRITY OF BRAIN REGIONS IMPORTANT FOR PROCESSING SPEED IN VERY OLD ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Tian, Q.; Erickson, K.; Aizenstein, H.; Glynn, N. W.; Newman, A. B.; Rosano, C.] Univ Pittsburgh, Pittsburgh, PA USA. [Simonsick, E. M.] NIA, Bethesda, MD 20892 USA. [Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 579 EP 579 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204138 ER PT J AU Tian, Q Simonsick, EM Glynn, NW Aizenstein, H Yaffe, K Harris, TB Newman, AB Rosano, C AF Tian, Q. Simonsick, E. M. Glynn, N. W. Aizenstein, H. Yaffe, K. Harris, T. B. Newman, A. B. Rosano, C. TI FREE-LIVING PHYSICAL ACTIVITY AND BRAIN STRUCTURES IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Tian, Q.; Glynn, N. W.; Aizenstein, H.; Newman, A. B.; Rosano, C.] Univ Pittsburgh, Pittsburgh, PA USA. [Simonsick, E. M.; Harris, T. B.] NIA, Bethesda, MD 20892 USA. [Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 579 EP 580 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204140 ER PT J AU Bellizzi, K Breslau, ES AF Bellizzi, K. Breslau, E. S. TI COLORECTAL CANCER SCREENING IN OLDER ADULTS BY 5 YEAR LIFE EXPECTANCY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bellizzi, K.] UConn, HDFS, Storrs, CT USA. [Breslau, E. S.] 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 582 EP 582 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204150 ER PT J AU Caserotti, P Harris, TB Puggaard, L Rasmussen, C Aagaard, P AF Caserotti, P. Harris, T. B. Puggaard, L. Rasmussen, C. Aagaard, P. TI POWER TRAINING IN OLDER ADULTS: MUSCLE MECHANICAL, MORPHOLOGICAL AND FUNCTIONAL CHANGES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Caserotti, P.; Puggaard, L.; Aagaard, P.] Univ So Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. [Caserotti, P.; Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Rasmussen, C.] Univ Aarhus, Inst Publ Hlth, Aarhus, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 608 EP 608 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204260 ER PT J AU Kim, DH Patel, K Newman, AB Chaves, PH Klein, R Sarnak, M Lipsitz, L AF Kim, D. H. Patel, K. Newman, A. B. Chaves, P. H. Klein, R. Sarnak, M. Lipsitz, L. TI BURDEN OF MICROVASCULAR AND MACROVASCULAR DISEASE AND FUNCTIONAL STATUS IN COMMUNITY-DWELLING OLDER ADULTS: THE CARDIOVASCULAR HEALTH STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kim, D. H.; Lipsitz, L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kim, D. H.; Lipsitz, L.] Hebrew SeniorLife, Boston, MA USA. [Kim, D. H.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Patel, K.] NIA, Bethesda, MD 20892 USA. [Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Chaves, P. H.] Johns Hopkins Univ, Baltimore, MD USA. [Klein, R.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Sarnak, M.] Tufts Med Ctr, Boston, MA 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 623 EP 623 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204333 ER PT J AU Whitson, HE Arnold, A Mukamal, K Kizer, JR Siscovick, D Thielke, SM Hirsch, C Zieman, S AF Whitson, H. E. Arnold, A. Mukamal, K. Kizer, J. R. Siscovick, D. Thielke, S. M. Hirsch, C. Zieman, S. TI ASSOCIATION OF N-CARBOXYMETHYL-LISINE (CML) AND FRAILTY IN OLDER MEN AND WOMEN: THE CARDIOVASCULAR HEALTH STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Whitson, H. E.] Duke, Internal Med, Durham, NC USA. [Whitson, H. E.] Durham VA, Durham, NC USA. [Arnold, A.; Siscovick, D.; Thielke, S. M.] Univ Washington, Seattle, WA 98195 USA. [Mukamal, K.] Harvard Univ, Sch Med, Boston, MA USA. [Kizer, J. R.] Cornell Weill Med Coll, New York, NY USA. [Hirsch, C.] Univ Calif Davis, Davis, CA USA. [Zieman, S.] NIH, Bethesda, MD 20892 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 623 EP 623 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204334 ER PT J AU Chang, M Snaedal, J Einarsson, B Saczynski, J Gudnason, V Launer, LJ Harris, TB Jonsson, PV AF Chang, M. Snaedal, J. Einarsson, B. Saczynski, J. Gudnason, V. Launer, L. J. Harris, T. B. Jonsson, P. V. TI THE ASSOCIATION BETWEEN MID-LIFE PHYSICAL ACTIVITY AND LOWER EXTREMITY FUNCTION IN OLDER ADULTS: ROLE OF COGNITIVE FUNCTION, AGE GENE/ENVIRONMENT SUSCEPTIBILITY (AGES) - REYKJAVIK STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Chang, M.; Snaedal, J.; Einarsson, B.; Jonsson, P. V.] Landspitali Univ Hosp, Geriatr Res Ctr, Reykjavik, Iceland. [Snaedal, J.; Einarsson, B.; Gudnason, V.; Jonsson, P. V.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Saczynski, J.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Saczynski, J.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA USA. [Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Launer, L. J.; Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 626 EP 626 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204345 ER PT J AU Patel, K AF Patel, K. TI ASSOCIATION OF CHRONIC BACK PAIN AND BALANCE IMPAIRMENT WITH MOBILITY LIMITATION AND PHYSICAL ACTIVITY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Patel, K.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 626 EP 627 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204348 ER PT J AU Deshpande, N Metter, E Guralnik, JM Ferrucci, L AF Deshpande, N. Metter, E. Guralnik, J. M. Ferrucci, L. TI FEAR OF FALLING IN OLDER PERSONS: INCIDENCE AND PROGRESSION OVER 3 YEARS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Deshpande, N.] Queens Univ, Kingston, ON, Canada. [Metter, E.; Ferrucci, L.] NIA, Washington, DC USA. [Guralnik, J. M.] Univ Maryland, College Pk, MD 20742 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 628 EP 628 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204352 ER PT J AU Kuo, J Parisi, JM Nahin, R Fitzpatrick, A Rapp, S Lopez, OL Snitz, B Carlson, M AF Kuo, J. Parisi, J. M. Nahin, R. Fitzpatrick, A. Rapp, S. Lopez, O. L. Snitz, B. Carlson, M. TI LATE-LIFE LIFESTYLE ACTIVITY AS A BUFFER FOR COGNITIVE DECLINE AND FUNCTIONAL IMPAIRMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kuo, J.; Carlson, M.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. [Kuo, J.; Parisi, J. M.; Carlson, M.] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Nahin, R.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. [Fitzpatrick, A.] Univ Washington, Seattle, WA 98195 USA. [Rapp, S.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Lopez, O. L.; Snitz, B.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 656 EP 656 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204494 ER PT J AU Murphy, RA Patel, K Kritchevsky, SB Houston, DK Tylavsky, FA Cawthon, PM Newman, AB Harris, TB AF Murphy, R. A. Patel, K. Kritchevsky, S. B. Houston, D. K. Tylavsky, F. A. Cawthon, P. M. Newman, A. B. Harris, T. B. TI ASSOCIATION OF CHANGES IN WEIGHT WITH BODY COMPOSITION AND MORTALITY IN OLDER ADULTS: HEALTH ABC SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Murphy, R. A.; Patel, K.; Harris, T. B.] NIA, Bethesda, MD 20892 USA. [Kritchevsky, S. B.; Houston, D. K.] Wake Forest Univ, Salem, NC USA. [Tylavsky, F. A.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Cawthon, P. M.] Calif Pacific Med Ctr, San Francisco, CA USA. [Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 658 EP 658 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204503 ER PT J AU Sanders, J Boudreau, R Penninx, B Simonsick, EM Kritchevsky, SB Satterfield, S Harris, TB Newman, AB AF Sanders, J. Boudreau, R. Penninx, B. Simonsick, E. M. Kritchevsky, S. B. Satterfield, S. Harris, T. B. Newman, A. B. TI ASSOCIATION OF A MODIFIED PHYSIOLOGIC INDEX WITH MORTALITY AND INCIDENT DISABILITY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Sanders, J.; Boudreau, R.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Penninx, B.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Simonsick, E. M.] Johns Hopkins Sch Med, Baltimore, MD USA. [Simonsick, E. M.; Harris, T. B.] NIA, Baltimore, MD 21224 USA. [Kritchevsky, S. B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Satterfield, S.] Univ Tennessee, Memphis, TN 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 658 EP 658 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204505 ER PT J AU Gomes, A Dioufa, N Price, N Rolo, A Mercken, E Palmeira, C De Cabo, R Sinclair, DA AF Gomes, A. Dioufa, N. Price, N. Rolo, A. Mercken, E. Palmeira, C. De Cabo, R. Sinclair, D. A. TI MEDICINES THAT MIMIC CALORIE RESTRICTION: HOW CLOSE ARE WE? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Gomes, A.; Dioufa, N.; Price, N.; Sinclair, D. A.] Harvard Univ, Sch Med, Boston, MA USA. [Gomes, A.; Rolo, A.; Palmeira, C.] Univ Coimbra, Coimbra, Portugal. [Mercken, E.; De Cabo, R.] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 667 EP 667 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204548 ER PT J AU Eggermont, L Shi, L Kiely, DK Bean, JF Guralnik, J Shmerling, RH Jones, R Leveille, SG AF Eggermont, L. Shi, L. Kiely, D. K. Bean, J. F. Guralnik, J. Shmerling, R. H. Jones, R. Leveille, S. G. TI PAIN CONTRIBUTES TO ONSET/WORSENING OF MOBILITY DIFFICULTY AND PERFORMANCE DECLINE IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Eggermont, L.] Vrije Univ Amsterdam, Deparment Neuropsychol, Amsterdam, Netherlands. [Kiely, D. K.; Jones, R.] Harvard Univ, Dept Med, Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Jones, R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Med, Boston, MA 02215 USA. [Shmerling, R. H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Rheumatol, Boston, MA 02215 USA. [Guralnik, J.] NIA, Lab Epidemiol Demog & Biometry, Bathesda, MD USA. [Bean, J. F.] Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Sch Med, Boston, MA 02115 USA. [Shi, L.; Leveille, S. G.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 685 EP 686 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204641 ER PT J AU Cohen, AA Langer, FDB Fried, LP Ferrucci, L AF Cohen, A. A. Langer, F. Dusseault-Be Fried, L. P. Ferrucci, L. TI MULTI-SYSTEM BIOMARKER ANALYSES IN TWO AGING POPULATIONS: SAME BIG PICTURE, DIFFERENT DETAILS FOR WHAS AND INCHIANTI SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Cohen, A. A.] Ctr Hosp Univ Sherbrooke, Grp Rech PRIMUS, Sherbrooke, PQ, Canada. [Cohen, A. A.; Langer, F. Dusseault-Be] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. [Fried, L. P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Ferrucci, L.] NIA, Baltimore, MD 21224 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 700 EP 700 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204712 ER PT J AU Langer, FDB Cohen, AA Xue, Q Fried, LP Ferrucci, L AF Langer, F. Dusseault-Be Cohen, A. A. Xue, Q. Fried, L. P. Ferrucci, L. TI UNDERSTANDING THE AGING PROCESS USING PRINCIPAL COMPONENT ANALYSIS ON LONGITUDINAL BIOMARKERS SUITES: INCHIANTI SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Langer, F. Dusseault-Be; Cohen, A. A.] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. [Xue, Q.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Fried, L. P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Ferrucci, L.] NIA, Baltimore, MD 21224 USA. NR 0 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2012 VL 52 SU 1 BP 700 EP 700 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 061ZG UT WOS:000312888204711 ER PT J AU Chuang, ML Gona, P Hautvast, GLTF Salton, CJ Blease, SJ Yeon, SB Breeuwer, M O'Donnell, CJ Manning, WJ AF Chuang, Michael L. Gona, Philimon Hautvast, Gilion L. T. F. Salton, Carol J. Blease, Susan J. Yeon, Susan B. Breeuwer, Marcel O'Donnell, Christopher J. Manning, Warren J. TI Correlation of Trabeculae and Papillary Muscles With Clinical and Cardiac Characteristics and Impact on CMR Measures of LV Anatomy and Function SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE cardiac magnetic resonance; left ventricular ejection fraction; papillary muscle; population study; trabeculae ID VENTRICULAR NON-COMPACTION; MAGNETIC-RESONANCE; SYSTOLIC DYSFUNCTION; MASS; HYPERTRABECULATION/NONCOMPACTION; REPRODUCIBILITY; CARDIOMYOPATHY; NONCOMPACTION; DIAGNOSIS; FLASH AB OBJECTIVES The goal of this study was to assess the relationship of left ventricular (LV) trabeculae and papillary muscles (TPM) with clinical characteristics in a community-based, free-living adult cohort and to determine the effect of TPM on quantitative measures of LV volume, mass, and ejection fraction (EF). BACKGROUND Hypertrabeculation has been associated with adverse cardiovascular events, but the distribution and clinical correlates of the volume and mass of the TPM in a normal left ventricle have not been well characterized. METHODS Short-axis cine cardiac magnetic resonance images, obtained using a steady-state free precession sequence from 1,494 members of the Framingham Heart Study Offspring cohort, were analyzed with software that automatically segments TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV) (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring and in a referent group of offspring free of clinical cardiovascular disease and hypertension. RESULTS In the referent group (mean age 61 +/- 9 years; 262 men and 423 women), mean TPM was 23 +/- 3% of LV EDV in both sexes (p = 0.9). TPM/EDV decreased with age (p < 0.02) but was not associated with body mass index. TPM mass as a fraction of LV mass was inversely correlated with age (p < 0.0001), body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all 1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%, and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial mass rather than part of the LV blood pool. CONCLUSIONS Global cardiac magnetic resonance LV parameters were significantly affected by whether TPM was considered as part of the LV blood pool or as part of LV mass. Our cross-sectional data from a healthy referent group of adults free of clinical cardiovascular disease demonstrated that TPM/EDV decreases with increasing age in both sexes but is not related to hypertension or obesity. (J Am Coll Cardiol Img 2012;5:1115-23) (C) 2012 by the American College of Cardiology Foundation C1 [Chuang, Michael L.; Gona, Philimon; Blease, Susan J.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Chuang, Michael L.; Salton, Carol J.; Yeon, Susan B.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med, Boston, MA 02215 USA. [Chuang, Michael L.; O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA. [Gona, Philimon] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Hautvast, Gilion L. T. F.; Breeuwer, Marcel] Philips Healthcare, Best, Netherlands. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Manning, WJ (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM wmanning@bidmc.harvard.edu FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01 HC 25195]; National Institutes of Health [RO1 HL70279]; Philips Healthcare; Philips Medical Systems FX This research was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01 HC 25195), a subcontract from the National Institutes of Health (RO1 HL70279), and by an unrestricted grant from Philips Healthcare. Drs. Hautvast and Breeuwer are employees of Philips Healthcare. Dr. Manning has received research support from Philips Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 20 TC 24 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD NOV PY 2012 VL 5 IS 11 BP 1115 EP 1123 DI 10.1016/j.jcmg.2012.05.015 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 066VG UT WOS:000313248600006 PM 23153911 ER PT J AU Daniels, MP AF Daniels, Mathew P. TI The role of agrin in synaptic development, plasticity and signaling in the central nervous system SO NEUROCHEMISTRY INTERNATIONAL LA English DT Review DE Agrin; Brain; Synapse development; Synaptic activity; Synaptic plasticity; Filopodia ID NEUROMUSCULAR-JUNCTION FORMATION; CULTURED MUSCLE-CELLS; TYROSINE KINASE MUSK; HIPPOCAMPAL-NEURONS; DENDRITIC FILOPODIA; CORTICAL-NEURONS; DEFICIENT MICE; IN-VIVO; ACETYLCHOLINE-RECEPTORS; MESSENGER-RNA AB Development of the neuromuscular junction (NMJ) requires secretion of specific isoforms of the proteoglycan agrin by motor neurons. Secreted agrin is widely expressed in the basal lamina of various tissues, whereas a transmembrane form is highly expressed in the brain. Expression in the brain is greatest during the period of synaptogenesis, but remains high in regions of the adult brain that show extensive synaptic plasticity. The well-established role of agrin in NMJ development and its presence in the brain elicited investigations of its possible role in synaptogenesis in the brain. Initial studies on the embryonic brain and neuronal cultures of agrin-null mice did not reveal any defects in synaptogenesis. However, subsequent studies in culture demonstrated inhibition of synaptogenesis by agrin antisense oligonucleotides or agrin siRNA. More recently, a substantial loss of excitatory synapses was found in the brains of transgenic adult mice that lacked agrin expression everywhere but in motor neurons. The mechanisms by which agrin influences synapse formation, maintenance and plasticity may include enhancement of excitatory synaptic signaling, activation of the "muscle-specific" receptor tyrosine kinase (MuSK) and positive regulation of dendritic filopodia. In this article I will review the evidence that agrin regulates synapse development, plasticity and signaling in the brain and discuss the evidence for the proposed mechanisms. Published by Elsevier Ltd. C1 NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. RP Daniels, MP (reprint author), NHLBI, Electron Microscopy Core Facil, NIH, 50 Serv Rd W,Bldg 14E,Room 111B, Bethesda, MD 20892 USA. EM danielsm2@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 66 TC 15 Z9 16 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD NOV PY 2012 VL 61 IS 6 BP 848 EP 853 DI 10.1016/j.neuint.2012.02.028 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 068NY UT WOS:000313374600007 PM 22414531 ER PT J AU Cui, F Cole, HA Clark, DJ Zhurkin, VB AF Cui, Feng Cole, Hope A. Clark, David J. Zhurkin, Victor B. TI Transcriptional activation of yeast genes disrupts intragenic nucleosome phasing SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HISTONE-DNA INTERACTIONS; SACCHAROMYCES-CEREVISIAE; MICROCOCCAL NUCLEASE; RNA-POLYMERASE; GENOME-WIDE; CHROMATIN STRUCTURE; SEQUENCE PATTERNS; EUKARYOTIC GENOME; HIGH-RESOLUTION; IN-VIVO AB Nucleosomes often undergo extensive rearrangement when genes are activated for transcription. We have shown previously, using paired-end sequencing of yeast nucleosomes, that major changes in chromatin structure occur when genes are activated by 3-aminotriazole (3AT), an inducer of the transcriptional activator Gcn4. Here, we provide a global analysis of these data. At the genomic level, nucleosomes are regularly phased relative to the transcription start site. However, for a subset of 234 strongly induced genes, this phasing is much more irregular after induction, consistent with the loss of some nucleosomes and the re-positioning of the remaining nucleosomes. To address the nature of this rearrangement, we developed the inter-nucleosome distance auto-correlation (DAC) function. At long range, DAC analysis indicates that nucleosomes have an average spacing of 162 bp, consistent with the reported repeat length. At short range, DAC reveals a 10.25-bp periodicity, implying that nucleosomes in overlapping positions are rotationally related. DAC analysis of the 3AT-induced genes suggests that transcription activation coincides with rearrangement of nucleosomes into irregular arrays with longer spacing. Sequence analysis of the +1 nucleosomes belonging to the 45 most strongly activated genes reveals a distinctive periodic oscillation in the A/T-dinucleotide occurrence that is present throughout the nucleosome and extends into the linker. This unusual pattern suggests that the +1 nucleosomes might be prone to sliding, thereby facilitating transcription. C1 [Cui, Feng; Zhurkin, Victor B.] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Cole, Hope A.; Clark, David J.] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Clark, DJ (reprint author), NICHHD, Program Genom Differentiat, NIH, Bldg 6A,Room 2A14,6 Ctr Dr,9000 Rockville Pike, Bethesda, MD 20892 USA. EM clarkda@mail.nih.gov; zhurkin@nih.gov FU National Institutes of Health (Center for Cancer Research, National Cancer Institute); National Institutes of Health (Program in Genomics of Differentiation, National Institute for Child Health and Human Development); National Institutes of Health FX The Intramural Research Program of the National Institutes of Health (Center for Cancer Research, National Cancer Institute; Program in Genomics of Differentiation, National Institute for Child Health and Human Development). Funding for open access charge: The Intramural Research Program of the National Institutes of Health. NR 60 TC 13 Z9 13 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV PY 2012 VL 40 IS 21 BP 10753 EP 10764 DI 10.1093/nar/gks870 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 068EU UT WOS:000313349100021 PM 23012262 ER PT J AU Meteyer, CU Barber, D Mandl, JN AF Meteyer, Carol U. Barber, Daniel Mandl, Judith N. TI Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome SO VIRULENCE LA English DT Article DE cave-hibernating bats; Geomyces destructans; hibernation-induced; immune suppression; immune cell trafficking; immune reconstitution inflammatory syndrome (IRIS); Myotis lucifugus; white nose syndrome ID GEOMYCES-DESTRUCTANS; GROUND-SQUIRRELS; HIBERNATION; INFECTION; SYSTEM; TEMPERATURE; RESPONSES; THERAPY AB White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology. C1 [Meteyer, Carol U.] US Geol Survey, Natl Wildlife Hlth Ctr, Madison, WI USA. [Barber, Daniel] NIAID, Lymphocyte Biol Unit T, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Mandl, Judith N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA. RP Mandl, JN (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mandlj@niaid.nih.gov FU US. Geological Survey FX Authors are grateful to Gregory Turner (Pennsylvania Game Commission), Mick Valent (New Jersey Division of Fish and Wild-life) and Jackie Kashmer (New Jersey Bat Sanctuary) for permission to use the photographs in Figure 1 and Ann Rivers (Acadia Wildlife Foundation) for submitting the Little Brown Bats from Maine. Diagnostic work was funded by the US. Geological Survey. Use of trade or product names does not imply endorsement by the US government. NR 39 TC 24 Z9 24 U1 7 U2 80 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD NOV PY 2012 VL 3 IS 7 BP 583 EP 588 DI 10.4161/viru.22330 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 067HU UT WOS:000313285700006 PM 23154286 ER PT J AU Huang, CH Nwe, K Al Zaki, A Brechbiel, MW Tsourkas, A AF Huang, Ching-Hui Nwe, Kido Al Zaki, Ajlan Brechbiel, Martin W. Tsourkas, Andrew TI Biodegradable Polydisulfide Dendrimer Nanoclusters as MRI Contrast Agents SO ACS NANO LA English DT Article DE gadolinium; magnetic resonance; nanoparticle; nanocluster; dendrimer; biodegradable ID NEPHROGENIC SYSTEMIC FIBROSIS; POROUS POLYMERSOMES; DRUG-DELIVERY; GADOLINIUM; CLEARANCE; CORES; NANOPARTICLES; ENHANCEMENT; RELAXIVITY; COMPLEXES AB Gadolinium-conjugated dendrimer nanoclusters (DNCs) are a promising platform for the early detection of disease; however, their clinical utility is potentially limited due to safety concerns related to nephrogenic systemic fibrosis (NSF). In this paper, biodegradable DNCs were prepared with polydisulfide linkages between the individual dendrimers to facilitate excretion. Further, DNCs were labeled with premetalated Gd chelates to eliminate the risk of free Gd becoming entrapped in dendrimer cavities. The biodegradable polydisulfide DNCs possessed a circulation half-life of >1.6 h in mice and produced significant contrast enhancement in the abdominal aorta and kidneys for as long as 4h. The DNCs were reduced in circulation as a result of thiol-disulfide exchange, and the degradation products were rapidly excreted via renal filtration. These agents demonstrated effective and prolonged in vivo contrast enhancement and yet minimized Gd tissue retention. Biodegradable polydisulfide DNCs represent a promising biodegradable macromolecular MRI contrast agent for magnetic resonance angiography and can potentially be further developed into target-specific MRI contrast agents. C1 [Huang, Ching-Hui; Al Zaki, Ajlan; Tsourkas, Andrew] Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA. [Nwe, Kido; Brechbiel, Martin W.] NCI, Riadioimmune Inorgan Chem Sect, Bethesda, MD 20892 USA. RP Tsourkas, A (reprint author), Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA. EM atsourk@seas.upenn.edu RI Tsourkas, Andrew/A-1074-2007 OI Tsourkas, Andrew/0000-0001-7758-1753 FU National Institute of Health (NIH) [NIBIB/R01-EB012065, NCI/R01-CA157766, NIBIB/R21-EB013226]; NIH, National Cancer Institute, Center for Cancer Research FX This research was supported in part by the National Institute of Health (NIH) NIBIB/R01-EB012065 (A.T.), NCI/R01-CA157766 (A.T.), NIBIB/R21-EB013226 (A.T.), and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (M.B.). NR 42 TC 40 Z9 40 U1 4 U2 108 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD NOV PY 2012 VL 6 IS 11 BP 9416 EP 9424 DI 10.1021/nn304160p PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 043CY UT WOS:000311521700009 PM 23098069 ER PT J AU Wakano, C Byun, JS Di, LJ Gardner, K AF Wakano, Clay Byun, Jung S. Di, Li-Jun Gardner, Kevin TI The dual lives of bidirectional promoters (vol 1819, pg 688, 2012) SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Correction C1 [Gardner, Kevin] NCI, Genet Branch, Bethesda, MD 20982 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20982 USA. RP Gardner, K (reprint author), NCI, Genet Branch, 41 Lib Dr,Rm D305, Bethesda, MD 20982 USA. EM gardnerk@mail.nih.gov RI Di, Li-jun/D-6160-2013 NR 1 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD NOV-DEC PY 2012 VL 1819 IS 11-12 BP 1228 EP 1229 DI 10.1016/j.bbagrm.2012.06.003 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 063AB UT WOS:000312965700012 ER PT J AU Chow, GV Marine, JE Fleg, JL AF Chow, Grant V. Marine, Joseph E. Fleg, Jerome L. TI Epidemiology of Arrhythmias and Conduction Disorders in Older Adults SO CLINICS IN GERIATRIC MEDICINE LA English DT Article DE Aging; Arrhythmia; Atrial fibrillation; Atrial flutter; Conduction disorders ID BUNDLE-BRANCH BLOCK; APPARENTLY HEALTHY-VOLUNTEERS; 1ST-DEGREE ATRIOVENTRICULAR-BLOCK; LONG-TERM PROGNOSIS; ATRIAL-FIBRILLATION; HEART-RATE; CARDIAC-ARRHYTHMIAS; AMBULATORY ELECTROCARDIOGRAPHY; SUPRAVENTRICULAR TACHYCARDIA; VENTRICULAR-TACHYCARDIA AB Normal aging is associated with a multitude of changes in the cardiovascular system, including decreased compliance of blood vessels, mild concentric left ventricular hypertrophy, an increased contribution of atrial contraction to left ventricular filling, and a higher incidence of many cardiac arrhythmias, both bradyarrhythmias and tachyarrhythmias. Conduction disorders also become more common with age, and may either be asymptomatic, or cause hemodynamic changes requiring treatment. The epidemiology of common arrhythmias and conduction disorders in the elderly is reviewed. C1 [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Chow, Grant V.; Marine, Joseph E.] Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21287 USA. RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, Room 8150,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM flegj@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 66 TC 15 Z9 15 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0690 EI 1879-8853 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD NOV PY 2012 VL 28 IS 4 BP 539 EP + DI 10.1016/j.cger.2012.07.003 PG 16 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 058FI UT WOS:000312619100002 PM 23101570 ER PT J AU Wang, E Marincola, FM AF Wang, E. Marincola, F. M. TI The Ying and Yang of the Tumour Microenvironment SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Wang, E.; Marincola, F. M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 12 BP 8 EP 8 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000012 ER PT J AU Holbeck, S Collins, JM Doroshow, JH AF Holbeck, S. Collins, J. M. Doroshow, J. H. TI NCI-60 Combination Screening Matrix of Approved Anticancer Drugs SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Holbeck, S.; Collins, J. M.] NCI, Rockville, MD USA. [Doroshow, J. H.] NCI, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 27 BP 11 EP 11 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000025 ER PT J AU Paoloni, M Webb, C Mazcko, C Cherba, D Ehrhart, EJ Lana, S Fehling, H Kingsley, C Khanna, C Trent, J AF Paoloni, M. Webb, C. Mazcko, C. Cherba, D. Ehrhart, E. J. Lana, S. Fehling, H. Kingsley, C. Khanna, C. Trent, J. TI Prospective Molecular Profiling of Canine Cancers Provides a Comparative Model for Evaluating Personalized Medicine Clinical Trials SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Paoloni, M.; Mazcko, C.; Khanna, C.] NCI, Comparatve Oncol Program, Bethesda, MD 20892 USA. [Webb, C.; Cherba, D.] Van Andel Res Inst, Grand Rapids, MI USA. [Ehrhart, E. J.; Lana, S.] Colorado State Univ, Ft Collins, CO 80523 USA. [Fehling, H.] Clin Reference Lab, Lenexa, KS USA. [Kingsley, C.; Trent, J.] TGEN, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 63 BP 21 EP 21 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000059 ER PT J AU Cook, KL Schwartz, JL Facey, COB Jin, L Zwart, A Abu-Azab, M Warri, A Clarke, R AF Cook, K. L. Schwartz, J. L. Facey, C. O. B. Jin, L. Zwart, A. Abu-Azab, M. Warri, A. Clarke, R. TI Un"Abl"ing Anti-estrogen Therapy Resistance in Estrogen Receptor-alpha Positive Breast Cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Cook, K. L.; Schwartz, J. L.; Facey, C. O. B.; Jin, L.; Zwart, A.; Warri, A.; Clarke, R.] Georgetown Univ, Washington, DC USA. [Abu-Azab, M.] NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 79 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000075 ER PT J AU Noonan, AM Chen, J Herrmann, M Annunziata, CM AF Noonan, A. M. Chen, J. Herrmann, M. Annunziata, C. M. TI Birinapant, a Novel Smac Mimetic, Activates Apoptosis in NF-kappaB-dependent Gynecologic Cancer Cell Lines SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Noonan, A. M.; Annunziata, C. M.] NCI, Translat Genom Sect, Med Oncol Branch, Bethesda, MD 20892 USA. [Chen, J.; Herrmann, M.] NCI, Collaborat Prot Technol Resource Lab Cell Biol, Ctr Canc Res, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 97 BP 31 EP 31 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000093 ER PT J AU Song, G Moore, S Tarrant, T Dobrovolskaia, M Barrow, D Kumar, P Newman, S Bae-Jump, V Gehrig, P Zamboni, W AF Song, G. Moore, S. Tarrant, T. Dobrovolskaia, M. Barrow, D. Kumar, P. Newman, S. Bae-Jump, V. Gehrig, P. Zamboni, W. TI Relationship Between Complement Factors and CC Chemokines and the Pharmacokinetics (PK) and Pharmacodynamics (PD) of PEGylated Liposomal Doxorubicin (PLD) in Patients with Refractory Epithelial Ovarian Cancer (EOC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Song, G.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. [Tarrant, T.] Univ N Carolina, Dept Med, Div Rheumatol Allergy & Immunol, Chapel Hill, NC USA. [Dobrovolskaia, M.] NCI, SAIC Frederick Inc, Nanotechnol Characterizat Lab, Chapel Hill, NC USA. [Barrow, D.] Univ N Carolina, Dent Res Ctr, Cytokine Anal Facil, Chapel Hill, NC 27599 USA. [Kumar, P.; Newman, S.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA. [Bae-Jump, V.; Gehrig, P.] Univ N Carolina, Div Gynecol Oncol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Zamboni, W.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut,Inst Pharmac, Lineberger Comprehens Canc Ctr,Carolina Ctr Canc, Chapel Hill, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 126 BP 39 EP 40 PG 2 WC Oncology SC Oncology GA 060FX UT WOS:000312763000122 ER PT J AU He, M Zuck, K Shipley, S Giddings, L DeLloyd, T Newman, D AF He, M. Zuck, K. Shipley, S. Giddings, L. DeLloyd, T. Newman, D. TI Potent Spliceostatin Analogs Isolated From Pseudomonas by Manipulations of Fermentation and Co-Culturing Conditions SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [He, M.; Giddings, L.; Newman, D.] NCI, DCTD, DTP, NPB, Frederick, MD USA. [Zuck, K.; Shipley, S.; DeLloyd, T.] SAIC Frederick Inc, NPSG, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 216 BP 66 EP 66 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000212 ER PT J AU Pommier, Y Reinhold, WC Sunshine, M Varma, SH Kohn, KW Doroshow, JH AF Pommier, Y. Reinhold, W. C. Sunshine, M. Varma, S. H. Kohn, K. W. Doroshow, J. H. TI CellMiner: a Web-Based Suite of Genomic and Pharmacologic Tools to Explore Transcript and Drug Patterns in the NCI-60 Cell Line Set SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Pommier, Y.; Reinhold, W. C.; Sunshine, M.; Varma, S. H.; Kohn, K. W.; Doroshow, J. H.] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 268 BP 82 EP 82 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000261 ER PT J AU Dexheimer, TS Nguyen, GH Rosenthal, AS Bohr, VA Harris, CC Jadhav, A Gileadi, O Maloney, DJ Simeonov, A Hickson, ID AF Dexheimer, T. S. Nguyen, G. H. Rosenthal, A. S. Bohr, V. A. Harris, C. C. Jadhav, A. Gileadi, O. Maloney, D. J. Simeonov, A. Hickson, I. D. TI A Small Molecule Inhibitor of the BLM Helicase That Modulates Chromosome Stability in Human Cells SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Dexheimer, T. S.; Rosenthal, A. S.; Jadhav, A.; Maloney, D. J.; Simeonov, A.] Natl Ctr Adv Translat Sci, Div Priclin Innovat, Rockville, MD USA. [Nguyen, G. H.; Harris, C. C.] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Bohr, V. A.] NIA, NIH, Baltimore, MD 21224 USA. [Gileadi, O.] Univ Oxford, Struct Genom Consortium, Oxford, England. [Hickson, I. D.] Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 276 BP 85 EP 85 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000269 ER PT J AU Pommier, Y Huang, SH Das, BB Renaud, A Zhang, Y Takeda, SH Doroshow, JH AF Pommier, Y. Huang, S. H. Das, B. B. Renaud, A. Zhang, Y. Takeda, S. H. Doroshow, J. H. TI Differential Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Pommier, Y.; Huang, S. H.; Das, B. B.; Renaud, A.; Zhang, Y.; Doroshow, J. H.] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Takeda, S. H.] Kyoto Univ, Dept Radiat Genet, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 2 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 284 BP 87 EP 87 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000277 ER PT J AU Abi-Habib, R Kassab, E Darwish, M Timsah, Z Liu, S Leppla, S Frankel, A AF Abi-Habib, R. Kassab, E. Darwish, M. Timsah, Z. Liu, S. Leppla, S. Frankel, A. TI Acute Myeloid Leukemia (AML) Cell Lines Are Sensitive to the Anthrax Lethal Toxin (LeTx)-Mediated Inhibition of the MAPK Pathway SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Abi-Habib, R.; Kassab, E.; Darwish, M.; Timsah, Z.] Lebanese Amer Univ, Beirut, Lebanon. [Liu, S.; Leppla, S.] NIAID, NIH, Bethesda, MD 20892 USA. [Frankel, A.] Scott & White Mem Hosp & Clin, Canc Res Inst, Temple, TX 76508 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 326 BP 100 EP 100 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000319 ER PT J AU Smith, M Kang, M Lock, R Carol, H Gorlick, R Kolb, A Maris, J Keir, S Kurmasheva, R Houghton, P AF Smith, M. Kang, M. Lock, R. Carol, H. Gorlick, R. Kolb, A. Maris, J. Keir, S. Kurmasheva, R. Houghton, P. TI Pediatric Preclinical Testing Program (PPTP) Stage 1 Evaluation of Eribulin SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Smith, M.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Kang, M.] Texas Tech Univ Hlth Sci Ctr, Ctr Canc, Lubbock, TX USA. [Lock, R.; Carol, H.] Childrens Canc Inst, Leukemia Biol Program, Randwick, NSW, Australia. [Gorlick, R.] Montefiore Med Ctr, Dept Pediat, Bronx, NY 10467 USA. [Kolb, A.] Alfred I DuPont Hosp Children, Dept Oncol, Wilmington, DE USA. [Maris, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Keir, S.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27706 USA. [Kurmasheva, R.; Houghton, P.] Nationwide Childrens Hosp, Ctr Childhood Canc & Blood Dis, Columbus, OH USA. RI Carol, Hernan/F-5750-2013 OI Carol, Hernan/0000-0002-9443-8032 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 345 BP 105 EP 105 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000338 ER PT J AU Nagy, Z Orosz, E Kovacs, I Torok, M Biro, T Blumberg, PM Czifral, G AF Nagy, Z. Orosz, E. Kovacs, I. Toeroek, M. Biro, T. Blumberg, P. M. Czifral, G. TI Investigation of RasGRP3 Expression and Function in Human Breast Cancers and Breast-derived Ductal Adenocarcinoma Cell Lines SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Nagy, Z.; Orosz, E.; Biro, T.; Czifral, G.] Univ Debrecen, Dept Physiol, Debrecen, Hungary. [Kovacs, I.; Toeroek, M.] Gyula Kenezy Hosp, Dept Pathol, Debrecen, Hungary. [Blumberg, P. M.] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 381 BP 116 EP 116 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000374 ER PT J AU Hernandez, L Kohlhammer, H Staudt, L Annunziata, CM AF Hernandez, L. Kohlhammer, H. Staudt, L. Annunziata, C. M. TI Genome-wide shRNa Library Screen Identifies CASPASE 8 as a Gene Sensitizing Ovarian Cancer Cells to IKK beta Inhibition SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Hernandez, L.; Annunziata, C. M.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Kohlhammer, H.; Staudt, L.] NCI, Metab Branch, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 392 BP 119 EP 119 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000385 ER PT J AU Nafi, SM Kong, A Gijsen, M Kramer-Marek, G Capala, J AF Nafi, S. Mohd Kong, A. Gijsen, M. Kramer-Marek, G. Capala, J. TI Investigating the Role of HER4 in Relation to Trastuzumab Treatment and Resistance in HER2 Positive Breast Cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Nafi, S. Mohd; Kong, A.; Gijsen, M.] Univ Oxford, Epidermal Growth Factor Grp, Weatherall Inst Mol Med, Oxford, England. [Kramer-Marek, G.; Capala, J.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RI Mohd Nafi, Siti Norasikin/M-4548-2015 OI Mohd Nafi, Siti Norasikin/0000-0002-0642-0909 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 415 BP 126 EP 126 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000408 ER PT J AU Forest, A Amatulli, M Damoci, C Ludwig, D Baltes, N Fiebig, H Houghton, P Smith, M Benjamin, L Novosyadlyy, R AF Forest, A. Amatulli, M. Damoci, C. Ludwig, D. Baltes, N. Fiebig, H. Houghton, P. Smith, M. Benjamin, L. Novosyadlyy, R. TI Two Insulin Receptor Isoforms Confer Intrinsic Resistance to the Antibody Against Insulin-like Growth Factor Receptor I SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Forest, A.; Amatulli, M.; Damoci, C.; Ludwig, D.; Benjamin, L.; Novosyadlyy, R.] Eli Lilly & Co, NYC, Indianapolis, IN USA. [Baltes, N.; Fiebig, H.] Oncotest, Freiburg, Germany. [Houghton, P.] Nationwide Childrens Hosp, Columbus, OH USA. [Smith, M.] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 451 BP 140 EP 140 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000444 ER PT J AU Yang, SX Kidwell, K Costantino, JC Mamounas, EP Nguyen, D Kim, C Wolmark, N Paik, S AF Yang, S. X. Kidwell, K. Costantino, J. C. Mamounas, E. P. Nguyen, D. Kim, C. Wolmark, N. Paik, S. TI Prognostic Significance of pAKT Plus Estrogen Receptor Status in Adjuvant Cytotoxic Treatment of Breast Cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Yang, S. X.; Nguyen, D.] NCI, NIH, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Kidwell, K.; Costantino, J. C.] Natl Surg Adjuvant Breast & Bowel Project, Dept Biostat, Pittsburgh, PA USA. [Mamounas, E. P.] Aultman Hlth Fdn, Dept Oncol, Canton, OH USA. [Kim, C.; Paik, S.] Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA USA. [Wolmark, N.] Natl Surg Adjuvant Breast & Bowel Project, Div Surg, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 478 BP 148 EP 148 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000471 ER PT J AU Parchment, RE Kinders, RJ Ji, J Srivastava, AK Ferry-Galow, K Tomaszewski, JE Doroshow, JH AF Parchment, R. E. Kinders, R. J. Ji, J. Srivastava, A. K. Ferry-Galow, K. Tomaszewski, J. E. Doroshow, J. H. TI Creating Clinical Target Validation Groups Via Quality Assured Transfer of Robust Clinical Pharmacodynamic (PD) Assays From the National Cancer Institute SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Parchment, R. E.; Kinders, R. J.; Srivastava, A. K.; Ferry-Galow, K.] Frederick Natl Lab Canc Res, Lab Human Toxicol & Pharmacol, Frederick, MD USA. [Ji, J.] Frederick Natl Lab Canc Res, Natl Clin Target Validat Lab, Frederick, MD USA. [Tomaszewski, J. E.; Doroshow, J. H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 493 BP 153 EP 153 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000486 ER PT J AU Kim, M Annunziata, C AF Kim, M. Annunziata, C. TI CHEK1 Cooperates with IKK epsilon to Promote Survival of Ovarian Cancer Patients SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Kim, M.; Annunziata, C.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 534 BP 164 EP 164 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000526 ER PT J AU Kummar, S Safgren, SL Lindenberg, M Kurdziel, K Reid, JM Streicher, H Ames, MM Jacobs, P Collins, J Doroshow, JH AF Kummar, S. Safgren, S. L. Lindenberg, M. Kurdziel, K. Reid, J. M. Streicher, H. Ames, M. M. Jacobs, P. Collins, J. Doroshow, J. H. TI Phase I Trial of Z-endoxifen with Estrogen Receptor Imaging in Adults with Refractory Hormone Receptor-positive Breast Cancer, Desmoid Tumors, Gynecologic Tumors, or Other Hormone Receptor-Positive Solid Tumors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Kummar, S.; Streicher, H.; Jacobs, P.; Collins, J.; Doroshow, J. H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Lindenberg, M.; Kurdziel, K.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Safgren, S. L.; Reid, J. M.; Ames, M. M.] Mayo Clin, Dept Oncol, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 591 BP 181 EP 181 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000583 ER PT J AU Kummar, S Anderson, L Hill, K Majerova, E Allen, D Horneffer, Y Ivy, P Harris, P Doroshow, JH Collins, J AF Kummar, S. Anderson, L. Hill, K. Majerova, E. Allen, D. Horneffer, Y. Ivy, P. Harris, P. Doroshow, J. H. Collins, J. TI First-in-human Phase 0 Trial of Oral 5-iodo-2-pyrimidinone-2 '-deoxyribose (IPdR) in Patients with Advanced Malignancies SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Kummar, S.; Anderson, L.; Ivy, P.; Harris, P.; Doroshow, J. H.; Collins, J.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Allen, D.; Horneffer, Y.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Hill, K.; Majerova, E.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 592 BP 181 EP 182 PG 2 WC Oncology SC Oncology GA 060FX UT WOS:000312763000584 ER PT J AU Cerna, D Carter, D Takebe, N Coleman, CN Yoo, S AF Cerna, D. Carter, D. Takebe, N. Coleman, C. N. Yoo, S. TI Radiosensitization of Glioma Cell Lines by a Novel Peptidomimetic of the Second Mitochondria-derived Activator of Caspases (SMAC) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Cerna, D.; Carter, D.] Frederick Natl Lab Canc Res, Mol Radiat Therapeut Branch Support, Frederick, MD USA. [Takebe, N.] NCI, Canc Therapy Evaluat Program, Rockville, MD USA. [Coleman, C. N.] NCI, Radiat Res Program, Rockville, MD USA. [Yoo, S.] NCI, Mol Radiat Therapeut Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 624 BP 192 EP 192 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000616 ER PT J AU Soto-Pantoja, D Manso, GGM Ridnour, LA DeGraff, W Wink, DA Roberts, DD AF Soto-Pantoja, D. Manso, G. Gema Martin Ridnour, L. A. DeGraff, W. Wink, D. A. Roberts, D. D. TI Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling is Associated with Selective Activation of Autophagy SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 06-09, 2012 CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co HO European Org Res & Treatment Canc (EORTC) C1 [Soto-Pantoja, D.; Manso, G. Gema Martin; Roberts, D. D.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Ridnour, L. A.; DeGraff, W.; Wink, D. A.] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 SU 6 MA 622 BP 192 EP 192 PG 1 WC Oncology SC Oncology GA 060FX UT WOS:000312763000614 ER PT J AU Bruce, I Chan, CC AF Bruce, Isaac Chan, Chi-Chao TI Interview with Chi-Chao Chan SO FUTURE MEDICINAL CHEMISTRY LA English DT Editorial Material C1 [Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 J9 FUTURE MED CHEM JI Future Med. Chem. PD NOV PY 2012 VL 4 IS 17 BP 2139 EP 2140 DI 10.4155/FMC.12.171 PG 2 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 059AG UT WOS:000312676200010 ER PT J AU Sallo, FB Peto, T Egan, C Wolf-Schnurrbusch, UEK Clemons, TE Gillies, MC Pauleikhoff, D Rubin, GS Chew, EY Bird, AC AF Sallo, Ferenc B. Peto, Tunde Egan, Catherine Wolf-Schnurrbusch, Ute E. K. Clemons, Traci E. Gillies, Mark C. Pauleikhoff, Daniel Rubin, Gary S. Chew, Emily Y. Bird, Alan C. CA MacTel Study Grp TI The IS/OS Junction Layer in the Natural History of Type 2 Idiopathic Macular Telangiectasia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; JUXTAFOVEOLAR RETINAL TELANGIECTASIS; CENTRAL SEROUS CHORIORETINOPATHY; FOVEAL PHOTORECEPTOR LAYER; FUNDUS AUTOFLUORESCENCE; VISUAL FUNCTION; VEIN OCCLUSION; HOLE SURGERY; MICROPERIMETRY; RESOLUTION AB PURPOSE. To document the progression of a break in the photoreceptor inner segment/outer segment (IS/OS) junction layer and its functional correlates over time in the natural history of type 2 idiopathic macular telangiectasia (type 2 MacTel). METHODS. Patients with at least 1 year of follow-up were selected from the MacTel Study. En face images were created by manual segmentation of the IS/OS junctional line in volume scans acquired using a spatial-domain optical coherence tomography retinal imaging unit. Retinal sensitivity thresholds were determined using a retinal microperimeter unit. Aggregate retinal sensitivity loss within IS/OS lesions was calculated. Changes over time in an area of IS/OS defects and retinal sensitivity were analyzed. RESULTS. Thirty-nine eyes of 23 patients (mean age: 62.3 +/- 9.2 years) were analyzed. Mean follow-up time was 1.9 years (range: 1-3 years). Mean IS/OS break area at baseline was 0.575 mm(2) (SE = 0.092, 95% confidence interval [CI]: 0.394-0.756 mm(2)). The cluster-adjusted mean annual progression rate in IS/OS break area was 0.140 mm(2) (SE = 0.040, 95% CI: 0.062-0.218 mm(2), P < 0.001). Mean aggregate retinal sensitivity loss was at baseline 28.56 dB (SE = 5.43, 95% CI: 17.32-39.80 dB, n = 28), a positive correlation with IS/OS lesion area was present (P < 0.001). The mean annual rate of change in aggregate sensitivity loss was 5.14 dB (SE = 1.51, 95% CI: 2.19-8.10 dB, P < 0.001, n = 37), a significant correlation with lesion area increase was found (P = 0.006). CONCLUSIONS. Both IS/OS break area and rate of enlargement correlate with aggregate retinal sensitivity loss in type 2 MacTel. En face OCT imaging of the IS/OS layer provides a functionally relevant method for documenting disease progression in type 2 MacTel. (Invest Ophthalmol Vis Sci. 2012; 53:7889-7895) DOI:10.1167/iovs.12-10765 C1 [Sallo, Ferenc B.] Moorfields Eye Hosp NHS Fdn Trust, Reading Ctr, Dept Res & Dev, Moorfields Eye Hosp, London EC1V 2PD, England. [Sallo, Ferenc B.; Rubin, Gary S.] UCL, Inst Opthalmol, London, England. [Sallo, Ferenc B.; Wolf-Schnurrbusch, Ute E. K.] Univ Bern, Univ Klin Augenheilkunde, Bern, Switzerland. [Peto, Tunde] Moorfields Eye Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr Ophthalmol, London, England. [Peto, Tunde] UCL Inst Ophthalmol, London, England. [Clemons, Traci E.] EMMES Corp, Rockville, MD USA. [Gillies, Mark C.] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia. [Pauleikhoff, Daniel] St Franziskus Hosp, Munster, Germany. [Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA. [Bird, Alan C.] Moorfields Eye Hosp, Div Inherited Eye Dis, London, England. RP Sallo, FB (reprint author), Moorfields Eye Hosp NHS Fdn Trust, Reading Ctr, Dept Res & Dev, Moorfields Eye Hosp, 162 City Rd, London EC1V 2PD, England. EM Ferenc.Sallo@moorfields.nhs.uk RI gillies, mark/B-3242-2012; Rubin, Gary/A-4928-2009; Wolf, Sebastian/B-8782-2008; Sahel, Jose-Alain/F-3172-2017 OI Rubin, Gary/0000-0002-2547-4953; Wolf, Sebastian/0000-0002-7467-7028; FU Lowy Medical Research Institute (LMRI); National Institute for Health Research FX Supported by the Lowy Medical Research Institute (LMRI) and the National Institute for Health Research. The LMRI also participated in the design of the study and in the review and approval of the manuscript. NR 40 TC 22 Z9 22 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2012 VL 53 IS 12 BP 7889 EP 7895 DI 10.1167/iovs.12-10765 PG 7 WC Ophthalmology SC Ophthalmology GA 064EE UT WOS:000313053500064 PM 23092925 ER PT J AU Parsa, N AF Parsa, N. TI Environmental Factors Inducing Human Cancers SO IRANIAN JOURNAL OF PUBLIC HEALTH LA English DT Review DE Environmental factors; Cancer causing genes; Human cancers ID TUMOR-SUPPRESSOR GENE; LYMPHOMA CELL-LINES; PREVENT CANCER; RISK; INFECTION; RADIATION; ONCOGENE; ALCOHOL; TRIAL AB Background: An explosion of research has been done in discovering how human health is affected by environmental factors. I will discuss the impacts of environmental cancer causing factors and how they continue to cause multiple disruptions in cellular networking. Some risk factors may not cause cancer. Other factors initiate consecutive genetic mutations that would eventually alter the normal pathway of cellular proliferations and differentiation. Genetic mutations in four groups of genes; (Oncogenes, Tumor suppressor genes, Apoptosis genes and DNA repairing genes) play a vital role in altering the normal cell division. In recent years, molecular genetics have greatly increased our understanding of the basic mechanisms in cancer development and utilizing these molecular techniques for cancer screening, diagnosis, prognosis and therapies. Inhibition of carcinogenic exposures wherever possible should be the goal of cancer prevention programs to reduce exposures from all environmental carcinogens. C1 NIH, Bethesda, MD 20892 USA. RP Parsa, N (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM nzparsa@yahoo.com NR 35 TC 4 Z9 4 U1 7 U2 17 PU IRANIAN SCIENTIFIC SOCIETY MEDICAL ENTOMOLOGY PI TEHRAN PA SCHOOL PUBLIC HEALTH & INST HEALTH RESEARCH, TEHRAN UNIV MEDICAL SCIENCES, P O BOX 6446-14155, TEHRAN, 00000, IRAN SN 2251-6085 J9 IRAN J PUBLIC HEALTH JI Iran J. Public Health PD NOV PY 2012 VL 41 IS 11 BP 1 EP 9 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 061SC UT WOS:000312867300001 PM 23304670 ER PT J AU Casoni, F Hutchins, BI Donohue, D Fornaro, M Condie, BG Wray, S AF Casoni, Filippo Hutchins, B. Ian Donohue, Duncan Fornaro, Michele Condie, Brian G. Wray, Susan TI SDF and GABA interact to regulate axophilic migration of GnRH neurons SO JOURNAL OF CELL SCIENCE LA English DT Article DE GABA; GIRK; GnRH; Motility; Neuronal migration; SDF ID HORMONE-RELEASING HORMONE; CELL-DERIVED FACTOR-1-ALPHA; GAMMA-AMINOBUTYRIC-ACID; LHRH NEURONS; INTERNEURON MIGRATION; OLFACTORY EXPLANTS; KALLMANN-SYNDROME; CEREBRAL-CORTEX; KNOCKOUT MICE; CLEFT-PALATE AB Stromal derived growth factor (SDF-1) and gamma-aminobutyric acid (GABA) are two extracellular cues that regulate the rate of neuronal migration during development and may act synergistically. The molecular mechanisms of this interaction are still unclear. Gonadotropin releasing hormone-1 (GnRH) neurons are essential for vertebrate reproduction. During development, these neurons emerge from the nasal placode and migrate through the cribriform plate into the brain. Both SDF-1 and GABA have been shown to regulate the rate of GnRH neuronal migration by accelerating and slowing migration, respectively. As such, this system was used to explore the mechanism by which these molecules act to produce coordinated cell movement during development. In the present study, GABA and SDF-1 are shown to exert opposite effects on the speed of cell movement by activating depolarizing or hyperpolarizing signaling pathways, GABA via changes in chloride and SDF-1 via changes in potassium. GABA and SDF-1 were also found to act synergistically to promote linear rather than random movement. The simultaneous activation of these signaling pathways, therefore, results in tight control of cellular speed and improved directionality along the migratory pathway of GnRH neurons. C1 [Casoni, Filippo; Hutchins, B. Ian; Donohue, Duncan; Fornaro, Michele; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Fornaro, Michele] Midwestern Univ, Dept Anat, Downers Grove, IL 60515 USA. [Condie, Brian G.] Univ Georgia, Dept Genet, Athens, GA 30602 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov RI Hutchins, Ian/A-5713-2009; OI Hutchins, Ian/0000-0001-7657-552X; Fornaro, Michele/0000-0003-1852-9167; wray, susan/0000-0001-7670-3915 FU Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke [ZIA NS002824-21]; National Institutes of Health [R01MH064794]; Pharmacology Research Associate (PRAT) Program of the National Institute of General Medical Sciences, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke [grant number ZIA NS002824-21]; and the National Institutes of Health [grant number R01MH064794 to B.G.C.]. B.I.H. was supported by the Pharmacology Research Associate (PRAT) Program of the National Institute of General Medical Sciences, National Institutes of Health. Deposited in PMC for release after 12 months. NR 76 TC 19 Z9 20 U1 1 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 1 PY 2012 VL 125 IS 21 BP 5015 EP 5025 DI 10.1242/jcs.101675 PG 11 WC Cell Biology SC Cell Biology GA 063GN UT WOS:000312984300010 PM 22976302 ER PT J AU Morens, DM Fauci, AS AF Morens, David M. Fauci, Anthony S. TI Emerging Infectious Diseases in 2012: 20 Years after the Institute of Medicine Report SO MBIO LA English DT Article ID PERPETUAL CHALLENGE; VIRUS; TRANSMISSION; EMERGENCE; INFLUENZA; SPREAD; GENOME; DEATH AB Twenty years ago (1992), a landmark Institute of Medicine report entitled "Emerging Infections: Microbial Threats to Health in the United States" underscored the important but often underappreciated concept of emerging infectious diseases (EIDs). A review of the progress made and setbacks experienced over the past 2 decades suggests that even though many new diseases have emerged, such as SARS (severe acute respiratory syndrome) and the 2009 pandemic influenza, significant advances have occurred in EID control, prevention, and treatment. Among many elements of the increase in the capacity to control EIDs are genomics-associated advances in microbial detection and treatment, improved disease surveillance, and greater awareness of EIDs and the complicated variables that underlie emergence. In looking back over the past 20 years, it is apparent that we are in a time of great change in which both the challenge of EIDs and our responses to them are being transformed. Recent advances support guarded optimism that further breakthroughs lie ahead. C1 [Morens, David M.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM dm270q@nih.gov NR 33 TC 7 Z9 7 U1 0 U2 29 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD NOV-DEC PY 2012 VL 3 IS 6 AR e00494-12 DI 10.1128/mBio.00494-12 PG 4 WC Microbiology SC Microbiology GA 064UK UT WOS:000313100700031 ER PT J AU Wasmuth, JD Pszenny, V Haile, S Jansen, EM Gast, AT Sher, A Boyle, JP Boulanger, MJ Parkinson, J Grigg, ME AF Wasmuth, James D. Pszenny, Viviana Haile, Simon Jansen, Emily M. Gast, Alexandra T. Sher, Alan Boyle, Jon P. Boulanger, Martin J. Parkinson, John Grigg, Michael E. TI Integrated Bioinformatic and Targeted Deletion Analyses of the SRS Gene Superfamily Identify SRS29C as a Negative Regulator of Toxoplasma Virulence SO MBIO LA English DT Article ID SURFACE-ANTIGENS; PLASMODIUM-FALCIPARUM; TRYPANOSOMA-BRUCEI; GONDII; FAMILY; OVERPRODUCTION; RECOMBINATION; TRANSCRIPTION; TACHYZOITES; EXPRESSION AB The Toxoplasma gondii SRS gene superfamily is structurally related to SRS29B (formerly SAG1), a surface adhesin that binds host cells and stimulates host immunity. Comparative genomic analyses of three Toxoplasma strains identified 182 SRS genes distributed across 14 chromosomes at 57 genomic loci. Eight distinct SRS subfamilies were resolved. A core 69 functional gene orthologs were identified, and strain-specific expansions and pseudogenization were common. Gene expression profiling demonstrated differential expression of SRS genes in a developmental-stage-and strain-specific fashion and identified nine SRS genes as priority targets for gene deletion among the tissue-encysting coccidia. A Delta sag1 Delta sag2A mutant was significantly attenuated in murine acute virulence and showed upregulated SRS29C (formerly SRS2) expression. Transgenic overexpression of SRS29C in the virulent RH parent was similarly attenuated. Together, these findings reveal SRS29C to be an important regulator of acute virulence in mice and demonstrate the power of integrated genomic analysis to guide experimental investigations. IMPORTANCE Parasitic species employ large gene families to subvert host immunity to enable pathogen colonization and cause disease. Toxoplasma gondii contains a large surface coat gene superfamily that encodes adhesins and virulence factors that facilitate infection in susceptible hosts. We generated an integrated bioinformatic resource to predict which genes from within this 182-gene superfamily of adhesin-encoding genes play an essential role in the host-pathogen interaction. Targeted gene deletion experiments with predicted candidate surface antigens identified SRS29C as an important negative regulator of acute virulence in murine models of Toxoplasma infection. Our integrated computational and experimental approach provides a comprehensive framework, or road map, for the assembly and discovery of additional key pathogenesis genes contained within other large surface coat gene superfamilies from a broad array of eukaryotic pathogens. C1 [Wasmuth, James D.; Parkinson, John] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1X8, Canada. [Wasmuth, James D.; Pszenny, Viviana; Gast, Alexandra T.; Grigg, Michael E.] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Haile, Simon; Jansen, Emily M.; Grigg, Michael E.] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Boyle, Jon P.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. [Boulanger, Martin J.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. [Parkinson, John] Univ Toronto, Dept Biochem, Toronto, ON, Canada. [Parkinson, John] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. RP Parkinson, J (reprint author), Hosp Sick Children, Program Mol Struct & Funct, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM john.parkinson@utoronto.ca; griggm@niaid.nih.gov RI Parkinson, John/A-4424-2008 OI Parkinson, John/0000-0001-9815-1189 FU CIHR (MOP) [84556, 82915]; NIH; NIAID; Ontario MRI FX This study was financially supported by the CIHR (MOP no. 84556 to J.P. and M. E. G.), the Intramural Research Program of the NIH and NIAID (M. E. G.), and the Ontario MRI (J.P.). M.J.B. was supported by the CIHR (MOP no. 82915). NR 36 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD NOV-DEC PY 2012 VL 3 IS 6 AR e00321-12 DI 10.1128/mBio.00321-12 PG 13 WC Microbiology SC Microbiology GA 064UK UT WOS:000313100700005 ER PT J AU Weinberger, AD Wolf, YI Lobkovsky, AE Gilmore, MS Koonin, EV AF Weinberger, Ariel D. Wolf, Yuri I. Lobkovsky, Alexander E. Gilmore, Michael S. Koonin, Eugene V. TI Viral Diversity Threshold for Adaptive Immunity in Prokaryotes SO MBIO LA English DT Article ID SINGLE-NUCLEOTIDE SUBSTITUTIONS; CRISPR RNA; SPONTANEOUS MUTATION; STREPTOCOCCUS-THERMOPHILUS; BACTERIAL; FITNESS; EVOLUTION; SYSTEM; DNA; RESISTANCE AB Bacteria and archaea face continual onslaughts of rapidly diversifying viruses and plasmids. Many prokaryotes maintain adaptive immune systems known as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (Cas). CRISPR-Cas systems are genomic sensors that serially acquire viral and plasmid DNA fragments (spacers) that are utilized to target and cleave matching viral and plasmid DNA in subsequent genomic invasions, offering critical immunological memory. Only 50% of sequenced bacteria possess CRISPR-Cas immunity, in contrast to over 90% of sequenced archaea. To probe why half of bacteria lack CRISPR-Cas immunity, we combined comparative genomics and mathematical modeling. Analysis of hundreds of diverse prokaryotic genomes shows that CRISPR-Cas systems are substantially more prevalent in thermophiles than in mesophiles. With sequenced bacteria disproportionately mesophilic and sequenced archaea mostly thermophilic, the presence of CRISPR-Cas appears to depend more on environmental temperature than on bacterial-archaeal taxonomy. Mutation rates are typically severalfold higher in mesophilic prokaryotes than in thermophilic prokaryotes. To quantitatively test whether accelerated viral mutation leads microbes to lose CRISPR-Cas systems, we developed a stochastic model of virus-CRISPR coevolution. The model competes CRISPR-Cas-positive (CRISPR-Cas +) prokaryotes against CRISPR-Cas-negative (CRISPR-Cas-) prokaryotes, continually weighing the antiviral benefits conferred by CRISPR-Cas immunity against its fitness costs. Tracking this cost-benefit analysis across parameter space reveals viral mutation rate thresholds beyond which CRISPR-Cas cannot provide sufficient immunity and is purged from host populations. These results offer a simple, testable viral diversity hypothesis to explain why mesophilic bacteria disproportionately lack CRISPR-Cas immunity. More generally, fundamental limits on the adaptability of biological sensors (Lamarckian evolution) are predicted. IMPORTANCE A remarkable recent discovery in microbiology is that bacteria and archaea possess systems conferring immunological memory and adaptive immunity. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (CRISPR-Cas) are genomic sensors that allow prokaryotes to acquire DNA fragments from invading viruses and plasmids. Providing immunological memory, these stored fragments destroy matching DNA in future viral and plasmid invasions. CRISPR-Cas systems also provide adaptive immunity, keeping up with mutating viruses and plasmids by continually acquiring new DNA fragments. Surprisingly, less than 50% of mesophilic bacteria, in contrast to almost 90% of thermophilic bacteria and Archaea, maintain CRISPR-Cas immunity. Using mathematical modeling, we probe this dichotomy, showing how increased viral mutation rates can explain the reduced prevalence of CRISPR-Cas systems in mesophiles. Rapidly mutating viruses outrun CRISPR-Cas immune systems, likely decreasing their prevalence in bacterial populations. Thus, viral adaptability may select against, rather than for, immune adaptability in prokaryotes. C1 [Weinberger, Ariel D.; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA. [Weinberger, Ariel D.; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Wolf, Yuri I.; Lobkovsky, Alexander E.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Weinberger, AD (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA. EM ariel_weinberger@meei.harvard.edu; koonin@ncbi.nlm.nih.gov FU NIH [AI072360]; U.S. Department of Health and Human Services (National Library of Medicine, NIH) FX We are grateful for the financial support from NIH grant AI072360 (to M. S. G.) and an NIH F32 Postdoctoral Fellowship (to A. D. W.). A. E. L., Y.I.W., and E. V. K. were supported by intramural funding from the U.S. Department of Health and Human Services (National Library of Medicine, NIH). We thank the Kavli Institute of Theoretical Physics (KITP) for hosting a cross-disciplinary workshop at which this collaboration began. NR 62 TC 18 Z9 18 U1 2 U2 35 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD NOV-DEC PY 2012 VL 3 IS 6 AR e00456-12 DI 10.1128/mBio.00456-12 PG 10 WC Microbiology SC Microbiology GA 064UK UT WOS:000313100700027 PM 23221803 ER PT J AU Apolo, AB Grossman, HB Bajorin, D Steinberg, G Kamat, AM AF Apolo, Andrea B. Grossman, Herbert Barton Bajorin, Dean Steinberg, Gary Kamat, Ashish M. TI Practical use of perioperative chemotherapy for muscle-invasive bladder cancer: Summary of session at the Society of Urologic Oncology annual meeting SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Review DE Bladder cancer; Neoadjuvant chemotherapy; Adjuvant chemotherapy; Perioperative chemotherapy; Muscle invasive bladder cancer ID TRANSITIONAL-CELL CARCINOMA; CISPLATIN-BASED CHEMOTHERAPY; GEMCITABINE PLUS CISPLATIN; PHASE-III TRIAL; RADICAL CYSTECTOMY; NEOADJUVANT CHEMOTHERAPY; UROTHELIAL CARCINOMA; RANDOMIZED-TRIAL; LYMPH-NODES; M-VAC AB At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for muscle-invasive bladder cancer. The discussion was structured as a case-based debate among the panelists. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of cisplatin-based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to cisplatin-based therapy, management of 'suboptimal' chemotherapy, residual disease after neoadjuvant chemotherapy, adjuvant chemotherapy, and key aspects of radical cystectomy and lymph-node dissection in multirnodal therapy. The presentations were derived from published literature. The panelists agreed that patients with muscle-invasive bladder cancer should be managed with a multidisciplinary team, including urologist and medical oncologist. Cisplatin-based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible patients with muscle-invasive bladder cancer. However, in some centers, neoadjuvant chemotherapy is reserved for patients with >T2 disease or high-risk features. There are no data for the administration of non-cisplatin-based neoadjuvant chemotherapy, such as carboplatin-combinations. Cisplatin-ineligible patients should proceed directly to surgical extirpation with adjuvant cisplatin-based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues, we may be able to better identify subsets of patients who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for muscle-invasive bladder cancer patients is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection. (c) 2012 Elsevier Inc. All rights reserved. C1 [Grossman, Herbert Barton; Kamat, Ashish M.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Apolo, Andrea B.] NCI, Med Oncol Branch, Bethesda, MD 20014 USA. [Bajorin, Dean] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10065 USA. [Steinberg, Gary] Univ Chicago, Med Ctr, Urol Sect, Chicago, IL 60637 USA. RP Kamat, AM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. EM akamat@mdanderson.org FU NCI NIH HHS [P30 CA016672] NR 64 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2012 VL 30 IS 6 BP 772 EP 780 DI 10.1016/j.urolonc.2012.01.012 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 056SI UT WOS:000312511300004 PM 23218068 ER PT J AU Filson, CP Miller, DC Colt, JS Ruterbusch, J Linehan, WM Chow, WH Schwartz, K AF Filson, Christopher P. Miller, David C. Colt, Joanne S. Ruterbusch, Julie Linehan, W. Marston Chow, Wong-Ho Schwartz, Kendra TI Surgical approach and the use of lymphadenectomy and adrenalectomy among patients undergoing radical nephrectomy for renal cell carcinoma SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Lymph node excision; Adrenalectomy; Renal cell carcinoma; Laparoscopy; Neoplasm staging ID LYMPH-NODE DISSECTION; CANCER; COMPONENT; TUMOR AB Objectives: We assessed the influence of tumor size and surgical approach on the use of lymphadenectomy and adrenalectomy with radical nephrectomy. Methods: We evaluated patients with renal cell carcinoma (RCC) enrolled in the U.S. Kidney Cancer Study, a case-control study in the metropolitan areas of Detroit and Chicago from 2002 to 2007. We identified patients who underwent open (URN) or laparoscopic radical nephrectomy (LRN). We used medical records and Surveillance, Epidemiology, and End Results (SEER) data to determine the proportion of patients who underwent lymphadenectomy or adrenalectomy. Bivariate analyses were performed to evaluate associations between tumor size, surgical approach, and receipt of lymphadenectomy or adrenalectomy. Results: We identified 730 patients who underwent URN (427, 58%) or LRN (303, 42%) for RCC from 2002 to 2007. Among this group, 11% and 24% underwent lymphadenectomy or adrenalectomy, respectively. Lymphadenectomy was more common among patients treated from an open surgical approach (14.1% URN vs. 5.9% LRN, P < 0.01); this difference was most pronounced for cases with tumors between 4 and 7 cm (15.9% vs. 2.9%, P = 0.01). Patients treated with URN were also more likely to undergo adrenalectomy, with the greatest discrepancy among cases with tumors <= 4 cm (21.7% vs. 11.4%, P < 0.01). Conclusions: Among patients undergoing radical nephrectomy for RCC, the use of lymphadenectomy and adrenalectomy is relatively uncommon and varies by tumor size and surgical approach. With an increasing number of patients with small tumors, the diffusion of laparoscopy, and the emergence of clinical trials evaluating systemic adjuvant therapies, our findings highlight important considerations for optimizing surgical management of patients with RCC. (C) 2012 Elsevier Inc. All rights reserved. C1 [Filson, Christopher P.; Miller, David C.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. [Miller, David C.] Vet Affairs Ctr Clin Management Res, Ann Arbor, MI 48105 USA. [Colt, Joanne S.; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Ruterbusch, Julie; Schwartz, Kendra] Karmanos Canc Inst, Detroit, MI 48201 USA. [Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Schwartz, Kendra] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI 48202 USA. RP Miller, DC (reprint author), Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. EM dcmiller@umich.edu OI Filson, Christopher/0000-0002-9353-871X; Filson, Christopher/0000-0002-8184-7275 FU National Institutes of Health [NIH-N02-CP-11004, NIH-T32-DK007782] FX This research was supported by the National Institutes of Health Intramural Research Program (NIH-N02-CP-11004) and Training in Clinical Investigation in Urology grant (NIH-T32-DK007782). NR 18 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2012 VL 30 IS 6 BP 856 EP 863 DI 10.1016/j.urolonc.2010.08.024 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 056SI UT WOS:000312511300016 PM 21419672 ER PT J AU Gulley, JL Emberton, M Kurhanewicz, J Choyke, P AF Gulley, James L. Emberton, Mark Kurhanewicz, John Choyke, Peter TI Progress in prostate cancer imaging SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostate cancer; Imaging AB There are multiple new technologies being developed for imaging of advanced prostate cancer. This Seminar article highlights several of these emerging modalities that were discussed at the Society of Urologic Oncology annual meeting in Bethesda, MD. (C) 2012 Elsevier Inc. All rights reserved. C1 [Gulley, James L.; Choyke, Peter] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Emberton, Mark] Univ Coll London Hosp, Div Surg & Intervent Sci, London, England. [Kurhanewicz, John] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Gulley, JL (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU NCI NIH HHS [R01 CA137207] NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2012 VL 30 IS 6 BP 938 EP 939 DI 10.1016/j.urolonc.2012.09.008 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 056SI UT WOS:000312511300028 PM 23218070 ER PT J AU Linehan, WM Rathmell, WK AF Linehan, W. Marston Rathmell, W. Kimryn TI Kidney cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Kidney cancer; Renal cancer ID RENAL-CELL CARCINOMA; FUMARATE-HYDRATASE; GENETIC-BASIS; INHIBITOR; PATHWAY AB Over 65,000 Americans are diagnosed with kidney cancer each year and nearly 13,000 die of this disease. Kidney cancer is not a single disease, it is made up of a number of different types of cancer, each with a different histology, a different clinical course, responding differently to therapy and caused by a different gene. Study of the 13 genes that are known to cause kidney cancer has led to the understanding that kidney cancer is a metabolic disease. Recent discoveries of chromatin remodeling/histone modifying genes, such as PBRM1 and SETD2, have opened up new areas of intense interest in the study of the fundamental genetic basis of kidney cancer. New approaches to immunotherapy with agents such as the CTLA4 inhibitor, ipilumumab, have opened up promising new directions for clinical trials. A number of new agents targeting of VEGF receptor signaling and the mTOR pathways as well as novel approaches targeting HIF2 will hopefully provide the foundation for the development of effective forms of therapy for this disease. (C) 2012 Published by Elsevier Inc. C1 [Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Rathmell, W. Kimryn] Univ N Carolina, Dept Med, Chapel Hill, NC 27514 USA. [Rathmell, W. Kimryn] Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. EM linehanm@mail.nih.gov FU Intramural NIH HHS [ZIA BC011028-05, ZIA BC011038-05, ZIA BC011043-05] NR 25 TC 7 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2012 VL 30 IS 6 BP 948 EP 951 DI 10.1016/j.urolonc.2012.08.021 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 056SI UT WOS:000312511300032 PM 23218074 ER PT J AU Ryugo, DK Menotti-Raymond, M AF Ryugo, David K. Menotti-Raymond, Marilyn TI Feline Deafness SO VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE LA English DT Article DE Auditory system; Brain; Cochlea; Congenital deafness; Genes; Synapse ID AUDITORY BRAIN-STEM; MEDIAL SUPERIOR OLIVE; ANTEROVENTRAL COCHLEAR NUCLEUS; SPIRAL GANGLION NEURONS; INTRACOCHLEAR ELECTRICAL-STIMULATION; WAARDENBURG-HIRSCHSPRUNG-DISEASE; SENSORINEURAL HEARING-LOSS; NEONATALLY DEAFENED CATS; ENDOTHELIN-B RECEPTOR; INFERIOR COLLICULUS AB Cats have among the best hearing of all mammals in that they are extremely sensitive to a broad range of frequencies. The ear is a highly complex structure that is delicately balanced in terms of its biochemistry, types of receptors, ion channels, mechanical properties, and cellular organization. Sensorineural deafness is caused by "flawed" genes that are inherited from one or both parents. Hearing loss can also be acquired as a result of noise trauma from industrialized environment, viral infection, or blunt trauma. To date, it is not practical to intervene and attempt to correct these forms of deafness in cats. C1 [Ryugo, David K.] Garvan Inst Med Res, Hearing Res Program, Sydney, NSW 2010, Australia. [Menotti-Raymond, Marilyn] NCI, Frederick Natl Lab Canc Res, Lab Genom Divers, Frederick, MD 21702 USA. RP Ryugo, DK (reprint author), Garvan Inst Med Res, Hearing Res Program, 384 Victoria St, Sydney, NSW 2010, Australia. EM d.ryugo@garvan.org.au RI Ryugo, David/G-1940-2012 OI Ryugo, David/0000-0002-5250-7503 FU NHMRC [1009842]; Garnett Passe and Rodney Williams Memorial Foundation; NSW Office of Science and Medical Research; Curran Foundation; NIH/NIDCD [DC004395]; National Cancer Institute, National Institutes of Health [HHSN26120080001E] FX D.K.R. is supported by NHMRC grant #1009842, The Garnett Passe and Rodney Williams Memorial Foundation, NSW Office of Science and Medical Research, the Curran Foundation, and NIH/NIDCD grant DC004395; M.M.R. is supported with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. The authors have nothing to disclose. NR 135 TC 4 Z9 4 U1 2 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0195-5616 J9 VET CLIN N AM-SMALL JI Vet. Clin. N. Am.-Small Anim. Pract. PD NOV PY 2012 VL 42 IS 6 BP 1179 EP + DI 10.1016/j.cvsm.2012.08.008 PG 30 WC Veterinary Sciences SC Veterinary Sciences GA 058ZZ UT WOS:000312675500007 PM 23122176 ER PT J AU Liu, W Phang, JM AF Liu, Wei Phang, James M. TI Proline dehydrogenase (oxidase) in cancer SO BIOFACTORS LA English DT Review DE proline dehydrogenase; oxidase; reactive oxygen species; tumor suppressor; oncogene; metabolic stress ID PPAR-GAMMA; INDUCED APOPTOSIS; PYRROLINE-5-CARBOXYLIC ACID; P53-INDUCED GENE-6; COLORECTAL-CANCER; TUMOR-SUPPRESSOR; OXIDIZED LDL; METABOLISM; STRESS; CELLS AB Proline dehydrogenase (oxidase, PRODH/POX), the first enzyme in the proline degradative pathway, plays a special role in tumorigenesis and tumor development. Proline metabolism catalyzed by PRODH/POX is closely linked with the tricarboxylic acid (TCA) cycle and urea cycle. The proline cycle formed by the interconversion of proline and ?1-pyrroline-5-carboxylate (P5C) between mitochondria and cytosol interlocks with pentose phosphate pathway. Importantly, by catalyzing proline to P5C, PRODH/POX donates electrons into the electron transport chain to generate ROS or ATP. In earlier studies, we found that PRODH/POX functions as a tumor suppressor to initiate apoptosis, inhibit tumor growth, and block the cell cycle, all by ROS signaling. It also suppresses hypoxia inducible factor signaling by increasing a-ketoglutarate. During tumor progression, PRODH/POX is under the control of various tumor-associated factors, such as tumor suppressor p53, inflammatory factor peroxisome proliferator-activated receptor gamma (PPAR?), onco-miRNA miR-23b*, and oncogenic transcription factor c-MYC. Recent studies revealed the two-sided features of PRODH/POX-mediated regulation. Under metabolic stress such as oxygen and glucose deprivation, PRODH/POX can be induced to serve as a tumor survival factor through ATP production or ROS-induced autophagy. The paradoxical roles of PRODH/POX can be understood considering the temporal and spatial context of the tumor. Further studies will provide additional insights into this protein and on its metabolic effects in tumors, which may lead to new therapeutic strategies.(C) 2012 International Union of Biochemistry and Molecular Biology, Inc. C1 [Liu, Wei; Phang, James M.] NIH, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD USA. RP Phang, JM (reprint author), Frederick Natl Lab, 1050 Boyles St,Bldg 538,Rm 144, Frederick, MD 21702 USA. EM phangj@mail.nih.gov RI liu, wei /E-7340-2012 FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, NIH [HHSN27612080001] FX The work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project also has been funded in part with Federal funds from the National Cancer Institute, NIH, under contract no. HHSN27612080001. The content of this review 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. The authors thank Dr. Ziqiang Zhu for his reading of the manuscript. NR 56 TC 18 Z9 18 U1 1 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-6433 J9 BIOFACTORS JI Biofactors PD NOV-DEC PY 2012 VL 38 IS 6 BP 398 EP 406 DI 10.1002/biof.1036 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 056YN UT WOS:000312528300002 PM 22886911 ER PT J AU Callahan, R Mudunuri, U Bargo, S Raafat, A McCurdy, D Boulanger, C Lowther, W Stephens, R Luke, BT Stewart, C Wu, XL Munroe, D Smith, GH AF Callahan, Robert Mudunuri, Uma Bargo, Sharon Raafat, Ahmed McCurdy, David Boulanger, Corinne Lowther, William Stephens, Robert Luke, Brian T. Stewart, Claudia Wu, Xiaolin Munroe, David Smith, Gilbert H. TI Genes affected by mouse mammary tumor virus (MMTV) proviral insertions in mouse mammary tumors are deregulated or mutated in primary human mammary tumors SO ONCOTARGET LA English DT Article DE mouse mammary tumor virus; premalignant lesions; mammary tumors; genes; human breast carcinomas; metastases ID ENVELOPE PROTEIN; TRANSGENIC MICE; BREAST-CANCER; PATHWAYS; ACTIVATION; EXPRESSION; FAMILY; TRANSPLANTATION; PROTOONCOGENES; PROGRESSION AB The accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. We have used a mouse model in which the carcinogen is the mouse mammary tumor virus (MMTV) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. Identification of the genes and signaling pathways affected in MMTV-induced mouse mammary lesions provides a rationale for determining whether genetic alteration of the human orthologues of these genes/pathways may contribute to human breast carcinogenesis. A high-throughput platform for inverse PCR to identify MMTV-host junction fragments and their nucleotide sequences in a large panel of MMTV-induced lesions was developed. Validation of the genes affected by MMTV-insertion was carried out by microarray analysis. Common integration site (CIS) means that the gene was altered by an MMTV proviral insertion in at least two independent lesions arising in different hosts. Three of the new genes identified as CIS for MMTV were assayed for their capability to confer on HC11 mouse mammary epithelial cells the ability for invasion, anchorage independent growth and tumor development in nude mice. Analysis of MMTV induced mammary premalignant hyperplastic outgrowth (HOG) lines and mammary tumors led to the identification of CIS restricted to 35 loci. Within these loci members of the Wnt, Fgf and Rspo gene families plus two linked genes (Npm3 and Ddn) were frequently activated in tumors induced by MMTV. A second group of 15 CIS occur at a low frequency (2-5 observations) in mammary HOGs or tumors. In this latter group the expression of either Phf19 or Sdc2 was shown to increase HC11 cells invasion capability. Foxl1 expression conferred on HC11 cells the capability for anchorage-independent colony formation in soft agar and tumor development in nude mice. The published transcriptome and nucleotide sequence analysis of gene expression in primary human breast tumors was interrogated. Twenty of the human orthologues of MMTV CIS associated genes are deregulated and/or mutated in human breast tumors. C1 [Callahan, Robert; Bargo, Sharon; Raafat, Ahmed; McCurdy, David; Boulanger, Corinne; Lowther, William; Smith, Gilbert H.] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. [Mudunuri, Uma; Stephens, Robert; Luke, Brian T.; Stewart, Claudia; Wu, Xiaolin; Munroe, David] NCI, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Stewart, Claudia; Wu, Xiaolin; Munroe, David] NCI, Lab Mol Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Callahan, R (reprint author), NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. EM rc54d@nih.gov FU Intramural Research Program of the National Cancer Institute (NCI); Center for Cancer Research (CCR) in the National Institutes of Health (NIH); NCI, NIH [HHSN261200800001E] FX This research was supported in part by the Intramural Research Program of the National Cancer Institute (NCI) and Center for Cancer Research (CCR) in the National Institutes of Health (NIH), and in part with federal funds from the NCI, NIH, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 37 TC 10 Z9 10 U1 0 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV PY 2012 VL 3 IS 11 BP 1320 EP 1334 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 056JE UT WOS:000312483600013 PM 23131872 ER PT J AU Sourbier, C Srivastava, G Ghosh, MC Ghosh, S Yang, YF Gupta, G DeGraff, W Krishna, MC Mitchell, JB Rouault, TA Linehan, WM AF Sourbier, Carole Srivastava, Gaurav Ghosh, Manik C. Ghosh, Sanchari Yang, Youfeng Gupta, Gopal DeGraff, William Krishna, Murali C. Mitchell, James B. Rouault, Tracey A. Linehan, W. Marston TI Targeting HIF2 alpha Translation with Tempol in VHL-Deficient Clear Cell Renal Cell Carcinoma SO ONCOTARGET LA English DT Article DE HIF; Tempol; RCC; VHL; IRP1; iron metabolism ID VON-HIPPEL-LINDAU; HYPOXIA-INDUCIBLE FACTORS; TUMOR-SUPPRESSOR PROTEIN; CARBONIC-ANHYDRASE IX; CANCER-CELLS; GENE; THERAPY; HIF-1-ALPHA; HIF1-ALPHA; IDENTIFICATION AB The tumor suppressor gene, Von Hippel-Lindau (VHL), is frequently mutated in the most common form of kidney cancer, clear cell renal cell carcinoma (CCRCC). In hypoxic conditions, or when there is a VHL mutation, the hypoxia inducible factors, HIF1 alpha and HIF2 alpha, are stabilized and transcribe a panel of genes associated with cancer such as vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor (PDGF), and glucose transporter 1 (GLUT1). Recent studies in clear cell kidney cancer have suggested that HIF2 alpha, but not HIF1 alpha, is the critical oncoprotein in the VHL pathway. Therefore, targeting HIF2 alpha could provide a potential therapeutic approach for patients with advanced CCRCC. Since iron regulatory protein 1 (IRP1) is known to inhibit the translation of HIF2 alpha, we investigated whether Tempol, a stable nitroxide that activates IRP1 towards IRE-binding, might have a therapeutic effect on a panel of human CCRCC cells expressing both HIF1 alpha and HIF2 alpha. We first evaluated the protein expression of HIF1 alpha and HIF2 alpha in 15 different clear cell renal carcinoma cell lines established from patient tumors in our laboratory. Tempol decreased the expression of HIF2 alpha, and its downstream targets in all the cell lines of the panel. This effect was attributed to a dramatic increase of IRE-binding activity of IRP1. Several cell lines were found to have an increased IRP1 basal activity at 20% O-2 compared to 5% O-2, which may lower HIF2 alpha expression in some of the cell lines in a VHL-independent manner. Taken together our data identify Tempol as an agent with potential therapeutic activity targeting expression of HIF2 alpha in VHL-deficient clear cell kidney cancer and illustrate the importance of studying biochemical processes at relevant physiological O2 levels. C1 [Sourbier, Carole; Srivastava, Gaurav; Ghosh, Sanchari; Yang, Youfeng; Gupta, Gopal; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Ghosh, Manik C.; Rouault, Tracey A.] NICHHD, Bethesda, MD 20892 USA. [DeGraff, William; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM WML@nih.gov FU Intramural NIH HHS [ZIA BC011028-05, ZIA BC011038-05, ZIE BC011023-05] NR 33 TC 7 Z9 9 U1 0 U2 19 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV PY 2012 VL 3 IS 11 BP 1472 EP 1482 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 056JE UT WOS:000312483600024 PM 23178531 ER PT J AU Pawlowski, J Audic, S Adl, S Bass, D Belbahri, L Berney, C Bowser, SS Cepicka, I Decelle, J Dunthorn, M Fiore-Donno, AM Gile, GH Holzmann, M Jahn, R Jirku, M Keeling, PJ Kostka, M Kudryavtsev, A Lara, E Lukes, J Mann, DG Mitchell, EAD Nitsche, F Romeralo, M Saunders, GW Simpson, AGB Smirnov, AV Spouge, JL Stern, RF Stoeck, T Zimmermann, J Schindel, D de Vargas, C AF Pawlowski, Jan Audic, Stephane Adl, Sina Bass, David Belbahri, Lassaad Berney, Cedric Bowser, Samuel S. Cepicka, Ivan Decelle, Johan Dunthorn, Micah Fiore-Donno, Anna Maria Gile, Gillian H. Holzmann, Maria Jahn, Regine Jirku, Miloslav Keeling, Patrick J. Kostka, Martin Kudryavtsev, Alexander Lara, Enrique Lukes, Julius Mann, David G. Mitchell, Edward A. D. Nitsche, Frank Romeralo, Maria Saunders, Gary W. Simpson, Alastair G. B. Smirnov, Alexey V. Spouge, John L. Stern, Rowena F. Stoeck, Thorsten Zimmermann, Jonas Schindel, David de Vargas, Colomban TI CBOL Protist Working Group: Barcoding Eukaryotic Richness beyond the Animal, Plant, and Fungal Kingdoms SO PLOS BIOLOGY LA English DT Article ID INTERNAL TRANSCRIBED SPACER; DNA BARCODE; SPECIES IDENTIFICATION; EVOLUTIONARY HISTORY; GENETIC-VARIATION; RDNA SEQUENCES; DIVERSITY; DIATOMS; RBCL; MACROALGAE C1 [Pawlowski, Jan; Holzmann, Maria; Kudryavtsev, Alexander] Univ Geneva, Dept Genet & Evolut, Geneva, Switzerland. [Audic, Stephane; Decelle, Johan; de Vargas, Colomban] Univ Paris 06, Stn Biol Roscoff, F-75252 Paris 05, France. [Audic, Stephane; Decelle, Johan; de Vargas, Colomban] CNRS, Unite Mixte Rech 7144, F-75700 Paris, France. [Adl, Sina] Univ Saskatchewan, Dept Soil Sci, Saskatoon, SK S7N 0W0, Canada. [Bass, David; Berney, Cedric] Nat Hist Museum, Dept Life Sci, London SW7 5BD, England. [Belbahri, Lassaad; Lara, Enrique; Mitchell, Edward A. D.] Univ Neuchatel, Lab Soil Biol, CH-2000 Neuchatel, Switzerland. [Bowser, Samuel S.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Cepicka, Ivan] Charles Univ Prague, Dept Zool, Prague, Czech Republic. [Dunthorn, Micah; Stoeck, Thorsten] Univ Kaiserslautern, Dept Ecol, Kaiserslautern, Germany. [Fiore-Donno, Anna Maria] Ernst Moritz Arndt Univ Greifswald, Inst Bot & Landscape Ecol, Greifswald, Germany. [Gile, Gillian H.] Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada. [Jahn, Regine; Zimmermann, Jonas] Free Univ Berlin, Bot Garten, Berlin, Germany. [Jahn, Regine; Zimmermann, Jonas] Free Univ Berlin, Bot Museum Berlin Dahlem, Berlin, Germany. [Jirku, Miloslav; Kostka, Martin; Lukes, Julius] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic. [Keeling, Patrick J.] Univ British Columbia, Canadian Inst Adv Res, Dept Bot, Vancouver, BC, Canada. [Kostka, Martin; Lukes, Julius] Univ S Bohemia, Fac Sci, Ceske Budejovice, Czech Republic. [Kudryavtsev, Alexander; Smirnov, Alexey V.] St Petersburg State Univ, Dept Invertebrate Zool, St Petersburg, Russia. [Mann, David G.] Royal Bot Garden Edinburgh, Edinburgh, Midlothian, Scotland. [Nitsche, Frank] Univ Cologne, D-50931 Cologne, Germany. [Romeralo, Maria] Uppsala Univ, Evolutionary Biol Ctr, Dept Systemat Biol, Uppsala, Sweden. [Saunders, Gary W.] Univ New Brunswick, Dept Biol, Fredericton, NB E3B 6E1, Canada. [Simpson, Alastair G. B.] Life Sci Ctr, Dept Biol, Halifax, NS, Canada. [Spouge, John L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Computat Biol Branch, Bethesda, MD 20892 USA. [Stern, Rowena F.] Sir Alister Hardy Fdn Ocean Sci, Plymouth, Devon, England. [Zimmermann, Jonas] Univ Giessen, Giessen, Germany. [Schindel, David] Natl Museum Nat Hist, Smithsonian Inst, Washington, DC 20560 USA. RP Pawlowski, J (reprint author), Univ Geneva, Dept Genet & Evolut, Geneva, Switzerland. EM Jan.Pawlowski@unige.ch; vargas@sb-roscoff.fr RI Mitchell, Edward/B-7259-2013; Saunders, Gary/D-8767-2014; Jirku, Miloslav/G-7823-2014; Mann, David/I-9018-2014; Kostka, Martin/G-9770-2014; Lukes, Julius/H-6760-2012; Smirnov, Alexey/K-3743-2013; Kudryavtsev, Alexander/J-2921-2013; Adl, Sina/R-3187-2016; OI Mitchell, Edward/0000-0003-0358-506X; Berney, Cedric/0000-0001-8689-9907; Audic, Stephane/0000-0001-6193-4374; Saunders, Gary/0000-0003-4813-6831; Mann, David/0000-0003-0522-6802; Lukes, Julius/0000-0002-0578-6618; Smirnov, Alexey/0000-0002-9844-5344; Kudryavtsev, Alexander/0000-0002-3818-3610; Simpson, Alastair/0000-0002-4133-1709; Pawlowski, Jan/0000-0003-2421-388X; Lara, Enrique/0000-0001-8500-522X FU Consortium for the Barcoding of Life; European ERA-net program BiodivErsA under the BioMarKs project; French ANR project [09-BLAN-0348 POSEIDON]; Swiss National Science Foundation [31003A-140766] FX The initial phase of the Protist Working Group activities presented in this paper were supported by the Consortium for the Barcoding of Life, the European ERA-net program BiodivErsA, under the BioMarKs project, the French ANR project 09-BLAN-0348 POSEIDON, and the Swiss National Science Foundation 31003A-140766. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 120 Z9 124 U1 4 U2 135 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2012 VL 10 IS 11 AR e1001419 DI 10.1371/journal.pbio.1001419 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 048CR UT WOS:000311888300002 PM 23139639 ER PT J AU Miller, FG AF Miller, Franklin G. TI The Enduring Legacy of Sham-Controlled Trials of Internal Mammary Artery Ligation SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review DE Sham surgery; Risk-benefit assessment; Research ethics ID STABLE CORONARY-DISEASE; ANGINA-PECTORIS; MYOCARDIAL REVASCULARIZATION; PARKINSONS-DISEASE; RANDOMIZED-TRIAL; PLACEBO SURGERY; VERTEBROPLASTY; FRACTURES; THERAPY; PCI AB In 1959 and 1960 the results of two randomized controlled trials demonstrated that bilateral internal mammary artery ligation was no better than a sham intervention in the treatment of angina. These landmark trials were the first to use blinded placebo controls to evaluate invasive procedures. Revisiting the story of internal mammary artery ligation offers valuable insights into the ethics of sham-controlled trials and the implications of the placebo effect for thinking about risk-benefit assessment of sham procedures. (Prog Cardiovasc Dis 2012;55:246-250) Published by Elsevier Inc. C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov FU Intramural Research Program of the Clinical Center, NIH FX This research was supported by the Intramural Research Program of the Clinical Center, NIH. NR 30 TC 11 Z9 11 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD NOV-DEC PY 2012 VL 55 IS 3 BP 246 EP 250 DI 10.1016/j.pcad.2012.09.002 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 055RA UT WOS:000312433100002 PM 23217427 ER PT J AU Sato, M Freedman, A Trovato, J Zhan, M Cunningham, F Smith, WS AF Sato, M. Freedman, A. Trovato, J. Zhan, M. Cunningham, F. Smith, Weiss S. TI IMPACT OF ERYTHROPOIESIS STIMULATING AGENTS ON SURVIVAL AMONG PATINETS WITH COLORECTAL CANCER RECEIVING CHEMOTHERAPY SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Sato, M.; Trovato, J.; Smith, Weiss S.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Freedman, A.] NCI, Bethesda, MD 20892 USA. [Zhan, M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Cunningham, F.] Vet Hlth Adm Pharm Benefits Management Serv, Hine, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2012 VL 15 IS 7 BP A653 EP A654 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 055JF UT WOS:000312411102139 ER PT J AU Jensen, MB Dunn, CA Keijzers, G Kulikowicz, T Rasmussen, LJ Croteau, DL Bohr, VA AF Jensen, Martin Borch Dunn, Christopher A. Keijzers, Guido Kulikowicz, Tomasz Rasmussen, Lene Juel Croteau, Deborah L. Bohr, Vilhelm A. TI The helicase and ATPase activities of RECQL4 are compromised by mutations reported in three human patients SO AGING-US LA English DT Article DE RecQ helicase; RECQL4; Rothmund-Thomson Syndrome; RAPADILINO Syndrome ID ROTHMUND-THOMSON-SYNDROME; SYNDROME GENE-PRODUCT; DNA-REPLICATION; GENOME STABILITY; SYNDROME PROTEIN; REPAIR; MAINTENANCE; CELLS; INVOLVEMENT; MECHANISMS AB RECQL4 is one of five members of the human RecQ helicase family, and is implicated in three syndromes displaying accelerating aging, developmental abnormalities and a predisposition to cancer. In this study, we purified three variants of RECQL4 carrying previously reported patient mutations. These three mutant proteins were analyzed for the known biochemical activities of RECQL4: DNA binding, unwinding of duplex DNA, ATP hydrolysis and annealing of simplex DNA. Further, the mutant proteins were evaluated for stability and recruitment to sites of laser-induced DNA damage. One mutant was helicase-dead, had marginal ATPase activity and may be structurally compromised, while the other two showed greatly reduced helicase and ATPase activities. The remaining biochemical activities and ability to recruit to damage sites were not significantly impaired for any of the mutants. Our findings demonstrate a consistent pattern of functional deficiency and provide further support for a helicase-dependent cellular function of RECQL4 in addition to its N-terminus-dependent role in initiation of replication, a function that may underlie the phenotype of RECQL4-linked disease. C1 [Jensen, Martin Borch; Dunn, Christopher A.; Keijzers, Guido; Rasmussen, Lene Juel; Bohr, Vilhelm A.] Univ Copenhagen, Dept Cellular & Mol Med, Ctr Healthy Aging, DK-2200 Copenhagen, Denmark. [Kulikowicz, Tomasz; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), Univ Copenhagen, Dept Cellular & Mol Med, Ctr Healthy Aging, DK-2200 Copenhagen, Denmark. EM vbohr@nih.gov FU Intramural Research Program of the NIH, National Institute on Aging; Nordea Foundation FX We would like to thank Dr. Takashi Tadokoro for help with the thermostability assay, and Alfred May for help with micropoint laser irradiation. We also thank Dr. Takashi Tadokoro and Dr. Evandro Fei Fang for critical reading of this manuscript. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging, as well as a grant from the Nordea Foundation. NR 51 TC 7 Z9 7 U1 0 U2 4 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD NOV PY 2012 VL 4 IS 11 BP 790 EP 802 PG 13 WC Cell Biology SC Cell Biology GA 053RE UT WOS:000312289900010 PM 23238538 ER PT J AU Smith, DH Feldstein, AC Perrin, N Rosales, AG Mosen, DM Liles, EG Schneider, JL Lafata, JE Myers, RE Glasgow, RE AF Smith, David H. Feldstein, Adrianne C. Perrin, Nancy Rosales, A. Gabriela Mosen, David M. Liles, Elizabeth G. Schneider, Jennifer L. Lafata, Jennifer E. Myers, Ronald E. Glasgow, Russell E. TI Automated Telephone Calls to Enhance Colorectal Cancer Screening: Economic Analysis SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID COST-EFFECTIVENESS ANALYSIS; NET BENEFIT REGRESSION; TRIAL; CARE; INTERVENTIONS; FRAMEWORK; SYSTEM AB Objectives: To estimate the cost-effectiveness of an automated telephone intervention for colorectal cancer screening from a managed care perspective, using data from a pragmatic randomized controlled trial. Methods: Intervention patients received calls for fecal occult blood testing (FOBT) screening. We searched patients' electronic medical records for any screening (defined as FOBT, flexible sigmoidoscopy, double-contrast barium enema, or colonoscopy) during follow-up. Intervention costs included project implementation and management, telephone calls, patient identification, and tracking. Screening costs included FOBT (kits, mailing, and processing) and any completed screening tests during follow-up. We estimated the incremental cost-effectiveness ratio (ICER) of the cost per additional screen. Results: At 6 months, average costs for intervention and control patients were $37 (25% screened) and $34 (19% screened), respectively. The ICER at 6 months was $42 per additional screen, less than half what other studies have reported. Cost-effectiveness probability was 0.49, 0.84, and 0.99 for willingness-to-pay thresholds of $40, $100, and $200, respectively. Similar results were seen at 9 months. A greater increase in FOBT testing was seen for patients aged >= 70 years (45/100 intervention, 33/100 control) compared with younger patients (25/100 intervention, 21/100 control). The intervention was dominant for patients aged >= 70 years and was $73 per additional screen for younger patients. It increased screening rates by about 6% and costs by $3 per patient. Conclusions: At willingness to pay of $100 or more per additional screening test, an automated telephone reminder intervention can be an optimal use of resources. (Am J Manag Care, 2012;18(11):691-699) C1 [Smith, David H.; Feldstein, Adrianne C.; Perrin, Nancy; Rosales, A. Gabriela; Mosen, David M.; Liles, Elizabeth G.; Schneider, Jennifer L.] Kaiser Permanence NW, Ctr Hlth Res, Portland, OR USA. [Feldstein, Adrianne C.] Kaiser Permanence NW, NW Perrnanente, Portland, OR USA. [Lafata, Jennifer E.] Henry Ford Hlth Syst, Detroit, MI USA. [Myers, Ronald E.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Glasgow, Russell E.] NCI, Disseminat & Implementat Sci Div Canc Control & P, Bethesda, MD 20892 USA. RP Smith, DH (reprint author), 3800 N Interstate Ave, Portland, OR 97227 USA. EM david.h.smith@kpchr.org OI Myers, Ronald E./0000-0002-8059-7390 FU National Cancer Institute [1R01CA132709] FX Funding Source: National Cancer Institute (1R01CA132709). NR 18 TC 6 Z9 6 U1 1 U2 6 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2012 VL 18 IS 11 BP 691 EP 699 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 052VM UT WOS:000312226900003 PM 23198712 ER PT J AU Morrison, DK AF Morrison, Deborah K. TI MAP Kinase Pathways SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID SCAFFOLD PROTEINS; MECHANISMS; CASCADES C1 NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. RP Morrison, DK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. EM morrisod@mail.nih.gov NR 17 TC 47 Z9 49 U1 1 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD NOV PY 2012 VL 4 IS 11 AR a011254 DI 10.1101/cshperspect.a011254 PG 5 WC Cell Biology SC Cell Biology GA 054MR UT WOS:000312348400011 ER PT J AU Narendra, D Walker, JE Youle, R AF Narendra, Derek Walker, John E. Youle, Richard TI Mitochondrial Quality Control Mediated by PINK1 and Parkin: Links to Parkinsonism SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID PINK1/PARKIN-MEDIATED MITOPHAGY; DEPOLARIZED MITOCHONDRIA; ENDOPLASMIC-RETICULUM; PROTEIN-DEGRADATION; AXONAL-TRANSPORT; OXIDATIVE STRESS; MTDNA MUTATIONS; DNA DELETIONS; NIGRA NEURONS; KINASE PINK1 AB Mutations in Parkin or PINK1 are the most common cause of recessive familial parkinsonism. Recent studies suggest that PINK1 and Parkin form a mitochondria quality control pathway that identifies dysfunctional mitochondria, isolates them from the mitochondrial network, and promotes their degradation by autophagy. In this pathway the mitochondrial kinase PINK1 senses mitochondrial fidelity and recruits Parkin selectively to mitochondria that lose membrane potential. Parkin, an E3 ligase, subsequently ubiquitinates outer mitochondrial membrane proteins, notably the mitofusins and Miro, and induces autophagic elimination of the impaired organelles. Here we review the recent rapid progress in understanding the molecular mechanisms of PINK1- and Parkin-mediated mitophagy and the identification of Parkin substrates suggesting how mitochondrial fission and trafficking are involved. We also discuss how defects in mitophagy may be linked to Parkinson's disease. C1 [Narendra, Derek; Youle, Richard] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Narendra, Derek; Walker, John E.] MRC, Mitochondrial Biol Unit, Cambridge CB0 2XY, England. RP Youle, R (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov FU intramural program at the NINDS; Medical Research Council; NIH [1F30AG039185-01] FX This review was supported by the intramural program at the NINDS (R.Y. and D.N.), the Medical Research Council (J.E.W. and D.N.), and NIH grant 1F30AG039185-01 (D.N.). We thank Drs. Ian Fearnley, Joe Carroll, and Shujing Ding for many helpful discussions and assistance in preparing proteomics data for Tables 1 and 2 and Figure 2 of this review. NR 94 TC 53 Z9 53 U1 1 U2 23 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD NOV PY 2012 VL 4 IS 11 AR a011338 DI 10.1101/cshperspect.a011338 PG 19 WC Cell Biology SC Cell Biology GA 054MR UT WOS:000312348400012 ER PT J AU Ramos, E Callier, SL Rotimi, CN AF Ramos, Edward Callier, Shawneequa L. Rotimi, Charles N. TI Why personalized medicine will fail if we stay the course SO PERSONALIZED MEDICINE LA English DT Article DE diversity; ethnicity; genomic medicine; global populations; personalized medicine ID GENOME-WIDE ASSOCIATION; DIABETES SUSCEPTIBILITY GENES; ADVERSE DRUG-REACTIONS; AFRICAN-AMERICANS; ETHICAL-ISSUES; WEST AFRICANS; PHARMACOGENOMICS; VARIANTS; POPULATIONS; IMPACT AB Genomic science and associated technologies are providing scientists and clinicians with novel insights that are transforming the delivery of healthcare and the overall well-being of society. However, these insights inform us that historical population sampling approaches for investigating rare and common genetic variations are not representative of the complex ancestral backgrounds of today's patients. In order for personalized medicine to be meaningful and applicable to the global populations, we will need to know how common and rare genetic variants found in different parts of the world influence health and drug response. This article demonstrates the importance of increasing ethnic and racial diversity among participants in genomic research, highlights areas of opportunity for improving our understanding of genomic diversity among populations, and provides examples of successful models that help to resolve these concerns. C1 [Ramos, Edward; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Callier, Shawneequa L.] George Washington Univ, Dept Clin Res & Leadership, Sch Med & Hlth Sci, Washington, DC 20037 USA. RP Ramos, E (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. EM ramose@mail.nih.gov FU Intramural Research Program of the Center for Research on Genomics and Global Health (CRGGH); Office of the Director, National Institute of Diabetes and Digestive and Kidney diseases (NIDDK); National Human Genome Research Institute (NHGRI) at the NIH [Z01HG200362] FX This work was supported in part by the Intramural Research Program of the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by funds from the Office of the Director, National Institute of Diabetes and Digestive and Kidney diseases (NIDDK) and National Human Genome Research Institute (NHGRI) at the NIH (Z01HG200362). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 65 TC 11 Z9 12 U1 0 U2 10 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD NOV PY 2012 VL 9 IS 8 BP 839 EP 847 DI 10.2217/PME.12.100 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 049JC UT WOS:000311977800010 PM 23543886 ER PT J AU Arnold, JJ Sharma, SD Feng, JY Ray, AS Smidansky, ED Kireeva, ML Cho, A Perry, J Vela, JE Park, Y Xu, YL Tian, Y Babusis, D Barauskus, O Peterson, BR Gnatt, A Kashlev, M Zhong, WD Cameron, CE AF Arnold, Jamie J. Sharma, Suresh D. Feng, Joy Y. Ray, Adrian S. Smidansky, Eric D. Kireeva, Maria L. Cho, Aesop Perry, Jason Vela, Jennifer E. Park, Yeojin Xu, Yili Tian, Yang Babusis, Darius Barauskus, Ona Peterson, Blake R. Gnatt, Averell Kashlev, Mikhail Zhong, Weidong Cameron, Craig E. TI Sensitivity of Mitochondrial Transcription and Resistance of RNA Polymerase II Dependent Nuclear Transcription to Antiviral Ribonucleosides SO PLOS PATHOGENS LA English DT Article ID HEPATITIS-C-VIRUS; PURINE NUCLEOSIDE ANALOGS; MAMMALIAN MITOCHONDRIA; DNA POLYMERASE; REPLICATION; TOXICITY; ELONGATION; INHIBITOR; REPLICON; THERAPY AB Ribonucleoside analogues have potential utility as anti-viral, -parasitic, -bacterial and -cancer agents. However, their clinical applications have been limited by off target effects. Development of antiviral ribonucleosides for treatment of hepatitis C virus (HCV) infection has been hampered by appearance of toxicity during clinical trials that evaded detection during preclinical studies. It is well established that the human mitochondrial DNA polymerase is an off target for deoxyribonucleoside reverse transcriptase inhibitors. Here we test the hypothesis that triphosphorylated metabolites of therapeutic ribonucleoside analogues are substrates for cellular RNA polymerases. We have used ribonucleoside analogues with activity against HCV as model compounds for therapeutic ribonucleosides. We have included ribonucleoside analogues containing 2'-C-methyl, 4'-methyl and 4'-azido substituents that are non-obligate chain terminators of the HCV RNA polymerase. We show that all of the anti-HCV ribonucleoside analogues are substrates for human mitochondrial RNA polymerase (POLRMT) and eukaryotic core RNA polymerase II (Pol II) in vitro. Unexpectedly, analogues containing 2'-C-methyl, 4'-methyl and 4'-azido substituents were inhibitors of POLRMT and Pol II. Importantly, the proofreading activity of TFIIS was capable of excising these analogues from Pol II transcripts. Evaluation of transcription in cells confirmed sensitivity of POLRMT to antiviral ribonucleosides, while Pol II remained predominantly refractory. We introduce a parameter termed the mitovir (mitochondrial dysfunction caused by antiviral ribonucleoside) score that can be readily obtained during preclinical studies that quantifies the mitochondrial toxicity potential of compounds. We suggest the possibility that patients exhibiting adverse effects during clinical trials may be more susceptible to damage by nucleoside analogs because of defects in mitochondrial or nuclear transcription. The paradigm reported here should facilitate development of ribonucleosides with a lower potential for toxicity. C1 [Arnold, Jamie J.; Sharma, Suresh D.; Smidansky, Eric D.; Cameron, Craig E.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. [Feng, Joy Y.; Ray, Adrian S.; Cho, Aesop; Perry, Jason; Vela, Jennifer E.; Park, Yeojin; Xu, Yili; Tian, Yang; Babusis, Darius; Barauskus, Ona; Zhong, Weidong] Gilead Sci Inc, Foster City, CA USA. [Kireeva, Maria L.; Kashlev, Mikhail] NCI, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Peterson, Blake R.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. [Gnatt, Averell] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA. RP Arnold, JJ (reprint author), Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. EM jja5@psu.edu; cec9@psu.edu RI SHARMA, Suresh/C-4431-2008; Peterson, Blake/O-2497-2016; OI SHARMA, Suresh/0000-0002-8633-4145; Peterson, Blake/0000-0001-8251-3579; Ray, Adrian/0000-0002-3508-3008 FU NIAID, NIH [AI045818] FX This work was supported by grants from NIAID, NIH: AI045818 (CEC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The contents of this publication do not necessarily reveal the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial product, or organizations imply endorsement by the U. S. Government. NR 50 TC 32 Z9 34 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2012 VL 8 IS 11 AR e1003030 DI 10.1371/journal.ppat.1003030 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 049PY UT WOS:000311997100045 PM 23166498 ER PT J AU Kwon-Chung, KJ Chang, YC AF Kwon-Chung, Kyung J. Chang, Yun C. TI Aneuploidy and Drug Resistance in Pathogenic Fungi SO PLOS PATHOGENS LA English DT Article ID CANDIDA-GLABRATA ISOLATE; CRYPTOCOCCUS-NEOFORMANS; YEAST; CELLS; VIRULENCE; HETERORESISTANCE; FLUCONAZOLE; ALBICANS; GENES C1 [Kwon-Chung, Kyung J.; Chang, Yun C.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by funds from the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 21 Z9 21 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2012 VL 8 IS 11 AR e1003022 DI 10.1371/journal.ppat.1003022 PG 4 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 049PY UT WOS:000311997100039 PM 23166494 ER PT J AU Nance, JP Vannella, KM Worth, D David, C Carter, D Noor, S Hubeau, C Fitz, L Lane, TE Wynn, TA Wilson, EH AF Nance, J. Philip Vannella, Kevin M. Worth, Danielle David, Clement Carter, David Noor, Shahani Hubeau, Cedric Fitz, Lori Lane, Thomas E. Wynn, Thomas A. Wilson, Emma H. TI Chitinase Dependent Control of Protozoan Cyst Burden in the Brain SO PLOS PATHOGENS LA English DT Article ID ALTERNATIVELY ACTIVATED MACROPHAGES; TOXOPLASMA-GONDII INFECTION; ACIDIC MAMMALIAN CHITINASE; CELL-MEDIATED-IMMUNITY; INDUCIBLE NITRIC-OXIDE; CD4(+) T-CELLS; IFN-GAMMA; DIFFERENTIAL EXPRESSION; FUNCTIONAL PLASTICITY; ALLERGIC INFLAMMATION AB Chronic infections represent a continuous battle between the host's immune system and pathogen replication. Many protozoan parasites have evolved a cyst lifecycle stage that provides it with increased protection from environmental degradation as well as endogenous host mechanisms of attack. In the case of Toxoplasma gondii, these cysts are predominantly found in the immune protected brain making clearance of the parasite more difficult and resulting in a lifelong infection. Currently, little is known about the nature of the immune response stimulated by the presence of these cysts or how they are able to propagate. Here we establish a novel chitinase-dependent mechanism of cyst control in the infected brain. Despite a dominant Th1 immune response during Toxoplasma infection there exists a population of alternatively activated macrophages (AAM circle divide) in the infected CNS. These cells are capable of cyst lysis via the production of AMCase as revealed by live imaging, and this chitinase is necessary for protective immunity within the CNS. These data demonstrate chitinase activity in the brain in response to a protozoan pathogen and provide a novel mechanism to facilitate cyst clearance during chronic infections. C1 [Nance, J. Philip; Worth, Danielle; David, Clement; Noor, Shahani; Wilson, Emma H.] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. [Vannella, Kevin M.; Wynn, Thomas A.] NIAID, NIH, Bethesda, MD 20892 USA. [Carter, David] Univ Calif Riverside, Inst Integrat Genome Biol, Riverside, CA 92521 USA. [Hubeau, Cedric; Fitz, Lori] Pfizer, Dept Inflammat & Immunol, Cambridge, MA USA. [Lane, Thomas E.] Univ Calif Irvine, Inst Immunol, Dept Mol Biol & Biochem, Irvine, CA USA. RP Wilson, EH (reprint author), Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. EM emmaw@ucr.edu OI Nance, Phil/0000-0002-3369-0015 FU CRCC; UCR Division of Biomedical Sciences; UCR academic senate; NIH [RNS071160A, RNS072298A, R01NS041249]; National Institute of Allergy and Infectious Diseases/NIH FX These studies were supported in part by grants to EHW from CRCC, the UCR Division of Biomedical Sciences, the UCR academic senate and NIH RNS071160A and RNS072298A and to TEL by NIH R01NS041249. TAW is supported by the intramural research program of the National Institute of Allergy and Infectious Diseases/NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 91 TC 23 Z9 25 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2012 VL 8 IS 11 AR e1002990 DI 10.1371/journal.ppat.1002990 PG 16 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 049PY UT WOS:000311997100013 PM 23209401 ER PT J AU Perkins, MR Ryschkewitsch, C Liebner, JC Monaco, MCG Himelfarb, D Ireland, S Roque, A Edward, HL Jensen, PN Remington, G Abraham, T Abraham, J Greenberg, B Kaufman, C LaGanke, C Monson, NL Xu, XN Frohman, E Major, EO Douek, DC AF Perkins, Molly R. Ryschkewitsch, Caroline Liebner, Julia C. Monaco, Maria Chiara G. Himelfarb, Danielle Ireland, Sara Roque, Annelys Edward, Heather L. Jensen, Peter N. Remington, Gina Abraham, Thomas Abraham, Jaspreet Greenberg, Benjamin Kaufman, Charles LaGanke, Chris Monson, Nancy L. Xu, Xiaoning Frohman, Elliot Major, Eugene O. Douek, Daniel C. TI Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy SO PLOS PATHOGENS LA English DT Article ID MULTIPLE-SCLEROSIS PATIENTS; PATIENTS RECEIVING NATALIZUMAB; CEREBROSPINAL-FLUID; IMMUNE-RESPONSES; DISCREPANT FINDINGS; MESSENGER-RNA; IN-VIVO; IL-15; PML; SERUM AB Progressive multifocal leukoencephalopathy (PML) induced by JC virus (JCV) is a risk for natalizumab-treated multiple sclerosis (MS) patients. Here we characterize the JCV-specific T cell responses in healthy donors and natalizumab-treated MS patients to reveal functional differences that may account for the development of natalizumab-associated PML. CD4 and CD8 T cell responses specific for all JCV proteins were readily identified in MS patients and healthy volunteers. The magnitude and quality of responses to JCV and cytomegalovirus (CMV) did not change from baseline through several months of natalizumab therapy. However, the frequency of T cells producing IL-10 upon mitogenic stimulation transiently increased after the first dose. In addition, MS patients with natalizumab-associated PML were distinguished from all other subjects in that they either had no detectable JCV-specific T cell response or had JCV-specific CD4 T cell responses uniquely dominated by IL-10 production. Additionally, IL-10 levels were higher in the CSF of individuals with recently diagnosed PML. Thus, natalizumab-treated MS patients with PML have absent or aberrant JCV-specific T cell responses compared with non-PML patients, and changes in T cell-mediated control of JCV replication may be a risk factor for developing PML. Our data suggest further approaches to improved monitoring, treatment and prevention of PML in natalizumab-treated patients. C1 [Perkins, Molly R.; Liebner, Julia C.; Himelfarb, Danielle; Roque, Annelys; Edward, Heather L.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Perkins, Molly R.; Xu, Xiaoning] Univ Oxford, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford, England. [Ryschkewitsch, Caroline; Monaco, Maria Chiara G.; Jensen, Peter N.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. [Ireland, Sara; Remington, Gina; Abraham, Thomas; Abraham, Jaspreet; Greenberg, Benjamin; Monson, Nancy L.; Frohman, Elliot] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Kaufman, Charles] Louisiana Neurol Consultants, Baton Rouge, LA USA. [LaGanke, Chris] N Cent Neurol, Cullman, AL USA. RP Perkins, MR (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov; ddouek@mail.nih.gov OI Greenberg, Benjamin/0000-0002-2091-8201; Ireland, Sara/0000-0002-7811-197X FU National Institute of Allergy and Infectious Diseases; National Institute of Neurological Disorders and Stroke; Sanofi Aventis; Greater Good Foundation; Biogen Idec; Elan; Applied Clinical Intelligence; DioGenix; Guthy Jackson Charitable Foundation; Amplimmune; Accelerated Cure Project; TEVA; Novartis; Acorda; Abbott; Genzyme FX This work was supported by intramural funding from the National Institute of Allergy and Infectious Diseases and the National Institute of Neurological Disorders and Stroke. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; I have read the journal's policy and have the following conflicts: Dr. Greenberg has received honoraria from the MSAA. He has received consulting fees from Sanofi Aventis, The Greater Good Foundation, Biogen Idec, Elan, Applied Clinical Intelligence and DioGenix. He holds equity in DioGenix, Inc. He receives grant support from the Guthy Jackson Charitable Foundation, Amplimmune and Accelerated Cure Project. Dr. Frohman has received speaker and consulting fees from Biogen Idec, TEVA, Novartis, and Acorda; and consulting fees from Abbott and Genzyme. This does not alter our adherence to all PLoS Pathogens policies on sharing data and materials. NR 41 TC 27 Z9 27 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2012 VL 8 IS 11 AR e1003014 DI 10.1371/journal.ppat.1003014 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 049PY UT WOS:000311997100033 PM 23144619 ER PT J AU Waki, K Durell, SR Soheilian, F Nagashima, K Butler, SL Freed, EO AF Waki, Kayoko Durell, Stewart R. Soheilian, Ferri Nagashima, Kunio Butler, Scott L. Freed, Eric O. TI Structural and Functional Insights into the HIV-1 Maturation Inhibitor Binding Pocket SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MAJOR HOMOLOGY REGION; GAG SPACER PEPTIDE-1; CA-SP1 CLEAVAGE SITE; BETULINIC ACID; CAPSID PROTEIN; MEMBRANE AFFINITY; HELICAL STRUCTURE; VIRAL PROTEASE; IN-VITRO AB Processing of the Gag precursor protein by the viral protease during particle release triggers virion maturation, an essential step in the virus replication cycle. The first-in-class HIV-1 maturation inhibitor dimethylsuccinyl betulinic acid [PA-457 or bevirimat (BVM)] blocks HIV-1 maturation by inhibiting the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA. A structurally distinct molecule, PF-46396, was recently reported to have a similar mode of action to that of BVM. Because of the structural dissimilarity between BVM and PF-46396, we hypothesized that the two compounds might interact differentially with the putative maturation inhibitor-binding pocket in Gag. To test this hypothesis, PF-46396 resistance was selected for in vitro. Resistance mutations were identified in three regions of Gag: around the CA-SP1 cleavage site where BVM resistance maps, at CA amino acid 201, and in the CA major homology region (MHR). The MHR mutants are profoundly PF-46396-dependent in Gag assembly and release and virus replication. The severe defect exhibited by the inhibitor-dependent MHR mutants in the absence of the compound is also corrected by a second-site compensatory change far downstream in SP1, suggesting structural and functional cross-talk between the HIV-1 CA MHR and SP1. When PF-46396 and BVM were both present in infected cells they exhibited mutually antagonistic behavior. Together, these results identify Gag residues that line the maturation inhibitor-binding pocket and suggest that BVM and PF-46396 interact differentially with this putative pocket. These findings provide novel insights into the structure-function relationship between the CA MHR and SP1, two domains of Gag that are critical to both assembly and maturation. The highly conserved nature of the MHR across all orthoretroviridae suggests that these findings will be broadly relevant to retroviral assembly. Finally, the results presented here provide a framework for increased structural understanding of HIV-1 maturation inhibitor activity. C1 [Waki, Kayoko; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Durell, Stewart R.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Soheilian, Ferri; Nagashima, Kunio] NCI, Electron Microscope Lab, Adv Technol Program, SAIC Frederick,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. [Butler, Scott L.] Sandwich Labs, Pfizer Global Res & Dev, Sandwich, Kent, England. RP Waki, K (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. EM efreed@nih.gov FU NIH, National Cancer Institute, Center for Cancer Research; Intramural AIDS targeted Antiviral Program; National Cancer Institute, National Institutes of Health [HHSN26120080001E] FX Research in the Freed lab is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and by the Intramural AIDS targeted Antiviral Program. This project has also been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 27 Z9 27 U1 1 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2012 VL 8 IS 11 AR e1002997 DI 10.1371/journal.ppat.1002997 PG 19 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 049PY UT WOS:000311997100018 PM 23144615 ER PT J AU Wang, X Li, J Schowalter, RM Jiao, J Buck, CB You, JX AF Wang, Xin Li, Jing Schowalter, Rachel M. Jiao, Jing Buck, Christopher B. You, Jianxin TI Bromodomain Protein Brd4 Plays a Key Role in Merkel Cell Polyomavirus DNA Replication SO PLOS PATHOGENS LA English DT Article ID HOST MITOTIC CHROMOSOMES; T-ANTIGEN; ACETYLATED CHROMATIN; NUCLEAR ANTIGEN; FACTOR-C; S-PHASE; CARCINOMA; INTERACTS; PROGRESSION; INHIBITION AB Merkel cell polyomavirus (MCV or MCPyV) is the first human polyomavirus to be definitively linked to cancer. The mechanisms of MCV-induced oncogenesis and much of MCV biology are largely unexplored. In this study, we demonstrate that bromodomain protein 4 (Brd4) interacts with MCV large T antigen (LT) and plays a critical role in viral DNA replication. Brd4 knockdown inhibits MCV replication, which can be rescued by recombinant Brd4. Brd4 colocalizes with the MCV LT/replication origin complex in the nucleus and recruits replication factor C (RFC) to the viral replication sites. A dominant negative inhibitor of the Brd4-MCV LT interaction can dissociate Brd4 and RFC from the viral replication complex and abrogate MCV replication. Furthermore, obstructing the physiologic interaction between Brd4 and host chromatin with the chemical compound JQ1(+) leads to enhanced MCV DNA replication, demonstrating that the role of Brd4 in MCV replication is distinct from its role in chromatin-associated transcriptional regulation. Our findings demonstrate mechanistic details of the MCV replication machinery; providing novel insight to elucidate the life cycle of this newly discovered oncogenic DNA virus. C1 [Wang, Xin; Li, Jing; Jiao, Jing; You, Jianxin] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schowalter, Rachel M.; Buck, Christopher B.] NCI, Tumor Virus Mol Biol Sect, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Wang, X (reprint author), Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. EM jianyou@mail.med.upenn.edu OI Buck, Christopher/0000-0003-3165-8094 FU HIV-Associated Malignancies Pilot Project Award (National Cancer Institute), National Institutes of Health (NIH) [R01CA148768, R01CA142723]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the HIV-Associated Malignancies Pilot Project Award (National Cancer Institute), National Institutes of Health (NIH) Grants R01CA148768 and R01CA142723 (to J.Y.) and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 31 Z9 31 U1 0 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2012 VL 8 IS 11 AR e1003021 DI 10.1371/journal.ppat.1003021 PG 16 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 049PY UT WOS:000311997100038 PM 23144621 ER PT J AU Wise, HM Hutchinson, EC Jagger, BW Stuart, AD Kang, ZH Robb, N Schwartzman, LM Kash, JC Fodor, E Firth, AE Gog, JR Taubenberger, JK Digard, P AF Wise, Helen M. Hutchinson, Edward C. Jagger, Brett W. Stuart, Amanda D. Kang, Zi H. Robb, Nicole Schwartzman, Louis M. Kash, John C. Fodor, Ervin Firth, Andrew E. Gog, Julia R. Taubenberger, Jeffery K. Digard, Paul TI Identification of a Novel Splice Variant Form of the Influenza A Virus M2 Ion Channel with an Antigenically Distinct Ectodomain SO PLOS PATHOGENS LA English DT Article ID PROTEIN CYTOPLASMIC TAIL; M1 MESSENGER-RNA; MONOCLONAL-ANTIBODY; MEMBRANE-PROTEINS; MATRIX PROTEIN-2; AVIAN INFLUENZA; TISSUE-CULTURE; NUCLEAR EXPORT; NS1 PROTEIN; SEGMENT 2 AB Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays important roles in virus entry and assembly, and is a target for antiviral drugs and vaccination. Surprisingly, M2 is not essential for virus replication in a laboratory setting, although its loss attenuates the virus. To better understand how IAV might replicate without M2, we studied the reversion mechanism of an M2-null virus. Serial passage of a virus lacking the mRNA2 splice donor site identified a single nucleotide pseudoreverting mutation, which restored growth in cell culture and virulence in mice by upregulating mRNA4 synthesis rather than by reinstating mRNA2 production. We show that mRNA4 encodes a novel M2-related protein (designated M42) with an antigenically distinct ectodomain that can functionally replace M2 despite showing clear differences in intracellular localisation, being largely retained in the Golgi compartment. We also show that the expression of two distinct ion channel proteins is not unique to laboratory-adapted viruses but, most notably, was also a feature of the 1983 North American outbreak of H5N2 highly pathogenic avian influenza virus. In identifying a 14th influenza A polypeptide, our data reinforce the unexpectedly high coding capacity of the viral genome and have implications for virus evolution, as well as for understanding the role of M2 in the virus life cycle. C1 [Wise, Helen M.; Hutchinson, Edward C.; Jagger, Brett W.; Stuart, Amanda D.; Kang, Zi H.; Firth, Andrew E.; Digard, Paul] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England. [Wise, Helen M.; Digard, Paul] Univ Edinburgh, Roslin Inst, Easter Bush, Midlothian, Scotland. [Jagger, Brett W.; Schwartzman, Louis M.; Kash, John C.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Gog, Julia R.] Univ Cambridge, Ctr Math Sci, DAMTP, Cambridge, England. [Robb, Nicole; Fodor, Ervin] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. RP Wise, HM (reprint author), Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England. EM paul.digard@roslin.ed.ac.uk RI Digard, Paul/B-7717-2008; Hutchinson, Edward/M-7136-2016; OI Digard, Paul/0000-0002-0872-9440; Hutchinson, Edward/0000-0003-3673-9096; Firth, Andrew/0000-0002-7986-9520 FU UK Medical Research Council [G0700815, G0801931, G0700848]; Wellcome Trust [088789, 075450]; National Institutes of Health-Oxford/Cambridge Research Scholars Program; US National Institutes of Health; NIAID FX This work was supported by grants from the UK Medical Research Council (nos. G0700815 and G0801931 to PD, and G0700848 to EF), the Wellcome Trust (no. 088789 to AEF and 075450 to ECH/PD), the National Institutes of Health-Oxford/Cambridge Research Scholars Program (to BWJ, PD and JKT) and in part by the intramural funds of the US National Institutes of Health and NIAID (to JKT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 77 Z9 82 U1 3 U2 22 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2012 VL 8 IS 11 AR e1002998 DI 10.1371/journal.ppat.1002998 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 049PY UT WOS:000311997100019 PM 23133386 ER PT J AU Roshandel, G Semnani, S Malekzadeh, R Dawsey, SM AF Roshandel, Gholamreza Semnani, Shahryar Malekzadeh, Reza Dawsey, Sanford M. TI Polycyclic Aromatic Hydrocarbons and Esophageal Squamous Cell Carcinoma SO ARCHIVES OF IRANIAN MEDICINE LA English DT Review DE Carcinogen; esophageal cancer; Iran; polycyclic aromatic hydrocarbons ID WHITE BLOOD-CELLS; INDOOR AIR-POLLUTION; 1-HYDROXYPYRENE GLUCURONIDE CONCENTRATIONS; URINARY HYDROXYLATED METABOLITES; HIGH-RISK POPULATION; NORTH-EASTERN IRAN; COKE-OVEN WORKERS; PAH-DNA-ADDUCTS; GRANDE-DO-SUL; OCCUPATIONAL-EXPOSURE AB Esophageal cancer (EC) is the 8th most common cancer and the eh most frequent cause of cancer mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common type of EC. Exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested as a risk factor for developing ESCC. In this paper we will review different aspects of the relationship between PAH exposure and ESCC. PAHs are a group of compounds that are formed by incomplete combustion of organic matter. Studies in humans have shown an association between PAH exposure and development of ESCC in many populations. The results of a recent case-control study in a high risk population in northeastern Iran showed a dramatic dose-response relationship between PAH content in non-tumor esophageal tissue (the target tissue for esophageal carcinogenesis) and ESCC case status, consistent with a causal role for PAH exposure in the pathogenesis of ESCC. Identifying the main sources of exposure to PAHs may be the first and most important step in designing appropriate PAH-reduction interventions for controlling ESCC, especially in high risk areas. Coal smoke and drinking mate have been suggested as important modifiable sources of PAH exposure in China and Brazil, respectively. But the primary source of exposure to PAHs in other high risk areas for ESCC, such as northeastern Iran, has not yet been identified. Thus, environmental studies to determining important sources of PAH exposure should be considered as a high priority in future research projects in these areas. C1 [Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20895 USA. [Roshandel, Gholamreza; Semnani, Shahryar] Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran. [Roshandel, Gholamreza; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. RP Dawsey, SM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Bethesda, MD 20895 USA. EM dawseys@mail.nih.gov RI Roshandel, gholamreza/N-2260-2016; Semnani, Shahryar/N-2270-2016; OI Roshandel, gholamreza/0000-0002-5494-0722; Semnani, Shahryar/0000-0002-8768-6142; Malekzadeh, Reza/0000-0003-1043-3814 FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute of the National Institutes of Health FX Preparation of this review was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute of the National Institutes of Health. NR 141 TC 8 Z9 8 U1 1 U2 19 PU ACAD MEDICAL SCIENCES I R IRAN PI TEHRAN PA PO BOX 19395-5655, TEHRAN, 00000, IRAN SN 1029-2977 J9 ARCH IRAN MED JI Arch. Iran. Med. PD NOV PY 2012 VL 15 IS 11 BP 713 EP 722 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 049EQ UT WOS:000311965400011 PM 23102250 ER PT J AU Cecchini, RS Costantino, JP Cauley, JA Cronin, WM Wickerham, DL Bandos, H Weissfeld, JL Wolmark, N AF Cecchini, Reena S. Costantino, Joseph P. Cauley, Jane A. Cronin, Walter M. Wickerham, D. Lawrence Bandos, Hanna Weissfeld, Joel L. Wolmark, Norman TI Baseline Mammographic Breast Density and the Risk of Invasive Breast Cancer in Postmenopausal Women Participating in the NSABP Study of Tamoxifen and Raloxifene (STAR) SO CANCER PREVENTION RESEARCH LA English DT Article ID SURGICAL ADJUVANT BREAST; AMERICAN WOMEN; BOWEL PROJECT; ROC CURVES; P-2 TRIAL; MODEL; VALIDATION; PREDICTION; MARKER; PREVENTION AB Mammographic breast density is an established risk factor for breast cancer. However, results are inconclusive regarding its use in risk prediction models. The current study evaluated 13,409 postmenopausal participants in the NSABP Study of Tamoxifen and Raloxifene. A measure of breast density as reported on the entry mammogram report was extracted and categorized according to The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) classifications. An increased risk of invasive breast cancer was associated with higher mammographic breast density (P < 0.001). The association remained significant after adjusting for age, treatment, and smoking history [HR 1.35, 95% confidence interval (CI): 1.16-1.58], as well as when added to a model including the Gail score (HR 1.33,95% CI: 1.14-1.55). At five years after random assignment, time-dependent area under the curve (AUC) improved from 0.63 for a model with Gail score alone to 0.64 when considering breast density and Gail score. Breast density was also significant when added to an abbreviated model tailored for estrogen receptor-positive breast cancers (P = 0.02). In this study, high BI-RADS breast density was significantly associated with increased breast cancer risk when considered in conjunction with Gail score but provided only slight improvement to the Gail score for predicting the incidence of invasive breast cancer. The BI-RADS breast composition classification system is a quick and readily available method for assessing breast density for risk prediction evaluations; however, its addition to the Gail model does not seem to provide substantial predictability improvements in this population of postmenopausal healthy women at increased risk for breast cancer. Cancer Prev Res; 5(11); 1321-9. (C) 2012 AACR. C1 [Cecchini, Reena S.; Costantino, Joseph P.; Cronin, Walter M.; Wickerham, D. Lawrence; Bandos, Hanna; Wolmark, Norman] NSABP Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15213 USA. [Cecchini, Reena S.; Costantino, Joseph P.; Cronin, Walter M.; Wickerham, D. Lawrence; Bandos, Hanna; Wolmark, Norman] NSABP Operat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15213 USA. [Cecchini, Reena S.; Costantino, Joseph P.; Cronin, Walter M.; Bandos, Hanna] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Wickerham, D. Lawrence; Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. [Weissfeld, Joel L.] Univ Pittsburgh, Dept Epidemiol, Inst Canc, Pittsburgh, PA 15261 USA. RP Cecchini, RS (reprint author), NSABP Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, 1 Sterling Plaza,201 N Craig St,Suite 350, Pittsburgh, PA 15213 USA. EM cecchini@nsabp.pitt.edu OI Cecchini, Reena/0000-0002-9075-9357; Cauley, Jane A/0000-0003-0752-4408 FU Public Health Service grants from the National Cancer Institute, Department of Health and Human Services [U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974]; Zeneca Pharmaceuticals, business unit of ZENECA Inc.; Eli Lilly and Company FX This work was supported by the Public Health Service grants (U10-CA-12027, U10-CA-69651, U10-CA-37377, and U10-CA-69974) from the National Cancer Institute, Department of Health and Human Services; Zeneca Pharmaceuticals, a business unit of ZENECA Inc., and Eli Lilly and Company NR 38 TC 9 Z9 11 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD NOV PY 2012 VL 5 IS 11 BP 1321 EP 1329 DI 10.1158/1940-6207.CAPR-12-0273 PG 9 WC Oncology SC Oncology GA 049VH UT WOS:000312011000008 PM 23060039 ER PT J AU Widemann, BC Kim, A Fox, E Baruchel, S Adamson, PC Ingle, AM Bender, JG Burke, M Weigel, B Stempak, D Balis, FM Blaney, SM AF Widemann, Brigitte C. Kim, AeRang Fox, Elizabeth Baruchel, Sylvain Adamson, Peter C. Ingle, Ashish M. Bender, Julia Glade Burke, Michael Weigel, Brenda Stempak, Diana Balis, Frank M. Blaney, Susan M. TI A Phase I Trial and Pharmacokinetic Study of Sorafenib in Children with Refractory Solid Tumors or Leukemias: A Children's Oncology Group Phase I Consortium Report SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; FACTOR RECEPTOR INHIBITOR; ACUTE MYELOGENOUS LEUKEMIA; RENAL-CELL CARCINOMA; DAYS ON/7 DAYS; RAF KINASE; HEPATOCELLULAR-CARCINOMA; MULTIKINASE INHIBITOR; GROWTH; CANCER AB Purpose: To determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of sorafenib in children with refractory extracranial solid tumors and evaluate the tolerability of the solid tumor MTD in children with refractory leukemias. Experimental Design: Sorafenib was administered orally every 12 hours for consecutive 28-day cycles. Pharmacokinetics (day 1 and steady-state) and pharmacodynamics were conducted during cycle 1. Results: Of 65 patients enrolled, 60 were eligible. In the solid tumor cohort (n = 49), 4 of 6 patients experienced a DLT [hypertension, pain, rash/urticaria, thrombocytopenia, alanine aminotransferase (ALT)/aspartate aminotransferase (AST)] at the starting dose (150 mg/m(2)/dose) which resulted in de-escalation to 105 mg/m(2)/dose. After eligibility criteria modification and dose re-escalation, the MTD was 200 mg/m(2)/dose for solid tumors and 150 mg/m(2)/dose for leukemias. Sorafenib exposure was highly variable between patients but was within the ranges reported in adults. The apparent sorafenib clearance increased with patient age. Diarrhea, rash, fatigue, and increased ALT/AST were the most common sorafenib-related toxicities. Stable disease for 4 or more cycles was observed in 14 solid tumor patients, and 2 patients with acute myeloid leukemia (AML) and FLT3 internal tandem duplication (FLT3ITD) experienced a decrease in bone marrow blasts to less than 5%. Conclusions: The recommended phase II dose of sorafenib administered every 12 hours continuously for children with solid tumors is 200 mg/m(2)/dose and 150 mg/m(2)/dose for children with leukemias. Sorafenib toxicities and distribution in children are similar to adults. The activity of sorafenib in children with AML and FLT3ITD is currently being evaluated, and a phase II study for select solid tumors is ongoing. Clin Cancer Res; 18(21); 6011-22. (C) 2012 AACR. C1 [Widemann, Brigitte C.; Kim, AeRang] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Kim, AeRang] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Fox, Elizabeth; Adamson, Peter C.; Balis, Frank M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Baruchel, Sylvain; Stempak, Diana] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Ingle, Ashish M.] Operat Ctr, Childrens Oncol Grp, Arcadia, CA USA. [Bender, Julia Glade] Columbia Univ, Med Ctr, New York, NY USA. [Burke, Michael; Weigel, Brenda] Univ Minnesota, Med Ctr Fairview, Minneapolis, MN USA. [Blaney, Susan M.] Texas Childrens Canc Ctr, Houston, TX USA. RP Widemann, BC (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 1-5750, Bethesda, MD 20892 USA. EM widemanb@mail.nih.gov FU NIH, National Cancer Institute (NCI), Center for Cancer Research; Phase I/Pilot Consortium Grant of the Children's Oncology Group from the NCI, NIH, Bethesda, MD [U01 CA97452] FX This research was in part supported by the Intramural Research Program of the NIH, National Cancer Institute (NCI), Center for Cancer Research, and by the Phase I/Pilot Consortium Grant U01 CA97452 of the Children's Oncology Group from the NCI, NIH, Bethesda, MD. NR 32 TC 37 Z9 38 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2012 VL 18 IS 21 BP 6011 EP 6022 DI 10.1158/1078-0432.CCR-11-3284 PG 12 WC Oncology SC Oncology GA 049YV UT WOS:000312020400020 PM 22962440 ER PT J AU Lee, EQ Puduvalli, VK Reid, JM Kuhn, JG Lamborn, KR Cloughesy, TF Chang, SM Drappatz, J Yung, WKA Gilbert, MR Robins, HI Lieberman, FS Lassman, AB McGovern, RM Xu, JH Desideri, S Ye, XB Ames, MM Espinoza-Delgado, I Prados, MD Wen, PY AF Lee, Eudocia Q. Puduvalli, Vinay K. Reid, Joel M. Kuhn, John G. Lamborn, Kathleen R. Cloughesy, Timothy F. Chang, Susan M. Drappatz, Jan Yung, W. K. Alfred Gilbert, Mark R. Robins, H. Ian Lieberman, Frank S. Lassman, Andrew B. McGovern, Renee M. Xu, Jihong Desideri, Serena Ye, Xiabu Ames, Matthew M. Espinoza-Delgado, Igor Prados, Michael D. Wen, Patrick Y. TI Phase I Study of Vorinostat in Combination with Temozolomide in Patients with High-Grade Gliomas: North American Brain Tumor Consortium Study 04-03 SO CLINICAL CANCER RESEARCH LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; ADJUVANT TEMOZOLOMIDE; TRIAL; GLIOBLASTOMA; SAHA; RADIOTHERAPY; CONCOMITANT; GROWTH; CANCER AB Purpose: A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG). Experimental Design: This phase I, dose-finding, investigational study was conducted in two parts. Part 1 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days every 28 days. Part 2 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days of the first cycle and 200 mg/m(2)/day for 5 days of the subsequent 28-day cycles. Results: In part 1, the MTD of vorinostat administered on days 1 to 7 and 15 to 21 of every 28-day cycle, in combination with TMZ, was 500 mg daily. Dose-limiting toxicities (DLT) included grade 3 anorexia, grade 3 ALT, and grade 5 hemorrhage in the setting of grade 4 thrombocytopenia. In part 2, the MTD of vorinostat on days 1 to 7 and 15 to 21 of every 28-day cycle, combined with TMZ, was 400 mg daily. No DLTs were encountered, but vorinostat dosing could not be escalated further due to thrombocytopenia. The most common serious adverse events were fatigue, lymphopenia, thrombocytopenia, and thromboembolic events. There were no apparent pharmacokinetic interactions between vorinostat and TMZ. Vorinostat treatment resulted in hyperacetylation of histones H3 and H4 in peripheral mononuclear cells. Conclusion: Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway. Clin Cancer Res; 18(21); 6032-9. (C) 2012 AACR. C1 [Lee, Eudocia Q.; Drappatz, Jan; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Puduvalli, Vinay K.; Yung, W. K. Alfred; Gilbert, Mark R.; Xu, Jihong] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Reid, Joel M.; McGovern, Renee M.; Ames, Matthew M.] Mayo Clin, Ctr Comprehens Canc, Rochester, MN USA. [Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. [Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA. [Drappatz, Jan; Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Ctr Canc, Pittsburgh, PA USA. [Robins, H. Ian] Univ Wisconsin, Madison, WI USA. [Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Desideri, Serena; Ye, Xiabu] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,SW 430, Boston, MA 02215 USA. EM pwen@partners.org RI Puduvalli, Vinay/A-2411-2016; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU NIH [U01 CA062399]; Merck; UpToDate; DEMOS Publishers; Genentech; Celgene; Schering; Abbott; Campus Bio; Eisai; GSK; Merck/Schering-Plough; Novartis; Kyowa Hakko Kirin Pharma; Keryx; Sigma Tau; Amgen; AstraZeneca; Esai; Sanofi-Aventis; Genzyme; Medimmune; Vascular Biogenics FX E. Q. Lee is on advisory board for Novartis and has royalties from UpToDate and DEMOS Publishers. Vinay K. Puduvalli has a research grant support from Merck, Genentech, and Celgene and is on advisory board for Novartis. Joel M. Reid has a funding from Merck for PK analysis. T. F. Cloughesy is a consultant/advisory member of Merck, Roche, Merck Sorano, Celgene, and Novartis, has honoraria from speakers bureau from Merck, and honoraria from ad board from Genentech and Roche. Susan M. Chang has a research support from Schering. Mark R. Gilbert is on advisory boards of Merck, Genentech and Abbott and has honoraria from Merck, Genentech and Abbott. H. Ian Robins is a consultant/advisory board member of Genentech and Abbott. Andrew B. Lassman is a consultant/advisory board member, is a Speaker, and has research funding from Abbott, Campus Bio, Eisai, Genentech, GSK, Merck/Schering-Plough, Novartis, Kyowa Hakko Kirin Pharma, Keryx, Sigma Tau. R. M. McGovern and Matthew M. Ames have funding from Merck for PK analysis. Patrick Y. Wen is a consultant/ advisory board member of Novartis and Merck, is a paid speaker for Merck, has research support from Amgen, AstraZeneca, Esai, Sanofi-Aventis, Genentech, Genzyme, Novartis, Medimmune, Vascular Biogenics, and has royalties from UpToDate and DEMOS Publishers. No potential conflicts of interest were disclosed by other authors.; This study was sponsored by NIH Grant number U01 CA062399. Funding for pharmacokinetic analysis was provided by Merck. NR 14 TC 20 Z9 22 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2012 VL 18 IS 21 BP 6032 EP 6039 DI 10.1158/1078-0432.CCR-12-1841 PG 8 WC Oncology SC Oncology GA 049YV UT WOS:000312020400022 PM 22923449 ER PT J AU Matsui, S Simon, R Qu, PP Shaughnessy, JD Barlogie, B Crowley, J AF Matsui, Shigeyuki Simon, Richard Qu, Pingping Shaughnessy, John D., Jr. Barlogie, Bart Crowley, John TI Developing and Validating Continuous Genomic Signatures in Randomized Clinical Trials for Predictive Medicine SO CLINICAL CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA; BREAST-CANCER; EXPRESSION; SURVIVAL; CLASSIFICATION; SELECTION; DESIGN; GENES; MODEL; BIAS AB Purpose: It is highly challenging to develop reliable diagnostic tests to predict patients' responsiveness to anticancer treatments on clinical endpoints before commencing the definitive phase III randomized trial. Development and validation of genomic signatures in the randomized trial can be a promising solution. Such signatures are required to predict quantitatively the underlying heterogeneity in the magnitude of treatment effects. Experimental Design: We propose a framework for developing and validating genomic signatures in randomized trials. Codevelopment of predictive and prognostic signatures can allow prediction of patient-level survival curves as basic diagnostic tools for treating individual patients. Results: We applied our framework to gene-expression microarray data from a large-scale randomized trial to determine whether the addition of thalidomide improves survival for patients with multiple myeloma. The results indicated that approximately half of the patients were responsive to thalidomide, and the average improvement in survival for the responsive patients was statistically significant. Cross-validated patient-level survival curves were developed to predict survival distributions of individual future patients as a function of whether or not they are treated with thalidomide and with regard to their baseline prognostic and predictive signature indices. Conclusion: The proposed framework represents an important step toward reliable predictive medicine. It provides an internally validated mechanism for using randomized clinical trials to assess treatment efficacy for a patient population in a manner that takes into consideration the heterogeneity in patients' responsiveness to treatment. It also provides cross-validated patient-level survival curves that can be used for selecting treatments for future patients. Clin Cancer Res; 18(21); 6065-73. (C) 2012 AACR. C1 [Matsui, Shigeyuki] Inst Stat Math, Dept Data Sci, Tachikawa, Tokyo 1908562, Japan. [Simon, Richard] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD USA. [Shaughnessy, John D., Jr.; Barlogie, Bart] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. RP Matsui, S (reprint author), Inst Stat Math, Dept Data Sci, 10-3 Midori Cho, Tachikawa, Tokyo 1908562, Japan. EM smatsui@ism.ac.jp FU NCI NIH HHS [P01 CA055819] NR 24 TC 11 Z9 12 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2012 VL 18 IS 21 BP 6065 EP 6073 DI 10.1158/1078-0432.CCR-12-1206 PG 9 WC Oncology SC Oncology GA 049YV UT WOS:000312020400026 PM 22927484 ER PT J AU Giacoia, GP Taylor-Zapata, P Zajicek, A AF Giacoia, George P. Taylor-Zapata, Perdita Zajicek, Anne TI Eunice Kennedy Shriver National Institute of Child Health and Human Development Pediatrics Formulation Initiative: Proceedings from the Second Workshop on Pediatric Formulations SO CLINICAL THERAPEUTICS LA English DT Editorial Material DE pediatric formulations; drug delivery systems; novel formulations ID DRUG-DELIVERY; YOUNG-CHILDREN; BEVACIZUMAB; MEDICINES; EFFICACY; SAFETY AB Background: The Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) organized a workshop held in November 2011 to address knowledge gaps that limit the availability of adequate pediatric formulations. This workshop was used as a means to identify the types of research innovations needed and to stimulate research efforts designed to improve the availability of pediatric formulations and the technologies required to make these formulations. Methods: Information for this article was gathered from the proceedings of the Second US PFI Workshop sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland, on November 1 and 2, 2011, as well as from post-workshop discussions. The workshop preparation began with formation of 4 working groups: Biopharmaceutics, Biopharmaceutics Classification System (BCS), New Technology and Drug Delivery Systems, and Taste and Flavor. Results: The recommendations of the 4 working groups will form the basis for the development of a blueprint to guide future research efforts. The pediatric-specific problems identified include the heterogeneity of the population, the small size of the pediatric drug market, the limited number of new formulations for the large number of off-patent and unlabeled drugs, and the lack of universal agreement on how to define appropriate formulations for different ages and stages of development. There was consensus on the need to develop a universal technology platform for flexible pediatric dosage forms, transforming an empirical process into a science-based platform. A number of problems affect the availability of drugs in the developing world. Age-appropriate solid oral pediatric medicines for common diseases can have a global impact. Success on a global scale depends on the commitment of policy makers, regulators, scientists, pharmaceutical companies, sponsors, government, and research foundations to address gaps in knowledge and solve public health issues related to the availability of formulations in the developing world. Conclusions: Solutions to the worldwide lack of appropriate pediatric formulations will require the development of a road map and the commitment of policy makers, regulators, scientists, pharmaceutical sponsors, academic institutions, governments, and research foundations. The development of a universal, cost-effective platform using existing or developing innovative technology that produces flexible pediatric dosage forms remains an important but elusive goal. (Clin Ther. 2012;34: S1-S10) Published by Elsevier HS Journals, Inc. C1 [Giacoia, George P.; Taylor-Zapata, Perdita; Zajicek, Anne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pharmacol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Giacoia, GP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pharmacol Branch, NIH, Dept Hlth & Human Serv, 6100 Execut Blvd,Room 4A01C MSC 7510, Bethesda, MD 20892 USA. EM giacoiag@exchange.nih.gov NR 28 TC 12 Z9 13 U1 1 U2 11 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD NOV PY 2012 VL 34 IS 11 BP S1 EP S10 DI 10.1016/j.clinthera.2012.09.013 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 051GS UT WOS:000312114900007 PM 23149008 ER PT J AU Zhang, XM Qi, QB Zhang, CL Hu, FB Sacks, FM Qi, L AF Zhang, Xiaomin Qi, Qibin Zhang, Cuilin Hu, Frank B. Sacks, Frank M. Qi, Lu TI FTO Genotype and 2-Year Change in Body Composition and Fat Distribution in Response to Weight-Loss Diets The POUNDS LOST Trial SO DIABETES LA English DT Article ID VISCERAL ADIPOSE-TISSUE; GENE-EXPRESSION; COMMON VARIANT; ADULT OBESITY; MASS INDEX; ASSOCIATION; RS9939609; HUMANS; WOMEN; INTERVENTION AB Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902. Diabetes 61:3005-3011, 2012 C1 [Zhang, Xiaomin; Qi, Qibin; Hu, Frank B.; Sacks, Frank M.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Zhang, Xiaomin] Huazhong Univ Sci & Technol, Dept Occupat & Environm Hlth, Wuhan 430074, Peoples R China. [Zhang, Xiaomin] Huazhong Univ Sci & Technol, Key Lab Environm & Hlth, Tongji Med Coll, Minist Educ,Sch Publ Hlth, Wuhan 430074, Peoples R China. [Zhang, Cuilin] Eunice Kennedy Shrivel Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Hu, Frank B.; Sacks, Frank M.; Qi, Lu] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hu, Frank B.; Sacks, Frank M.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu FU National Heart, Lung, and Blood Institute [HL071981]; National Institute of Diabetes and Digestive and Kidney Diseases [DK091718]; General Clinical Research Center [RR-02635]; Boston Obesity Nutrition Research Center [DK46200]; American Heart Association [0730094N]; Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health; National Natural Science Foundation of China [NNSFC 30972453] FX This study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718), the General Clinical Research Center (RR-02635), and the Boston Obesity Nutrition Research Center (DK46200). L.Q. was a recipient of the American Heart Association Scientist Development Award (0730094N). C.Z. was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health. X.Z. was supported by the National Natural Science Foundation of China (NNSFC 30972453). NR 39 TC 39 Z9 39 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2012 VL 61 IS 11 BP 3005 EP 3011 DI 10.2337/db11-1799 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GQ UT WOS:000312041600040 PM 22891219 ER PT J AU Howson, JMM Cooper, JD Smyth, DJ Walker, NM Stevens, H She, JX Eisenbarth, GS Rewers, M Todd, JA Akolkar, B Concannon, P Erlich, HA Julier, C Morahan, G Nerup, J Nierras, C Pociot, F Rich, SS AF Howson, Joanna M. M. Cooper, Jason D. Smyth, Deborah J. Walker, Neil M. Stevens, Helen She, Jin-Xiong Eisenbarth, George S. Rewers, Marian Todd, John A. Akolkar, Beena Concannon, Patrick Erlich, Henry A. Julier, Cecile Morahan, Grant Nerup, Jorn Nierras, Concepcion Pociot, Flemming Rich, Stephen S. CA Type 1 Diabet Genetics Consortium TI Evidence of Gene-Gene Interaction and Age-at-Diagnosis Effects in Type 1 Diabetes SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; CTLA4 GENES; CLASS-I; HLA-B; PTPN22; SUSCEPTIBILITY; VARIANTS; GENOTYPE; MELLITUS; DISEASES AB The common genetic loci that independently influence the risk of type 1 diabetes have largely been determined. Their interactions with age-at-diagnosis of type 1 diabetes, sex, or the major susceptibility locus, HLA class II, remain mostly unexplored. A large collection of more than 14,866 type 1 diabetes samples (6,750 British diabetic individuals and 8,116 affected family samples of European descent) were genotyped at 38 confirmed type 1 diabetes-associated non-HLA regions and used to test for interaction of association with age-at-diagnosis, sex, and HLA class II genotypes using regression models. The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 x 10(-6) and 2.5 x 10(-5), respectively). For both loci, individuals carrying the susceptible homozygous genotype were, on average, 7.2 months younger at diagnosis than those carrying the protective homozygous genotypes. In addition to protein tyrosine phosphatase nonreceptor type 22 (PTPN22), evidence of statistical interaction between HLA class II genotypes and rs3087243 at cytotoxic T-lymphocyte antigen 4 (CTLA4)/2q33.2 was obtained (P = 7.90 X 10(-5)). No evidence of differential risk by sex was obtained at any loci (P >= 0.01). Statistical interaction effects can be detected in type 1 diabetes although they provide a relatively small contribution to our understanding of the familial clustering of the disease. Diabetes 61:3012-3017, 2012 C1 [Howson, Joanna M. M.; Cooper, Jason D.; Smyth, Deborah J.; Walker, Neil M.; Stevens, Helen; Todd, John A.] Univ Cambridge, Wellcome Trust Diabet & Inflammat Lab, Cambridge Inst Med Res, Juvenile Diabet Res Fdn,Dept Med Genet, Cambridge, England. [She, Jin-Xiong] Georgia Hlth Sci Univ, Ctr Biotechnol & Genom Med, Augusta, GA USA. [Eisenbarth, George S.; Rewers, Marian] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA. [Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA. [Concannon, Patrick] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Concannon, Patrick; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Erlich, Henry A.] Roche Mol Syst, Pleasanton, CA USA. [Julier, Cecile] Univ Paris 07, Paris, France. [Morahan, Grant] Univ Western Australia, Ctr Diabet Res, Western Australian Inst Med Res, Perth, WA 6009, Australia. [Morahan, Grant] Univ Western Australia, Med Res Ctr, Perth, WA 6009, Australia. [Nerup, Jorn] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Nerup, Jorn] Hagedorn Res Inst, Gentofte, Denmark. [Nierras, Concepcion] Juvenile Diabet Res Fdn, New York, NY USA. [Pociot, Flemming] Glostrup Cty Hosp, Glostrup Res Inst, Glostrup, Denmark. [Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. RP Howson, JMM (reprint author), Univ Cambridge, Wellcome Trust Diabet & Inflammat Lab, Cambridge Inst Med Res, Juvenile Diabet Res Fdn,Dept Med Genet, Cambridge, England. EM joanna.howson@cimr.cam.ac.uk RI Todd, John/A-3542-2010; OI Walker, Neil/0000-0001-9796-7688; smyth, deborah/0000-0002-6330-2669; Concannon, Patrick/0000-0002-5801-1859; Pociot, Flemming/0000-0003-3274-5448 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Human Genome Research Institute; National Institute of Child Health and Human Development; Juvenile Diabetes Research Foundation International (JDRF); Wellcome Trust (WT) [076113]; National Institute for Health Research Cambridge Biomedical Centre; WT Strategic Award [079895]; JDRF; [U01 DK-062418] FX This research uses resources provided by the T1DGC, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development, and Juvenile Diabetes Research Foundation International (JDRF) and is supported by U01 DK-062418. This work was funded by the JDRF, the Wellcome Trust (WT), under award 076113, and by the National Institute for Health Research Cambridge Biomedical Centre. The Cambridge Institute for Medical Research (CIMR) is in receipt of a WT Strategic Award (079895). T1DGC supplied samples. NR 29 TC 24 Z9 25 U1 1 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2012 VL 61 IS 11 BP 3012 EP 3017 DI 10.2337/db11-1694 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050GQ UT WOS:000312041600041 PM 22891215 ER PT J AU Katz, DM Berger-Sweeney, JE Eubanks, JH Justice, MJ Neul, JL Pozzo-Miller, L Blue, ME Christian, D Crawley, JN Giustetto, M Guy, J Howell, CJ Kron, M Nelson, SB Samaco, RC Schaevitz, LR St Hillaire-Clarke, C Young, JL Zoghbi, HY Mamounas, LA AF Katz, David M. Berger-Sweeney, Joanne E. Eubanks, James H. Justice, Monica J. Neul, Jeffrey L. Pozzo-Miller, Lucas Blue, Mary E. Christian, Diana Crawley, Jacqueline N. Giustetto, Maurizio Guy, Jacky Howell, C. James Kron, Miriam Nelson, Sacha B. Samaco, Rodney C. Schaevitz, Laura R. St Hillaire-Clarke, Coryse Young, Juan L. Zoghbi, Huda Y. Mamounas, Laura A. TI Preclinical research in Rett syndrome: setting the foundation for translational success SO DISEASE MODELS & MECHANISMS LA English DT Review ID MECP2 MUTANT MICE; SEVERE MENTAL-RETARDATION; CPG-BINDING PROTEIN-2; NEUROTROPHIC FACTOR EXPRESSION; MOUSE MODEL; BEHAVIORAL-PHENOTYPE; RESPIRATORY-FUNCTION; SYNAPTIC PLASTICITY; SOCIAL INTERACTIONS; PYRAMIDAL NEURONS AB In September of 2011, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross-section of basic scientists, clinicians and representatives from the National Institutes of Health (N H), the US Food and Drug Administration (FDA), the pharmaceutical industry and private foundations to assess the state of the art in animal studies of Rett syndrome (RTT). The aim of the workshop was to identify crucial knowledge gaps and to suggest scientific priorities and best practices for the use of animal models in preclinical evaluation of potential new RTT therapeutics. This review summarizes outcomes from the workshop and extensive follow-up discussions among participants, and includes: (1) a comprehensive summary of the physiological and behavioral phenotypes of RTT mouse models to date, and areas in which further phenotypic analyses are required to enhance the utility of these models for translational studies; (2) discussion of the impact of genetic differences among mouse models, and methodological differences among laboratories, on the expression and analysis, respectively, of phenotypic traits; and (3) definitions of the standards that the community of RTT researchers can implement for rigorous preclinical study design and transparent reporting to ensure that decisions to initiate costly clinical trials are grounded in reliable preclinical data. C1 [Katz, David M.; Christian, Diana; Howell, C. James; Kron, Miriam] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44120 USA. [Berger-Sweeney, Joanne E.; Schaevitz, Laura R.] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Eubanks, James H.] Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada. [Justice, Monica J.; Neul, Jeffrey L.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Neul, Jeffrey L.; Samaco, Rodney C.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Neul, Jeffrey L.; Samaco, Rodney C.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Neul, Jeffrey L.; Samaco, Rodney C.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. [Neul, Jeffrey L.; Samaco, Rodney C.; Zoghbi, Huda Y.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA. [Pozzo-Miller, Lucas] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA. [Blue, Mary E.] Hugo W Moser Res Inst Kennedy Krieger, Baltimore, MD 21209 USA. [Crawley, Jacqueline N.] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. [Giustetto, Maurizio] Univ Turin, Dept Neurosci, I-10126 Turin, Italy. [Giustetto, Maurizio] Univ Turin, Natl Inst Neurosci Italy, I-10126 Turin, Italy. [Guy, Jacky] Univ Edinburgh, Edinburgh EH9 3JR, Midlothian, Scotland. [Nelson, Sacha B.] Brandeis Univ, Shapiro Sci Ctr, Waltham, MA 02454 USA. [St Hillaire-Clarke, Coryse; Mamounas, Laura A.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. [Young, Juan L.] Hussman Inst Human Genom, Miami, FL 33136 USA. [Zoghbi, Huda Y.] Howard Hughes Med Inst, Houston, TX 77030 USA. RP Katz, DM (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurosci, 10900 Euclid Ave, Cleveland, OH 44120 USA. EM david.katz@case.edu; hzoghbi@bcm.edu; mamounal@ninds.nih.gov OI Nelson, Sacha/0000-0002-0108-8599; Christian, Diana/0000-0002-1799-0771; Neul, Jeffrey/0000-0002-5628-5872; Giustetto, Maurizio/0000-0003-1323-4060 FU National Institute of Neurological Disorders and Stroke (NINDS); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); International Rett Syndrome Research Foundation (IRSF); Rett Syndrome Research Trust (RSRT); NINDS [NS-057398, NS-065027]; Rett Syndrome Research Trust; International Rett Syndrome Foundation (ANGEL) [2608]; ANGEL award [2583]; Canadian Institutes of Health [MOP-106481]; Fondazione Telethon FX Support for the September 2011 workshop on which this paper reports ('Setting Priorities for Therapy Development in Rett Syndrome') was provided by the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Research Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT). Grant support includes NINDS (NS-057398 to D.M.K. and NS-065027 to L.P.-M.), Rett Syndrome Research Trust (to M.J.J.), the International Rett Syndrome Foundation (ANGEL award 2608 to M.J.J. and ANGEL award 2583 to D.M.K.) and Canadian Institutes of Health (MOP-106481 to J.H.E.). NR 141 TC 64 Z9 64 U1 0 U2 23 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD NOV PY 2012 VL 5 IS 6 BP 733 EP 745 DI 10.1242/dmm.011007 PG 13 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 047RT UT WOS:000311859700006 PM 23115203 ER PT J AU Qi, QB Menzaghi, C Smith, S Liang, LM de Rekeneire, N Garcia, ME Lohman, KK Miljkovic, I Strotmeyer, ES Cummings, SR Kanaya, AM Tylavsky, FA Satterfield, S Ding, JZ Rimm, EB Trischitta, V Hu, FB Liu, YM Qi, L AF Qi, Qibin Menzaghi, Claudia Smith, Shelly Liang, Liming de Rekeneire, Nathalie Garcia, Melissa E. Lohman, Kurt K. Miljkovic, Iva Strotmeyer, Elsa S. Cummings, Steve R. Kanaya, Alka M. Tylavsky, Frances A. Satterfield, Suzanne Ding, Jingzhong Rimm, Eric B. Trischitta, Vincenzo Hu, Frank B. Liu, Yongmei Qi, Lu TI Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels SO HUMAN MOLECULAR GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; LINKED-IMMUNOSORBENT-ASSAY; INSULIN-RESISTANCE; PLASMA RESISTIN; SERUM RESISTIN; HEART-DISEASE; ADIPONECTIN LEVELS; HORMONE RESISTIN; GENETIC-VARIANTS; MESSENGER-RNA AB Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses Health Study (n 1590) and the Health, Aging and Body Composition Study (n 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P 6.37 10(12)) and SNP rs13144478 (P 6.19 10(18)), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P 3.68 10(7)). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio 1.18 (95 CI, 1.031.34); P 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease. C1 [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA. [Qi, Qibin; Rimm, Eric B.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Liang, Liming; Rimm, Eric B.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Menzaghi, Claudia; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Garcia, Melissa E.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [de Rekeneire, Nathalie] Yale Univ, Sch Med, Dept Geriatr, New Haven, CT USA. [Miljkovic, Iva; Strotmeyer, Elsa S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Cummings, Steve R.; Kanaya, Alka M.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Tylavsky, Frances A.; Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Rimm, Eric B.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. [Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. RP Liu, YM (reprint author), Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27157 USA. EM yoliu@wakehealth.edu; nhlqi@channing.harvard.edu RI Strotmeyer, Elsa/F-3015-2014; Trischitta, Vincenzo/K-1487-2016; OI Trischitta, Vincenzo/0000-0003-1174-127X; Miljkovic, Iva/0000-0002-3155-9777; Strotmeyer, Elsa/0000-0002-4093-6036; Menzaghi, Claudia/0000-0002-7438-8955 FU NHS; HPFS [DK091718, HL071981, U01HG004399, HL71981, HL073168, DK58845, DK46200]; American Heart Association Scientist Development Award [0730094N]; Merck Research Laboratories, North Wales, PA, USA; NIH/NIA [N01AG62101, N01AG62103, N01AG62106]; NIA [1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C]; Intramural Research Program of the NIH, National Institute on Aging; Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST, Italian Ministry of Health [RC2011, RC2012]; EFSD/Pfizer FX This research in the NHS and HPFS is supported by grants DK091718, HL071981, U01HG004399, HL71981, HL073168, U01HG004399, DK58845 and DK46200. L. Q. is a recipient of the American Heart Association Scientist Development Award (0730094N). The genotyping of the HPFS and NHS CHD GWAS was supported by an unrestricted grant from Merck Research Laboratories, North Wales, PA, USA. This research in the Health ABC was supported by NIH/NIA contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study in the Health ABC was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences, and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. Part of the research described in this paper was supported by Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST 2006, an Italian Ministry of Health grant (RC2011 and RC2012), an EFSD/Pfizer grant (C. M.). NR 43 TC 8 Z9 8 U1 5 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2012 VL 21 IS 21 BP 4774 EP 4780 DI 10.1093/hmg/dds300 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 025DN UT WOS:000310165500015 PM 22843503 ER PT J AU Boraska, V Jeroncic, A Colonna, V Southam, L Nyholt, DR Rayner, NW Perry, JRB Toniolo, D Albrecht, E Ang, W Bandinelli, S Barbalic, M Barroso, I Beckmann, JS Biffar, R Boomsma, D Campbell, H Corre, T Erdmann, J Esko, T Fischer, K Franceschini, N Frayling, TM Girotto, G Gonzalez, JR Harris, TB Heath, AC Heid, IM Hoffmann, W Hofman, A Horikoshi, M Zhao, JH Jackson, AU Hottenga, JJ Jula, A Kahonen, M Khaw, KT Kiemeney, LA Klopp, N Kutalik, Z Lagou, V Launer, LJ Lehtimaki, T Lemire, M Lokki, ML Loley, C Luan, JA Mangino, M Leach, IM Medland, SE Mihailov, E Montgomery, GW Navis, G Newnham, J Nieminen, MS Palotie, A Panoutsopoulou, K Peters, A Pirastu, N Polasek, O Rehnstrom, K Ripatti, S Ritchie, GRS Rivadeneira, F Robino, A Samani, NJ Shin, SY Sinisalo, J Smit, JH Soranzo, N Stolk, L Swinkels, DW Tanaka, T Teumer, A Tonjes, A Traglia, M Tuomilehto, J Valsesia, A van Gilst, WH van Meurs, JBJ Smith, AV Viikari, J Vink, JM Waeber, G Warrington, NM Widen, E Willemsen, G Wright, AF Zanke, BW Zgaga, L Boehnke, M d'Adamo, AP de Geus, E Demerath, EW den Heijer, M Eriksson, JG Ferrucci, L Gieger, C Gudnason, V Hayward, C Hengstenberg, C Hudson, TJ Jarvelin, MR Kogevinas, M Loos, RJF Martin, NG Metspalu, A Pennell, CE Penninx, BW Perola, M Raitakari, O Salomaa, V Schreiber, S Schunkert, H Spector, TD Stumvoll, M Uitterlinden, AG Ulivi, S van der Harst, P Vollenweider, P Volzke, H Wareham, NJ Wichmann, HE Wilson, JF Rudan, I Xue, YL Zeggini, E AF Boraska, Vesna Jeroncic, Ana Colonna, Vincenza Southam, Lorraine Nyholt, Dale R. Rayner, Nigel William Perry, John R. B. Toniolo, Daniela Albrecht, Eva Ang, Wei Bandinelli, Stefania Barbalic, Maja Barroso, Ines Beckmann, Jacques S. Biffar, Reiner Boomsma, Dorret Campbell, Harry Corre, Tanguy Erdmann, Jeanette Esko, Tonu Fischer, Krista Franceschini, Nora Frayling, Timothy M. Girotto, Giorgia Gonzalez, Juan R. Harris, Tamara B. Heath, Andrew C. Heid, Iris M. Hoffmann, Wolfgang Hofman, Albert Horikoshi, Momoko Zhao, Jing Hua Jackson, Anne U. Hottenga, Jouke-Jan Jula, Antti Kahonen, Mika Khaw, Kay-Tee Kiemeney, Lambertus A. Klopp, Norman Kutalik, Zoltan Lagou, Vasiliki Launer, Lenore J. Lehtimaki, Terho Lemire, Mathieu Lokki, Marja-Liisa Loley, Christina Luan, Jian'an Mangino, Massimo Leach, Irene Mateo Medland, Sarah E. Mihailov, Evelin Montgomery, Grant W. Navis, Gerjan Newnham, John Nieminen, Markku S. Palotie, Aarno Panoutsopoulou, Kalliope Peters, Annette Pirastu, Nicola Polasek, Ozren Rehnstrom, Karola Ripatti, Samuli Ritchie, Graham R. S. Rivadeneira, Fernando Robino, Antonietta Samani, Nilesh J. Shin, So-Youn Sinisalo, Juha Smit, Johannes H. Soranzo, Nicole Stolk, Lisette Swinkels, Dorine W. Tanaka, Toshiko Teumer, Alexander Tonejes, Anke Traglia, Michela Tuomilehto, Jaakko Valsesia, Armand van Gilst, Wiek H. van Meurs, Joyce B. J. Smith, Albert Vernon Viikari, Jorma Vink, Jacqueline M. Waeber, Gerard Warrington, Nicole M. Widen, Elisabeth Willemsen, Gonneke Wright, Alan F. Zanke, Brent W. Zgaga, Lina Boehnke, Michael d'Adamo, Adamo Pio de Geus, Eco Demerath, Ellen W. den Heijer, Martin Eriksson, Johan G. Ferrucci, Luigi Gieger, Christian Gudnason, Vilmundur Hayward, Caroline Hengstenberg, Christian Hudson, Thomas J. Jarvelin, Marjo-Riitta Kogevinas, Manolis Loos, Ruth J. F. Martin, Nicholas G. Metspalu, Andres Pennell, Craig E. Penninx, Brenda W. Perola, Markus Raitakari, Olli Salomaa, Veikko Schreiber, Stefan Schunkert, Heribert Spector, Tim D. Stumvoll, Michael Uitterlinden, Andre G. Ulivi, Sheila van der Harst, Pim Vollenweider, Peter Volzke, Henry Wareham, Nicholas J. Wichmann, H-Erich Wilson, James F. Rudan, Igor Xue, Yali Zeggini, Eleftheria CA Wellcome Trust Case Control TI Genome-wide meta-analysis of common variant differences between men and women SO HUMAN MOLECULAR GENETICS LA English DT Article ID HUMAN SEX-RATIO; ASSOCIATION; SIMULATION; DISEASE; BIRTH; TIME AB The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency 0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P 5 10(8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across approximate to 115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits. C1 [Boraska, Vesna; Colonna, Vincenza; Southam, Lorraine; Rayner, Nigel William; Barroso, Ines; Palotie, Aarno; Panoutsopoulou, Kalliope; Rehnstrom, Karola; Ritchie, Graham R. S.; Shin, So-Youn; Soranzo, Nicole; Xue, Yali; Zeggini, Eleftheria] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England. [Boraska, Vesna; Rudan, Igor] Univ Split, Sch Med, Dept Med Biol, Split, Croatia. [Jeroncic, Ana] Univ Split, Sch Med, Dept Res Biomed & Hlth, Split, Croatia. [Polasek, Ozren] Univ Split, Sch Med, Dept Publ Hlth, Split, Croatia. [Colonna, Vincenza] Natl Res Council CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy. [Nyholt, Dale R.; Medland, Sarah E.; Montgomery, Grant W.; Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Rayner, Nigel William; Perry, John R. B.; Horikoshi, Momoko; Lagou, Vasiliki] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Rayner, Nigel William; Horikoshi, Momoko; Lagou, Vasiliki] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Perry, John R. B.; Frayling, Timothy M.] Univ Exeter, Peninsula Med Sch, Exeter EX4 4QJ, Devon, England. [Perry, John R. B.; Mangino, Massimo; Soranzo, Nicole; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Toniolo, Daniela; Corre, Tanguy; Traglia, Michela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy. [Albrecht, Eva; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Ang, Wei; Newnham, John; Warrington, Nicole M.; Pennell, Craig E.] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Barbalic, Maja] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Barroso, Ines] Univ Cambridge, Metab Res Labs, Cambridge, England. [Zhao, Jing Hua; Luan, Jian'an; Loos, Ruth J. F.; Wareham, Nicholas J.] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England. [Beckmann, Jacques S.; Kutalik, Zoltan; Valsesia, Armand] Univ Lausanne, Dept Med Genet, CH-1015 Lausanne, Switzerland. [Beckmann, Jacques S.] Univ Lausanne Hosp, CHU Vaudois, Serv Med Genet, Lausanne, Switzerland. [Biffar, Reiner] Univ Med Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany. [Hoffmann, Wolfgang; Volzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Boomsma, Dorret; Hottenga, Jouke-Jan; Vink, Jacqueline M.; Willemsen, Gonneke; de Geus, Eco] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Campbell, Harry; Zgaga, Lina; Wilson, James F.; Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland. [Erdmann, Jeanette; Schunkert, Heribert] Med Univ Lubeck, Med Klin 2, Lubeck, Germany. [Erdmann, Jeanette; Schunkert, Heribert] Deutsch Zentrum Herz Kreislauf Forsch ev DZHK, Lubeck, Germany. [Loley, Christina] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Esko, Tonu; Fischer, Krista; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Esko, Tonu; Metspalu, Andres] Estonian Bioctr, Tartu, Estonia. [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Girotto, Giorgia; Pirastu, Nicola; Robino, Antonietta; d'Adamo, Adamo Pio] Univ Trieste, IRCCS Burlo Garofolo Trieste, Inst Maternal & Child Hlth, I-34127 Trieste, Italy. [Gonzalez, Juan R.; Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Gonzalez, Juan R.; Kogevinas, Manolis] CIBER Epidemiol Salud & Publ CIBERESP, Barcelona, Spain. [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Heid, Iris M.] Univ Regensburg, Med Ctr, Inst Epidemiol & Prevent Med, Regensburg, Germany. [Heid, Iris M.; Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany. [Rivadeneira, Fernando; Stolk, Lisette; van Meurs, Joyce B. J.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Hofman, Albert; Rivadeneira, Fernando; Stolk, Lisette; van Meurs, Joyce B. J.; Uitterlinden, Andre G.] Netherlands Consortium Hlth Ageing, Rotterdam, Netherlands. [Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Populat Studies Unit, Turku, Finland. [Lehtimaki, Terho] Univ Tampere, Fimlab Labs, Dept Clin Chem, FIN-33101 Tampere, Finland. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Kahonen, Mika; Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [Kiemeney, Lambertus A.; den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Swinkels, Dorine W.] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, NL-6525 ED Nijmegen, Netherlands. [den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands. [Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Klopp, Norman] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Unit Mol Epidemiol, Neuherberg, Germany. [Kutalik, Zoltan; Valsesia, Armand] Swiss Inst Bioinformat, Lausanne, Switzerland. [Lemire, Mathieu; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Palotie, Aarno; Rehnstrom, Karola; Ripatti, Samuli; Widen, Elisabeth; Perola, Markus] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Lokki, Marja-Liisa] Univ Helsinki, Transplantat Lab, Haartman Inst, Helsinki, Finland. [Leach, Irene Mateo; van Gilst, Wiek H.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Nieminen, Markku S.; Sinisalo, Juha] Univ Helsinki, Cent Hosp, Div Cardiol, Cardiovasc Lab, Helsinki, Finland. [Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Palotie, Aarno] Broad Inst MIT & Harvard, Cambridge, MA USA. [Ritchie, Graham R. S.] European Bioinformat Inst, Cambridge, England. [Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. [Smit, Johannes H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, EMGO Inst,Ctr Neurogen & Cognit Res, Amsterdam, Netherlands. [Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, EMGO Inst,Inst Neurosci, Amsterdam, Netherlands. [Tanaka, Toshiko] NIA, Clin Res Branch, NIH, Baltimore, MD 21250 USA. [Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Tonejes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany. [Tonejes, Anke; Stumvoll, Michael] Univ Leipzig, IFB Adipos Dis, Leipzig, Germany. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki 00271, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki 60220, Finland. [Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid 28046, Spain. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria. [Valsesia, Armand] Ludwig Inst Canc Res, Lausanne, Switzerland. [Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland. [Waeber, Gerard; Vollenweider, Peter] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland. [Wright, Alan F.; Hayward, Caroline] Western Gen Hosp, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Zanke, Brent W.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. [Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41000, Croatia. [Demerath, Ellen W.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Eriksson, Johan G.; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland. [Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Publ Hlth Genom, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.] Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Hengstenberg, Christian] Med Klin & Poliklin 2, Regensburg, Germany. [Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu, Finland. [Kogevinas, Manolis] IMIM Hosp Mar Res Inst, Barcelona, Spain. [Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece. [Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland. [Schreiber, Stefan] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany. [Ulivi, Sheila] Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Trieste, Italy. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Palotie, Aarno] Univ Cent Hosp Helsinki, Helsinki, Finland. RP Boraska, V (reprint author), Wellcome Trust Sanger Inst, Morgan Bldg,Wellcome Trust Genome Campus, Cambridge CB10 1HH, England. EM vboraska@mefst.hr RI Colonna, Vincenza/H-2021-2014; Erdmann, Jeanette/P-7513-2014; Jeroncic, Ana/D-6191-2017; Boraska Perica, Vesna/D-8230-2017; Study, Raine/G-9547-2015; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Polasek, Ozren/B-6002-2011; de Geus, Eco/M-9318-2015; Montgomery, Grant/B-7148-2008; Peters, Annette/A-6117-2011; Rudan, Igor/I-1467-2012; Smith, Albert/K-5150-2015; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; Kogevinas, Manolis/C-3918-2017; Swinkels, D.W./H-8098-2014; Warrington, Nicole/P-4868-2014; Pirastu, Nicola/G-4358-2011; Medland, Sarah/C-7630-2013; Nyholt, Dale/C-8384-2013; Beckmann, Jacques S /A-9772-2008; Ulivi, Sheila/H-3700-2013; Colaus, PsyColaus/K-6607-2013; Lagou, Vasiliki/N-8451-2013; d'Adamo, Adamo Pio/G-4064-2011; Kiemeney, Lambertus/D-3357-2009; Schreiber, Stefan/B-6748-2008 OI Sinisalo, Juha/0000-0002-0169-5137; Martin, Nicholas/0000-0003-4069-8020; Colonna, Vincenza/0000-0002-3966-0474; Erdmann, Jeanette/0000-0002-4486-6231; Soranzo, Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554; Rivadeneira, Fernando/0000-0001-9435-9441; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Girotto, Giorgia/0000-0003-4507-6589; Eriksson, Johan/0000-0002-2516-2060; Newnham, John/0000-0001-9983-7457; Jeroncic, Ana/0000-0003-1621-1956; Pirastu, Nicola/0000-0002-5363-3886; Zeggini, Eleftheria/0000-0003-4238-659X; Zgaga, Lina/0000-0003-4089-9703; Ritchie, Graham/0000-0002-6456-9736; Esko, Tonu/0000-0003-1982-6569; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; de Geus, Eco/0000-0001-6022-2666; Montgomery, Grant/0000-0002-4140-8139; Rudan, Igor/0000-0001-6993-6884; Smith, Albert/0000-0003-1942-5845; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Warrington, Nicole/0000-0003-4195-775X; Medland, Sarah/0000-0003-1382-380X; Beckmann, Jacques S /0000-0002-9741-1900; Ulivi, Sheila/0000-0003-3606-835X; d'Adamo, Adamo Pio/0000-0001-9367-4909; Kiemeney, Lambertus/0000-0002-2368-1326; Schreiber, Stefan/0000-0003-2254-7771 FU Wellcome Trust [076113, 098051]; NIH [N01-AG-1-2100, LM010098, HL65234, HL67466, RR018787]; NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); National Heart, Lung, and Blood Institute [HHSN26820 1100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN26820 1100010C, HHSN268201100011C, HHSN2682011 00012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; National Institutes of Health and NIH Roadmap for Medical Research [UL1RR025005]; Intramural Research Program of the NIH, National Institute on Aging; MedStar Research Institute; GlaxoSmithKline; Faculty of Biology and Medicine of Lausanne, Switzerland; Swiss National Science Foundation [33CSCO-122661]; Medical Research Council (UK); Republic of Croatia Ministry of Science, Education and Sports research [108-1080315-0302]; Republic of Croatia Ministry of Science, Education and Sports [108-1080315-0302]; European Commission [LSHG-CT-2006-018947]; Spanish Ministry of Science and Innovation [MTM2008-02457]; Fondo de Investigaciones Santarias [97/0035-01, 99/0034-01, 99/0034-02]; Hospital Universitario de Albacete; Consejeria de Sanidad; FWO (Fund for Scientific Research) [G.0402.00]; University of Antwerp; Flemish Health Ministry; Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Public Health Service [R01 HL62633-01]; Consell Interdepartamental de Recerca i Innovacio Tecnologica (CIRIT) [1999SGR 00241]; Red Respira Instituto de Salud Carlos III (ISCIII); FP7 programs (ENGAGE, OPENGENE); Estonian Government [SF0180142s08]; Estonian Research Roadmap through Estonian Ministry of Education and Research, Center of Excellence in Genomics (EXCEGEN); University of Tartu [SP1GVARENG]; Estonian Science Foundation [EstSF ETF9353]; European Community [HEALTH-F4-2007-201413]; Medical Research Council UK; Cancer Research UK; Deutsche Forschungsgemeinschaft; German Federal Ministry of Education and Research (BMBF); EU [LSHM-CT-2006-037593]; ENGAGE [201413]; CARDomics [01KU0908A]; DZHK (Deutsches Zentrum fur Herz-Kreislauf-Forschung - German Centre for Cardiovascular Research); BMBF (German Ministry of Education and Research); U.S. National Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; Intramural research program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland; Sir Henry Wellcome Postdoctoral Fellowship [092447/Z/10/Z]; Regione FVG [L.26.2008]; Compagnia di San Paolo, Torino, Italy; Fondazione Cariplo, Italy; Ministry of Health, Ricerca Finalizzata and Telethon, Italy; State of Bavaria; German National Genome Research Network [NGFN-2, NGFNPlus: 01GS0823]; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; Radboud University Nijmegen Medical Centre; Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health; GAIN; NIMH [MH081802]; Netherlands Heart Foundation [90.313, 86.083, 88.042, 2006B140, 2006T003]; Netherlands Organization for Scientific Research [904-61-090]; Genetics of individual differences in smoking initiation and persistence [NWO 985-10-002]; Resolving cause and effect in the association between exercise and well-being [904-61-193]; Twin family database for behaviour genomics studies [480-04-004]; Twin research focusing on behaviour [400-05-717]; Genetic determinants of risk behaviour in relation to alcohol use and alcohol use disorder [Addiction-31160008]; Genotype/phenotype database for behaviour genetic and genetic epidemiological studies [911-09-032]; Spinozapremie [SPI 56-464-14192]; CMSB: Center for Medical Systems Biology (NWO Genomics); BBMRI -NL: Biobanking and Biomolecular Resources Research Infrastructure; VU University; Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); European Science Foundation (ESF): Genomewide analyses of European twin and population cohorts [EU/QLRT-2001-01254]; European Community's Seventh Framework Program [HEALTH-F4-2007-201413]; European Science Council (ERC) Genetics of Mental Illness [230374]; Rutgers University Cell and DNA Repository cooperative agreement [NIMH U24 MH068457-06]; Collaborative study of the genetics of DZ twinning [NIH R01D0042157-01A]; Genetic Association Information Network; Pfizer Inc.; Affymetrix Inc.; Abbott Laboratories; Netherlands Organization for Scientific Research (NWO: MagW/ZonMW): Twin family database for behaviour genomics studies [480-04-004]; Chief Scientist Office of the Scottish Government; Royal Society; European Union [LSHG-CT-2006-018947]; Dutch Kidney Foundation [E033]; EU project grant GENECURE [FP-6 LSHM CT 2006 037697]; NWO VENI [91676170]; Dutch Inter University Cardiology Institute Netherlands (ICIN); Australian National Health and Medical Research Council (NHMRC) [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498]; Australian Research Council (ARC) [A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; U.S. National Institutes of Health (NIH) [AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206]; Netherlands Scientific Organization [NWO 480-05-003]; NHMRC [619667]; ARC Future Fellowship [FT0991022, FT110100548]; National Health and Medical Research Council of Australia [403981, 003209]; Canadian Institutes of Health Research [MOP-82893]; Netherlands Organisation of Scientific Research NWO Investments; Research Institute for Diseases in the Elderly; Netherlands Genomics Initiative (NGI) Netherlands Consortium of Healthy Aging (NCHA); EC; Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Bundesministerium fuer Forschung und Technology; Federal Ministry of Education and Research; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Greifswald Approach to Individualized Medicine (GANI_MED); Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg- West Pomerania; Interdisciplinary Centre for Clinical Research at the University of Leipzig; German Diabetes Association; BIF; DHFD, Diabetes Hilfs-und Forschungsfonds Deutschland; ENGAGE (European Network for Genetic and Genomic Epidemiology) Consortium, the European Community; European Community's Seventh Framework Programme; European Union FP-5 GenomEUtwin Project; Framework 6 Project EUroClot; National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre; Academy of Finland; Social Insurance Institution of Finland; University Hospital Medical; Turku University Hospitals; Finnish Foundation of Cardiovascular Research Emil Aaltonen Foundation; Tampere Tuberculosis Foundation; Unity Through Knowledge Fund CONNECTIVITY PROGRAM; National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia FX WTCCC: This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available in the Supplementary Material and at www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under award 076113.; AGES: The researchers are indebted to the participants for their willingness to participate in the study. This study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063.; ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN26820 1100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN26820 1100010C, HHSN268201100011C, and HHSN2682011 00012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research.; BLSA: The BLSA was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. A portion of that support was through a R&D contract with MedStar Research Institute.; CoLaus: The authors express their gratitude to the participants in the Lausanne CoLaus study and to the investigators who have contributed to the recruitment. We would like to thank Drs Vincent Mooser and Dawn Waterworth from GlaxoSmithKline for helpful comments and for their continuous support for the CoLaus project. Part of the computation has been performed on the Vital-IT cluster (www.vital-it.ch). We are grateful to Dr. Toby Johnson and Pr. Sven Bergmann for statistical discussions. The CoLaus study was supported by research grants from GlaxoSmithKline; the Faculty of Biology and Medicine of Lausanne, Switzerland; and the Swiss National Science Foundation (grant no: 33CSCO-122661). Gerard Waeber and Peter Vollenweider received an unrestricted grant from GSK to build the CoLaus study.; CROATIA-Korcula: We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools and Croatian Institute for Public Health. The SNP genotyping for the CROATIA-Korcula cohort was performed in Helmholtz Zentrum Munchen, Neuherberg, Germany. The CROATIA-Korcula study was funded by grants from the Medical Research Council (UK), and Republic of Croatia Ministry of Science, Education and Sports research (108-1080315-0302).; CROATIA-Split: We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools and Croatian Institute for Public Health. The SNP genotyping for the CROATIA-Split cohort was performed by AROS Applied Biotechnology, Aarhus, Denmark. The CROATIA-Split study is funded by grants from the Medical Research Council (UK) and Republic of Croatia Ministry of Science, Education and Sports research grants to I. R. (108-1080315-0302).; CROATIA-Vis: We would like to acknowledge the staff of several institutions in Croatia that supported the field work, including but not limited to The University of Split and Zagreb Medical Schools, Institute for Anthropological Research in Zagreb and Croatian Institute for Public Health. The SNP genotyping for the CROATIA-Vis cohort was performed in the core genotyping laboratory of the Wellcome Trust Clinical Research Facility at the Western General Hospital, Edinburgh, Scotland, UK. The CROATIA-Vis study was funded by grants from the Medical Research Council (UK), European Commission Framework 6 project EUROSPAN (Contract No. LSHG-CT-2006-018947) and Republic of Croatia Ministry of Science, Education and Sports research grants (108-1080315-0302).; ECHRS-Spain: Spanish Ministry of Science and Innovation grant MTM2008-02457; Fondo de Investigaciones Santarias grants 97/0035-01, 99/0034-01 and 99/0034-02; Hospital Universitario de Albacete; Consejeria de Sanidad; FWO (Fund for Scientific Research) grant G.0402.00; University of Antwerp; the Flemish Health Ministry; Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Public Health Service grant R01 HL62633-01; Consell Interdepartamental de Recerca i Innovacio Tecnologica (CIRIT) grant 1999SGR 00241; Red Respira Instituto de Salud Carlos III (ISCIII).; EGCUT: EGCUT received financial support from FP7 programs (ENGAGE, OPENGENE), targeted financial support from Estonian Government SF0180142s08, Estonian Research Roadmap through Estonian Ministry of Education and Research, Center of Excellence in Genomics (EXCEGEN) and University of Tartu (SP1GVARENG). The work of K. F. was supported by Estonian Science Foundation grant EstSF ETF9353. We acknowledge EGCUT technical personnel, especially Mr V. Soo and S. Smit. Data analyzes were carried out in part in the High Performance Computing Center of University of Tartu.; ENGAGE: This research was supported through funds from The European Community's Seventh Framework Programme (FP7/2007-2013), ENGAGE Consortium, grant agreement HEALTH-F4-2007-201413.; EPIC-Obesity: The EPIC Norfolk Study is funded by program grants from the Medical Research Council UK and Cancer Research UK.; GerMIFS: Supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2 and NGFN-plus), the FP6 and FP7 EU funded integrated projects Cardiogenics (LSHM-CT-2006-037593) and ENGAGE (201413), and the bi-national BMBF/ANR funded project CARDomics (01KU0908A). Supported by the DZHK (Deutsches Zentrum fur Herz-Kreislauf-Forschung - German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research).; HBCS: Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland (Grant No. 120315 and 129287 to EW, 1129457 and 1216965 to KR, 120386 and 125876 to JGE), the Finnish Diabetes Research Society, Folkhalsan Research Foundation, Novo Nordisk Foundation, Finska Lakaresallskapet, the European Science Foundation (EuroSTRESS), the Wellcome Trust (Grant No. 89061/Z/09/Z and 089062/Z/09/Z), Samfundet Folkhalsan, Finska Lakaresallskapet and the Signe and Ane Gyllenberg foundation.; InCHIANTI: We thank the Intramural Research Program of the NIH, National Institute on Aging who are responsible for the InCHIANTI samples. We also thank the InCHIANTI participants. The 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 U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Followups 2 and 3 studies (2004-2010) were financed by the U.S. National Institute on Aging (Contract: N01-AG-5-0002); supported in part by the Intramural research program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland. JRBP is funded by a Sir Henry Wellcome Postdoctoral Fellowship (092447/Z/10/Z).; INGI-CARLANTINO and INGI-FVG: The study was funded Regione FVG (L.26.2008). We thank Laura Esposito, Angela D'Eustacchio and Emmanouil Athanasakis for technical support. We are very grateful to the municipal administrators for their collaboration on the project and for logistic support. We would like to thank all participants to this study.; INGI-VB: We thank the inhabitants of the VB that made this study possible, the local administrations, the Tortona and Genova archdiocese and the ASL-22, Novi Ligure (Al) for support. We also thank Cinzia Sala and Clara Camaschella for data collection supervision and organization of the clinical data collection, Fiammetta Vigano for technical help, Corrado Masciullo and Massimiliano Cocca for building the analysis platform. The research was supported by funds from Compagnia di San Paolo, Torino, Italy; Fondazione Cariplo, Italy and Ministry of Health, Ricerca Finalizzata 2008 and Telethon, Italy to DT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; KORA: The KORA authors acknowledge the contribution of Peter Lichtner, Gertrud Eckstein, Guido Fischer and all members of the Helmholtz Center Munich genotyping staff for generating the SNP data, as well as all members of field staffs who were involved in the planning and conduction of the KORA Augsburg studies. The KORA research platform was initiated and financed by the Helmholtz Center Munich, German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823). Our research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ.; NBS: We thank the participants from the Municipality of Nijmegen for their continued support to the Nijmegen Biomedical Study. The study was partly funded by an investment grant of the Radboud University Nijmegen Medical Centre.; NESDA: Neuroscience Campus Amsterdam; EMGO+ Institute for Health and Care Research; NIMH R01 MH059160; Geestkracht program of ZonMW (10-000-1002); matching funds from universities and mental health care institutes involved in NESDA. Genotyping was funded by the Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health, and analysis was supported by grants from GAIN and the NIMH (MH081802).; NTR: We thank the twins and their families for their participation.; NTR1: Funding was obtained from the Netherlands Heart Foundation (90.313, 86.083 and 88.042), the Netherlands Organization for Scientific Research (NWO: MagW/ZonMW): Genetic basis of anxiety and depression (904-61-090); Genetics of individual differences in smoking initiation and persistence (NWO 985-10-002); Resolving cause and effect in the association between exercise and well-being (904-61-193); Twin family database for behaviour genomics studies (480-04-004); Twin research focusing on behaviour (400-05-717); Genetic determinants of risk behaviour in relation to alcohol use and alcohol use disorder (Addiction-31160008); Genotype/phenotype database for behaviour genetic and genetic epidemiological studies (911-09-032); Spinozapremie (SPI 56-464-14192); CMSB: Center for Medical Systems Biology (NWO Genomics); NBIC/BioAssist/RK/2008.024); BBMRI -NL: Biobanking and Biomolecular Resources Research Infrastructure; the VU University: Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the European Science Foundation (ESF): Genomewide analyses of European twin and population cohorts (EU/QLRT-2001-01254); European Community's Seventh Framework Program (FP7/2007-2013): ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC) Genetics of Mental Illness (230374); Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06); Collaborative study of the genetics of DZ twinning (NIH R01D0042157-01A); the Genetic Association Information Network, a public-private partnership between the NIH and Pfizer Inc., Affymetrix Inc. and Abbott Laboratories.; NTR2: Funding is acknowledged from the Netherlands Organization for Scientific Research (NWO: MagW/ZonMW): Twin family database for behaviour genomics studies (480-04-004); Twin research focusing on behaviour (400-05-717); Genetic determinants of risk behaviour in relation to alcohol use (Addiction-31160008); Genotype/phenotype database for behaviour genetic and genetic epidemiological studies (911-09-032); Spinozapremie (SPI 56-464-14192); CMSB: Center for Medical Systems Biology (NWO Genomics); NBIC/BioAssist/RK/2008.024); BBMRI -NL: Biobanking and Biomolecular Resources Research Infrastructure; European Science Foundation (ESF): Genomewide analyses of European twin and population cohorts (EU/QLRT-2001-01254); European Community's Seventh Framework Program (FP7/2007-2013): ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC) Genetics of Mental Illness (230374); Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06).; ORCADES: ORCADES DNA extractions were performed at the Wellcome Trust Clinical Research Facility in Edinburgh. We would like to acknowledge the invaluable contributions of Lorraine Anderson and the research nurses in Orkney, the administrative team in Edinburgh and the people of Orkney. ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). PREVEND: PREVEND genetics is supported by the Dutch Kidney Foundation (Grant E033), The Netherlands Heart Foundation (Grant 2006B140, 2006T003), National Institutes of Health (grant LM010098, HL65234, HL67466, RR018787) and the EU project grant GENECURE (FP-6 LSHM CT 2006 037697). P.vd.H is supported by NWO VENI grant 91676170 and Dutch Inter University Cardiology Institute Netherlands (ICIN). QIMR: We thank the twins and their families for their participation. We also thank Dixie Statham, Ann Eldridge, Marlene Grace, Kerrie McAloney (sample collection); Anjali Henders, Megan Campbell, Lisa Bowdler and Steven Crooks (sample and DNA processing); Scott Gordon, David Smyth, Harry Beeby, and Daniel Park (IT support). We also acknowledge David Duffy, Peter Visscher, Margaret Wright, Pamela Madden and Wendy Slutske for their funding contributions. Genotype imputation was carried out on the Genetic Cluster Computer. Funding was provided by the Australian National Health and Medical Research Council (NHMRC grants 241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498), the Australian Research Council (ARC grants A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921), the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254), and the U.S. National Institutes of Health (NIH grants AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206). The Genetic Cluster Computer is financially supported by the Netherlands Scientific Organization (NWO 480-05-003). G. W. M. was supported by an NHMRC Fellowship (619667), D.R.N. (FT0991022) and S. E. M. (FT110100548) were supported by an ARC Future Fellowship. RAINE: The authors are grateful to the Raine Study participants and their families and to the Raine Study research staff for cohort coordination and data collection. The authors gratefully acknowledge the NH&MRC for their long term contribution to funding the study over the last 20 years and also the following Institutions for providing funding for Core Management of the Raine Study: The University of Western Australia (UWA), Raine Medical Research Foundation, UWA Faculty of Medicine, Dentistry and Health Sciences, The Telethon Institute for Child Health Research and Women and Infants Research Foundation. The authors gratefully acknowledge the assistance of the Western Australian DNA Bank (National Health and Medical Research Council of Australia National Enabling Facility). The authors also acknowledge the support of the National Health and Medical Research Council of Australia (Grant ID 403981 and ID 003209) and the Canadian Institutes of Health Research (Grant ID MOP-82893).; RS: We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, and Lisbeth Herrera for their help in creating the GWAS database. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. We would like to thank Dr. Tobias A. Knoch, Karol Estrada, Luc V. de Zeeuw, Anis Abuseiris and Rob de Graaf as well as their institutions the Erasmus Computing Grid, Rotterdam, The Netherlands, and especially the national German MediGRID and Services@MediGRID part of the German D-Grid for access to their grid resources. The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI) Netherlands Consortium of Healthy Aging (NCHA) project nr. 050-060-810, and funding from the European Commission (HEALTH-F2-2008-201865, GEFOS; HEALTH-F2-2008-35627, TREAT-OA). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. German MediGRID and Services@MediGRID are part of the German D-Grid and are both funded by the German Bundesministerium fuer Forschung und Technology under grants # 01 AK 803 A-H and # 01 IG 07015 G.; SHIP: We thank all staff members and participants of the SHIP study, as well as all of the genotyping staff for generating the SHIP SNP data set. The genetic data analysis workflow was created using the Software InforSense. Genetic data were stored using the database Cache (InterSystems). SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network 'Greifswald Approach to Individualized Medicine (GANI_MED)' funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG.; SORBS: We thank all those who participated in the study. Sincere thank is given to Peter Kovacs who was significantly involved in the planning and procedure of the Sorbs study. We also thank Knut Krohn (Microarray Core Facility of the Interdisciplinary Centre for Clinical Research, University of Leipzig) for the genotyping support and Inga Prokopenko and Nigel W. Rayner (WTCHG, University of Oxford, UK) for the excellent analytical and bioinformatics support. This work was supported by grants from the Interdisciplinary Centre for Clinical Research at the University of Leipzig (B27 to A. T.) from the German Diabetes Association (to A. T.), a Travel Grant from BIF (to A. T.) and by the DHFD, Diabetes Hilfs-und Forschungsfonds Deutschland. The work of Vasiliki Lagou was funded through the ENGAGE (European Network for Genetic and Genomic Epidemiology) Consortium, the European Community's Seventh Framework Programme (HEALTH-F4-2007-201413).; TwinsUK: We thank the staff from the TwinsUK, the DNA Collections and Genotyping Facilities at the Wellcome Trust Sanger Institute for sample preparation; Quality Control of the Twins UK cohort for genotyping (in particular Amy Chaney, Radhi Ravindrarajah, Douglas Simpkin, Cliff Hinds, and Thomas Dibling); Paul Martin and Simon Potter of the DNA and Genotyping Informatics teams for data handling; Le Centre National de Genotypage, France, led by Mark Lathrop, for genotyping; Duke University, North Carolina, USA, led by David Goldstein, for genotyping; and the Finnish Institute of Molecular Medicine, Finnish Genome Center, University of Helsinki, led by Aarno Palotie. The authors declare they have no conflicts of interest. The study was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F2-2008-ENGAGE and the European Union FP-5 GenomEUtwin Project (QLG2-CT-2002-01254) and Framework 6 Project EUroClot. The study also receives support from the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London.; YFS: The Cardiovascular Risk in Young Finns study (YFS) is supported by the Academy of Finland (grant no. 117797, 121584 and 126925), the Social Insurance Institution of Finland, University Hospital Medical funds to Tampere, and Turku University Hospitals, the Finnish Foundation of Cardiovascular Research Emil Aaltonen Foundation (T. L), and Tampere Tuberculosis Foundation.; V. B. is supported by Unity Through Knowledge Fund CONNECTIVITY PROGRAM ('Gaining Experience' Grant 2A), The National Foundation for Science, Higher Education and Technological Development of the Republic of Croatia (BRAIN GAIN-Postdoc fellowship) and the Wellcome Trust (098051). E.Z. is supported by the Wellcome Trust (098051). Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust (098051). NR 32 TC 9 Z9 9 U1 0 U2 29 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2012 VL 21 IS 21 BP 4805 EP 4815 DI 10.1093/hmg/dds304 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 025DN UT WOS:000310165500018 PM 22843499 ER PT J AU Blanch-Hartigan, D AF Blanch-Hartigan, Danielle TI An effective training to increase accurate recognition of patient emotion cues SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Emotion recognition; Training; Emotion cue; Medical education; Accuracy ID MEDICAL-STUDENTS; COMMUNICATION-SKILLS; NONVERBAL-COMMUNICATION; INTERPERSONAL SENSITIVITY; INTERVIEWING SKILLS; SELF-ASSESSMENT; CANCER-PATIENTS; PRIMARY-CARE; SATISFACTION; PHYSICIANS AB Objective: For healthcare providers, accurate perception of patients, particularly accurate recognition of patient emotions, is an ability associated with better patient care and more satisfied patients. Despite the importance of accurately recognizing patient cues for provider-patient communication, research on clinically relevant training programs is limited. The effectiveness of a multi-component training program designed to enhance emotion cue recognition ability was experimentally assessed. Methods: The comprehensive training included raising awareness about the importance of emotion cues in healthcare interactions, providing instruction on increasing emotion cue recognition accuracy, and practicing emotion recognition while receiving feedback. Undergraduate participants were randomly assigned to one of five training conditions or an untrained control condition to experimentally test the efficacy of the comprehensive training and each training component. Results: Participants were significantly more accurate on a standardized test of patient emotion cue recognition in the comprehensive condition, as compared to those participants in the control condition, with Practice with Feedback emerging as the most effective component. Conclusions: Results suggest that a 30-min emotion recognition training intervention can significantly improve emotion recognition accuracy. Practice implications: The results can be used to guide development and implementation of future research and programs aimed at increasing providers' emotion recognition. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. RP Blanch-Hartigan, D (reprint author), NCI, Canc Prevent Fellowship Program, Execut Plaza S,Suite 150E,6120 Execut Blvd,MSC 71, Bethesda, MD 20892 USA. EM danielleblanch@gmail.com NR 48 TC 8 Z9 8 U1 2 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD NOV PY 2012 VL 89 IS 2 BP 274 EP 280 DI 10.1016/j.pec.2012.08.002 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 046LO UT WOS:000311766700009 PM 22906744 ER PT J AU Kent, EE Arora, NK Rowland, JH Bellizzi, KM Forsythe, LP Hamilton, AS Oakley-Girvan, I Beckjord, EB Aziz, NM AF Kent, Erin E. Arora, Neeraj K. Rowland, Julia H. Bellizzi, Keith M. Forsythe, Laura P. Hamilton, Ann S. Oakley-Girvan, Ingrid Beckjord, Ellen B. Aziz, Noreen M. TI Health information needs and health-related quality of life in a diverse population of long-term cancer survivors SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Cancer survivorship; Information needs; Self-efficacy; Quality of care; Health-related quality of life ID BREAST-CANCER; SOCIAL SUPPORT; SELF-EFFICACY; CARE PLANS; PREVALENCE; CHALLENGE; LITERACY; IMPACT AB Objective: To investigate health information needs and their association with health-related quality of life (HRQOL) in a diverse, population-based sample of long-term cancer survivors. Methods: We analyzed health information needs from 1197 cancer survivors 4-14 years post-diagnosis drawn from two cancer registries in California. Multivariable regression models were used to identify factors associated with endorsement of total number and different categories of needs. The relationship between number of needs and HRQOL and effect modification by confidence for obtaining information was examined. Results: Survivors reported a high prevalence of unmet information needs in the following categories: side effects & symptoms: 75.8%; tests & treatment: 71.5%; health promotion: 64.5%; interpersonal & emotional: 60.2%; insurance: 39.0%; and sexual functioning & fertility: 34.6%. Survivors who were younger, non-White, and did not receive but wanted a written treatment summary reported a higher number of needs. Number of information needs was inversely related to mental well-being, particularly for those with low confidence for obtaining information (P < 0.05). Conclusion: These patterns suggest disparities in access to important health information in long-term survivors and that affect HRQOL Practice Implications: Findings suggest a need for tailored interventions to equip survivors with comprehensive health information and to bolster skills for obtaining information. Published by Elsevier Ireland Ltd. C1 [Kent, Erin E.; Arora, Neeraj K.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. [Kent, Erin E.; Forsythe, Laura P.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Kent, Erin E.; Rowland, Julia H.; Forsythe, Laura P.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Bellizzi, Keith M.] Univ Connecticut, Storrs, CT USA. [Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Oakley-Girvan, Ingrid] Canc Prevent Inst Calif, Fremont, CA USA. [Beckjord, Ellen B.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Aziz, Noreen M.] NINR, NIH, Bethesda, MD 20892 USA. RP Kent, EE (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, 6130 Execut Blvd,Room 4020, Bethesda, MD 20892 USA. EM Erin.Kent@nih.gov FU NCI SEER [N01-PC-35136, N01-PC-35139] FX This study was supported under NCI SEER contract numbers: N01-PC-35136, N01-PC-35139 (http://cancercontrol.cancer.gov/ocs/focus.html). The authors would like to acknowledge Ms. Gretchen Keel (Information Management Services, Inc., Rockville, MD) for her assistance with data analysis on this project. This study has been presented in part at a poster at the 2011 American Association of Cancer Research Science of Cancer Health Disparities Meeting, on September 19, 2011, in Washington, DC. NR 46 TC 38 Z9 38 U1 0 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD NOV PY 2012 VL 89 IS 2 BP 345 EP 352 DI 10.1016/j.pec.2012.08.014 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 046LO UT WOS:000311766700019 PM 23021856 ER PT J AU Li, JX Ferraris, JD Yu, DN Singh, T Izumi, Y Wang, GH Gucek, M Burg, MB AF Li, Jinxi Ferraris, Joan D. Yu, Danni Singh, Taruna Izumi, Yuichiro Wang, Guanghui Gucek, Marjan Burg, Maurice B. TI Proteomic analysis of high NaCl-induced changes in abundance of nuclear proteins SO PHYSIOLOGICAL GENOMICS LA English DT Article DE NFAT5; hypertonicity; nucleoskeleton; DDX5/DDX17; 14-3-3 ID QUANTITATIVE PROTEOMICS; BINDING PROTEIN; DNA-DAMAGE; HEAT-SHOCK; CELLS; TRANSCRIPTION; STRESS; ACTIVATION; UREA; PHOSPHORYLATION AB Li J, Ferraris JD, Yu D, Singh T, Izumi Y, Wang G, Gucek M, Burg MB. Proteomic analysis of high NaCl-induced changes in abundance of nuclear proteins. Physiol Genomics 44: 1063-1071, 2012. First published September 18, 2012; doi: 10.1152/physiolgenomics.00068.2012.-Mammalian cells are normally stressed by high interstitial NaCl in the renal medulla and by lesser elevation of NaCl in several other tissues. High NaCl damages proteins and DNA and can kill cells. Known protective responses include nuclear translocation of the transcription factor NFAT5 and other proteins. In order better to understand the extent and significance of changes in nuclear protein abundance, we extracted nuclear and cytoplasmic proteins separately from HEK293 cells and measured by LC-MS/MS (iTRAQ) changes of abundance of proteins in the extracts in response to high NaCl at three time points: 1 h, 8 h, and adapted for two passages. We confidently identified a total of 3,190 proteins; 163 proteins changed significantly at least at one time point in the nucleus. We discerned the biological significance of the changes by Gene Ontology and protein network analysis. Proteins that change in the nucleus include ones involved in protein folding and localization, microtubule-based process, regulation of cell death, cytoskeleton organization, DNA metabolic process, RNA processing, and cell cycle. Among striking changes in the nucleus, we found a decrease of all six 14-3-3 isoforms; dynamic changes of "cytoskeletal" proteins, suggestive of nucleoskeletal reorganization; rapid decrease of tubulins; and dynamic changes of heat shock proteins. Identification of these changes of nuclear protein abundance enhances our understanding of high NaCl-induced cellular stress, and provides leads to previously unknown damages and protective responses. C1 [Li, Jinxi; Ferraris, Joan D.; Yu, Danni; Singh, Taruna; Izumi, Yuichiro; Wang, Guanghui; Gucek, Marjan; Burg, Maurice B.] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NIH, Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. EM maurice_burg@nih.gov FU IRP of the NHLBI FX This research was supported by the IRP of the NHLBI. NR 35 TC 6 Z9 6 U1 3 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD NOV PY 2012 VL 44 IS 21 BP 1063 EP 1071 DI 10.1152/physiolgenomics.00068.2012 PG 9 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 032FU UT WOS:000310699800006 PM 22991206 ER PT J AU Walker, A Pao, M Nguyen, N AF Walker, Audrey Pao, Maryland Ngoc Nguyen TI Pediatric Psychosomatic Medicine: Creating a Template for Training SO PSYCHOSOMATICS LA English DT Article ID PREVALENCE; DISORDERS; HEALTH; CHILD AB There is a critical public health problem in the United States today, the problem of childhood psychiatric disorders in youngsters with physical illnesses. Currently there is a pressing need for well-trained pediatric psychosomatic medicine practitioners as well as advanced training in the field. Yet, this training does not currently exist. This article will present the innovative Montefiore Medical Center/Albert Einstein College of Medicine (MMC/AECOM) program as a model for a training curriculum, clinical training experience, and clinical research training setting in this important and rapidly expanding area of need in pediatric mental health. (Psychosomatics 2012; 53:532-540) C1 [Walker, Audrey] Montefiore Med Ctr, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. [Pao, Maryland] NIMH, Clin Res Ctr, Bethesda, MD 20892 USA. [Ngoc Nguyen] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Psychiat, Bronx, NY USA. RP Walker, A (reprint author), Montefiore Med Ctr, Dept Psychiat & Behav Sci, 3331 Bainbridge Ave, Bronx, NY 10467 USA. EM auwalker@montefiore.org FU Intramural NIH HHS [ZIA MH002922-04] NR 8 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2012 VL 53 IS 6 BP 532 EP 540 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 049KC UT WOS:000311980900004 PM 22658325 ER PT J AU Dyda, F Chandler, M Hickman, AB AF Dyda, Fred Chandler, Michael Hickman, Alison Burgess TI The emerging diversity of transpososome architectures SO QUARTERLY REVIEWS OF BIOPHYSICS LA English DT Review ID EUKARYOTIC TRANSPOSABLE ELEMENTS; CLEAVAGE SYNAPTIC COMPLEX; DNA STRAND TRANSFER; V(D)J RECOMBINATION; ESCHERICHIA-COLI; MU-TRANSPOSOSOME; MOLECULAR ARCHITECTURE; RETROVIRAL INTEGRATION; PARAMECIUM-TETRAURELIA; PIGGYBAC TRANSPOSASE AB DNA transposases are enzymes that catalyze the movement of discrete pieces of DNA from one location in the genome to another. Transposition occurs through a series of controlled DNA strand cleavage and subsequent integration reactions that are carried out by nucleoprotein complexes known as transpososomes. Transpososomes are dynamic assemblies which must undergo conformational changes that control DNA breaks and ensure that, once started, the transposition reaction goes to completion. They provide a precise architecture within which the chemical reactions involved in transposon movement occur, but adopt different conformational states as transposition progresses. Their components also vary as they must, at some stage, include target DNA and sometimes even host-encoded proteins. A very limited number of transpososome states have been crystallographically captured, and here we provide an overview of the various structures determined to date. These structures include examples of DNA transposases that catalyze transposition by a cut-and-paste mechanism using an RNaseH-like nuclease catalytic domain, those that transpose using only single-stranded DNA substrates and targets, and the retroviral integrases that carry out an integration reaction very similar to DNA transposition. Given that there are a number of common functional requirements for transposition, it is remarkable how these are satisfied by complex assemblies that are so architecturally different. C1 [Dyda, Fred; Hickman, Alison Burgess] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Chandler, Michael] CNRS, Lab Microbiol & Genet Mol, F-31062 Toulouse, France. RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM fred.dyda@nih.gov OI Chandler, Michael/0000-0002-0292-6662 FU Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda MD; CNRS (France); ANR; European contract [LSHM-CT-2005-019023] FX This work was supported at the NIH by the Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda MD and in France by continuous intramural funding from the CNRS (France) and, in its later stages, by ANR grant Mobigen (M.C.), and by European contract LSHM-CT-2005-019023 (M.C.). NR 118 TC 18 Z9 18 U1 2 U2 21 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-5835 J9 Q REV BIOPHYS JI Q. Rev. Biophys. PD NOV PY 2012 VL 45 IS 4 BP 493 EP 521 DI 10.1017/S0033583512000145 PG 29 WC Biophysics SC Biophysics GA 050NA UT WOS:000312058800003 PM 23217365 ER PT J AU Candotti, F Shaw, KL Muul, L Carbonaro, D Sokolic, R Choi, C Schurman, SH Garabedian, E Kesserwan, C Jagadeesh, GJ Fu, PY Gschweng, E Cooper, A Tisdale, JF Weinberg, KI Crooks, GM Kapoor, N Shah, A Abdel-Azim, H Yu, XJ Smogorzewska, M Wayne, AS Rosenblatt, HM Davis, CM Hanson, C Rishi, RG Wang, XY Gjertson, D Yang, OO Balamurugan, A Bauer, G Ireland, JA Engel, BC Podsakoff, GM Hershfield, MS Blaese, RM Parkman, R Kohn, DB AF Candotti, Fabio Shaw, Kit L. Muul, Linda Carbonaro, Denise Sokolic, Robert Choi, Christopher Schurman, Shepherd H. Garabedian, Elizabeth Kesserwan, Chimene Jagadeesh, G. Jayashree Fu, Pei-Yu Gschweng, Eric Cooper, Aaron Tisdale, John F. Weinberg, Kenneth I. Crooks, Gay M. Kapoor, Neena Shah, Ami Abdel-Azim, Hisham Yu, Xiao-Jin Smogorzewska, Monika Wayne, Alan S. Rosenblatt, Howard M. Davis, Carla M. Hanson, Celine Rishi, Radha G. Wang, Xiaoyan Gjertson, David Yang, Otto O. Balamurugan, Arumugam Bauer, Gerhard Ireland, Joanna A. Engel, Barbara C. Podsakoff, Gregory M. Hershfield, Michael S. Blaese, R. Michael Parkman, Robertson Kohn, Donald B. TI Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; MARROW TRANSPLANT RECIPIENTS; HEMATOPOIETIC STEM-CELLS; EXPRESSION; MURINE; ADA; VIRUS; EFFICACY; DISEASE; IL-7 AB We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency. (Blood. 2012;120(18):3635-3646) C1 [Candotti, Fabio; Muul, Linda; Sokolic, Robert; Schurman, Shepherd H.; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G. Jayashree] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Shaw, Kit L.; Carbonaro, Denise; Choi, Christopher; Fu, Pei-Yu; Gschweng, Eric; Kohn, Donald B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Cooper, Aaron] Univ Calif Los Angeles, David Geffen Sch Med, Mol Biol Interdept PhD Program, Los Angeles, CA 90095 USA. [Tisdale, John F.] NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. [Weinberg, Kenneth I.] Stanford Sch Med, Dept Pediat, Stanford, CA USA. [Crooks, Gay M.; Gjertson, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Ireland, Joanna A.; Parkman, Robertson] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Res Immunol Bone Marrow Transplant,Dept Pedia, Los Angeles, CA 90033 USA. [Rosenblatt, Howard M.] Dell Childrens Med Ctr Cent Texas, Austin, TX USA. [Wayne, Alan S.] NCI, Hematol Dis Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Davis, Carla M.; Hanson, Celine] Texas Childrens Hosp, Dept Pediat, Sect Allergy & Immunol, Houston, TX 77030 USA. [Wang, Xiaoyan; Gjertson, David] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Rishi, Radha G.] Arizona Allergy Associates, Scottsdale, AZ USA. [Yang, Otto O.; Balamurugan, Arumugam] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA 90095 USA. [Bauer, Gerhard] Calif State Univ Sacramento, Davis Sch Med, Dept Internal Med, Div Hematol Oncol, Sacramento, CA 95819 USA. [Engel, Barbara C.] Childrens Hosp, Philadelphia Res Inst, Philadelphia, PA 19104 USA. [Podsakoff, Gregory M.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA USA. [Podsakoff, Gregory M.] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA USA. [Hershfield, Michael S.] Duke Univ, Sch Med, Dept Biochem, Durham, NC USA. [Blaese, R. Michael] Immune Deficiency Fdn, Towson, MD USA. [Kohn, Donald B.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA USA. RP Kohn, DB (reprint author), 3163 Terasaki Life Sci Bldg,610 Charles E Young D, Los Angeles, CA 90095 USA. EM dkohn@mednet.ucla.edu RI Kohn, Donald/N-5085-2016; OI Kohn, Donald/0000-0003-1840-6087; Schurman, Shepherd/0000-0002-9133-7906; Cooper, Aaron/0000-0003-4588-2513 FU Clinical Research Award from the Saban Research Institute of Children's Hospital Los Angeles, a Distinguished Clinical Scientist Award from the Doris Duke Charitable Foundation; NHLBI SCOR grant [1P50 HL54850]; FDA [1 RO1 FD003005]; UCLA GCRC [MO1 RR000865]; Sigma-Tau Pharmaceuticals; NHGRI; NIDDK; NCI FX This study was supported by the following awards: a Clinical Research Award from the Saban Research Institute of Children's Hospital Los Angeles, a Distinguished Clinical Scientist Award (2000-654) from the Doris Duke Charitable Foundation, an NHLBI SCOR grant to R. Parkman (1P50 HL54850), and FDA 1 RO1 FD003005. The Clinical Gene Therapy Core Laboratory of the CHLA/USC General Clinical Research Center (MO1 RR0043) was vital to performance of this trial and the UCLA GCRC also helped support this study (MO1 RR000865). Sigma-Tau Pharmaceuticals provides research grant support to M.S.H. This study was also supported in part by intramural funds of NHGRI, NIDDK, and NCI.; M.S.H. receives grant support from Sigma-Tau Pharmaceuticals. The remaining authors declare no competing financial interests. NR 40 TC 95 Z9 98 U1 5 U2 28 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2012 VL 120 IS 18 BP 3635 EP 3646 DI 10.1182/blood-2012-02-400937 PG 12 WC Hematology SC Hematology GA 044MW UT WOS:000311624800007 PM 22968453 ER PT J AU Gil, MP Ploquin, MJY Watford, WT Lee, SH Kim, K Wang, X Kanno, Y O'Shea, JJ Biron, CA AF Gil, M. Pilar Ploquin, Mickael J. Y. Watford, Wendy T. Lee, Seung-Hwan Kim, Kwangsin Wang, Xin Kanno, Yuka O'Shea, John J. Biron, Christine A. TI Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function SO BLOOD LA English DT Article ID INTERFERON-GAMMA PRODUCTION; NATURAL-KILLER-CELLS; FLOW-CYTOMETRY; I INTERFERONS; RESPONSES; ALPHA/BETA; ACTIVATION; PATHWAYS; LYMPHOCYTES; CANCER AB Type 1 IFNs can conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally stimulate STAT1- and STAT4- dependent effects in CD8 T cells, but that CD8 T cells responding to infections of mice with lymphocytic choriomenigitis virus have elevated STAT4 and lower STAT1 expression with significant consequences for modifying the effects of type 1 IFN exposure. The phenotype was associated with preferential type 1 IFN activation of STAT4 compared with STAT1. Stimulation through the TCR induced elevated STAT4 expression, and STAT4 was required for peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells, with STAT4 acting as a key molecule in driving optimal antigen-specific responses and overcoming STAT1-dependent inhibition of proliferation. (Blood. 2012;120(18):3718-3728) C1 [Gil, M. Pilar; Ploquin, Mickael J. Y.; Lee, Seung-Hwan; Kim, Kwangsin; Wang, Xin; Biron, Christine A.] Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02903 USA. [Watford, Wendy T.; Kanno, Yuka; O'Shea, John J.] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Biron, CA (reprint author), Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Box G-B6,171 Meeting St, Providence, RI 02903 USA. EM christine_biron@brown.edu RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 FU National Institutes of Health (NIH) [AI55677]; Canadian Institute of Health Research; NIH National Center for Research Resources Shared Instrumentation Grant [1S10RR021051-01] FX The work was supported by the National Institutes of Health (NIH; grant AI55677) and a fellowship from the Canadian Institute of Health Research. Purchase and operation of FACSAria was supported by the NIH National Center for Research Resources Shared Instrumentation Grant (grant 1S10RR021051-01). NR 45 TC 31 Z9 31 U1 1 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2012 VL 120 IS 18 BP 3718 EP 3728 DI 10.1182/blood-2012-05-428672 PG 11 WC Hematology SC Hematology GA 044MW UT WOS:000311624800015 PM 22968462 ER PT J AU Ranuncolo, SM Pittaluga, S Evbuomwan, MO Jaffe, ES Lewis, BA AF Ranuncolo, Stella M. Pittaluga, Stefania Evbuomwan, Moses O. Jaffe, Elaine S. Lewis, Brian A. TI Hodgkin lymphoma requires stabilized NIK and constitutive RelB expression for survival SO BLOOD LA English DT Article ID NF-KAPPA-B; REED-STERNBERG CELLS; MULTIPLE-MYELOMA; ALPHA-GENE; MUTATIONS; RECEPTOR; KINASE; PATHOGENESIS; PATHWAY; DISEASE AB We have analyzed the role of the REL family members in Hodgkin lymphoma (HL). shRNA targeting of each REL member showed that HL was uniquely dependent on relB, in contrast to several other B-cell lymphomas. In addition, relA and c-rel shRNA expression also decreased HL cell viability. In exploring relB activation further, we found stable NF-kappa B inducing kinase (NIK) protein in several HL cell lines and that NIK shRNA also affected HL cell line viability. More importantly, 49 of 50 HL patient biopsies showed stable NIK protein, indicating that NIK and the noncanonical pathway are very prevalent in HL. Lastly, we have used a NIK inhibitor that reduced HL but not other B-cell lymphoma cell viability. These data show that HL is uniquely dependent on relB and that the noncanonical pathway can be a therapeutic target for HL. Furthermore, these results show that multiple REL family members participate in the maintenance of a HL phenotype. (Blood.2012;120(18):3756-3763) C1 [Ranuncolo, Stella M.; Lewis, Brian A.] NCI, Metab Branch, Ctr Canc Res, Transcript Regulat & Biochem Unit,NIH, Rockville, MD 20852 USA. [Pittaluga, Stefania; Evbuomwan, Moses O.; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Rockville, MD 20852 USA. RP Lewis, BA (reprint author), NCI, Metab Branch, Ctr Canc Res, Transcript Regulat & Biochem Unit,NIH, Bldg 10,Rm 6B05,9000 Rockville Pike, Rockville, MD 20852 USA. EM lewisbri@mail.nih.gov OI Jaffe, Elaine/0000-0003-4632-0301 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 46 TC 26 Z9 28 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2012 VL 120 IS 18 BP 3756 EP 3763 DI 10.1182/blood-2012-01-405951 PG 8 WC Hematology SC Hematology GA 044MW UT WOS:000311624800019 PM 22968463 ER PT J AU Helmich, RC Hallett, M Deuschl, G Toni, I Bloem, BR AF Helmich, Rick C. Hallett, Mark Deuschl, Guenther Toni, Ivan Bloem, Bastiaan R. TI Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits? SO BRAIN LA English DT Review DE Parkinson's disease; tremor; basal ganglia; cerebellum; thalamus ID DEEP BRAIN-STIMULATION; MPTP-TREATED MONKEYS; SINGLE-UNIT ANALYSIS; PRIMARY MOTOR CORTEX; POSITRON-EMISSION-TOMOGRAPHY; THALAMIC NUCLEAR GROUP; CAUDAL ZONA INCERTA; RE-EMERGENT TREMOR; 5-YEAR FOLLOW-UP; SUBTHALAMIC NUCLEUS AB Tremor in Parkinson's disease has several mysterious features. Clinically, tremor is seen in only three out of four patients with Parkinson's disease, and tremor-dominant patients generally follow a more benign disease course than non-tremor patients. Pathophysiologically, tremor is linked to altered activity in not one, but two distinct circuits: the basal ganglia, which are primarily affected by dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical circuit, which is also involved in many other tremors. The purpose of this review is to integrate these clinical and pathophysiological features of tremor in Parkinson's disease. We first describe clinical and pathological differences between tremor-dominant and non-tremor Parkinson's disease subtypes, and then summarize recent studies on the pathophysiology of tremor. We also discuss a newly proposed 'dimmer-switch model' that explains tremor as resulting from the combined actions of two circuits: the basal ganglia that trigger tremor episodes and the cerebello-thalamo-cortical circuit that produces the tremor. Finally, we address several important open questions: why resting tremor stops during voluntary movements, why it has a variable response to dopaminergic treatment, why it indicates a benign Parkinson's disease subtype and why its expression decreases with disease progression. C1 [Helmich, Rick C.; Toni, Ivan] Radboud Univ Nijmegen, Ctr Cognit Neuroimaging, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands. [Helmich, Rick C.; Bloem, Bastiaan R.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, NL-6500 HB Nijmegen, Netherlands. [Helmich, Rick C.; Bloem, Bastiaan R.] Parkinson Ctr Nijmegen ParC, NL-6500 HB Nijmegen, Netherlands. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Deuschl, Guenther] Univ Kiel, Dept Neurol, D-24118 Kiel, Germany. RP Helmich, RC (reprint author), Radboud Univ Nijmegen, Med Ctr, Neurol Dept HP 935, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM r.helmich@neuro.umcn.nl RI Helmich, Rick/A-3058-2013; Bloem, Bastiaan/E-3812-2010; Deuschl, Gunther/A-7986-2010; Bloem, B.R./H-8013-2014; Helmich, Rick/R-6333-2016; OI Helmich, Rick/0000-0003-4035-6573; Toni, Ivan/0000-0003-0936-3601 FU Alkemade-Keuls Foundation; Netherlands Organisation for Scientific Research (NWO) [016.076.352, 452-03-339, 433-09-248]; German Research Council [SFB 855]; NIH Intramural Program FX The Alkemade-Keuls Foundation (to B.R.B.); the Netherlands Organisation for Scientific Research (NWO; VIDI grant No. 016.076.352 to B.R.B.; VIDI grant No. 452-03-339 to I.T.; Brain & Cognition grant No. 433-09-248 to I.T.); the German Research Council (SFB 855 to G.D.) and the NIH Intramural Program (to M.H.). NR 187 TC 121 Z9 126 U1 2 U2 32 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2012 VL 135 BP 3206 EP 3226 DI 10.1093/brain/aws023 PN 11 PG 21 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 044SV UT WOS:000311644800010 PM 22382359 ER PT J AU Moeller, SJ Hajcak, G Parvaz, MA Dunning, JP Volkow, ND Goldstein, RZ AF Moeller, Scott J. Hajcak, Greg Parvaz, Muhammad A. Dunning, Jonathan P. Volkow, Nora D. Goldstein, Rita Z. TI Psychophysiological prediction of choice: relevance to insight and drug addiction SO BRAIN LA English DT Article DE cocaine addiction; insight; choice behaviour; event-related potentials; late positive potential; unconscious motivation ID CURRENT COCAINE USERS; ATTENTIONAL BIAS; MOTIVATED ATTENTION; EMOTION REGULATION; HEROIN DEPENDENCE; NEURAL RESPONSES; MONETARY REWARD; CUES; BRAIN; ASSOCIATIONS AB An important goal of addiction research and treatment is to predict behavioural responses to drug-related stimuli. This goal is especially important for patients with impaired insight, which can interfere with therapeutic interventions and potentially invalidate self-report questionnaires. This research tested (i) whether event-related potentials, specifically the late positive potential, predict choice to view cocaine images in cocaine addiction; and (ii) whether such behaviour prediction differs by insight (operationalized in this study as self-awareness of image choice). Fifty-nine cocaine abusers and 32 healthy controls provided data for the following laboratory components that were completed in a fixed-sequence (to establish prediction): (i) event-related potential recordings while passively viewing pleasant, unpleasant, neutral and cocaine images, during which early (400-1000 ms) and late (1000-2000 ms) window late positive potentials were collected; (ii) self-reported arousal ratings for each picture; and (iii) two previously validated tasks: one to assess choice for viewing these same images, and the other to group cocaine abusers by insight. Results showed that pleasant-related late positive potentials and arousal ratings predicted pleasant choice (the choice to view pleasant pictures) in all subjects, validating the method. In the cocaine abusers, the predictive ability of the late positive potentials and arousal ratings depended on insight. Cocaine-related late positive potentials better predicted cocaine image choice in cocaine abusers with impaired insight. Another emotion-relevant event-related potential component (the early posterior negativity) did not show these results, indicating specificity of the late positive potential. In contrast, arousal ratings better predicted respective cocaine image choice (and actual cocaine use severity) in cocaine abusers with intact insight. Taken together, the late positive potential could serve as a biomarker to help predict drug-related choice-and possibly associated behaviours (e.g. drug seeking in natural settings, relapse after treatment)-when insight (and self-report) is compromised. C1 [Moeller, Scott J.; Parvaz, Muhammad A.; Goldstein, Rita Z.] Brookhaven Natl Lab, Upton, NY 11973 USA. [Hajcak, Greg] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Dunning, Jonathan P.] Nevada State Coll, Dept Social Sci, Henderson, NV 89002 USA. [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. [Volkow, Nora D.] NIAAA, Bethesda, MD 20892 USA. RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, 30 Bell Ave,Bldg 490, Upton, NY 11973 USA. EM rgoldstein@bnl.gov RI Moeller, Scott/L-5549-2016; OI Moeller, Scott/0000-0002-4449-0844; Parvaz, Muhammad/0000-0002-2671-2327 FU U.S. Department of Energy [DE-AC02-98CHI-886]; National Institute on Drug Abuse [1R01DA023579, 1F32DA030017-01] FX The authors gratefully acknowledge the contributions of Thomas Maloney, Patricia A. Woicik, Nelly Alia-Klein, Frank Telang, Gene-Jack Wang and Nicasia Beebe-Wang. This article has been authored by Brookhaven Science Associates, LLC under Contract No. DE-AC02-98CHI-886 with the U.S. Department of Energy. The United States Government retains, and the publisher, by accepting the article for publication, acknowledges, a world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for the United States Government purposes.; This study was supported by grants from the National Institute on Drug Abuse (to R.Z.G.: 1R01DA023579; to S.J.M.: 1F32DA030017-01). NR 59 TC 18 Z9 18 U1 3 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2012 VL 135 BP 3481 EP 3494 DI 10.1093/brain/aws252 PN 11 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 044SV UT WOS:000311644800031 PM 23148349 ER PT J AU Wegner, JK Sterling, A Guha, R Bender, A Faulon, JL Hastings, J O'Boyle, N Overington, J Van Vlijmen, H Willighagen, E AF Wegner, Joerg Kurt Sterling, Aaron Guha, Rajarshi Bender, Andreas Faulon, Jean-Loup Hastings, Janna O'Boyle, Noel Overington, John Van Vlijmen, Herman Willighagen, Egon TI Cheminformatics SO COMMUNICATIONS OF THE ACM LA English DT Article ID ELECTRONIC LABORATORY NOTEBOOKS; CHEMICAL-STRUCTURES; CHEMISTRY; INFORMATION; MOLECULES; COMPUTER; LANGUAGE; BIOLOGY; DESIGN; SYSTEM C1 [Wegner, Joerg Kurt] Johnson & Johnson, Janssen Pharmaceut Co, Integrat Syst Biol Dept, Beerse, Belgium. [Sterling, Aaron] Iowa State Univ, Dept Comp Sci, Ames, IA USA. [Guha, Rajarshi] NIH, Bethesda, MD 20892 USA. [Bender, Andreas] Univ Cambridge, Unilever Ctr Mol Informat, Cambridge, England. [Faulon, Jean-Loup] UniverSud Paris, Evry Univ, Dept Biol, Paris, France. [Faulon, Jean-Loup] French Natl Ctr Sci Res, Inst Syst & Synthet Biol, Paris, France. [O'Boyle, Noel] Natl Univ Ireland Univ Coll Cork, Sch Pharm, Cork, Ireland. [Overington, John] European Bioinformat Inst, Hinxton, South Cambs, England. [Overington, John] European Mol Biol Lab, Heidelberg, Germany. [Van Vlijmen, Herman] Leiden Univ, NL-2300 RA Leiden, Netherlands. [Van Vlijmen, Herman] Johnson & Johnson, Janssen Pharmaceut Co, Dept Mol Sci, Beerse, Belgium. [Willighagen, Egon] Maastricht Univ, Dept Bioinformat, Maastricht, Netherlands. RP Wegner, JK (reprint author), Johnson & Johnson, Janssen Pharmaceut Co, Integrat Syst Biol Dept, Beerse, Belgium. EM jwegner@its.jnj.com; sterling@iastate.edu; guhar@mail.nih.gov; andreas.bender@cantab.net; Jean-Loup.Faulon@univ-evry.fr; hastings@ebi.ac.uk; baoilleach@gmail.com; jpo@ebi.ac.uk; hvvlijme@its.jnj.com; egon.willighagen@maastrichtuniversity.nl RI Willighagen, Egon/C-6136-2008; Bender, Andreas/C-6942-2009; Overington, John/G-8607-2015; OI Willighagen, Egon/0000-0001-7542-0286; Bender, Andreas/0000-0002-6683-7546; Overington, John/0000-0002-5859-1064; Hastings, Janna/0000-0002-3469-4923; O'Boyle, Noel/0000-0003-4879-2003 FU National Science Foundation [CCF-1049899]; Unilever; European Union project EU-OPEN-SCREEN FX We would like to thank Danny Verbinnen of Janssen Pharmaceutical Companies for sharing his insight into ELNs and John Van Drie of Van Drie Consulting for his insight into cheminformatics. This article was written while Aaron Sterling was visiting the Department of Electrical Engineering and Computer Science at Northwestern University where he was supported in part by National Science Foundation grant CCF-1049899. Andreas Bender thanks Unilever for funding. Janna Hastings thanks the European Union project EU-OPEN-SCREEN for funding. NR 40 TC 8 Z9 8 U1 0 U2 16 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 2 PENN PLAZA, STE 701, NEW YORK, NY 10121-0701 USA SN 0001-0782 J9 COMMUN ACM JI Commun. ACM PD NOV PY 2012 VL 55 IS 11 BP 65 EP 75 DI 10.1145/2366316.2366334 PG 11 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA 040BE UT WOS:000311293300026 ER PT J AU Lester, BM Lin, H DeGarmo, DS Fisher, PA LaGasse, LL Levine, TP Shankaran, S Bada, HS Bauer, CR Hammond, JA Whitaker, TM Higgins, RD AF Lester, Barry M. Lin, Hai DeGarmo, David S. Fisher, Philip A. LaGasse, Linda L. Levine, Todd P. Shankaran, Seetha Bada, Henrietta S. Bauer, Charles R. Hammond, Jane A. Whitaker, Toni M. Higgins, Rosemary D. TI Neurobehavioral disinhibition predicts initiation of substance use in children with prenatal cocaine exposure SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Neurodevelopmental disinhibition; Substance use initiation; Prenatal cocaine exposure ID COMMUNITY VIOLENCE PROJECT; MATERNAL LIFE-STYLE; USE DISORDER; EARLY ADOLESCENCE; DRUG-USE; BEHAVIORAL DISINHIBITION; EXTERNALIZING SPECTRUM; ADULT PSYCHOPATHOLOGY; CONDUCT PROBLEMS; EARLY AGE AB Background: In previous work we (Fisher et al., 2011) examined the emergence of neurobehavioral disinhibition (ND) in adolescents with prenatal substance exposure. We computed ND factor scores at three age points (8/9, 11 and 13/14 years) and found that both prenatal substance exposure and early adversity predicted ND. The purpose of the current study was to determine the association between these ND scores and initiation of substance use between ages Sand 16 in this cohort as early initiation of substance use has been related to later substance use disorders. Our hypothesis was that prenatal cocaine exposure predisposes the child to ND, which, in turn, is associated with initiation of substance use by age 16. Methods: We studied 386 cocaine exposed and 517 unexposed children followed since birth in a longitudinal study. Five dichotomous variables were computed based on the subject's report of substance use: alcohol only; tobacco only; marijuana only; illicit substances and any substance. Results: Cox proportional hazard regression showed that the 8/9 year ND score was related to initiation of alcohol, tobacco, illicit and any substance use but not marijuana use. The trajectory of ND across the three age periods was related to substance use initiation in all five substance use categories. Prenatal cocaine exposure, although initially related to tobacco, marijuana and illicit substance initiation, was no longer significant with ND scores in the models. Conclusion: Prenatal drug exposure appears to be a risk pathway to ND, which by 8/9 years portends substance use initiation. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Lester, Barry M.] Brown Univ, Women & Infants Hosp Rhode Isl, Warren Alpert Med Sch, Brown Ctr Study Children Risk,Dept Pediat, Providence, RI 02905 USA. [Lester, Barry M.; Lin, Hai; Levine, Todd P.] Brown Univ, Dept Pediat, Warren Alpert Med Sch, Providence, RI 02905 USA. [Lester, Barry M.; Lin, Hai; LaGasse, Linda L.; Levine, Todd P.] Brown Univ, Dept Psychiat & Human Behav, Warren Alpert Med Sch, Providence, RI 02905 USA. [DeGarmo, David S.; Fisher, Philip A.] Oregon Social Learning Ctr, Eugene, OR 97401 USA. [Fisher, Philip A.] Univ Oregon, Dept Pediat, Eugene, OR 97403 USA. [Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Bada, Henrietta S.] Univ Kentucky, Coll Med, Dept Pediat, Lexington, KY USA. [Bauer, Charles R.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Hammond, Jane A.] Res Triangle Inst, Stat & Epidemiol Unit, Res Triangle Pk, NC 27709 USA. [Whitaker, Toni M.] Univ Tennessee, Dept Pediat, Memphis, TN USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Lester, BM (reprint author), Brown Univ, Women & Infants Hosp Rhode Isl, Warren Alpert Med Sch, Brown Ctr Study Children Risk,Dept Pediat, 101 Dudley St, Providence, RI 02905 USA. EM Barry_Lester@Brown.edu FU NIH; National Institute of Child Health and Human Development (NICHD) Neonatal Research Network; National Institute on Drug Abuse (NIDA) [U10-DA-024117-01, U10-HD-21385, U10-DA-024128-06, U10-HD-2786, U10-DA-024119-01, U10-HD-27904, U10-DA-024118-01, U10-HD-21397]; NICHD [N01-HD-2-3159] FX This work was supported by NIH grants: Supported by the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network and an interinstitute agreement with the National Institute on Drug Abuse (NIDA) through cooperative agreements: U10-DA-024117-01, U10-HD-21385 (to SS), U10-DA-024128-06, U10-HD-2786 (to HSB), U10-DA-024119-01, U10-HD-27904 (to BML), and U10-DA-024118-01, U10-HD-21397 (to CRB); NICHD contract N01-HD-2-3159 (to BML). NR 58 TC 19 Z9 20 U1 6 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 1 PY 2012 VL 126 IS 1-2 BP 80 EP 86 DI 10.1016/j.drugalcdep.2012.04.014 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 045PA UT WOS:000311708100012 PM 22608010 ER PT J AU Jalah, R Patel, V Kulkarni, V Rosati, M Alicea, C Ganneru, B von Gegerfelt, A Huang, WS Guan, YJ Broderick, KE Sardesai, NY LaBranche, C Montefiori, DC Pavlakis, GN Felber, BK AF Jalah, Rashmi Patel, Vainav Kulkarni, Viraj Rosati, Margherita Alicea, Candido Ganneru, Brunda von Gegerfelt, Agneta Huang, Wensheng Guan, Yongjun Broderick, Kate E. Sardesai, Niranjan Y. LaBranche, Celia Montefiori, David C. Pavlakis, George N. Felber, Barbara K. TI IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Article; Proceedings Paper CT DNA Vaccines Meeting CY JUL 12-14, 2011 CL San Diego, CA DE in vivo electroporation; HIV; SIVsmE660; SIVmac239; antibody; neutralizing antibody; avidity; central memory; transitional memory; effector memory ID RHESUS MACAQUES; IN-VIVO; IFN-GAMMA; THERAPEUTIC VACCINATION; INTERLEUKIN-12 IL-12; SHIV89.6P CHALLENGE; SIVMAC251 CHALLENGE; COMPARATIVE ABILITY; INFECTED MACAQUES; MEMORY RESPONSE AB Intramuscular injection of macaques with an IL-12 expression plasmid (0.1 or 0.4 mg DNA/animal) optimized for high level of expression and delivered using in vivo electroporation, resulted in the detection of systemic IL-12 cytokine in the plasma. Peak levels obtained by day 4-5 post injection were paralleled by a rapid increase of IFN-gamma, indicating bioactivity of the IL-12 cytokine. Both plasma IL-12 and IFN-gamma levels were reduced to basal levels by day 14, indicating a short presence of elevated levels of the bioactive IL-12. The effect of IL-12 as adjuvant together with an SIVmac239 DNA vaccine was further examined comparing two groups of rhesus macaques vaccinated in the presence or absence of IL-12 DNA. The IL-12 DNA-adjuvanted group developed significantly higher SIV-specific cellular immune responses, including IFN-gamma(+) Granzyme B+ T cells, demonstrating increased levels of vaccine-induced T cells with cytotoxic potential, and this difference persisted for 6 mo after the last vaccination. Coinjection of IL-12 DNA led to increases in Gag-specific CD4(+) and CD4(+)CD8(+) double-positive memory T cell subsets, whereas the Env-specific increases were mainly mediated by the CD8(+) and CD4(+) CD8(+) double-positive memory T cell subsets. The IL-12 DNA-adjuvanted vaccine group developed higher binding antibody titers to Gag and mac251 Env, and showed higher and more durable neutralizing antibodies to heterologous SIVsmE660. Therefore, co-delivery of IL-12 DNA with the SIV DNA vaccine enhanced the magnitude and breadth of immune responses in immunized rhesus macaques, and supports the inclusion of IL-12 DNA as vaccine adjuvant. C1 [Jalah, Rashmi; Patel, Vainav; Kulkarni, Viraj; Rosati, Margherita; Alicea, Candido; Ganneru, Brunda; von Gegerfelt, Agneta; Pavlakis, George N.; Felber, Barbara K.] Frederick Natl Lab Canc Res, Human Retrovirus Sect, Vaccine Branch, CCR, Frederick, MD USA. [Huang, Wensheng; Guan, Yongjun] Univ Maryland, Sch Med, Inst Human Virol, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Broderick, Kate E.; Sardesai, Niranjan Y.] Inovio Pharmaceut Inc, Blue Bell, PA USA. [LaBranche, Celia; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC 27710 USA. RP Pavlakis, GN (reprint author), Frederick Natl Lab Canc Res, Human Retrovirus Sect, Vaccine Branch, CCR, Frederick, MD USA. EM pavlakig@mail.nih.gov; felberb@mail.nih.gov RI bebarta, vikhyat/K-3476-2015 FU Intramural Research Program of the National Cancer Institute, National Institutes of Health (NCI/NIH); NIH HHSN [27201100016C] FX We are grateful to D. Weiss, J. Treece, I. Kalisz, V. Kalyanaraman, P. Markham and staff at Advanced BioScience Laboratories, Inc., Rockville, for their expert help. We thank A. Valentin for discussions, J. Bear and B. Chowdhury for technical assistance, and T. Jones for editorial assistance. This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health (NCI/NIH) and by NIH HHSN 27201100016C. NR 65 TC 24 Z9 26 U1 0 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD NOV PY 2012 VL 8 IS 11 SI SI BP 1620 EP 1629 DI 10.4161/hv.21407 PG 10 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 048GD UT WOS:000311897900016 PM 22894956 ER PT J AU Ferreira, VP Saggu, G Pereira, MH Araujo, RN Vale, VF Lima-Ill, KF Pangburn, MK Ribeiro, JMC Gontijo, NF Collin, N Valenzuela, JG AF Ferreira, Viviana P. Saggu, Gurpanna Pereira, Marcos H. Araujo, Ricardo N. Vale, Vladimir F. Lima-Ill, Kolyvan F. Pangburn, Michael K. Ribeiro, Jose M. C. Gontijo, Nelder F. Collin, Nicolas Valenzuela, Jesus G. TI LJM19, a salivary protein from the sand fly vector that transmits leishmaniasis, is a novel inhibitor of the classical pathway of complement SO IMMUNOBIOLOGY LA English DT Meeting Abstract C1 [Ferreira, Viviana P.; Saggu, Gurpanna] Univ Toledo, Dept Med Microbiol & Immunol, Coll Med & Hlth Sci, Toledo, OH 43606 USA. [Pereira, Marcos H.; Araujo, Ricardo N.; Vale, Vladimir F.; Lima-Ill, Kolyvan F.; Gontijo, Nelder F.] Univ Fed Minas Gerais, Dept Parasitol, Lab Physiol Hematophagous Insects, Belo Horizonte, MG, Brazil. [Pangburn, Michael K.] Univ Texas Hlth Ctr Tyler, Dept Biochem, Tyler, TX 75710 USA. [Ribeiro, Jose M. C.] NIAID, Vector Biol Sect, LMVR, NIH, Rockville, MD USA. [Collin, Nicolas] Univ Lausanne, Dept Biochem, Fac Biol & Med, Lausanne, Switzerland. [Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, LMVR, NIH, Rockville, MD USA. RI Pereira, Marcos/A-3774-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD NOV PY 2012 VL 217 IS 11 MA 151 BP 1182 EP 1182 DI 10.1016/j.imbio.2012.08.153 PG 1 WC Immunology SC Immunology GA 038PY UT WOS:000311187800165 ER PT J AU Gomez-Lopez, N Laresgoiti-Servitje, E AF Gomez-Lopez, Nardhy Laresgoiti-Servitje, Estibalitz TI T regulatory cells: regulating both term and preterm labor? SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Editorial Material ID DISTINCT SUBSETS; PREGNANCY; TREGS C1 [Gomez-Lopez, Nardhy] Wayne State Univ, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, Perinatol Res Branch,NICHD,NIH, Detroit, MI 48202 USA. [Laresgoiti-Servitje, Estibalitz] Univ Panamer, Dept Immunol, Amer British Cowdray Med Ctr, Mexico City, DF, Mexico. RP Gomez-Lopez, N (reprint author), Wayne State Univ, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, Perinatol Res Branch,NICHD,NIH, Detroit, MI 48202 USA. EM ngomezlo@med.wayne.edu RI Gomez-Lopez, Nardhy/R-7664-2016; Laresgoiti-Servitje, Estibalitz/B-7658-2014 OI Gomez-Lopez, Nardhy/0000-0002-3406-5262; Laresgoiti-Servitje, Estibalitz/0000-0002-3271-9955 NR 13 TC 6 Z9 6 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD NOV-DEC PY 2012 VL 90 IS 10 BP 919 EP 920 DI 10.1038/icb.2012.48 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 047IL UT WOS:000311833200002 PM 23032368 ER PT J AU Roschewski, M Dunleavy, K Wilson, WH AF Roschewski, Mark Dunleavy, Kieron Wilson, Wyndham H. TI Diffuse large B cell lymphoma: molecular targeted therapy SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE Diffuse large B cell lymphoma; DLBCL; NF-kappa B; STAT3; BCR signaling ID NON-HODGKINS-LYMPHOMA; PROTEASOME INHIBITOR BORTEZOMIB; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; TYROSINE KINASE INHIBITOR; CHOP-LIKE CHEMOTHERAPY; DOSE-ADJUSTED EPOCH; TRIAL MINT GROUP; NF-KAPPA-B; GERMINAL-CENTER; PHASE-II AB Diffuse large B cell lymphoma (DLBCL) is a biologically heterogeneous disease and the most common subtype of B cell non-Hodgkin's lymphoma in the USA. Even though it is a curable lymphoma in advanced stages, up to 40 % of patients eventually relapse or fail to achieve remission. Improved understanding of the biologic complexity of DLBCL reveals a diverse range of oncogenic driver mutations and signaling pathways that are essential for growth and survival of malignant cells. Since many of these signaling pathways can be targeted by small-molecule inhibitors, the therapy for DLBCL is currently undergoing a paradigm shift away from conventional chemotherapy and toward targeted agents that capitalize on an improved biologic understanding of the subsets with the highest risk of treatment failure. Participation in well-conducted and rationally designed clinical trials will be essential to realize the potential of these targeted agents and realize the goal of improving overall outcomes in the most common B cell lymphoma in the world. C1 [Roschewski, Mark; Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Roschewski, M (reprint author), NCI, Lymphoma Therapeut Sect, Metab Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM roschewskimj@mail.nih.gov; dunleavk@mail.nih.gov; wilsonw@mail.nih.gov OI Roschewski, Mark/0000-0003-0278-2635 FU NIH FX All research support came from the Intramural Research Program of the NIH. NR 95 TC 12 Z9 12 U1 0 U2 6 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD NOV PY 2012 VL 96 IS 5 BP 552 EP 561 DI 10.1007/s12185-012-1198-3 PG 10 WC Hematology SC Hematology GA 043BQ UT WOS:000311518300006 PM 23086603 ER PT J AU Abbineni, G Bisht, K Roth, H Hergenrother, P Haglund, K AF Abbineni, G. Bisht, K. Roth, H. Hergenrother, P. Haglund, K. TI S-PAC-1, a Small Molecule Activator of Procaspase 3, Sensitizes Human Breast Cancer and Other Cell Lines to Ionizing Radiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Abbineni, G.; Bisht, K.; Haglund, K.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Roth, H.; Hergenrother, P.] Univ Illinois, Dept Chem, Urbana, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S698 EP S698 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902274 ER PT J AU Chen, Y Calkins, G Hornicek, F Harmon, D Giraud, C Nielsen, G Meltzer, P Suit, H Michaelson, J DeLaney, T AF Chen, Y. Calkins, G. Hornicek, F. Harmon, D. Giraud, C. Nielsen, G. Meltzer, P. Suit, H. Michaelson, J. DeLaney, T. TI Prognosis of Radiation Associated Bone and Soft-tissue Sarcomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Chen, Y.; Calkins, G.; Hornicek, F.; Harmon, D.; Giraud, C.; Nielsen, G.; Suit, H.; Michaelson, J.; DeLaney, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meltzer, P.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S138 EP S138 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900342 ER PT J AU Citrin, DE Horton, J White, A Hudak, K Scroggins, B Chung, E AF Citrin, D. E. Horton, J. White, A. Hudak, K. Scroggins, B. Chung, E. TI Bone Marrow Mesenchymal Stromal Cell Infusion Improves Radiation-induced Cutaneous Fibrosis in a Murine Model SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Citrin, D. E.; Horton, J.; White, A.; Hudak, K.; Scroggins, B.; Chung, E.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S105 EP S106 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900262 ER PT J AU Greer, LL Ning, H Zhuge, Y Erickson, D Kaushal, A Kamrava, M Kramer, K Kiteley, R Belard, A O'Connell, JJ AF Greer, L. L. Ning, H. Zhuge, Y. Erickson, D. Kaushal, A. Kamrava, M. Kramer, K. Kiteley, R. Belard, A. O'Connell, J. J. TI Dosimetric Comparison of Photon Stereotactic Ablative Radiation Therapy (SABR) and Proton SABR in the treatment of Prostate Cancer Patients SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Greer, L. L.; Erickson, D.; Kiteley, R.; O'Connell, J. J.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Ning, H.; Zhuge, Y.; Kaushal, A.] NIH, Bethesda, MD 20892 USA. [Kamrava, M.] UCLA Dept Radiat Oncol, Los Angeles, CA USA. [Kramer, K.; Belard, A.] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S411 EP S411 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901229 ER PT J AU Ho, J Edgerly, M Alimchandani, M Quezado, M Camphausen, K Fojo, T Kaushal, A AF Ho, J. Edgerly, M. Alimchandani, M. Quezado, M. Camphausen, K. Fojo, T. Kaushal, A. TI The Role of Radiation Therapy in Adrenocortical Carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Ho, J.; Edgerly, M.; Alimchandani, M.; Quezado, M.; Camphausen, K.; Fojo, T.; Kaushal, A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S422 EP S422 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901257 ER PT J AU Jones, G Camphausen, K Wyndham, W Smart, D AF Jones, G. Camphausen, K. Wyndham, W. Smart, D. TI Characterization of Unconventional Response of Gray Zone Lymphoma to Conventional Radiation Treatment SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Jones, G.; Camphausen, K.; Wyndham, W.; Smart, D.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S622 EP S623 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902076 ER PT J AU Kahn, J Hayman, TJ Camphausen, K Tofilon, PJ AF Kahn, J. Hayman, T. J. Camphausen, K. Tofilon, P. J. TI The mTORC1/mTORC2 Inhibitor AZD2014 Enhances the Radiosensitivity of Glioblastoma Stem-like Cells SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Kahn, J.; Hayman, T. J.; Camphausen, K.; Tofilon, P. J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S697 EP S697 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902272 ER PT J AU Kahn, J Gillespie, A Ondos, J Dombi, E Camphausen, K Widemann, B Kaushal, A AF Kahn, J. Gillespie, A. Ondos, J. Dombi, E. Camphausen, K. Widemann, B. Kaushal, A. TI Radiation Therapy in Management of Sporadic and Neurofibromatosis Type 1 (NF1) Associated Malignant Peripheral Nerve Sheath Tumors (MPNST) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Kahn, J.; Gillespie, A.; Ondos, J.; Dombi, E.; Camphausen, K.; Widemann, B.; Kaushal, A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S638 EP S638 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902116 ER PT J AU Kesarwala, AH Lu, DJ Xanthopoulos, E Apisarnthanarax, S Evans, T Aggarwal, C Cohen, RB Langer, CJ Rengan, R Simone, CB AF Kesarwala, A. H. Lu, D. J. Xanthopoulos, E. Apisarnthanarax, S. Evans, T. Aggarwal, C. Cohen, R. B. Langer, C. J. Rengan, R. Simone, C. B. TI The Role of Advanced Imaging in Assessing Response to Definitive Chemoradiation Prior to Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Kesarwala, A. H.] NCI, Bethesda, MD 20892 USA. [Lu, D. J.; Xanthopoulos, E.; Apisarnthanarax, S.; Evans, T.; Aggarwal, C.; Cohen, R. B.; Langer, C. J.; Rengan, R.; Simone, C. B.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S581 EP S581 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901676 ER PT J AU Kesarwala, AH Ko, C O'Meara, WP Ning, H Haglund, KE Xanthopoulos, E Rengan, R AF Kesarwala, A. H. Ko, C. O'Meara, W. P. Ning, H. Haglund, K. E. Xanthopoulos, E. Rengan, R. TI Feasibility of Proton Therapy for Elective Nodal Irradiation in Patients With Locally Advanced Non-small Cell Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Kesarwala, A. H.; Ning, H.; Haglund, K. E.] NCI, Bethesda, MD 20892 USA. [Ko, C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [O'Meara, W. P.] Lahey Clin Fdn, Burlington, MA USA. [Xanthopoulos, E.; Rengan, R.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S577 EP S578 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901667 ER PT J AU Kesarwala, AH Pfalzer, LA Stout, NL O'Meara, WP AF Kesarwala, A. H. Pfalzer, L. A. Stout, N. L. O'Meara, W. P. TI Symptoms, Physical Impairments, and Function in Breast Cancer Patients with 1-3 Positive Axillary Lymph Nodes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Kesarwala, A. H.] NCI, Bethesda, MD 20892 USA. [Pfalzer, L. A.] Univ Michigan, Flint, MI 48503 USA. [Stout, N. L.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [O'Meara, W. P.] Lahey Clin Fdn, Burlington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S114 EP S115 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900286 ER PT J AU Lawrence, Y Vikram, B Dignam, JJ Chakravarti, A Freidlin, B Curran, W Bentzen, SM Okunieff, P Coleman, CN AF Lawrence, Y. Vikram, B. Dignam, J. J. Chakravarti, A. Freidlin, B. Curran, W. Bentzen, S. M. Okunieff, P. Coleman, C. N. TI NCI-RTOG Translational-Program Strategic Guidelines for the Early Stage Development of Radiosensitizers SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Lawrence, Y.] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. [Lawrence, Y.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Vikram, B.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Dignam, J. J.] Univ Chicago, Chicago, IL 60637 USA. [Chakravarti, A.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Freidlin, B.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Curran, W.] Emory Univ, Atlanta, GA 30322 USA. [Bentzen, S. M.] Univ Wisconsin, Madison, WI USA. [Okunieff, P.] Univ Florida, Gainesville, FL USA. [Coleman, C. N.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RI Bentzen, Soren/E-3997-2012 OI Bentzen, Soren/0000-0002-7444-7564 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S708 EP S708 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902302 ER PT J AU Matsuo, M Matsumoto, S Saito, K Takakusagi, Y Morris, D Munasinghe, J Devasahayam, N Subramanian, S Mitchell, J Krishna, M AF Matsuo, M. Matsumoto, S. Saito, K. Takakusagi, Y. Morris, D. Munasinghe, J. Devasahayam, N. Subramanian, S. Mitchell, J. Krishna, M. TI Chronic and Cyclic Hypoxia in Fractionated Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Matsuo, M.; Matsumoto, S.; Saito, K.; Takakusagi, Y.; Morris, D.; Munasinghe, J.; Devasahayam, N.; Subramanian, S.; Mitchell, J.; Krishna, M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S687 EP S687 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902244 ER PT J AU Mirabeau-Beale, KL Chen, M Sun, L D'Amico, AV AF Mirabeau-Beale, K. L. Chen, M. Sun, L. D'Amico, A. V. TI Metachronous Cancer Diagnosis in Men With Prostate Cancer and the Risk of Prostate Cancer-specific Mortality: A Competing Risks Analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Mirabeau-Beale, K. L.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, M.] Univ Connecticut, Storrs, CT USA. [Sun, L.] NCI, DCCPS, Bethesda, MD 20892 USA. [D'Amico, A. V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, A. V.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S540 EP S540 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901569 ER PT J AU Russo, AL Chen, M Sun, L Aizer, A Hattangadi, J D'Amico, AV AF Russo, A. L. Chen, M. Sun, L. Aizer, A. Hattangadi, J. D'Amico, A. V. TI Advancing Age Within Established Gleason Score Categories and the Risk of Prostate Cancer-specific Mortality SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Russo, A. L.; Aizer, A.; Hattangadi, J.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, M.] Univ Connecticut, Storrs, CT USA. [Sun, L.] NCI, Bethesda, MD 20892 USA. [D'Amico, A. V.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S535 EP S535 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901557 ER PT J AU Simone, CB Sibley, C Dan, TD Boyce, DM Smith, S Lippman, M Glatstein, E Bluemke, DA Camphausen, K Simone, NL AF Simone, C. B. Sibley, C. Dan, T. D. Boyce, D. M. Smith, S. Lippman, M. Glatstein, E. Bluemke, D. A. Camphausen, K. Simone, N. L. TI Cardiac Toxicity is Not Increased 25 Years After Treatment of Early-stage Breast Carcinoma With Mastectomy or Breast Conservation Therapy From the National Cancer Institute Randomized Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Simone, C. B.; Glatstein, E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Sibley, C.; Bluemke, D. A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Dan, T. D.; Smith, S.; Camphausen, K.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Boyce, D. M.] Johns Hopkins Univ, Sch Med Pulm & Crit Care Med, Baltimore, MD USA. [Lippman, M.] Univ Miami Hlth Syst, Dept Med, Div Hematol Oncol, Miami, FL USA. [Simone, N. L.] Thomas Jefferson Univ Hosp, Dept Radiat Oncol, Philadelphia, PA 19107 USA. RI Sibley, Christopher/C-9900-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S35 EP S36 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900091 ER PT J AU Vogel, J Sia-Atanacio, A Adams, K Martucci, V Prodanov, T Camphausen, K Fojo, A Pacak, K Kaushal, A AF Vogel, J. Sia-Atanacio, A. Adams, K. Martucci, V. Prodanov, T. Camphausen, K. Fojo, A. Pacak, K. Kaushal, A. TI Radiation Therapy in Management of Malignant Pheochromocytoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Vogel, J.; Sia-Atanacio, A.; Adams, K.; Martucci, V.; Prodanov, T.; Camphausen, K.; Fojo, A.; Pacak, K.; Kaushal, A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S421 EP S421 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901256 ER PT J AU Zheng, S Acerbi, I Kuhn, NZ Au, A Park, CC Weaver, VM AF Zheng, S. Acerbi, I. Kuhn, N. Z. Au, A. Park, C. C. Weaver, V. M. TI Ionizing Radiation Modifies Tissue Tension, Mechanosignaling, and Apoptosis in Human Breast SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Zheng, S.; Acerbi, I.; Weaver, V. M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Zheng, S.; Acerbi, I.; Weaver, V. M.] Univ Calif San Francisco, Ctr Bioengn & Tissue Regenerat, San Francisco, CA 94143 USA. [Kuhn, N. Z.] NCI, Off Phys Sci Oncol, Ctr Strateg Sci Initiat, Off Director,NIH, Bethesda, MD 20892 USA. [Au, A.] UCSF Carol Franc Buck Breast Care Ctr, San Francisco, CA USA. [Park, C. C.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Weaver, V. M.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S669 EP S669 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902197 ER PT J AU Hasumi, H Baba, M Hasumi, Y Huang, Y Oh, H Hughes, RM Klein, ME Takikita, S Nagashima, K Schmidt, LS Linehan, WM AF Hasumi, Hisashi Baba, Masaya Hasumi, Yukiko Huang, Ying Oh, Hyoungbin Hughes, Robert M. Klein, Mara E. Takikita, Shoichi Nagashima, Kunio Schmidt, Laura S. Linehan, W. Marston TI Regulation of Mitochondrial Oxidative Metabolism by Tumor Suppressor FLCN SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; TUBEROUS SCLEROSIS COMPLEX; RENAL-CELL CARCINOMA; HOGG-DUBE-SYNDROME; SKELETAL-MUSCLE; GENE-EXPRESSION; MTOR ACTIVATION; KIDNEY TUMORS; PROTEIN; CANCER AB Background Birt-Hogg-Dub (BHD) syndrome is a hereditary hamartoma syndrome that predisposes patients to develop hair follicle tumors, lung cysts, and kidney cancer. Genetic studies of BHD patients have uncovered the causative gene, FLCN, but its function is incompletely understood. Methods Mice with conditional alleles of FLCN and/or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), a transcriptional coactivator that regulates mitochondrial biogenesis, were crossbred with mice harboring either muscle creatine kinase (CKM) Cre or myogenin (MYOG) Cre transgenes to knock out FLCN and/or PPARGC1A in muscle, or cadherin 16 (CDH16)Cre transgenes to knock out FLCN and/or PPARGC1A in kidney. Real-time polymerase chain reaction, immunoblotting, electron microscopy, and metabolic profiling assay were performed to evaluate mitochondrial biogenesis and function in muscle. Immunoblotting, electron microscopy, and histological analysis were used to investigate expression and the pathological role of PPARGC1A in FLCN-deficient kidney. Real-time polymerase chain reaction, oxygen consumption measurement, and flow cytometry were carried out using a FLCN-null kidney cancer cell line. All statistical analyses were two-sided. Results Muscle-targeted FLCN knockout mice underwent a pronounced metabolic shift toward oxidative phosphorylation, including increased mitochondrial biogenesis (FLCNf/f vs FLCNf/f/CKMCre: % mitochondrial area mean 7.8% vs 17.8%; difference 10.0%; 95% confidence interval 5.7% to 14.3%; P < .001), and the observed increase in mitochondrial biogenesis was PPARGC1A dependent. Reconstitution of FLCN-null kidney cancer cells with wild-type FLCN suppressed mitochondrial metabolism and PPARGC1A expression. Kidney-targeted PPARGC1A inactivation partially rescued the enlarged kidney phenotype and abrogated the hyperplastic cells observed in the FLCN-deficient kidney. Conclusion FLCN deficiency and subsequent increased PPARGC1A expression result in increased mitochondrial function and oxidative metabolism as the source of cellular energy, which may give FLCN-null kidney cells a growth advantage and drive hyperplastic transformation. C1 [Hasumi, Hisashi; Baba, Masaya; Hasumi, Yukiko; Huang, Ying; Oh, Hyoungbin; Hughes, Robert M.; Klein, Mara E.; Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Takikita, Shoichi] NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. [Nagashima, Kunio] SAIC Frederick Inc, Image Anal Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. [Schmidt, Laura S.] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, 10 Ctr Dr,MSC 1107,CRC Rm 1-5940W, Bethesda, MD 20892 USA. EM wml@nih.gov RI Baba, Masaya/L-7490-2013 OI Baba, Masaya/0000-0002-5308-6683 FU National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research; Frederick National Laboratory for Cancer Research, NIH [HHSN261200800001E] FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. This project was funded in part with federal funds from the Frederick National Laboratory for Cancer Research, NIH, under contract HHSN261200800001E. NR 59 TC 25 Z9 25 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD NOV PY 2012 VL 104 IS 22 BP 1750 EP 1764 DI 10.1093/jnci/djs418 PG 15 WC Oncology SC Oncology GA 045BK UT WOS:000311669100010 PM 23150719 ER PT J AU Robert, MA Legros, M Facchinelli, L Valerio, L Ramsey, JM Scott, TW Gould, F Lloyd, AL AF Robert, Michael A. Legros, Mathieu Facchinelli, Luca Valerio, Laura Ramsey, Janine M. Scott, Thomas W. Gould, Fred Lloyd, Alun L. TI Mathematical Models as Aids for Design and Development of Experiments: The Case of Transgenic Mosquitoes SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Aedes aegypti; transgenic female-killing; field cage experiment; experimental design; mathematical model ID AEDES-AEGYPTI DIPTERA; GENETIC-CONTROL SYSTEMS; STERILE MALES; BORNE DISEASES; INSECT PESTS; HUMAN BLOOD; CULICIDAE; DENGUE; POPULATION; RELEASE AB We demonstrate the utility of models as aids in the design and development of experiments aimed at measuring the effects of proposed vector population control strategies. We describe the exploration of a stochastic, age-structured model that simulates field cage experiments that test the ability of a female-killing strain of the mosquito Aedes aegypti (L.) to suppress a wild-type population. Model output predicts that choices of release ratio and population size can impact mean extinction time and variability in extinction time among experiments. We find that unless fitness costs are >80% they will not be detectable in experiments with high release ratios. At lower release ratios, the predicted length of the experiment increases significantly for fitness costs >20%. Experiments with small populations may more accurately reflect field conditions, but extinction can occur even in the absence of a functional female-killing construct because of stochastic effects. We illustrate how the model can be used to explore experimental designs that aim to study the impact of density dependence and immigration; predictions indicate that cage population eradication may not always be obtainable in an operationally realistic time frame. We propose a method to predict the extinction time of a cage population based on the rate of population reduction with the goal of shortening the duration of the experiment. We discuss the model as a tool for exploring and assessing the utility of a wider range of scenarios than would be feasible to test experimentally because of financial and temporal restraints. C1 [Robert, Michael A.; Lloyd, Alun L.] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA. [Robert, Michael A.; Lloyd, Alun L.] N Carolina State Univ, Biomath Grad Progarm, Raleigh, NC 27695 USA. [Legros, Mathieu; Gould, Fred] N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA. [Legros, Mathieu; Facchinelli, Luca; Valerio, Laura; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Valerio, Laura] Univ Roma La Sapienza, Cenci Bolognetti Fdn, Inst Pasteur, Rome, Italy. [Ramsey, Janine M.] Ctr Reg Invest Salud Publ, Inst Nacl Salud Publ, Tapachula, Chiapas, Mexico. [Scott, Thomas W.; Gould, Fred; Lloyd, Alun L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Robert, MA (reprint author), N Carolina State Univ, Dept Math, Box 8203, Raleigh, NC 27695 USA. EM marober5@ncsu.edu RI Legros, Mathieu/E-6767-2011; Lloyd, Alun/H-4944-2012; OI Legros, Mathieu/0000-0003-3807-8594; Facchinelli, Luca/0000-0002-8987-1472 FU National Institutes of Health (NIH) [R01AI091980-01A1]; Foundation for the NIH through the Grand Challenges in Global Health initiative; North Carolina State University Mathematics Research Experience for Graduate Students (NSF) [DMS-EMSW21-MCTP-0943855]; Pasteur Institute-Cenci Bolognetti Foundation FX This work is funded by National Institutes of Health (NIH) grant R01AI091980-01A1, a grant to the Regents of the University of California from the Foundation for the NIH through the Grand Challenges in Global Health initiative. Our analysis was improved by discussions fostered by the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directory, Department of Homeland Security, and Fogarty International Center, NIH. M. A. Robert was supported in part by the North Carolina State University Mathematics Research Experience for Graduate Students (NSF grant DMS-EMSW21-MCTP-0943855). L. V. was supported by a Pasteur Institute-Cenci Bolognetti Foundation grant. We extend our gratitude to two anonymous reviewers and Steven Juliano for comments that improved the content of this article. NR 49 TC 3 Z9 3 U1 3 U2 26 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD NOV PY 2012 VL 49 IS 6 BP 1177 EP 1188 DI 10.1603/ME11205 PG 12 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 040EC UT WOS:000311303200002 PM 23270145 ER PT J AU Kohlmeier, KA Ishibashi, M Wess, J Bickford, ME Leonard, CS AF Kohlmeier, Kristi A. Ishibashi, Masaru Wess, Juergen Bickford, Martha E. Leonard, Christopher S. TI Knockouts reveal overlapping functions of M-2 and M-4 muscarinic receptors and evidence for a local glutamatergic circuit within the laterodorsal tegmental nucleus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE muscarinic receptors; GIRK channels; R-type Ca2+ channels; cholinergic neural pathways; brain slice; sleep; arousal; motivation; ascending arousal system ID PONTINE RETICULAR-FORMATION; MESOPONTINE CHOLINERGIC NEURONS; EVOKED CALCIUM TRANSIENTS; EYE-MOVEMENT SLEEP; BRAIN-STEM CORE; ACETYLCHOLINE-RECEPTORS; RAT-BRAIN; PONTOMESENCEPHALIC TEGMENTUM; BASAL FOREBRAIN; C57BL/6J MOUSE AB Kohlmeier KA, Ishibashi M, Wess J, Bickford ME, Leonard CS. Knockouts reveal overlapping functions of M-2 and M-4 muscarinic receptors and evidence for a local glutamatergic circuit within the laterodorsal tegmental nucleus. J Neurophysiol 108: 2751-2766, 2012. First published September 5, 2012; doi:10.1152/jn.01120.2011.-Cholinergic neurons in the laterodorsal tegmental (LDT) and peduncolopontine tegmental (PPT) nuclei regulate reward, arousal, and sensory gating via major projections to midbrain dopamine regions, the thalamus, and pontine targets. Muscarinic acetylcholine receptors (mAChRs) on LDT neurons produce a membrane hyperpolarization and inhibit spike-evoked Ca2+ transients. Pharmacological studies suggest M-2 mAChRs are involved, but the role of these and other localized mAChRs (M1--M-4) has not been definitively tested. To identify the underlying receptors and to circumvent the limited receptor selectivity of available mAChR ligands, we used light- and electron-immunomicroscopy and whole cell recording with Ca2+ imaging in brain slices from knockout mice constitutively lacking either M-2, M-4, or both mAChRs. Immunomicroscopy findings support a role for M-2 mAChRs, since cholinergic and noncholinergic LDT and pedunculopontine tegmental neurons contain M-2-specific immunoreactivity. However, whole cell recording revealed that the presence of either M-2 or M-4 mAChRs was sufficient, and that the presence of at least one of these receptors was required for these carbachol actions. Moreover, in the absence of M-2 and M-4 mAChRs, carbachol elicited both direct excitation and barrages of spontaneous excitatory postsynaptic potentials (sEPSPs) in cholinergic LDT neurons mediated by M-1 and/or M-3 mAChRs. Focal carbachol application to surgically reduced slices suggest that local glutamatergic neurons are a source of these sEPSPs. Finally, neither direct nor indirect excitation were knockout artifacts, since each was detected in wild-type slices, although sEPSP barrages were delayed, suggesting M 2 and M 4 receptors normally delay excitation of glutamatergic inputs. Collectively, our findings indicate that multiple mAChRs coordinate cholinergic outflow from the LDT in an unexpectedly complex manner. An intriguing possibility is that a local circuit transforms LDT muscarinic inputs from a negative feedback signal for transient inputs into positive feedback for persistent inputs to facilitate different firing patterns across behavioral states. C1 [Ishibashi, Masaru; Leonard, Christopher S.] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. [Kohlmeier, Kristi A.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark. [Wess, Juergen] NIDDK, Bethesda, MD USA. [Bickford, Martha E.] Univ Louisville, Sch Med, Louisville, KY 40292 USA. RP Leonard, CS (reprint author), New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. EM chris_leonard@nymc.edu FU National Institutes of Health [NS27881, HL64150, NS35377] FX Research was supported by National Institutes of Health grants NS27881 (C. S. Leonard), HL64150 (C. S. Leonard), and NS35377 (M. E. Bickford). NR 77 TC 9 Z9 10 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2012 VL 108 IS 10 BP 2751 EP 2766 DI 10.1152/jn.01120.2011 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 039EK UT WOS:000311226600010 PM 22956788 ER PT J AU Kurdziel, KA AF Kurdziel, Karen A. TI Radiation Exposure Should Not Limit Bone Scintigraphy with F-18-NaF REPLY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter C1 NCI, NIH, Bethesda, MD 20892 USA. RP Kurdziel, KA (reprint author), NCI, NIH, 10 Ctr Dr,Room B3B403, Bethesda, MD 20892 USA. EM kurdziek@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2012 VL 53 IS 11 BP 1818 EP 1819 DI 10.2967/jnumed.112.111484 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 037TC UT WOS:000311128400031 ER PT J AU Volkin, D Yerram, N Ahmed, F Lankford, D Baccala, A Gupta, GN Hoang, A Nix, J Metwalli, AR Lang, DM Bratslavsky, G Linehan, WM Pinto, PA AF Volkin, Dmitry Yerram, Nitin Ahmed, Faisal Lankford, Dawud Baccala, Angelo Gupta, Gopal N. Hoang, Anthony Nix, Jeffrey Metwalli, Adam R. Lang, David M. Bratslavsky, Gennady Linehan, W. Marston Pinto, Peter A. TI Partial adrenalectomy minimizes the need for long-term hormone replacement in pediatric patients with pheochromocytoma and von Hippel-Lindau syndrome SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Adrenalectomy; Partial adrenalectomy; Pediatric VHL; Pheochromocytoma ID LAPAROSCOPIC PARTIAL ADRENALECTOMY; QUALITY-OF-LIFE; HEREDITARY PHEOCHROMOCYTOMA; BILATERAL ADRENALECTOMY; SURGERY; DISEASE; INSUFFICIENCY; EXPERIENCE; MANAGEMENT; NEOPLASIA AB Purpose: Children with von Hippel-Lindau syndrome (VHL) are at an increased risk for developing bilateral pheochromocytomas. In an effort to illustrate the advantage of partial adrenalectomy (PA) over total adrenalectomy in children with VHL, we report the largest single series on PA for pediatric patients with VHL, demonstrating a balance between tumor removal and preservation of adrenocortical function. Methods: From 1994 to 2011, a prospectively maintained database was reviewed to evaluate 10 pediatric patients with hereditary pheochromocytoma for PA. Surgery was performed if there was clinical evidence of pheochromocytoma and if normal adrenocortical tissue was evident on preoperative imaging and/or intraoperative ultrasonography. Perioperative data were collected, and patients were observed for postoperative steroid use and tumor recurrence. Results: Ten pediatric patients with a diagnosis of VHL underwent 18 successful partial adrenalectomies (4 open, 14 laparoscopic). The median tumor size removed was 2.6 cm (range, 1.2-6.5 cm). Over a median follow-up of 7.2 years (range, 2.6-15.8 years), additional tumors in the ipsilateral adrenal gland were found in 2 patients. One patient underwent completion adrenalectomy, and 1 underwent a salvage PA with resection of the ipsilateral lesion. One patient required short-term steroid replacement therapy. At last follow-up, 7 patients had no radiographic or laboratory evidence of pheochromocytoma. Conclusion: At our institution, PA is the preferred form of management for pheochromocytoma in the (VHL) pediatric population. This surgical approach allows for removal of tumor while preserving adrenocortical function and minimizing the adverse effects of long-term steroid replacement on puberty and quality of life. (c) 2012 Published by Elsevier Inc. C1 [Pinto, Peter A.] NCI, Fellowship Program, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Pinto, PA (reprint author), NCI, Fellowship Program, Urol Oncol Branch, Ctr Canc Res, 10 Ctr Dr,MSC 1210, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov FU Intramural Research Program of the National Cancer Institute, National Institutes of Health FX This research was supported, in part, by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 30 TC 12 Z9 12 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD NOV PY 2012 VL 47 IS 11 BP 2077 EP 2082 DI 10.1016/j.jpedsurg.2012.07.003 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 039DG UT WOS:000311222500031 PM 23164001 ER PT J AU Chen, AP Setser, A Anadkat, MJ Cotliar, J Olsen, EA Garden, BC Lacouture, ME AF Chen, Alice P. Setser, Ann Anadkat, Milan J. Cotliar, Jonathan Olsen, Elise A. Garden, Benjamin C. Lacouture, Mario E. TI Grading dermatologic adverse events of cancer treatments: The Common Terminology Criteria for Adverse Events Version 4.0 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE adverse events; cancer treatment; Common Terminology Criteria for Adverse Events; drug reactions; grading system; side effects ID HAND-FOOT SYNDROME; INDUCED SKIN RASH; CUTANEOUS REACTIONS; CELL CARCINOMA; MANAGEMENT; TOXICITY; CHEMOTHERAPY; CETUXIMAB; RADIOTHERAPY; INHIBITORS AB Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer. (J Am Acad Dermatol 2012;67:1025-39.) C1 [Garden, Benjamin C.; Lacouture, Mario E.] Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10022 USA. [Chen, Alice P.] NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Setser, Ann] NCI, Invest Drug Branch, NIH, Canc Therapy Evaluat Program, Rockville, MD USA. [Anadkat, Milan J.] Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USA. [Cotliar, Jonathan] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA. [Olsen, Elise A.] Duke Univ, Med Ctr, Dept Med, Div Dermatol, Durham, NC 27710 USA. [Olsen, Elise A.] Duke Univ, Med Ctr, Dept Med, Div Oncol, Durham, NC 27710 USA. RP Lacouture, ME (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, Suite 228,160 E 53 St, New York, NY 10022 USA. EM lacoutum@mskcc.org FU US National Institutes of Health; Zell Scholarship from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Dermatology Foundation Career Development Award FX Supported by US National Institutes of Health; Dr Lacouture receives funding from a Zell Scholarship from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and a Dermatology Foundation Career Development Award. NR 34 TC 44 Z9 52 U1 1 U2 9 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 NOV PY 2012 VL 67 IS 5 BP 1025 EP 1039 DI 10.1016/j.jaad.2012.02.010 PG 15 WC Dermatology SC Dermatology GA 033EI UT WOS:000310776600064 PM 22502948 ER PT J AU Sahasrabuddhe, VV Sherman, ME AF Sahasrabuddhe, Vikrant V. Sherman, Mark E. TI Human Papillomavirus Vaccines for Cervical Cancer Prevention: Translating Possibility Into Reality SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID EFFICACY C1 [Sahasrabuddhe, Vikrant V.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. RP Sahasrabuddhe, VV (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 5032, Rockville, MD 20852 USA. EM vikrant.sahasrabuddhe@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 11 TC 2 Z9 2 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV PY 2012 VL 104 IS 22 BP 1698 EP 1701 DI 10.1093/jnci/djs453 PG 4 WC Oncology SC Oncology GA 045BK UT WOS:000311669100005 PM 23104325 ER PT J AU Wentzensen, N Sun, C Ghosh, A Kinney, W Mirabello, L Wacholder, S Shaber, R LaMere, B Clarke, M Lorincz, AT Castle, PE Schiffman, M Burk, RD AF Wentzensen, Nicolas Sun, Chang Ghosh, Arpita Kinney, Walter Mirabello, Lisa Wacholder, Sholom Shaber, Ruth LaMere, Brandon Clarke, Megan Lorincz, Attila T. Castle, Philip E. Schiffman, Mark Burk, Robert D. TI Methylation of HPV18, HPV31, and HPV45 Genomes and Cervical Intraepithelial Neoplasia Grade 3 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-PAPILLOMAVIRUS DNA; CANCER; PROGRESSION; PRECANCER; BIOMARKER; TESTS; WOMEN; RISK; GENE AB Background Persistent infections with carcinogenic human papillomavirus (HPV) types are the necessary cause of cervical cancer. We recently demonstrated that the HPV16 genome is strongly methylated in cervical precancer compared with transient infections. However, the extent of methylation in other HPV types and its role in progression to cancer is poorly understood. Methods We analyzed whole-genome methylation patterns of the three next most carcinogenic HPV genotypes: HPV31 (closely related to HPV16), and two other closely related types, HPV18 and HPV45. DNA was extracted from cervical cytology specimens from 92 women with precancer and 96 women infected with HPV31, HPV18, or HPV45, but who had no cytological or histological abnormalities. After bisulfite modification, genome-wide pyrosequencing was performed covering 80106 sites. We calculated differences in median methylation, odds ratios, areas under the curve, and Spearman rank correlation coefficients for methylation levels between different sites. All statistical tests were two-sided. Results For all three HPV types, we observed strongly elevated methylation levels at multiple CpG sites in the E2, L2, and L1 regions among women with cervical intraepithelial neoplasia grade 3 compared with women with transient infections. We observed high correlation of methylation patterns between phylogenetically related types. The highest areas under the curve were 0.81 for HPV31, 0.85 for HPV18, and 0.98 for HPV45. Differential methylation patterns in cervical intraepithelial neoplasia grade 3 patients with multiple infections suggest that methylation can clarify which of the infections is causal. Conclusions Carcinogenic HPV DNA methylation indicates transforming HPV infections. Our findings show that methylation of carcinogenic HPV types is a general phenomenon that warrants development of diagnostic assays. C1 [Wentzensen, Nicolas; Ghosh, Arpita; Mirabello, Lisa; Wacholder, Sholom; Clarke, Megan; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Sun, Chang; Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Sun, Chang] Yunnan Univ, Lab Conservat & Utilizat Bioresources, Minist Educ, Kunming, Peoples R China. [Sun, Chang] Yunnan Univ, Minist Educ, Key Lab Microbial Div SW China, Kunming, Peoples R China. [Kinney, Walter] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA. [Shaber, Ruth] Kaiser Permanente, Care Management Inst, Oakland, CA USA. [LaMere, Brandon] Kaiser Permanente, Div Res, Womens Hlth Res Inst, Oakland, CA USA. [Lorincz, Attila T.] Univ London, Wolfson Inst Prevent Med, Ctr Canc Prevent, London, England. RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5024, Rockville, MD 20852 USA. EM wentzenn@mail.nih.gov; burk@aecom.yu.edu RI Sun, Chang/I-6326-2012 FU National Cancer Institute FX The research was funded by the Intramural Research Program of the National Cancer Institute. The funding source had no influence on the design, conduct, and evaluation of the study. NR 24 TC 46 Z9 48 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV PY 2012 VL 104 IS 22 BP 1738 EP 1749 DI 10.1093/jnci/djs425 PG 12 WC Oncology SC Oncology GA 045BK UT WOS:000311669100009 PM 23093560 ER PT J AU Patlolla, AK Todorov, TI Tchounwou, PB van der Voet, G Centeno, JA AF Patlolla, Anita K. Todorov, Todor I. Tchounwou, Paul B. van der Voet, Gijsbert Centeno, Jose A. TI Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats SO MICROCHEMICAL JOURNAL LA English DT Article DE Arsenic exposure; Tissue distribution; Genotoxicity; Hepatotoxicity; Rats ID INDUCED CELL-TRANSFORMATION; HAMSTER EMBRYO CELLS; SODIUM ARSENITE; HYPERENDEMIC VILLAGES; DRINKING-WATER; IN-VITRO; TRIOXIDE; EXPOSURE; TOXICITY; MECHANISMS AB Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 +/- 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15,20 mg/kg BW of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p < 0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GFT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. in contrast, the mitotic index in these cells was significantly reduced (p < 0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels. Published by Elsevier B.V. C1 [Patlolla, Anita K.; Tchounwou, Paul B.] Jackson State Univ, NIH RCMI Ctr Environm Hlth, Jackson, MS USA. [Todorov, Todor I.] US Geol Survey, Crustal Geophys & Geochem Sci Ctr, Denver, CO 80225 USA. [Centeno, Jose A.] Joint Pathol Ctr, Biophys Toxicol Lab, Silver Spring, MD 20910 USA. [van der Voet, Gijsbert] Hlth Council Netherlands, The Hague, Netherlands. RP Centeno, JA (reprint author), Joint Base Andrews Air Naval Facil Washington, Biophys Toxicol Lab, Joint Pathol Ctr, Malcolm Grow Med Clin, 1057 W Perimeter Rd, Joint Base Andrews, MD 20762 USA. EM Jose.Centeno@afncr.af.mil FU National Institutes of Health-RCMI Grant [1G12RR13459] FX This research was financially supported by the National Institutes of Health-RCMI Grant No. 1G12RR13459 awarded to PBT. NR 77 TC 7 Z9 7 U1 1 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0026-265X J9 MICROCHEM J JI Microchem J. PD NOV PY 2012 VL 105 SI SI BP 101 EP 107 DI 10.1016/j.microc.2012.08.013 PG 7 WC Chemistry, Analytical SC Chemistry GA 039QE UT WOS:000311260800017 PM 23175155 ER PT J AU Fang, F Chen, HL Feldman, AL Kamel, F Ye, WM Wirdefeldt, K AF Fang, Fang Chen, Honglei Feldman, Adina L. Kamel, Freya Ye, Weimin Wirdefeldt, Karin TI Head injury and Parkinson's disease: A population-based study SO MOVEMENT DISORDERS LA English DT Article DE Parkinson disease; head injury; nested case-control study; odds ratio ID ENVIRONMENTAL RISK-FACTORS; TRAUMATIC BRAIN-INJURY; HISTORY AB Background: The epidemiological evidence on head injury and the risk of Parkinson's disease (PD) has been inconsistent. Methods: We examined the relation between previous hospitalization for head injury and PD using a population-based nested case-control design based on the Swedish National Patient Register from 2001 until 2007, including 18,648 PD cases and 93,240 controls, randomly selected from the general population. Exposure was defined as hospitalization for head injury between 1987 and index date. Results: Overall, previous hospitalization resulting from head injury was associated with an increased risk of PD; this association appeared to be largely explained by head injuries experienced recently, especially within 1 year before PD ascertainment. Conclusions: Our results do not provide convincing evidence for a causal relationship between head injury later in life and PD. (C) 2012 Movement Disorder Society C1 [Fang, Fang; Feldman, Adina L.; Ye, Weimin; Wirdefeldt, Karin] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Chen, Honglei; Kamel, Freya] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Wirdefeldt, Karin] Karolinska Inst, Dept Clin Neurosci, SE-17177 Stockholm, Sweden. RP Wirdefeldt, K (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, SE-17177 Stockholm, Sweden. EM karin.wirdefeldt@ki.se RI Feldman, Adina/H-3435-2012; OI Feldman, Adina/0000-0002-9388-6896; Fang, Fang/0000-0002-3310-6456; Kamel, Freya/0000-0001-5052-6615; Chen, Honglei/0000-0003-3446-7779 FU Swedish Research Council (SIMSAM) [80748301]; Swedish Parkinson Foundation; Swedish Medical Society; Swedish Society for Medical Research; Swedish Brain Foundation; National Institutes of Health, the National Institute of Environmental Health Sciences [Z01-ES-101986] FX The study was supported by the Swedish Research Council (SIMSAM grant no. 80748301), the Swedish Parkinson Foundation, the Swedish Medical Society, the Swedish Society for Medical Research, the Swedish Brain Foundation, and the intramural research program of the National Institutes of Health, the National Institute of Environmental Health Sciences (Z01-ES-101986 and unmet need funding). The funding sources had no role in the design of the study or the decision to submit the manuscript for publication. NR 22 TC 10 Z9 10 U1 0 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2012 VL 27 IS 13 BP 1632 EP 1635 DI 10.1002/mds.25143 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 045KU UT WOS:000311695500013 PM 23143933 ER PT J AU Goldman, SM Kamel, F Ross, GW Bhudhikanok, GS Hoppin, JA Korell, M Marras, C Meng, C Umbach, DM Kasten, M Chade, AR Comyns, K Richards, MB Sandler, DP Blair, A Langston, JW Tanner, CM AF Goldman, Samuel M. Kamel, Freya Ross, G. Webster Bhudhikanok, Grace S. Hoppin, Jane A. Korell, Monica Marras, Connie Meng, Cheryl Umbach, David M. Kasten, Meike Chade, Anabel R. Comyns, Kathleen Richards, Marie B. Sandler, Dale P. Blair, Aaron Langston, J. William Tanner, Caroline M. TI Genetic modification of the association of paraquat and Parkinson's disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; paraquat; glutathione transferase; pesticide; gene-environment interaction ID GLUTATHIONE-S-TRANSFERASE; ENVIRONMENTAL RISK-FACTORS; PESTICIDE EXPOSURE; OXIDATIVE STRESS; AGRICULTURAL HEALTH; P1 POLYMORPHISMS; NEURON LOSS; O-QUINONES; POPULATION; MECHANISM AB Paraquat is one of the most widely used herbicides worldwide. It produces a Parkinson's disease (PD) model in rodents through redox cycling and oxidative stress (OS) and is associated with PD risk in humans. Glutathione transferases provide cellular protection against OS and could potentially modulate paraquat toxicity. We investigated PD risk associated with paraquat use in individuals with homozygous deletions of the genes encoding glutathione S-transferase M1 (GSTM1) or T1 (GSTT1). Eighty-seven PD subjects and 343 matched controls were recruited from the Agricultural Health Study, a study of licensed pesticide applicators and spouses in Iowa and North Carolina. PD was confirmed by in-person examination. Paraquat use and covariates were determined by interview. We genotyped subjects for homozygous deletions of GSTM1 (GSTM1*0) and GSTT1 (GSTT1*0) and tested interaction between paraquat use and genotype using logistic regression. Two hundred and twenty-three (52%) subjects had GSTM1*0, 95 (22%) had GSTT1*0, and 73 (17%; all men) used paraquat. After adjustment for potential confounders, there was no interaction with GSTM1. In contrast, GSTT1 genotype significantly modified the association between paraquat and PD. In men with functional GSTT1, the odds ratio (OR) for association of PD with paraquat use was 1.5 (95% confidence interval [CI]: 0.63.6); in men with GSTT1*0, the OR was 11.1 (95% CI: 3.044.6; P interaction: 0.027). Although replication is needed, our results suggest that PD risk from paraquat exposure might be particularly high in individuals lacking GSTT1. GSTT1*0 is common and could potentially identify a large subpopulation at high risk of PD from oxidative stressors such as paraquat. (C) 2012 Movement Disorder Society C1 [Goldman, Samuel M.; Bhudhikanok, Grace S.; Korell, Monica; Meng, Cheryl; Comyns, Kathleen; Langston, J. William; Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA 94085 USA. [Kamel, Freya; Hoppin, Jane A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Marras, Connie] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. [Umbach, David M.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Kasten, Meike] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Kasten, Meike] Med Univ Lubeck, Dept Clin & Mol Neurogenet, D-23538 Lubeck, Germany. [Chade, Anabel R.] Favaloro Univ, Inst Neurosci, Inst Cognit Neurol, Buenos Aires, DF, Argentina. [Richards, Marie B.] Westat Corp, Durham, NC USA. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Goldman, SM (reprint author), Parkinsons Inst, 675 Almanor Ave, Sunnyvale, CA 94085 USA. EM sgoldman@thepi.org RI Goldman, Samuel/A-2225-2014; OI Goldman, Samuel/0000-0002-3039-9927; Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) [Z01-ES044007, Z01-ES049030]; National Cancer Institute [Z01-CP010119]; NIEHS [R01-ES10803, U54 ES012077]; Michael J. Fox Foundation FX This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) grants (Z01-ES044007 and Z01-ES049030), a National Cancer Institute grant (Z01-CP010119), NIEHS grants R01-ES10803 and U54 ES012077, the Michael J. Fox Foundation, and James and Sharron Clark. NR 74 TC 25 Z9 25 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2012 VL 27 IS 13 BP 1652 EP 1658 DI 10.1002/mds.25216 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 045KU UT WOS:000311695500016 PM 23045187 ER PT J AU Hua, P Liu, WG Kuo, SH Zhao, YY Chen, L Zhang, N Wang, C Guo, SW Wang, L Xiao, H Kwan, JY Wu, TX AF Hua, Ping Liu, Weiguo Kuo, Sheng-Han Zhao, Yanyan Chen, Ling Zhang, Ning Wang, Chun Guo, Suwan Wang, Li Xiao, Hong Kwan, Justin Y. Wu, Tianxia TI Association of Tef polymorphism with depression in Parkinson disease SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; depression; Tef; circadian genes ID SEROTONIN TRANSPORTER GENE; MINI-MENTAL-STATE; ALLELIC VARIATION; MAJOR DEPRESSION; MOOD DISORDERS; CLOCK; NUCLEOTIDE; EXPRESSION; THERAPY; IMPACT AB Background: Circadian rhythm disturbance has been implicated in depression, and polymorphisms of circadian genes Cry1, Cry2, and Tef are associated with depression. However, the relationship between these genes and depression symptoms in Parkinson's disease (PD) has not been established. Methods: Four hundred eight subjects with PD participated in this study. Demographics, UPDRS, MiniMental Status Examination (MMSE), and Hamilton Rating Scale for Depression (HAMD) were obtained in all subjects. Frequency of polymorphisms of Cry1 rs2287161, Cry2 rs10838524, and Tef rs738499 was determined, and the association between genetic polymorphisms of circadian genes and HAMD scores in patients with PD was examined. Results: Tef, but not Cry1 or Cry2, is associated with HAMD scores in patients with PD in a linear regression model after adjusting for clinical variables (P = 0.004). Conclusions: The polymorphism of Tef rs738499 is associated with depression symptoms in PD. (C) 2012 Movement Disorder Society C1 [Hua, Ping; Liu, Weiguo; Zhao, Yanyan] Nanjing Med Univ, Affiliated Brain Hosp, Dept Neurol, Nanjing 210029, Jiangsu, Peoples R China. [Kuo, Sheng-Han] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. [Wang, Li] Nanjing Med Univ, Affiliated Brain Hosp, Clin Lab, Nanjing 210029, Jiangsu, Peoples R China. [Xiao, Hong] Nanjing Med Univ, Affiliated Brain Hosp, Inst Sci Res, Nanjing 210029, Jiangsu, Peoples R China. [Kwan, Justin Y.] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. [Wu, Tianxia] NINDS, NIH, Bethesda, MD 20892 USA. RP Liu, WG (reprint author), Nanjing Med Univ, Nanjing Brain Hosp, Dept Neurol, Nanjing 210029, Jiangsu, Peoples R China. EM liuweiguo1111@sina.com FU National Natural Science [81170309]; Medical Science and Technology Foundation Project of Chinese Traditional Medicine from Jiangsu Province [LB09088]; Key Project of Medical Science and Technology Development Foundation from the Nanjing Department of Health [200905016]; American Academy of Neurology Research Fellowship; Parkinson Disease Foundation FX The study was supported by the National Natural Science (81170309), Medical Science and Technology Foundation Project of Chinese Traditional Medicine from Jiangsu Province (LB09088), and Key Project of Medical Science and Technology Development Foundation from the Nanjing Department of Health (200905016), an American Academy of Neurology Research Fellowship, and the Parkinson Disease Foundation. NR 35 TC 9 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2012 VL 27 IS 13 BP 1694 EP 1697 DI 10.1002/mds.25195 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 045KU UT WOS:000311695500024 PM 23138696 ER PT J AU Raphaelson, M Inati, SK AF Raphaelson, Marc Inati, Sara K. TI Treating Sleep Disorders in Neurology Practice SO NEUROLOGIC CLINICS LA English DT Article DE Sleep disorders; Neurology; Practice; Diagnosis; Treatment; Integrate ID POSTTRAUMATIC-STRESS-DISORDER; POSITIVE AIRWAY PRESSURE; RESTLESS LEGS SYNDROME; EXCESSIVE DAYTIME SLEEPINESS; AMYOTROPHIC-LATERAL-SCLEROSIS; SEXUAL-ASSAULT SURVIVORS; MULTIPLE SYSTEM ATROPHY; ACUTE ISCHEMIC-STROKE; MARIE-TOOTH-DISEASE; QUALITY-OF-LIFE AB Neurologists treat many people with unrecognized sleep disorders. This review recommends that new and established patients routinely complete standard sleep questionnaires as an aid to clinical history. Because there is high prevalence of treatable primary sleep disorders among neurologic patients, routine diagnostic sleep testing is indicated for patients with stroke, neuromuscular disease, dementia, REM behavioral disorder, atypical or treatment-refractory insomnia, and chronic and unexplained fatigue or sleepiness. As local and national regulatory momentum favors increasing care coordination and integration, neurologists should develop a clinical pathway to diagnose and treat sleep disorders within the practice or through a collegial expert network. C1 [Inati, Sara K.] NINDS, EEG Sect, NIH, Bethesda, MD 20894 USA. RP Raphaelson, M (reprint author), 224D Cornwall St,Suite 101B, Leesburg, VA 20176 USA. EM raphaels4@aol.com FU Intramural Research Program on the NIH, NINDS FX This research was supported in part by the Intramural Research Program on the NIH, NINDS. NR 124 TC 0 Z9 0 U1 3 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2012 VL 30 IS 4 BP 1007 EP + DI 10.1016/j.ncl.2012.08.015 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047XI UT WOS:000311874400004 PM 23099127 ER PT J AU Aziz, NM Miller, JL Curtis, JR AF Aziz, Noreen M. Miller, Jeri L. Curtis, J. Randall TI Palliative and end-of-life care research: Embracing new opportunities SO NURSING OUTLOOK LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ADVANCE DIRECTIVES; ADVANCED CANCER; COMMUNICATION; OUTCOMES; HEALTH; ASSOCIATIONS; ONCOLOGISTS; PREFERENCES; DISCUSSIONS AB The past two decades have witnessed dramatic advances in palliative and end-of-life care research with increased understanding of the burden of life-limiting diseases on patients, families, clinicians, and our healthcare system; and researchers have documented palliative care interventions that improve patient and family outcomes and reduce the costs of care (Detering, Hancock, Reade, & Silvester, 2010). These advances have led to a new era of palliative and end-of-life care research and practice with widespread recognition of its accomplishments and successes. Consequently, we now have an important opportunity to reassess our recent successes and challenges and to identify the goals and benchmarks that will ensure ongoing robust advances in this now-recognized and critical scientific area. High-quality palliative and end-of-life care will be best informed by methodologically strong research efforts that generate a body of evidence with the capacity to support and direct care and effect changes in practice. It is in this context that the National Institute of Nursing Research conceptualized and led a Summit titled The Science of Compassion: Future Directions in End-of-Life and Palliative Care Research in August, 2011. In this summary article, we present brief overviews of the six articles chosen for this Special Issue of Nursing Outlook, examine their key conclusions, articulate gaps and needs, and discuss next steps in palliative and end-of-life care research through the lens of these six topics. Cite this article: Aziz, N. M., Miller, J. L., & Curtis, J. R. (2012, DECEMBER). Palliative and end-of-life care research: Embracing new opportunities. Nursing Outlook, 60(6), 384-390. http://dx.doi.or/10.1016/j.outlook.2012.08.006. C1 [Aziz, Noreen M.; Miller, Jeri L.] NINR, NIH, Off Extramural Programs, Div Extramural Act, Bethesda, MD 20892 USA. [Curtis, J. Randall] Univ Washington, Sch Med, Seattle, WA USA. [Curtis, J. Randall] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. RP Aziz, NM (reprint author), NINR, NIH, Off Extramural Programs, Div Extramural Act, 6701 Democracy Blvd,Suite 710,1 Democracy Plaza, Bethesda, MD 20892 USA. EM azizn@mail.nih.gov FU Intramural NIH HHS [Z99 NR999999] NR 50 TC 12 Z9 12 U1 6 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD NOV-DEC PY 2012 VL 60 IS 6 BP 384 EP 390 DI 10.1016/j.outlook.2012.08.006 PG 7 WC Nursing SC Nursing GA 043EU UT WOS:000311526500010 PM 23141198 ER PT J AU Li, Y Deng, C Hu, X Patel, B Fu, X Qiu, Y Brand, M Zhao, K Huang, S AF Li, Y. Deng, C. Hu, X. Patel, B. Fu, X. Qiu, Y. Brand, M. Zhao, K. Huang, S. TI Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis SO ONCOGENE LA English DT Article DE TAL1/SCL; LSD1; H3K4 demethylation; serine phosphorylation; epigenetic regulation; leukemogenesis ID ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL LEUKEMIA; TRANSCRIPTION FACTOR TAL1/SCL; BETA-GLOBIN LOCUS; STEM-CELLS; CHROMOSOME-TRANSLOCATION; ERYTHROID-CELLS; GENE-EXPRESSION; TRANSGENIC MICE; SCL GENE AB TAL1/SCL is a hematopoietic-specific oncogene and its activity is regulated by associated transcriptional co-activators and corepressors. Dysregulation of TAL1 activity has been associated with T-cell leukemogenesis. However, it remains unclear how the interactions between TAL1 and corepressors versus co-activators are properly regulated. Here, we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis. Knockdown of TAL1 or LSD1 led to a derepression of the TAL1 target genes in T-cell acute lymphoblast leukemia (T-ALL) Jurkat cells, which is accompanied by elevating promoter H3K4 methylation. Similarly, treatment of PKA activator forskolin resulted in derepression of target genes by reducing its interaction with LSD1 while PKA inhibitor H89 represses them by suppressing H3K4 methylation levels. Consistent with the dual roles of TAL1 in transcription, TAL1-associated LSD1 is decreased while recruitment of hSET1 is increased at the TAL1 targets during erythroid differentiation. This process is accompanied by a dramatic increase in H3K4 methylation. Thus, our data revealed a novel interplay between PKA phosphorylation and TAL1-mediated epigenetic regulation that regulates hematopoietic transcription and differentiation programs during hematopoiesis and leukemogenesis. Oncogene (2012) 31, 5007-5018; doi:10.1038/onc.2012.8; published online 6 February 2012 C1 [Li, Y.; Hu, X.; Fu, X.] Jilin Univ, Coll Life Sci, Changchun 130023, Peoples R China. [Qiu, Y.] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32610 USA. [Qiu, Y.; Huang, S.] Univ Florida, Coll Med, Shands Canc Ctr, Gainesville, FL 32610 USA. [Brand, M.] Ottawa Hosp, Sprott Ctr Stem Cell Res, Res Inst, Ottawa, ON, Canada. [Zhao, K.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Li, Y.; Deng, C.; Hu, X.; Patel, B.; Huang, S.] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. RP Huang, S (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. EM sumingh@ufl.edu FU National Institute of Health [R01HL090589, R01HL091929, R01HL091929-01A1S1, R01HL095674]; NIH [5T32-CA9126-34]; Intramural Research programs, National Heart Lung Blood Institute and National Institute of Health FX We are grateful to members of the Huang laboratory for their suggestions and comments. This work was supported by grants from the National Institute of Health (SH, R01HL090589, R01HL091929 and R01HL091929-01A1S1-the ARRA Administrative supplement; YQ, R01HL095674). BP is supported by NIH T32 training grant (5T32-CA9126-34). KZ is supported by the Intramural Research programs, National Heart Lung Blood Institute and National Institute of Health. NR 59 TC 17 Z9 17 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 2012 VL 31 IS 48 BP 5007 EP 5018 DI 10.1038/onc.2012.8 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 048CU UT WOS:000311888600005 PM 22310283 ER PT J AU Moore, SC Patel, AV Matthews, CE de Gonzalez, AB Park, Y Katki, HA Linet, MS Weiderpass, E Visvanathan, K Helzlsouer, KJ Thun, M Gapstur, SM Hartge, P Lee, IM AF Moore, Steven C. Patel, Alpa V. Matthews, Charles E. de Gonzalez, Amy Berrington Park, Yikyung Katki, Hormuzd A. Linet, Martha S. Weiderpass, Elisabete Visvanathan, Kala Helzlsouer, Kathy J. Thun, Michael Gapstur, Susan M. Hartge, Patricia Lee, I-Min TI Leisure Time Physical Activity of Moderate to Vigorous Intensity and Mortality: A Large Pooled Cohort Analysis SO PLOS MEDICINE LA English DT Article ID CARDIOVASCULAR-DISEASE MORTALITY; RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE ASPIRIN; LIFE EXPECTANCY; PRIMARY PREVENTION; ALL-CAUSE; POSTMENOPAUSAL WOMEN; REGRESSION-MODELS; MEASUREMENT ERROR; BREAST-CANCER AB Background: Leisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis. Methods and Findings: We examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21-90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1-3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6-2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3-4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5-24.9) was associated with a gain of 7.2 (95% CI: 6.5-7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report. Conclusions: More leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups. C1 [Moore, Steven C.; Matthews, Charles E.; de Gonzalez, Amy Berrington; Park, Yikyung; Katki, Hormuzd A.; Linet, Martha S.; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Patel, Alpa V.; Thun, Michael; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway. [Weiderpass, Elisabete] Dept Community Med, Tromso, Norway. [Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland. [Visvanathan, Kala; Helzlsouer, Kathy J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Lee, I-Min] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Moore, SC (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM moorest@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; matthews, Charles/E-8073-2015; Weiderpass, Elisabete/M-4029-2016; Moore, Steven/D-8760-2016; OI matthews, Charles/0000-0001-8037-3103; Weiderpass, Elisabete/0000-0003-2237-0128; Moore, Steven/0000-0002-8169-1661; Park, Yikyung/0000-0002-6281-489X FU Intramural Research Program of the US National Institutes of Health (NIH); Division of Cancer Control and Population Sciences, National Cancer Institute (NCI), NIH; Intramural Research Program of the NCI; National Institute of Aging [U01 AG18033]; NCI [CA105069]; Swedish Research Council; Swedish Cancer Society; [CA047988]; [HL043851]; [HL080467] FX Supported by the Intramural Research Program of the US National Institutes of Health (NIH) and the Division of Cancer Control and Population Sciences, National Cancer Institute (NCI), NIH. The NIH-AARP Diet and Health study was supported by the Intramural Research Program of the NCI. CLUE was supported by the National Institute of Aging, grant number: U01 AG18033 and NCI, grant number: CA105069. The US Radiologic Technologists study was supported by the Intramural Research Program of the NCI. The Women's Health Study was supported by grant numbers CA047988, HL043851, and HL080467. The Swedish Women's Lifestyle and Health study is supported by grants from the Swedish Research Council and Swedish Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 110 Z9 112 U1 4 U2 34 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD NOV PY 2012 VL 9 IS 11 AR e1001335 DI 10.1371/journal.pmed.1001335 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 048CW UT WOS:000311888800001 PM 23139642 ER PT J AU Forsythe, LP Romano, JM Jensen, MP Thorn, BE AF Forsythe, Laura P. Romano, Joan M. Jensen, Mark P. Thorn, Beverly E. TI Attachment Style Is Associated With Perceived Spouse Responses and Pain-Related Outcomes SO REHABILITATION PSYCHOLOGY LA English DT Article DE chronic pain; attachment; spouse responses; pain behavior; depression ID STUDIES DEPRESSION SCALE; ADULT ATTACHMENT; BEHAVIORAL INTERACTIONS; MARITAL SATISFACTION; SOCIAL SUPPORT; SELF; DISABILITY; INVENTORY; COUPLES; MODELS AB Purpose/Objective: Attachment theory can provide a heuristic model for examining factors that may influence the relationship of social context to adjustment in chronic pain. This study examined the associations of attachment style with self-reported pain behavior, pain intensity, disability, depression, and perceived spouse responses to pain behavior. We also examined whether attachment style moderates associations between perceived spouse responses and self-reported pain behavior and depressive symptoms, as well as perceived spouse responses as a mediator of these associations. Method: Individuals with chronic pain (N = 182) completed measures of self-reported attachment style, perceived spouse responses, and pain-related criterion variables. Results: Secure attachment was inversely associated with self-reported pain behaviors, pain intensity, disability, depressive symptoms, and perceived negative spouse responses; preoccupied and fearful attachment scores were positively associated with these variables. In multivariable regression models, both attachment style and perceived spouse responses were uniquely associated with self-reported pain behavior and depressive symptoms. Attachment style did not moderate associations between perceived spouse responses to self-reported pain behavior and pain criterion variables, but negative spouse responses partially mediated some relationships between attachment styles and pain outcomes. Conclusions/Implications: Findings suggest that attachment style is associated with pain-related outcomes and perceptions of spouse responses. The hypothesized moderation effects for attachment were not found; however, mediation analyses showed that perceived spouse responses may partially explain associations between attachment and adjustment to pain. Future research is needed to clarify how attachment style and the social environment affect the pain experience. C1 [Forsythe, Laura P.; Thorn, Beverly E.] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. [Romano, Joan M.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Jensen, Mark P.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. RP Forsythe, LP (reprint author), NCI, Off Canc Survivorship, 6116 Execut Blvd,Suite 404,MSC 8336, Bethesda, MD 20892 USA. EM laura.forsythe@nih.gov FU NICHD NIH HHS [P01 HD033988, P01 HD33988] NR 55 TC 8 Z9 9 U1 1 U2 21 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 EI 1939-1544 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD NOV PY 2012 VL 57 IS 4 BP 290 EP 300 DI 10.1037/a0030083 PG 11 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 047EG UT WOS:000311819900003 PM 23148713 ER PT J AU Leopold, A Krueger, F dal Monte, O Pardini, M Pulaski, SJ Solomon, J Grafman, J AF Leopold, Anne Krueger, Frank dal Monte, Olga Pardini, Matteo Pulaski, Sarah J. Solomon, Jeffrey Grafman, Jordan TI Damage to the left ventromedial prefrontal cortex impacts affective theory of mind SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE affective theory of mind; ventromedial prefrontal cortex; traumatic brain injury; emotional intelligence; empathy ID EMOTIONAL INTELLIGENCE; BRAIN-LESIONS; RHESUS-MONKEY; FALSE BELIEF; HEAD-INJURY; DISSOCIATION; IMPAIRMENTS; EMPATHY; DEPRESSION; AUTISM AB Studies investigating theory of mind (ToM) abilities (i.e. ability to understand and predict others' mental states) have revealed that affective and cognitive functions play a significant role and that each of those functions are associated with distinct neural networks. Cognitive facets of ToM have implicated the medial prefrontal cortex, temporo-parietal junction and the anterior paracingulate cortex, whereas affective facets have implicated the ventromedial prefrontal cortex (vmPFC). Although the vmPFC has repeatedly shown to be critical for affective functions, knowledge regarding the exact role of the left and right vmPFC in affective ToM is still obscure. Here, we compared performances of 30 patients with left, right and bilateral vmPFC lesions to two comparison groups (one without and one with brain injuries) on the Faux Pas Recognition task measuring the facets of ToM. We also investigated whether any deficits may be associated with other emotional measures, namely emotional empathy and emotional intelligence. Our results extend earlier findings by showing that the vmPFC is associated with abilities in affective ToM. More importantly, our results revealed that the left, and not the right vmPFC as indicated previously, is involved in affective ToM and that this deficit is associated with emotional intelligence. C1 [Krueger, Frank] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA. [Grafman, Jordan] Kessler Fdn Res Ctr, Traumat Brain Injury Res Lab, W Orange, NJ 07052 USA. [Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [dal Monte, Olga] Univ Turin, Dept Neuropsychol, Turin, Italy. [dal Monte, Olga] Henry M Jackson Fdn, Rockville, MD USA. [Pardini, Matteo] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. [Solomon, Jeffrey] Med Numer, Germantown, MD USA. [Leopold, Anne; dal Monte, Olga; Pulaski, Sarah J.] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Leopold, Anne] Univ Utrecht, Dept Social & Hlth Psychol, Utrecht, Netherlands. RP Krueger, F (reprint author), George Mason Univ, Dept Mol Neurosci, 4400 Univ Dr,Mail Stop 2A1, Fairfax, VA 22030 USA. EM FKrueger@gmu.edu; jgrafman@kesslerfoundation.org RI Pardini, Matteo/F-8414-2010; OI Pardini, Matteo/0000-0002-4740-1982; Grafman, Jordan H./0000-0001-8645-4457; dal monte, olga/0000-0002-7823-4769 FU National Naval Medical Center; U.S. National Institute of Neurological Disorders and Stroke; U.S. Army Medical Research and Material Command [DAMD17-01-1-0675] FX The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of Defense, or the U. S. Government. The authors are grateful to all the Vietnam veterans who participated in this study. Without their long-term commitment to improving the health care of veterans, this study could not have been completed. We thank the National Naval Medical Center for their support and provision of their facilities. We are grateful to S. Bonifant, B. Cheon, C. Ngo, A. Greathouse, K. Reding and G. Tasick for their invaluable help with the testing of participants and organization of this study. The work was supported by the U.S. National Institute of Neurological Disorders and Stroke intramural research program and a project grant from the U.S. Army Medical Research and Material Command administrated by the Henry M. Jackson Foundation (Vietnam Head Injury Study Phase III: a 30-year post-injury follow-up study), grant number: DAMD17-01-1-0675. NR 72 TC 32 Z9 33 U1 7 U2 47 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD NOV PY 2012 VL 7 IS 8 BP 871 EP 880 DI 10.1093/scan/nsr071 PG 10 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 045BZ UT WOS:000311671100001 PM 22021651 ER PT J AU Chen, KG Mallon, BS Hamilton, RS Kozhich, OA Park, K Hoeppner, DJ Robey, PG McKay, RDG AF Chen, Kevin G. Mallon, Barbara S. Hamilton, Rebecca S. Kozhich, Olga A. Park, Kyeyoon Hoeppner, Daniel J. Robey, Pamela G. McKay, Ronald D. G. TI Non-colony type monolayer culture of human embryonic stem cells SO STEM CELL RESEARCH LA English DT Article ID TERM SELF-RENEWAL; ROCK INHIBITOR; IN-VIVO; SURVIVAL; GROWTH; DISSOCIATION; EXPRESSION; SUPPORTS; LINES; ESCS AB Regenerative medicine, relying on human embryonic stem cell (hESC) technology, opens promising new avenues for therapy of many severe diseases. However, this approach is restricted by limited production of the desired cells due to the refractory properties of hESC growth in vitro. It is further hindered by insufficient control of cellular stress, growth rates, and heterogeneous cellular states under current culture conditions. In this study, we report a novel cell culture method based on a non-colony type monotayer (NCM) growth. Human ESCs under NCM remain pluripotent as determined by teratoma assays and sustain the potential to differentiate into three germ layers. This NCM culture has been shown to homogenize cellular states, precisely control growth rates, significantly increase cell production, and enhance hESC recovery from cryopreservation without compromising chromosomal integrity. This culture system is simple, robust, scalable, and suitable for high-throughput screening and drug discovery. Published by Elsevier B.V. C1 [Chen, Kevin G.; Mallon, Barbara S.; Hamilton, Rebecca S.; Park, Kyeyoon; Robey, Pamela G.; McKay, Ronald D. G.] Natl Inst Neurol Disorders & Stroke, NIH, Stem Cell Unit, Bethesda, MD 20892 USA. [Kozhich, Olga A.; Hoeppner, Daniel J.; McKay, Ronald D. G.] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Chen, KG (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Stem Cell Unit, 37 Convent Dr,Room 1000, Bethesda, MD 20892 USA. EM cheng@mail.nih.gov; ronald.mckay@libd.org RI Robey, Pamela/H-1429-2011; Chen, Kevin/D-6769-2011 OI Robey, Pamela/0000-0002-5316-5576; Chen, Kevin/0000-0003-2983-6330 FU NIH FX The NIH Stem Cell Unit is supported by NIH funds. We thank Dr. Joshua Chenoweth for the discussion, Dr. Peter Andrews for providing antibodies described in Supplemental information, Dr. Guokai Chen for the BC1 line, and Dr. Tianmin Ivy Zhang and Dr. Qi Zheng (Applied StemCell Inc.) for conducting the teratoma assays. NR 42 TC 14 Z9 14 U1 0 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 J9 STEM CELL RES JI Stem Cell Res. PD NOV PY 2012 VL 9 IS 3 BP 237 EP 248 DI 10.1016/j.scr.2012.06.003 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 044XP UT WOS:000311658800008 PM 22910561 ER PT J AU Jaiswal, KR Xin, HW Anderson, A Wiegand, G Kim, B Miller, T Hari, D Ray, S Koizumi, T Rudloff, U Thorgeirsson, SS Avital, I AF Jaiswal, Kshama R. Xin, Hong-Wu Anderson, Andrew Wiegand, Gordon Kim, Bo Miller, Tyler Hari, Danielle Ray, Satyajit Koizumi, Tomotake Rudloff, Udo Thorgeirsson, Snorri S. Avital, Itzhak TI Comparative testing of various pancreatic cancer stem cells results in a novel class of pancreatic-cancer-initiating cells SO STEM CELL RESEARCH LA English DT Article ID SIDE POPULATION CELLS; LINES; HYPOXIA AB No systemic therapy is effective against pancreatic cancer (PC). Pancreatic cancer stem cells (PCSC) are hypothesized to account for therapeutic resistance. Several PCSC subpopulations were reported, each characterized by different markers. To be able to target PCSC, we sought to better define this putative heterogeneity. Therefore, we tested most of the known putative PCSC markers in established and fresh tumor cell lines. CD20, CD24, CD44, CD133, CD184 (CXCR4), CD326 (EpCam, ESA), Sox-2, OCT 3/4, and the side-population (SP) were tested in five PC cell lines, and the effects of confluency, hypoxia, radiation, and gemcitabine on the SP. The testing phase suggested several putative PCSC populations that were further tested and validated for their tumor-initiating capacity against known PCSC in 3 established and 1 fresh PC cell lines. Cell surface and intracellular markers showed significant variability among cell lines. SP was the only common marker in all cell lines and consistently less than 1%. SP response to confluence, hypoxia, radiation, and gemcitabine was inconsistent between cell lines. The initial testing phase suggested that SP/CD44-CD24-CD326+ cells might be a novel PCSC subpopulation. Tumor initiation capacity tests in nude mice confirmed their increased tumorigenicity over previously reported PCSC. Our data better define the heterogeneity of reported PCSC in cell lines tested in this study. We propose that prior to targeting PC via PCSC, one will need to gain more insight into this heterogeneity. Finally, we show that SP/CD44-CD24-CD326+ cells are a novel subpopulation of pancreatic cancer tumor initiating cells. Further mechanistic studies may lead to better targeting of PC via targeting this novel PCSC. (C) 2012 Elsevier B.V. All rights reserved. C1 [Thorgeirsson, Snorri S.] NCI, Ctr Excellence Integrat Canc Biol & Genom, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Jaiswal, Kshama R.; Xin, Hong-Wu; Anderson, Andrew; Wiegand, Gordon; Kim, Bo; Miller, Tyler; Hari, Danielle; Ray, Satyajit; Koizumi, Tomotake; Rudloff, Udo; Avital, Itzhak] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Jaiswal, Kshama R.] Univ Colorado, Denver Hlth Med Ctr, Denver, CO 80204 USA. RP Thorgeirsson, SS (reprint author), NCI, Ctr Excellence Integrat Canc Biol & Genom, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov; itzhak.avital@gmail.com FU NIH/National Cancer Institute; National Cancer Institute FX Douglas Burka and Chenwi Ambe have contributed to this work. This study was supported by the intramural grant provided by the NIH/National Cancer Institute.; Research was supported by intramural funding from the National Cancer Institute. NR 29 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 J9 STEM CELL RES JI Stem Cell Res. PD NOV PY 2012 VL 9 IS 3 BP 249 EP 260 DI 10.1016/j.scr.2012.08.001 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 044XP UT WOS:000311658800009 PM 22963768 ER PT J AU Sinert, R Brandler, E Subramanian, RA Miller, AC AF Sinert, Richard Brandler, Ethan Subramanian, Ramanand Arun Miller, Andrew C. TI Does the Current Definition of Contrast-induced Acute Kidney Injury Reflect a True Clinical Entity? SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID ACUTE-RENAL-FAILURE; PERCUTANEOUS CORONARY INTERVENTION; ENHANCED COMPUTED-TOMOGRAPHY; SERUM CREATININE CHANGES; LENGTH-OF-STAY; INDUCED NEPHROPATHY; RISK-FACTORS; HOSPITALIZED-PATIENTS; MORTALITY; NEPHROTOXICITY AB Objectives Contrast-induced acute kidney injury (CI-AKI) is defined as either a 25% increase in or an absolute elevation in serum creatinine (SCr) of 0.5 mg/dL, 48 to 72 hours after parenteral contrast exposure. The objective of this study was to compare the incidence and complications of AKI between patients exposed and those unexposed to intravenous (IV) contrast. Methods This was a retrospective cohort study using the electronic medical record of adult patients (>18 years) with and without contrast-enhanced abdominal or chest computed tomography (CT) between May 2008 and April 2009. Inclusion criteria were emergency department (ED) patients with normal renal function who received either a contrast-enhanced abdominal or a contrast-enhanced chest CT, compared to those unexposed to IV contrast, with a repeat SCr within 48 to 72 hours. Exclusion criteria were contrast exposure within 7 days before the index visit. CI-AKI in the contrast-exposed group and AKI in the contrast-unexposed group were defined by the same changes in SCr 48 to 72 hours after contrast or ED admission. Data were described by proportions or medians with 95% confidence intervals (CIs) or interquartile ranges (IQR; 25% to 75%). Group comparisons were by Mann-Whitney U or Fisher's exact test (a = 0.05, two tails). Results The contrast-exposed (n = 773) and contrast-unexposed (n = 2,956) patients were evenly matched for initial demographic, renal, and metabolic parameters. The incidence of CI-AKI/AKI was significantly higher for the patients unexposed versus exposed to contrast (8.96% vs. 5.69%, p = 0.003). There was no significant difference in mortality rates between contrast-exposed and unexposed patients (9.09% vs. 6.79%, p = 0.533). Conclusions The definition of CI-AKI for ED patients with normal renal function may not represent a true clinical entity and the definition warrants revision. C1 [Sinert, Richard; Brandler, Ethan] Suny Downstate Med Ctr, Dept Emergency Med, Brooklyn, NY 11203 USA. [Subramanian, Ramanand Arun] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Falls Church, VA USA. [Miller, Andrew C.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Miller, Andrew C.] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. RP Sinert, R (reprint author), Suny Downstate Med Ctr, Dept Emergency Med, Brooklyn, NY 11203 USA. EM Richard.Sinert@Downstate.edu OI Brandler, Ethan/0000-0003-4647-8483; Miller, Andrew/0000-0001-8474-5090 NR 35 TC 16 Z9 16 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2012 VL 19 IS 11 BP 1261 EP 1267 DI 10.1111/acem.12011 PG 7 WC Emergency Medicine SC Emergency Medicine GA 041DQ UT WOS:000311377300007 PM 23167857 ER PT J AU Whitehead, NS Hammond, JA Williams, MA Huggins, W Hoover, S Hamilton, CM Ramos, EM Junkins, HA Harlan, WR Hogue, CJ AF Whitehead, Nedra S. Hammond, Jane A. Williams, Michelle A. Huggins, Wayne Hoover, Sonja Hamilton, Carol M. Ramos, Erin M. Junkins, Heather A. Harlan, William R. Hogue, Carol J. CA Phenx Reprod Hlth Working Grp TI The PhenX Toolkit pregnancy and birth collections SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material DE Pregnancy; Birth; Risk factors; Pregnancy outcomes ID GENOME-WIDE ASSOCIATION; GESTATIONAL DIABETES-MELLITUS; PRETERM BIRTH; INSIGHTS; GENETICS; CONSEQUENCES; QUALITY; WOMEN AB Purpose: Pregnancy and childbirth are normal conditions, but complications and adverse outcomes are common. Both genetic and environmental factors influence the course of pregnancy. Genetic epidemiologic research into pregnancy outcomes could be strengthened by the use of common measures, which would allow data from different studies to be combined or compared. Here, we introduce perinatal researchers to the PhenX Toolkit and the Collections related to pregnancy and childbirth. Methods: The Pregnancy and Birth Collections were drawn from measures in the PhenX Tooklit. The lead author selected a list of measures for each Collection, which was reviewed by the remaining authors and revised on the basis of their comments. We chose the measures we thought were most relevant for perinatal research and had been linked most strongly to perinatal outcomes. Results: The Pregnancy and Birth Health Conditions Collection includes 24 measures related to pregnancy and fertility history, maternal complications, and infant complications. The Pregnancy and Birth Outcome Risk Factors Collection includes 43 measures of chemical, medical, psychosocial, and personal factors associated with pregnancy outcomes. Conclusions: The biological complexity of pregnancy and its sensitivity to environmental and genomic influences suggest that multidisciplinary approaches are needed to generate new insights or practical interventions. To fully exploit new research methods and resources, we encourage the biomedical research community to adopt standard measures to facilitate pooled or meta-analyses. (C) 2012 Elsevier Inc. All rights reserved. C1 [Whitehead, Nedra S.; Hammond, Jane A.; Huggins, Wayne; Hoover, Sonja; Hamilton, Carol M.] RTI Int, San Francisco, CA USA. [Williams, Michelle A.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Ramos, Erin M.; Junkins, Heather A.] NIH, Natl Human Genet Res Inst, Bethesda, MD 20892 USA. [Hamilton, Carol M.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Whitehead, NS (reprint author), RTI Int, 2951 Flowers Rd,Suite 119, Atlanta, GA 30341 USA. EM nwhitehead@rti.org RI Haines, Jonathan/C-3374-2012; Hogue, Carol/H-5442-2012 FU NHGRI NIH HHS [U01 HG004597, U01 HG004597-01] NR 30 TC 1 Z9 1 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2012 VL 22 IS 11 BP 753 EP 758 DI 10.1016/j.annepidem.2012.08.004 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 036YI UT WOS:000311067800001 PM 22954959 ER PT J AU Zadeh, S Wiener, L Pao, M AF Zadeh, Sima Wiener, Lori Pao, Maryland TI MY CHOICE, MY VOICE: END OF LIFE PLANNING WITH ADOLESCENTS AND YOUNG ADULTS SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract ID PALLIATIVE CARE; CHILDREN C1 [Zadeh, Sima; Wiener, Lori] NCI, Bethesda, MD 20892 USA. [Pao, Maryland] NIMH, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1743-7555 J9 ASIA-PAC J CLIN ONCO JI Asia-Pac. J. Clin. Oncol. PD NOV PY 2012 VL 8 SU 3 SI SI MA 520 BP 258 EP 258 PG 1 WC Oncology SC Oncology GA 030CB UT WOS:000310544400118 ER PT J AU Kim, TH Jiang, HH Lim, SM Youn, YS Choi, KY Lee, S Chen, XY Byun, Y Lee, KC AF Kim, Tae Hyung Jiang, Hai Hua Lim, Sung Mook Youn, Yu Seok Choi, Ki Young Lee, Seulki Chen, Xiaoyuan Byun, Youngro Lee, Kang Choon TI Site-Specific PEGylated Exendin-4 Modified with a High Molecular Weight Trimeric PEG Reduces Steric Hindrance and Increases Type 2 Antidiabetic Therapeutic Effects SO BIOCONJUGATE CHEMISTRY LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; APOPTOSIS-INDUCING LIGAND; POLYETHYLENE-GLYCOL; SYNTHETIC EXENDIN-4; CONJUGATION; PROTEINS; DESIGN; POTENT AB The purpose of this study was to optimize an Exendin-4 (Ex4-Cys) site-specific PEGylation method with a high-molecular-weight trimeric PEG. Here, we describe the preparation of C-terminal specific PEGylated Ex4-Cys (C40-tPEG-Ex4-Cys), which was performed using cysteine and amine residue specific coupling reactions between Ex4-Cys and activated trimeric PEG. The C40-PEG-Ex4-Cys was obtained at high yields (similar to 83%) and characterized by MALDI-TOF mass spectrometry. The receptor binding affinity of C40-PEG(5K)-Ex4-Cys was 3.5-fold higher than that of N-terminal PEGylated Ex4-Cys (N-ter-PEG(5K)-Ex4-Cy5), and receptor binding by the trimeric PEG (tPEG; 23, 50 kDa) adduct was much higher than that of branched PEG (20 kDa). Furthermore, C40-tPEG(50K)-Ex4-Cys was found to have greater blood circulating t(1/2) and AUC(inf) values than native Ex4-Cys by 7.53- and 45.61-fold, respectively. Accordingly; its hypoglycemic duration was much greater at 59.2 h than that of native Ex4-Cys at 7.3 h, with a dose of 25 nM/kg. The results of this study; show that C-terminal specific PEGylation using trimeric PEG is effective when applied to Ex4-Cys and suggest that C40-tPEG(50K)-Ex4-Cys has considerable potential as a type 2 antidiabetic agent. C1 [Kim, Tae Hyung; Jiang, Hai Hua; Lim, Sung Mook; Youn, Yu Seok; Lee, Kang Choon] Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. [Choi, Ki Young; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Byun, Youngro] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. RP Lee, KC (reprint author), Sungkyunkwan Univ, Coll Pharm, 300 Chonchon Dong, Suwon 440746, South Korea. EM kcleep@skku.edu RI BYUN, YOUNG RO/D-5735-2013; CHOI, KI YOUNG/Q-7177-2016 FU Converging Research Center Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science, and Technology [2011-K000796] FX This work was supported in part by the Converging Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2011-K000796). NR 25 TC 14 Z9 15 U1 3 U2 39 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV PY 2012 VL 23 IS 11 BP 2214 EP 2220 DI 10.1021/bc300265n PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 040LV UT WOS:000311325000008 PM 23116483 ER PT J AU Lim, J Turkbey, B Bernardo, M Bryant, LH Garzoni, M Pavan, GM Nakajima, T Choyke, PL Simanek, EE Kobayashi, H AF Lim, Jongdoo Turkbey, Baris Bernardo, Marcelino Bryant, L. Henry, Jr. Garzoni, Matteo Pavan, Giovanni M. Nakajima, Takahito Choyke, Peter L. Simanek, Eric E. Kobayashi, Hisataka TI Gadolinium MRI Contrast Agents Based on Triazine Dendrimers: Relaxivity and In Vivo Pharmacokinetics SO BIOCONJUGATE CHEMISTRY LA English DT Article ID NEPHROGENIC SYSTEMIC FIBROSIS; MAGNETIC RESONANCE LYMPHANGIOGRAPHY; DRUG-DELIVERY; CAPILLARY-ELECTROPHORESIS; EFFICIENT GENERATION; MOLECULAR-DYNAMICS; AM1-BCC MODEL; FORCE-FIELD; MICE; SIZE AB Four gadolinium (Gd)-based macromolecular contrast agents, G3-(Gd-DOTA)(24), GS-(Gd-DOTA)(96), G3-(Gd-DTPA)(24), and G5-(Gd-DTPA)(96), were prepared that varied in the size of dendrimer (generation three and five), the type of chelate group (DTPA or DOTA), and the theoretical number of metalated chelates (24 and 96). Synthesis relied on a dichlorotriazine derivatized with a DOTA or DTPA. ligand that was incorporated into the dendrimer and ultimately metalated with Gd ions. Paramagnetic characteristics and in vivo pharmacokinetics of all four contrast agents were investigated. The DOTA-containing agents, G3-(Gd-DOTA)(24) and GS-(Gd-DOTA)(96), demonstrated exceptionally high r1 relaxivity values at off-peak magnetic fields. Additionally, G5-(Gd-DOTA)(96) showed increased r1 relaxivity in serum compared to that in PBS, which was consistent with in vivo images. While G3-(Gd-DOTA)(24) and G3-(Gd-DTPA)(24) were rapidly excreted into the urine, GS-(Gd-DOTA)(96) and GS-(Gd-DTPA)(96) did not clear as quickly through the kidneys. Molecular simulation of the DOTA-containing dendrimers suggests that a majority of the metalated ligands are accessible to water. These triazine dendrimer-based MRI contrast agents exhibit several promising features such as high in vivo r1 relaxivity, desirable pharmacokinetics, and well-defined structure. C1 [Turkbey, Baris; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lim, Jongdoo; Simanek, Eric E.] Texas Christian Univ, Dept Chem, Ft Worth, TX 76129 USA. [Bernardo, Marcelino] NCI, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA. [Bryant, L. Henry, Jr.] NIH, Lab Diagnost Radiol Res Radiol & Imaging Sci, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Garzoni, Matteo; Pavan, Giovanni M.] Univ Appl Sci So Switzerland, Dept Innovat Technol, CH-6928 Galleria 2, Manno, Switzerland. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov RI Pavan, Giovanni M./E-7474-2011 OI Pavan, Giovanni M./0000-0002-3473-8471 FU National Institutes of Health [GM 65460]; Robert A. Welch Foundation [A-0008]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and the National Institutes of Health (GM 65460 to EES) and the Robert A. Welch Foundation (EES, A-0008). NR 40 TC 22 Z9 23 U1 6 U2 57 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV PY 2012 VL 23 IS 11 BP 2291 EP 2299 DI 10.1021/bc300461r PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 040LV UT WOS:000311325000016 PM 23035964 ER PT J AU Palmer, JM Lee, SJ Chai, XY Storer, BE Flowers, MED Schultz, KR Inamoto, Y Cutler, C Pidala, J Arora, M Jacobsohn, DA Carpenter, PA Pavletic, SZ Martin, PJ AF Palmer, Jeanne M. Lee, Stephanie J. Chai, Xiaoyu Storer, Barry E. Flowers, Mary E. D. Schultz, Kirk R. Inamoto, Yoshihiro Cutler, Corey Pidala, Joseph Arora, Mukta Jacobsohn, David A. Carpenter, Paul A. Pavletic, Steven Z. Martin, Paul J. TI Poor Agreement between Clinician Response Ratings and Calculated Response Measures in Patients with Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic cell transplantation; Chronic graft-versus-host disease; Response assessment ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; THERAPEUTIC RESPONSE; CHRONIC GVHD; PHASE-II; CRITERIA; RELIABILITY; TRIALS AB In 2005, a National Institutes of Health consensus conference was held to refine methods for research in patients with chronic graft-versus-host disease, including proposed objective response measures and a provisional algorithm for calculating organ-specific and overall response. In this study, we used weighted kappa statistics to evaluate the level of agreement between clinician response ratings and calculated response categories in patients with chronic graft-versus-host disease. The study included 290 patients who had paired enrollment and follow-up visits. Based on a set of objective measures, 37% of the patients had an overall complete or partial response, whereas clinicians reported an overall complete or partial response rate of 71% (slight to fair agreement, weighted kappa 0.20). Agreement rates between calculated organ-specific responses and clinician-reported changes in skin, mouth, and eyes were fair to moderate (weighted kappa, 0.28-0.54). We conclude that for both overall and organ-specific comparisons, clinician response ratings did not agree well with calculated response categories. Possible reasons for this discrepancy include a high clinical sensitivity for detecting response, a clinical predisposition to recognize selective improvements as overall response, the large change in objective measures proposed to define response, and the high incidence of progressive disease based on new manifestations. Conclusions from prior literature reporting high overall response rates based on clinician judgment would not be supported if the provisional algorithm had been applied to calculate response. Our analysis also highlights the need to define an overall response measure that incorporates both patient-reported and objective measures and accurately reflects the outcome in patients with a mixed response in which one organ or site improves, whereas another shows new involvement. Biol Blood Marrow Transplant 18: 1649-1655 (2012) (C) 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. C1 [Palmer, Jeanne M.] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Lee, Stephanie J.; Chai, Xiaoyu; Storer, Barry E.; Flowers, Mary E. D.; Inamoto, Yoshihiro; Carpenter, Paul A.; Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Schultz, Kirk R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Jacobsohn, David A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA. RP Palmer, JM (reprint author), Med Coll Wisconsin, Div Hematol & Oncol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM sjlee@fhcrc.org FU NIH/NCI [CA 118953] FX This work was supported by grant CA 118953 (PI: Lee, SJ) NIH/NCI. NR 21 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2012 VL 18 IS 11 BP 1649 EP 1655 DI 10.1016/j.bbmt.2012.05.005 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 029KF UT WOS:000310493700006 PM 22691695 ER PT J AU Ribeiro, LA Roessler, E Hu, P Pineda-Alvarez, DE Zhou, N Jones, M Chandrasekharappa, S Richieri-Costa, A Muenke, M AF Ribeiro, Lucilene A. Roessler, Erich Hu, Ping Pineda-Alvarez, Daniel E. Zhou, Nan Jones, MaryPat Chandrasekharappa, Settara Richieri-Costa, Antonio Muenke, Maximilian TI Comparison of mutation findings in ZIC2 between microform and classical holoprosencephaly in a Brazilian cohort SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE ZIC2; mutation; alanine tract expansion or contraction; poly-histidine tract expansion; holoprosencephaly; polymorphism ID NEURAL-TUBE DEFECTS; LOSS-OF-FUNCTION; POLYHISTIDINE TRACT POLYMORPHISM; MOLECULAR EVALUATION; GENE; PHENOTYPE; TGIF; SIX3; ASSOCIATION; DISEASE AB BACKGROUND Holoprosencephaly is the most frequent congenital malformation of the forebrain in humans. It is anatomically classified by the relative degree of abnormal formation and separation of the developing central nervous system. Mutations of ZIC2 are the second most common heterozygous variations detected in holoprosencephaly (HPE) patients. Mutations in most known HPE genes typically result in variable phenotypes that rage from classic alobar HPE to microforms represented by hypotelorism, solitary central maxillary incisor (SCMI), and cleft lip/palate, among others. Patients with HPE owing to ZIC2 mutations have recently been described by a distinct phenotype compared with mutations in other HPE causative genes. METHODS We report the comparison of ZIC2 molecular findings by Sanger bidirectional DNA sequencing and ad hoc genotyping in a cohort of 105 Brazilian patients within the clinical spectrum of HPE, including classic and microform groups. RESULTS We detected a total of five variants in the ZIC2 gene: a common histidine tract expansion c.716_718dup (p.His239dup), a rare c.1377_1391del_homozygous (p.Ala466_470del, or Ala 15 to 10 contraction), a novel intronic c.1239+18G>A variant, a novel frameshift c.1215dupC (p.Ser406Glnfs*11), and a c.1401_1406dup (p.Ala469_470dup, or alanine tract expansion to 17 residues). CONCLUSIONS From these patients, only the latter two mutations found in classic HPE are likely to be medically significant. In contrast, variants detected in the microform group are not likely to be pathogenic. We show conclusively that the histidine tract expansion is a polymorphic alteration that demonstrates considerable differences in allele frequencies across different ethnic groups. Therefore, careful population studies of rare variants can improve genotype-phenotype correlations. Birth Defects Research (Part A) 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Roessler, Erich; Hu, Ping; Pineda-Alvarez, Daniel E.; Zhou, Nan; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Ribeiro, Lucilene A.; Richieri-Costa, Antonio] Univ Sao Paolo, Hosp Rehabil & Craniofacial Anomalies, Mol Genet Lab, Bauru, Sao Paolo, Brazil. [Ribeiro, Lucilene A.; Richieri-Costa, Antonio] Univ Sao Paolo, Hosp Rehabil & Craniofacial Anomalies, Clin Genet Serv, Bauru, Sao Paolo, Brazil. [Jones, MaryPat; Chandrasekharappa, Settara] NHGRI, Genome Technol Branch, NIH, Bethesda, MD USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,Bldg 35,Room 1B403, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov RI Richieri-Costa, Antonio/B-2514-2013; Ribeiro-Bicudo, Lucilene/G-9528-2013 FU Division of Intramural Research, National Human Genome Research, the National Institutes of Health FX Supported by funds from the Division of Intramural Research, National Human Genome Research, the National Institutes of Health. NR 46 TC 3 Z9 3 U1 0 U2 7 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 NOV PY 2012 VL 94 IS 11 BP 912 EP 917 DI 10.1002/bdra.23047 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 039HD UT WOS:000311234400008 PM 22847929 ER PT J AU Zibly, Z Schlaff, CD Gordon, I Munasinghe, J Camphausen, KA AF Zibly, Zion Schlaff, Cody D. Gordon, Ira Munasinghe, Jeeva Camphausen, Kevin A. TI A novel rodent model of spinal metastasis and spinal cord compression SO BMC NEUROSCIENCE LA English DT Article DE Spinal metastasis; Spinal cord compression; Animal model; Rat ID BONE; NEOPLASMS; CANCER AB Background: Spinal cord metastatic lesions affect a high number of cancer patients usually resulting in spinal cord compression syndrome. A major obstacle in the research of spinal metastatic disease is the lack of a simple reproducible animal model that mimics the natural course of the disease. In this study, we present a highly reproducible rodent model that can be used for different types of cancers while mimicking the natural course of human metastatic spinal cord compression syndrome. Results: All sixteen Fisher 344 rats survived the dorsal approach intraosseous implantation of CRL-1666 adenocarcinoma cells and both rats survived the sham control surgery. By Day 13 functional analysis via the modified Basso-Beattie-Bresnahan (BBB) locomotor rating scale showed significant decrease in motor function; median functional score was 3 for the tumor group (p = 0.0011). Median time to paresis was 8.7 days post-operatively. MR imaging illustrated repeated and consistent tumor formation, furthermore, onset of neurological sequale was the result of tumor formation and cord compression as confirmed by histological examination. Conclusions: Analysis of these findings demonstrates a repeatable and consistent tumor growth model for cancer spinal metastases in rats. This novel rat model requires a less intricate surgical procedure, and as a result minimizes procedure time while subsequently increasing consistency. Therefore, this model allows for the preclinical evaluation of therapeutics for spinal metastases that more closely replicates physiological findings. C1 [Zibly, Zion; Schlaff, Cody D.; Gordon, Ira; Camphausen, Kevin A.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Zibly, Zion] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Munasinghe, Jeeva] Natl Inst Neurol Disorders & Stroke, Cell & Canc Biol Branch, NCI, NIH, Bethesda, MD 20892 USA. RP Zibly, Z (reprint author), NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM zzibly@yahoo.com FU Intramural Research Program of the National Institutes of Health, National Cancer Institute FX Financial support: This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 10 TC 2 Z9 4 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD NOV 1 PY 2012 VL 13 AR 137 DI 10.1186/1471-2202-13-137 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 045GB UT WOS:000311682300001 PM 23116234 ER PT J AU Turkbey, EB Nacif, MS Noureldin, RA Sibley, CT Liu, S Lima, JAC Bluemke, DA AF Turkbey, E. B. Nacif, M. S. Noureldin, R. A. Sibley, C. T. Liu, S. Lima, J. A. C. Bluemke, D. A. TI Differentiation of myocardial scar from potential pitfalls and artefacts in delayed enhancement MRI SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID SENSITIVE INVERSION-RECOVERY; STATE FREE PRECESSION; INFARCTION; VIABILITY; 3D AB Delayed enhancement cardiac magnetic resonance (DE-CMR) imaging is used increasingly to identify and quantify focal myocardial scar. Our objective is to describe factors used in the interpretation of DE-CMR images and to highlight potential pitfalls and artefacts that mimic myocardial scar. Inversion recovery gradient recalled echo sequence is commonly accepted as the standard of reference for DE-CMR. There are also alternative sequences that can be performed in a single breath-hold or with free breathing. Radiologists need to be aware of factors affecting image quality, and potential pitfalls and artefacts that may generate focal hyperintense areas that mimic myocardial scar. C1 [Turkbey, E. B.; Nacif, M. S.; Noureldin, R. A.; Sibley, C. T.; Liu, S.; Bluemke, D. A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Turkbey, E. B.; Nacif, M. S.; Lima, J. A. C.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Nacif, M. S.; Lima, J. A. C.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. [Sibley, C. T.; Liu, S.; Bluemke, D. A.] Natl Inst Biomed Imaging & Bioengn, NIH Clin Ctr, Bethesda, MD USA. RP Bluemke, DA (reprint author), NIH, Ctr Clin, 9000 Rockville Pike,Bldg 10,Room 1C355, Bethesda, MD 20892 USA. EM bluemked@nih.gov RI Sibley, Christopher/C-9900-2013; OI Bluemke, David/0000-0002-8323-8086 NR 20 TC 3 Z9 3 U1 0 U2 4 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD NOV PY 2012 VL 85 IS 1019 BP E1145 EP E1154 DI 10.1259/bjr/25893477 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 044EY UT WOS:000311603400025 PM 23091294 ER PT J AU Gong, J Hutter, C Baron, JA Berndt, S Caan, B Campbell, PT Casey, G Chan, AT Cotterchio, M Fuchs, CS Gallinger, S Giovannucci, E Harrison, T Hayes, R Hsu, L Jiao, S Lin, Y Lindor, NM Newcomb, P Pflugeisen, B Phipps, AI Rohan, T Schoen, R Seminara, D Slattery, ML Stelling, D Thomas, F Warnick, G White, E Potter, J Peters, U AF Gong, Jian Hutter, Carolyn Baron, John A. Berndt, Sonja Caan, Bette Campbell, Peter T. Casey, Graham Chan, Andrew T. Cotterchio, Michelle Fuchs, Charles S. Gallinger, Steven Giovannucci, Edward Harrison, Tabitha Hayes, Richard Hsu, Li Jiao, Shuo Lin, Yi Lindor, Noralane M. Newcomb, Polly Pflugeisen, Bethann Phipps, Amanda I. Rohan, Thomas Schoen, Robert Seminara, Daniela Slattery, Martha L. Stelling, Deanna Thomas, Fridtjof Warnick, Greg White, Emily Potter, John Peters, Ulrike TI A Pooled Analysis of Smoking and Colorectal Cancer: Timing of Exposure and Interactions with Environmental Factors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CIGARETTE-SMOKING; COLON-CANCER; UNITED-STATES; TOBACCO USE; RESPONSE RELATIONSHIPS; ALCOHOL-CONSUMPTION; PROSPECTIVE COHORT; LUNG-CANCER; FOLLOW-UP; RISK AB Background: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association. Methods: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors. Results: Current smokers [OR, 1.26; 95% confidence interval (Cl), 1.11-1.43] and former smokers (OR, 1.18; 95% CI, 1.09-1.27), relative to never smokers, showed higher risks of CRC. Former smokers remained at higher CRC risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: The excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer but not until about 20 years post-quitting for distal colon cancer. Furthermore, we observed borderline statistically significant additive interactions between smoking status and body mass index [BMI; relative excess risk due to interaction (RERI]), 0.15; 95% CI, -0.01 to 0.31; P = 0.06] and significant additive interaction between smoking status and fruit consumption (RERI, 0.16; 95% CI, 0.01-0.30; P = 0.04). Conclusion: CRC risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking. Impact: These results contribute to a better understanding of the mechanisms through which smoking impacts CRC etiology. Cancer Epidemiol Biomarkers Prev; 21(11); 1974-85. (C)2012 AACR. C1 [Gong, Jian; Hutter, Carolyn; Harrison, Tabitha; Hsu, Li; Jiao, Shuo; Lin, Yi; Newcomb, Polly; Pflugeisen, Bethann; Phipps, Amanda I.; Stelling, Deanna; Warnick, Greg; White, Emily; Potter, John; Peters, Ulrike] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Hutter, Carolyn; Newcomb, Polly; Phipps, Amanda I.; White, Emily; Potter, John; Peters, Ulrike] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98109 USA. [Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98109 USA. [Berndt, Sonja] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Seminara, Daniela] NCI, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA. [Caan, Bette] Kaiser Permanente, Div Res, Med Care Program, Oakland, CA USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Casey, Graham] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Cotterchio, Michelle] Canc Care Ontario, Populat Studies & Surveillance, Toronto, ON, Canada. [Gallinger, Steven] Toronto Gen Hosp, Div Gen Surg, Univ Hlth Network, Toronto, ON, Canada. [Baron, John A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. [Baron, John A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. [Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Hayes, Richard] NYU, Dept Environm Med, Div Epidemiol, Sch Med, New York, NY 10016 USA. [Schoen, Robert] Univ Pittsburgh, Dept Epidemiol, Med Ctr, Pittsburgh, PA 15261 USA. [Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Rohan, Thomas] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Potter, John] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA. RP Peters, U (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM upeters@fhcrc.org RI Gallinger, Steven/E-4575-2013; OI Potter, John/0000-0001-5439-1500 FU National Cancer Institute, NIH under RFA [CA-95-011]; Australasian Colorectal Cancer Family Registry [U01 CA097735]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01 CA074800]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Ontario Research Fund; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; NIH [P01 CA 055075, R01 137178, P50 CA 127003]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, U.S. Department of Health and Human Services; Intramural Research Program of the National Cancer Institute; NIH from the National Cancer Institute and Office of Dietary Supplements [K05 CA154337]; National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX CCFR was supported by the National Cancer Institute, NIH under RFA # CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s.; The following Colon CFR centers contributed data to the manuscript and were supported by the following sources: Australasian Colorectal Cancer Family Registry (U01 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Seattle Colorectal Cancer Family Registry (U01 CA074794), and the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783). The OFCCR was also supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute.; HPFS is supported by the NIH (P01 CA 055075, R01 137178, and P50 CA 127003).; PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, U.S. Department of Health and Human Services. Control samples were derived from the PLCO Screening Trial, which was supported by the Intramural Research Program of the National Cancer Institute.; VITAL is supported in part by the NIH (K05 CA154337) from the National Cancer Institute and Office of Dietary Supplements.; The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 61 TC 18 Z9 18 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2012 VL 21 IS 11 BP 1974 EP 1985 DI 10.1158/1055-9965.EPI-12-0692 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 035GP UT WOS:000310931700010 PM 23001243 ER PT J AU Wu, LC Kleinerman, RA Curtis, RE Savage, SA de Gonzalez, AB AF Wu, Lindsey C. Kleinerman, Ruth A. Curtis, Rochelle E. Savage, Sharon A. de Gonzalez, Amy Berrington TI Patterns of Bone Sarcomas as a Second Malignancy in Relation to Radiotherapy in Adulthood and Histologic Type SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ATOMIC-BOMB SURVIVORS; CHILDHOOD-CANCER; SOFT-TISSUE; OSTEOSARCOMA; COHORT; RISK; AGE; CHEMOTHERAPY; NEOPLASMS; EXPOSURE AB Background: Radiotherapy decreases cancer mortality, but is associated with an increased incidence of second primary cancers, including osteosarcomas, especially after exposure in childhood. It remains uncertain whether radiation is related to other histologic types of bone sarcomas such as chondrosarcomas that are more common in adulthood. Methods: Using data from 1973 to 2008 Surveillance Epidemiology and End Results registries, we evaluated long-term risk of bone cancer in 1,284,537 adult 5-year cancer survivors. We used standardized incidence ratios (SIR) to compare second bone sarcoma rates to the general population for each histologic type. We also used multivariate Poisson regression to estimate the relative risk (RR) associated with radiotherapy for the most common subtypes, osteosarcoma and chondrosarcoma. Results: By the end of 2008, 159 second bone sarcomas were reported. Compared with the general population, the risk of developing any bone sarcoma was increased by 25% in patients with no history of radiotherapy [Observed (0) = 89, SIR = 1.25(1.00-1.54)] and by 257% in patients with a history of radiotherapy [O = 70, SIR = 3.57 (2.78-4.50)]. For each histologic subtype, SIRs were higher among patients who had previously received radiotherapy than among those who had not. The RR for radiotherapy for osteosarcorna (n = 63) was 5.08 (3.05-8.59) and for chondrosarcoma = 69) was 1.54 (0.88-2.59), and these risks were even greater for second sarcomas that arose in the radiotherapy field used to treat the first cancer [osteosarcoma, RR = 10.35 (4.96-23.66); chondrosarcoma RR = 8.21 (2.09-39.89)]. Conclusions: Our findings provide the first evidence of a likely association between radiation exposure and chondrosarcoma. Impact: These results further our understanding of radiotherapy-related cancer risks and will potentially direct practices in long-term surveillance of cancer survivors. Cancer Epidemiol Biomarkers Prev; 21(11); 1993-9. (C)2012 AACR. C1 [Wu, Lindsey C.] NCI, NIH, HHMI, Rockville, MD 20852 USA. [Wu, Lindsey C.; Kleinerman, Ruth A.; Curtis, Rochelle E.; de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, NIH, Rockville, MD 20852 USA. [Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Wu, Lindsey C.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Wu, LC (reprint author), NCI, NIH, HHMI, 6120 Execut Blvd, Rockville, MD 20852 USA. EM lindsey.c.wu@gmail.com RI Savage, Sharon/B-9747-2015; OI Savage, Sharon/0000-0001-6006-0740; Kleinerman, Ruth/0000-0001-7415-2478 FU Howard Hughes Medical Institute Research Scholar Program; intramural research program of the NIH FX This work was supported by Howard Hughes Medical Institute Research Scholar Program (to L. Wu). This research was also supported in part by the intramural research program of the NIH (R. Kleinerman, R. Curtis, S. Savage, and A. Berrington). NR 33 TC 4 Z9 5 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2012 VL 21 IS 11 BP 1993 EP 1999 DI 10.1158/1055-9965.EPI-12-0810 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 035GP UT WOS:000310931700012 PM 22964827 ER PT J AU Huang, WY Su, LJ Hayes, RB Moore, LE Katki, HA Berndt, SI Weissfeld, JL Yegnasubramanian, S Purdue, MP AF Huang, Wen-Yi Su, L. Joseph Hayes, Richard B. Moore, Lee E. Katki, Hormuzd A. Berndt, Sonja I. Weissfeld, Joel L. Yegnasubramanian, Srinivasan Purdue, Mark P. TI Prospective Study of Genomic Hypomethylation of Leukocyte DNA and Colorectal Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOLIC-ACID; LINE-1 HYPOMETHYLATION; MICROSATELLITE INSTABILITY; FOLATE INTAKE; METHYLATION; ADENOMA; TRIAL; DEFICIENCY; PREVENTION; BIOMARKER AB Background: Systematic genome-wide reductions of methylated cytosine (5-mC) levels have been observed in colorectal cancer tissue and are suspected to play a role in carcinogenesis, possibly as a consequence of inadequate folate intake. Reduced 5-mC levels in peripheral blood leukocytes have been associated with increased risk of colorectal cancer and adenoma in cross-sectional studies. Methods: To minimize disease- and/or treatment-related effects, we studied leukocyte 5-mC levels in prospectively collected blood specimens of 370 cases and 493 controls who were cancer-free at blood collection from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Leukocyte 5-mC level was determined by a high-pressure liquid chromatography (HPLC)/tandem mass spectrometry method and expressed as the relative amount of methyl to total cytosine residues, or %5-mC. We estimated the association between colorectal cancer risk and %5-mC categories by computing ORs and 95% confidence intervals (CI) through logistic regression modeling. Results: We observed no dose-dependent association between colorectal cancer and%5-mC categories (lowest vs. highest tertile: OR, 1.14; 95% CI, 0.80-1.63; P-trend = 0.51). However, among subjects whose 5-mC levels were at the highest tertile, we observed an inverse association between natural folate intake and colorectal cancer (highest tertile of natural folate vs. lowest: OR, 0.35; 95% CI, 0.17-0.71; P-trend = 0.003; P-interaction = 0.003). Conclusions: This prospective investigation show no clear association between leukocyte 5-mC level and subsequent colorectal cancer risk but a suggestive risk modification between 5-mC level and natural folate intake. Impact: Adequate folate status may protect against colorectal carcinogenesis through mechanisms involving adequate DNA methylation in the genome. Cancer Epidemiol Biomarkers Prev; 21(11); 2014-21. (C)2012 AACR. C1 [Huang, Wen-Yi; Moore, Lee E.; Katki, Hormuzd A.; Berndt, Sonja I.; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Su, L. Joseph] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA. [Weissfeld, Joel L.] Univ Pittsburgh, Dept Epidemiol, Inst Canc, Pittsburgh, PA 15261 USA. [Yegnasubramanian, Srinivasan] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Huang, WY (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8110,MSC 7240, Bethesda, MD 20892 USA. EM huangw@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Purdue, Mark/C-9228-2016; OI Purdue, Mark/0000-0003-1177-3108; Hayes, Richard/0000-0002-0918-661X FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, Department of Health and Human Services FX This research was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, Department of Health and Human Services. NR 32 TC 11 Z9 11 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2012 VL 21 IS 11 BP 2014 EP 2021 DI 10.1158/1055-9965.EPI-12-0700-T PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 035GP UT WOS:000310931700015 PM 23001241 ER PT J AU Cook, MB Kamangar, F Weinstein, SJ Albanes, D Virtamo, J Taylor, PR Abnet, CC Wood, RJ Petty, G Cross, AJ Dawsey, SM AF Cook, Michael B. Kamangar, Farin Weinstein, Stephanie J. Albanes, Demetrius Virtamo, Jarmo Taylor, Philip R. Abnet, Christian C. Wood, Richard J. Petty, Gayle Cross, Amanda J. Dawsey, Sanford M. TI Iron in Relation to Gastric Cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HELICOBACTER-PYLORI; SERUM FERRITIN; STOMACH-CANCER; CARDIA CANCER; RISK; ADENOCARCINOMAS; DEFICIENCY; JAPANESE; STORES; CARCINOGENESIS AB Background: Iron is an essential micronutrient that can have carcinogenic effects when at high or low concentrations. Previous studies of iron in relation to gastric cancer have not assessed subtype-specific relationships. We used the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study to assess whether iron metrics were associated with gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Methods: We selected 341 incident gastric cancer cases (86 cardia, 172 noncardia, and 83 nonspecified), accrued during 22 years of follow-up, and 341 individually matched controls. We measured prediagnostic serum iron, ferritin, unsaturated iron binding capacity, and C-reactive protein. Total iron-binding capacity (TIBC) and transferrin saturation were estimated from these metrics. Dietary iron exposures were estimated from a food frequency questionnaire. Multivariable logistic regression was used for analysis. Results: Serum iron metrics were not associated with GCC, except for a potential "n"-shaped relationship with TIBC (global P = 0.038). GNCC was inversely associated with serum ferritin (global P = 0.024), serum iron (global P = 0.060) and, possibly, transferrin saturation. TIBC appeared to share a "u"-shaped relationship with GNCC (global P = 0.033). Dietary iron exposures were not associated with either subsite. Adjustment for Helicobacter pylori and gastric atrophy had little effect on observed associations. Conclusions: We found little evidence for the involvement of iron exposure in the pathogenesis of GCC. GNCC was associated with an iron profile similar to that of iron deficiency. Impact: Our findings indicate that inverse associations between iron metrics and gastric cancer are driven by associations with GNCC. Further elucidation of potential mechanisms is warranted. Cancer Epidemiol Biomarkers Prev; 21(11); 2033-42. (C)2012 AACR. C1 [Cook, Michael B.; Kamangar, Farin; Weinstein, Stephanie J.; Albanes, Demetrius; Taylor, Philip R.; Abnet, Christian C.; Cross, Amanda J.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. [Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21239 USA. [Wood, Richard J.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Boston, MA 02125 USA. [Wood, Richard J.; Petty, Gayle] Tufts Univ, Nutr Evaluat Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Cook, MB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS Suite 550,Room 5014, Rockville, MD 20852 USA. EM michael.cook@nih.gov RI Cook, Michael/A-5641-2009; Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015 OI Cook, Michael/0000-0002-0533-7302; Abnet, Christian/0000-0002-3008-7843 FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services FX Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services. NR 41 TC 8 Z9 8 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2012 VL 21 IS 11 BP 2033 EP 2042 DI 10.1158/1055-9965.EPI-12-0799 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 035GP UT WOS:000310931700017 PM 23001240 ER PT J AU Weaver, KE Forsythe, LP Reeve, BB Alfano, CM Rodriguez, JL Sabatino, SA Hawkins, NA Rowland, JH AF Weaver, Kathryn E. Forsythe, Laura P. Reeve, Bryce B. Alfano, Catherine M. Rodriguez, Juan L. Sabatino, Susan A. Hawkins, Nikki A. Rowland, Julia H. TI Mental and Physical Health-Related Quality of Life among US Cancer Survivors: Population Estimates from the 2010 National Health Interview Survey SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER; PSYCHOLOGICAL DISTRESS; IMPACT; INTERVENTIONS; METAANALYSIS; DISPARITIES; BEHAVIORS; OUTCOMES; SCORES; ADULTS AB Background: Despite extensive data on health-related quality of life (HRQOL) among cancer survivors, we do not yet have an estimate of the percentage of survivors with poor mental and physical HRQOL compared with population norms. HRQOL population means for adult-onset cancer survivors of all ages and across the survivorship trajectory also have not been published. Methods: Survivors (N = 1,822) and adults with no cancer history (N = 24,804) were identified from the 2010 National Health Interview Survey. The PROMIS (R) Global Health Scale was used to assess HRQOL. Poor HRQOL was defined as 1 SD or more below the PROMIS (R) population norm. Results: Poor physical and mental HRQOL were reported by 24.5% and 10.1% of survivors, respectively, compared with 10.2% and 5.9% of adults without cancer (both P < 0.0001). This represents a population of approximately 3.3 million and 1.4 million U.S. survivors with poor physical and mental HRQOL. Adjusted mean mental and physical HRQOL scores were similar for breast, prostate, and melanoma survivors compared with adults without cancer. Survivors of cervical, colorectal, hematologic, short-survival, and other cancers had worse physical HRQOL; cervical and short-survival cancer survivors reported worse mental HROOL. Conclusion: These data elucidate the burden of cancer diagnosis and treatment among U.S. survivors and can be used to monitor the impact of national efforts to improve survivorship care and outcomes. Impact: We present novel data on the number of U.S. survivors with poor HRQOL. Interventions for high-risk groups that can be easily implemented are needed to improve survivor health at a population level. Cancer Epidemiol Biomarkers Prev; 21(11); 2108-17. (C) 2012 AACR. C1 [Weaver, Kathryn E.] Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC 27157 USA. [Forsythe, Laura P.; Alfano, Catherine M.; Rowland, Julia H.] NCI, Off Canc Survivorship, NIH, DHHS, Bethesda, MD 20892 USA. [Forsythe, Laura P.] NCI, Ctr Canc Training, NIH, DHHS, Bethesda, MD 20892 USA. [Reeve, Bryce B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Rodriguez, Juan L.; Sabatino, Susan A.; Hawkins, Nikki A.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. RP Weaver, KE (reprint author), Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM keweaver@wakehealth.edu FU National Cancer Institute at the NIH [HHSN 261201100189P] FX This work was supported by the National Cancer Institute at the NIH. Contract no. HHSN 261201100189P. NR 36 TC 62 Z9 63 U1 6 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2012 VL 21 IS 11 BP 2108 EP 2117 DI 10.1158/1055-9965.EPI-12-0740 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 035GP UT WOS:000310931700026 PM 23112268 ER PT J AU Benicky, J Hafko, R Sanchez-Lemus, E Aguilera, G Saavedra, JM AF Benicky, Julius Hafko, Roman Sanchez-Lemus, Enrique Aguilera, Greti Saavedra, Juan M. TI Six Commercially Available Angiotensin II AT(1) Receptor Antibodies are Non-specific SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE GPCR receptor antibodies; Antibody characterization; Angiotensin II receptors; Renin-angiotensin System; AT(1) receptor immunocytochemistry; AT(1) receptor antibodies; AT(1A) receptor knock-out ID BLOOD-PRESSURE REGULATION; HYPOTHALAMIC CELL-LINE; ADRENERGIC-RECEPTORS; DEFICIENT MICE; RAT-BRAIN; EXPRESSION; SPECIFICITY; SUBTYPES; MOUSE; GENE AB Commercially available Angiotensin II AT(1) receptor antibodies are widely employed for receptor localization and quantification, but they have not been adequately validated. In this study, six commercially available AT(1) receptor antibodies were characterized by established criteria: sc-1173 and sc-579 from Santa Cruz Biotechnology, Inc., AAR-011 from Alomone Labs, Ltd., AB15552 from Millipore, and ab18801 and ab9391 from Abcam. The immunostaining patterns observed were different for every antibody tested, and were unrelated to the presence or absence of AT(1) receptors. The antibodies detected a 43 kDa band in western blots, corresponding to the predicted size of the native AT(1) receptor. However, identical bands were observed in wild-type mice and in AT(1A) knock-out mice not expressing the target protein. Moreover, immunoreactivity detected in rat hypothalamic 4B cells not expressing AT(1) receptors or transfected with AT(1A) receptor construct was identical, as revealed by western blotting and immunocytochemistry in cultured 4B cells. Additional prominent immunoreactive bands above and below 43 kDa were observed by western blotting in extracts from tissues of AT(1A) knock-out and wild-type mice and in 4B cells with or without AT(1) receptor expression. In all cases, the patterns of immunoreactivity were independent of the AT(1) receptor expression and different for each antibody studied. We conclude that, in our experimental setup, none of the commercially available AT(1) receptor antibodies tested met the criteria for specificity and that competitive radioligand binding remains the only reliable approach to study AT(1) receptor physiology in the absence of full antibody characterization. C1 [Benicky, Julius; Hafko, Roman; Sanchez-Lemus, Enrique; Saavedra, Juan M.] NIMH, Pharmacol Sect, DIRP, NIH, Bethesda, MD 20892 USA. [Aguilera, Greti] NICHD, Sect Endocrine Physiol, PDEGEN, NIH,CRC, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, DIRP, NIH, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. EM Saavedrj@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 39 TC 33 Z9 33 U1 0 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD NOV PY 2012 VL 32 IS 8 BP 1353 EP 1365 DI 10.1007/s10571-012-9862-y PG 13 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 045AR UT WOS:000311666900013 PM 22843099 ER PT J AU Zakharov, AV Lagunin, AA Filimonov, DA Poroikov, VV AF Zakharov, Alexey V. Lagunin, Alexey A. Filimonov, Dmitry A. Poroikov, Vladimir V. TI Quantitative Prediction of Antitarget Interaction Profiles for Chemical Compounds SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ACUTE TOXICITY; MODELS; TARGETS AB The evaluation of possible interactions between chemical compounds and antitarget proteins is an important task of the research and development process. Here, we describe the development and validation of QSAR models for the prediction of antitarget end-points, created on the basis of multilevel and quantitative neighborhoods of atom descriptors and self-consistent regression. Data on 4000 chemical compounds interacting with 18 antitarget proteins (13 receptors, 2 enzymes, and 3 transporters) were used to model 32 sets of end-points (IC50, K-i, and K-act). Each set was randomly divided into training and test sets in a ratio of 80% to 20%, respectively. The test sets were used for external validation of QSAR models created on the basis of the training sets. The coverage of prediction for all test sets exceeded 95%, and for half of the test sets, it was 100%. The accuracy of prediction for 29 of the end-points, based on the external test sets, was typically in the range of R-test(2) = 0.6-0.9; three tests sets had lower R-test(2) values, specifically 0.55-0.6. The proposed approach showed a reasonable accuracy of prediction for 91% of the antitarget end-points and high coverage for all external test sets. On the basis of the created models, we have developed a freely available online service for in silica prediction of 32 antitarget end-points: http://www.pharmaexpert.ru/GUSAR/antitargets.html. C1 [Zakharov, Alexey V.] NCI, NIH, Frederick, MD 21702 USA. [Zakharov, Alexey V.; Lagunin, Alexey A.; Filimonov, Dmitry A.; Poroikov, Vladimir V.] Russian Acad Med Sci, Inst Biomed Chem, Moscow 119121, Russia. RP Zakharov, AV (reprint author), NCI, NIH, 376 Boyles St, Frederick, MD 21702 USA. EM alexey.zakharov@nih.gov RI Poroikov, Vladimir/O-2769-2013; Lagunin, Alexey/G-3745-2010 OI Poroikov, Vladimir/0000-0001-7937-2621; Lagunin, Alexey/0000-0003-1757-8004 FU RFBR [12-07-00597]; RFBR/NIH [12-04-91445/RUBI-31081-MO-12] FX This work is partially supported by RFBR grant number 12-07-00597 (to D.A.F. and A.A.L.) and RFBR/NIH grant number 12-04-91445/RUBI-31081-MO-12 (to V.V.P.). NR 26 TC 21 Z9 23 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 2012 VL 25 IS 11 BP 2378 EP 2385 DI 10.1021/tx300247r PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 038KO UT WOS:000311173800010 PM 23078046 ER PT J AU Wang, L Song, YQ Manson, JE Pilz, S Marz, W Michaelsson, K Lundqvist, A Jassal, SK Barrett-Connor, E Zhang, CL Eaton, CB May, HT Anderson, JL Sesso, HD AF Wang, Lu Song, Yiqing Manson, JoAnn E. Pilz, Stefan Maerz, Winfried Michaelsson, Karl Lundqvist, Annamari Jassal, Simerjot K. Barrett-Connor, Elizabeth Zhang, Cuilin Eaton, Charles B. May, Heidi T. Anderson, Jeffrey L. Sesso, Howard D. TI Circulating 25-Hydroxy-Vitamin D and Risk of Cardiovascular Disease A Meta-Analysis of Prospective Studies SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE 25-hydroxy-vitamin D; cardiovascular disease; meta-analysis; prospective study ID VITAMIN-D DEFICIENCY; SERUM 25-HYDROXYVITAMIN D; RENIN-ANGIOTENSIN SYSTEM; SUDDEN CARDIAC DEATH; ALL-CAUSE MORTALITY; DOSE-RESPONSE DATA; PARATHYROID-HORMONE; MYOCARDIAL-INFARCTION; CORONARY-ANGIOGRAPHY; GENERAL-POPULATION AB Background-Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear. Methods and Results-We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6123 CVD cases in 65 994 participants were included for a meta-analysis. In a comparison of the lowest with the highest 25(OH)-vitamin D categories, the pooled relative risk was 1.52 (95% confidence interval, 1.30-1.77) for total CVD, 1.42 (95% confidence interval, 1.19-1.71) for CVD mortality, 1.38 (95% confidence interval, 1.21-1.57) for coronary heart disease, and 1.64 (95% confidence interval, 1.27-2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and were better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose-response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below approximate to 60 nmol/L, with a relative risk of 1.03 (95% confidence interval, 1.00-1.06) per 25-nmol/L decrement in 25(OH)-vitamin D. Conclusions-This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations. (Circ Cardiovasc Qual Outcomes. 2012;5:819-829.) C1 [Wang, Lu; Song, Yiqing; Manson, JoAnn E.; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. [Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02215 USA. [Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Pilz, Stefan] Med Univ Graz, Dept Internal Med, Div Endocrinol & Metab, Graz, Austria. [Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Maerz, Winfried] Synlab Serv LLC, Synlab Acad, Mannheim, Germany. [Maerz, Winfried] Univ Mannheim, Mannheim Inst Publ Hlth, Mannheim, Germany. [Michaelsson, Karl] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden. [Lundqvist, Annamari] Natl Inst Hlth & Welfare, Helsinki, Finland. [Jassal, Simerjot K.] Univ Calif, Dept Med, Div Gen Internal Med & Geriatr, La Jolla, CA USA. [Jassal, Simerjot K.] VA San Diego Healthcare Syst, San Diego, CA USA. [Barrett-Connor, Elizabeth] Univ Calif, Div Epidemiol, Dept Family & Prevent Med, La Jolla, CA USA. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Eaton, Charles B.] Brown Univ, Alpert Med Sch, Ctr Primary Care & Prevent, Pawtucket, RI USA. [May, Heidi T.] Intermt Med Ctr, Cardiovasc Dept, Murray, KY USA. [Anderson, Jeffrey L.] Univ Utah, Sch Med, Div Cardiol, Salt Lake City, UT USA. RP Wang, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM luwang@rics.bwh.harvard.edu OI May, Heidi/0000-0002-7524-5905 FU National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD [R00-HL095649]; NIH/National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) [R01-DK088078]; NIH [HL34594, CA138962]; Intramural Research Program of the Eunice Kennedy Shriver NIH/National Institute of Child Health & Human Development (NICHD); NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/National Institute on Aging (NIA)/National Center for Research Resources (NCRR); NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140] FX Dr Wang is supported by grant R00-HL095649 from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD. Dr Song is funded by grant R01-DK088078 from the NIH/National Institute of Diabetes and Digestive and Kidney Disease (NIDDK). Dr JoAnn Manson is funded by grants HL34594 and CA138962 from the NIH. Dr Zhang is supported by the Intramural Research Program of the Eunice Kennedy Shriver NIH/National Institute of Child Health & Human Development (NICHD). The Osteoporotic Fractures in Men (MrOS) Study is supported by the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/National Institute on Aging (NIA)/National Center for Research Resources (NCRR) and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. These funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article. NR 49 TC 190 Z9 200 U1 2 U2 32 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2012 VL 5 IS 6 BP 819 EP 829 DI 10.1161/CIRCOUTCOMES.112.967604 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 041NZ UT WOS:000311409800018 PM 23149428 ER PT J AU Lamprea-Montealegre, JA Astor, BC McClelland, RL de Boer, IH Burke, GL Sibley, CT O'Leary, D Sharrett, AR Szklo, M AF Lamprea-Montealegre, Julio A. Astor, Brad C. McClelland, Robin L. de Boer, Ian H. Burke, Gregory L. Sibley, Christopher T. O'Leary, Daniel Sharrett, A. Richey Szklo, Moyses TI CKD, Plasma Lipids, and Common Carotid Intima-Media Thickness: Results from the Multi-Ethnic Study of Atherosclerosis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; CORONARY-HEART-DISEASE; NONTRADITIONAL RISK-FACTORS; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; DIALYSIS PATIENTS; TOTAL CHOLESTEROL; LIPOPROTEIN ABNORMALITIES; MALNUTRITION AB Background and objectives Altered levels of atherogenic lipoproteins have been shown to be common in mild kidney dysfunction. This study sought to determine the associations between plasma lipids (including LDL particle distribution) and subclinical atherosclerosis measured by the common carotid intima-media thickness (TMT) across levels of estimated GFR (eGFR) and to assess whether inflammation modifies these associations. Design, setting, participants, & measurements Cross-sectional analyses of 6572 participants in the Multi-Ethnic Study of Atherosclerosis enrolled from 2000 to 2002 were performed. Results CKD, defined as eGFR <60 ml/min per 1.73 m(2), was present in 853 individuals (13.0%). Associations of total cholesterol and LDL cholesterol (LDL-C) with IMT were J shaped, particularly among participants with CKD (P value for interaction, P=0.01). HDL cholesterol (HDL-C) and small-dense LDL-C were consistently and linearly associated with IMT across levels of eGFR. The results showed differences in IMT of -21.41 (95% confidence interval, -41.00, -1.57) in eGFR >= 60 and -58.49 (-126.61, 9.63) in eGFR <60 per unit difference in log-transformed HDL-C, and 4.83 (3.16, 6.50) in eGFR >= 60 and 7.48 (1.45, 13.50) in eGFR <60 per 100 nmol/L difference in small-dense LDL. Among participants with CKD, inflammation significantly modified the associations of total cholesterol and LDL-C with IMT (P values for interaction, P<0.01 and P<0.001, respectively). Conclusions Compared with total cholesterol and LDL-C, abnormalities in HDL-C and small-dense LDL-C are more strongly and consistently associated with subclinical atherosclerosis in CKD. Inflammation modifies the association between total cholesterol and LDL-C with IMT. Clin J Am Soc Nephrol 7: 1777-1785, 2012. doi: 10.2215/CJN.02090212 C1 [Lamprea-Montealegre, Julio A.; Sharrett, A. Richey; Szklo, Moyses] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Lamprea-Montealegre, Julio A.; Sharrett, A. Richey; Szklo, Moyses] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. [Astor, Brad C.] Univ Wisconsin, Dept Med & Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA. [McClelland, Robin L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [de Boer, Ian H.] Univ Washington, Dept Med, Seattle, WA USA. [Burke, Gregory L.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Sibley, Christopher T.] NIH, Bethesda, MD 20892 USA. [O'Leary, Daniel] Tufts Med Ctr, Dept Radiol, Boston, MA USA. RP Szklo, M (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM mszklo@jhsph.edu RI Sibley, Christopher/C-9900-2013 NR 39 TC 14 Z9 15 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2012 VL 7 IS 11 BP 1777 EP 1785 DI 10.2215/CJN.02090212 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 033CO UT WOS:000310770600007 PM 22879436 ER PT J AU Bahta, M Burke, TR AF Bahta, M. Burke, T. R. TI Yersinia pestis and Approaches to Targeting its Outer Protein H Protein-Tyrosine Phosphatase (YopH) SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE Inhibitors; plague; protein-tyrosine phosphatase (PTP); Yersinia pestis; YopH; TTSS; P-loop; WPD-loop; EGFR; F(2)Pmp ID SIGNAL-TRANSDUCTION INHIBITORS; ALPHA-KETOCARBOXYLIC ACIDS; SMALL-MOLECULE INHIBITORS; CRYSTAL-STRUCTURE; CLICK CHEMISTRY; DRUG DISCOVERY; PHOSPHOTYROSYL MIMETICS; VIRULENCE DETERMINANT; BIDENTATE INHIBITORS; POTENT INHIBITION AB Plague is an infectious disease with a high mortality rate that has repeatedly impacted human society. It remains a threat in many parts of the world today. Plague is caused by the bacterium, Yersinia pestis (Y. pestis), which has as one of its required virulence factors, the protein-tyrosine phosphatase, YopH. Therefore, YopH represents a potential target for the treatment of Y. pestis infection. Recent recognition of Y. pestis as a possible bioterrorism agent and the fact that it is still the cause of endemic disease around the world make it an important object of study and heighten the need for new anti-plague agents. The current review covers aspects of plague and its historical occurrence and summarizes approaches to developing YopH inhibitors. C1 [Bahta, M.; Burke, T. R.] NCI, Biol Chem Lab, Frederick Natl Lab Canc Res, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Burke, TR (reprint author), 1050 Boyles St Room 217, Frederick, MD 21702 USA. EM burkete@helix.nih.gov RI Burke, Terrence/N-2601-2014 FU NIH, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported in part by the Intramural Research Program of the NIH, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health. 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 92 TC 9 Z9 9 U1 1 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD NOV PY 2012 VL 19 IS 33 BP 5726 EP 5734 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 038CL UT WOS:000311152700014 PM 22934808 ER PT J AU Biancotto, A Feng, XM Langweiler, M Young, NS McCoy, JP AF Biancotto, Angelique Feng, Xingmin Langweiler, Marc Young, Neal S. McCoy, J. Philip TI Effect of anticoagulants on multiplexed measurement of cytokine/chemokines in healthy subjects SO CYTOKINE LA English DT Article DE Cytokines/chemokines; Plasma; Serum; Anticoagulants ID SOLUBLE CD40 LIGAND; STORAGE-CONDITIONS; CYTOKINE LEVELS; PLASMA SAMPLES; SERUM; ELISA; IMMUNOASSAY; ASSAYS; BLOOD AB Introduction: Cytokines are humoral regulatory molecules that act together in immunologic pathways. Monitoring cytokines and their variations within physiologic ranges is critical for biomarker discovery. Therefore, we evaluated the performance characteristics of 72 analytes measured by multiplex cytokine immunoassay, with an emphasis on the differences of analytes measured in serum compared to plasma, and, in plasma, on the impact of anticoagulants on the cytokine measurement. Methods: We used fluorescent bead-based (Luminex) immunoassay kits to simultaneously measure 72 analytes. We tested serum and plasma samples from 11 matched donors. Plasma samples were anticoagulated with sodium heparin, sodium citrate dextrose and ethylene diamine tetra-acetic acid (EDTA), respectively. Results: Of the 72 cytokines, 12 were undetectable in all types of specimen samples. Nineteen analytes, including PDGF-bb, IL-4, IL-8, IL-9, FGF-b, PAI-1, CXCL-5, CCL-5, CD40L, EGF, VEGF, IL-2ra, IL-3, SDF-1a, PCT, MCP-3, GIP, IL-16 and fibrinogen, showed significant differences between measurements in serum and all types of plasma, regardless of anticoagulant. Among plasma samples, 10 analytes (eotaxin, SCGF-b, MCP-1, SCF, MIP-1b, VEGF, RANTES, PDGF-b, PAI-1 and ITAC) showed significantly higher concentrations in heparinized plasma compared to citrated and EDTA plasma. IP-10, and CTAK were the only 2 cytokines that presented different concentrations in citrate and EDTA plasma. Conclusions: With their small volume, low cost per test, and multiplex capacity, Luminex-based cytokine assays have enormous potential utility for screening in epidemiologic studies. In our study, we showed that many cytokines' concentrations differed between serum and plasma samples, and that different anticoagulants used in preparation of plasma samples also affected the measurement of some cytokines. There was no optimal sample preparation that was clearly superior for the measurement of all analytes measured. Ultimately, the utility of cytokine measurement, as biomarker or to monitor the immune system, will depend on attention to detail in the collection and processing of samples in addition to assay precision. Published by Elsevier Ltd. C1 [Biancotto, Angelique; Langweiler, Marc; Young, Neal S.; McCoy, J. Philip] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 28092 USA. [Feng, Xingmin; Young, Neal S.; McCoy, J. Philip] NHLBI, Hematol Branch, NIH, Bethesda, MD 28092 USA. RP McCoy, JP (reprint author), NIH, 10 Ctr Dr,MSC 1357,Bldg 10,Rm 8C103D, Bethesda, MD 20892 USA. EM mccoyjp@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999, ZIC HL005905-04] NR 20 TC 30 Z9 30 U1 2 U2 15 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD NOV PY 2012 VL 60 IS 2 BP 438 EP 446 DI 10.1016/j.cyto.2012.05.019 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 029KL UT WOS:000310494300018 PM 22705152 ER PT J AU Morley, K Seth, D Monteleone, P Duly, A Haber, P Addolorato, G Leggio, L AF Morley, Kirsten Seth, Devanshi Monteleone, Palmiero Duly, Alastair Haber, Paul Addolorato, Giovanni Leggio, Lorenzo TI GHRELIN GENE POLYMORPHISMS IN ALCOHOL DEPENDENCE SO DRUG AND ALCOHOL REVIEW LA English DT Meeting Abstract C1 [Morley, Kirsten; Haber, Paul] Univ Sydney, Sydney Med Sch, Discipline Addict Med, Sydney, NSW 2006, Australia. [Seth, Devanshi; Duly, Alastair] Univ Sydney, Centenary Inst Canc Med & Cell Biol, Sydney, NSW 2006, Australia. [Monteleone, Palmiero] Univ Naples SUN, Dept Psychiat, Naples, Italy. [Haber, Paul] Royal Prince Alfred Hosp, Drug Hlth Serv, Sydney, NSW, Australia. [Addolorato, Giovanni] Univ Cattolica Sacro Cuore, Inst Internal Med, Rome, Italy. [Leggio, Lorenzo] NIAAA, Bethesda, MD 90034 USA. EM kirsten.morley@sydney.edu.au RI Leggio, Lorenzo/M-2972-2016 NR 1 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0959-5236 J9 DRUG ALCOHOL REV JI Drug Alcohol Rev. PD NOV PY 2012 VL 31 SU 1 SI SI BP 52 EP 53 PG 2 WC Substance Abuse SC Substance Abuse GA 039HX UT WOS:000311236700162 ER PT J AU Reid, BC Ghazarian, AA DeMarini, DM Sapkota, A Jack, D Lan, Q Winn, DM Birnbaum, LS AF Reid, Britt C. Ghazarian, Armen A. DeMarini, David M. Sapkota, Amir Jack, Darby Lan, Qing Winn, Deborah M. Birnbaum, Linda S. TI Research Opportunities for Cancer Associated with Indoor Air Pollution from Solid-Fuel Combustion SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cancer; environmental exposures; environmental health risks; epidemiology; household air pollution; indoor air pollution; public health; solid-fuel combustion ID POLYCYCLIC AROMATIC-HYDROCARBONS; HOUSEHOLD STOVE IMPROVEMENT; LUNG-CANCER; RISK-FACTORS; WOOD SMOKE; SUSCEPTIBILITY LOCUS; CERVICAL NEOPLASIA; NORTHEAST CHINA; TOBACCO-SMOKE; XUAN WEI AB BACKGROUND: Indoor air pollution (LAP) derived largely from the use of solid fuels for cooking and heating affects about 3 billion people worldwide, resulting in substantial adverse health outcomes, including cancer. Women and children from developing countries are the most exposed populations. A workshop was held in Arlington, Virginia, 9-11 May 2011, to better understand women's and children's potential health effects from LAP in developing countries. Workshop participants included international scientists, manufacturers, policy and regulatory officials, community leaders, and advocates who held extensive discussions to help identify future research needs. OBJECTIVES: Our objective was to identify research opportunities regarding IAP and cancer, including research questions that could be incorporated into studies of interventions to reduce LAP exposure. In this commentary, we describe the state of the science in understanding LAP and its associations with cancer and suggest research opportunities for improving our understanding of the issues. DISCUSSION: Opportunities for research on LAP and cancer include studies of the effect of LAP on cancers other than lung cancer; studies of genetic factors that modify susceptibility; studies to determine whether the effects of TAP are mediated via germline, somatic, and/or epigenetic changes; and studies of the effects of TAP exposure via dermal and/or oral routes. CONCLUSIONS: LAP from indoor coal use increases the risk of lung cancer. Installing chimneys can reduce risk, and some genotypes, including GSTM1-null, can increase risk. Additional research is needed regarding the effects of IAP on other cancers and the effects of different types of solid fuels, oral and dermal routes of LAP exposure, genetic and epigenetic mechanisms, and genetic susceptibility. C1 [Reid, Britt C.] NCI, Modifiable Risk Factors Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH,DHHS, Bethesda, MD 20892 USA. [DeMarini, David M.] US EPA, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27711 USA. [Sapkota, Amir] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. [Jack, Darby] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA. [Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Birnbaum, Linda S.] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NCI, NIH, DHHS, Res Triangle Pk, NC USA. RP Reid, BC (reprint author), NCI, Modifiable Risk Factors Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH,DHHS, 6130 Execut Blvd,Room 5134, Bethesda, MD 20892 USA. EM reidbr@mail.nih.gov RI Sapkota, Amir/A-5968-2011 FU NICHD NIH HHS [R24 HD041041] NR 53 TC 11 Z9 13 U1 6 U2 46 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2012 VL 120 IS 11 BP 1495 EP 1498 DI 10.1289/ehp.1204962 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 036ZE UT WOS:000311070000015 PM 22846419 ER PT J AU Cote, I Anastas, PT Birnbaum, LS Clark, RM Dix, DJ Edwards, SW Preuss, PW AF Cote, Ila Anastas, Paul T. Birnbaum, Linda S. Clark, Rebecca M. Dix, David J. Edwards, Stephen W. Preuss, Peter W. TI Advancing the Next Generation of Health Risk Assessment SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE bioinformatics; molecular biology; NexGen; "omics"; risk assessment; systems biology ID NATIONAL TOXICOLOGY PROGRAM; ENVIRONMENTAL CHEMICALS; EXPOSURE AB BACKGROUND: Over the past 20 years, knowledge of the genome and its function has increased dramatically, but risk assessment methodologies using such knowledge have not advanced accordingly. OBJECTIVE: This commentary describes a collaborative effort among several federal and state agencies to advance the next generation of risk assessment. The objective of the NexGen program is to begin to incorporate recent progress in molecular and systems biology into risk assessment practice. The ultimate success of this program will be based on the incorporation of new practices that facilitate faster, cheaper, and/or more accurate assessments of public health risks. METHODS: We are developing prototype risk assessments that compare the results of traditional, data-rich risk assessments with insights gained from new types of molecular and systems biology data. In this manner, new approaches can be validated, traditional approaches improved, and the value of different types of new scientific information better understood. DISCUSSION AND CONCLUSIONS: We anticipate that these new approaches will have a variety of applications, such as assessment of new and existing chemicals in commerce and the design of chemical products and processes that reduce or eliminate the use or generation of hazardous substances. Additionally, results of the effort are likely to spur further research and test methods development. Full implementation of new approaches is likely to take 10-20 years. C1 [Cote, Ila; Clark, Rebecca M.; Preuss, Peter W.] US EPA, Washington, DC 20460 USA. [Cote, Ila; Dix, David J.; Edwards, Stephen W.] US EPA, Res Triangle Pk, NC 27711 USA. [Anastas, Paul T.] Yale Univ, New Haven, CT USA. [Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cote, I (reprint author), US EPA, 1200 Penn Ave NW,MD 8601P, Washington, DC 20460 USA. EM cote.ila@epa.gov RI Anastas, Paul/L-3258-2013 OI Anastas, Paul/0000-0003-4777-5172 NR 33 TC 14 Z9 14 U1 1 U2 28 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2012 VL 120 IS 11 BP 1499 EP 1502 DI 10.1289/ehp.1104870 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 036ZE UT WOS:000311070000016 PM 22875311 ER PT J AU Little, MP Azizova, TV Bazyka, D Bouffler, SD Cardis, E Chekin, S Chumak, VV Cucinotta, FA de Vathaire, F Hall, P Harrison, JD Hildebrandt, G Ivanov, V Kashcheev, VV Klymenko, SV Kreuzer, M Laurent, O Ozasa, K Schneider, T Tapio, S Taylor, AM Tzoulaki, I Vandoolaeghe, WL Wakeford, R Zablotska, LB Zhang, W Lipshultz, SE AF Little, Mark P. Azizova, Tamara V. Bazyka, Dimitry Bouffler, Simon D. Cardis, Elisabeth Chekin, Sergey Chumak, Vadim V. Cucinotta, Francis A. de Vathaire, Florent Hall, Per Harrison, John D. Hildebrandt, Guido Ivanov, Victor Kashcheev, Valeriy V. Klymenko, Sergiy V. Kreuzer, Michaela Laurent, Olivier Ozasa, Kotaro Schneider, Thierry Tapio, Soile Taylor, Andrew M. Tzoulaki, Ioanna Vandoolaeghe, Wendy L. Wakeford, Richard Zablotska, Lydia B. Zhang, Wei Lipshultz, Steven E. TI Systematic Review and Meta-analysis of Circulatory Disease from Exposure to Low-Level Ionizing Radiation and Estimates of Potential Population Mortality Risks SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE cancer; circulatory disease; heart disease; radiation; stroke ID ATOMIC-BOMB SURVIVORS; CORONARY-HEART-DISEASE; POWER INDUSTRY WORKERS; NUCLEAR-FUELS PLC; LOW-DOSE EXPOSURE; CARDIOVASCULAR-DISEASE; EPIDEMIOLOGIC EVIDENCE; MAYAK PA; CANCER; COHORT AB BACKGROUND: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels. OBJECTIVES: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures. METHODS: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms "radiation" AND "heart" AND "disease," OR "radiation" AND "stroke," OR "radiation" AND "circulatory" AND "disease." Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries. RESULTS: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (Cl): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia. CONCLUSIONS: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations). C1 [Little, Mark P.] NCI, Radiat Epidemiol Branch, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Azizova, Tamara V.] So Urals Biophys Inst, Ozyorsk, Russia. [Bazyka, Dimitry; Chumak, Vadim V.] Res Ctr Radiat Med, Kiev, Ukraine. [Bouffler, Simon D.; Harrison, John D.; Zhang, Wei] Hlth Protect Agcy, Ctr Radiat Chem & Environm Hazards, Chilton, England. [Cardis, Elisabeth] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Chekin, Sergey; Ivanov, Victor; Kashcheev, Valeriy V.] Russian Acad Med Sci, Med Radiol Res Ctr, Obninsk, Russia. [Cucinotta, Francis A.] NASA, Lyndon B Johnson Space Ctr, Space Radiat Program, Houston, TX 77058 USA. [de Vathaire, Florent] Inst Gustave Roussy, INSERM, Radiat Epidemiol Grp, Unite U1018, F-94805 Villejuif, France. [Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Hildebrandt, Guido] Univ Leipzig, Dept Radiotherapy & Radiat Oncol, Leipzig, Germany. [Hildebrandt, Guido] Univ Rostock, Dept Radiotherapy & Radiat Oncol, Rostock, Germany. [Kreuzer, Michaela] Fed Off Radiat Protect, Dept Radiat Protect & Hlth, Oberschleissheim, Germany. [Laurent, Olivier] Inst Radioprotect & Surete Nucl, Lab Epidemiol, Fontenay Aux Roses, France. [Ozasa, Kotaro] Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan. [Schneider, Thierry] CEPN Nucl Evaluat Protect Ctr, Fontenay Aux Roses, France. [Tapio, Soile] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Radiat Biol ISB, Oberschleissheim, Germany. [Taylor, Andrew M.] UCL, Inst Cardiovasc Sci, London, England. [Taylor, Andrew M.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Tzoulaki, Ioanna; Vandoolaeghe, Wendy L.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Biostat, London, England. [Wakeford, Richard] Univ Manchester, Dalton Nucl Inst, Manchester, Lancs, England. [Zablotska, Lydia B.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. [Lipshultz, Steven E.] Univ Miami, Dept Pediat, Leonard M Miller Sch Med, Miami, FL 33152 USA. RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, NIH, Dept Hlth & Human Serv, Execut Plaza S,6120 Execut Blvd,MSC 7238, Rockville, MD 20852 USA. EM mark.little@nih.gov RI Taylor, Andrew/C-4311-2008; Tapio, Soile/M-7358-2014; Kashcheev, Valeriy/L-7794-2015; Chumak, Vadim/N-6960-2015; de Vathaire, Florent/L-2983-2016; Ivanov, Victor/R-9385-2016; Cardis, Elisabeth/C-3904-2017; OI Little, Mark/0000-0003-0980-7567; Klymenko, Sergiy/0000-0002-9758-7316; Tapio, Soile/0000-0001-9860-3683; Wakeford, Richard/0000-0002-2934-0987; Kashcheev, Valeriy/0000-0003-4108-9761; Chumak, Vadim/0000-0001-6045-9356; Ivanov, Victor/0000-0003-1372-0018; Bazyka, Dimitry/0000-0001-9982-5990 FU European Commission (EC) [FP6-036465]; Intramural Research Program of the National Institutes of Health (NIH); National Cancer Institute; Japanese Ministry of Health, Labour and Welfare; U.S. Department of Energy through the National Academy of Sciences FX This work was funded partially by the European Commission (EC) under contract FP6-036465 [NOn-Targeted Effects of ionising radiation (NOTE) integrated project]. This research was also supported by the Intramural Research Program of the National Institutes of Health (NIH) and the National Cancer Institute. This report makes use of data obtained from the Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan. RERF is a private, nonprofit foundation funded by the Japanese Ministry of Health, Labour and Welfare and the U.S. Department of Energy, the latter through the National Academy of Sciences. NR 59 TC 83 Z9 93 U1 3 U2 27 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2012 VL 120 IS 11 BP 1503 EP 1511 DI 10.1289/ehp.1204982 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 036ZE UT WOS:000311070000017 PM 22728254 ER PT J AU Cupul-Uicab, LA Skjaerven, R Haug, K Travlos, GS Wilson, RE Eggesbo, M Hoppin, JA Whitworth, KW Longnecker, MP AF Cupul-Uicab, Lea A. Skjaerven, Rolv Haug, Kjell Travlos, Gregory S. Wilson, Ralph E. Eggesbo, Merete Hoppin, Jane A. Whitworth, Kristina W. Longnecker, Matthew P. TI Exposure to Tobacco Smoke in Utero and Subsequent Plasma Lipids, ApoB, and CRP among Adult Women in the MoBa Cohort SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE clinical chemistry; C-reactive protein; metabolic syndrome; plasma lipids; prenatal exposure delayed effects; smoking; women ID MATERNAL-SMOKING; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; NORWEGIAN MOTHER; CHILD COHORT; PARENTAL SMOKING; BIRTH-WEIGHT; RISK-FACTORS; PREGNANCY; HYPERTENSION AB BACKGROUND: Recent findings suggest that maternal smoking during pregnancy may play a role in the development of metabolic alterations in offspring during childhood. However, whether such exposure increases the risk of developing similar metabolic alterations during adulthood is uncertain. OBJECTIVE: We evaluated the association of in utero exposure to maternal tobacco smoke with plasma lipids, apolipoprotein B (apoB), and C-reactive protein (CRP) in adulthood. METHODS: The study was based on a subsample of the Norwegian Mother and Child Cohort Study (MoBa) and included 479 pregnant women with plasma lipids, apoB, and CRP measurements. Information on in utero exposure to tobacco smoke, personal smoking, and other factors were obtained from the women by a self-completed questionnaire at enrollment, at approximately 17 weeks of gestation. RESULTS: Women exposed to tobacco smoke in utero had higher triglycerides [10.7% higher; 95% confidence interval (CI): 3.9, 17.9] and lower high-density lipoprotein cholesterol (HDL) (-1.9 mg/dL; 95% CI: -4.3, 0.5) compared with unexposed women, after adjusting for age, physical activity, education, personal smoking, and current body mass index (BMI). Exposed women were also more likely to have triglycerides >= 200 mg/dL., [adjusted odds ratio (aOR) = 2.5; 95% CI: 1.3, 5.1] and HDL < 50 mg/dL (aOR = 2.3; 95% CI: 1.1, 5.0). Low-density lipoprotein cholesterol, total cholesterol, and apoB were not associated with the exposure. CRP was increased among exposed women; however, after adjustment for BMI, the association was completely attenuated. CONCLUSIONS: In this population, in utero exposure to tobacco smoke was associated with high triglycerides and low HDL in adulthood, 18-44 years after exposure. C1 [Cupul-Uicab, Lea A.; Hoppin, Jane A.; Whitworth, Kristina W.; Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Skjaerven, Rolv; Haug, Kjell] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway. [Skjaerven, Rolv] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway. [Travlos, Gregory S.; Wilson, Ralph E.] NIEHS, Cellular & Mol Pathol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Eggesbo, Merete] Norwegian Inst Publ Hlth, Dept Genes & Environm, Div Epidemiol, Oslo, Norway. RP Cupul-Uicab, LA (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cupuluicabl@niehs.nih.gov RI CUPUL UICAB, LEA/C-8699-2014; OI CUPUL UICAB, LEA/0000-0001-6190-4474; Longnecker, Matthew/0000-0001-6073-5322; Eggesbo, Merete/0000-0002-0006-5336 FU Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS); Norwegian Ministry of Health [N01-ES-75558]; NIH/NIEHS, NIH/National Institute of Neurological Disorders and Stroke [1 UO1 NS 047537-01]; Norwegian Research Council/FUGE [151918/S10] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health, contract N01-ES-75558 with the NIH/NIEHS, NIH/National Institute of Neurological Disorders and Stroke (grant 1 UO1 NS 047537-01), and the Norwegian Research Council/FUGE (grant 151918/S10). NR 38 TC 7 Z9 7 U1 3 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2012 VL 120 IS 11 BP 1532 EP 1537 DI 10.1289/ehp.1104563 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 036ZE UT WOS:000311070000021 PM 22814200 ER PT J AU Chulada, PC Kennedy, S Mvula, MM Jaffee, K Wildfire, J Thornton, E Cohn, RD Grimsley, LF Mitchell, H El-Dahr, J Sterling, Y Martin, WJ White, L Stephens, KU Lichtveld, M AF Chulada, Patricia C. Kennedy, Suzanne Mvula, Mosanda M. Jaffee, Katy Wildfire, Jeremy Thornton, Eleanor Cohn, Richard D. Grimsley, L. Faye Mitchell, Herman El-Dahr, Jane Sterling, Yvonne Martin, William J. White, LuAnn Stephens, Kevin U. Lichtveld, Maureen TI The Head-off Environmental Asthma in Louisiana (HEAL) Study-Methods and Study Population SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE asthma; asthma case management; asthma counselor; environmental intervention; Hurricane Katrina; indoor allergens; mold ID INNER-CITY ASTHMA; KATRINA NEW-ORLEANS; HURRICANE-KATRINA; URBAN COMMUNITIES; CHILDREN; HOMES; INTERVENTION; MANAGEMENT; MORBIDITY; EXPOSURES AB BACKGROUND: In the city of New Orleans, Louisiana, and surrounding parishes (NOLA), children with asthma were perilously impacted by Hurricane Katrina as a result of disrupted health care, high home mold and allergen levels, and high stress. OBJECTIVES: The Head-off Environmental Asthma in Louisiana (HEAL) study was conducted to examine relationships between the post-Katrina environment and childhood asthma in NOLA and assess a novel asthma counselor intervention that provided case management and guidance for reducing home mold and allergen levels. METHODS: Children (4-12 years old) with moderate-to-severe asthma were recruited from NOLA schools. Over 1 year, they received two clinical evaluations, three home environmental evaluations, and the asthma intervention. Quarterly end points included symptom days, medication use, and unscheduled emergency department or clinic visits. A community advisory group was assembled and informed HEAL at all phases. RESULTS: Of the children (n = 182) enrolled in HEAL, 67% were African American, and 25% came from households with annual incomes < $15,000: HEAL children were symptomatic, averaging 6.6 symptom days in the 2 weeks before baseline, and had frequent unscheduled visits to clinics or emergency departments (76% had at least one unscheduled visit in the preceding 3 months). In this report, we describe study design and baseline characteristics of HEAL children. CONCLUSIONS: Despite numerous challenges faced by investigators, study staff, and participants, including destroyed infrastructure, disrupted lives, and lost jobs, HEAL was successful in terms of recruitment and retention, the high quality of data collected that will provide insight into asthma-allergen relationships, and the asthma intervention. This success was attributable to using an adaptive approach and refining processes as needed. C1 [Chulada, Patricia C.] NIEHS, Clin Res Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Kennedy, Suzanne; Jaffee, Katy; Wildfire, Jeremy; Mitchell, Herman] Rho Fed Syst Div Inc, Chapel Hill, NC USA. [Mvula, Mosanda M.; Stephens, Kevin U.] New Orleans Hlth Dept, New Orleans, LA USA. [Thornton, Eleanor] Visionary Consulting Partners LLC, Fairfax Stn, VA USA. [Cohn, Richard D.] SRA Int Inc, Durham, NC USA. [Grimsley, L. Faye; White, LuAnn; Lichtveld, Maureen] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [El-Dahr, Jane] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. [Sterling, Yvonne] Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA. [Martin, William J.] NICHD, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Chulada, PC (reprint author), Westat Corp, 1009 Slater Rd,Suite 110, Durham, NC 27703 USA. EM patriciachulada@westat.com FU National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH) [NO1-ES-55553]; Merck Childhood Asthma Network; National Center on Minority Health and Health Disparities under Foundation for the NIH; 501(c)(3) charitable organization; Louisiana Board of Regents RC/EEP FX This project has been funded, in whole or in part, with federal funds from the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), under contract NO1-ES-55553.. Additional funding support was provided by the Merck Childhood Asthma Network and the National Center on Minority Health and Health Disparities under the auspices of the Foundation for the NIH, a nonprofit, 501(c)(3) charitable organization that raises private-sector funds for a broad portfolio of unique programs that complement and enhance the NIH priorities and activities. Other organizations that contributed include the National Toxicology Program (NIEHS), the U.S. Environmental Protection Agency (Cincinnati, OH), and the de Laski Family Foundation. The Clinical and Translational Research Center of Tulane and Louisiana State Universities Schools of Medicine was supported in whole or in part by funds provided through the Louisiana Board of Regents RC/EEP. H.M., J.W., KJ., and S.K. are employed by Rho Federal Systems Division, Inc., R.D.C. is employed by SEA International, Inc., ET. is employed by Visionary Consulting Partners, LLC, Rho Federal Systems Division, Inc. NR 31 TC 5 Z9 5 U1 1 U2 14 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2012 VL 120 IS 11 BP 1592 EP 1599 DI 10.1289/ehp.1104239 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 036ZE UT WOS:000311070000030 PM 22895349 ER PT J AU Grimsley, LF Chulada, PC Kennedy, S White, L Wildfire, J Cohn, RD Mitchell, H Thornton, E El-Dahr, J Mvula, MM Sterling, Y Martin, WJ Stephens, KU Lichtveld, M AF Grimsley, L. Faye Chulada, Patricia C. Kennedy, Suzanne White, LuAnn Wildfire, Jeremy Cohn, Richard D. Mitchell, Herman Thornton, Eleanor El-Dahr, Jane Mvula, Mosanda M. Sterling, Yvonne Martin, William J. Stephens, Kevin U. Lichtveld, Maureen TI Indoor Environmental Exposures for Children with Asthma Enrolled in the HEAL Study, Post-Katrina New Orleans SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE allergens; asthma; endotoxin; environmental remediation; glucan; Hurricane Katrina; mold ID INNER-CITY CHILDREN; RELATIVE MOLDINESS INDEX; DUST-MITE ALLERGENS; ALTERNARIA-ALTERNATA; HURRICANE-KATRINA; ENDOTOXIN EXPOSURE; US HOMES; MOLD; ATOPY; CHILDHOOD AB BACKGROUND: Rain and flooding from Hurricane Katrina resulted in widespread growth of mold and bacteria and production of allergens in New Orleans, Louisiana, which may have led to increased exposures and morbidity in children with asthma. OBJECTIVES: The goal of the Head-off Environmental Asthma in Louisiana (HEAL) study was to characterize post-Katrina exposures to mold and allergens in children with asthma. METHODS: The homes of 182 children with asthma in New Orleans and surrounding parishes were evaluated by visual inspection, temperature and moisture measurements, and air and dust sampling. Air was collected using vacuum-pump spore traps and analyzed for > 30 mold taxa using bright field microscopy. Dust was collected from the children's beds and bedroom floors and analyzed for mouse (Mus m 1), dust mite (Der p 1), cockroach (Bla g 1), and mold (Alternaria mix) allergens using ELISA. RESULTS: More than half (62%) of the children were living in homes that had been damaged by rain, flooding, or both. Geometric mean indoor and outdoor airborne mold levels were 501 and 3,958 spores/m(3), respectively. Alternaria antigen was detected in dust from 98% of homes, with 58% having concentrations > 10 mu g/g. Mus m 1, Der p 1, and Bla g 1 were detected in 60%, 35%, and 20% of homes, respectively, at low mean concentrations. CONCLUSIONS: Except for Alternaria antigen in dust, concentrations of airborne mold (ratio of indoor to outdoor mold) and dust allergens in the homes of HEAL children were lower than measurements found in other studies, possibly because of extensive post-Katrina mold remediation and renovations, or because children moved into cleaner homes upon returning to New Orleans. C1 [Grimsley, L. Faye; White, LuAnn; Lichtveld, Maureen] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Chulada, Patricia C.] NIEHS, Clin Res Program, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Kennedy, Suzanne; Wildfire, Jeremy; Mitchell, Herman] Rho Fed Syst Div Inc, Chapel Hill, NC USA. [Cohn, Richard D.] SRA Int Inc, Durham, NC USA. [Thornton, Eleanor] Visionary Consulting Partners LLC, Fairfax Stn, VA USA. [El-Dahr, Jane] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Mvula, Mosanda M.; Stephens, Kevin U.] New Orleans Hlth Dept, New Orleans, LA USA. [Sterling, Yvonne] Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA. [Martin, William J.] NICHD, NIH, US Dept HHS, Bethesda, MD USA. RP Grimsley, LF (reprint author), 1440 Canal St,Suite 2100,SL-29, New Orleans, LA 70112 USA. EM Grimsley@tulane.edu FU National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH) [NO1-ES-55553]; Merck Childhood Asthma Network; National Center on Minority Health and Health Disparities under the auspices of the Foundation for the NIH; 501(c)(3) charitable organization; Louisiana Board of Regents RC/EEP FX This project has been funded, in whole or in part, with federal funds from the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), under contract NO1-ES-55553. Additional funding support was provided by the Merck Childhood Asthma Network and the National Center on Minority Health and Health Disparities under the auspices of the Foundation for the NIH, a nonprofit, 501(c)(3) charitable organization that raises private-sector funds for a broad portfolio of unique programs that complement and enhance the NIH priorities and activities. Other organizations that contributed include the National Toxicology Program (NIEHS), the U.S. Environmental Protection Agency (Cincinnati, OH), and the de Laski Family Foundation. The Clinical and Translational Research Center of Tulane and Louisiana State Universities, Schools of Medicine was supported in whole or in part by funds provided through the Louisiana Board of Regents RC/EEP. H.M., J.W., and S.K. are employed by Rho Federal Systems Division, Inc. R.D.C. is employed by SRA International, Inc. E.T. is employed by Visionary Consulting Partners, LLC. NR 48 TC 10 Z9 10 U1 2 U2 27 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2012 VL 120 IS 11 BP 1600 EP 1606 DI 10.1289/ehp.1104840 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 036ZE UT WOS:000311070000031 PM 22894816 ER PT J AU Mitchell, H Cohn, RD Wildfire, J Thornton, E Kennedy, S El-Dahr, JM Chulada, PC Mvula, MM Grimsley, LF Lichtveld, MY White, LE Sterling, YM Stephens, KU Martin, WJ AF Mitchell, Herman Cohn, Richard D. Wildfire, Jeremy Thornton, Eleanor Kennedy, Suzanne El-Dahr, Jane M. Chulada, Patricia C. Mvula, Mosanda M. Grimsley, L. Faye Lichtveld, Maureen Y. White, LuAnn E. Sterling, Yvonne M. Stephens, Kevin U., Sr. Martin, William J., II TI Implementation of Evidence-based Asthma Interventions in Post-Katrina New Orleans: The Head-off Environmental Asthma in Louisiana (HEAL) Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE asthma case management; asthma counselor; asthma morbidity; environmental intervention; Hurricane Katrina; indoor allergens; mold ID INNER-CITY ASTHMA; CHILDREN; MORBIDITY; SYMPTOMS; CARE; HOME AB BACKGROUND: Childhood asthma morbidity and mortality in New Orleans, Louisiana, is among the highest in the nation. In August 2005, Hurricane Katrina created an environmental disaster that led to high levels of mold and other allergens and disrupted health care for children with asthma. OBJECTIVES: We implemented a unique hybrid asthma counselor and environmental intervention based on successful National Institutes of Health asthma interventions from the National Cooperative Inner City Asthma (NCICAS) and Inner-City Asthma (ICAS) Studies with the goal of reducing asthma symptoms in New Orleans children after Hurricane Katrina. METHODS: Children (4-12 years old) with moderate-to-severe asthma (fl = 182) received asthma counseling and environmental intervention for approximately 1 year. HEAL was evaluated employing several analytical approaches including a pre post evaluation of symptom changes over the entire year, an analysis of symptoms according to the timing of asthma counselor contact, and a comparison to previous evidence-based interventions. RESULTS: Asthma symptoms during the previous 2 weeks decreased from 6.5 days at enrollment to 3.6 days at the 12-month symptom assessment (a 45% reduction, p < 0.001), consistent with changes observed after NCICAS and ICAS interventions.(35% and 62% reductions in symptom days, respectively). Children whose families had contact with a HEAL asthma counselor by 6 months showed a 4.09-day decrease [95% confidence interval (CI): 3.25 to 4.94-day decrease] in symptom days, compared with a 1.79-day decrease (95% Cl: 0.90, 2.67) among those who had not yet seen an asthma counselor (p < 0.001). CONCLUSIONS: The novel combination of evidence-based asthma interventions was associated with improved asthma symptoms among children in post-Katrina New Orleans. Post-intervention changes in symptoms were consistent with previous randomized trials of NCICAS and ICAS interventions. C1 [Mitchell, Herman; Wildfire, Jeremy; Kennedy, Suzanne] Rho Fed Syst Div Inc, Chapel Hill, NC 27517 USA. [Cohn, Richard D.] SRA Int Inc, Durham, NC USA. [Thornton, Eleanor] Visionary Consulting Partners LLC, Fairfax Stn, VA USA. [El-Dahr, Jane M.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. [Chulada, Patricia C.] NIEHS, Clin Res Program, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. [Mvula, Mosanda M.; Stephens, Kevin U., Sr.] New Orleans Hlth Dept, New Orleans, LA USA. [Grimsley, L. Faye; Lichtveld, Maureen Y.; White, LuAnn E.] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Sterling, Yvonne M.] Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA. [Martin, William J., II] NICHD, NIH, US Dept HHS, Bethesda, MD USA. RP Mitchell, H (reprint author), Rho Fed Syst Div Inc, 6330 Quadrangle Dr, Chapel Hill, NC 27517 USA. EM herman_mitchell@rhoworld.com FU National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH) [NO1-ES-55553]; Merck Childhood Asthma Network; National Center on Minority Health and Health Disparities under Foundation for the NIH; 501(c)(3) charitable organization; Louisiana Board of Regents RC/EEP FX This project has been funded, in whole or in part, with federal funds from the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), under contract NO1-ES-55553. Additional funding support was provided by the Merck Childhood Asthma Network and the National Center on Minority Health and Health Disparities under the auspices of the Foundation for the NIH, a nonprofit, 501(c)(3) charitable organization that raises private-sector funds for a broad portfolio of unique programs that complement and enhance the NIH priorities and activities. Other organizations that contributed include the National Toxicology Program (NIEHS), the U.S. Environmental Protection Agency (Cincinnati, OH), and the de Laski Family Foundation. The Clinical and Translational Research Center of Tulane and Louisiana State Universities Schools of Medicine was supported in whole or in part by funds provided through the Louisiana Board of Regents RC/EEP. H.M., J.W., and S.K. are employed by Rho Federal Systems Division, Inc. R.D.C. is employed by SRA International, Inc. E.T. is employed by Visionary Consulting Partners, LLC. NR 21 TC 7 Z9 7 U1 0 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2012 VL 120 IS 11 BP 1607 EP 1612 DI 10.1289/ehp.1104242 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 036ZE UT WOS:000311070000032 PM 22894795 ER PT J AU Karp, JE Garrett-Mayer, E Estey, EH Rudek, MA Smith, BD Greer, JM Drye, DM Mackey, K Dorcy, KS Gore, SD Levis, MJ McDevitt, MA Carraway, HE Pratz, KW Gladstone, DE Showel, MM Othus, M Doyle, LA Wright, JJ Pagel, JM AF Karp, Judith E. Garrett-Mayer, Elizabeth Estey, Elihu H. Rudek, Michelle A. Smith, B. Douglas Greer, Jacqueline M. Drye, D. Michelle Mackey, Karen Dorcy, Kathleen Shannon Gore, Steven D. Levis, Mark J. McDevitt, Michael A. Carraway, Hetty E. Pratz, Keith W. Gladstone, Douglas E. Showel, Margaret M. Othus, Megan Doyle, L. Austin Wright, John J. Pagel, John M. TI Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE acute myelogenous leukemia; poor risk; flavopiridol; ara-C; mitoxantrone ID ACUTE MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; 72-HOUR CONTINUOUS-INFUSION; BREAST-CARCINOMA CELLS; GROUP-B; TRANSCRIPTIONAL REPRESSION; CYTOTOXIC SYNERGY; CLINICAL-TRIALS; DOWN-REGULATION; OLDER PATIENTS AB Background Flavopiridol is a protein-bound, cytotoxic, cyclin dependent kinase inhibitor. A phase II trial of flavopiridol followed by ara-C and mitoxantrone with flavopiridol given by 1-h bolus for adults with newly-diagnosed, poor-risk acute myelogenous leukemia yielded 67% complete remission with median disease-free survival of 13.6 months. Design and Methods We compared bolus flavopiridol (50 mg/m(2)/day, Arm A) versus 'hybrid' flavopiridol (30 mg/m(2) over 30 min followed by 40 mg/m(2) over 4 h, Arm B) followed by ara-C and mitoxantrone in 78 patients (39 per arm) with newly diagnosed, poor-risk acute myelogenous leukemia. To mitigate imbalance, patients were stratified by presence or absence of secondary leukemia and therapy for antecedent disorder. Results Death at or before Day 60 occurred in 8% of patients per arm. Complete remission plus complete remission with incomplete recovery was 68% (Arm A, 62%; Arm B, 74%) overall, and 65% or over in both arms for patients with secondary leukemia and leukemia with adverse genetics. In Arm A 91% and in Arm B 86% of patients received chemotherapy and/or allogeneic transplantation in complete remission. Median overall survival for all remission patients has not been reached for either arm, with median disease free survival of 13.6 months for Arm A and of 12.0 months for Arm B. Conclusions Both flavopiridol schedules produce comparably encouraging results in adults with poor-risk acute myelogenous leukemia. Given the greater ease of bolus administration, we are conducting a randomized phase II study of bolus flavopiridol followed by ara-c and mitoxantrone versus conventional induction therapy for patients aged 70 years and under with intermediate or poor-risk acute myelogenous leukemia. This study is registered at www.clinicaltrials.gov as #NCT 00407966. C1 [Karp, Judith E.; Smith, B. Douglas; Greer, Jacqueline M.; Drye, D. Michelle; Mackey, Karen; Gore, Steven D.; Levis, Mark J.; McDevitt, Michael A.; Carraway, Hetty E.; Pratz, Keith W.; Gladstone, Douglas E.; Showel, Margaret M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Hematol Malignancies, Baltimore, MD 21231 USA. [Garrett-Mayer, Elizabeth] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Estey, Elihu H.; Dorcy, Kathleen Shannon; Othus, Megan; Pagel, John M.] Seattle Canc Care Alliance, Seattle, WA USA. [Estey, Elihu H.; Dorcy, Kathleen Shannon; Othus, Megan; Pagel, John M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Estey, Elihu H.; Dorcy, Kathleen Shannon; Othus, Megan; Pagel, John M.] Univ Washington, Seattle, WA 98195 USA. [Rudek, Michelle A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Chem Therapeut, Baltimore, MD 21231 USA. [Doyle, L. Austin; Wright, John J.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Karp, JE (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Hematol Malignancies, 1650 Orleans St,CRB 1,Room 2M44, Baltimore, MD 21231 USA. EM jkarp2@jhmi.edu FU NCI Cooperative Agreement [U01 CA70095]; NCI Cancer Center Support Grant [2P30 CA06973-46]; National Center for Research Resources Grant [UL1 RR025005] FX this work was supported in part by NCI Cooperative Agreement U01 CA70095 (JEK and MAR), NCI Cancer Center Support Grant 2P30 CA06973-46, National Center for Research Resources Grant UL1 RR025005 (a component of the National Institutes of Health Roadmap for Medical Research), and philanthropic funds from Dr. Robert E. Fischell in memory of his late wife Marian (JEK). The contents of the project are solely the responsibility of the authors and do not necessarily represent the official view of NCI, NCRR, or NIH. NR 38 TC 21 Z9 23 U1 0 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2012 VL 97 IS 11 BP 1736 EP 1742 DI 10.3324/haematol.2012.062539 PG 7 WC Hematology SC Hematology GA 043WL UT WOS:000311581300023 PM 22733022 ER PT J AU Bereal-Williams, C Machado, RF McGowan, V Chi, A Hunter, CJ Kato, GJ AF Bereal-Williams, Candice Machado, Roberto F. McGowan, Vicki, II Chi, Amy Hunter, Christian J. Kato, Gregory J. TI Atorvastatin reduces serum cholesterol and triglycerides with limited improvement in vascular function in adults with sickle cell anemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Letter DE atorvastatin; sickle cell anemia; nitric oxide resistance; vascular fuction ID PULMONARY-HYPERTENSION; MEDIATED VASODILATION; DISEASE; DYSFUNCTION; SIMVASTATIN; ADHESION; MOUSE; MEN C1 [Bereal-Williams, Candice; McGowan, Vicki, II; Chi, Amy; Hunter, Christian J.; Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Machado, Roberto F.] Univ Illinois, Coll Med, Div Pulm Crit Care Sleep & Allergy, Chicago, IL USA. RP Kato, GJ (reprint author), 9000 Rockville Pike,MSC 1476,Bldg 10CRC,Room 5-51, Bethesda, MD 20892 USA. EM gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [Z01 CL008052-05]; NHLBI NIH HHS [ZIA HL006023]; PHS HHS [1 ZIAHL006023-03] NR 12 TC 6 Z9 6 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2012 VL 97 IS 11 BP 1768 EP 1770 DI 10.3324/haematol.2011.054957 PG 3 WC Hematology SC Hematology GA 043WL UT WOS:000311581300028 PM 22773602 ER PT J AU Marton, A Vizler, C Kusz, E Temesfoi, V Szathmary, Z Nagy, K Szegletes, Z Varo, G Siklos, L Katona, RL Tubak, V Howard, OMZ Duda, E Minarovits, J Nagy, K Buzas, K AF Marton, Annamaria Vizler, Csaba Kusz, Erzsebet Temesfoi, Viktoria Szathmary, Zsuzsa Nagy, Krisztina Szegletes, Zsolt Varo, Gyorgy Siklos, Laszlo Katona, Robert L. Tubak, Vilmos Howard, O. M. Zack Duda, Erno Minarovits, Janos Nagy, Katalin Buzas, Krisztina TI Melanoma cell-derived exosomes alter macrophage and dendritic cell functions in vitro SO IMMUNOLOGY LETTERS LA English DT Article DE Melanoma; Tumor immunity; Exosomes; Cytokine profile ID NF-KAPPA-B; PROGRESSION; INHIBITOR; TUMORS AB To clarify controversies in the literature of the field, we have purified and characterized B16F1 melanoma cell derived exosomes (mcd-exosomes) then we attempted to dissect their immunological activities. We tested how mcd-exosomes influence CD4+T cell proliferation induced by bone marrow derived dendritic cells; we quantified NF-kappa B activation in mature macrophages stimulated with mcd-exosomes, and we compared the cytokine profile of LPS-stimulated, IL-4 induced, and mcd-exosome treated macrophages. We observed that mcd-exosomes helped the maturation of dendritic cells, enhancing T cell proliferation induced by the treated dendritic cells. The exosomes also activated macrophages, as measured by NF-kappa B activation. The cytokine and chemokine profile of macrophages treated with tumor cell derived exosomes showed marked differences from those induced by either LPS or IL-4, and it suggested that exosomes may play a role in the tumor progression and metastasis formation through supporting tumor immune escape mechanisms. (C) 2012 Elsevier B.V. All rights reserved. C1 [Marton, Annamaria; Vizler, Csaba; Kusz, Erzsebet; Temesfoi, Viktoria; Tubak, Vilmos; Duda, Erno; Buzas, Krisztina] Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6701 Szeged, Hungary. [Szathmary, Zsuzsa] Galenbio Kft, Mosonmagyarovar, Hungary. [Nagy, Krisztina; Szegletes, Zsolt; Varo, Gyorgy; Siklos, Laszlo] Hungarian Acad Sci, Biol Res Ctr, Inst Biophys, H-6701 Szeged, Hungary. [Katona, Robert L.] Hungarian Acad Sci, Biol Res Ctr, Inst Genet, H-6701 Szeged, Hungary. [Howard, O. M. Zack] NCI, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. [Minarovits, Janos] Natl Ctr Epidemiol, Microbiol Res Grp, Budapest, Hungary. [Nagy, Katalin; Buzas, Krisztina] Univ Szeged, Fac Dent, Szeged, Hungary. RP Buzas, K (reprint author), Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6701 Szeged, Hungary. EM kr.buzas@gmail.com RI Howard, O M Zack/B-6117-2012; OI Howard, O M Zack/0000-0002-0505-7052; Duda, Erno/0000-0002-0964-1627 FU National Science Fund of Hungary OTKA [PD 84064, OTKA K 81180, GOP-1.1.1-11-2011-0003, TAMOP-4.2.2/B-10/1-2010-0012]; Hungarian Academy of Sciences FX This work was supported by the National Science Fund of Hungary OTKA PD 84064, OTKA K 81180 and GOP-1.1.1-11-2011-0003 and TAMOP-4.2.2/B-10/1-2010-0012. C. Vizier was the recipient of a Bolyai fellowship of the Hungarian Academy of Sciences. NR 18 TC 18 Z9 23 U1 4 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD NOV-DEC PY 2012 VL 148 IS 1 BP 34 EP 38 DI 10.1016/j.imlet.2012.07.006 PG 5 WC Immunology SC Immunology GA 042IH UT WOS:000311464400004 PM 22898052 ER PT J AU Biesecker, LG AF Biesecker, Leslie G. TI The New World of Clinical Genomics SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,Room 4A56, Bethesda, MD 20892 USA. EM lesb@helix.nih.gov NR 10 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2012 VL 97 IS 11 BP 3912 EP 3914 DI 10.1210/jc.2012-3288 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 032IT UT WOS:000310710500036 PM 23129594 ER PT J AU Havens, PL Mulligan, K Hazra, R Flynn, P Rutledge, B Van Loan, MD Lujan-Zilbermann, J Kapogiannis, BG Wilson, CM Stephensen, CB AF Havens, Peter L. Mulligan, Kathleen Hazra, Rohan Flynn, Patricia Rutledge, Brandy Van Loan, Marta D. Lujan-Zilbermann, Jorge Kapogiannis, Bill G. Wilson, Craig M. Stephensen, Charles B. CA HIV AIDS Interventions ATN 063 TI Serum 25-Hydroxyvitamin D Response to Vitamin D-3 Supplementation 50,000 IU Monthly in Youth with HIV-1 Infection SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; D-DEFICIENCY RICKETS; ERGOCALCIFEROL VITAMIN-D-2; ANTIRETROVIRAL THERAPY; ABACAVIR-LAMIVUDINE; CONTROLLED-TRIAL; D INSUFFICIENCY; CHOLECALCIFEROL; TENOFOVIR; ADOLESCENTS AB Context: Vitamin D deficiency and insufficiency occur frequently in youth with HIV infection, particularly among those receiving the antiretroviral drug efavirenz. Optimal vitamin D dosing for treatment is unclear. Objective: Our objective was to evaluate safety and measure change in 25-hydroxyvitamin D (25-OHD) concentration from baseline to study wk 4 and 12 during treatment with vitamin D-3, 50,000 IU monthly. Design, Setting, and Participants: We conducted a randomized double-blind, placebo-controlled multicenter trial of HIV-infected youth ages 18-24 yr, with viral load below 5000 copies/ml, on stable antiretroviral therapy. Intervention: Intervention included vitamin D-3, 50,000 IU (n = 102), or matching placebo (n = 101) administered in three directly observed oral doses at monthly intervals. Results: At baseline, mean (SD) age was 20.9 (2.0) yr; 37% were female and 52% African-American, and 54% were vitamin D deficient/insufficient (25-OHD < 20 ng/ml), with no randomized group differences. Of evaluable participants vitamin D deficient/insufficient at baseline who were administered vitamin D, 43 of 46 (93%) had sufficient 25-OHD by wk 12. Vitamin D supplementation increased 25-OHD serum concentration from a baseline of 21.9 (13.3) to 35.9 (19.1) ng/ml at wk 12 (P < 0.001) with no change for placebo. Although use of the antiretroviral efavirenz was associated with lower baseline 25-OHD concentration, efavirenz did not diminish the response to vitamin D supplementation. There was no treatment-related toxicity. Conclusions: Supplementation with vitamin D-3 50,000 IU monthly for three doses was safe. Increases in 25-OHD occurred in treated participants regardless of antiretroviral regimen. (J Clin Endocrinol Metab 97: 4004-4013, 2012) C1 [Havens, Peter L.] Med Coll Wisconsin, Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53201 USA. [Mulligan, Kathleen] Univ Calif San Francisco, San Francisco, CA 94110 USA. [Hazra, Rohan; Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Flynn, Patricia] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Rutledge, Brandy] WESTAT Corp, Rockville, MD 20850 USA. [Van Loan, Marta D.; Stephensen, Charles B.] ARS, USDA, Western Human Nutr Res Ctr, Davis, CA 95616 USA. [Lujan-Zilbermann, Jorge] Univ S Florida, Coll Med, Tampa, FL 33606 USA. [Wilson, Craig M.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. RP Havens, PL (reprint author), Suite C450,POB 1997, Milwaukee, WI 53201 USA. EM phavens@mcw.edu FU National Institutes of Health (NIH) through the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [U01 HD 040533, U01 HD 040474]; National Institutes on Drug Abuse and Mental Health; National Institute of Allergy and Infectious Diseases; NICHD; National Institute of Mental Health [U01 A1068632]; General Clinical Research Center Program of the National Center for Research Resources; NIH; Department of Health and Human Services; Children's National Medical Center [M01RR020359]; University of Pennsylvania/Children's Hospital of Philadelphia [NCRRUL1-RR-024134]; University of California at San Francisco [UL1 RR024131]; Seattle Children's Hospital [UL1-RR025014]; Texas Children's Hospital and Baylor College of Medicine [M01-RR00188]; Boston University Medical Center [UL1-RR02517]; SUNY Stony Brook [M01RR10710]; Louisiana Board of Regents RC/EEP [RC/EEP-06] FX This work was supported by the ATN from the National Institutes of Health (NIH) (U01 HD 040533 and U01 HD 040474) through the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (to B.G.K.), with supplemental funding from the National Institutes on Drug Abuse (N. Borek) and Mental Health (P. Brouwers and S. Allison). The protocol was co-endorsed by the IMPAACT Group. Support for the IMPAACT Group was provided by the National Institute of Allergy and Infectious Diseases, the NICHD, and the National Institute of Mental Health (U01 A1068632). The study was scientifically reviewed by the ATN's Therapeutic Leadership Group. Network, scientific, and logistical support was provided by the ATN Coordinating Center (C.W. and C. Partlow) at The University of Alabama at Birmingham. Network operations and analytic support was provided by the ATN Data and Operations Center at Westat, Inc. (J. Korelitz and B. Driver).; Eight of the participating sites used their General Clinical Research Center/Pediatric Clinical Research Center for the study; the centers were supported by grants from the General Clinical Research Center Program of the National Center for Research Resources, NIH, Department of Health and Human Services as follows: Children's National Medical Center, M01RR020359; University of Pennsylvania/Children's Hospital of Philadelphia, NCRRUL1-RR-024134; University of California at San Francisco, UL1 RR024131; Seattle Children's Hospital, UL1-RR025014; Texas Children's Hospital and Baylor College of Medicine, M01-RR00188; Boston University Medical Center, UL1-RR02517; and SUNY Stony Brook, M01RR10710. The Tulane University Health Sciences Center used its Clinical and Translational Research Center for the study; the center was supported in whole or in part by funds provided through the Louisiana Board of Regents RC/EEP (RC/EEP-06). NR 39 TC 20 Z9 21 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2012 VL 97 IS 11 BP 4004 EP 4013 DI 10.1210/jc.2012-2600 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 032IT UT WOS:000310710500049 PM 22933542 ER PT J AU Kritchevsky, SB Tooze, JA Neiberg, RH Schwartz, GG Hausman, DB Johnson, MA Bauer, DC Cauley, JA Shea, MK Cawthon, PM Harris, TB Rubin, SM Tylavsky, FA Houston, DK AF Kritchevsky, Stephen B. Tooze, Janet A. Neiberg, Rebecca H. Schwartz, Gary G. Hausman, Dorothy B. Johnson, Mary Ann Bauer, Douglas C. Cauley, Jane A. Shea, M. Kyla Cawthon, Peggy M. Harris, Tamara B. Rubin, Susan M. Tylavsky, Francis A. Houston, Denise K. CA Hlth ABC Study TI 25-Hydroxyvitamin D, Parathyroid Hormone, and Mortality in Black and White Older Adults: The Health ABC Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE MORTALITY; RANDOMIZED CONTROLLED-TRIALS; VITAMIN-D DEFICIENCY; SERUM CONCENTRATIONS; RISK; COMMUNITY; ASSOCIATION; POPULATION; WOMEN AB Context: Previous 25-hydroxyvitamin D [25(OH)D] and mortality studies have included mostly individuals of European descent. Whether the relationship is similar in Blacks and to what extent differences in 25(OH)D explain racial disparities in mortality is unclear. Objective: The objective of the study was to examine the relationship between 25(OH)D, PTH, and mortality in Black and white community-dwelling older adults over 8.5 yr of follow-up. Design and Setting: Health ABC is a prospective cohort study conducted in Memphis, TN, and Pittsburgh, PA. Participants: Well-functioning Blacks and whites aged 71-80 yr with measured 25(OH)D and PTH (n = 2638; 49% male, 39% Black) were included in the study. Main Outcome Measure: Multivariate-adjusted proportional hazards models estimated the hazard ratios (HR) for all-cause, cardiovascular, cancer, and noncancer, noncardiovascular mortality (n = 691 deaths). Results: Mean 25(OH)D concentrations were higher in whites than in Blacks [mean (SD): 29.0 (9.9) and 20.8 (8.7) ng/ml, respectively; P < 0.001]. Serum 25(OH)D by race interactions were not significant, however. Lower 25(OH)D concentrations were associated with higher mortality in Blacks and whites combined [HR (95% confidence interval [CI] 2.27 (1.59-3.24), 1.48 (1.20-1.84), and 1.25 (1.02-1.52) for <10, 10 to <20, and 20 to <30 vs. >= 30 ng/ml]. In the multivariate model without 25(OH)D, Blacks had 22% higher mortality than whites [HR (95% CI) 1.22 (1.01, 1.48)]; after including 25(OH)D in the model, the association was attenuated [1.09 (0.90-1.33)]. The mortality population attributable risks (95% CI) for 25(OH)D concentrations less than 20 ng/ml and less than 30 ng/ml in Blacks were 16.4% (3.1-26.6%) and 37.7% (11.6-55.1%) and in whites were 8.9% (3.9-12.7%) and 11.1% (-2.7 to 22.0%), respectively. PTH was also associated with mortality [HR (95% CI) 1.80 (1.33-2.43) for >= 70 vs. <23 pg/ml]. Conclusions: Low 25(OH)D and high PTH concentrations were associated with increased mortality in Black and white community-dwelling older adults. Because 25(OH)D concentrations were much lower in Blacks, the potential impact of remediating low 25(OH)D concentrations was greater in Blacks than whites. (J Clin Endocrinol Metab 97: 4156-4165, 2012) C1 [Kritchevsky, Stephen B.] Wake Forest Sch Med, Dept Internal Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA. [Tooze, Janet A.; Neiberg, Rebecca H.] Wake Forest Sch Med, Dept Biostat, Winston Salem, NC 27157 USA. [Schwartz, Gary G.] Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. [Hausman, Dorothy B.; Johnson, Mary Ann] Univ Georgia, Dept Food & Nutr, Athens, GA 30602 USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94120 USA. [Harris, Tamara B.] NIA, Lab Epidemiol & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Tylavsky, Francis A.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA. RP Kritchevsky, SB (reprint author), Wake Forest Sch Med, Dept Internal Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM skritche@wakehealth.edu OI Kritchevsky, Stephen/0000-0003-3336-6781; Cauley, Jane A/0000-0003-0752-4408 FU National Institutes of Health, National Institute on Aging; National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01 AG029364, R01 AG028050]; National Institute of Nursing Research [R01 NR012459]; Wake Forest University Claude D. Pepper Older Americans Independence Center [P30 AG021332] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, and National Institute on Aging Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; National Institute on Aging Grants R01 AG029364 and R01 AG028050; National Institute of Nursing Research Grant R01 NR012459; and the Wake Forest University Claude D. Pepper Older Americans Independence Center Grant P30 AG021332. NR 40 TC 32 Z9 33 U1 1 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2012 VL 97 IS 11 BP 4156 EP 4165 DI 10.1210/jc.2012-1551 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 032IT UT WOS:000310710500066 PM 22942386 ER PT J AU Crocker, MK Barak, S Millo, CM Beall, SA Niyyati, M Chang, R Avila, NA Van Ryzin, C Segars, J Quezado, M Merke, DP AF Crocker, Melissa K. Barak, Stephanie Millo, Corina M. Beall, Stephanie A. Niyyati, Mahtab Chang, Richard Avila, Nilo A. Van Ryzin, Carol Segars, James Quezado, Martha Merke, Deborah P. TI Use of PET/CT with Cosyntropin Stimulation to Identify and Localize Adrenal Rest Tissue following Adrenalectomy in a Woman with Congenital Adrenal Hyperplasia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 21-HYDROXYLASE DEFICIENCY; ADRENOCORTICOTROPIN HYPERSECRETION; BILATERAL ADRENALECTOMY; TUMORS; PATIENT; PREVALENCE; MALES AB Context: Adrenalectomy is an experimental treatment option for select patients with congenital adrenal hyperplasia who have failed medical therapy. After adrenalectomy, adrenal rest tissue can remain in extraadrenal locations, cause recurrent hyperandrogenism, and be difficult to localize. Objective: The aim of the study was to investigate the usefulness of positron emission tomography/computerized tomography (PET/CT) in identifying adrenal rest tissue. Subject: A female with salt-wasting 21-hydroxylase deficiency who had bilateral adrenalectomy at age 17 yr presented with hyperandrogenism at age 32 yr. Pelvic magnetic resonance imaging and ultrasound imaging were nondiagnostic for the source of androgen production. Methods and Results: A baseline F-18 labeled fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT scan showed no active uptake; however, a second scan preceded by a 250-mu g cosyntropin injection identified three areas of active uptake near both ovaries. Subsequent ovarian venous sampling showed elevations in 17-hydroxyprogesterone, androstenedione, and 21-deoxycortisol in both ovarian veins compared to a peripheral vein at baseline and more so after cosyntropin administration. At laparoscopy, three well-circumscribed nodules (2.4 x 0.9 x 1.3 cm, 1.2 x 1.5 x 1.5 cm, and 2 x 1.5 x 1 cm) lying lateral to the fallopian tubes adjacent to the broad ligaments were removed. The paraovarian nodules and previously removed adrenal glands had similar histology and immunohistochemistry. Postoperatively, androgen concentrations were undetectable, with no response to cosyntropin stimulation. Conclusions: Patients with CAH after an adrenalectomy may experience recurrent hyperandrogenism due to adrenal rest tissue. 18F-FDG PET/CT with cosyntropin stimulation accurately identified adrenal rest tissue not visualized with conventional imaging, allowing for successful surgical resection. (J Clin Endocrinol Metab 97: E2084-E2089, 2012) C1 [Crocker, Melissa K.; Segars, James; Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Crocker, Melissa K.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Barak, Stephanie; Quezado, Martha] NCI, NIH, Bethesda, MD 20892 USA. [Millo, Corina M.; Beall, Stephanie A.; Chang, Richard; Van Ryzin, Carol; Merke, Deborah P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Niyyati, Mahtab] NIDDK, NIH, Bethesda, MD 20892 USA. [Avila, Nilo A.] Vet Affairs Med Ctr, Serv Radiol, Washington, DC 20422 USA. [Avila, Nilo A.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Crocker, MK (reprint author), 330 Longwood Ave, Boston, MA 02115 USA. EM melissa.crocker@childrens.harvard.edu FU The Intramural Research Programs of The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health Clinical Center FX This work was funded by The Intramural Research Programs of The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institutes of Health Clinical Center. NR 18 TC 13 Z9 14 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2012 VL 97 IS 11 BP E2084 EP E2089 DI 10.1210/jc.2012-2298 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 032IT UT WOS:000310710500007 PM 22904181 ER PT J AU Dauber, A LaFranchi, SH Maliga, Z Lui, JC Moon, JE McDeed, C Henke, K Zonana, J Kingman, GA Pers, TH Baron, J Rosenfeld, RG Hirschhorn, JN Harris, MP Hwa, V AF Dauber, Andrew LaFranchi, Stephen H. Maliga, Zoltan Lui, Julian C. Moon, Jennifer E. McDeed, Cailin Henke, Katrin Zonana, Jonathan Kingman, Garrett A. Pers, Tune H. Baron, Jeffrey Rosenfeld, Ron G. Hirschhorn, Joel N. Harris, Matthew P. Hwa, Vivian TI Novel Microcephalic Primordial Dwarfism Disorder Associated with Variants in the Centrosomal Protein Ninein SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-I; MEIER-GORLIN-SYNDROME; DNA-SEQUENCING DATA; SECKEL-SYNDROME; MOLECULAR CHARACTERIZATION; POSTNATAL-GROWTH; GENE; MUTATIONS; ORGANIZATION; DUPLICATION AB Context: Microcephalic primordial dwarfism (MPD) is a rare, severe form of human growth failure in which growth restriction is evident in utero and continues into postnatal life. Single causative gene defects have been identified in a number of patients with MPD, and all involve genes fundamental to cellular processes including centrosome functions. Objective: The objective of the study was to find the genetic etiology of a novel presentation of MPD. Design: The design of the study was whole-exome sequencing performed on two affected sisters in a single family. Molecular and functional studies of a candidate gene were performed using patient-derived primary fibroblasts and a zebrafish morpholino oligonucleotides knockdown model. Patients: Two sisters presented with a novel subtype of MPD, including severe intellectual disabilities. Main Outcome Measures: NIN, encoding Ninein, a centrosomal protein critically involved in asymmetric cell division, was identified as a candidate gene, and functional impacts in fibroblasts and zebrafish were studied. Results: From 34,606 genomic variants, two very rare missense variants in NIN were identified. Both pro-bands were compound heterozygotes. In the zebrafish, ninein knock down led to specific and novel defects in the specification and morphogenesis of the anterior neuroectoderm, resulting in a deformity of the developing cranium with a small, squared skull highly reminiscent of the human phenotype. Conclusion: We identified a novel clinical subtype of MPD in two sisters who have rare variants in NIN. We show, for the first time, that reduction of ninein function in the developing zebrafish leads to specific deficiencies of brain and skull development, offering a developmental basis for the myriad phenotypes in our patients. (J Clin Endocrinol Metab 97: E2140-E2151, 2012) C1 [Dauber, Andrew; Pers, Tune H.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Moon, Jennifer E.; Pers, Tune H.; Hirschhorn, Joel N.] Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA. [McDeed, Cailin; Henke, Katrin; Harris, Matthew P.] Childrens Hosp, Dept Orthopaed Res, Boston, MA 02115 USA. [Kingman, Garrett A.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Dauber, Andrew; Moon, Jennifer E.; Pers, Tune H.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [LaFranchi, Stephen H.; Rosenfeld, Ron G.; Hwa, Vivian] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA. [Zonana, Jonathan] Oregon Hlth & Sci Univ, Dept Mol & Med Genet & Pediat, Portland, OR 97239 USA. [Maliga, Zoltan] Max Planck Inst Cell Biol & Genet, D-01307 Dresden, Germany. [Lui, Julian C.; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [McDeed, Cailin; Henke, Katrin; Hirschhorn, Joel N.; Harris, Matthew P.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Kingman, Garrett A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Pers, Tune H.] Tech Univ Denmark, Ctr Biol Sequence, DK-5617 BA Eindhoven, Denmark. RP Dauber, A (reprint author), Childrens Hosp, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA. EM andrew.dauber@childrens.harvard.edu RI Lui, Chun Kin Julian/E-2253-2012 FU National Institutes of Health [5K12HD052896]; March of Dimes Grant [6-FY09-507]; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Nikon Imaging Center at Harvard Medical School; Danish Council for Independent Research Medical Sciences FX This work was supported by National Institutes of Health Grant 5K12HD052896 (to A.D.), March of Dimes Grant 6-FY09-507 (to J.N.H.), The Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (to J.C.L. and J.B.) as well as The Nikon Imaging Center at Harvard Medical School. T.H.P. is supported by The Danish Council for Independent Research Medical Sciences (FSS). NR 40 TC 25 Z9 26 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2012 VL 97 IS 11 BP E2140 EP E2151 DI 10.1210/jc.2012-2150 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 032IT UT WOS:000310710500017 PM 22933543 ER PT J AU Vezzosi, D Libe, R Baudry, C Rizk-Rabin, M Horvath, A Levy, I Rene-Corail, F Ragazzon, B Stratakis, CA Vandecasteele, G Bertherat, J AF Vezzosi, Delphine Libe, Rossella Baudry, Camille Rizk-Rabin, Marthe Horvath, Anelia Levy, Isaac Rene-Corail, Fernande Ragazzon, Bruno Stratakis, Constantine A. Vandecasteele, Gregoire Bertherat, Jerome TI Phosphodiesterase 11A (PDE11A) Gene Defects in Patients with ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH): Functional Variants May Contribute to Genetic Susceptibility of Bilateral Adrenal Tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NODULAR ADRENOCORTICAL DISEASE; CUSHINGS-SYNDROME; REGULATORY SUBUNIT; CARNEY COMPLEX; I-ALPHA; MUTATIONS; PROTEIN; EXPRESSION; RECEPTORS; FREQUENT AB Context: Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP levels. PDE11A function has been linked to predisposition to adrenocortical tumors. Objective: The aim of the study was to study the PDE11A gene in a large cohort of patients with ACTH-independent macronodular adrenal hyperplasia (AIMAH) and in control subjects. Design: The PDE11A entire coding region was sequenced in 46 patients with AIMAH and 192 controls. Two variants found in AIMAH patients were transiently expressed in HEK 293 and adrenocortical H295R cells for further functional studies. Results: The frequency of all PDE11A variants was significantly higher among patients with AIMAH (28%) compared to controls (7.2%) (P = 5 x 10(-5)). Transfection of the two PDE11A variants found in AIMAH patients only (D609N or M878V) showed that cAMP levels were higher, after forskolin stimulation, in cells transfected with the PDE11A mutants, compared to cells transfected with the wild-type PDE11A in HEK 293 cells (P < 0.05). Moreover, transfection with mutants PDE11A increased transcriptional activity of a cAMP-response element reporter construct compared to wild-type PDE11A in HEK 293 cells (P < 0.0004 for D609N and P < 0.003 for M878V) and in the adrenocortical H295R cells (P < 0.05 for D609N and M878V). In addition, analysis of cAMP levels in intact living culture cells by fluorescence resonance energy transfer probes showed increased cAMP in forskolin-treated cells transfected with PDE11A variants compared with wild-type PDE11A (P < 0.05). Conclusion: We conclude that PDE11A genetic variants may increase predisposition to AIMAH. (J Clin Endocrinol Metab 97: E2063-E2069, 2012) C1 [Vezzosi, Delphine; Libe, Rossella; Baudry, Camille; Rizk-Rabin, Marthe; Rene-Corail, Fernande; Ragazzon, Bruno; Bertherat, Jerome] INSERM, Unite 1016, CNRS, UMR 8104,Inst Cochin, F-75014 Paris, France. [Vezzosi, Delphine; Libe, Rossella; Baudry, Camille; Rizk-Rabin, Marthe; Ragazzon, Bruno; Bertherat, Jerome] Univ Paris 05, Fac Med Paris 5, F-75005 Paris, France. [Vezzosi, Delphine] Hop Larrey, Dept Endocrinol, F-31480 Toulouse, France. [Libe, Rossella; Baudry, Camille; Bertherat, Jerome] Hop Cochin, Reference Ctr Rare Adrenal Dis, AP HP, Dept Endocrinol, F-75014 Paris, France. [Horvath, Anelia; Levy, Isaac; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol Genet, NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA. [Vandecasteele, Gregoire] INSERM, UMR S 769, Labex Lab Excellence Res Medicat & Innovat Therap, F-92296 Chatenay Malabry, France. [Vandecasteele, Gregoire] Univ Paris Sud, Inst Federatif Rech 141, F-92296 Chatenay Malabry, France. RP Bertherat, J (reprint author), Hop Cochin 27, Serv Endocrinol, Rue Faubourg St Jacques, F-75014 Paris, France. EM jerome.bertherat@cch.aphp.fr RI Ragazzon, Bruno/E-6541-2017 OI Ragazzon, Bruno/0000-0001-9476-4973 FU Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Agence Nationale de la Recherche [ANR08-GENOPAT-002, ANR-10-Blan-1136]; Institut National du Cancer FX This work was supported by the Intramural Program (to A.H., I.L., C.S.) of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; and by the Agence Nationale de la Recherche (ANR08-GENOPAT-002; and ANR-10-Blan-1136). D.V. is the recipient of a fellowship from the Institut National du Cancer. NR 40 TC 24 Z9 24 U1 0 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2012 VL 97 IS 11 BP E2063 EP E2069 DI 10.1210/jc.2012-2275 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 032IT UT WOS:000310710500004 PM 22996146 ER PT J AU Magnani, JW Newton-Cheh, C O'Donnell, CJ Levy, D AF Magnani, Jared W. Newton-Cheh, Christopher O'Donnell, Christopher J. Levy, Daniel TI Development and application of a longitudinal electrocardiogram repository: the Framingham Heart Study SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Electrocardiography; Epidemiology; Repository; Framingham ID CHRONIC ATRIAL-FIBRILLATION AB The electrocardiogram (ECG) has widespread use in clinical care and research. Despite its extensive use and study, important gaps remain in examining prospective, repeated longitudinal ECG measures, and their association with cardiovascular outcomes. The Framingham Heart Study (FRS) is a community-based study designed to examine risk factors and outcomes associated with cardiovascular disease. Here, we describe a novel effort in the FHS to develop a unique resource: serial ECGs conducted on 3 generations of study participants spanning multiple decades (1986 to the present). We describe the FHS and the role the ECG has had in conducting cardiovascular epidemiology in the FHS. We then describe potential applications for a longitudinal ECG repository. We expect the Framingham ECG repository to enhance cardiovascular research and epidemiologic study. Such a resource will complement the phenotypic and genotypic characterization of FHS, facilitating novel investigations of cardiovascular epidemiology. (C) 2012 Elsevier Inc. All rights reserved. C1 [Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, Boston, MA 02118 USA. [Magnani, Jared W.; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Levy, Daniel] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Newton-Cheh, Christopher; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Magnani, Jared W.; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Framingham, MA USA. [O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu FU National Institutes of Health (NIH) [R21HL106092]; American Heart Association [09FTF219028]; NIH [6R01-NS17950, N01-HC25195] FX Dr Magnani is supported by grants from the National Institutes of Health (NIH) (R21HL106092) and the American Heart Association (09FTF219028). This work was supported by NIH grants 6R01-NS17950, N01-HC25195. NR 13 TC 3 Z9 3 U1 0 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2012 VL 45 IS 6 BP 673 EP 676 DI 10.1016/j.jelectrocard.2012.06.016 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 032ZZ UT WOS:000310763300026 PM 22832152 ER PT J AU Eberlein, M Reed, RM Permutt, S Chahla, MF Bolukbas, S Nathan, SD Iacono, A Pearse, DB Fessler, HE Shah, AS Orens, JB Brower, RG AF Eberlein, Michael Reed, Robert M. Permutt, Solbert Chahla, Mayy F. Bolukbas, Servet Nathan, Steven D. Iacono, Aldo Pearse, David B. Fessler, Henry E. Shah, Ashish S. Orens, Jonathan B. Brower, Roy G. TI Parameters of donor-recipient size mismatch and survival after bilateral lung transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE lung transplantation; lung size mismatch; gender mismatch ID BRONCHIOLITIS OBLITERANS SYNDROME; MAXIMAL EXPIRATORY FLOW; INTERNATIONAL-SOCIETY; PULMONARY-FIBROSIS; RECOIL PRESSURE; SURFACE-TENSION; HEART; MECHANICS; CAPACITY; REGISTRY AB BACKGROUND: The purpose of this study was to investigate the relationship between donor recipient height, gender and predicted estimates of total lung capacity (pTLC) mismatches and post-transplant survival. METHODS: The lung transplant databases at three programs were reviewed. The pTLC ratios (donor pTLC/recipient pTLC) and height ratios (donor height/recipient height) were calculated retrospectively. Patients were grouped according to pTLC ratio <= 1.0 or >1.0 and height ratio <= 1.0 or >1.0, and according to gender (mis-)matching. A time-to-event analysis was performed for risk of death after transplantation conditional on 30-day survival using Kaplan-Meier survival and Cox proportional hazard models. RESULTS: There were 211 adult bilateral lung transplant recipients who qualified for the analysis. Mean follow-up was comparable for all cohorts (range 2.21 to 3.85 years). In the univariate Cox proportional hazard models, a pTLC ratio >1.0 (HR 0.43, p = 0.002) and a height ratio >1.0 (HR 0.61, p = 0.03) were associated with better survival, and a female-donor-to-male-recipient gender mismatch (F-to-M) was associated with worse survival (HR 2.35, p = 0.01). In the multivariate Cox proportional hazard model accounting for F-to-M gender mismatch and height ratio >1.0, a pTLC ratio >1.0 remained associated with survival (HR 0.38, p = 0.015). However, accounting for a pTLC ratio >1.0, a height ratio of >1.0 and F-to-M mismatch were not associated with survival. CONCLUSIONS: A pTLC ratio >1.0 is associated with improved survival after bilateral lung transplantation. The pTLC ratio might better reflect allograft thorax mismatch than the height ratio, as it also accounts for effects of gender on lung and thoracic volumes. J Heart Lung Transplant 2012;31:1207-13 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved. C1 [Eberlein, Michael; Permutt, Solbert; Pearse, David B.; Fessler, Henry E.; Orens, Jonathan B.; Brower, Roy G.] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. [Chahla, Mayy F.] Johns Hopkins Univ, Sch Med, Dept Med, Div Hosp Med, Baltimore, MD 21205 USA. [Eberlein, Michael] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Reed, Robert M.; Iacono, Aldo] Univ Maryland, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA. [Bolukbas, Servet] Dr Horst Schmidt Klin, Dept Thorac Surg, Wiesbaden, Germany. [Nathan, Steven D.] Inova Fairfax Hosp, Adv Lung Dis Program, Falls Church, VA USA. [Shah, Ashish S.] Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA. RP Eberlein, M (reprint author), Univ Iowa, Carver Coll Med, Div Pulm Crit Care & Occupat Med, 200 Hawkins Dr,C326, Iowa City, IA 52242 USA. EM michael-eberlein@uiowa.edu OI Shah, Ashish/0000-0002-1821-9110 NR 24 TC 27 Z9 27 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 2012 VL 31 IS 11 BP 1207 EP 1213 DI 10.1016/j.healun.2011.07.015 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 028II UT WOS:000310415600010 PM 22036314 ER PT J AU Jones, TH Adams, RMM Spande, TF Garraffo, HM Kaneko, T Schultz, TR AF Jones, Tappey H. Adams, Rachelle M. M. Spande, Thomas F. Garraffo, H. Martin Kaneko, Tetsuo Schultz, Ted R. TI Histrionicotoxin Alkaloids Finally Detected in an Ant SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID DENDROBATID POISON FROGS; ARTHROPOD SOURCE; SKIN ALKALOIDS; DIETARY SOURCE; C-13 NMR; DECAHYDROQUINOLINES; PUMILIOTOXINS; MADAGASCAR; CHEMISTRY; COMMON AB Workers of the ant Carebarella bicolor collected in Panama were found to have two major poison-frog alkaloids, cis- and trans-fused decahydroquinolines (DHQs) of the 269AB type, four minor 269AB isomers, two minor 269B isomers, and three isomers of DHQ 271D. For the first time in an ant, however, the DHQs were accompanied by six histrionicotoxins (HIXs), viz, 283A, 285A, 285B, 285C, 287A, and 287D. This co-occurrence of the HTX and DHQ alkaloids is the usual pattern seen in dendrobatid frogs. This finding contrasts with our earlier study, where workers of a Brazilian ant, Solenopsis (Diplorhoptrum) sp., were found to have a very similar DHQ complex but failed to show HTXs. Several new DHQ alkaloids of MW 271 (named in the frog as 271G) are reported from the above ants that have both m/z 202 and 204 as major fragment ions, unlike the spectrum seen for the poison-frog alkaloid 271D, which has only an m/z 204 base peak. Found also for the first time in skin extracts from the comparison frog Oophaga granulifera of Costa Rica is a trace DHQ of MW 273. It is coded as 273F in the frog; a different isomer is found in the ant. C1 [Jones, Tappey H.] Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. [Adams, Rachelle M. M.] Univ Copenhagen, Ctr Social Evolut, Dept Biol, DK-2100 Copenhagen, Denmark. [Spande, Thomas F.; Garraffo, H. Martin; Kaneko, Tetsuo] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Schultz, Ted R.] Smithsonian Inst, Dept Entomol, NHB, Washington, DC 20013 USA. RP Jones, TH (reprint author), Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA. EM jonesth@vmi.edu RI Adams, Rachelle/J-8846-2013 OI Adams, Rachelle/0000-0002-0918-9861 NR 24 TC 5 Z9 5 U1 3 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD NOV PY 2012 VL 75 IS 11 BP 1930 EP 1936 DI 10.1021/np300485v PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 042HC UT WOS:000311461300009 PM 23088730 ER PT J AU Mozer, BA Sandstrom, DJ AF Mozer, Brian A. Sandstrom, David J. TI Drosophila neuroligin 1 regulates synaptic growth and function in response to activity and phosphoinositide-3-kinase SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Drosophila; Neuroligin; Neurexin; Synapse; Activity; Phosphoinositide-3-kinase ID FRAGILE-X-SYNDROME; NEUROMUSCULAR-JUNCTION; GLUTAMATERGIC SYNAPSES; INHIBITORY SYNAPSES; TRANSMITTER RELEASE; HIPPOCAMPAL-NEURONS; GENETIC DISSECTION; AMPA RECEPTORS; PLASTICITY; NEUREXINS AB Neuroligins are postsynaptic neural cell adhesion molecules that mediate synaptic maturation and function in vertebrates and invertebrates, but their mechanisms of action and regulation are not well understood. At the Drosophila larval neuromuscular junction (NMJ), previous analysis demonstrated a requirement for Drosophila neuroligin 1 (dnlg1) in synaptic growth and maturation. The goal of the present study was to better understand the effects and mechanisms of loss-of-function and overexpression of dnlg1 on synapse size and function, and to identify signaling pathways that control dnlg1 expression. Consistent with reduced synapse size, evoked excitatory junctional currents (EJCs) were diminished in dnlg1 mutants but displayed normal Ca2+ sensitivity and short-term plasticity. However, postsynaptic function was also perturbed, in that glutamate receptor staining and the distribution of amplitudes of miniature excitatory junctional currents (mEJCs) were abnormal in mutants. All the above phenotypes were rescued by a genomic transgene. Overexpression of dnlg1 in muscle resulted in synaptic overgrowth, but reduced the amplitudes of EJCs and mEJCs. Overgrowth and reduced EJC amplitude required Drosophila neurexin 1 (dnrx1) function, suggesting that increased DNlg1/DNrx1 signaling attenuates synaptic transmission and regulates growth through a retrograde mechanism. In contrast, reduced mEJC amplitude was independent of dnrx1. Synaptic overgrowth, triggered by neuronal hyperactivity, absence of the E3 ubiquitin ligase highwire, and increased phosphoinositide-3-kinase (PI3K) signaling in motor neurons reduced synaptic DNlg1 levels. Likewise, postsynaptic attenuation of PI3K, which increases synaptic strength, was associated with reduced DNlg1 levels. These observations suggest that activity and PI3K signaling pathways modulate growth and synaptic transmission through dnlg1-dependent mechanisms. Published by Elsevier Inc. C1 [Mozer, Brian A.] NHLBI, Ctr Dev Biol, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. [Sandstrom, David J.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mozer, BA (reprint author), NHLBI, Ctr Dev Biol, Lab Biochem Genet, NIH, Bldg 10,Rm 7N317,10 Ctr Dr, Bethesda, MD 20892 USA. EM mozerb@nhlbi.nih.gov FU National Institute of Heart, Lung and Blood; National Institute of Mental Health FX The work was supported by the intramural research program of the National Institute of Heart, Lung and Blood (B.A.M.) and the National Institute of Mental Health (D.J.S.). We thank Marshall Nirenberg for his early support of this work, Shu-Hwa Yu for assistance with immuno-staining experiments, Devera Schoenberg (DIR, NINDS) for proofreading of the manuscript, the NHLBI Intramural Light Microscope Core Facility, and Jun Zhu and Ting Ni for help with qPCR. We thank Howard Nash, NIMH, for support and critical reading of the manuscript, Benjamin White, NIMH, for critical reading of the manuscript and the use of equipment, and our colleagues at the NIH and elsewhere that provided equipment, reagents and fly strains. NR 78 TC 7 Z9 7 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD NOV PY 2012 VL 51 IS 3-4 BP 89 EP 100 DI 10.1016/j.mcn.2012.08.010 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 044DL UT WOS:000311599500004 PM 22954894 ER PT J AU Miao, YL Williams, CJ AF Miao, Yi-Liang Williams, Carmen J. TI Calcium signaling in mammalian egg activation and embryo development: The influence of subcellular localization SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Review DE fertilization; oocyte; calcium influx; SOCE; CaMKII ID PROTEIN-KINASE-C; GREEN-FLUORESCENT PROTEIN; FERTILIZED MOUSE EGGS; OPERATED CA2+ ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; STROMAL INTERACTION MOLECULE; DOMAIN-MEDIATED ACTIVATION; GERMINAL VESICLE BREAKDOWN; SRC FAMILY KINASE; PHOSPHOLIPASE-C AB Calcium (Ca2+) signals drive the fundamental events surrounding fertilization and the activation of development in all species examined to date. Initial studies of Ca2+ signaling at fertilization in marine animals were tightly linked to new discoveries of bioluminescent proteins and their use as fluorescent Ca2+ sensors. Since that time, there has been rapid progress in our understanding of the key functions for Ca2+ in many cell types and of the impact of cellular localization on Ca2+ signaling pathways. In this review, which focuses on mammalian egg activation, we consider how Ca2+ is regulated and stored at different stages of oocyte development and examine the functions of molecules that serve as both regulators of Ca2+ release and effectors of Ca2+ signals. We then summarize studies exploring how Ca2+ directs downstream effectors mediating both egg activation and later signaling events required for successful preimplantation embryo development. Throughout this review, we focus attention on how localization of Ca2+ signals influences downstream signaling events, and attempt to highlight gaps in our knowledge that are ripe for future research. Mol. Reprod. Dev. 79: 742756, 2012. Published 2012. This article is a US government work and, as such, is in the public domain in the United States of America. C1 [Miao, Yi-Liang; Williams, Carmen J.] NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Williams, CJ (reprint author), NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH,DHHS, POB 12233,MD E4-05, Res Triangle Pk, NC 27709 USA. EM williamsc5@niehs.nih.gov FU Intramural Research Program of the NIH; National Institutes of Environmental Health Sciences [Z01ES102985] FX Grant sponsor: Intramural Research Program of the NIH; Grant sponsor: National Institutes of Environmental Health Sciences; Grant number: Z01ES102985 NR 139 TC 26 Z9 27 U1 3 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD NOV PY 2012 VL 79 IS 11 BP 742 EP 756 DI 10.1002/mrd.22078 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 040CL UT WOS:000311297000001 PM 22888043 ER PT J AU Chang, S Sharan, SK AF Chang, Suhwan Sharan, Shyam K. TI BRCA1 and MicroRNAs: Emerging networks and potential therapeutic targets SO MOLECULES AND CELLS LA English DT Review DE antagomir; breast cancer; BRCA1; microRNA mimic; microRNAs ID BREAST-CANCER RISK; POLYMERASE-II HOLOENZYME; OVARIAN-CANCER; MUTATION CARRIERS; DOWN-REGULATION; CELL-PROLIFERATION; EZH2 EXPRESSION; IN-VIVO; GENE; GROWTH AB BRCA1 is a well-known tumor suppressor implicated in familial breast and ovarian cancer. Since its cloning in 1994, numerous studies have established BRCA1's role in diverse cellular and biochemical processes, such as DNA damage repair, cell cycle control, and transcriptional regulation as well as ubiquitination. In addition, a number of recent studies have functionally linked this tumor suppressor to another important cellular regulator, microRNAs, which are short (19-22 nt) RNAs that were discovered in the nematode in 1993. Soon their presence and function were validated in mammals, and since then, the role of microRNAs has been actively investigated in almost all biological processes, including cancer. In this review, we will describe recent progress in the understanding of the BRCA1 function through microRNAs and the role of microRNAs in regulating BRCA1, with emphasis on the implication of these processes on the development and progression of cancer. We will also discuss the therapeutic potential of microRNA mimics or inhibitors of microRNAs to affect BRCA1 function. C1 [Chang, Suhwan; Sharan, Shyam K.] Frederick Natl Lab Canc Res, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Sharan, SK (reprint author), Frederick Natl Lab Canc Res, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. EM sharans@mail.nih.gov FU Center for Cancer Research Intramural Program, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services FX This work is supported by the Center for Cancer Research Intramural Program, National Cancer Institute, National Institutes of Health, a part of the U.S. Department of Health and Human Services. NR 80 TC 12 Z9 12 U1 0 U2 5 PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY PI SEOUL PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD NOV PY 2012 VL 34 IS 5 BP 425 EP 432 DI 10.1007/s10059-012-0118-y PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 043AZ UT WOS:000311516400002 PM 22936386 ER PT J AU Gargis, AS Kalman, L Berry, MW Bick, DP Dimmock, DP Hambuch, T Lu, F Lyon, E Voelkerding, KV Zehnbauer, BA Agarwala, R Bennett, SF Chen, B Chin, ELH Compton, JG Das, S Farkas, DH Ferber, MJ Funke, BH Furtado, MR Ganova-Raeva, LM Geigenmuller, U Gunselman, SJ Hegde, MR Johnson, PLF Kasarskis, A Kulkarni, S Lenk, T Liu, CSJ Manion, M Manolio, TA Mardis, ER Merker, JD Rajeevan, MS Reese, MG Rehm, HL Simen, BB Yeakley, JM Zook, JM Lubin, IM AF Gargis, Amy S. Kalman, Lisa Berry, Meredith W. Bick, David P. Dimmock, David P. Hambuch, Tina Lu, Fei Lyon, Elaine Voelkerding, Karl V. Zehnbauer, Barbara A. Agarwala, Richa Bennett, Sarah F. Chen, Bin Chin, Ephrem L. H. Compton, John G. Das, Soma Farkas, Daniel H. Ferber, Matthew J. Funke, Birgit H. Furtado, Manohar R. Ganova-Raeva, Lilia M. Geigenmueller, Ute Gunselman, Sandra J. Hegde, Madhuri R. Johnson, Philip L. F. Kasarskis, Andrew Kulkarni, Shashikant Lenk, Thomas Liu, C. S. Jonathan Manion, Megan Manolio, Teri A. Mardis, Elaine R. Merker, Jason D. Rajeevan, Mangalathu S. Reese, Martin G. Rehm, Heidi L. Simen, Birgitte B. Yeakley, Joanne M. Zook, Justin M. Lubin, Ira M. TI Assuring the quality of next-generation sequencing in clinical laboratory practice SO NATURE BIOTECHNOLOGY LA English DT Letter C1 [Gargis, Amy S.; Kalman, Lisa; Zehnbauer, Barbara A.; Chen, Bin; Lubin, Ira M.] Ctr Dis Control & Prevent, Div Lab Sci & Stand, Atlanta, GA 30333 USA. [Berry, Meredith W.; Lu, Fei] SeqWright Inc, Houston, TX USA. [Bick, David P.; Dimmock, David P.] Med Coll Wisconsin, Dept Pediat, Div Genet, Milwaukee, WI 53226 USA. [Hambuch, Tina] Illumina Clin Serv, San Diego, CA USA. [Lyon, Elaine; Voelkerding, Karl V.] Univ Utah, Dept Pathol, Salt Lake City, UT USA. [Lyon, Elaine; Voelkerding, Karl V.] ARUP Labs, Inst Clin & Expt Pathol, Salt Lake City, UT USA. [Agarwala, Richa] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Bennett, Sarah F.] Ctr Medicare & Medicaid Serv, Div Lab Serv, Baltimore, MD USA. [Chin, Ephrem L. H.; Hegde, Madhuri R.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA. [Compton, John G.] GeneDx Inc, Gaithersburg, MD USA. [Das, Soma] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Farkas, Daniel H.] Sequenom Ctr Mol Med Inc, Grand Rapids, MI USA. [Ferber, Matthew J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Funke, Birgit H.; Rehm, Heidi L.] Partners Healthcare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA USA. [Funke, Birgit H.; Rehm, Heidi L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Furtado, Manohar R.] Life Technol, Foster City, CA USA. [Ganova-Raeva, Lilia M.] Ctr Dis Control & Prevent, Natl Ctr HIV Viral Hepatitis STD & TB Prevent, Atlanta, GA USA. [Geigenmueller, Ute] Correlagen Diagnost Inc, Waltham, MA USA. [Gunselman, Sandra J.] Kailos Genet Inc, Huntsville, AL USA. [Johnson, Philip L. F.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA. [Kasarskis, Andrew] Pacific Biosci, Menlo Pk, CA USA. [Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. [Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Lenk, Thomas] Celera Corp, Alameda, CA USA. [Liu, C. S. Jonathan; Manion, Megan] Softgenet LLC, State Coll, PA USA. [Manolio, Teri A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Mardis, Elaine R.] Washington Univ, Genome Ctr, St Louis, MO USA. [Mardis, Elaine R.] Washington Univ, Dept Genet & Mol Microbiol, St Louis, MO USA. [Merker, Jason D.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. [Rajeevan, Mangalathu S.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA. [Reese, Martin G.] Omica Inc, Emeryville, CA USA. [Simen, Birgitte B.] A Roche Co, Life Sci 454, Branford, CT USA. [Yeakley, Joanne M.] Illumina Inc, San Diego, CA USA. [Zook, Justin M.] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RP Gargis, AS (reprint author), Ctr Dis Control & Prevent, Div Lab Sci & Stand, Atlanta, GA 30333 USA. EM ILubin@cdc.gov RI Zook, Justin/B-7000-2008; Dimmock, David/I-7913-2015 OI Zook, Justin/0000-0003-2309-8402; Dimmock, David/0000-0001-6690-2523 FU NHGRI NIH HHS [R44 HG006579] NR 4 TC 180 Z9 183 U1 0 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2012 VL 30 IS 11 BP 1033 EP 1036 DI 10.1038/nbt.2403 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 037FL UT WOS:000311087500014 PM 23138292 ER PT J AU Bilke, S Gindin, Y AF Bilke, Sven Gindin, Yevgeniy TI Analyzing the association of SCNA boundaries with replication timing SO NATURE BIOTECHNOLOGY LA English DT Letter C1 [Bilke, Sven; Gindin, Yevgeniy] NCI, Bethesda, MD 20892 USA. RP Bilke, S (reprint author), NCI, Bethesda, MD 20892 USA. EM bilkes@mail.nih.gov NR 4 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2012 VL 30 IS 11 BP 1043 EP 1045 DI 10.1038/nbt.2415 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 037FL UT WOS:000311087500017 PM 23138295 ER PT J AU Tan, IL McArthur, JC Venkatesan, A Nath, A AF Tan, Ik L. McArthur, Justin C. Venkatesan, Arun Nath, Avindra TI Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised SO NEUROLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; POLYMERASE-CHAIN-REACTION; CLINICAL PRESENTATIONS; MULTIPLE-SCLEROSIS; VIRUS ENCEPHALITIS; 1 INFECTION; MULTICENTER; DEFICIENCY; EXPERIENCE; THERAPY AB Objective: To characterize clinical features, neuroimaging, and outcomes of herpes simplex encephalitis (HSE) in immunocompromised individuals. Methods: We performed a retrospective case control review of patients diagnosed with HSE. Adult patients were dichotomized into immunocompromised (n=14) and immunocompetent groups (n=15). Results: Fewer immunocompromised patients presented with prodromal symptoms and focal deficits. While the majority of CSF profiles in the immunocompromised patients were mononuclear cells predominant, 3 had polymorphonuclear predominance and another 3 had normal profiles. MRI showed widespread cortical involvement, with brainstem or cerebellar involvement in some. Two immunocompromised patients had recurrent HSE. The immunosuppressed state was associated with a decrease in Karnofsky Performance Status Scale (KPSS) score of 23.1 (p=0.018). Every 1-day delay in initiation of acyclovir was associated with a decrease in KPSS of 10.2 (p=0.002), and every 10 cell/mm(3) increase of CSF leukocytosis was associated with an increase in KPSS of 0.7 (p=0.009). Mortality rate was 6 times higher in the immunocompromised patients. Conclusions: Immunocompromised states may predispose to HSE with atypical clinical and neuro-radiologic features. Immunocompromised individuals with HSE have significantly worse outcomes and mortality. Early diagnosis and treatment is associated with improved outcome. The findings are particularly important in light of the increasing use of potent immunosuppressive and immunomodulatory therapies. Neurology (R) 2012; 79: 2125-2132 C1 [Tan, Ik L.; McArthur, Justin C.; Venkatesan, Arun] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. [Nath, Avindra] Natl Inst Neurol Disorders & Stroke, Sect Infect Nervous Syst, NIH, Bethesda, MD USA. RP Nath, A (reprint author), Natl Inst Neurol Disorders & Stroke, Sect Infect Nervous Syst, NIH, Bethesda, MD USA. EM natha@ninds.nih.gov FU NIH [1P30MH075673, UL1RR025005, R01NS056884, NS44807]; National Institute of Neurological Disorders and Stroke; Steg family; Biogen-Idec FX Supported in part by NIH grants 1P30MH075673, UL1RR025005, R01NS056884, 1P30MH075673, and NS44807 (J.C.M.), National Institute of Neurological Disorders and Stroke intramural funds, and the Steg family.; I.L. Tan reports no disclosures. J.C. McArthur has received grants from NIH and Biogen-Idec and stock options from Gliamed. A. Venkatesan and A. Nath report no disclosures. Go to Neurology.org for full disclosures. NR 34 TC 27 Z9 27 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV PY 2012 VL 79 IS 21 BP 2125 EP 2132 DI 10.1212/WNL.0b013e3182752ceb PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 039YK UT WOS:000311284300011 PM 23136265 ER PT J AU Chuang, JY Wang, SA Yang, WB Yang, HC Hung, CY Su, TP Chang, WC Hung, JJ AF Chuang, J-Y Wang, S-A Yang, W-B Yang, H-C Hung, C-Y Su, T-P Chang, W-C Hung, J-J TI Sp1 phosphorylation by cyclin-dependent kinase 1/cyclin B1 represses its DNA-binding activity during mitosis in cancer cells SO ONCOGENE LA English DT Article DE Sp1; CDK1; PP2A; myosin; mitosis ID TRANSCRIPTION FACTOR SP1; GENE-TRANSCRIPTION; HEAT-SHOCK; PROTEIN; EXPRESSION; PROMOTER; OVEREXPRESSION; ACTIVATION; STABILITY; FACTOR-1 AB Sp1 is important for the transcription of many genes. Our previous studies have shown that Sp1 is degraded in normal cell, but it is preserved in cancer cells during mitosis and exists a priori in the daughter cells, ready to engage in gene transcription and thereby contributes to the proliferation and survival of cancer cells. The mechanism by which Sp1 is preserved in cancer cells during mitosis remains unknown. In this study, we observed that Sp1 strongly colocalized with cyclin-dependent kinase 1 (CDK1)/cyclin B1 during mitosis. Moreover, we showed that Sp1 is a novel mitotic substrate of CDK1/cyclin B1 and is phosphorylated by it at Thr 739 before the onset of mitosis. Phospho-Sp1 reduced its DNA-binding ability and facilitated the chromatin condensation process during mitosis. Mutation of Thr739 to alanine resulted in Sp1 remaining in the chromosomes, delayed cell-cycle progression, and eventually led to apoptosis. Screening of Sp1-associated proteins during mitosis by using liquid chromatography/mass spectrometry indicated the tethering of Sp1 to myosin/F-actin. Furthermore, phospho-Sp1 and myosin/F-actin appeared to exist as a congregated ring at the periphery of the chromosome. However, at the end of mitosis and the beginning of interphase, Sp1 was dephosphorylated by PP2A and returned to the chromatin. These results indicate that cancer cells use CDK1 and PP2A to regulate the movement of Sp1 in and out of the chromosomes during cell-cycle progression, which may benefit cancer-cell proliferation. Oncogene (2012) 31, 4946-4959; doi:10.1038/onc.2011.649; published online 23 January 2012 C1 [Chuang, J-Y; Wang, S-A; Yang, W-B; Yang, H-C; Hung, J-J] Natl Cheng Kung Univ, Inst Bioinformat & Biosignal Transduct, Coll Biosci & Biotechnol, Tainan 701, Taiwan. [Hung, C-Y; Chang, W-C; Hung, J-J] Natl Cheng Kung Univ, Coll Med, Inst Med, Tainan 70101, Taiwan. [Su, T-P] Natl Inst Drug Abuse, NIH, Baltimore, MD USA. [Chang, W-C; Hung, J-J] Dept Pharmacol, Tainan, Taiwan. [Chang, W-C; Hung, J-J] Natl Cheng Kung Univ, Ctr Infect Dis & Signal Transduct, Tainan 701, Taiwan. [Chang, W-C] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei, Taiwan. RP Hung, JJ (reprint author), Natl Cheng Kung Univ, Inst Bioinformat & Biosignal Transduct, Coll Biosci & Biotechnol, Tainan 701, Taiwan. EM petehung@mail.ncku.edu.tw OI Yang, Wen-Bin/0000-0002-6497-4176 FU National Cheng Kung University project of the Program for Promoting Academic Excellence and Developing World Class Research Centers; National Science Council, Taiwan [NSC 97-2320-B-006-016-MY3, NSC 97-2311-B-006-002-MY3] FX This work was supported by the National Cheng Kung University project of the Program for Promoting Academic Excellence and Developing World Class Research Centers, together with grants NSC 97-2320-B-006-016-MY3 and NSC 97-2311-B-006-002-MY3 obtained from the National Science Council, Taiwan. NR 31 TC 5 Z9 5 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 2012 VL 31 IS 47 BP 4946 EP 4959 DI 10.1038/onc.2011.649 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 041VU UT WOS:000311430200006 PM 22266860 ER PT J AU Zhao, BY Pisitkun, T Hoffert, JD Knepper, MA Saeed, F AF Zhao, Boyang Pisitkun, Trairak Hoffert, Jason D. Knepper, Mark A. Saeed, Fahad TI CPhos: A program to calculate and visualize evolutionarily conserved functional phosphorylation sites SO PROTEOMICS LA English DT Article DE Bioinformatics; Conservation; Functional significance; Information theory; Phosphorylation sites ID PROTEIN-PHOSPHORYLATION; MATHEMATICAL-THEORY; SEQUENCE ALIGNMENT; PREDICTION; COMMUNICATION AB Profiling using high-throughput MS has discovered an overwhelming number of novel protein phosphorylation sites (phosphosites). However, the functional relevance of these sites is not always clear. In light of recent studies on the evolutionary mechanism of phosphorylation, we have developed CPhos, a Java program that can assess the conservation of phosphosites among species using an information theory-based approach. The degree of conservation established using CPhos can be used to assess the functional significance of phosphosites. CPhos has a user friendly graphical user interface and is available both as a web service and as a standalone Java application to assist phosphoproteomic researchers in analyzing and prioritizing lists of phosphosites for further experimental validation. CPhos can be accessed or downloaded at http://helixweb.nih.gov/CPhos/. C1 [Zhao, Boyang; Pisitkun, Trairak; Hoffert, Jason D.; Knepper, Mark A.; Saeed, Fahad] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Saeed, F (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, Bldg 10,Room 6N312,MSC 1603, Bethesda, MD 20892 USA. EM fahad.saeed@nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU NHLBI [Z01-HL-001285]; National Institute of Biomedical Imaging and Bioengineering FX We thank members of the Knepper lab and Kelly Brock for discussions and suggestions. This work was supported by the Intramural Budget of the NHLBI (NHLBI Project no. Z01-HL-001285). Boyang Zhao was a student intern from the University of Michigan in the National Institutes of Health Biomedical Engineering Summer Internship Program, funded by the National Institute of Biomedical Imaging and Bioengineering. NR 29 TC 15 Z9 15 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD NOV PY 2012 VL 12 IS 22 BP 3299 EP 3303 DI 10.1002/pmic.201200189 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 044JR UT WOS:000311616000004 PM 23001821 ER PT J AU Cornblatt, BA Carrion, RE Addington, J Seidman, L Walker, EF Cannon, TD Cadenhead, KS McGlashan, TH Perkins, DO Tsuang, MT Woods, SW Heinssen, R Lencz, T AF Cornblatt, Barbara A. Carrion, Ricardo E. Addington, Jean Seidman, Larry Walker, Elaine F. Cannon, Tyronne D. Cadenhead, Kristin S. McGlashan, Thomas H. Perkins, Diana O. Tsuang, Ming T. Woods, Scott W. Heinssen, Robert Lencz, Todd TI Risk Factors for Psychosis: Impaired Social and Role Functioning SO SCHIZOPHRENIA BULLETIN LA English DT Article DE clinical high risk; functional deficits; prodromal; social risk factors; functional outcome; attenuated positive symptoms ID CLINICAL HIGH-RISK; 2ND-GENERATION ANTIPSYCHOTICS; NEUROCOGNITIVE DEFICITS; SCHIZOPHRENIA PRODROME; NEGATIVE SYMPTOMS; ADOLESCENTS; INDIVIDUALS; PERFORMANCE; REHABILITATION; COMPETENCE AB Objectives: Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. Methods: Age-appropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. Results: At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. Conclusions: Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability. C1 [Cornblatt, Barbara A.; Carrion, Ricardo E.; Lencz, Todd] N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY 11004 USA. [Cornblatt, Barbara A.; Lencz, Todd] Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. [Cornblatt, Barbara A.; Carrion, Ricardo E.; Lencz, Todd] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Seidman, Larry] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat,Publ Psychiat Div,Beth Israel Deaco, Boston, MA 02115 USA. [Seidman, Larry] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Cannon, Tyronne D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cadenhead, Kristin S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Dept Psychiat, Boston, MA USA. [Heinssen, Robert] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Cornblatt, BA (reprint author), N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM Cornblat@lij.edu RI Lencz, Todd/J-3418-2014; OI Lencz, Todd/0000-0001-8586-338X; Carrion, Ricardo/0000-0002-6393-392X FU National Institute of Mental Health [R01 MH061523, U01 MH081857, R18 MH43518, U01 MH081928, P50 MH080272, R01 MH65079, RO1 MH062066, 5U01 MH081988, R01 MH60720, K24 MH76191, K05 MH01654, U01 MH066069, P50 MH064065, U01 MH74356, U01 MH082022, R41 MH083436, U01 MH066134]; Eli Lilly; Merck; Clinical Data Inc.; GoldenHelix, Inc.; Guidepoint Global; Cowen Co; Janssen Pharmaceuticals; Dainippon Sumitomo Pharma; AstraZeneca Pharmaceuticals; Bristol-Myers Squibb; Otsuka Pharmaceutical Co Ltd; Eli Lilly and Company; Pfizer; GlaxoSmithKline; Forest Labs; Shire; UCB Pharma; Bristol- Myers Squibb FX National Institute of Mental Health (R01 MH061523, U01 MH081857 to Dr B.A.C.; R18 MH43518, U01 MH081928, P50 MH080272 to Dr L.S.; R01 MH65079 to Dr T.D.C.; RO1 MH062066, 5U01 MH081988 to Dr E.F.W.; R01 MH60720, K24 MH76191 to Dr K.S.C.; K05 MH01654 to Dr T.H.M.; U01 MH066069, P50 MH064065 to Dr D.O.P.; R18 MH43518 to Dr M.T.; U01 MH74356, U01 MH082022, R41 MH083436 to Dr S.W.W.; and U01 MH066134 to Dr J.A.).; We thank the study participants for their time and effort. We also thank Jennifer Johnson, PhD (UCLA), Diane Kirsopp, BA (University of Toronto), and Roy Money, MS (Yale University) for their contributions to the NAPLS I database described in this article. The authors also thank Andrea Auther, PhD, Lauren Baskir, PhD, and Ruth Olsen, BS. Conflict of interest: Dr. Cornblatt was the original developer of the CPT-IP and has been an advisor for Bristol-Myers Squibb and Merck. Dr. Lencz has received consulting fees and/or honoraria from Eli Lilly, Merck, Clinical Data Inc., GoldenHelix, Inc., Guidepoint Global, and Cowen & Co. Dr. Carrion has not received funding from for-profit entities. Dr. Seidman has not received funding from for-profit entities in the past 12 months. In the past he received unrestricted educational support from Janssen Pharmaceuticals and has served as a consultant for Shire. Dr. Walker has not received funding from for-profit entities. Dr. Cannon has served as a consultant for Janssen Pharmaceuticals and Eli Lilly and Company. Dr. Cadenhead has not received funding from for-profit entities. Dr. McGlashan has served as a consultant for Eli Lilly and Company, Pfizer, Solvay/Wyeth, and Roche Pharmaceuticals. Dr. Perkins has received research funding from Janssen Pharmaceuticals and Dainippon Sumitomo Pharma in the past 12 months. In the past Dr. Perkins received research funding from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Otsuka Pharmaceutical Co Ltd, Eli Lilly and Company, Janssen Pharmaceuticals, and Pfizer and consulting and educational fees from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly and Company, Janssen Pharmaceuticals, GlaxoSmithKline, Forest Labs, Pfizer, and Shire. Dr. Tsuang has received research grants from Janssen Pharmaceuticals. Dr. Woods has received research funding support from multiple for-profit entities including UCB Pharma and Bristol- Myers Squibb and has consulted for Otsuka and Schering-Plough. Dr Woods has not served on speaker's bureaus. Dr. Heinssen is an employee of the nonprofit National Institutes of Health and has had no financial relationships with for-profit entities. Dr. Addington has served as a consultant for Pfizer, AstraZeneca Pharmaceuticals, and Janssen Pharmaceuticals. NR 44 TC 59 Z9 58 U1 7 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD NOV PY 2012 VL 38 IS 6 BP 1247 EP 1257 DI 10.1093/schbul/sbr136 PG 11 WC Psychiatry SC Psychiatry GA 035KD UT WOS:000310944500020 PM 22080497 ER PT J AU Foroud, T Koller, DL Lai, DB Sauerbeck, L Anderson, C Ko, N Deka, R Mosley, TH Fornage, M Woo, D Moomaw, CJ Hornung, R Huston, J Meissner, I Bailey-Wilson, JE Langefeld, C Rouleau, G Connolly, ES Worrall, BB Kleindorfer, D Flaherty, ML Martini, S Mackey, J La Rosa, FD Brown, RD Broderick, JP AF Foroud, Tatiana Koller, Daniel L. Lai, Dongbing Sauerbeck, Laura Anderson, Craig Ko, Nerissa Deka, Ranjan Mosley, Thomas H. Fornage, Myriam Woo, Daniel Moomaw, Charles J. Hornung, Richard Huston, John Meissner, Irene Bailey-Wilson, Joan E. Langefeld, Carl Rouleau, Guy Connolly, E. Sander Worrall, Bradford B. Kleindorfer, Dawn Flaherty, Matthew L. Martini, Sharyl Mackey, Jason La Rosa, Felipe De Los Rios Brown, Robert D., Jr. Broderick, Joseph P. CA FIA Study Investigators TI Genome-Wide Association Study of Intracranial Aneurysms Confirms Role of Anril and SOX17 in Disease Risk SO STROKE LA English DT Article DE genome-wide association study; intracranial aneurysm ID ABDOMINAL AORTIC-ANEURYSM; SUBARACHNOID HEMORRHAGE; CHROMOSOME 9P21; SMOKING; POPULATIONS; ALCOHOL; VARIANT; STROKE; LOCI AB Background-Genome-wide association studies have identified novel genetic factors that contribute to intracranial aneurysm (IA) susceptibility. We sought to confirm previously reported loci, to identify novel risk factors, and to evaluate the contribution of these factors to familial and sporadic IA. Method-We utilized 2 complementary samples, one recruited on the basis of a dense family history of IA (discovery sample 1: 388 IA cases and 397 controls) and the other without regard to family history (discovery sample 2: 1095 IA cases and 1286 controls). Imputation was used to generate a common set of single nucleotide polymorphisms (SNP) across samples, and a logistic regression model was used to test for association in each sample. Results from each sample were then combined in a meta-analysis. Results-There was only modest overlap in the association results obtained in the 2 samples. In neither sample did results reach-genome-wide significance. However, the-meta-analysis yielded-genome-wide significance for SNP on chromosome 9p (CDKN2BAS; rs6475606; P = 3.6x10(-8)) and provided further evidence to support the previously reported association of IA with SNP in SOX17 on chromosome 8q (rs1072737; P = 8.7x10(-5)). Analyses suggest that the effect of smoking acts multiplicatively with the SNP genotype, and smoking has a greater effect on risk than SNP genotype. Conclusion-In addition to replicating several previously reported loci, we provide further evidence that the association on chromosome 9p is attributable to variants in CDKN2BAS (also known as ANRIL, an antisense noncoding RNA). (Stroke. 2012; 43: 2846-2852.) C1 [Foroud, Tatiana; Koller, Daniel L.; Lai, Dongbing; Mackey, Jason] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Sauerbeck, Laura; Deka, Ranjan; Woo, Daniel; Moomaw, Charles J.; Hornung, Richard; Kleindorfer, Dawn; Flaherty, Matthew L.; Martini, Sharyl; La Rosa, Felipe De Los Rios; Broderick, Joseph P.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Anderson, Craig] Royal Prince Alfred Hosp, George Inst Global Hlth, Sydney, NSW, Australia. [Anderson, Craig] Univ Sydney, Sydney, NSW 2006, Australia. [Ko, Nerissa] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Huston, John; Meissner, Irene; Brown, Robert D., Jr.] Mayo Clin, Rochester, MN USA. [Bailey-Wilson, Joan E.] Natl Human Genome Res Inst, Baltimore, MD USA. [Langefeld, Carl] Wake Forest Univ, Winston Salem, NC 27109 USA. [Rouleau, Guy] Univ Montreal, Montreal, PQ, Canada. [Connolly, E. Sander] Columbia Univ, Sch Med, New York, NY USA. [Worrall, Bradford B.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. RP Foroud, T (reprint author), Indiana Univ Sch Med, 410 W 10th St, Indianapolis, IN 46202 USA. EM tforoud@iupui.edu RI Mackey, Jason/I-6445-2013 OI Mackey, Jason/0000-0002-6867-8630 FU Intramural Research Program of NGHRI (NIH); National Health and Medical Research Council of Australia; Health Research Council of New Zealand; [R01NS39512]; [R01NS36695]; [K02NS060892]; [HHMI P0012375]; [HHSN268201100005C]; [HHSN268201100006C]; [HHSN268201100007C]; [HHSN268201100008C]; [HHSN268201100009C]; [HHSN268201100010C]; [HHSN268201100011C]; [HHSN268201100012C]; [R01HL087641] FX This project was supported by R01NS39512, R01NS36695, K02NS060892, HHMI P0012375, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367 R01HL086694, U01HG004402, HHSN268200625226C N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, R01HL087641, UL1RR025005, U01 HL096917, and R01HL093029, and the Intramural Research Program of NGHRI (NIH). Addition funding was provided by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand. NR 27 TC 34 Z9 37 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP 2846 EP U134 DI 10.1161/STROKEAHA.112.656397 PG 23 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800265 PM 22961961 ER PT J AU Cheng, B Ebinger, M Kufner, A Koehrmann, M Wu, O Kang, DW Liebeskind, D Tourdias, T Singer, OC Christensen, S Warach, S Luby, M Fiebach, JB Fiehler, J Gerloff, C Thomalla, G AF Cheng, Bastian Ebinger, Martin Kufner, Anna Koehrmann, Martin Wu, Ona Kang, Dong-Wha Liebeskind, David Tourdias, Thomas Singer, Oliver C. Christensen, Soren Warach, Steve Luby, Marie Fiebach, Jochen B. Fiehler, Jens Gerloff, Christian Thomalla, Goetz CA Stroke Imaging Repository STIR TI Hyperintense Vessels on Acute Stroke Fluid-Attenuated Inversion Recovery Imaging Associations With Clinical and Other MRI Findings SO STROKE LA English DT Article DE acute stroke; diffusion-weighted; fluid-attenuated inversion recovery; magnetic resonance imaging; stroke ID FLAIR MRI; ABNORMALITIES; TRIAL AB Background and Purpose-Hyperintense vessels (HVs) have been observed in fluid-attenuated inversion recovery imaging of patients with acute ischemic stroke and been linked to slow flow in collateral arterial circulation. Given the potential importance of HV, we used a large, multicenter data set of patients with stroke to clarify which clinical and imaging factors play a role in HV. Methods-We analyzed data of 516 patients from the previously published PRE-FLAIR study (PREdictive value of FLAIR and DWI for the identification of acute ischemic stroke patients <= 3 and <= 4.5 hours of symptom onset-a multicenter study) study. Patients were studied by MRI within 12 hours of symptom onset. HV were defined as hyperintensities in fluid-attenuated inversion recovery corresponding to the typical course of a blood vessel that was not considered the proximal, occluded main artery ipsilateral to the diffusion restriction. Presence of HV was rated by 2 observers and related to clinical and imaging findings. Results-Presence of HV was identified in 240 of all 516 patients (47%). Patients with HV showed larger initial ischemic lesion volumes (median, 12.3 versus 4.9 mL; P<0.001) and a more severe clinical impairment (median National Institutes of Health Stroke Scale 10.5 versus 6; P<0.001). In 198 patients with MR angiography, HVs were found in 80% of patients with vessel occlusion and in 17% without vessel occlusion. In a multivariable logistic regression model, vessel occlusion was associated with HV (OR, 21.7%; 95% CI, 9.6-49.9; P<0.001). HV detected vessel occlusion with a specificity of 0.86 (95% CI, 0.80-0.90) and sensitivity of 0.76 (95% CI, 0.69-0.83). Conclusions-HVs are a common finding associated with proximal arterial occlusions and more severe strokes. HVs predict arterial occlusion with high diagnostic accuracy. (Stroke. 2012;43:2957-2961.) C1 [Cheng, Bastian; Gerloff, Christian; Thomalla, Goetz] Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neurol, Kopf & Neurozentrum, D-20246 Hamburg, Germany. [Ebinger, Martin; Kufner, Anna; Fiebach, Jochen B.] Charite, Centrum Schlaganfallforsch, D-13353 Berlin, Germany. [Koehrmann, Martin] Univ Erlangen Nurnberg, Neurol Klin, Erlangen, Germany. [Wu, Ona] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Boston, MA USA. [Kang, Dong-Wha] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea. [Liebeskind, David] Univ Calif, Dept Neurol, Oakland, CA USA. [Tourdias, Thomas] Univ Bordeaux, Serv NeuroImagerie Diagnost Therapeut, Bordeaux, France. [Singer, Oliver C.] Univ Klinikum Erlangen Nurnberg, Kliniken Neuroradiol, Erlangen, Germany. [Christensen, Soren] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic, Australia. [Warach, Steve; Luby, Marie] NINDS, Bethesda, MD 20892 USA. Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neuroradiol Diagnost & Intervent, D-20246 Hamburg, Germany. RP Cheng, B (reprint author), Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neurol, Kopf & Neurozentrum, Martinistr 52, D-20246 Hamburg, Germany. EM b.cheng@uke.uni-hamburg.de OI Fiebach, Jochen B./0000-0002-7936-6958 FU Boehringer Ingelheim; Lundbeck; Siemens; Syngis; Synarc; Bayer Vital; EBS Technologies; Glaxo Smith Kline; Pfizer; Sanofi Aventis; Silk Road Medical; UCB; CoAxia; Concentric Medical, Inc.; Else Kro-ner-Fresenius-Stiftung; French Government (PHRC); National Institutes of Health [R01NS059775, R01NS063925, P50NS051343]; GE; Olea; Imaging Biometrics; National Institute of Neurological Disorders and Stroke (NINDS); Else-Kroner-Fresenius-Stiftung [2009_A36]; Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin [01 EO 0801]; European Union [202213, 223153]; Volkswagen Foundation; Deutsche Forschungsgemeinschaft; National Health and Medical Research Council (Australia); National Stroke Foundation (Australia); Heart Foundation of Australia; French national grant "Le programme hospitalier de recherche Clinique" (PHRC) FX J.B.F. has received fees as a board member, consultant, or lecturer from Boehringer Ingelheim, Lundbeck, Siemens, Syngis, and Synarc. C.G. has received fees as a consultant or lecture fees from Bayer Vital, Boehringer Ingelheim, EBS Technologies, Glaxo Smith Kline, Lundbeck, Pfizer, Sanofi Aventis, Silk Road Medical, and UCB. D.L. has received fees as a consultant for CoAxia and Concentric Medical, Inc. G.T. has received a research grant from the Else Kro-ner-Fresenius-Stiftung. T.T. has received a national grant from the French Government (PHRC). O.W. was supported in part by grants from the National Institutes of Health (R01NS059775, R01NS063925, P50NS051343) and received royalties and licensing fees from GE, Olea, and Imaging Biometrics.; This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS). The PREdictive value of FLAIR and DWI for the identification of acute ischemic stroke patients <= 3 and <= 4.5 h of symptom onset-a multicenter study (PRE-FLAIR) has received funding from the Else-Kroner-Fresenius-Stiftung (2009_A36). In Berlin, data were collected within the 1000+ study, which has received funding from the Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin (01 EO 0801). This work was further supported by the European Union's Seventh Framework Programme grant agreement No. 202213 and No 223153 (European Stroke Network), the Volkswagen Foundation, and the Deutsche Forschungsgemeinschaft. Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) was a Phase II prospective, randomized, double-blinded, placebo-controlled, multinational trial funded by the National Health and Medical Research Council (Australia), the National Stroke Foundation (Australia), and the Heart Foundation of Australia. Valeur predictive des parametres IRM a la phase aigue de l'accident vasculaire cerebral: application a la gestion des essaistherapeutiques (VIRAGE) is a national multicentre study supported by French national grant "Le programme hospitalier de recherche Clinique" (PHRC). NR 17 TC 16 Z9 23 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP 2957 EP 2961 DI 10.1161/STROKEAHA.112.658906 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800282 PM 22933582 ER PT J AU Dani, KA An, L Henning, EC Shen, J Warach, S AF Dani, Krishna A. An, Li Henning, Erica C. Shen, Jun Warach, Steven CA Natl Inst Neurological Disorders S TI Multivoxel MR Spectroscopy in Acute Ischemic Stroke Comparison to the Stroke Protocol MRI SO STROKE LA English DT Article DE magnetic resonance spectroscopy; spectroscopy; stroke ID MAGNETIC-RESONANCE-SPECTROSCOPY; FOCAL ISCHEMIA; BRAIN; HYPERGLYCEMIA; INFARCTION; DIFFUSION; PENUMBRA; LACTATE; TIME AB Background and Purpose-Few patients with stroke have been imaged with MR spectroscopy (MRS) within the first few hours after onset. We compared data from current MRI protocols to MRS in subjects with ischemic stroke. Methods-MRS was incorporated into the standard clinical MRI stroke protocol for subjects <24 hours after onset. MRI and clinical correlates for the metabolic data from MRS were sought. Results-One hundred thirty-six MRS voxels from 32 subjects were analyzed. Lactate preceded the appearance of the lesion on diffusion-weighted imaging in some voxels but in others lagged behind it. Current protocols may predict up to 41% of the variance of MRS metabolites. Serum glucose concentration and time to maximum partially predicted the concentration of all major metabolites. Conclusion-MRS may be helpful in acute stroke, especially for lactate detection when perfusion-weighted imaging is unavailable. Current MRI protocols do provide surrogate markers for some indices of metabolic activity. (Stroke. 2012;43:2962-2967.) C1 [Dani, Krishna A.; An, Li; Henning, Erica C.; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. [Shen, Jun] NIMH, NIH, Bethesda, MD 20892 USA. RP Warach, S (reprint author), UT SW Med Ctr, Dept Neurol & Neurotherapeut, Seton UT SW Clin Res Inst, 1400 N IH 35,Suite 2-240, Austin, TX 78701 USA. EM swarach@seton.org FU Division of Intramural Research of the National Institutes of Health, National Institute of Neurological Disorders and Stroke; Patrick Berthoud Charitable Trust FX This research was supported by the Division of Intramural Research of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. Dr Dani was supported by the Patrick Berthoud Charitable Trust. NR 17 TC 7 Z9 8 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP 2962 EP 2967 DI 10.1161/STROKEAHA.112.656058 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800283 PM 23091121 ER PT J AU Romero, JR Preis, SR Beiser, AS DeCarli, C Lee, DY Viswanathan, A Benjamin, EJ Fontes, J Au, R Pikula, A Wang, J Kase, CS Wolf, PA Irrizary, MC Seshadri, S AF Romero, Jose Rafael Preis, Sarah R. Beiser, Alexa S. DeCarli, Charles Lee, Dong Young Viswanathan, Anand Benjamin, Emelia J. Fontes, Joao Au, Rhoda Pikula, Aleksandra Wang, Jimmy Kase, Carlos S. Wolf, Philip A. Irrizary, Michael C. Seshadri, Sudha TI Lipoprotein Phospholipase A2 and Cerebral Microbleeds in the Framingham Heart Study SO STROKE LA English DT Article DE cerebral microbleed; intracranial hemorrhage; inflammation; lipids and lipoprotein; magnetic; resonance; microcirculation ID APOLIPOPROTEIN-E POLYMORPHISM; INTRACEREBRAL HEMORRHAGE; RISK-FACTORS; ISCHEMIC-STROKE; ROTTERDAM SCAN; A(2); PREVALENCE; DISEASE; PLASMA; ASSOCIATION AB Background and Purpose-Cerebral microbleeds (CMB) attributable to cerebral amyloid angiopathy generally occur in lobar regions, whereas those attributable to hypertensive vasculopathy are deep. Inflammation may be an underlying mechanism for CMB, with varying associations according to CMB location. Lipoprotein phospholipase-A2 (Lp-PLA2) is a circulating enzyme marker of vascular inflammation associated with risk of ischemic stroke and dementia. We hypothesized that higher Lp-PLA2 levels would be related to higher prevalence of CMB, with possible regional specificity. Methods-Framingham Offspring participants aged 65 years or older with available Lp-PLA2 measures and brain magnetic resonance imaging were included. Logistic regression models were used to relate Lp-PLA2 activity and mass to presence of CMB, adjusted for age, sex, medication use (aspirin, anticoagulants, and statins), systolic blood pressure, APOE, current smoking, and diabetes. Results-Eight--hundred nineteen participants (mean age, 73 years; 53% women) were included; 106 (13%) had CMB, 82 (10%) were lobar, and 27 (3%) were deep. We did not observe significant associations of CMB and LpPLA2 measures in multivariable adjusted analyses. However, there was a significant interaction between APOE genotype and Lp-PLA2 activity in their relation to presence of deep CMB (P interaction=0.01). Among persons with APOE e3/ e3, the odds ratio for deep CMB was 0.95 (confidence interval, 0.59-1.53; P=0.83), whereas among those with at least 1 e2 or e4 allele, odds ratio was 3.46 (confidence interval, 1.43-8.36; P=0.006). Conclusions-In our -community--based sample of older adults, there was no significant association of Lp-PLA2 with total or lobar CMB. The association of higher levels of Lp-PLA2 activity with deep CMB among those with at least 1 APOE e2 or e4 allele merits replication. (Stroke. 2012; 43: 3091-3094.) C1 [Romero, Jose Rafael; Beiser, Alexa S.; Au, Rhoda; Pikula, Aleksandra; Kase, Carlos S.; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Dept Neurol, Sect Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.; Fontes, Joao] Boston Univ, Dept Neurol, Cardiol Sect, Boston, MA 02118 USA. [Wang, Jimmy] Boston Univ, Dept Neurol, Dept Radiol, Boston, MA 02118 USA. [Preis, Sarah R.; Beiser, Alexa S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [Viswanathan, Anand] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Irrizary, Michael C.] GlaxoSmithKline, WW Epidemiol Res & Dev Neurosci Sect, Res Triangle Pk, NC USA. [Romero, Jose Rafael; Preis, Sarah R.; Beiser, Alexa S.; Benjamin, Emelia J.; Fontes, Joao; Au, Rhoda; Pikula, Aleksandra; Kase, Carlos S.; Wolf, Philip A.; Seshadri, Sudha] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Romero, JR (reprint author), Boston Univ, Dept Neurol, Sch Med, 715 Albany St,B-608, Boston, MA 02118 USA. EM joromero@bmc.org RI Lee, Dong Young/J-5575-2012; OI Preis, Sarah/0000-0002-9360-4166; Seshadri, Sudha/0000-0001-6135-2622; Pikula, Aleksandra/0000-0002-8378-5522; Au, Rhoda/0000-0001-7742-4491; Benjamin, Emelia/0000-0003-4076-2336; Beiser, Alexa/0000-0001-8551-7778 FU Framingham Heart Study's National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institute of Neurological Disorders and Stroke [R01 NS17950]; National Institute on Aging [R01 AG16495, AG08122, AG033193, AG031287, K23AG038444]; National Institutes of Health [1RO1 HL64753, R01 HL076784, 1 R01 AG028321] FX This work (design and conduct of the study, collection, and management of the data) was supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC-25195) and by grants from the National Institute of Neurological Disorders and Stroke (R01 NS17950), the National Institute on Aging (R01 AG16495; AG08122; AG033193; AG031287; K23AG038444), and National Institutes of Health grants (1RO1 HL64753; R01 HL076784; 1 R01 AG028321). NR 35 TC 13 Z9 14 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP 3091 EP U525 DI 10.1161/STROKEAHA.112.656744 PG 13 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800305 PM 22961963 ER PT J AU Lee, HJ Chung, JY Hewitt, SM Yu, E Hong, SM AF Lee, Hee Jin Chung, Joon-Yong Hewitt, Stephen M. Yu, Eunsil Hong, Seung-Mo TI HER3 overexpression is a prognostic indicator of extrahepatic cholangiocarcinoma SO VIRCHOWS ARCHIV LA English DT Article DE Extrahepatic; Bile duct; Cholangiocarcinoma; HER2; HER3; Immunohistochemistry; Prognosis ID EPIDERMAL-GROWTH-FACTOR; C-ERBB-3 PROTEIN EXPRESSION; TYROSINE KINASE-ACTIVITY; IN-SITU HYBRIDIZATION; BILIARY-TRACT; FACTOR-RECEPTOR; GASTRIC-CANCER; LUNG-CANCER; INTRAHEPATIC CHOLANGIOCARCINOMA; PANCREATIC-CANCER AB Members of the HER (ERBB) receptor protein tyrosine kinase family play an important role in regulating cellular division, proliferation, differentiation, and migration and have prognostic significance in a number of cancers. Here, we sought to define their role in extrahepatic cholangiocarcinoma (EHCC). HER2 and HER3 protein expression was studied in 230 EHCC cases using a tissue microarray and compared with clinicopathological variables, including the survival of EHCC patients. HER3 was predominantly localized to the cytoplasm, whereas HER2 exhibited a membranous expression pattern. Overexpression of HER2 and HER3 was observed in 6 % (13/224) and 39 % (90/230) of EHCCs, respectively. Membranous HER2 overexpression occurred more frequently in intraductal papillary neoplasms with an associated invasive carcinoma than in tubular adenocarcinomas (P = 0.02). HER3 protein was more commonly overexpressed in nodular and infiltrative than in papillary tumors (P = 0.03). HER3 overexpression was associated with decreased survival in both univariate (P = 0.01) and multivariate (P = 0.008) analyses, whereas HER2 overexpression was not associated with survival. HER2 and HER3 are overexpressed in subsets of EHCC patients. Notably, HER3 overexpression is correlated with decreased patient survival, suggesting that HER3 constitutes a prognostic factor as well as a potential candidate for targeted therapy. C1 [Lee, Hee Jin; Yu, Eunsil; Hong, Seung-Mo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea. [Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, NIH, Bethesda, MD 20892 USA. [Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Hong, SM (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, 388-1 Pungnap Dong, Seoul 138736, South Korea. EM smhong28@gmail.com OI Hewitt, Stephen/0000-0001-8283-1788; Hong, Seung-Mo/0000-0002-8888-6007; Chung, Joon-Yong/0000-0001-5041-5982 NR 62 TC 5 Z9 5 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD NOV PY 2012 VL 461 IS 5 BP 521 EP 530 DI 10.1007/s00428-012-1321-0 PG 10 WC Pathology SC Pathology GA 029ZK UT WOS:000310537200006 PM 23052372 ER PT J AU Engelhardt, K Gertz, E Keles, S Schaffer, A Ceja, R Sassi, A Graham, L Massaad, M Mellouli, F Benmustapha, I Khemiri, M Kilic, S Etzioni, A Freeman, A Thiel, J Schulze, I Al-Herz, W Metin, A Sanal, O Yeganeh, M Niehues, T Siepermann, K Weinspach, S Unal, E Patiroglu, T Dasouki, M Yilmaz, M Genel, F Aytekin, C Kutukculer, N Somer, A Kilic, M Reisli, I Camcioglu, Y Gennery, A Cant, A Jones, A Gaspar, H Pietrogrande, M Baz, Z Al-Tamemi, S Lougaris, V Lefranc, G Megarbane, A Boutros, J Galal, N Bejaoui, M Barbouche, M Geha, R Chatila, T Grimbacher, B AF Engelhardt, K. Gertz, E. Keles, S. Schaeffer, A. Ceja, R. Sassi, A. Graham, L. Massaad, M. Mellouli, F. Benmustapha, I Khemiri, M. Kilic, S. Etzioni, A. Freeman, A. Thiel, J. Schulze, I Al-Herz, W. Metin, A. Sanal, O. Yeganeh, M. Niehues, T. Siepermann, K. Weinspach, S. Unal, E. Patiroglu, T. Dasouki, M. Yilmaz, M. Genel, F. Aytekin, C. Kutukculer, N. Somer, A. Kilic, M. Reisli, I Camcioglu, Y. Gennery, A. Cant, A. Jones, A. Gaspar, H. Pietrogrande, M. Baz, Z. Al-Tamemi, S. Lougaris, V Lefranc, G. Megarbane, A. Boutros, J. Galal, N. Bejaoui, M. Barbouche, M. Geha, R. Chatila, T. Grimbacher, B. TI DOCK8 deficiency and diagnostic guidelines for hyper-IgE syndromes SO ALLERGY LA English DT Meeting Abstract CT 31st Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 16-20, 2012 CL Geneva, SWITZERLAND SP European Acad Allergy & Clin Immunol (EAACI) C1 [Engelhardt, K.; Graham, L.] UCL, Dept Immunol & Mol Pathol, London, England. [Gertz, E.; Schaeffer, A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Keles, S.; Ceja, R.; Chatila, T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Immunol Allergy & Rheumatol, Los Angeles, CA 90095 USA. [Sassi, A.; Benmustapha, I; Barbouche, M.] Inst Pasteur, Dept Immunol, Tunis, Tunisia. [Massaad, M.; Geha, R.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Mellouli, F.; Bejaoui, M.] Bone Marrow Transplantat Ctr, Dept Pediat, Tunis, Tunisia. [Khemiri, M.] Childrens Hosp, Dept Pediat, Tunis, Tunisia. [Kilic, S.] Uludag Univ, Fac Med, Dept Pediat Immunol, Bursa, Turkey. [Etzioni, A.] Technion Israel Inst Technol, Rappaport Fac Med, Meyers Children Hosp, Haifa, Israel. [Freeman, A.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Thiel, J.; Schulze, I; Grimbacher, B.] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany. [Al-Herz, W.] Al Sabah Hosp, Dept Pediat, Kuwait, Kuwait. [Metin, A.] SB Ankara Diskapi Childrens Hosp, Pediat Immunol Unit, Ankara, Turkey. [Sanal, O.] Hacettepe Univ, Childrens Hosp, Div Immunol, Ankara, Turkey. [Yeganeh, M.] Univ Tehran Med Sci, Children Med Ctr, Immunol Asthma & Allergy Res Inst, Tehran, Iran. [Niehues, T.; Siepermann, K.] HELIOS Klinikum Krefeld, Zentrum Kinder & Jugendmed, Krefeld, Germany. [Weinspach, S.] Univ Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol 18, Ctr Child & Adolescent Med, Dusseldorf, Germany. [Unal, E.; Patiroglu, T.] Erciyes Univ, Fac Med, Dept Pediat, Div Pediat Immunol, Kayseri, Turkey. [Dasouki, M.] Univ Kansas, Med Ctr, Dept Pediat, Kansas City, KS 66103 USA. [Yilmaz, M.] Cukurova Univ, Adana, Turkey. [Genel, F.] Behcet Uz State Hosp, Div Pediat Immunol, Izmir, Turkey. [Aytekin, C.] Dr Sami Ulus State Hosp, Ankara, Turkey. [Kutukculer, N.] Ege Univ, Fac Med, Dept Pediat, Izmir, Turkey. [Somer, A.] Istanbul Univ, Istanbul Fac Med, Div Infect Dis & Immunol, Istanbul, Turkey. [Kilic, M.] Firat Univ, TR-23169 Elazig, Turkey. [Reisli, I] Selcuk Univ, Div Pediat Allergy & Immunol, Konya, Turkey. [Camcioglu, Y.] Istanbul Univ, Cerrahpasa Med Fac, Div Pediat Allergy Immunol & Infect Dis, Istanbul, Turkey. [Gennery, A.; Cant, A.] Newcastle Univ, Childrens Bone Marrow Transplant Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Jones, A.; Gaspar, H.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Pietrogrande, M.] Univ Milan, Dept Maternal & Pediat Sci, Fdn IRCCS Policlin Milano, Milan, Italy. [Baz, Z.] St George Hosp Univ, Med Ctr, Dept Pediat, Beirut, Lebanon. [Al-Tamemi, S.] Sultan Qaboos Univ, Dept Pediat, Muscat, Oman. [Lougaris, V] Univ Brescia, Dept Pediat, Brescia, Italy. [Lougaris, V] Univ Brescia, Inst Mol Med, Brescia, Italy. [Lefranc, G.] Univ Montpellier 2, Montpellier, France. [Lefranc, G.] CNRS, Inst Human Genet, Montpellier, France. [Megarbane, A.] St Joseph Univ, Med Genet Unit, Beirut, Lebanon. [Boutros, J.; Galal, N.] Cairo Univ, Primary Immunodeficiency Clin, Specialized Pediat Hosp, Cairo, Egypt. [Etzioni, A.] Rambam Hlth Care Campus, Haifa, Israel. 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 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2012 VL 67 SU 96 SI SI MA 387 BP 163 EP 164 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 026CA UT WOS:000310247700373 ER PT J AU Carter, M Clayton, S Wilson, T Scott, L Maric, I Simakova, O Jung, M Metcalfe, D AF Carter, M. Clayton, S. Wilson, T. Scott, L. Maric, I Simakova, O. Jung, M. Metcalfe, D. TI Idiopathic anaphylaxis and the occurrence of clonal mast cell disease SO ALLERGY LA English DT Meeting Abstract CT 31st Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 16-20, 2012 CL Geneva, SWITZERLAND SP European Acad Allergy & Clin Immunol (EAACI) C1 [Carter, M.; Clayton, S.; Wilson, T.; Scott, L.; Jung, M.; Metcalfe, D.] NIH, Lab Allerg Dis, 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 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2012 VL 67 SU 96 SI SI MA 760 BP 297 EP 297 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 026CA UT WOS:000310247701363 ER PT J AU Albanese, E Hardy, R Wills, A Kuh, D Guralnik, J Richards, M AF Albanese, Emiliano Hardy, Rebecca Wills, Andrew Kuh, Diana Guralnik, Jack Richards, Marcus TI No association between gain in body mass index across the life course and midlife cognitive function and cognitive reserve-The 1946 British birth cohort study SO ALZHEIMERS & DEMENTIA LA English DT Article DE Epidemiology; Cognitive function; Body size; Adiposity; Vascular risk factors ID ALZHEIMER-DISEASE; CENTRAL OBESITY; METABOLIC SYNDROME; ADULT LIFE; DEMENTIA; RISK; ADIPOSITY; DECLINE; WEIGHT; WOMEN AB Background: The association between lifelong body mass index (BMI) and cognitive function has not been comprehensively studied. Methods: In more than 2000 men and women born in 1946, we tested associations between BMI gain at 15, 20, 26, 36, 43, and 53 years with respect to the previous measure (gain at age 15 years with respect to BMI at age 11 years), and semantic fluency (animal naming) and cognitive reserve (the National Adult Reading Test) at age 53 years, and verbal memory (word list recall) and speed/concentration (letter cancellation) at ages 43 and 53 years. Measures of BMI gain were adjusted in stages for childhood intelligence, education, socioeconomic position (SEP), lifestyle, and vascular risk factors. Results: Independent of childhood intelligence, BMI gain between ages 26 and 36 years was associated with lower memory scores (beta per SD increase in BMI in men = -0.11; 95% confidence interval [CI]: -0.19, -0.02), verbal fluency (beta in women = -0.11; 95% CI: -0.20, -0.02), and lower National Adult Reading Test score (beta in women = -0.08; 95% CI: -0.15, -0.01), but not with speed/concentration (beta in men = 0.02; 95% CI: -0.11, 0.07). Associations were largely explained by educational attainment and SEP (P >= .10). However, BMI gain at 53 years in men was independently associated with better memory (beta = 0.12; 95% CI: 0.03, 0.22), and both underweight (beta = -1.54; 95% CI: -2.52, -0.57) and obese (beta = -0.30; 95% CI: -2.52, -0.57) women at 53 years had significantly lower memory scores. Conclusion: The adverse effect of higher BMI gain on midlife cognitive function and cognitive reserve is independent of childhood intelligence but not of education and SEP. The independent association between greater BMI gain in midlife and better cognitive function deserves further investigation. (C) 2012 The Alzheimer's Association. All rights reserved. C1 [Albanese, Emiliano; Hardy, Rebecca; Wills, Andrew; Kuh, Diana; Richards, Marcus] Royal Free & Univ Coll Med Sch, Dept Epidemiol & Publ Hlth, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England. [Albanese, Emiliano; Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Albanese, E (reprint author), Royal Free & Univ Coll Med Sch, Dept Epidemiol & Publ Hlth, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England. EM emiliano.albanese@nih.gov FU MRC Unit for Lifelong Health and Ageing, United Kingdom; Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This study was funded by the MRC Unit for Lifelong Health and Ageing, United Kingdom, and is supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 47 TC 2 Z9 2 U1 3 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2012 VL 8 IS 6 BP 470 EP 482 DI 10.1016/j.jalz.2011.09.228 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 038KW UT WOS:000311174600002 PM 22858531 ER PT J AU Guttmacher, AE AF Guttmacher, Alan E. TI Every birth a healthy birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID SYSTEMATIC ANALYSIS; TRENDS C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Guttmacher, AE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2012 VL 207 IS 5 BP 343 EP 344 DI 10.1016/j.ajog.2012.09.015 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 030JM UT WOS:000310567000010 PM 23107077 ER PT J AU Caritis, SN Sharma, S Venkataramanan, R Hankins, GD Miodovnik, M Hebert, MF Umans, JG Benedetti, T Mattison, D Zajicek, A Fischer, D Jackson, A AF Caritis, Steve N. Sharma, Shringi Venkataramanan, Raman Hankins, Gary D. Miodovnik, Menachem Hebert, Mary F. Umans, Jason G. Benedetti, Thomas Mattison, Donald Zajicek, Anne Fischer, Dawn Jackson, Aimee CA Eunice Kennedy Shriver Natl Inst C TI Pharmacology and placental transport of 17-hydroxyprogesterone caproate in singleton gestation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cord blood; pharmacokinetics; placenta; preterm birth ID RANDOMIZED CONTROLLED-TRIAL; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; PRETERM BIRTH; HYDROXYPROGESTERONE CAPROATE; PREVENTION; METABOLISM; PROGESTERONE; PREGNANCY; AGENT AB OBJECTIVE: The purpose of this study was to estimate pharmacokinetic parameters and to evaluate placental transport of 17-hydroxyprogesterone caproate (17-OHPC) in singleton gestation. STUDY DESIGN: Sixty-one women who received weekly injections of 17-OHPC underwent 2 pharmacokinetic studies at 20 + 0 to 24 + 6 weeks' gestation (study 1) and 31 + 0 to 34 + 6 weeks' gestation (study 2); daily blood samples were obtained between injections. In 18 women, blood samples were obtained over a 28-day period beyond the last injection (extended study). Maternal and/or cord blood were obtained at delivery. RESULTS: The half-life (median +/- SD) of 17-OHPC was 16.2 +/- 6 days. Concentrations of 17-OHPC were higher during study 2 than during study 1. Body mass index affected maternal 17-OHPC concentrations. Cord: maternal 17-OHPC concentration ratios averaged 0.2; 17-OHPC was detectible in cord plasma 44 days after the last maternal injection. CONCLUSION: The apparent half-life of 17-OHPC is long, and pharmacokinetic parameters vary widely between subjects and are affected by maternal body mass index. The drug crosses the placental barrier. C1 [Caritis, Steve N.; Fischer, Dawn] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. [Sharma, Shringi; Venkataramanan, Raman] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Hankins, Gary D.; Jackson, Aimee] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA. [Miodovnik, Menachem; Umans, Jason G.] Washington Hosp Ctr, Washington, DC 20010 USA. [Miodovnik, Menachem; Umans, Jason G.] MedStar Hlth Res Inst, Hyattsville, MD USA. [Umans, Jason G.] Georgetown Howard Univ Ctr Clin & Translat Sci, Washington, DC USA. [Hebert, Mary F.] Univ Washington, Dept Pharm, Sch Med, Seattle, WA USA. [Benedetti, Thomas] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Mattison, Donald; Zajicek, Anne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Caritis, SN (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. RI Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; caritis, steve/0000-0002-2169-0712 FU Obstetric Fetal Pharmacology Research Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10HD047905, U10HD047892]; [1 UL1RR031975] FX Supported by the Obstetric Fetal Pharmacology Research Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development through cooperative agreements U10HD047905, U10HD047892, U10HD047892, and U10HD047892 with additional support by 1 UL1RR031975. NR 21 TC 0 Z9 0 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2012 VL 207 IS 5 AR 398.e1 DI 10.1016/j.ajog.2012.08.015 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 030JM UT WOS:000310567000024 PM 22967833 ER PT J AU Caritis, SN Simhan, HN Zhao, Y Rouse, DJ Peaceman, AM Sciscione, A Spong, CY Varner, MW Malone, FD Iams, JD Mercer, BM Thorp, JM Sorokin, Y Carpenter, M Lo, J Ramin, SM Harper, M AF Caritis, Steve N. Simhan, Hyagriv N. Zhao, Yuan Rouse, Dwight J. Peaceman, Alan M. Sciscione, Anthony Spong, Catherine Y. Varner, Michael W. Malone, Fergal D. Iams, Jay D. Mercer, Brian M. Thorp, John M., Jr. Sorokin, Yoram Carpenter, Marshall Lo, Julie Ramin, Susan M. Harper, Margaret CA Eunice Kennedy Shriver Natl Inst C TI Relationship between 17-hydroxyprogesterone caproate concentrations and gestational age at delivery in twin gestation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE 17-hydroxyprogesterone caproate; pharmacodynamics; twin gestation ID 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; PREMATURITY; PREVENTION; PREGNANCY AB OBJECTIVE: We sought to evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action. STUDY DESIGN: Blood was obtained between 24-28 weeks (epoch 1) and 32-35 weeks (epoch 2) in 217 women with twin gestation receiving 17-OHPC or placebo. Gestational age at delivery and concentrations of 17-OHPC, 17-hydroxyprogesterone, progesterone, C-reactive protein (CRP), and corticotrophin-releasing hormone were assessed. RESULTS: Women with higher concentrations of 17-OHPC delivered at earlier gestational ages than women with lower concentrations (P < .001). Women receiving 17-OHPC demonstrated significantly higher (P = .005) concentrations of CRP in epoch 1 than women receiving placebo but CRP values were similar in epoch 2 in both groups. A highly significant (P < .0001) positive relationship was observed between 17-OHPC concentration and progesterone and 17-hydroxyprogesterone concentrations at both epochs. Corticotropin-releasing hormone concentrations did not differ by treatment group. CONCLUSION: 17-OHPC may adversely impact gestational age at delivery in women with twin gestation. C1 [Caritis, Steve N.; Simhan, Hyagriv N.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. [Rouse, Dwight J.] Univ Alabama Birmingham, Dept Obstet, Med Sch Birmingham, Birmingham, AL USA. [Rouse, Dwight J.] Univ Alabama Birmingham, Dept Gynecol, Med Sch Birmingham, Birmingham, AL USA. [Peaceman, Alan M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Sciscione, Anthony] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Varner, Michael W.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Malone, Fergal D.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Iams, Jay D.] Ohio State Univ, Ohio State Coll Med, Cleveland, OH USA. [Mercer, Brian M.] Case Western Reserve Univ, Sch Med, Metrohlth Med Ctr, Cleveland, OH USA. [Thorp, John M., Jr.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Sorokin, Yoram] Wayne State Univ, Sch Med, Detroit, MI USA. [Carpenter, Marshall] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Lo, Julie] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Zhao, Yuan] George Washington Univ, Ctr Biostat, Washington, DC USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Caritis, SN (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27869, HD21410, HD40512, HD34136, HD34208, HD40485, HD27915, HD40544, HD40560, HD27917, HD40500, HD34116, HD40545, HD27860, HD3680] FX The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD27869, HD21410, HD40512, HD34136, HD34208, HD40485, HD27915, HD40544, HD40560, HD27917, HD40500, HD34116, HD40545, HD27860, HD3680) and does not necessarily represent the official views of the NICHD or the National Institutes of Health. NR 14 TC 0 Z9 1 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2012 VL 207 IS 5 AR 396.e1 DI 10.1016/j.ajog.2012.08.001 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 030JM UT WOS:000310567000023 PM 22959763 ER PT J AU Grobman, WA Thom, EA Spong, CY Iams, JD Saade, GR Mercer, BM Tita, ATN Rouse, DJ Sorokin, Y Wapner, RJ Leveno, KJ Blackwell, S Esplin, MS Tolosa, JE Thorp, JM Caritis, SN Van Dorsten, JP AF Grobman, William A. Thom, Elizabeth A. Spong, Catherine Y. Iams, Jay D. Saade, George R. Mercer, Brian M. Tita, Alan T. N. Rouse, Dwight J. Sorokin, Yoram Wapner, Ronald J. Leveno, Kenneth J. Blackwell, Sean Esplin, M. Sean Tolosa, Jorge E. Thorp, John M., Jr. Caritis, Steve N. Van Dorsten, J. Peter CA Eunice Kennedy Shriver Natl Inst C TI 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE nulliparous; progesterone; progestogen; short cervix ID SPONTANEOUS PRETERM BIRTH; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; DOUBLE-BLIND; CLINICAL-TRIALS; WEEKS GESTATION; RISK; DELIVERY; PROGESTERONE; WOMEN; PREDICTION AB OBJECTIVE: We sought to evaluate whether 17 alpha-hydroxyprogesterone caproate (17-OHP) reduces preterm birth (PTB) in nulliparous women with a midtrimester cervical length (CL) <30 mm. STUDY DESIGN: In this multicenter randomized controlled trial, nulliparous women with a singleton gestation between 16 and 22 3/7 weeks with an endovaginal CL <30 mm (<10th percentile in this population) were randomized to weekly intramuscular 17-OHP (250 mg) or placebo through 36 weeks. The primary outcome was PTB <37 weeks. RESULTS: The frequency of PTB did not differ between the 17-OHP (n = 327) and placebo (n = 330) groups (25.1% vs 24.2%; relative risk, 1.03; 95% confidence interval, 0.79-1.35). There also was no difference in the composite adverse neonatal outcome (7.0% vs 9.1%; relative risk, 0.77; 95% confidence interval, 0.46-1.30). CONCLUSION: Weekly 17-OHP does not reduce the frequency of PTB in nulliparous women with a midtrimester CL <30 mm. C1 [Grobman, William A.] Northwestern Univ, Chicago, IL 60611 USA. [Thom, Elizabeth A.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA. [Saade, George R.] Univ Texas Med Branch, Galveston, TX USA. [Mercer, Brian M.] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. [Tita, Alan T. N.] Univ Alabama Birmingham, Birmingham, AL USA. [Rouse, Dwight J.] Brown Univ, Providence, RI 02912 USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Wapner, Ronald J.] Columbia Univ, New York, NY USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Blackwell, Sean] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Esplin, M. Sean] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. [Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA. [Van Dorsten, J. Peter] Med Univ S Carolina, Charleston, SC 29425 USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Grobman, WA (reprint author), Northwestern Univ, Chicago, IL 60611 USA. OI caritis, steve/0000-0002-2169-0712 FU National Center for Research Resources [NCRR] from NICHD [HD21410, UL1 RR024153, UL1 TR000005, HD27869, HD27915, HD27917, HD34116, HD34208, 5UL1RR025764, HD36801, HD40500, HD40512, HD40544, M01 RR00080, UL1 RR024989]; NICHD [HD40545, HD40560, HD40485, HD53097, HD53118] FX The project described was supported by grant numbers HD21410, UL1 RR024153, UL1 TR000005, HD27869, HD27915, HD27917, HD34116, HD34208, 5UL1RR025764, HD36801, HD40500, HD40512, HD40544, M01 RR00080, UL1 RR024989 (National Center for Research Resources [NCRR]), HD40545, HD40560, HD40485, HD53097, and HD53118 from the NICHD. NR 23 TC 1 Z9 2 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2012 VL 207 IS 5 AR 390.e1 DI 10.1016/j.ajog.2012.09.013 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 030JM UT WOS:000310567000021 PM 23010094 ER PT J AU McElrath, TF Lim, KH Pare, E Rich-Edwards, J Pucci, D Troisi, R Parry, S AF McElrath, Thomas F. Lim, Kee-Hak Pare, Emmanuelle Rich-Edwards, Janet Pucci, Dominick Troisi, Rebecca Parry, Samuel TI Longitudinal evaluation of predictive value for preeclampsia of circulating angiogenic factors through pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE angiogenic factor; PlGF; preeclampsia; sFlt-1 ID PLACENTAL GROWTH-FACTOR; FOR-GESTATIONAL-AGE; TYROSINE KINASE-1; MATERNAL PLASMA; 1ST-TRIMESTER; RISK; 2ND-TRIMESTER; PATHOGENESIS; ENDOGLIN; MARKERS AB OBJECTIVE: The purpose of this study was to examine whether longitudinally sampled maternal angiogenic concentrations predict preeclampsia. STUDY DESIGN: Plasma sFlt-1 and placental growth factor (PlGF) concentrations in healthy pregnant women were quantified at 10, 17, 25, and 35 weeks' gestation. Preeclampsia was diagnosed with criteria from the American College of Obstetricians and Gynecologists. RESULTS: In the first trimester, sensitivity/specificity for PlGF and sFlt-1 were 55/43% and 57/40%, respectively, and did not improve appreciably as the pregnancy progressed. Among pregnancies that later experienced preeclampsia, median PlGF was lower beginning in the second trimester, but sFlt-1 was not higher until the third trimester. Analyte positive predictive values approached 10% in the third trimester. Negative predictive values were >90% for the entire pregnancy. CONCLUSION: Prediction of preeclampsia in early pregnancy was not possible with the use of maternal angiogenic protein concentrations. Even in late pregnancy, positive predictive values were not useful clinically. Negative predictive values are similarly unlikely to prove useful as a tool with which to a rule out suspected disease. C1 [McElrath, Thomas F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Maternal Fetal Med, Boston, MA 02115 USA. [Lim, Kee-Hak] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Div Maternal Fetal Med, Boston, MA USA. [Pare, Emmanuelle; Parry, Samuel] Hosp Univ Penn, Div Maternal Fetal Med, Philadelphia, PA 19104 USA. [Pucci, Dominick] Abbott Diagnost Div, Abbott Pk, IL USA. [Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP McElrath, TF (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Maternal Fetal Med, Boston, MA 02115 USA. FU Abbott Diagnostics Division [9MZ-04-06N03] FX Supported by an unrestricted grant from Abbott Diagnostics Division (9MZ-04-06N03). NR 36 TC 16 Z9 17 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2012 VL 207 IS 5 AR 407.e1 DI 10.1016/j.ajog.2012.08.010 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 030JM UT WOS:000310567000028 PM 22981320 ER PT J AU Zyczynski, HM Rickey, L Dyer, KY Wilson, T Stoddard, AM Gormley, EA Hsu, Y Kusek, JW Brubaker, L AF Zyczynski, Halina M. Rickey, Leslie Dyer, Keisha Y. Wilson, Tracey Stoddard, Anne M. Gormley, E. Ann Hsu, Yvonne Kusek, John W. Brubaker, Linda CA Urinary Incontinence Treatment TI Sexual activity and function in women more than 2 years after midurethral sling placement SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE mesh; midurethral sling; sexual function; surgery; urinary incontinence ID STRESS URINARY-INCONTINENCE; SURGERY AB OBJECTIVE: The purpose of this study was to assess prospectively the effects of midurethral sling surgery on sexual function and activity. STUDY DESIGN: Sexual activity and function was assessed in 597 women with stress urinary incontinence who were enrolled in a randomized equivalence trial of retropubic compared with transobturator midurethral slings. Repeated measures analysis of variance was used to assess changes in Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire scores over a 2-year period. RESULTS: Significant, similar improvements in sexual function were seen in both midurethral sling groups. Mean Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire scores increased from 32.8 at baseline to 37.6 at 6 months and 37.3 at 24 months (P < .0001). Dyspareunia, incontinence during sex, and fear of incontinence during sex each significantly improved after surgery. Preoperative urge incontinence was associated with abstinence after surgery (P = .02); postoperative urge incontinence negatively impacted sexual function (P = .047). CONCLUSION: Midurethral sling surgery for stress urinary incontinence significantly improves sexual function, although coexistent urge incontinence has a negative impact. C1 [Zyczynski, Halina M.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. [Rickey, Leslie] Univ Maryland, Sch Med, Dept Urol, Baltimore, MD 21201 USA. [Kusek, John W.] NIDDKD, Bethesda, MD USA. [Dyer, Keisha Y.] Kaiser Permanente, Dept Obstet & Gynecol, San Diego, CA USA. [Wilson, Tracey] Univ Alabama Birmingham, Div Urol, Birmingham, AL USA. [Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA. [Gormley, E. Ann] Dartmouth Hitchcock Med Ctr, Div Urol, Lebanon, NH 03766 USA. [Hsu, Yvonne] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Brubaker, Linda] Loyola Univ Chicago, Stritch Sch Med, Dept Obstet & Gynecol, Maywood, IL USA. [Brubaker, Linda] Loyola Univ Chicago, Stritch Sch Med, Dept Urol, Maywood, IL USA. RP Zyczynski, HM (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01DK60393, U01 DK60395, U01 DK60397, U01DK 60401]; National Institute of Child Health and Human Development and Office of Research in Women's Health, National Institutes of Health; Pfizer FX Supported by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases (U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01DK60393, U01 DK60395, U01 DK60397, and U01DK 60401) and by the National Institute of Child Health and Human Development and Office of Research in Women's Health, National Institutes of Health.; H.M.Z. is a consultant for Johnson & Johnson Inc. L. R. holds a research grant from Pfizer. The remaining authors report no potential conflict of interest. NR 18 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2012 VL 207 IS 5 AR 421.e1 DI 10.1016/j.ajog.2012.06.053 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 030JM UT WOS:000310567000035 PM 22840975 ER PT J AU Bolger, SJ Hurtado, PAG Hoffert, JD Saeed, F Pisitkun, T Knepper, MA AF Bolger, Steven J. Hurtado, Patricia A. Gonzales Hoffert, Jason D. Saeed, Fahad Pisitkun, Trairak Knepper, Mark A. TI Quantitative phosphoproteomics in nuclei of vasopressin-sensitive renal collecting duct cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE beta-catenin; c-Jun; mpkCCD cells; systems biology; transcription ID EPITHELIAL SODIUM-CHANNEL; LIGHT-CHAIN KINASE; LONG-TERM REGULATION; TANDEM MASS-SPECTRA; BETA-CATENIN; PROTEIN-KINASE; C-JUN; WATER CHANNEL; RAT-KIDNEY; MODIFIED PEPTIDES AB Bolger SJ, Gonzales Hurtado PA, Hoffert JD, Saeed F, Pisitkun T, Knepper MA. Quantitative phosphoproteomics in nuclei of vasopressin-sensitive renal collecting duct cells. Am J Physiol Cell Physiol 303: C1006-C1020, 2012. First published September 19, 2012; doi:10.1152/ajpcell.00260.2012.-Vasopressin regulates transport across the collecting duct epithelium in part via effects on gene transcription. Transcriptional regulation occurs partially via changes in phosphorylation of transcription factors, transcriptional coactivators, and protein kinases in the nucleus. To test whether vasopressin alters the nuclear phosphoproteome of vasopressin-sensitive cultured mouse mpkCCD cells, we used stable isotope labeling and mass spectrometry to quantify thousands of phosphorylation sites in nuclear extracts and nuclear pellet fractions. Measurements were made in the presence and absence of the vasopressin analog dDAVP. Of the 1,251 sites quantified, 39 changed significantly in response to dDAVP. Network analysis of the regulated proteins revealed two major clusters ("cell-cell adhesion" and "transcriptional regulation") that were connected to known elements of the vasopressin signaling pathway. The hub proteins for these two clusters were the transcriptional coactivator beta-catenin and the transcription factor c-Jun. Phosphorylation of beta-catenin at Ser552 was increased by dDAVP [log(2)(dDAVP/vehicle) = 1.79], and phosphorylation of c-Jun at Ser73 was decreased [log2(dDAVP/vehicle) = -0.53]. The beta-catenin site is known to be targeted by either protein kinase A or Akt, both of which are activated in response to vasopressin. The c-Jun site is a canonical target for the MAP kinase Jnk2, which is downregulated in response to vasopressin in the collecting duct. The data support the idea that vasopressin-mediated control of transcription in collecting duct cells involves selective changes in the nuclear phosphoproteome. All data are available to users at http://helixweb.nih.gov/ESBL/Database/mNPPD/. C1 [Bolger, Steven J.; Hurtado, Patricia A. Gonzales; Hoffert, Jason D.; Saeed, Fahad; Pisitkun, Trairak; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov RI Saeed, Fahad/D-1545-2013; OI Pisitkun, Trairak/0000-0001-6677-2271 FU Division of Intramural Research of the National Heart, Lung, and Blood Institute [Z01-HL001285] FX This work was funded by the Division of Intramural Research of the National Heart, Lung, and Blood Institute (Project Z01-HL001285 to M. A. Knepper). NR 67 TC 14 Z9 14 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 2012 VL 303 IS 10 BP C1006 EP C1020 DI 10.1152/ajpcell.00260.2012 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 038YB UT WOS:000311208900003 PM 22992673 ER PT J AU Izumi, Y Li, JX Villers, C Hashimoto, K Burg, MB Ferraris, JD AF Izumi, Yuichiro Li, Jinxi Villers, Courtney Hashimoto, Kosuke Burg, Maurice B. Ferraris, Joan D. TI Mutations that reduce its specific DNA binding inhibit high NaCl-induced nuclear localization of the osmoprotective transcription factor NFAT5 SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE high NaCl; NUP88; leptomycin B; XPO1 ID OSMOTIC RESPONSE ELEMENT; DAMAGE-INDUCIBLE KINASE; FACTOR TONEBP/OREBP; NUCLEOCYTOPLASMIC TRAFFICKING; GENE-EXPRESSION; PROTEIN; TONICITY; STRESS; PHOSPHORYLATION; CONTRIBUTES AB Izumi Y, Li J, Villers C, Hashimoto K, Burg MB, Ferraris JD. Mutations that reduce its specific DNA binding inhibit high NaCl-induced nuclear localization of the osmoprotective transcription factor NFAT5. Am J Physiol Cell Physiol 303: C1061-C1069, 2012. First published September 19, 2012; doi:10.1152/ajpcell.00265.2012.The transcription factor nuclear factor of activated T cell 5 (NFAT5) is activated by the stress of hypertonicity (e.g., high NaCl). Increased expression of NFAT5 target genes causes accumulation of protective organic osmolytes and heat shock proteins. Under normotonic conditions (similar to 300 mosmol/kgH(2)O), NFAT5 is distributed between the nucleus and cytoplasm, hypertonicity causes it to translocate into the nucleus, and hypotonicity causes it to translocate into the cytoplasm. The mechanism of translocation is complex and not completely understood. NFAT5-T298 is a known contact site of NFAT5 with its specific DNA element [ osmotic response element (ORE)]. In the present study, we find that mutation of NFAT5-T298 to alanine or aspartic acid not only reduces binding of NFAT5 to OREs (EMSA) but also proportionately reduces high NaCl-induced nuclear translocation of NFAT5. Combined mutation of other NFAT5 DNA contact sites (R293A/E299A/R302A) also greatly reduces both specific DNA binding and nuclear localization of NFAT5. NFAT5-T298 is a potential phosphorylation site, but, using protein mass spectrometry, we do not find phosphorylation at NFAT5-T298. Further, decreased high NaCl-induced nuclear localization of NFAT5 mutated at T298 does not involve previously known regulatory mechanisms, including hypotonicity-induced export of NFAT5, regulated by phosphorylation of NFAT5-S155, XPO1 (CRM1/exportin1)-mediated export of NFAT5 from the nucleus, or hypertonicity-induced elevation of NUP88, which enhances nuclear localization of NFAT5. We conclude that specific DNA binding of NFAT5 contributes to its nuclear localization, by mechanisms, as yet undetermined, but independent of ones previously described to regulate NFAT5 distribution. C1 [Izumi, Yuichiro; Li, Jinxi; Villers, Courtney; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA. [Hashimoto, Kosuke] Natl Lib Med, Computat Biol Branch, NIH, Bethesda, MD USA. RP Ferraris, JD (reprint author), 10 Ctr Dr, Bethesda, MD USA. EM ferraris@nhlbi.nih.gov FU Intramural Research Program of the National Heart, Lung, and Blood Institute FX This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute. NR 36 TC 2 Z9 2 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 2012 VL 303 IS 10 BP C1061 EP C1069 DI 10.1152/ajpcell.00265.2012 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 038YB UT WOS:000311208900008 PM 22992674 ER PT J AU Patterson, K Catalan, MA Melvin, JE Yule, DI Crampin, EJ Sneyd, J AF Patterson, Kate Catalan, Marcelo A. Melvin, James E. Yule, David I. Crampin, Edmund J. Sneyd, James TI A quantitative analysis of electrolyte exchange in the salivary duct SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE salivary glands; tubular transport; membrane transport ID TRANSMEMBRANE CONDUCTANCE REGULATOR; RAT SUBMANDIBULAR-GLAND; CYSTIC-FIBROSIS; MATHEMATICAL-MODEL; TRANSDUCTAL FLUXES; FLUID SECRETION; HCO3-SECRETION; CFTR ACTIVITY; MAIN DUCT; MOUSE AB Patterson K, Catalan MA, Melvin JE, Yule DI, Crampin EJ, Sneyd J. A quantitative analysis of electrolyte exchange in the salivary duct. Am J Physiol Gastrointest Liver Physiol 303: G1153-G1163, 2012. First published August 16, 2012; doi:10.1152/ajpgi.00364.2011.-A healthy salivary gland secretes saliva in two stages. First, acinar cells generate primary saliva, a plasma-like, isotonic fluid high in Na+ and Cl-. In the second stage, the ducts exchange Na+ and Cl- for K+ and HCO3-, producing a hypotonic final saliva with no apparent loss in volume. We have developed a tool that aims to understand how the ducts achieve this electrolyte exchange while maintaining the same volume. This tool is part of a larger multi-scale model of the salivary gland and can be used at the duct or gland level to investigate the effects of genetic and chemical alterations. In this study, we construct a radially symmetric mathematical model of the mouse salivary gland duct, representing the lumen, the cell, and the interstitium. For a given flow and primary saliva composition, we predict the potential differences and the luminal and cytosolic concentrations along a duct. Our model accounts well for experimental data obtained in wild-type animals as well as knockouts and chemical inhibitors. Additionally, the luminal membrane potential of the duct cells is predicted to be very depolarized compared with acinar cells. We investigate the effects of an electrogenic vs. electroneutral anion exchanger in the luminal membrane on concentration and the potential difference across the luminal membrane as well as how impairing the cystic fibrosis transmembrane conductance regulator channel affects other ion transporting mechanisms. Our model suggests the electrogenicity of the anion exchanger has little effect in the submandibular duct. C1 [Patterson, Kate; Sneyd, James] Univ Auckland, Dept Math, Auckland 1142, New Zealand. [Catalan, Marcelo A.; Melvin, James E.] Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, Div Intramural Res, NIH, Bethesda, MD USA. [Yule, David I.] Univ Rochester, Med Ctr, Dept Pharmacol & Physiol, Rochester, NY 14642 USA. [Yule, David I.] Univ Rochester, Med Ctr, Ctr Oral Biol, Rochester, NY 14642 USA. [Crampin, Edmund J.] Univ Auckland, Auckland Bioengn Inst, Auckland 1142, New Zealand. [Crampin, Edmund J.] Univ Auckland, Dept Engn Sci, Auckland 1142, New Zealand. RP Patterson, K (reprint author), Univ Auckland, Dept Math, Private Bag 92019, Auckland 1142, New Zealand. EM k.patterson@math.auckland.ac.nz RI Sneyd, James/C-8995-2009; OI Sneyd, James/0000-0001-7305-2862; Catalan, Marcelo/0000-0003-3544-2821 FU National Institute of Dental Research Grant [R01-DE-19245] FX This work was supported by the National Institute of Dental Research Grant R01-DE-19245. NR 58 TC 4 Z9 4 U1 2 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 2012 VL 303 IS 10 BP G1153 EP G1163 DI 10.1152/ajpgi.00364.2011 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 039DH UT WOS:000311222700009 PM 22899825 ER PT J AU McMurray, B AF McMurray, Bob TI Bob McMurray Award for Distinguished Scientific Early Career Contributions to Psychology SO AMERICAN PSYCHOLOGIST LA English DT Biographical-Item C1 [McMurray, Bob] Natl Inst Environm Hlth Sci, Chris Portiers Lab, Res Triangle Pk, NC 27709 USA. [McMurray, Bob] Univ Rochester, Rochester, NY 14627 USA. [McMurray, Bob] Cornell, Dept Psychol, Ithaca, NY USA. [McMurray, Bob] Delta Ctr, Iowa City, IA USA. [McMurray, Bob] Univ Illinois, Chicago, IL 60680 USA. [McMurray, Bob] Univ Kansas, Lawrence, KS 66045 USA. RP McMurray, B (reprint author), Natl Inst Environm Hlth Sci, Chris Portiers Lab, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD NOV PY 2012 VL 67 IS 8 BP 635 EP 637 DI 10.1037/a0030052 PG 3 WC Psychology, Multidisciplinary SC Psychology GA 036EC UT WOS:000311008200010 ER PT J AU Watson, DLB Sanoff, R Mackintosh, JE Saver, JL Ford, GA Price, C Starkman, S Eckstein, M Conwit, R Grace, A Murtagh, MJ AF Watson, Duika L. Burges Sanoff, Randy Mackintosh, Joan E. Saver, Jeffrey L. Ford, Gary A. Price, Christopher Starkman, Sidney Eckstein, Marc Conwit, Robin Grace, Anna Murtagh, Madeleine J. TI Evidence From the Scene: Paramedic Perspectives on Involvement in Out-of-Hospital Research SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY MEDICAL-SERVICES; RANDOMIZED CONTROLLED-TRIALS; EXPLICIT INFORMED-CONSENT; CLINICAL-RESEARCH; HEALTH-CARE; STROKE; THROMBOLYSIS; PARTICIPATION; SYSTEMS; ELICITATION AB Study objective: In the context of calls to develop better systems for out-of-hospital clinical research, we seek to understand paramedics' perceptions of involvement in research and the barriers and facilitators to that involvement. Methods: This was a qualitative study using semistructured focus groups with 58 United Kingdom paramedics and interviews with 30 US firefighter-paramedics. The study focused on out-of-hospital research (trials of out-of-hospital treatment for stroke), whereby paramedics identified potential study subjects or obtained consent and administered study treatment in the field. Data were analyzed with a thematic and discourse approach. Results: Three key themes emerged as significant facilitators and barriers to paramedic involvement in research: patient benefit, professional identity and responsibility, and time. Paramedics showed willingness and capacity to engage in research but also some reticence because of the perceived sacrifice of autonomy and challenge to their identity. Paramedics work in a time-sensitive environment and were concerned that research would increase time taken in the field. Conclusion: Awareness of these perspectives will help with development of out-of-hospital research protocols and potentially facilitate greater participation. [Ann Emerg Med. 2012;60:641-650.] C1 [Murtagh, Madeleine J.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Watson, Duika L. Burges; Mackintosh, Joan E.; Murtagh, Madeleine J.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Watson, Duika L. Burges] Univ Durham, Sch Med & Hlth, Durham DH1 3HP, England. [Sanoff, Randy; Saver, Jeffrey L.; Starkman, Sidney; Grace, Anna] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Price, Christopher] Northumbria Healthcare NHS Fdn Trust, Stroke Res Grp, Northumbria, Northd, England. [Ford, Gary A.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Eckstein, Marc] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Eckstein, Marc] Los Angeles City Fire Dept, Los Angeles, CA USA. [Conwit, Robin] NINDS, Bethesda, MD 20892 USA. RP Murtagh, MJ (reprint author), Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. EM mm399@le.ac.uk OI Burges Watson, Duika/0000-0002-5791-9670; Saver, Jeffrey/0000-0001-9141-2251 FU United Kingdom-based National Institute for Health Research (NIHR); US-based National Institutes of Health (NIH); NIHR [RP-PG-0606-1241]; NIH-NINDS [U01 NS 44364] FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). This interview study forms part of an integrated program of research, the Developing and Assessing Services for Hyper-acute Stroke (DASH) trial, conducted in England. This incorporates an international comparative component involving the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 trial. DASH is funded by the United Kingdom-based National Institute for Health Research (NIHR). FAST-MAG is funded by the US-based National Institutes of Health (NIH). This article presents independent research commissioned by the NIHR under its Programme Grants for Applied Research (RP-PG-0606-1241). Professor Ford is supported by an NIHR Senior Investigator Award. Supported in part by NIH-NINDS Award U01 NS 44364. NR 40 TC 10 Z9 10 U1 0 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2012 VL 60 IS 5 BP 641 EP 650 DI 10.1016/j.annemergmed.2011.12.002 PG 10 WC Emergency Medicine SC Emergency Medicine GA 035FN UT WOS:000310928800019 ER PT J AU Grady, PA AF Grady, Patricia A. TI "The National Institute of Nursing Research: Delivering on the promise" SO APPLIED NURSING RESEARCH LA English DT Editorial Material C1 NINR, NIH, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), NINR, NIH, Bethesda, MD 20892 USA. EM info@ninr.nih.gov NR 4 TC 1 Z9 1 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 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD NOV PY 2012 VL 25 IS 4 BP 229 EP 230 DI 10.1016/j.apnr.2012.06.002 PG 2 WC Nursing SC Nursing GA 035FJ UT WOS:000310928400001 PM 23102109 ER PT J AU Shankaran, S Barnes, PD Hintz, SR Laptook, AR Zaterka-Baxter, KM McDonald, SA Ehrenkranz, RA Walsh, MC Tyson, JE Donovan, EF Goldberg, RN Bara, R Das, A Finer, NN Sanchez, PJ Poindexter, BB Van Meurs, KP Carlo, WA Stoll, BJ Duara, S Guillet, R Higgins, RD AF Shankaran, Seetha Barnes, Patrick D. Hintz, Susan R. Laptook, Abbott R. Zaterka-Baxter, Kristin M. McDonald, Scott A. Ehrenkranz, Richard A. Walsh, Michele C. Tyson, Jon E. Donovan, Edward F. Goldberg, Ronald N. Bara, Rebecca Das, Abhik Finer, Neil N. Sanchez, Pablo J. Poindexter, Brenda B. Van Meurs, Krisa P. Carlo, Waldemar A. Stoll, Barbara J. Duara, Shahnaz Guillet, Ronnie Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst C TI Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION LA English DT Article ID WHOLE-BODY HYPOTHERMIA; SYSTEMIC HYPOTHERMIA; RANDOMIZED-TRIAL; TERM NEWBORNS; MRI; ASPHYXIA; PATTERNS; INFANTS; AGE AB Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic-ischaemic encephalopathy treated with hypothermia. Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18-22 months of age. Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability. Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18-22 months following hypothermia for neonatal encephalopathy. C1 [Shankaran, Seetha] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Neonatol, Detroit, MI 48201 USA. [Barnes, Patrick D.] Stanford Univ, Sch Med, Dept Radiol & Pediat, Palo Alto, CA 94304 USA. [Hintz, Susan R.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. [Laptook, Abbott R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. [Zaterka-Baxter, Kristin M.] RTI Int, Dept Stat & Epidemiol, Research Pk, NC USA. [McDonald, Scott A.; Das, Abhik] RTI Int, Stat & Epidemiol, Research Pk, NC USA. [Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Walsh, Michele C.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Tyson, Jon E.] Univ Texas Houston, Med Sch Houston, Ctr Clin Res & Evidence Based Med, Houston, TX USA. [Donovan, Edward F.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Bara, Rebecca] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [Finer, Neil N.] Univ Calif San Diego, Med Ctr, Dept Paediat Neonatol, La Jolla, CA 92093 USA. [Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA. [Van Meurs, Krisa P.] Lucile Packard Childrens Hosp, Div Neonatol, Palo Alto, CA USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Duara, Shahnaz] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Guillet, Ronnie] Univ Rochester, Sch Med & Dent, Rochester, NY USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Shankaran, S (reprint author), Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Neonatol, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM sshankar@med.wayne.edu FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Pfizer; Environmental Protection Agency; Gerber Foundation FX The National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provided grant support for the Neonatal Research Network's whole-body hypothermia and follow-up studies.; Dr Cotten reports having served on the data and safety monitoring board for the Inhibitex phase 3 study of Vernonate for the prevention of infections in preterm infants. Dr Donovan reports having received support from the Environmental Protection Agency (Lanphear) and the Gerber Foundation. Dr Carlo reports holding stock options at the Pediatrix Medical Group. Dr Stevenson reports having received research support from Pfizer. NR 24 TC 43 Z9 45 U1 0 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1359-2998 J9 ARCH DIS CHILD-FETAL JI Arch. Dis. Child.-Fetal Neonatal Ed. PD NOV PY 2012 VL 97 IS 6 BP F398 EP F404 DI 10.1136/archdischild-2011-301524 PG 7 WC Pediatrics SC Pediatrics GA 036JS UT WOS:000311022800003 PM 23080477 ER PT J AU Mortimer, K Gordon, SB Jindal, SK Accinelli, RA Balmes, J Martin, WJ AF Mortimer, Kevin Gordon, Stephen B. Jindal, Surinder K. Accinelli, Roberto A. Balmes, John Martin, William J., II TI Household Air Pollution Is a Major Avoidable Risk Factor for Cardiorespiratory Disease SO CHEST LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; WOOD SMOKE EXPOSURE; SOLID-FUEL USE; CHRONIC-BRONCHITIS; BIOMASS FUEL; LUNG-CANCER; RESPIRATORY SYMPTOMS; CHILDHOOD PNEUMONIA; CARBON-MONOXIDE; BIRTH-WEIGHT AB Household air pollution (HAP) from biomass fuels, coal, and kerosene burned in open fires, primitive stoves, and lamps causes at least 2 million deaths per year. Many of these deaths occur in children <5 years of age with pneumonia and in women with COPD, lung cancer, and cardiovascular disease. HAP is inextricably linked to poverty, with activities to obtain fuel consuming a large proportion of the time and financial resources of poor households. Thus, fewer resources used in this way means less is available for basic needs like food, education, and health care. The burden of work and the exposure to smoke, particularly during cooking, are predominantly borne by women and children. Although historically HAP has not received sufficient attention from the scientific, medical, public health, development, and policy-making communities, the tide has clearly changed with the broad-based support and launch of the Global Alliance for Clean Cookstoves in 2010. There is now considerable reason for optimism that this substantial cause of cardiorespiratory morbidity and mortality will be addressed comprehensively and definitively. Drawing on our experience from four continents, we provide background information on the problem of HAP, health impacts of HAP, opportunities for research, and the current best solutions. CHEST 2012; 142(5):1308-1315 C1 [Martin, William J., II] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Mortimer, Kevin; Gordon, Stephen B.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. [Jindal, Surinder K.] Postgrad Inst Med Educ & Res, Dept Pulm Med, Chandigarh 160012, India. [Accinelli, Roberto A.] Univ Peruana Cayetano Heredia, Inst Invest Altura, Lima, Peru. [Balmes, John] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Balmes, John] Univ Calif San Francisco, Berkeley, CA USA. RP Martin, WJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, 31 Ctr Dr, Bethesda, MD 20892 USA. EM wjmartin@mail.nih.gov OI Gordon, Stephen/0000-0001-6576-1116; Mortimer, Kevin/0000-0002-8118-8871 FU Medical Research Council [MR/K006533/1] NR 59 TC 31 Z9 32 U1 1 U2 51 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2012 VL 142 IS 5 BP 1308 EP 1315 DI 10.1378/chest.12-1596 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 036EV UT WOS:000311010100036 PM 23131939 ER PT J AU Saavedra, JM AF Saavedra, Juan M. TI Angiotensin II AT(1) receptor blockers as treatments for inflammatory brain disorders SO CLINICAL SCIENCE LA English DT Review DE angiotensin II type I receptor blocker (ARB); brain; inflammation; neuronal injury; renin-angiotensin system ID SPONTANEOUSLY HYPERTENSIVE-RATS; CEREBRAL-BLOOD-FLOW; CENTRAL-NERVOUS-SYSTEM; QUALITY-OF-LIFE; INNATE IMMUNE-RESPONSE; FACTOR-KAPPA-B; CONVERTING ENZYME-INHIBITORS; RENIN-ANGIOTENSIN; PPAR-GAMMA; ALZHEIMERS-DISEASE AB The effects of brain AngII (angiotensin II) depend on AT(1) receptor (AngII type I receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT(1) receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurodegerative, mood and traumatic brain disorders, and cognitive decline. In rodents, ARBs (AT(1) receptor blockers) ameliorate stress-induced disorders, anxiety and depression, protect cerebral blood flow during stroke, decrease brain inflammation and amyloid-beta neurotoxicity and reduce traumatic brain injury. Direct anti-inflammatory protective effects, demonstrated in cultured microglia, cerebrovascular endothelial cells, neurons and human circulating monocytes, may result not only in AT(1) receptor blockade, but also from PPAR gamma (peroxisome-proliferator-activated receptor gamma) stimulation. Controlled clinical studies indicate that ARBs protect cognition after stroke and during aging, and cohort analyses reveal that these compounds significantly reduce the incidence and progression of Alzheimer's disease. ARBs are commonly used for the therapy of hypertension, diabetes and stroke, but have not been studied in the context of neurodegenerative, mood or traumatic brain disorders, conditions lacking effective therapy. These compounds are well-tolerated pleiotropic neuroprotective agents with additional beneficial cardiovascular and metabolic profiles, and their use in central nervous system disorders offers a novel therapeutic approach of immediate translational value. ARBs should be tested for the prevention and therapy of neurodegenerative disorders, in particular Alzheimer's disease, affective disorders, such as co-morbid cardiovascular disease and depression, and traumatic brain injury. C1 NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM Saavedrj@mail.nih.gov FU Division of Intramural Research Programs, National Institute of Mental Health, Department of Health and Human Services, U.S.A FX My own work is supported by the Division of Intramural Research Programs, National Institute of Mental Health, Department of Health and Human Services, U.S.A. NR 257 TC 51 Z9 53 U1 3 U2 29 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD NOV PY 2012 VL 123 IS 9-10 BP 567 EP 590 DI 10.1042/CS20120018 PG 24 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 035FC UT WOS:000310927600005 PM 22827472 ER PT J AU Casagrande, SS Cowie, CC AF Casagrande, Sarah Stark Cowie, Catherine C. TI Health Insurance Coverage Among People With and Without Diabetes in the U.S. Adult Population SO DIABETES CARE LA English DT Article ID PREVENTIVE CARE; RISK; COMPLICATIONS; RECEIPT; DISEASE; ACCESS AB OBJECTIVE-To compare health insurance coverage and type of coverage for adults with and without diabetes. RESEARCH DESIGN AND METHODS-The data used were from 2,704 adults who self-reported diabetes and 25,008 adults without reported diabetes in the 2009 National Health Interview Survey. Participants reported on their current type of health insurance coverage, demographic information, diabetes-related factors, and comorbidities. If uninsured, participants reported reasons for not having health insurance. RESULTS-Among all adults with diabetes, 90% had some form of health insurance coverage, including 85% of people 18-64 years of age and similar to 100% of people >= 65 years of age; 81% of people without diabetes had some type of coverage (vs. diabetes, P < 0.0001), including 78% of people 18-64 years of age and 99% of people >= 65 years of age. More adults 18-64 years of age with diabetes had Medicare coverage (14% vs. no diabetes, 3%; P < 0.0001); fewer people with diabetes had private insurance (58% vs. no diabetes, 66%; P < 0.0001). People 18-64 years of age with diabetes more often had two health insurance sources compared with people without diabetes (13 vs. 5%, P < 0.0001). The most common private plan was a preferred provider organization (PPO) followed by a health maintenance organization/independent practice organization (HMO/IPA) plan regardless of diabetes status. For participants 18-64 years of age, high health insurance cost was the most common reason for not having coverage. CONCLUSIONS-Two million adults,65 years of age with diabetes had no health insurance coverage, which has considerable public health and economic impact. Health care reform should work toward ensuring that people with diabetes have coverage for routine care. Diabetes Care 35: 2243-2249, 2012 C1 [Casagrande, Sarah Stark] Social & Sci Syst Inc, Silver Spring, MD USA. [Cowie, Catherine C.] NIDDKD, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA. RP Casagrande, SS (reprint author), Social & Sci Syst Inc, Silver Spring, MD USA. EM scasagrande@s-3.com FU National Institute of Diabetes and Digestive and Kidney Diseases [HH-SN-267200700001G] FX This work was financially supported by the National Institute of Diabetes and Digestive and Kidney Diseases (HH-SN-267200700001G). NR 21 TC 4 Z9 4 U1 3 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2012 VL 35 IS 11 BP 2243 EP 2249 DI 10.2337/dc12-0257 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 041TM UT WOS:000311424100026 ER PT J AU Steinert, EM Schwartz, RH Singh, NJ AF Steinert, Elizabeth M. Schwartz, Ronald H. Singh, Nevil J. TI At low precursor frequencies, the T-cell response to chronic self-antigen results in anergy without deletion SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Clonal anergy; Clonal deletion; Immunological tolerance; Precursor frequency; T cells ID IN-VIVO; ADAPTIVE TOLERANCE; NAIVE; COMPETITION; PROLIFERATION; DIFFERENTIATION; EXPOSURE AB The behavior of self-reactive T cells in the peripheral immune system has often been studied by following the fate of adoptively transferred antigen-specific T cells in antigen expressing mice. In most cases, after a period of expansion, such cells undergo a slow clonal deletion, accompanied by the onset of anergy and/or suppression in the remaining cells. Here, we demonstrate that at initial frequencies approaching those found in normal repertoires, it is possible to completely avoid deletion and still maintain peripheral tolerance. At starting numbers of <1000 T cells, stimulation by chronic self-antigens resulted in a period of robust clonal expansion, followed by a steady plateau phase extending beyond 4 months. Despite their stable persistence, the self-reactive T cells did not convert to a Foxp3+ fate. However, they displayed a considerable block in their ability to make IL-2, consistent with the onset of anergy in a precursor frequency or deletion independent fashion. C1 [Singh, Nevil J.] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. [Steinert, Elizabeth M.] Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA. RP Singh, NJ (reprint author), NIAID, Lab Cellular & Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM nsingh@niaid.nih.gov FU NIH, NIAID FX We thank Eleanore Chuang for assistance with experiments, and Pascal Chappert for discussions. This research was supported by the Intramural Research Program of the NIH, NIAID. NR 21 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2012 VL 42 IS 11 BP 2875 EP 2880 DI 10.1002/eji.201242518 PG 6 WC Immunology SC Immunology GA 030BY UT WOS:000310544000007 PM 22806568 ER PT J AU Baig, S Garcia, F Fricano, K Deng, J Mao, M Christman, J Chatterjee, S Block, M Minshall, R Ye, R Gantner, B Bonini, MG AF Baig, Saqib Garcia, Farnaz Fricano, Kristine Deng, Jing Mao, Mao Christman, John Chatterjee, Saurabh Block, Michelle Minshall, Richard Ye, Richard Gantner, Benjamin Bonini, Marcelo G. TI Ablation of NNOS/NOS1 Leads to the Suppression of the Systemic Inflammatory Response via Suppressor of Cytokine Signaling (SOCS-1) Upregulation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Baig, Saqib; Garcia, Farnaz; Fricano, Kristine; Deng, Jing; Mao, Mao; Christman, John; Minshall, Richard; Ye, Richard; Gantner, Benjamin; Bonini, Marcelo G.] Univ Illinois, Chicago, IL 60680 USA. [Chatterjee, Saurabh] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Block, Michelle] Virginia Commonwealth Univ, Richmond, VA 23284 USA. RI Mao, Mao/E-3783-2013 OI Mao, Mao/0000-0003-1524-8853 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S74 EP S74 DI 10.1016/j.freeradbiomed.2012.10.221 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600188 ER PT J AU Bellavia, L Solomon, SB Sweeney, D Piknova, B Perlegas, A Helms, CC King, SB Raat, NJH Kern, SJ Sun, JF Mcphail, LC Schechter, AN Natanson, C Gladwin, MT Kim-Shapiro, DB AF Bellavia, Landon Solomon, Steven B. Sweeney, Daniel Piknova, Barbora Perlegas, Andreas Helms, Christine C. King, S. Bruce Raat, Nicolaas J. H. Kern, Steven J. Sun, Junfeng Mcphail, Linda C. Schechter, Alan N. Natanson, Charles Gladwin, Mark T. Kim-Shapiro, Daniel B. TI Angeli's Salt Counteracts the Vasoactive Effects of Elevated Plasma Hemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Mcphail, Linda C.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Solomon, Steven B.; Sweeney, Daniel; Piknova, Barbora; Kern, Steven J.; Sun, Junfeng; Schechter, Alan N.; Natanson, Charles] NIH, Bethesda, MD USA. [Gladwin, Mark T.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RI McPhail, Linda/D-9505-2013 OI McPhail, Linda/0000-0002-8670-306X NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S178 EP S178 DI 10.1016/j.freeradbiomed.2012.10.489 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600469 ER PT J AU Bhattacharjee, S Jiang, JJ Chatterjee, S Deterding, L Sinha, B Mason, R AF Bhattacharjee, Suchandra Jiang, Jinjie Chatterjee, Saurabh Deterding, Leesa Sinha, Birandra Mason, Ron TI Site-Specific Detection and Imaging of Free Radicals in DNA Induced by Cu(11)-H2O2 Oxidizing System and Its Repair Using ESR, Immuno-Spin Trapping, Confocal Microscopy, LC-MS and MS/MS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Bhattacharjee, Suchandra; Jiang, Jinjie; Deterding, Leesa; Sinha, Birandra; Mason, Ron] NIEHS, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S133 EP S133 DI 10.1016/j.freeradbiomed.2012.10.361 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600346 ER PT J AU Ehrenshaft, M Roberts, JE Mason, RP AF Ehrenshaft, Marilyn Roberts, Joan E. Mason, Ronald P. TI Hypericin Photosensitization of alpha-Crystallin in Human Lens Epithelial Cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, NIH, Bethesda, MD USA. [Roberts, Joan E.] Fordham Univ, Bronx, NY 10458 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S134 EP S134 DI 10.1016/j.freeradbiomed.2012.10.365 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600350 ER PT J AU Esworthy, RS Kim, BW Doroshow, JH Leto, TL Chu, FF AF Esworthy, Robert Steven Kim, Byung-Wook Doroshow, James H. Leto, Thomas L. Chu, Fong-Fong TI Glutathione Peroxidase-1 and-2 Protect Mice from Salmonella-Induced Colitis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Esworthy, Robert Steven; Kim, Byung-Wook; Chu, Fong-Fong] Beckman Res Inst City Hope, Duarte, CA USA. [Doroshow, James H.] NCI, Bethesda, MD 20892 USA. [Leto, Thomas L.] NIAID, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S75 EP S75 DI 10.1016/j.freeradbiomed.2012.10.224 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600191 ER PT J AU Ganini, D Mason, RP AF Ganini, Douglas Mason, Ronald P. TI Lipoperoxidation with Consequent Protein Radical Formation During LDL Oxidation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Ganini, Douglas; Mason, Ronald P.] NIEHS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S135 EP S135 DI 10.1016/j.freeradbiomed.2012.10.366 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600351 ER PT J AU Helms, CC Marvel, M Stahle, M Hantgan, RR Kato, GJ Lee, JS Gladwin, M Kim-Shapiro, DB AF Helms, Christine Carlisle Marvel, Madison Stahle, Mary Hantgan, Roy R. Kato, Gregory J. Lee, Janet S. Gladwin, Mark Kim-Shapiro, Daniel B. TI The Role of Free Radicals in Hemolysis Associated Platelet Activation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Helms, Christine Carlisle; Marvel, Madison; Stahle, Mary; Hantgan, Roy R.; Kim-Shapiro, Daniel B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Kato, Gregory J.] NHLBI, NIH, Bethesda, MD USA. [Lee, Janet S.; Gladwin, Mark] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S162 EP S163 DI 10.1016/j.freeradbiomed.2012.10.444 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600426 ER PT J AU Horinouchi, Y Summers, FA Ehrenshaft, M Mason, RP AF Horinouchi, Yuya Summers, Fiona A. Ehrenshaft, Marilyn Mason, Ronald P. TI An Aromatic Nitroso Compound, N,N-Dimethyl-4-Nitrosoaniline, Generates Free Radicals in Hepatocytes as Detected Via Immuno-Spin Trapping SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Horinouchi, Yuya; Summers, Fiona A.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S22 EP S23 DI 10.1016/j.freeradbiomed.2012.10.053 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600049 ER PT J AU Jang, S Gao, Y Abdelmegeed, MA Banerjee, A Yu, LR Song, BJ AF Jang, Sehwan Gao, Yuan Abdelmegeed, Mohamed A. Banerjee, Atrayee Yu, Li-Rong Song, B. J. TI Role of JNK-Mediated Phosphorylation in Mitochondrial Dysfunction and Liver Injury SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Jang, Sehwan; Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Song, B. J.] NIAAA, NIH, Bethesda, MD USA. [Gao, Yuan; Yu, Li-Rong] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S143 EP S144 DI 10.1016/j.freeradbiomed.2012.10.389 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600373 ER PT J AU Kumar, A Ganini-Da Silva, D Deterding, LJ Ehrenshaft, M Mason, RP AF Kumar, Ashutosh Ganini-Da Silva, Douglas Deterding, Leesa J. Ehrenshaft, Marilyn Mason, Ronald P. TI Immuno-Spin Trapping of Heme-Induced Protein Radicals; Implications for Heme Oxygenase-1 Induction and Heme Degradation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Kumar, Ashutosh; Ganini-Da Silva, Douglas; Deterding, Leesa J.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S135 EP S136 DI 10.1016/j.freeradbiomed.2012.10.369 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600354 ER PT J AU Mukhopadhyay, P Horvath, B Zsengeller, Z Batkai, S Cao, ZX Kechrid, M Erdelyi, K Tanchian, G Liaudet, L Stillman, IE Joseph, J Kalyanaraman, B Pacher, P AF Mukhopadhyay, Partha Horvath, Bela Zsengeller, Zsuzsanna Batkai, Sandor Cao, Zongxian Kechrid, Malek Erdelyi, Katalin Tanchian, Galin Liaudet, Lucas Stillman, Isaac E. Joseph, Joy Kalyanaraman, Balaraman Pacher, Pal TI Mitochondrially Targeted Antioxidants Ameliorate Inflammatory Response and Tissue Injury Associated with Hepatic Ischemia-Reperfusion in Mice SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Mukhopadhyay, Partha; Horvath, Bela; Batkai, Sandor; Cao, Zongxian; Kechrid, Malek; Erdelyi, Katalin; Tanchian, Galin; Pacher, Pal] NIH, Bethesda, MD USA. [Zsengeller, Zsuzsanna; Stillman, Isaac E.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Zsengeller, Zsuzsanna; Stillman, Isaac E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Horvath, Bela/A-7368-2009; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S113 EP S113 DI 10.1016/j.freeradbiomed.2012.10.276 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600293 ER PT J AU Nagababu, E Hesdorffer, CS Rifkind, JM AF Nagababu, Enika Hesdorffer, Charles S. Rifkind, Joseph M. TI Increased Oxidative Stress in Humans Under Pathological Conditions Measured by Fluorescent Heme Degradation Product in Red Blood Cells and Whole Blood SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Nagababu, Enika; Hesdorffer, Charles S.; Rifkind, Joseph M.] NIA, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S127 EP S127 DI 10.1016/j.freeradbiomed.2012.10.315 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600331 ER PT J AU Nam, Y Dang, DK Tu, THT Bach, JH Shin, EJ Bing, G Hong, JS Kim, HC AF Nam, Yunsung Dang, Duy-Khanh Thu-Hien Thi Tu Bach, Jae-Hyung Shin, Eun-Joo Bing, Guoying Hong, Jau-Shyong Kim, Hyoung-Chun TI Dynorphin Provides Neuroprotection Against Methamphetamine-Induced Neurotoxicity via Activating Glutathione-Dependent Antioxidant Enzymes, but not via Modulating Classical kappa-Opioid Receptors SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Nam, Yunsung; Dang, Duy-Khanh; Thu-Hien Thi Tu; Bach, Jae-Hyung; Shin, Eun-Joo; Kim, Hyoung-Chun] Kangwon Natl Univ, Kangwon Do, South Korea. [Nam, Yunsung] Chung Ang Univ, Seoul, South Korea. [Bing, Guoying] Univ Kentucky, Med Ctr, Lexington, KY 40506 USA. [Hong, Jau-Shyong] NIEHS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S69 EP S69 DI 10.1016/j.freeradbiomed.2012.10.208 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600176 ER PT J AU Park, JW Piknova, B Schechter, AN AF Park, Ji-Won Piknova, Barbora Schechter, Alan N. TI Effect of Blood Nitrite and Nitrate Levels on Platelet Function in Mice SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Park, Ji-Won; Piknova, Barbora; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S184 EP S185 DI 10.1016/j.freeradbiomed.2012.10.509 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600489 ER PT J AU Piknova, B Silva, AC Schechter, AN AF Piknova, Barbora Silva, Afonso C. Schechter, Alan N. TI NO Production in Rat Brain - Possible Non-enzymatic Pathways SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Piknova, Barbora; Schechter, Alan N.] NIDDK, NIH, Bethesda, MD 20892 USA. [Silva, Afonso C.] NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S185 EP S185 DI 10.1016/j.freeradbiomed.2012.10.510 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600490 ER PT J AU Summers, FA Mason, RP Ehrenshaft, M AF Summers, Fiona A. Mason, Ronald P. Ehrenshaft, Marilyn TI Development of Immunoblotting Techniques for DNA Radical Detection SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Summers, Fiona A.; Mason, Ronald P.; Ehrenshaft, Marilyn] NIEHS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S139 EP S139 DI 10.1016/j.freeradbiomed.2012.10.379 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600364 ER PT J AU Takakusagi, Y Matsumoto, S Saito, K Matsuo, M DeGraff, W Choudhuri, R Devasahayam, N Subramanian, S Munasinghe, JP Hart, CP Krishna, MC Mitchell, JB AF Takakusagi, Yoichi Matsumoto, Shingo Saito, Keita Matsuo, Masayuki DeGraff, William Choudhuri, Rajani Devasahayam, Nallathamby Subramanian, Sankaran Munasinghe, Jeeva P. Hart, Charles P. Krishna, Murali C. Mitchell, James B. TI Enhancement of the Efficacy of Hypoxia Dependent Cytotoxicity of the Bioreductively Activated Hypoxia-Activated Prodrug TH-302 SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Takakusagi, Yoichi; Matsumoto, Shingo; Saito, Keita; Matsuo, Masayuki; DeGraff, William; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Krishna, Murali C.; Mitchell, James B.] Natl Canc Inst, Bethesda, MD USA. [Munasinghe, Jeeva P.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S119 EP S119 DI 10.1016/j.freeradbiomed.2012.10.294 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600311 ER PT J AU Sokolov, MV Panyutin, IG Neumann, RD AF Sokolov, Mykyta V. Panyutin, Igor G. Neumann, Ronald D. TI Whole-genome gene expression profiling reveals the major role of nitric oxide in mediating the cellular transcriptional response to ionizing radiation in normal human fibroblasts SO GENOMICS LA English DT Article DE Nitric oxide; Normal human fibroblast; Ionizing radiation; DNA microarray ID TARGETED CYTOPLASMIC IRRADIATION; HUMAN-CELLS; RADIOADAPTIVE RESPONSE; GLIOMA-CELLS; RADIORESISTANCE; PARTICLES; INDUCTION; APOPTOSIS; SURVIVAL; ARREST AB The indirect biological effects of ionizing radiation (IR) are thought to be mediated largely by reactive oxygen and nitrogen species (ROS and RNS). However, no data are available on how nitric oxide (NO) modulates the response of normal human cells to IR exposures at the level of the whole transcriptome. Here, we examined the effects of NO and ROS scavengers, carboxy-PTIO and DMSO, on changes in global gene expression in cultured normal human fibroblasts after exposures to gamma-rays, aiming to elucidate the involvement of ROS and RNS in transcriptional response to IR. We found that NO depletion dramatically affects the gene expression in normal human cells following irradiation with gamma-rays. We observed striking (more than seven-fold) reduction of the number of upregulated genes upon NO scavenging compared to reference irradiated cell cultures. NO scavenging in irradiated IMR-90 cells results in induction of p53 signaling, DNA damage and DNA repair pathways. Published by Elsevier Inc. C1 [Sokolov, Mykyta V.; Panyutin, Igor G.; Neumann, Ronald D.] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Sokolov, MV (reprint author), 9000 Rockville Pike,Bldg 10,Room 4049, Bethesda, MD 20892 USA. EM sokolovm@mail.nih.gov; ipanyuting@mail.nih.gov; rneumann@mail.nih.gov FU National Institutes of Health, Clinical Center FX We wish to thank W. DeGraff for his invaluable help with cell culture irradiation. This work was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center. NR 34 TC 1 Z9 1 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 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 2012 VL 100 IS 5 BP 277 EP 281 DI 10.1016/j.ygeno.2012.07.007 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 035GJ UT WOS:000310931100003 PM 22814268 ER PT J AU Soto-Pantoja, D Miller, T Pendrak, M DeGraff, W Sullivan, C Ridnour, L Abu-Asab, M Wink, D Tsokos, M Roberts, D AF Soto-Pantoja, David Miller, Thomas Pendrak, Michael DeGraff, William Sullivan, Camille Ridnour, Lisa Abu-Asab, Mones Wink, David Tsokos, Maria Roberts, David TI Thrombospondin-1 signaling through CD47 regulates cell and tissue radiosensitivity via autophagy SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Soto-Pantoja, David; Miller, Thomas; Pendrak, Michael; Sullivan, Camille; Abu-Asab, Mones; Tsokos, Maria; Roberts, David] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [DeGraff, William; Ridnour, Lisa; Wink, David] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RI Miller, Thomas/G-1215-2011 OI Miller, Thomas/0000-0001-8645-2785 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1519 EP 1520 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700016 ER PT J AU Tran, D Lim, JM Liu, M Stalnaker, S Wells, L Ten Hagen, K David, L AF Tran, Duy Lim, Jae-Min Liu, Mian Stalnaker, Stephanie Wells, Lance Ten Hagen, Kelly David, Live TI alpha-Dystroglycan O-mannosylation influences the subsequent addition of GalNAc by UDP-GalNAc polypeptide N-acetylgalactosaminyltransferases SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Tran, Duy; Ten Hagen, Kelly] NIDCR, NIH, Bethesda, MD USA. [Lim, Jae-Min; Liu, Mian; Stalnaker, Stephanie; Wells, Lance; David, Live] Univ Georgia, CCRC, Athens, GA 30602 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1546 EP 1546 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700087 ER PT J AU Bond, M Ghosh, S Krause, M Hanover, J AF Bond, Michelle Ghosh, Salil Krause, Michael Hanover, John TI The Caenorhabditis elegans innate immune response to S-aureus is modulated by O-GlcNAc transferase SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Bond, Michelle; Krause, Michael; Hanover, John] NIDDK, NIH, Bethesda, MD 20892 USA. [Ghosh, Salil] US FDA, Rockville, MD 20857 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1551 EP 1552 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700105 ER PT J AU Petrie, R Yamada, K AF Petrie, Ryan Yamada, Kenneth TI Actomyosin cytoskeletal organization distinguishes lobopodia from lamellipodia SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Petrie, Ryan; Yamada, Kenneth] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1583 EP 1583 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700194 ER PT J AU Tian, E Hoffman, M Ten Hagen, K AF Tian, E. Hoffman, Matthew Ten Hagen, Kelly TI O-glycosylation modulates integrin and FGF signaling by influencing the secretion of basement membrane SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Tian, E.; Hoffman, Matthew; Ten Hagen, Kelly] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1621 EP 1621 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700309 ER PT J AU Tsutsui, Y Ramakrishnan, B Qasba, P AF Tsutsui, Yuko Ramakrishnan, Boopathy Qasba, Pradman TI A Crystal Structure of Human beta-1,4-Galactosyltransferase 7 SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 Frederick Natl Lab Canc Res, Frederick, MD USA. SAIC Frederick Inc, SGS, CCR NP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1641 EP 1641 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700367 ER PT J AU Wang, LL Campbell, C Cummings, R Gerlach, JQ Gildersleeve, JC Huflejt, M Joshi, L Kane, M Pieters, R Reichardt, N Smith, D Mahal, LK AF Wang, Linlin Campbell, Christopher Cummings, Richard Gerlach, Jared Q. Gildersleeve, Jeffrey C. Huflejt, Margaret Joshi, Lokesh Kane, Marian Pieters, Roland Reichardt, Neils Smith, David Mahal, Lara K. TI Cross-platform comparison of carbohydrate microarrays: Six groups and five lectins SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Huflejt, Margaret] NYU, Langone Med Ctr, New York, NY 10003 USA. [Campbell, Christopher] NCI, Bethesda, MD 20892 USA. [Cummings, Richard; Smith, David] Emory Univ, Atlanta, GA 30322 USA. [Gerlach, Jared Q.; Joshi, Lokesh; Kane, Marian] NUI Galway, Natl Diagnost Ctr, Galway, Ireland. [Pieters, Roland] Univ Utrecht, NL-3508 TC Utrecht, Netherlands. RI Gildersleeve, Jeffrey/N-3392-2014 NR 0 TC 0 Z9 0 U1 0 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1647 EP 1647 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700383 ER PT J AU Heroux, M Iannotti, RJ Currie, D Pickett, W Janssen, I AF Heroux, Mariane Iannotti, Ronald J. Currie, Dorothy Pickett, William Janssen, Ian TI The food retail environment in school neighborhoods and its relation to lunchtime eating behaviors in youth from three countries SO HEALTH & PLACE LA English DT Article DE Food retail environment; Lunchtime eating behavior; Obesity; School; Youth ID US PUBLIC-SCHOOLS; PHYSICAL-ACTIVITY; OBESITY; OVERWEIGHT; ADOLESCENTS; CONSUMPTION; CHILDHOOD; PATTERNS; ASSOCIATIONS; RESTAURANTS AB This study examined the relation between the chain food retail environment surrounding schools, youths' lunchtime eating behavior, and youths' obesity levels across three countries. Participants consisted of 26,778 students 13-15 years old from 687 schools across Canada, Scotland and the US. The density of convenience stores, chain fast food restaurants, and chain cafes within 1 km of each school was measured. Lunchtime eating behaviors, weight, and height were self-reported. Although the density of chain food retailers was highest in the US, fewer American students (2.6%) routinely ate their lunch at a food retailer during the school week than did Canadian (7.7%) and Scottish (43.7%) students. The density of chain food retailers was associated with eating lunch at a food retailer in Canada only whereby students attending schools with 1-2, 3-4, and 5+ chain food retailers within 1 km from their schools were 1.39 (95% CI: 0.84-2.29), 1.87 (95% CI: 1.10-3.20), and 2.50 (95% CI: 1.56-4.01) times more likely to eat at a chain food retailer compared to students attending schools with no nearby chain food retailers. No associations were found between chain food retailer density and obesity. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Heroux, Mariane; Janssen, Ian] Queens Univ, Sch Kinesiol & Hlth Studies, Kingston, ON K7L 3N6, Canada. [Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Chil Hlth & Huma, Prevent Res Branch, Bethesda, MD 20892 USA. [Currie, Dorothy] Univ St Andrews, Child & Adolescent Hlth Res Unit, St Andrews KY16 9TF, Fife, Scotland. [Pickett, William; Janssen, Ian] Queens Univ, Dept Epidemiol & Community Hlth, Kingston, ON K7L 3N6, Canada. [Pickett, William] Kingston Gen Hosp, Dept Emergency Med, Kingston, ON K7L 3N6, Canada. RP Janssen, I (reprint author), Queens Univ, Sch Kinesiol & Hlth Studies, 28 Div St, Kingston, ON K7L 3N6, Canada. EM ian.janssen@queensu.ca RI Janssen, Ian/B-7700-2009 FU Public Health Agency of Canada, Health Canada; Canadian Institutes of Health Research [MOP 97962]; Heart and Stroke Foundation of Canada [PCR 101415]; NHS Health Scotland; Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; Maternal and Child Health Bureau of the Health Resources and Services Administration; Canadian Institutes of Health Research doctoral award; Canada Research Chair award FX The HBSC is a WHO/Euro collaborative study; International Coordinator of the 2009-2010 study is Candace Currie, St. Andrews University, Scotland; Data Bank Manager is Oddrun Samdal, University of Bergen, Norway. This Canadian HBSC (PI: John Freeman, William Pickett) was funded by the Public Health Agency of Canada, Health Canada, the Canadian Institutes of Health Research (MOP 97962), and the Heart and Stroke Foundation of Canada (PCR 101415). The Scottish HBSC (PI: Candace Currie) was supported by NHS Health Scotland. The US HBSC (PI: Ronald J Iannotti) was partially supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Maternal and Child Health Bureau of the Health Resources and Services Administration. M Heroux was supported by a Canadian Institutes of Health Research doctoral award and I Janssen was supported by a Canada Research Chair award. NR 53 TC 14 Z9 14 U1 2 U2 19 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8292 J9 HEALTH PLACE JI Health Place PD NOV PY 2012 VL 18 IS 6 BP 1240 EP 1247 DI 10.1016/j.healthplace.2012.09.004 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 037XW UT WOS:000311140800005 PM 23041489 ER PT J AU Ferrer, RA Klein, WMP Zajac, LE Sutton-Tyrrell, K Muldoon, MF Kamarck, TW AF Ferrer, Rebecca A. Klein, William M. P. Zajac, Laura E. Sutton-Tyrrell, Kim Muldoon, Matthew F. Kamarck, Thomas W. TI Unrealistic Optimism Is Associated With Subclinical Atherosclerosis SO HEALTH PSYCHOLOGY LA English DT Article DE unrealistic optimism; risk perceptions; cardiovascular disease; subclinical atherosclerosis ID INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; RISK PERCEPTIONS; SELF-AFFIRMATION; PERSONAL RISK; ATTACK RISK; HEALTH; SMOKING; PREDICTION; FUTURE AB Objective: Unrealistic-optimism typically conceptualized as underestimation of comparative risk-has been previously associated with poorer health behaviors and outcomes, but no research to date has examined the association between unrealistic optimism and subclinical or clinical disease endpoints. Here, cross-sectional data from one time point in the Pittsburgh Healthy Heart study are used to examine whether unrealistic optimism about risk of heart disease is associated with carotid artery intima-media thickness (IMT), a subclinical marker of atherosclerosis. Methods: Participants were 148 adults aged 57-77. Objective risk score was calculated using the Framingham calculator, and IMT was regressed on risk score and perceived risk. Controlling for the Framingham risk score effectively equated risk across the sample, meaning that lower risk perceptions represented unrealistic optimism. Results: When controlling for the risk score, risk perceptions were negatively associated with IMT (beta = -.21, p < .01, t = -2.79, d = .46), a finding that was not moderated by gender. The risk score was also associated with IMT (beta = .42, p < .001, t = 5.55, d = .91). Conclusions: Unrealistic optimism was associated with subclinical atherosclerosis. Future longitudinal research is necessary to evaluate the temporal sequence as well as to examine putative explanatory mechanisms. C1 [Ferrer, Rebecca A.] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Klein, William M. P.; Zajac, Laura E.; Kamarck, Thomas W.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Sutton-Tyrrell, Kim] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Muldoon, Matthew F.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. RP Ferrer, RA (reprint author), NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4056, Rockville, MD 20852 USA. EM ferrerra@mail.nih.gov FU Heart, Lung, and Blood Institute [HL56346] FX This study was supported by Heart, Lung, and Blood Institute (HL56346). NR 38 TC 5 Z9 5 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD NOV PY 2012 VL 31 IS 6 BP 815 EP 820 DI 10.1037/a0027675 PG 6 WC Psychology, Clinical; Psychology SC Psychology GA 036IA UT WOS:000311018400017 PM 22429124 ER PT J AU Tarantal, AF Skarlatos, SI AF Tarantal, Alice F. Skarlatos, Sonia I. TI Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases: An NHLBI Resource for the Gene Therapy Community SO HUMAN GENE THERAPY LA English DT Review ID MESENCHYMAL STEM-CELLS; SEVERE COMBINED IMMUNODEFICIENCY; HIV-1-DERIVED LENTIVIRAL VECTORS; CHRONIC GRANULOMATOUS-DISEASE; LEBER CONGENITAL AMAUROSIS; RHESUS-MONKEYS; MACACA-MULATTA; IN-VIVO; NONHUMAN-PRIMATES; RETROVIRAL VECTORS AB The goals of the National Heart, Lung, and Blood Institute (NHLBI) Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases are to conduct gene transfer studies in monkeys to evaluate safety and efficiency; and to provide NHLBI-supported investigators with expertise, resources, and services to actively pursue gene transfer approaches in monkeys in their research programs. NHLBI-supported projects span investigators throughout the United States and have addressed novel approaches to gene delivery; "proof-of-principle"; assessed whether findings in small-animal models could be demonstrated in a primate species; or were conducted to enable new grant or IND submissions. The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases successfully aids the gene therapy community in addressing regulatory barriers, and serves as an effective vehicle for advancing the field. C1 [Tarantal, Alice F.] Univ Calif Davis, Calif Natl Primate Res Ctr, Ctr Fetal Monkey Gene Transfer Heart Lung & Blood, Davis, CA 95616 USA. [Tarantal, Alice F.] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA. [Tarantal, Alice F.] Univ Calif Davis, Dept Cell Biol & Human Anat, Davis, CA 95616 USA. [Skarlatos, Sonia I.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Tarantal, AF (reprint author), Univ Calif Davis, Calif Natl Primate Res Ctr, Ctr Fetal Monkey Gene Transfer Heart Lung & Blood, Pedrick & Hutchison Rd, Davis, CA 95616 USA. EM aftarantal@primate.ucdavis.edu FU NIH [HL069748, HL085794]; California National Primate Research Center base operating grant (NIH) [RR00169, OD011107] FX The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases is supported by NIH grants (HL069748 and HL085794) and by the California National Primate Research Center base operating grant (NIH grant RR00169 and OD011107). NR 62 TC 6 Z9 6 U1 0 U2 23 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2012 VL 23 IS 11 BP 1130 EP 1135 DI 10.1089/hum.2012.178 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 037BV UT WOS:000311076900002 PM 22974119 ER PT J AU Klebanoff, CA Gattinoni, L Restifo, NP AF Klebanoff, Christopher A. Gattinoni, Luca Restifo, Nicholas P. TI Sorting Through Subsets: Which T-Cell Populations Mediate Highly Effective Adoptive Immunotherapy? SO JOURNAL OF IMMUNOTHERAPY LA English DT Review DE adoptive cell transfer; CD8(+) T cell; naive CD8(+) T cell; central memory CD8(+) T cell; effector CD8(+) T cell; memory lymphocyte; T-cell subsets; gene engineering; chimeric antigen receptor; clinical trials ID TUMOR-INFILTRATING LYMPHOCYTES; SUPERIOR ANTITUMOR IMMUNITY; HLA-PEPTIDE TETRAMERS; IN-VIVO PERSISTENCE; IFN-GAMMA SECRETION; MEMORY STEM-CELLS; METASTATIC MELANOMA; PERIPHERAL-BLOOD; TRANSFER THERAPY; GENE-EXPRESSION AB CD8(+) T cells have been described as being naive or one of 4 antigen (Ag)-experienced subtypes representing a continuum of differentiation and maturation: T memory stem cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cells. In mice, adoptive cell transfer of less-differentiated naive T cells, T memory stem cell, and central memory T cell subsets have consistently demonstrated superior in vivo expansion, persistence, and antitumor capacities relative to the more differentiated effector memory T cell and effector T cell subsets. Retrospective analyses from human adoptive cell transfer trials have confirmed that transfer of less-differentiated T-cell subsets is highly correlated with objective clinical responses. These findings, combined with the recent ability to convey de novo Ag reactivity with high efficiency through genetic engineering of exogenous T-cell or chimeric Ag receptors, now challenge the field with 3 important questions: (1) how should less-differentiated T-cell subsets be isolated for human clinical trials?; (2) what is the best means of expanding T cells ex vivo in such a way as to not corrupt the beneficial traits of the younger subsets?; and (3) is it necessary to physically separate younger subsets from their more differentiated counterparts? Answering these questions will allow for the rational development of the next generation of highly effective and potentially curative T-cell therapies for the treatment of cancer. C1 [Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gattinoni, Luca] NCI, Expt Transplant & Immunol Branch, Bethesda, MD 20892 USA. [Restifo, Nicholas P.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 3-5762, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [ZIA BC010763-07] NR 125 TC 75 Z9 80 U1 1 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 651 EP 660 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100001 PM 23090074 ER PT J AU Zhu, SG Van den Eynde, BJ Coulie, PG Li, YF El-Gamil, M Rosenberg, SA Robbins, PF AF Zhu, Shigui Van den Eynde, Benoit J. Coulie, Pierre G. Li, Yong F. El-Gamil, Mona Rosenberg, Steven A. Robbins, Paul F. TI Characterization of T-cell Receptors Directed Against HLA-A*01-restricted and C*07-restricted Epitopes of MAGE-A3 and MAGE-A12 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE T-cell receptors; cancer/germline antigens; T-cell epitopes; cancer immunotherapy ID TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; ENGINEERED LYMPHOCYTES; MONOCLONAL-ANTIBODY; CANCER REGRESSION; GENE-THERAPY; PHASE-II; ANTIGEN; EXPRESSION; TCR AB The ability of T cells that have been genetically engineered to express T-cell receptors (TCRs) directed against tumor antigens to mediate tumor regression has been demonstrated in several clinical trials. These TCRs have primarily targeted HLAA*0201-restricted TCRs, as approximately 50% of whites, who represent the predominant population of patients who develop melanomas, expresses this HLA class I allele. These therapies could be extended to additional patients through the use of TCRs that target epitopes that are presented by additional class I alleles that are prevalent in this population such as HLA-C*07 and HLAA* 01, which are expressed by approximately 50% and 30% of the patient population respectively. Therefore, 2 TCRs that recognize an epitope of MAGE-A12 in the context of HLA-C*07 and 2 TCRs that recognize an epitope of MAGE-A3 in the context of HLA-A*01 were isolated from tumor-reactive T-cell clones and cloned in a recombinant retroviral expression vector. Comparative studies indicated that one of the 2 MAGE-A3-reactive TCRs and one of the 2 MAGE-A12-reactive TCRs were superior to the additional TCRs in conferring transduced peripheral blood mononuclear cells with the capacity to recognize a broad array of antigen and MHC-positive target cells. These results provide support for the use of these TCRs in cancer adoptive immunotherapy trials. C1 [Zhu, Shigui; Li, Yong F.; El-Gamil, Mona; Rosenberg, Steven A.; Robbins, Paul F.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Van den Eynde, Benoit J.] de Duve Inst, Ludwig Inst Canc Res, Brussels, Belgium. [Coulie, Pierre G.] Catholic Univ Louvain, de Duve Inst, B-1200 Brussels, Belgium. RP Robbins, PF (reprint author), NCI, Surg Branch, NIH, CRC 3-5744,10 Ctr Dr, Bethesda, MD 20892 USA. EM paul_robbins@nih.gov FU Intramural NIH HHS [ZIC BC010948-02] NR 40 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 680 EP 688 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100004 PM 23090077 ER PT J AU Gros, A Turcotte, S Tran, E Hanada, K Wunderlich, JR Rosenberg, S AF Gros, Alena Turcotte, Simon Tran, Eric Hanada, Ken-ichi Wunderlich, John R. Rosenberg, Steven TI Selection of PD-1, LAG-3, TIM-3 and 41BB Positive CD8 T Cells in the Fresh Tumor Digest Enriches for Melanoma-Reactive Cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Melanoma immunotherapy; Adoptive immunotherapy; Tumor infiltration lymphocytes C1 [Gros, Alena; Turcotte, Simon; Tran, Eric; Hanada, Ken-ichi; Wunderlich, John R.; Rosenberg, Steven] NCI, Surg Branch, Bethesda, MD 20892 USA. RI Hanada, Ken-ichi/L-2481-2013 OI Hanada, Ken-ichi/0000-0003-2959-1257 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 722 EP 723 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100014 ER PT J AU Haso, W Lee, DW Pastan, IH Dimitrov, DS Fitzgerald, D Mackall, CL Orentas, RJ AF Haso, Waleed Lee, Daniel W. Pastan, Ira H. Dimitrov, Dimiter S. Fitzgerald, David Mackall, Crystal L. Orentas, Rimas J. TI Targeting CD22 Expressing B Cell Leukemia With Chimeric Antigen Receptors (CAR): Engineering Membrane Proximity and Second Signaling Motifs for Optimal Activity SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Adoptive immunotherapy; B-ALL; Chimeric receptors C1 [Haso, Waleed; Lee, Daniel W.; Mackall, Crystal L.; Orentas, Rimas J.] NCI, Pediat Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Pastan, Ira H.; Fitzgerald, David] NCI, Mol Biol Lab, CCR, NIH, Frederick, MD 21701 USA. [Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, 2BRP,SAIC Frederick Inc,NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 723 EP 723 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100016 ER PT J AU Ji, Y Escobar, T Klebanoff, C Yu, ZY Sukumar, M Franco, Z Palmer, D Roychoudhuri, R Leonardi, A Muljo, S Restifo, N Gattinoni, L AF Ji, Yun Escobar, Thelma Klebanoff, Christopher Yu, Zhiya Sukumar, Madhusudhanan Franco, Zulmarie Palmer, Douglas Roychoudhuri, Rahul Leonardi, Anthony Muljo, Stefan Restifo, Nicholas Gattinoni, Luca TI MIR155 Augments the Anti-Tumor Activity of CD8+T Cells by Enhancing Responsiveness to Homeostatic Cytokines in the Absence of Lymphodepletion SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Engineering; Adoptive immunotherapy; CD8+T cells C1 [Ji, Yun; Klebanoff, Christopher; Yu, Zhiya; Sukumar, Madhusudhanan; Franco, Zulmarie; Palmer, Douglas; Roychoudhuri, Rahul; Leonardi, Anthony; Restifo, Nicholas; Gattinoni, Luca] NCI, Surg Branch, Bethesda, MD 20892 USA. [Escobar, Thelma; Muljo, Stefan] NIAID, Immunol Lab, Bethesda, MD 20892 USA. RI Muljo, Stefan/F-5671-2015 OI Muljo, Stefan/0000-0003-1013-446X NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 724 EP 724 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100020 ER PT J AU Long, AH Haso, W Lee, D Highfill, S Orentas, R Mackall, C AF Long, Adrienne H. Haso, Waleed Lee, Daniel Highfill, Steven Orentas, Rimas Mackall, Crystal TI Evaluating the Susceptibility of Solid Tumors to Chimeric Antigen Receptor Modified T Cell Therapies SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Cancer immunotherapy; Adoptive immunotherapy; Chimeric receptors C1 [Long, Adrienne H.; Haso, Waleed; Lee, Daniel; Highfill, Steven; Orentas, Rimas; Mackall, Crystal] NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Long, Adrienne H.] Northwestern Univ, Dept Microbiol Immunol, Feinberg Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 726 EP 726 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100024 ER PT J AU Bergamaschi, C Valentin, A Kulkarni, V Bear, J Rosati, M Alicea, C Sowder, R Chertova, E Felber, BK Pavlakis, GN AF Bergamaschi, Cristina Valentin, Antonio Kulkarni, Viraj Bear, Jenifer Rosati, Margherita Alicea, Candido Sowder, Raymond Chertova, Elena Felber, Barbara K. Pavlakis, George N. TI Pharmacokinetics and Immunological Effects of Human IL-15/IL-15RA Heterodimeric Complexes in Mice and Macaques SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Cancer immunotherapy; Interleukin-15; CD8+T cells C1 [Bergamaschi, Cristina; Valentin, Antonio; Kulkarni, Viraj; Bear, Jenifer; Rosati, Margherita; Alicea, Candido; Felber, Barbara K.; Pavlakis, George N.] Frederick Natl Lab Canc Res, Vaccine Branch, Ctr Canc Res, Frederick, MD USA. [Sowder, Raymond; Chertova, Elena] SAIC Frederick Inc, Retroviral Prot Chem Core, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 728 EP 729 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100032 ER PT J AU Hollevoet, K Antignani, A Fitzgerald, D Pastan, I AF Hollevoet, Kevin Antignani, Antonella Fitzgerald, David Pastan, Ira TI Combining the Recombinant Immunotoxin SS1P With the BH3-MIMETIC ABT-737 Induces Cell Death in Pancreatic Cancer Cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Cancer immunotherapy; Apoptosis; Targeted therapeutics C1 [Hollevoet, Kevin; Pastan, Ira] NCI, Moleculary Biol Sect, Mol Biol Lab, Bethesda, MD 20892 USA. [Antignani, Antonella; Fitzgerald, David] NCI, Biotherapy Sect, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 729 EP 730 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100035 ER PT J AU Wolfl, M Schwinn, S Yoo, YE Ress, ML Chopra, M Schreiber, SC Ayala, VI Ohlen, C Eyrich, M Beilhack, A Schlegel, PG AF Woelfl, Matthias Schwinn, Stefanie Yoo, Young-Eun Ress, Marie L. Chopra, Martin Schreiber, Susanne C. Ayala, Victor I. Ohlen, Claes Eyrich, Matthias Beilhack, Andreas Schlegel, Paul G. TI Dasatinib Primes Human Cells of Myeloid Origin to TLR-induced IL12 Synthesis SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Combination immunotherapy; Dendritic cell; Targeted therapeutics C1 [Woelfl, Matthias; Schwinn, Stefanie; Yoo, Young-Eun; Ress, Marie L.; Schreiber, Susanne C.; Eyrich, Matthias; Schlegel, Paul G.] Univ Wurzburg, Childrens Hosp, Wurzburg, Germany. [Chopra, Martin; Beilhack, Andreas] Univ Wurzburg, Dept Med 2, Wurzburg, Germany. [Ayala, Victor I.; Ohlen, Claes] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA. RI Woelfl, Matthias/J-9946-2012 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 736 EP 736 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100053 ER PT J AU Castiello, L Stroncek, DF Terabe, M Khuu, H Wood, LV Berzofsky, JA Sabatino, M AF Castiello, Luciano Stroncek, David F. Terabe, Masaki Khuu, Hanh Wood, Lauren V. Berzofsky, Jay A. Sabatino, Marianna TI Transcriptional Signatures in Dendritic Cells: Correlation of Patient Variability With Clinical Outcome SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE DC-based vaccine; Biomarker; Prostate cancer C1 [Castiello, Luciano; Stroncek, David F.; Khuu, Hanh; Sabatino, Marianna] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Terabe, Masaki; Wood, Lauren V.; Berzofsky, Jay A.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RI Castiello, Luciano/K-8616-2016 OI Castiello, Luciano/0000-0001-7146-3158 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 739 EP 739 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100060 ER PT J AU Ascierto, ML Schechterly, C Bedognetti, D De Giorgi, V Reinboth, J Tomei, S Uccelini, L Liu, QZ Wang, EN Alter, H De Maria, A Marincola, F AF Ascierto, Maria Libera Schechterly, Cathy Bedognetti, Davide De Giorgi, Valeria Reinboth, Jenny Tomei, Sara Uccelini, Lorenzo Liu, Quizhen Wang, Ena Alter, Harvey De Maria, Andrea Marincola, Francesco TI Effect of HCV Viraemia on NK Cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE HAV/HBV/HCV infections; Immune escape; Innate immunity C1 [Ascierto, Maria Libera; Schechterly, Cathy; Bedognetti, Davide; De Giorgi, Valeria; Reinboth, Jenny; Tomei, Sara; Uccelini, Lorenzo; Liu, Quizhen; Wang, Ena; Alter, Harvey; Marincola, Francesco] NIH, Bethesda, MD 20892 USA. [Ascierto, Maria Libera; De Maria, Andrea] Univ Genoa, Genoa, Italy. RI De Giorgi, Valeria/D-4582-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 748 EP 748 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100087 ER PT J AU Reinboth, J Ascierto, ML Chen, NG Zhang, Q Yu, YA Aguilar, RJ Worschech, A Zhao, YD Wang, E Marincola, FM Szalay, AA AF Reinboth, Jennifer Ascierto, Maria L. Chen, Nanhai G. Zhang, Qian Yu, Yong A. Aguilar, Richard J. Worschech, Andrea Zhao, Yingdong Wang, Ena Marincola, Francesco M. Szalay, Aladar A. TI Correlation Between Human and Oncolytic Vaccinia Virus Transcriptional Profile SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Engineering; Therapeutic vaccine; Melanoma C1 [Reinboth, Jennifer; Chen, Nanhai G.; Zhang, Qian; Yu, Yong A.; Aguilar, Richard J.; Szalay, Aladar A.] Genelux Corp, San Diego Sci Ctr, San Diego, CA USA. [Reinboth, Jennifer; Ascierto, Maria L.; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, CC & Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA. [Reinboth, Jennifer; Szalay, Aladar A.] Univ Wurzburg, Dept Biochem, Wurzburg, Germany. [Ascierto, Maria L.] Univ Genoa, Dept Hlth Sci, Genoa, Italy. [Ascierto, Maria L.] Univ Genoa, Ctr Excellence Biomed Res, Genoa, Italy. [Chen, Nanhai G.; Zhang, Qian; Yu, Yong A.; Szalay, Aladar A.] Univ Calif San Diego, Dept Radiat Oncol, Rebecca & John Moores Comprehens Canc Ctr, San Diego, CA 92103 USA. [Worschech, Andrea] Univ Wurzburg, Dept Internal Med 2, Wurzburg, Germany. [Zhao, Yingdong] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 748 EP 748 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100089 ER PT J AU Bedognetti, D Zoppoli, G Sertoli, MR Ascierto, ML Marincola, F Ansaldi, F De Maria, A AF Bedognetti, Davide Zoppoli, Gabriele Sertoli, Mario Roberto Ascierto, Maria Libera Marincola, Francesco Ansaldi, Filippo De Maria, Andrea TI Attenuated Humoral Response to Seasonal and Pandemic (A/H1N1 2009) Virosomal and MF-59 Adjuvated Influenza Vaccines in Complete Remission Non-hodgkin Lymphoma Patients Previously Treated With Rituximab Containing Regimens SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE B cell; Lymphoma; Immunotherapy C1 [Bedognetti, Davide; Ascierto, Maria Libera; Marincola, Francesco] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Zoppoli, Gabriele; Sertoli, Mario Roberto; Ansaldi, Filippo; De Maria, Andrea] IRCCS San Martino IST, Genoa, Italy. RI de maria, andrea/F-7116-2016 OI de maria, andrea/0000-0001-5782-333X NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 749 EP 749 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100091 ER PT J AU Bouchlaka, MN Sckisel, GD Chen, MY Mirsoian, A Zamora, AE Maverakis, E Hsiao, HH Monjazeb, AM Murphy, WJ Taub, D AF Bouchlaka, Myriam N. Sckisel, Gail D. Chen, Mingyi Mirsoian, Annie Zamora, Anthony E. Maverakis, Emanual Hsiao, Hui-Hua Monjazeb, Arta M. Murphy, William J. Taub, Dennis TI Aging Results in Acute TNF-alpha-dependent Lethality Following Systemic Immunotherapy: Impact of Body Fat Content SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Toxicity; Combination immunotherapy; Macrophages C1 [Bouchlaka, Myriam N.] Univ Nevada, Sch Med, Reno, NV 89557 USA. [Sckisel, Gail D.; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E.; Hsiao, Hui-Hua; Monjazeb, Arta M.; Murphy, William J.] Univ Calif Davis, Sacramento, CA USA. [Taub, Dennis] NIA, IRP, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RI Maverakis, Emanual/E-1185-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 751 EP 751 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100096 ER PT J AU Salerno, EP Wang, E Marincola, F Slingluff, CL AF Salerno, Elise P. Wang, Ena Marincola, Franco Slingluff, Craig L. TI Topical Imiquimod Induces Immune Activation and Regressions of Cutaneous Melanoma Metastases SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Advanced cancer immune response; Combination immunotherapy; Tumor microenvironment C1 [Salerno, Elise P.; Slingluff, Craig L.] Univ Virginia, Dept Surg, Div Surg Oncol, Charlottesville, VA USA. [Wang, Ena; Marincola, Franco] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Franco] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 751 EP 752 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100098 ER PT J AU Subleski, J Back, T Scarzello, A Weiss, J Robert, WH AF Subleski, Jeff Back, Tim Scarzello, Anthony Weiss, Jonathan Robert, Wiltrout H. TI Blocking IL-18 During IL-12+IL-15 Therapy Ameliorates Toxicity and Eradicates Malignancy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE IL-12; Interleukin-15; Toxicity C1 [Subleski, Jeff; Back, Tim; Scarzello, Anthony; Weiss, Jonathan; Robert, Wiltrout H.] NCI, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 752 EP 752 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100099 ER PT J AU Weiss, JM Subleski, JJ Back, T Chen, X Watkins, SK Yagita, H Sayers, TJ Murphy, WJ Wiltrout, RH AF Weiss, Jonathan M. Subleski, Jeff J. Back, Tim Chen, Xin Watkins, Stephanie K. Yagita, Hideo Sayers, Thomas J. Murphy, William J. Wiltrout, Robert H. TI Regulatory T Cells and Myeloid-derived Suppressor Cells in the Tumor Microenvironment Undergo FAS-dependent Cell Death During IL-2/ACD40 Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Combination immunotherapy; Treg cells; Tumor microenvironment C1 [Weiss, Jonathan M.; Subleski, Jeff J.; Back, Tim; Watkins, Stephanie K.; Wiltrout, Robert H.] Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD USA. [Chen, Xin; Sayers, Thomas J.] SAIC Frederick, Basic Sci Program, Frederick, MD USA. [Yagita, Hideo] Juntendo Univ, Sch Med, Tokyo 113, Japan. [Murphy, William J.] Univ Calif Davis, Davis, CA 95616 USA. RI Sayers, Thomas/G-4859-2015; Chen, Xin/I-6601-2015 OI Chen, Xin/0000-0002-2628-4027 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 753 EP 753 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100102 ER PT J AU Ascierto, ML Idowu, MO Zhao, YD Bedognetti, D Tomei, S Ascierto, PA Wang, E Marincola, F De Maria, A Manjili, M AF Ascierto, Maria Libera Idowu, Michael O. Zhao, Yingdong Bedognetti, Davide Tomei, Sara Ascierto, Paolo A. Wang, Ena Marincola, Francesco De Maria, Andrea Manjili, Masoud TI NK Cell Molecular Signatures are Predictive of Relapse Free Survival of Favorable Prognosis of Breast Cancer Patients SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Micrenvironment; Tumor immunity; Innate immunity C1 [Ascierto, Maria Libera; Zhao, Yingdong; Bedognetti, Davide; Tomei, Sara; Wang, Ena; Marincola, Francesco] NIH, Bethesda, MD 20892 USA. [Ascierto, Paolo A.] Ist Tumori Fdn G Pascale, Naples, Italy. [Idowu, Michael O.; De Maria, Andrea; Manjili, Masoud] Virginia Commonwealth Univ, Richmond, VA USA. RI de maria, andrea/F-7116-2016 OI de maria, andrea/0000-0001-5782-333X 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 1524-9557 EI 1537-4513 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 754 EP 755 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100106 ER PT J AU De Giorgi, V Tomei, S Liu, QZ Wunderlich, J Uccellini, L Ascierto, ML Bedognetti, D Wang, E Marincola, FM AF De Giorgi, Valeria Tomei, Sara Liu, Qiuzhen Wunderlich, John Uccellini, Lorenzo Ascierto, Maria L. Bedognetti, Davide Wang, Ena Marincola, Franco M. TI Genomic Characterization of Melanoma Cell Lines SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Tumor immunity; Immunomodulation; Melanoma C1 [De Giorgi, Valeria; Tomei, Sara; Liu, Qiuzhen; Uccellini, Lorenzo; Ascierto, Maria L.; Bedognetti, Davide; Wang, Ena; Marincola, Franco M.] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Bethesda, MD 20892 USA. [Wunderlich, John] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RI De Giorgi, Valeria/D-4582-2017 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 755 EP 756 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100109 ER PT J AU Wennerberg, E Kremer, V Childs, R Lundqvist, A AF Wennerberg, Erik Kremer, Veronika Childs, Richard Lundqvist, Andreas TI IFN-GAMMA-inducible Protein-10 Stimulates Migration of Activated Natural Killer Cells Toward Melanoma Tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Adoptive immunotherapy; Chemokines; NK cells C1 [Wennerberg, Erik; Kremer, Veronika; Lundqvist, Andreas] Karolinska Inst, Stockholm, Sweden. [Childs, Richard; Lundqvist, Andreas] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 757 EP 757 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100114 ER PT J AU Riccobon, A Ancarani, V Pancisi, E Petrini, M Fiammenghi, L Granato, AM Soldati, V Ridolfi, L de Rosa, F Valmorri, L Gentili, G Nanni, O Migliori, G Amadori, D Marincola, FM Ridolfi, R Guidoboni, M AF Riccobon, Angela Ancarani, Valentina Pancisi, Elena Petrini, Massimiliano Fiammenghi, Laura Granato, Anna Maria Soldati, Valentina Ridolfi, Laura de Rosa, Francesco Valmorri, Linda Gentili, Giorgia Nanni, Oriana Migliori, Giuseppe Amadori, Dino Marincola, Francesco M. Ridolfi, Ruggero Guidoboni, Massimo TI DC Vaccine Potency Correlates With Efficient Induction of Tumor-specific Immune Responses After Vaccination of Advanced Melanoma Patients: Preliminary Data With an in vitro Functional Assay SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE DC-based vaccine; Immunotherapy C1 [Valmorri, Linda; Gentili, Giorgia; Nanni, Oriana] IRCCS IRST, Biostat & Clin Trial Unit, Meldola, FC, Italy. [Migliori, Giuseppe] Morgagni Pierantoni Hosp, Blood Transfus Unit, Forli, FC, Italy. [Marincola, Francesco M.; Guidoboni, Massimo] NIH, IDIS DTM, 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 762 EP 763 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100129 ER PT J AU Klebanoff, CA Scott, CD Leonardi, AJ Ji, Y Roychoudhuri, R Wang, E Yu, ZY Marincola, FM Gattinoni, L Restifo, NP AF Klebanoff, Christopher A. Scott, Christopher D. Leonardi, Anthony J. Ji, Yun Roychoudhuri, Rahul Wang, Ena Yu, Zhiya Marincola, Francesco M. Gattinoni, Luca Restifo, Nicholas P. TI Memory CD8(+) T Cells Induce Precocious Effector Differentiation of NAiVE CD8(+) T Cells in a FASL-FAS Dependent Manner: A New Mode of T-T Lymphocyte Interaction and Cross Talk SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Melanoma immunotherapy; Adoptive immunotherapy; Memory CD8+T cells C1 [Klebanoff, Christopher A.; Scott, Christopher D.; Leonardi, Anthony J.; Ji, Yun; Roychoudhuri, Rahul; Yu, Zhiya; Gattinoni, Luca; Restifo, Nicholas P.] NCI, CCR, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] NCI, CC, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 765 EP 765 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100136 ER PT J AU Sukumar, M Liu, J Ji, Y Roychoudhuri, R Yu, ZY Klebanoff, C Finkel, T Restifo, N Gattinoni, L AF Sukumar, Madhusudhanan Liu, Jie Ji, Yun Roychoudhuri, Rahul Yu, Zhiya Klebanoff, Christopher Finkel, Toren Restifo, Nicholas Gattinoni, Luca TI Inhibition of Glycolytic Flux Enhances CD8+T Cell Memory, Stemness and Anti-tumor Function SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Adoptive immunotherapy; Memory CD8+T cells; Immune-mediated tumor rejection C1 [Sukumar, Madhusudhanan; Ji, Yun; Roychoudhuri, Rahul; Yu, Zhiya; Klebanoff, Christopher; Restifo, Nicholas; Gattinoni, Luca] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Liu, Jie; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 766 EP 766 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100139 ER PT J AU Highfill, SL Mackall, CL AF Highfill, Steven L. Mackall, Crystal L. TI Overcoming Tumor-induced Negative Regulatory Pathways in Murine Models of Rhabdomyosarcoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE MDSC; PD-1 C1 [Highfill, Steven L.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 776 EP 777 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100168 ER PT J AU Liu, QZ Tomei, S Ascierto, ML Giorgi, VD Dai, CL Uccellini, L Spivey, T Pos, Z Thomas, J Reinboth, J Murtas, D Bedognetti, D Wang, E Marincola, FM AF Liu, Qiuzhen Tomei, Sara Ascierto, Maria L. Giorgi, Valeria D. Dai, Cuilian Uccellini, Lorenzo Spivey, Tara Pos, Zoltan Thomas, Jaime Reinboth, Jennifer Murtas, Daniela Bedognetti, Davide Wang, Ena Marincola, Francesco M. TI NOS1 Overexpression by Melanoma Cells Contributes to Type I IFN alpha Signal Dysfunction in Immune Cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Immunosuppression; IFNalpha; Melanoma C1 [Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria L.; Giorgi, Valeria D.; Uccellini, Lorenzo; Spivey, Tara; Pos, Zoltan; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria L.; Giorgi, Valeria D.; Uccellini, Lorenzo; Spivey, Tara; Pos, Zoltan; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA. [Liu, Qiuzhen] So Med Univ, Canc Res Inst, Guangzhou, Guangdong, Peoples R China. [Dai, Cuilian] Zunyi Med Coll, Affiliated Hosp, Dept Cardiol, Zunyi, Peoples R China. 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 777 EP 778 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100171 ER PT J AU Ma, C Kapanadze, T Gamrekelashvili, J Manns, MP Korangy, F Greten, TF AF Ma, Chi Kapanadze, Tamar Gamrekelashvili, Jaba Manns, Michael P. Korangy, Firouzeh Greten, Tim F. TI Anti-GR-1 Antibody Depletion Fails to Eliminate Hepatic Myeloid Derived Suppressor Cells in Tumor Bearing Mice SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Myeloid derived suppressor cell C1 [Ma, Chi; Kapanadze, Tamar; Gamrekelashvili, Jaba; Korangy, Firouzeh; Greten, Tim F.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Kapanadze, Tamar; Gamrekelashvili, Jaba; Manns, Michael P.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany. RI Greten, Tim/B-3127-2015 OI Greten, Tim/0000-0002-0806-2535 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 778 EP 778 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100172 ER PT J AU Maccalli, C Volonte, A Wang, E Sanvito, F Albarello, L Doglioni, C Marincola, FM Parmiani, G AF Maccalli, Cristina Volonte, Andrea Wang, Ena Sanvito, Francesca Albarello, Luca Doglioni, Claudio Marincola, Francesco M. Parmiani, Giorgio TI Cancer Stem Cells Isolated From Solid Tumors can Display Immunomodulatory Activity for T Cell Responses SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Tumor immunity; Indoleamine 2,3-dioxygenase 1; Immunomodulation C1 [Sanvito, Francesca; Albarello, Luca; Doglioni, Claudio] Ist Sci San Raffaele, Unit Pathol, I-20132 Milan, Italy. [Wang, Ena; Marincola, Francesco M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 778 EP 778 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100173 ER PT J AU Fujisawa, T Rubin, B Suzuki, A Patel, PS Gahl, WA Joshi, BH Puri, RK AF Fujisawa, Toshio Rubin, Benjamin Suzuki, Akiko Patel, Prabhudas S. Gahl, Wiiliam A. Joshi, Bharat H. Puri, Raj K. TI Cysteamine Inhibits Invasion, Metastasis and Extends Survival by Down-regulating Matrix Metalloproteinases in vivo Mouse Model of Human Pancreatic Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Metastases; Animal model; Tumor microenvironment C1 [Fujisawa, Toshio; Suzuki, Akiko; Patel, Prabhudas S.; Joshi, Bharat H.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Fujisawa, Toshio] NTT Med Ctr Tokyo, Dept Gastroenterol, Tokyo, Japan. [Rubin, Benjamin] Suburban Hosp, Johns Hopkins Sch Med, Dept Ophthalmol, Bethesda, MD USA. [Gahl, Wiiliam A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 785 EP 785 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100194 ER PT J AU Izhak, L Ambrosino, E O'Konek, JJ Parish, ST Xia, Z Venzon, D Berzofsky, JA Terabe, M AF Izhak, Liat Ambrosino, Elena O'Konek, Jessica J. Parish, Stanley T. Xia, Zheng Venzon, David Berzofsky, Jay A. Terabe, Masaki TI Delicate Balance Among Three Types of T Cells in Concurrent Regulation of Tumor Immunity SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Immunosuppression; Tumor immunity; Regulatory T cells C1 [Izhak, Liat; Ambrosino, Elena; O'Konek, Jessica J.; Parish, Stanley T.; Xia, Zheng; Berzofsky, Jay A.; Terabe, Masaki] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 786 EP 786 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100198 ER PT J AU Jin, P Civini, S Wang, HD Ren, JQ Sabatino, M Wang, E Marincola, F Stroncek, D AF Jin, Ping Civini, Sara Wang, Heidi Ren, Jiaqiang Sabatino, Marianna Wang, Ena Marincola, Francesco Stroncek, David TI Bone Marrow-derived Stromal Cells (BMSC) Show Both Pro-inflammatory and Immunosuppressive Characteristics in Melanoma Microenvironment: An in vitro Study by Co-culture of BMSC, TIL and Melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Immunomodulation; Tumor microenvironment; Tumor stromal cells C1 [Jin, Ping; Civini, Sara; Wang, Heidi; Ren, Jiaqiang; Sabatino, Marianna; Wang, Ena; Marincola, Francesco; Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 787 EP 787 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100200 ER PT J AU Kotlan, B Liszkay, G Naszados, G Godeny, M Toth, L Gobor, L Szollar, A Plotar, V Toth, E Kasler, M Marincola, FM AF Kotlan, Beatrix Liszkay, Gabriella Naszados, Gyorgy Godeny, Maria Toth, Laszlo Gobor, Laszlo Szollar, Andras Plotar, Vanda Toth, Erika Kasler, Miklos Marincola, Francesco M. TI Tracking Tumor Infiltrating B Cells Revealed Cancer Initiating Cells That Coexpress Unique GD3 Sialilated Glycosphingolipides and CD20 in Metastatic Malignant Melanomas SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Metastases; B cell; Melanoma C1 [Plotar, Vanda; Toth, Erika] Natl Inst Oncol, Ctr Surg & Mol Tumorpathol, Budapest, Hungary. [Kasler, Miklos] Natl Inst Oncol, Board Directors, Budapest, Hungary. [Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 787 EP 787 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100201 ER PT J AU Scarzello, A Stauffer, J Subleski, J Weiss, J Ortaldo, J Wiltrout, R AF Scarzello, Anthony Stauffer, Jim Subleski, Jeff Weiss, Jon Ortaldo, John Wiltrout, Robert TI AKT plus beta-CAT Liver Tumor Development is Dependent on B Cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE B cell; Tumor microenvironment C1 [Scarzello, Anthony; Stauffer, Jim; Subleski, Jeff; Weiss, Jon; Ortaldo, John; Wiltrout, Robert] NCI, Canc & Inflammat Program, LEI, Frederick, MD 21701 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 788 EP 788 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100203 ER PT J AU Tomei, S Civini, S Bedognetti, D De Giorgi, V Reinboth, J Ascierto, ML Liu, QZ Uccellini, L Wang, E Marincola, FM AF Tomei, Sara Civini, Sara Bedognetti, Davide De Giorgi, Valeria Reinboth, Jennifer Ascierto, Maria Libera Liu, Qiuzhen Uccellini, Lorenzo Wang, Ena Marincola, Francesco M. TI The Immune-related Role of BRAF Mutation in Melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Melanoma C1 [Tomei, Sara; Bedognetti, Davide; De Giorgi, Valeria; Reinboth, Jennifer; Ascierto, Maria Libera; Liu, Qiuzhen; Uccellini, Lorenzo; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Tomei, Sara; Bedognetti, Davide; De Giorgi, Valeria; Reinboth, Jennifer; Ascierto, Maria Libera; Liu, Qiuzhen; Uccellini, Lorenzo; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA. [Civini, Sara] NIH, CPS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RI De Giorgi, Valeria/D-4582-2017 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 788 EP 789 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100205 ER PT J AU Stijleman, IJ Swaner, K Nilson, D Jensen, T Lubet, RA Cessna, MH Davis, CA Bernard, PS AF Stijleman, I. J. Swaner, K. Nilson, D. Jensen, T. Lubet, R. A. Cessna, M. H. Davis, C. A. Bernard, P. S. TI Analysis of Biomarkers for Colon Cancer Progression and Chemoprevention Using RT-qPCR in Formalin Fixed Paraffin Embedded Colon Tissues SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Stijleman, I. J.; Davis, C. A.; Bernard, P. S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Swaner, K.; Nilson, D.; Jensen, T.; Cessna, M. H.] Intermt Hlth Care, Salt Lake City, UT USA. [Lubet, R. A.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 709 EP 709 PG 1 WC Pathology SC Pathology GA 025HG UT WOS:000310178600304 ER PT J AU Xi, L Navarro, W Quezado, MM Oberholtzer, CJ Fine, HA Raffeld, M AF Xi, L. Navarro, W. Quezado, M. M. Oberholtzer, C. J. Fine, H. A. Raffeld, M. TI Quantitative MGMT Promoter Methylation Analysis Using Bisulfite Pyrosequencing for Molecular Diagnostic Testing in Glioblastoma Multiforme SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Xi, L.; Navarro, W.; Quezado, M. M.; Oberholtzer, C. J.; Fine, H. A.; Raffeld, M.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 713 EP 713 PG 1 WC Pathology SC Pathology GA 025HG UT WOS:000310178600319 ER PT J AU Tangrea, MA Hipp, JD Armani, MD Hanson, JC Rodriguez-Canales, J Blackler, AR Chowdhuri, SR Xi, L Raffeld, M O'Flaherty, N Markey, SP Filie, AC Cheng, J Morgan, NY Pohida, TJ Bonner, RF Balis, U Emmert-Buck, MR AF Tangrea, M. A. Hipp, J. D. Armani, M. D. Hanson, J. C. Rodriguez-Canales, J. Blacklert, A. R. Chowdhuri, S. Roy Xi, L. Raffeld, M. O'Flaherty, N. Markey, S. P. Filie, A. C. Cheng, J. Morgan, N. Y. Pohida, T. J. Bonner, R. F. Balis, U. Emmert-Buck, M. R. TI Advanced Microdissection Technologies with Potential Clinical Applications SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Tangrea, M. A.; Armani, M. D.; Hanson, J. C.; Rodriguez-Canales, J.; Blacklert, A. R.; Xi, L.; Raffeld, M.; O'Flaherty, N.; Filie, A. C.; Emmert-Buck, M. R.] NCI, Bethesda, MD 20892 USA. [Hipp, J. D.; Cheng, J.; Balis, U.] Univ Michigan, Ann Arbor, MI 48109 USA. [Chowdhuri, S. Roy] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Markey, S. P.] NIMH, Bethesda, MD 20892 USA. [Morgan, N. Y.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. [Pohida, T. J.] NIH, Bethesda, MD 20892 USA. [Bonner, R. F.] NICHHD, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 0 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 739 EP 739 PG 1 WC Pathology SC Pathology GA 025HG UT WOS:000310178600422 ER PT J AU Xi, L Evbuomwan, MO Raffeld, M AF Xi, L. Evbuomwan, M. O. Raffeld, M. TI Evaluation of the Ion Torrent AmpliSeq 1.0 Cancer Panel for Molecular Profiling in Thoracic Malignancies SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Xi, L.; Evbuomwan, M. O.; Raffeld, M.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 743 EP 743 PG 1 WC Pathology SC Pathology GA 025HG UT WOS:000310178600438 ER PT J AU Baratz, R Rubovitch, V Tweedie, D Greig, NH Pick, CG AF Baratz, R. Rubovitch, V Tweedie, D. Greig, N. H. Pick, C. G. TI Thalidomide analog, 3 ' 6,dithiothalidomide, administration post minimal traumatic brain injury reduce TNF-alpha and improve cognitive performance in mice SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Israel-Society-for-Neuroscience CY DEC 11-13, 2011 CL Eilat, ISRAEL SP Israel Soc Neurosci C1 [Baratz, R.; Rubovitch, V; Pick, C. G.] Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. [Tweedie, D.; Greig, N. H.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RI Pick, Chaim/D-4789-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S91 EP S92 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600235 ER PT J AU Eiden, LE Stroth, N Holighaus, Y Ait-Ali, D Mustafa, T AF Eiden, Lee E. Stroth, Nikolas Holighaus, Yvonne Ait-Ali, Djida Mustafa, Tomris TI PACAP's dual role as a stress transducer and neuroprotectant in the brain SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC) CY MAY 22-25, 2011 CL Boston, MA SP European Neuropeptide Club (ENC) C1 [Eiden, Lee E.; Stroth, Nikolas; Holighaus, Yvonne; Ait-Ali, Djida; Mustafa, Tomris] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, IRP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S195 EP S195 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600445 ER PT J AU Gal, R Kaiser, M Haspel, G Libersat, F AF Gal, R. Kaiser, M. Haspel, G. Libersat, F. TI Stereotaxis in the wild: how a parasitoid wasp finds its host's brain SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Israel-Society-for-Neuroscience CY DEC 11-13, 2011 CL Eilat, ISRAEL SP Israel Soc Neurosci C1 [Gal, R.; Kaiser, M.; Libersat, F.] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel. [Haspel, G.] NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S38 EP S38 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600091 ER PT J AU Harel, A Kravitz, DJ Baker, CI AF Harel, A. Kravitz, D. J. Baker, C., I TI Deconstructing visual scenes in cortex: gradients of object and spatial layout information SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Israel-Society-for-Neuroscience CY DEC 11-13, 2011 CL Eilat, ISRAEL SP Israel Soc Neurosci C1 [Harel, A.; Kravitz, D. J.; Baker, C., I] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S50 EP S50 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600126 ER PT J AU Jensen, RT Moody, TW Coy, DH AF Jensen, R. T. Moody, T. W. Coy, D. H. TI GPCR peptide receptor mediated imaging/cytotoxicity SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC) CY MAY 22-25, 2011 CL Boston, MA SP European Neuropeptide Club (ENC) C1 NIH, Bethesda, MD 20892 USA. Tulane Univ, New Orleans, LA 70118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S192 EP S193 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600441 ER PT J AU Levi, YF Vedin, I Cederholm, T Basun, H Irving, GF Jonhagen, ME Vessby, B Wahlund, LO Salem, N Palmblad, J AF Levi, Freund Y. Vedin, I Cederholm, T. Basun, H. Irving, Faxen G. Jonhagen, Eriksdotter M. Vessby, B. Wahlund, L. O. Salem, N., Jr. Palmblad, J. TI Effects of a DHA rich omega-3 fatty acid supplementation for Alzheimer disease patients on fatty acid composition in cerebrospinal fluid, disease biomarkers and cognition: The OmegAD study SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Israel-Society-for-Neuroscience CY DEC 11-13, 2011 CL Eilat, ISRAEL SP Israel Soc Neurosci C1 [Levi, Freund Y.; Irving, Faxen G.; Jonhagen, Eriksdotter M.; Wahlund, L. O.] Karolinska Inst, Dept Neurobiol Caring Sci & Soc, Karoli Stockholm, Sweden. [Levi, Freund Y.; Vedin, I; Palmblad, J.] Karolinska Inst, Dept Med, Karoli Stockholm, Sweden. [Cederholm, T.; Vessby, B.] Univ Uppsala Hosp, Div Clin Nutr, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Cederholm, T.; Vessby, B.] Univ Uppsala Hosp, Div Metab Res, Uppsala, Sweden. [Basun, H.] Univ Uppsala Hosp, Div Geriatr, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Salem, N., Jr.] NIAAA, NIH, Rockville, MD 20852 USA. RI Eriksdotter, Maria/I-5427-2015 OI Eriksdotter, Maria/0000-0003-2498-4000 NR 0 TC 0 Z9 0 U1 0 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S36 EP S36 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600086 ER PT J AU Loh, YP AF Loh, Y. Peng TI Serpinins promote granule biogenesis and neuroprotection SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC) CY MAY 22-25, 2011 CL Boston, MA SP European Neuropeptide Club (ENC) C1 [Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hisatsugu Koshimizu & Niamh X Cawley Sect Cellula, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S189 EP S189 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600435 ER PT J AU Moody, TW Osefo, N Mantey, SA Jensen, RT AF Moody, Terry W. Osefo, Nauramy Mantey, Samuel A. Jensen, Robert T. TI Peptide transactivation of epidermal growth factor receptors SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC) CY MAY 22-25, 2011 CL Boston, MA SP European Neuropeptide Club (ENC) C1 NCI Off Director, DHHS, NIH, CCR, Bethesda, MD USA. NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S194 EP S194 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600444 ER PT J AU Moody, TW Leyton, J Osefo, N Jensen, RT AF Moody, Terry W. Leyton, Julius Osefo, Nauramy Jensen, Robert T. TI PACAP causes tyrosine phosphorylation of focal adhesion kinase, paxillin and epidermal growth factor receptors in lung cancer cells SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 10th International Symposium on VIP-PACAP and Related Peptides CY DEC 13-16, 2011 CL Eilat, ISRAEL C1 NCI, DHHS, NIH, Off Director,CCR, Bethesda, MD USA. NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S145 EP S145 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600363 ER PT J AU Pick, CG Rachmany, L Rubovitch, V Tweedie, D Hoffer, BJ Greig, NH AF Pick, C. G. Rachmany, L. Rubovitch, V Tweedie, D. Hoffer, B. J. Greig, N. H. TI Exendin-4 reverses behavioral impairments induced by traumatic brain injury in mice SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC) CY MAY 22-25, 2011 CL Boston, MA SP European Neuropeptide Club (ENC) C1 [Pick, C. G.; Rachmany, L.; Rubovitch, V] Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, Tel Aviv, Israel. [Tweedie, D.; Greig, N. H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Hoffer, B. J.] Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA. RI Pick, Chaim/D-4789-2009 NR 0 TC 0 Z9 0 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S184 EP S184 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600428 ER PT J AU Rachmany, L Rubovitch, V Tweedie, D Greig, NH Schreiber, S Pick, CG AF Rachmany, L. Rubovitch, V Tweedie, D. Greig, N. H. Schreiber, S. Pick, C. G. TI Cognitive amelioration as a result of Exendin-4 (GLP-1R agonist) administration after inducing minimal traumatic brain injury from blast in mice SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Israel-Society-for-Neuroscience CY DEC 11-13, 2011 CL Eilat, ISRAEL SP Israel Soc Neurosci C1 [Rachmany, L.; Rubovitch, V; Pick, C. G.] Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. [Tweedie, D.; Greig, N. H.] NIA, Drug Design & Dev Sect, IRP, NIH, Baltimore, MD 21224 USA. [Schreiber, S.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Psychiat, IL-69978 Tel Aviv, Israel. RI Schreiber, Shaul/E-5821-2010; Pick, Chaim/D-4789-2009 OI Schreiber, Shaul/0000-0002-2189-0693; NR 0 TC 0 Z9 0 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S94 EP S94 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600242 ER PT J AU Rapoport, S Lavzin, M Polsky, A Garion, L Schiller, J AF Rapoport, S. Lavzin, M. Polsky, A. Garion, L. Schiller, J. TI Active dendritic processing in layer-4 neurons of the rat barrel cortex in-vivo SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Israel-Society-for-Neuroscience CY DEC 11-13, 2011 CL Eilat, ISRAEL SP Israel Soc Neurosci C1 [Rapoport, S.; Lavzin, M.; Garion, L.; Schiller, J.] Technion Israel Inst Technol, Dept Physiol, Rappaport Fac Med, IL-31096 Haifa, Israel. [Rapoport, S.; Lavzin, M.; Garion, L.; Schiller, J.] Technion Israel Inst Technol, Res Inst, IL-31096 Haifa, Israel. [Polsky, A.] Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S65 EP S65 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600165 ER PT J AU Reitman, M AF Reitman, Marc TI BRS-3 (Bombesin Receptor Subtype-3) agonists for the treatment of obesity SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC) CY MAY 22-25, 2011 CL Boston, MA SP European Neuropeptide Club (ENC) C1 [Reitman, Marc] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S179 EP S179 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600420 ER PT J AU Shneider, BL Abel, B Haber, B Karpen, SJ Magee, JC Romero, R Schwarz, K Bass, LM Kerkar, N Miethke, AG Rosenthal, P Turmelle, Y Robuck, PR Sokol, RJ AF Shneider, Benjamin L. Abel, Bob Haber, Barbara Karpen, Saul J. Magee, John C. Romero, Rene Schwarz, Kathleen Bass, Lee M. Kerkar, Nanda Miethke, Alexander G. Rosenthal, Philip Turmelle, Yumirle Robuck, Patricia R. Sokol, Ronald J. CA Childhood Liver Dis Res Educ TI Portal Hypertension in Children and Young Adults With Biliary Atresia SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE ascites; hepatopulmonary syndrome; hypersplenism; pediatric; varices ID EXPERT PEDIATRIC OPINION; PLATELET RATIO INDEX; KASAI OPERATION; VARICEAL HEMORRHAGE; CONSENSUS WORKSHOP; ESOPHAGEAL-VARICES; PROGNOSTIC VALUE; HEPATITIS-C; EXPERIENCE; LIVER AB Objective: Biliary atresia (BA) frequently results in portal hypertension (PHT), complications of which lead to significant morbidity and mortality. The Childhood Liver Disease Research and Education Network was used to perform a cross-sectional multicentered analysis of PHT in children with BA. Methods: Subjects with BA receiving medical management at a Childhood Liver Disease Research and Education Network site were enrolled. A priori, clinically evident PHT was defined as "definite'' when there was either history of a complication of PHT or clinical findings consistent with PHT (both splenomegaly and thrombocytopenia). PHT was denoted as "possible'' if one of the findings was present in the absence of a complication, whereas PHT was "absent'' if none of the criteria were met. Results: A total of 163 subjects were enrolled between May 2006 and December 2009. At baseline, definite PHT was present in 49%, possible in 17%, and absent in 34% of subjects. Demographics, growth, and anthropometrics were similar amongst the 3 PHT categories. Alanine aminotransferase, gamma-glutamyl transpeptidase, and sodium levels were similar, whereas there were significant differences in aspartate aminotransferase (AST), AST/alanine aminotransferase, albumin, total bilirubin, prothrombin time, white blood cell count, platelet count, and AST/platelet count between definite and absent PHT. Thirty-four percent of those with definite PHT had either prothrombin time >15 seconds or albumin <3 g/dL. Conclusions: Clinically definable PHT is present in two-thirds of North American long-term BA survivors with their native livers. The presence of PHT is associated with measures of hepatic injury and dysfunction, although in this selected cohort, the degree of hepatic dysfunction is relatively mild and growth is preserved. C1 [Shneider, Benjamin L.] UPMC, Childrens Hosp Pittsburgh, Div Pediat Gastoenterol Hepatol & Nutr, Pittsburgh, PA 15224 USA. [Abel, Bob; Magee, John C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Haber, Barbara] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Karpen, Saul J.] Texas Childrens Hosp, Houston, TX 77030 USA. [Romero, Rene] Emory Univ, Atlanta, GA USA. [Schwarz, Kathleen] Johns Hopkins Univ, Baltimore, MD USA. [Bass, Lee M.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Kerkar, Nanda] Mt Sinai Sch Med, New York, NY USA. [Miethke, Alexander G.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Rosenthal, Philip] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Turmelle, Yumirle] Washington Univ, St Louis, MO USA. [Robuck, Patricia R.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Sokol, Ronald J.] Univ Colorado, Aurora, CO USA. [Sokol, Ronald J.] Childrens Hosp Colorado, Aurora, CO USA. RP Shneider, BL (reprint author), UPMC, Childrens Hosp Pittsburgh, Div Pediat Gastoenterol Hepatol & Nutr, 4401 Penn Ave, Pittsburgh, PA 15224 USA. EM Benjamin.Shneider@chp.edu FU National Center for Research Resources [5M01 RR00069, UL1RR025780, UL1RR024153, UL1RR024134, UL1RR024131, UL1RR025005, UL1RR025741, UL1RR029877]; National Institute of Diabetes, Digestive and Kidney Diseases [DK 62453, DK 62497, DK 62481, DK 62470, DK 62500, DK 62530, DK 62445, DK 62466, DK 62456, DK 62452, DK 62436, DK 84585] FX This work was financially supported by the National Center for Research Resources (5M01 RR00069 [R.J.S.], UL1RR025780 [Colorado], UL1RR024153 [Pittsburgh], UL1RR024134 [Philadelphia], UL1RR024131 [San Francisco], UL1RR025005 [Baltimore], UL1RR025741 [Chicago]), UL1RR029877 [New York] and the National Institute of Diabetes, Digestive and Kidney Diseases (DK 62453 [R.J.S.], DK 62497 [A.G.M.], DK 62481 [B.A.H.], DK 62470 [S.J.K.], DK 62500 [P.R.], DK 62530 [K.S.], DK 62445 [N.K.], DK 62466 [B.L.S.], DK 62456 [J.C.M.], DK 62452 [Y.T.], DK 62436 [L.B.], DK 84585 [R.R.]. NR 29 TC 16 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2012 VL 55 IS 5 BP 567 EP 573 DI 10.1097/MPG.0b013e31826eb0cf PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 030LH UT WOS:000310571700024 PM 22903006 ER PT J AU Briassoulis, G Kuburovic, V Xekouki, P Patronas, N Keil, MF Lyssikatos, C Stajevic, M Kovacevic, G Stratakis, CA AF Briassoulis, George Kuburovic, Vladimir Xekouki, Paraskevi Patronas, Nicholas Keil, Meg F. Lyssikatos, Charalampos Stajevic, Mila Kovacevic, Gordana Stratakis, Constantine A. TI Recurrent Left Atrial Myxomas in Carney Complex: A Genetic Cause of Multiple Strokes that can be Prevented SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Carney complex; embolic; myxomas; regulatory subunit of the protein kinase gene; stroke ID CARDIAC MYXOMAS; REGULATORY SUBUNIT; MUTATIONS; PATIENT; ANEURYSMS; PRKAR1A AB Background: Intracardiac myxomas in Carney complex are significant causes of cardiovascular morbidity and mortality through embolic stroke and heart failure. The genetic, clinical, and laboratory characteristics of Carney complex-related strokes from atrial myxomas have not been described. The regulatory subunit (R1A) of the protein kinase gene (PRKAR1A) is mutated in >60% of patients with Carney complex. Methods: We studied patients with strokes and cardiac myxomas that were hospitalized in our institution and elsewhere; a total of 7 patients with 16 recurrent atrial myxomas and >14 episodes of strokes were identified. Results: Neurologic deficits were reported; in 1 patient, an aneurysm developed at the site of a previous stroke. All patients were females, were also diagnosed with Cushing syndrome, and all had additional tumors or other Carney complex manifestations. Other than gender, although there was a trend for patients being overweight and hypertensive, no other risk factors were identified. A total of 5 patients (71%) had a PRKAR1A mutation; all mutations (c418_419delCA, c.340delG/p.Val113fsX15, c.353_365del13/p.Ile118fsX6, c.491_492delTG/p.Val164fsX4, and c.17711G.A) were located in exons 3 to 5 and introns 2 to 3, and all led to a non-sense PRKAR1A mRNA. Conclusions: Female patients with Carney complex appear to be at a high risk for recurrent atrial myxomas that lead to multiple strokes. Early identification of a female patient with Carney complex is of paramount importance for the early diagnosis of atrial myxomas and the prevention of strokes. C1 [Briassoulis, George; Xekouki, Paraskevi; Keil, Meg F.; Lyssikatos, Charalampos; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Kuburovic, Vladimir] Mother & Child Hlth Care Inst Serbia Dr Vukan Cup, Dept Pediat Cardiol, Belgrade, Serbia. [Stajevic, Mila] Mother & Child Hlth Care Inst Serbia Dr Vukan Cup, Dept Pediat Cardiac Surg, Belgrade, Serbia. [Kovacevic, Gordana] Mother & Child Hlth Care Inst Serbia Dr Vukan Cup, Dept Pediat Neurol, Belgrade, Serbia. [Patronas, Nicholas] NIH, Clin Res Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) [Z01-HD-000642-04]; Intensive Care Unit, Department of Pediatrics, Regional University Hospital, University of Crete, Heraklion, Greece FX Supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), intramural National Institutes of Health (NIH) project Z01-HD-000642-04 to Dr. Stratakis, and by the Intensive Care Unit, Department of Pediatrics, Regional University Hospital, University of Crete, Heraklion, Greece (Dr. Briassoulis). NR 17 TC 3 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD NOV PY 2012 VL 21 IS 8 AR 914.e1 DI 10.1016/j.jstrokecerebrovasdis.2012.01.006 PG 8 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 031LM UT WOS:000310641900079 PM 22341669 ER PT J AU Nansel, TR Haynie, DL Lipsky, LM Laffel, LMB Mehta, SN AF Nansel, Tonja R. Haynie, Denise L. Lipsky, Leah M. Laffel, Lori M. B. Mehta, Sanjeev N. TI Multiple Indicators of Poor Diet Quality in Children and Adolescents with Type 1 Diabetes Are Associated with Higher Body Mass Index Percentile but not Glycemic Control SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Diabetes mellitus, type 1; Diet; Disease management; Body weight ID NUTRIENT-RICH FOODS; BLOOD-GLUCOSE CONTROL; WEIGHT-GAIN; COMPLICATIONS TRIAL; INSULIN THERAPY; RISK-FACTORS; US CHILDREN; YOUTH; PREVALENCE; NUTRITION AB Background Diet is a cornerstone of type 1 diabetes treatment, and poor diet quality may affect glycemic control and other health outcomes. Yet diet quality in children and adolescents with type 1 diabetes remains understudied. Objective To evaluate multiple indicators of diet quality in children and adolescents with type I diabetes and their associations with hemoglobin A1c and body mass index percentile. Design In this cross-sectional study, participants completed 3-day diet records, and data were abstracted from participants' medical records. Diet quality indicators included servings of fruit, vegetables, and whole grains; Healthy Eating Index-2005 (HEI-2005) score; Nutrient Rich Foods 9.3 score (NRF 9.3); and glycemic index. Participants/setting Children and adolescents with type >= 1 diabetes year, aged 8 to 18 years, were recruited at routine clinic visits. Of 291 families enrolled, 252 provided diet data. Statistical analyses Associations of diet quality indicators to HbA1c and body mass index percentile were examined using analysis of covariance and multiple linear regression. Results Participants demonstrated low adherence to dietary guidelines; mean HEI-2005 score was 53.4 +/- 11.0 (range=26.7 to 81.2). Intake of fruit, vegetables, and whole grains was less than half the recommended amount. Almost half of the participants' daily energy intake was derived from refined-grain products, desserts, chips, and sweetened beverages. Higher fruit (P=0.04) and whole-grain (P=0.03) intake were associated with lower HbA1c in unadjusted, but not adjusted analyses; vegetable intake, HEI-2005 score, NRF 9.3 score, and glycemic index were not associated with HbA1c. Higher fruit (P=0.01) and whole-grain (P=0.04) intake and NRF 9.3 score (P=0.02), but not other diet quality indicators, were associated with lower body mass index percentile in adjusted analyses. Conclusions Data demonstrate poor diet quality in youth with type 1 diabetes and provide support for the importance of diet quality for weight management. Future research on determinants of dietary intake and methods to promote improved diet quality would be useful to inform clinical care. J Acad Nutr Diet. 2012;112:1728-1735. C1 [Nansel, Tonja R.; Haynie, Denise L.; Lipsky, Leah M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Laffel, Lori M. B.] Harvard Univ, Sch Med, Pediat Adolescent & Young Adult Sect, Boston, MA USA. [Laffel, Lori M. B.; Mehta, Sanjeev N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, 6100 Execut Blvd,Room 7B13R,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079; Lipsky, Leah/0000-0003-2645-4388 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703434C] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract no. HHSN267200703434C). NR 54 TC 19 Z9 21 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD NOV PY 2012 VL 112 IS 11 BP 1728 EP 1735 DI 10.1016/j.jand.2012.08.029 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 033RT UT WOS:000310819200005 PM 23102173 ER PT J AU Tse, J Nansel, TR Haynie, DL Mehta, SN Laffel, LMB AF Tse, Julia Nansel, Tonja R. Haynie, Denise L. Mehta, Sanjeev N. Laffel, Lori M. B. TI Disordered Eating Behaviors Are Associated with Poorer Diet Quality in Adolescents with Type 1 Diabetes SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Type 1 diabetes; Disordered eating; Dietary quality; Diabetes management; Diabetes Eating Problem Survey ID COMPLICATIONS TRIAL; BODY-WEIGHT; OVERWEIGHT; CHILDREN; MELLITUS; BARRIERS; FEMALES; OBESITY; ADULTS; GIRLS AB Disordered eating behaviors may pose a risk for poor long-term health outcomes in patients with type 1 diabetes. This cross-sectional study examined associations of disordered eating behaviors with diet quality, diet-related attitudes, and diabetes management in adolescents with type 1 diabetes (N=151, 48% female). Participants, recruited July 2008 through February 2009, completed 3-day diet records and survey measures, including the Diabetes Eating Problem Survey (DEPS) and measures of eating-related attitudes. Biomedical data were obtained from medical records. Participants scoring more than 1 standard deviation above the mean DEPS were classified as at risk for disordered eating. The Healthy Eating Index-2005 was calculated to assess diet quality. Analysis of covariance was used to test for differences between risk groups in diet quality, eating attitudes, and diabetes management controlling forage, sex, and body mass index (BMI) percentile. Youth at risk for disordered eating were more likely to be overweight/obese than those at low risk (59.1% vs 31.8%, P=0.01). The at-risk group had poorer diet quality (P=0.003) as well as higher intake of total fat (P=0.01) and saturated fat (P=0.007) compared with the low-risk group. The at-risk group reported lower self-efficacy (P=0.005), greater barriers (P<0.001), and more negative outcome expectations (P<0.001) for healthful eating, as well as worse dietary satisfaction (P=0.004). The at-risk group had lower diabetes adherence (P<0.01), less-frequent blood glucose monitoring (P<0.002), and higher hemoglobin A1c (P<0.001). The constellation of excess weight, poorer dietary intake, and poorer diabetes management associated with youth at risk for disordered eating suggests potential risk of future poor health outcomes. Attention should be given to healthful weight management, especially among overweight youth with type 1 diabetes. J Acad Nutr Diet 2012;112:1810-1814. C1 [Tse, Julia; Nansel, Tonja R.; Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Mehta, Sanjeev N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. [Laffel, Lori M. B.] Harvard Univ, Sch Med, Adolescent & Young Adult Sect, Boston, MA 02115 USA. RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bldg 6100,Room 7805,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703434C] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract number HHSN267200703434C. NR 28 TC 11 Z9 11 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD NOV PY 2012 VL 112 IS 11 BP 1810 EP 1814 DI 10.1016/j.jand.2012.06.359 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 033RT UT WOS:000310819200014 PM 23102180 ER PT J AU Shaw, P AF Shaw, Philip TI Attention-Deficit/Hyperactivity Disorder and the Battle for Control of Attention SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID DEFICIT HYPERACTIVITY DISORDER; WORKING-MEMORY; PLASTICITY; BRAIN C1 NIMH, Sect Neurobehav Clin Res, Social & Behav Res Branch, NHGRI, Bethesda, MD 20892 USA. RP Shaw, P (reprint author), NIMH, Sect Neurobehav Clin Res, Social & Behav Res Branch, NHGRI, Bldg 13,Room B1B36, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov FU Intramural NIH HHS NR 13 TC 3 Z9 3 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2012 VL 51 IS 11 BP 1116 EP 1118 DI 10.1016/j.jaac.2012.06.016 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 035IF UT WOS:000310939300004 PM 23101738 ER PT J AU Smith, L Brinton, LA Freedman, ND Gierach, GL AF Smith, Llewellyn Brinton, Louise A. Freedman, Neal D. Gierach, Gretchen L. TI Re: Body Mass Index and Risk of Lung Cancer Among Never, Former, and Current Smokers Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Smith, Llewellyn; Brinton, Louise A.; Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Rockville, MD USA. [Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Gierach, GL (reprint author), 6120 Execut Blvd,Ste 550,Rm 5016, Rockville, MD 20852 USA. EM gierachg@mail.nih.gov RI Brinton, Louise/G-7486-2015; Freedman, Neal/B-9741-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Freedman, Neal/0000-0003-0074-1098; Gierach, Gretchen/0000-0002-0165-5522 NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV PY 2012 VL 104 IS 21 BP 1681 EP 1681 DI 10.1093/jnci/djs382 PG 1 WC Oncology SC Oncology GA 035SS UT WOS:000310969600012 ER PT J AU Guise, JM Nagel, JD Regensteiner, JG AF Guise, Jeanne-Marie Nagel, Joan D. Regensteiner, Judith G. CA Bldg Interdisciplinary Res Careers TI Best Practices and Pearls in Interdisciplinary Mentoring from Building Interdisciplinary Research Careers in Women's Health Directors SO JOURNAL OF WOMENS HEALTH LA English DT Article ID ACADEMIC MEDICINE; SCIENCE; OPPORTUNITIES; CHALLENGES; FACULTY; PROGRAM AB Background: Increasingly, national programs and leaders are looking at interdisciplinary collaborations as essential to future research. Twelve years ago, the National Institutes of Health (NIH) Office of Research on Women's Health (ORWH) developed and implemented the Building Interdisciplinary Research Careers in Women's Health (BIRCWH) K12 program to focus on interdisciplinary mentored career development for junior faculty in women's health research. Methods: We applied a mixed-methods approach using an electronic survey and in-person presentations and discussions to understand best practices and lessons learned for interdisciplinary mentoring across BIRCWH K12 program leaders. Results and Conclusions: We received responses from all 29 active BIRCWH programs. Factors associated with success included ensuring sufficient protected time for regular (weekly or biweekly) mentoring; mentors promoting the research independence of the Scholar; a team mentoring approach, including career as well as content mentors; and explicit and clear expectations outlined between the Scholar and mentor. The majority of programs conduct formal evaluations of mentorship, and 79% of programs offer training in mentorship for either Scholars, mentors, or both. This article presents program leaders' best practices, challenges, and lessons learned from mentoring junior faculty who are conducting women's health research, whether basic, clinical, behavioral, translational, or health services research, using an interdisciplinary mentoring approach. C1 [Guise, Jeanne-Marie] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, Portland, OR 97239 USA. [Nagel, Joan D.] NIH, Off Res Womens Hlth, Washington, DC USA. [Regensteiner, Judith G.] Univ Colorado, Sch Med, Dept Med, Ctr Womens Hlth Res, Denver, CO USA. [Guise, Jeanne-Marie] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Guise, Jeanne-Marie] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA. RP Guise, JM (reprint author), Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, Mail Code L466,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM guisej@ohsu.edu OI Sherman, Bonnie/0000-0002-6322-8366 FU NICHD NIH HHS [K12 HD043488, K12 HD051953, K12 HD055884]; NIDA NIH HHS [P50 DA005312] NR 12 TC 3 Z9 3 U1 0 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2012 VL 21 IS 11 BP 1114 EP 1127 DI 10.1089/jwh.2012.3788 PG 14 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 034BI UT WOS:000310844700002 PM 22994986 ER PT J AU Breman, JG AF Breman, Joel G. TI Resistance to artemisinin-based combination therapy SO LANCET INFECTIOUS DISEASES LA English DT Editorial Material ID ARTEMETHER-LUMEFANTRINE; FALCIPARUM-MALARIA; SELECTION; AFRICA C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM jbreman@nih.gov NR 8 TC 22 Z9 24 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD NOV PY 2012 VL 12 IS 11 BP 820 EP 822 DI 10.1016/S1473-3099(12)70226-8 PG 3 WC Infectious Diseases SC Infectious Diseases GA 029JT UT WOS:000310492300004 PM 22940026 ER PT J AU Amaratunga, C Sreng, S Suon, S Phelps, ES Stepniewska, K Lim, P Zhou, CJ Mao, S Anderson, JM Lindegardh, N Jiang, HY Song, JP Su, XZ White, NJ Dondorp, AM Anderson, TJC Fay, MP Mu, JB Duong, S Fairhurst, RM AF Amaratunga, Chanaki Sreng, Sokunthea Suon, Seila Phelps, Erika S. Stepniewska, Kasia Lim, Pharath Zhou, Chongjun Mao, Sivanna Anderson, Jennifer M. Lindegardh, Niklas Jiang, Hongying Song, Jianping Su, Xin-zhuan White, Nicholas J. Dondorp, Arjen M. Anderson, Tim J. C. Fay, Michael P. Mu, Jianbing Duong, Socheat Fairhurst, Rick M. TI Artemisinin-resistant Plasmodium falciparum in Pursat province, western Cambodia: a parasite clearance rate study SO LANCET INFECTIOUS DISEASES LA English DT Article ID POPULATION-STRUCTURE; G6PD VIANGCHAN; HEMOGLOBIN-E; MALARIA; ARTESUNATE; SUSCEPTIBILITY; HERITABILITY; THALASSEMIA; MECHANISM; VARIANT AB Background Artemisinin-resistant Plasmodium falciparum has been reported in Pailin, western Cambodia, detected as a slow parasite clearance rate in vivo. Emergence of this phenotype in western Thailand and possibly elsewhere threatens to compromise the effectiveness of all artemisinin-based combination therapies. Parasite genetics is associated with parasite clearance rate but does not account for all variation. We investigated contributions of both parasite genetics and host factors to the artemisinin-resistance phenotype in Pursat, western Cambodia. Methods Between June 19 and Nov 28,2009, and June 26 and Dec 6,2010, we enrolled patients aged 10 years or older with uncomplicated falciparum malaria, a density of asexual parasites of at least 10000 per mu L of whole blood, no symptoms or signs of severe malaria, no other cause of febrile illness, and no chronic illness. We gave participants 4 mg/kg artesunate at 0,24, and 48 h, 15 mg/kg mefloquine at 72 h, and 10 mg/kg mefloquine at 96 h. We assessed parasite density on thick blood films every 6 h until undetectable. The parasite clearance half-life was calculated from the parasite clearance curve. We genotyped parasites with 18 microsatellite markers and patients for haemoglobin E, alpha-thalassaeinia, and a mutation of GOD, which encodes glucose-6-phosphate dehydrogenase. To account for the possible effects of acquired immunity on half-life, we used three surrogates for increased likelihood of exposure to P falciparum: age, sex, and place of residence. This study is registered with ClinicalTrials.gov, number NCT00341003. Findings We assessed 3504 individuals from all six districts of Pursat province seeking treatment for malaria symptoms. We enrolled 168 patients with falciparum malaria who met inclusion criteria. The geometric mean half-life was 5.85 h (95% CI 5.54-6.18) in Pursat, similar to that reported in Pailin (p=0.109). We identified two genetically different parasite clone groups: parasite group 1 (PG1) and parasite group 2 (PG2). Non-significant increases in parasite clearance half-life were seen in patients with haemoglobin E (0.55 h; p=0.078), those of male sex (0.96 h; p=0.064), and in 2010 (0.68 h; p=0.068); PG1 was associated with a significant increase (0.79 h; p=0.033). The mean parasite heritability of half-life was 0.40 (SD 0.17). Interpretation Heritable artemisinin resistance is established in a second Cambodian province. To accurately identify parasites that are intrinsically susceptible or resistant to artemisinins, future studies should explore the effect of erythrocyte polymorphisms and specific immune responses on half-life variation. C1 [Amaratunga, Chanaki; Phelps, Erika S.; Lim, Pharath; Anderson, Jennifer M.; Jiang, Hongying; Su, Xin-zhuan; Mu, Jianbing; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Fay, Michael P.] NIAID, Biostat Res Brand, NIH, Rockville, MD 20852 USA. [Sreng, Sokunthea; Suon, Seila; Lim, Pharath; Duong, Socheat] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia. [Stepniewska, Kasia] Univ Oxford, Nuffield Dept Clin Med, Worldwide Antimalarial Resistance Network, Oxford, England. [Stepniewska, Kasia] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England. [Zhou, Chongjun; Song, Jianping] Guangzhou Univ Tradit Chinese Med, Res Ctr Qinghao, Guangzhou, Guangdong, Peoples R China. [Mao, Sivanna] Sampov Meas Referral Hosp, Pursat, Cambodia. [Lindegardh, Niklas; White, Nicholas J.; Dondorp, Arjen M.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok 10700, Thailand. [Anderson, Tim J. C.] Texas Biomed Res Inst, San Antonio, TX USA. RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM rfairhurst@niaid.nih.gov OI Fay, Michael P./0000-0002-8643-9625; Su, Xinzhuan/0000-0003-3246-3248 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX Funding Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 36 TC 155 Z9 158 U1 4 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD NOV PY 2012 VL 12 IS 11 BP 851 EP 858 DI 10.1016/S1473-3099(12)70181-0 PG 8 WC Infectious Diseases SC Infectious Diseases GA 029JT UT WOS:000310492300024 PM 22940027 ER PT J AU Kikuchi, J Takashina, T Kinoshita, I Kikuchi, E Shimizu, Y Sakakibara-Konishi, J Oizumi, S Marquez, VE Nishimura, M Dosaka-Akita, H AF Kikuchi, Junko Takashina, Taichi Kinoshita, Ichiro Kikuchi, Eiki Shimizu, Yasushi Sakakibara-Konishi, Jun Oizumi, Satoshi Marquez, Victor E. Nishimura, Masaharu Dosaka-Akita, Hirotoshi TI Epigenetic therapy with 3-deazaneplanocin A, an inhibitor of the histone methyltransferase EZH2, inhibits growth of non-small cell lung cancer cells SO LUNG CANCER LA English DT Article DE 3-Deazaneplanocin A (DZNep); Polycomb-group protein; EZH2; Non-small cell lung cancer; Epigenetics; Proliferation; Apoptosis ID ZESTE HOMOLOG 2; S-ADENOSYLHOMOCYSTEINE HYDROLASE; BRONCHIAL EPITHELIAL-CELLS; PROSTATE-CANCER; CYCLIN-A; PHARMACOLOGICAL DISRUPTION; GROUP PROTEINS; EXPRESSION; POLYCOMB; ENHANCER AB EZH2 (enhancer of zeste homolog 2) is the catalytic subunit of PRC2 (polycomb repressive complex 2), which mediates histone methyltransferase activity and functions as transcriptional repressor involved in gene silencing. EZH2 is involved in malignant transformation and biological aggressiveness of several human malignancies. We previously demonstrated that non-small cell lung cancers (NSCLCs) also overexpress EZH2 and that high expression of EZH2 correlates with poor prognosis. Growing evidence indicates that EZH2 may be an appropriate therapeutic target in malignancies, including NSCLCs. Recently, an S-adenosyl-L-homocysteine hydrolase inhibitor, 3-Deazaneplanocin A (DZNep), has been shown to deplete and inhibit EZH2. The aim of this study was to determine the effect of DZNep in NSCLC cells. Knockdown of EZH2 by small-interfering RNA (siRNA) resulted in decreased growth of four NSCLC cell lines. MTT assays demonstrated that DZNep treatment resulted in dose-dependent inhibition of proliferation in the NSCLC cell lines with a half maximal inhibitory concentration (IC50) ranging from 0.08 to 0.24 mu M. Immortalized but non-cancerous bronchial epithelial and fibroblast cell lines were less sensitive to DZNep than the NSCLC cell lines. Soft agarose assays demonstrated that anchorage-independent growth was also reduced in all three NSCLC cell lines that were evaluated using this assay. Flow cytometry analysis demonstrated that DZNep induced apoptosis and G1 cell cycle arrest in NSCLC cells, which was partially associated with cyclin A decrease and p27(Kip1) accumulation. DZNep depleted cellular levels of EZH2 and inhibited the associated histone H3 lysine 27 trimethylation. These results indicated that an epigenetic therapy that pharmacologically targets EZH2 via DZNep may constitute a novel approach to treatment of NSCLCs. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Kinoshita, Ichiro] Hokkaido Univ, Grad Sch Med, Dept Med Oncol, Kita Ku, Sapporo, Hokkaido 0608638, Japan. [Kikuchi, Junko; Takashina, Taichi; Kikuchi, Eiki; Sakakibara-Konishi, Jun; Oizumi, Satoshi; Nishimura, Masaharu] Hokkaido Univ, Sch Med, Dept Med 1, Sapporo, Hokkaido 0608638, Japan. [Marquez, Victor E.] NCI, Biol Chem Lab, FNLCR, NIH, Frederick, MD 21702 USA. RP Kinoshita, I (reprint author), Hokkaido Univ, Grad Sch Med, Dept Med Oncol, Kita Ku, North 15,West 7, Sapporo, Hokkaido 0608638, Japan. EM kinoshii@med.hokudai.ac.jp RI Kikuchi, Eiki/M-9688-2014; Nishimura, Masaharu/A-4062-2012 FU Japan Society for the Promotion of Science; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This study was supported in part by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science. This research was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors thank Namiko Sawada for technical assistance. NR 40 TC 52 Z9 53 U1 1 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD NOV PY 2012 VL 78 IS 2 BP 138 EP 143 DI 10.1016/j.lungcan.2012.08.003 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 035JZ UT WOS:000310944000003 PM 22925699 ER PT J AU Kang, C Drayna, D AF Kang, Changsoo Drayna, Dennis TI A role for inherited metabolic deficits in persistent developmental stuttering SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Stuttering; Linkage; Lysosomal targeting pathway; GNPTAB; NAGPA ID 6-PHOSPHATE UNCOVERING ENZYME; PSEUDO-HURLER POLYDYSTROPHY; MUCOLIPIDOSIS-II; ULTRASONIC VOCALIZATION; ALPHA/BETA-SUBUNITS; MICE; MUTATIONS; LINKAGE; GENE; TWIN AB Stuttering is a common but poorly understood speech disorder. Consistent evidence for the involvement of genetic factors in stuttering has motivated studies aimed at identifying causative genetic variants that could shed light on the underlying molecular and cellular deficits in this disorder. Such studies have begun to identify causative genes. The purpose of this review is to summarize the gene discoveries to date, and to cover the subsequent functional studies that are beginning to provide insights into how these gene mutations might cause stuttering. Surprisingly, the first variant genes to be associated with stuttering are those encoding the lysosomal targeting system, GNPTAB, GNPTG, and NAGPA. Although mutations in NAGPA have not been associated with a disorder in humans, mutations in GNPTAB and GNPTG cause mucolipidosis types II and III, which are rare autosomal recessive lysosomal storage disorders, associated with pathology of bone, connective tissue, liver, spleen, and brain. Analysis of mutations in these genes has so far identified predominantly missense mutations in stuttering, in contrast to the truncating and other mutations that result in very low GNPTAB/G enzyme activity and are historically associated with mucolipidosis. Genetic evidence for the role of lysosomal targeting mutations in stuttering has now been buttressed by biochemical studies of the mutant enzymes found in this disorder. While data on the GlcNAc-phosphotransferase encoded by GNPTAB/G remains limited and only suggestive, a study of the enzyme encoded by NAGPA has shown that the mutations found in stuttering reduce the overall cellular activity of this enzyme by about half, and that they result in deficits in intracellular processing and trafficking that lead to a reduced cellular half life. How these deficits result in the presumed speech-specific neuropathology associated with stuttering is not yet known. However these findings have opened several new lines of inquiry, including studies in mice carrying human stuttering mutations, that represent promising approaches to this disorder. Published by Elsevier Inc. C1 [Kang, Changsoo; Drayna, Dennis] NIDCD, NIH, Rockville, MD 20850 USA. RP Drayna, D (reprint author), NIDCD, NIH, 5 Res Court,Room 2B-46, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov FU NIH/NIDCD [Z01-000046-12]; Stuttering Foundation of America FX We thank Stuart Kornfeld, Thomas Friedman, and Allen Braun for valuable comments on the manuscript. This work was supported by the NIH/NIDCD intramural grant Z01-000046-12 and by the Stuttering Foundation of America. NR 47 TC 6 Z9 6 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2012 VL 107 IS 3 BP 276 EP 280 DI 10.1016/j.ymgme.2012.07.020 PG 5 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 032LM UT WOS:000310720200006 PM 22884963 ER PT J AU Punwani, D Gonzalez-Espinosa, D Comeau, AM Dutra, A Pak, E Puck, J AF Punwani, Divya Gonzalez-Espinosa, Diana Comeau, Anne Marie Dutra, Amalia Pak, Evgenia Puck, Jennifer TI Cellular calibrators to quantitate T-cell receptor excision circles (TRECs) in clinical samples SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE TREC; SCID; newborn screening; Calibrator; Test standardization; Primary immunodeficiency ID SEVERE COMBINED IMMUNODEFICIENCY; RECENT THYMIC EMIGRANTS; TRANSPLANTATION; GENE; THERAPY; DISEASE; OUTPUT; PCR AB T-cell receptor excision circles (TRECs) are circular DNA molecules formed during rearrangement of the T-cell receptor (TCR) genes during lymphocyte development. Copy number of the junctional portion of the delta Rec-psi J alpha TREC, assessed by quantitative PCR (qPCR) using DNA from dried blood spots (DBS), is a biomarker for newly formed T cells and absent or low numbers of TRECs indicate SCID (severe combined immunodeficiency) or T lymphocytopenia. No quantitation standard for TRECs exists. To permit comparison of TREC qPCR results with a reliable method for counting TRECs across different laboratories, we sought to construct a stable cell line containing a normal human chromosomal constitution and a single copy of the TREC junction sequence. A human EBV (Epstein Barr virus)-transformed B-cell line was transduced with a lentivirus encoding mCherry fluorescence, puromycin resistance and the delta Rec-psi J alpha. TREC sequence. A TREC-EBV cell line, with each cell carrying a single lentiviral insertion was established, expanded and shown to have one TREC copy per diploid genome. Graded numbers of TREC-EBV cells added to aliquots of T lymphocyte depleted blood showed TREC copy number proportional to TREC-EBV cell number. TREC-EBV cells, therefore, constitute a reproducible cellular calibrator for TREC assays, useful for both population-based screening for severe combined immunodeficiency and evaluation of naive T-cell production in clinical settings. (C) 2012 Elsevier Inc. All rights reserved. C1 [Punwani, Divya; Gonzalez-Espinosa, Diana; Puck, Jennifer] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Comeau, Anne Marie] Univ Massachusetts, Sch Med, Dept Pediat, New England Newborn Screening Program, Worcester, MA 01610 USA. [Dutra, Amalia; Pak, Evgenia] NHGRI, NIH, Bethesda, MD 20892 USA. RP Puck, J (reprint author), UCSF Dept Pediat, Box 0519,513 Parnassus Ave,HSE 301A, San Francisco, CA 94143 USA. EM puckj@peds.ucsf.edu FU UMMS [DHHS/CDC U01EH000362]; NIH NHGRI Intramural Research Program; NIH [RO3 HD060311]; Jeffrey Modell Foundation FX The authors thank Robert Vogt, CDC, Atlanta, for helpful discussions and Michael McManus, UCSF, who provided the MP-283 lentiviral vector. This study was supported by DHHS/CDC U01EH000362 subcontract from UMMS, the NIH NHGRI Intramural Research Program (AD and EP) and by NIH RO3 HD060311 and the Jeffrey Modell Foundation (JMP). The authors declare no competing financial interests. NR 32 TC 4 Z9 5 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2012 VL 107 IS 3 BP 586 EP 591 DI 10.1016/j.ymgme.2012.09.018 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 032LM UT WOS:000310720200049 PM 23062576 ER PT J AU Chandler, RJ Venditti, CP AF Chandler, Randy J. Venditti, Charles P. TI Pre-clinical efficacy and dosing of an AAV8 vector expressing human methylmalonyl-CoA mutase in a murine model of methylmalonic acidemia (MMA) SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Methylmalonic acidemia; MMA; Gene therapy; Adeno-associated virus; AAV; Organic acidemia ID GENE DELIVERY RESCUES; MUT(0) AB We demonstrate that human methylmalonyl-CoA mutase (MUT), delivered using an AAV serotype 8 vector, rescues the lethal phenotype displayed by mice with MMA and provides long-term phenotypic correction. In addition to defining a lower limit of effective dosing, our studies establish that neither a species barrier to mitochondrial processing nor an apparent immune response to MUT limits the murine model as an experimental platform to test the efficacy of human gene therapy vectors for MMA. Published by Elsevier Inc. C1 [Chandler, Randy J.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, NIH, Bethesda, MD 20892 USA. RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, NIH, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov FU Intramural NIH HHS [Z99 HG999999, ZIA HG200318-09] NR 11 TC 5 Z9 5 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2012 VL 107 IS 3 BP 617 EP 619 DI 10.1016/j.ymgme.2012.09.019 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 032LM UT WOS:000310720200056 PM 23046887 ER PT J AU Zhao, JF Stagno, JR Varticovski, L Nimako, E Rishi, V McKinnon, K Akee, R Shoemaker, RH Ji, XH Vinson, C AF Zhao, Jianfei Stagno, Jason R. Varticovski, Lyuba Nimako, Eric Rishi, Vikas McKinnon, Kathy Akee, Rhone Shoemaker, Robert H. Ji, Xinhua Vinson, Charles TI P6981, An Arylstibonic Acid, Is a Novel Low Nanomolar Inhibitor of cAMP Response Element-Binding Protein Binding to DNA SO MOLECULAR PHARMACOLOGY LA English DT Article ID CLEAR-CELL SARCOMA; HELIX-LOOP-HELIX; GCN4 LEUCINE-ZIPPER; COILED-COIL; TRANSCRIPTION FACTORS; DIMERIZATION SPECIFICITY; MALIGNANT-MELANOMA; MYELOID-LEUKEMIA; SOFT PARTS; CREB AB Several basic leucine zipper (B-ZIP) transcription factors have been implicated in cancer, substance abuse, and other pathological conditions. We previously identified arylstibonic acids that bind to B-ZIP proteins and inhibit their interaction with DNA. In this study, we used electrophoretic mobility shift assay to analyze 46 arylstibonic acids for their activity to disrupt the DNA binding of three B-ZIP [CCAAT/enhancer-binding protein alpha, cyclic AMP-response element-binding protein (CREB), and vitellogenin gene-binding protein (VBP)] and two basic helix-loop-helix leucine zipper (B-HLH-ZIP) [USF (upstream stimulating factor) and Mitf] proteins. Twenty-five arylstibonic acids showed activity at micromolar concentrations. The most active compound, P6981 [2-(3-stibonophenyl)malonic acid], had half-maximal inhibition at similar to 5 nM for CREB. Circular dichroism thermal denaturation studies indicated that P6981 binds both the B-ZIP domain and the leucine zipper. The crystal structure of an arylstibonic acid, NSC13778, bound to the VBP leucine zipper identified electrostatic interactions between both the stibonic and carboxylic acid groups of NSC13778 [(E)-3-(3-stibonophenyl)acrylic acid] and arginine side chains of VBP, which is also involved in interhelical salt bridges in the leucine zipper. P6981 induced GFP-B-ZIP chimeric proteins to partially localize to the cytoplasm, demonstrating that it is active in cells. P6981 inhibited the growth of a patient-derived clear cell sarcoma cell line whose oncogenic potential is driven by a chimeric protein EWS-ATF1 (Ewing's sarcoma protein-activating transcription factor 1), which contains the DNA binding domain of ATF1, a B-ZIP protein. NSC13778 inhibited the growth of xenografted clear cell sarcoma, and no toxicity was observed. These experiments suggest that antimony containing arylstibonic acids are promising leads for suppression of DNA binding activities of B-ZIP and B-HLH-ZIP transcription factors. C1 [Vinson, Charles] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Stagno, Jason R.; Ji, Xinhua] Natl Canc Inst, Macromol Crystallog Lab, Frederick, MD USA. [Varticovski, Lyuba; McKinnon, Kathy] NCI, Lab Receptor Biol & Gene Express, Vaccine Branch, Bethesda, MD 20892 USA. [Akee, Rhone] SAIC Frederick, Nat Prod Support Grp, Frederick, MD USA. [Shoemaker, Robert H.] Frederick Natl Lab Canc Res, Dev Therapeut Program, Frederick, MD USA. RP Vinson, C (reprint author), NCI, Lab Metab, Ctr Canc Res, Bldg 37,Room 3128,37 Convent Dr, Bethesda, MD 20892 USA. EM vinsonc@mail.nih.gov FU Center for Cancer Research, National Institutes of Health National Cancer Institute FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Institutes of Health National Cancer Institute. NR 51 TC 5 Z9 5 U1 1 U2 10 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2012 VL 82 IS 5 BP 814 EP 823 DI 10.1124/mol.112.080820 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 037WS UT WOS:000311137800005 PM 22851716 ER PT J AU Amalou, H Wood, BJ AF Amalou, Hayet Wood, Bradford J. TI Biopsy and personalized medicine SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY LA English DT Letter ID OVARIAN-CANCER; FUSION; NAVIGATION; ABLATION; GUIDANCE C1 [Amalou, Hayet; Wood, Bradford J.] NIH, Ctr Intervent Oncol, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol, MSC 1182, Bethesda, MD 20892 USA. EM bwood@nih.gov FU Intramural NIH HHS [ZID BC011242-04, ZIA CL040011-05, ZIA CL040015-04] NR 10 TC 1 Z9 1 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5045 J9 NAT REV GASTRO HEPAT JI Nat. Rev. Gastroenterol. Hepatol. PD NOV PY 2012 VL 9 IS 11 BP 683 EP 683 DI 10.1038/nrgastro.2012.100-c1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 033FQ UT WOS:000310780000010 PM 23026901 ER PT J AU Csiszovszki, Z Lewis, DEA Le, P Sneppen, K Semsey, S AF Csiszovszki, Zsolt Lewis, Dale E. A. Le, Phuoc Sneppen, Kim Semsey, Szabolcs TI Specific contacts of the -35 region of the galP1 promoter by RNA polymerase inhibit GalR-mediated DNA looping repression SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI; TRANSCRIPTION INITIATION; COMPLEX-FORMATION; ALPHA-SUBUNIT; REPRESSOSOME; BINDING; PROTEIN; SEQUENCES; OPERON; GENE AB The P1 promoter of the galactose operon in Escherichia coli is one of the best studied examples of 'extended -10' promoters. Recognition of the P1 promoter does not require specific contacts between RNA polymerase and its poor -35 element. To investigate whether specific recognition of the -35 element would affect the regulation of P1 by GalR, we mutagenized the -35 element of P1, isolated variants of the -35 element and studied the regulation of the mutant promoters by in vitro transcription assays and by mathematical modeling. The results show that the GalR-mediated DNA loop is less efficient in repressing P1 transcription when RNA polymerase binds to the -10 and -35 elements concomitantly. Our results suggest that promoters that lack specific -35 element recognition allow decoupling of local chromosome structure from transcription initiation. C1 [Sneppen, Kim; Semsey, Szabolcs] Univ Copenhagen, Niels Bohr Inst, CMOL, DK-2100 Copenhagen, Denmark. [Csiszovszki, Zsolt; Lewis, Dale E. A.; Le, Phuoc] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Semsey, S (reprint author), Univ Copenhagen, Niels Bohr Inst, CMOL, Blegdamsvej 17, DK-2100 Copenhagen, Denmark. EM semsey@nbi.dk RI Semsey, Szabolcs/L-6329-2013; OI Semsey, Szabolcs/0000-0002-4522-5495; Sneppen, Kim/0000-0001-9820-3567 FU Danish Council for Independent Research, Natural Sciences; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Danish National Research Foundation FX Danish Council for Independent Research, Natural Sciences, the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and the Danish National Research Foundation. Funding for open access charge: Danish National Research Foundation. NR 43 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV PY 2012 VL 40 IS 20 BP 10064 EP 10072 DI 10.1093/nar/gks796 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035TC UT WOS:000310970700017 PM 22941635 ER PT J AU Dickey, JS Baird, BJ Redon, CE Avdoshina, V Palchik, G Wu, JF Kondratyev, A Bonner, WM Martin, OA AF Dickey, Jennifer S. Baird, Brandon J. Redon, Christophe E. Avdoshina, Valeriya Palchik, Guillermo Wu, Junfang Kondratyev, Alexei Bonner, William M. Martin, Olga A. TI Susceptibility to bystander DNA damage is influenced by replication and transcriptional activity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; PRIMARY HUMAN FIBROBLASTS; IRRADIATED GLIOMA-CELLS; TOPOISOMERASE-I; NITRIC-OXIDE; INTERCELLULAR COMMUNICATION; IONIZING-RADIATION; HUMAN-LYMPHOCYTES; EXCISION-REPAIR; HISTONE H2A.X AB Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to bystander DSB formation from single strand lesions. To examine whether transcription predisposes non-replicating cells to bystander effect-induced DNA DSBs, we examined two types of primary cells that exhibit high levels of transcription in the absence of replication, rat neurons and human lymphocytes. We found that non-replicating bystander cells with high transcription rates exhibited substantial levels of DNA DSBs, as monitored by gamma-H2AX foci formation. Additionally, as reported in proliferating cells, TGF-beta and NO were found to mimic bystander effects in cell populations lacking DNA synthesis. These results indicate that cell vulnerability to bystander DSB damage may result from transcription as well as replication. The findings offer insights into which tissues may be vulnerable to bystander genomic destabilization in vivo. C1 [Dickey, Jennifer S.; Baird, Brandon J.; Redon, Christophe E.; Bonner, William M.; Martin, Olga A.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20952 USA. [Avdoshina, Valeriya; Wu, Junfang] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. [Palchik, Guillermo; Kondratyev, Alexei] Georgetown Univ, Med Ctr, Interdisciplinary Program Neurosci, Washington, DC 20057 USA. [Kondratyev, Alexei] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20057 USA. RP Dickey, JS (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Vitro Diagnost, Silver Spring, MD 20993 USA. EM Jennifer.Dickey@fda.hhs.gov; Olga.Martin@petermac.org OI Palchik, Guillermo/0000-0003-2161-3976 FU National Cancer Institute, National Institutes of Health, USA; National Institute for Allergies and Infectious Disease (NIAID) Trans-NIH Biodefense Program; National Institute of Neuorlogical Disorders and Stroke [NS056057] FX The Intramural Funding Program of the National Cancer Institute, National Institutes of Health, USA, and the National Institute for Allergies and Infectious Disease (NIAID) Trans-NIH Biodefense Program; National Institute of Neuorlogical Disorders and Stroke [NS056057 to A. K., in part]. Funding for open access charge: Intramural funding program of the National Cancer Institute, National Institutes of Health, USA. NR 59 TC 18 Z9 18 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV PY 2012 VL 40 IS 20 BP 10274 EP 10286 DI 10.1093/nar/gks795 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035TC UT WOS:000310970700035 PM 22941641 ER PT J AU Zheng, XH Mueller, GA DeRose, EF London, RE AF Zheng, Xunhai Mueller, Geoffrey A. DeRose, Eugene F. London, Robert E. TI Metal and ligand binding to the HIV-RNase H active site are remotely monitored by Ile556 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID VIRUS REVERSE-TRANSCRIPTASE; CARBON-13 MAGNETIC RESONANCE; RIBONUCLEASE-H; ESCHERICHIA-COLI; RNA/DNA HYBRID; METHYL-GROUPS; CATALYTIC MECHANISM; BACKBONE DYNAMICS; CRYSTAL-STRUCTURE; STRUCTURAL BASIS AB HIV-1 reverse transcriptase (RT) contains a C-terminal ribonuclease H (RH) domain on its p66 subunit that can be expressed as a stable, although inactive protein. Recent studies of several RH enzymes demonstrate that substrate binding plays a major role in the creation of the active site. In the absence of substrate, the C-terminal helix E of the RT RNase H domain is dynamic, characterized by severe exchange broadening of its backbone amide resonances, so that the solution characterization of this region of the protein has been limited. Nuclear magnetic resonance studies of C-13-labeled RH as a function of experimental conditions reveal that the delta 1 methyl resonance of Ile556, located in a short, random coil segment following helix E, experiences a large C-13 shift corresponding to a conformational change of Ile556 that results from packing of helix E against the central beta-sheet. This shift provides a useful basis for monitoring the effects of various ligands on active site formation. Additionally, we report that the RNase H complexes formed with one or both divalent ions can be individually observed and characterized using diamagnetic Zn2+ as a substitute for Mg2+. Ordering of helix E results specifically from the interaction with the lower affinity binding to the A divalent ion site. C1 [Zheng, Xunhai; Mueller, Geoffrey A.; DeRose, Eugene F.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov RI Zheng, Xunhai/G-1187-2015 OI Zheng, Xunhai/0000-0003-0390-2491 FU Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health [Z01-ES050147]; National Institutes of Health, NIEHS [HHSN273200700046U]; National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services [HHSN273201100001C] FX Research Project Number Z01-ES050147 to R. E. L. in the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. E. F. D. is supported by National Institutes of Health, NIEHS, under Delivery Order HHSN273200700046U. Chemical synthesis of 2-hydroxyisoquinoline-1,3(2H,4H)-dione was performed for the National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract No. HHSN273201100001C. Funding for open access charge: Research Project Number Z01-ES050147 to R. E. L. in the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. NR 50 TC 6 Z9 6 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV PY 2012 VL 40 IS 20 BP 10543 EP 10553 DI 10.1093/nar/gks791 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035TC UT WOS:000310970700057 PM 22941642 ER PT J AU Richards, JM Plate, RC Ernst, M AF Richards, Jessica M. Plate, Rista C. Ernst, Monique TI Neural systems underlying motivated behavior in adolescence: Implications for preventive medicine SO PREVENTIVE MEDICINE LA English DT Review DE Triadic Model; Risk-taking; Neuroimaging; Striatum; Amygdala; Prefrontal cortex; Development; Prevention ID ANTERIOR CINGULATE CORTEX; WORKING-MEMORY; PREFRONTAL CORTEX; DEVELOPMENTAL DIFFERENCES; ORBITOFRONTAL CORTEX; ACTIVATION TREATMENT; DEPRESSIVE SYMPTOMS; FACIAL EXPRESSIONS; BRAIN-DEVELOPMENT; CHOICE SELECTION AB Objective: Although a time of increased independence and autonomy, adolescence is also a time of vulnerabilities, through increased risk-taking and the emergence of psychopathology. Neurodevelopmental changes during this period may provide a neurobiological basis for this normative rise in deleterious behaviors. Thus, the objective of this review was to identify neurodevelopmental processes underlying the emergence of risk-taking and psychopathology in adolescence, and discuss implications of these findings for prevention. Method: This article reviews literature examining developmental and contextual factors influencing neural functioning in systems mediating threat, reward, and cognitive control. This literature is discussed from the perspective of the Triadic Neural Systems Model of motivated behavior. Results: Neuroimaging research suggests that neurodevelopmental and contextual factors both contribute to a shift in the functional equilibrium among the Triadic nodes. This equilibrium shift may contribute to negative outcomes of adolescent risk behavior. Most importantly, the balance of this equilibrium and its sensitivity to social and appetitive contexts may be exploited to facilitate prevention of deleterious outcomes. Conclusion: Understanding developmental and contextual factors that influence functioning in motivational neural circuits can inform research on adolescent risk-taking, and may provide targets for novel preventions, for example through the use of incentives to reduce deleterious outcomes. (C) 2011 Elsevier Inc. All rights reserved. C1 [Plate, Rista C.; Ernst, Monique] Natl Inst Mental Hlth, Bethesda, MD 20817 USA. [Richards, Jessica M.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Ernst, M (reprint author), Natl Inst Mental Hlth, NIMH Bldg 15-K,Room 110,MSC-2670, Bethesda, MD 20817 USA. EM jessic1@umd.edu; rista.plate@nih.gov; ernstm@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 64 TC 8 Z9 8 U1 2 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 J9 PREV MED JI Prev. Med. PD NOV 1 PY 2012 VL 55 SU 1 BP S7 EP S16 DI 10.1016/j.ypmed.2011.11.016 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 036VV UT WOS:000311061300003 PM 22198622 ER PT J AU Babu, S Nutman, TB AF Babu, Subash Nutman, Thomas B. TI Immunopathogenesis of lymphatic filarial disease SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE Filariasis; Pathology; Lymphedema; Hydrocele; Cytokines; Immunity ID WUCHERERIA-BANCROFTI INFECTION; TUMOR-NECROSIS-FACTOR; ENDOSYMBIOTIC WOLBACHIA BACTERIA; TROPICAL PULMONARY EOSINOPHILIA; ANTIGEN-PRESENTING CELLS; PARASITE-SPECIFIC ANERGY; SELECTIVE UP-REGULATION; NEMATODE BRUGIA-MALAYI; HUMAN DENDRITIC CELLS; REGULATORY T-CELLS AB Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, similar to 40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process-the first initiated by the parasite and host innate immune system and the second propagated mainly by the host's adaptive immune system and by other factors (including secondary infections). C1 [Babu, Subash] Natl Inst Res TB, Chennai 600031, Tamil Nadu, India. [Nutman, Thomas B.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. [Babu, Subash] NIRT, Chennai, Tamil Nadu, India. RP Babu, S (reprint author), Natl Inst Res TB, 1 Mayor Sathiyamurthy Rd, Chennai 600031, Tamil Nadu, India. EM sbabu@mail.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 141 TC 32 Z9 32 U1 0 U2 21 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1863-2297 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD NOV PY 2012 VL 34 IS 6 BP 847 EP 861 DI 10.1007/s00281-012-0346-4 PG 15 WC Immunology; Pathology SC Immunology; Pathology GA 035XX UT WOS:000310988000009 PM 23053393 ER PT J AU Skolnick, P AF Skolnick, Phil TI Anxioselective anxiolytics: on a quest for the Holy Grail SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID GENERALIZED ANXIETY DISORDER; GABA(A) RECEPTOR SUBTYPE; AMINOBUTYRIC ACID(A) RECEPTORS; SELECTIVE PARTIAL AGONIST; BENZODIAZEPINE-RECEPTORS; A RECEPTORS; BETA-CARBOLINE; PHARMACOLOGICAL PROFILE; PSYCHOMOTOR PERFORMANCE; ALPHA-SUBUNIT AB The discovery of benzodiazepine receptors provided the impetus to discover and develop anxioselective anxiolytics (Valium without the side effects'). The market potential for an anxioselective based on the gamma-aminobutyric acid A (GABA(A)) receptor resulted in clinical trials of multiple compounds. In contrast to the anxioselective profile displayed in preclinical models, compounds such as bretazenil, TPA023, and MRK 409 produced benzodiazepine-like side effects (sedation, dizziness) in Phase I studies, whereas alpidem and ocinaplon exhibited many of the characteristics of an anxioselective in the clinic. Alpidem was briefly marketed for the treatment of anxiety, but was withdrawn because of liver toxicity. Reversible elevations in liver enzymes halted development of ocinaplon in Phase III. The clinical profiles of these two molecules demonstrate that it is possible to develop GABA(A) receptor-based anxioselectives. However, despite the formidable molecular toolbox at our disposal, we are no better informed about the GABA(A) receptors responsible for an anxioselective profile in the clinic. Here, I discuss the evolution of a quest, spanning four decades, for molecules that retain the rapid and robust anti-anxiety actions of benzodiazepines without the side effects that limit their usefulness. C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Skolnick, P (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Suite 4123, Bethesda, MD 20892 USA. EM phil.skolnick@nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 73 TC 27 Z9 29 U1 0 U2 12 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD NOV PY 2012 VL 33 IS 11 BP 611 EP 620 DI 10.1016/j.tips.2012.08.003 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 038LT UT WOS:000311176900008 PM 22981367 ER PT J AU Robertson, BD Altmann, D Barry, C Bishai, B Cole, S Dick, T Duncan, K Dye, C Ehrt, S Esmail, H Flynn, J Hafner, R Handley, G Hanekom, W van Helden, P Kaplan, G Kaufmann, SHE Kim, P Lienhardt, C Mizrahi, V Rubin, E Schnappinger, D Sherman, D Thole, J Vandal, O Walzl, G Warner, D Wilkinson, R Young, D AF Robertson, Brian D. Altmann, Danny Barry, Clif Bishai, Bill Cole, Stewart Dick, Thomas Duncan, Ken Dye, Chris Ehrt, Sabine Esmail, Hanif Flynn, JoAnne Hafner, Richard Handley, Gray Hanekom, Willem van Helden, Paul Kaplan, Gilla Kaufmann, Stefan H. E. Kim, Peter Lienhardt, Christian Mizrahi, Valerie Rubin, Eric Schnappinger, Dirk Sherman, David Thole, Jelle Vandal, Omar Walzl, Gerhard Warner, Digby Wilkinson, Robert Young, Douglas TI Detection and treatment of subclinical tuberculosis SO TUBERCULOSIS LA English DT Editorial Material DE Detection; Treatment; Subclinical; Tuberculosis ID NONREPLICATING MYCOBACTERIUM-TUBERCULOSIS; RANDOMIZED-TRIAL; SYSTEMS BIOLOGY; STRATEGIES; VACCINE; TB; PREVALENCE; INFECTION; THERAPY AB Reduction of active disease by preventive therapy has the potential to make an important contribution towards the goal of tuberculosis (TB) elimination. This report summarises discussions amongst a Working Group convened to consider areas of research that will be important in optimising the design and delivery of preventative therapies. The Working Group met in Cape Town on 26th February 2012, following presentation of results from the GC11 Grand Challenges in Global Health project to discover drugs for latent TB. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Robertson, Brian D.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Mol Bacteriol & Infect, London SW7 2AZ, England. [Altmann, Danny] Wellcome Trust Res Labs, London, England. [Barry, Clif] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA. [Bishai, Bill] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Cole, Stewart] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland. [Dick, Thomas] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore. [Duncan, Ken; Vandal, Omar] Bill & Melinda Gates Fdn, Seattle, WA USA. [Dye, Chris; Lienhardt, Christian] WHO, Stop TB Dept, CH-1211 Geneva, Switzerland. [Ehrt, Sabine; Schnappinger, Dirk] Weill Cornell Med Coll, New York, NY USA. [Flynn, JoAnne] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Hanekom, Willem; Mizrahi, Valerie; Warner, Digby; Wilkinson, Robert] Univ Cape Town, ZA-7700 Rondebosch, South Africa. [van Helden, Paul; Walzl, Gerhard] Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa. [Kaplan, Gilla] Publ Hlth Res Inst Ctr, Newark, NJ USA. [Kaufmann, Stefan H. E.] Max Planck Inst Infect Biol, Berlin, Germany. [Rubin, Eric] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Sherman, David] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Thole, Jelle] TB Vaccine Initiat, Lelystad, Netherlands. [Wilkinson, Robert; Young, Douglas] Univ London Imperial Coll Sci Technol & Med, MRC Natl Inst Med Res, London SW7 2AZ, England. RP Robertson, BD (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC Ctr Mol Bacteriol & Infect, Flowers Bldg,S Kensington Campus, London SW7 2AZ, England. EM b.robertson@imperial.ac.uk RI Barry, III, Clifton/H-3839-2012; Kaufmann, Stefan HE/I-5454-2014; OI Dye, Christopher/0000-0002-2957-1793; Esmail, Hanif/0000-0002-4278-9316; Walzl, Gerhard/0000-0003-2487-125X; Robertson, Brian D./0000-0001-5785-5307; Kaufmann, Stefan HE/0000-0001-9866-8268; Altmann, Daniel/0000-0002-2436-6192; Rubin, Eric/0000-0001-5120-962X; Wilkinson, Robert/0000-0002-2753-1800 FU Medical Research Council [MC_U117588499]; Wellcome Trust [077381] NR 41 TC 16 Z9 16 U1 0 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 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD NOV PY 2012 VL 92 IS 6 BP 447 EP 452 DI 10.1016/j.tube.2012.06.004 PG 6 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 039PQ UT WOS:000311259400001 PM 22819716 ER PT J AU Ginther, DK Haak, LL Schaffer, WT Kington, R AF Ginther, Donna K. Haak, Laurel L. Schaffer, Walter T. Kington, Raynard TI Are Race, Ethnicity, and Medical School Affiliation Associated With NIH R01 Type 1 Award Probability for Physician Investigators? SO ACADEMIC MEDICINE LA English DT Article ID SCIENCE AB Purpose To analyze the relationship among National Institutes of Health (NIH) R01 Type 1 applicant degree, institution type, and race/ethnicity, and application award probability. Method The authors used 2000-2006 data from the NIH IMPAC II grants database and other sources to determine which individual and institutional characteristics of applicants may affect the probability of applications being awarded funding. They used descriptive statistics and probit models to estimate correlations between race/ethnicity, degree (MD or PhD), and institution type (medical school or other institution), and application award probability, controlling for a large set of observable characteristics. Results Applications from medical schools were significantly more likely than those from other institutions to receive funding, as were applications from MDs versus PhDs. Overall, applications from blacks and Asians were less likely than those from whites to be awarded funding; however, among applications from MDs at medical schools, there was no difference in funding probability between whites and Asians, and the difference between blacks and whites decreased to 7.8%. The inclusion of human subjects significantly decreased the likelihood of receiving funding. Conclusions Compared with applications from whites, applications from blacks have a lower probability of being awarded R01 Type 1 funding, regardless of the investigator's degree. However, funding probability is increased for applications with MD investigators and for those from medical schools. To some degree, these advantages combine so that applications from black MDs at medical schools have the smallest difference in funding probability compared with those from whites. C1 [Ginther, Donna K.] Univ Kansas, Dept Econ, Lawrence, KS 66045 USA. [Ginther, Donna K.] Univ Kansas, Ctr Sci Technol & Econ Policy, Lawrence, KS 66045 USA. [Haak, Laurel L.] Thomson Reuters, Discovery Log, Rockville, MD USA. [Schaffer, Walter T.; Kington, Raynard] NIH, Bethesda, MD 20892 USA. [Kington, Raynard] Grinnell Coll, Grinnell, IA 50112 USA. RP Ginther, DK (reprint author), Univ Kansas, Dept Econ, 1460 Jayhawk Blvd, Lawrence, KS 66045 USA. EM dginther@ku.edu RI Haak, Laurel/C-4986-2008; Ginther, Donna/F-7317-2016; OI Haak, Laurel/0000-0001-5109-3700; Ginther, Donna/0000-0002-0881-7969; Schaffer, Walter/0000-0002-2276-4656 FU NIH [1R01AG36820-01, HHSN276200800458U, HHSN276200900100U, 07-6008 OD OER] FX Dr. Ginther acknowledges financial support from NIH grant 1R01AG36820-01. Dr. Schaffer is an employee of the NIH, and, as a result, the NIH supported this work. Dr. Haak of Discovery Logic, a Thomson Reuters company, acknowledges support from NIH contracts HHSN276200800458U and HHSN276200900100U, made possible through an NIH Evaluation Set-Aside Award to W. T. S. (07-6008 OD OER). NR 22 TC 15 Z9 15 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 2012 VL 87 IS 11 BP 1516 EP 1524 DI 10.1097/ACM.0b013e31826d726b PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 030OI UT WOS:000310579600035 PM 23018334 ER PT J AU Klot, JF Auerbach, JD Veronese, F Brown, G Pei, A Wira, CR Hope, TJ M'boup, S AF Klot, Jennifer F. Auerbach, Judith D. Veronese, Fulvia Brown, Gina Pei, April Wira, Charles R. Hope, Thomas J. M'boup, Souleymane CA Greentree Meeting Sexual Violence TI Greentree White Paper: Sexual Violence, Genitoanal Injury, and HIV: Priorities for Research, Policy, and Practice SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID INTIMATE PARTNER VIOLENCE; GENDER-BASED VIOLENCE; HEALTHY-YOUNG WOMEN; SOUTH-AFRICA; ANAL INTERCOURSE; ANOGENITAL INJURY; EPITHELIAL-CELLS; GENITAL INJURY; KENYAN WOMEN; RISK-FACTOR AB The links between sexual violence, genitoanal injury, and HIV are understudied but potentially significant for understanding the epidemic's disproportionate impacts on young women and girls, particularly in sub-Saharan Africa, other hyperendemic areas, and conflict-affected regions. A Scientific Research Planning Meeting was convened by the Social Science Research Council at the Greentree Foundation in New York, March 19-20, 2012, bringing together an interdisciplinary group of researchers, clinicians, and policy makers to identify knowledge needs and gaps in three key areas: (1) the role of genitoanal injury on HIV transmission, acquisition, and pathogenesis; (2) the influence of sex and age-related anatomic characteristics on HIV transmission, acquisition, and pathogenesis; and (3) the role of heterosexual anal intercourse in HIV transmission. This article reflects the consensus that emerged from the Greentree Meeting regarding priority scientific research questions in these three areas, associated data collection and measurement challenges and opportunities, and implications for policy and practice. C1 [Klot, Jennifer F.; Pei, April] Social Sci Res Council, Brooklyn, NY 11201 USA. [Veronese, Fulvia; Brown, Gina] NIH, Bethesda, MD 20892 USA. [Wira, Charles R.] Dartmouth Med Sch, Lebanon, NH USA. [Hope, Thomas J.] Northwestern Univ, Feinberg Sch Med, Evanston, IL USA. [M'boup, Souleymane] Univ Cheikh Anta Diop, Hop Le Dantec, Dakar, Senegal. RP Klot, JF (reprint author), Social Sci Res Council, 15 Pierrepont Plaza, Brooklyn, NY 11201 USA. EM klot@ssrc.org RI Hossain, Mazeda/G-1953-2014; Shacklett, Barbara/A-7288-2009; OI Shacklett, Barbara/0000-0002-7067-732X; Hossain, Mazeda/0000-0002-1878-8145; Klot, Jennifer/0000-0002-0593-4326 FU National Institutes of Health; Office of AIDS Research; UNAIDS; UN Action Against Sexual Violence in Armed Conflict; Greentree Foundation FX Funding for this meeting was provided by the National Institutes of Health, Office of AIDS Research; UNAIDS, UN Action Against Sexual Violence in Armed Conflict and the Greentree Foundation. The authors wish to thank SSRC research assistants and meeting organizers, Miranda Berry, Patience Mungwari, and April Pei. NR 90 TC 9 Z9 9 U1 3 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2012 VL 28 IS 11 BP 1379 EP 1388 DI 10.1089/aid.2012.0273 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 032XP UT WOS:000310754100002 PM 22953712 ER PT J AU Karasavvas, N Billings, E Rao, M Williams, C Zolla-Pazner, S Bailer, RT Koup, RA Madnote, S Arworn, D Shen, XY Tomaras, GD Currier, JR Jiang, M Magaret, C Andrews, C Gottardo, R Gilbert, P Cardozo, TJ Rerks-Ngarm, S Nitayaphan, S Pitisuttithum, P Kaewkungwal, J Paris, R Greene, K Gao, HM Gurunathan, S Tartaglia, J Sinangil, F Korber, BT Montefiori, DC Mascola, JR Robb, ML Haynes, BF Ngauy, V Michael, NL Kim, JH de Souza, MS AF Karasavvas, Nicos Billings, Erik Rao, Mangala Williams, Constance Zolla-Pazner, Susan Bailer, Robert T. Koup, Richard A. Madnote, Sirinan Arworn, Duangnapa Shen, Xiaoying Tomaras, Georgia D. Currier, Jeffrey R. Jiang, Mike Magaret, Craig Andrews, Charla Gottardo, Raphael Gilbert, Peter Cardozo, Timothy J. Rerks-Ngarm, Supachai Nitayaphan, Sorachai Pitisuttithum, Punnee Kaewkungwal, Jaranit Paris, Robert Greene, Kelli Gao, Hongmei Gurunathan, Sanjay Tartaglia, Jim Sinangil, Faruk Korber, Bette T. Montefiori, David C. Mascola, John R. Robb, Merlin L. Haynes, Barton F. Ngauy, Viseth Michael, Nelson L. Kim, Jerome H. de Souza, Mark S. CA MOPH TAVEG Collaboration TI The Thai Phase III HIV Type 1 Vaccine Trial (RV144) Regimen Induces Antibodies That Target Conserved Regions Within the V2 Loop of gp120 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT GLYCOPROTEIN-120 VACCINE; QUATERNARY NEUTRALIZING EPITOPE; HIV-1/SIV CHIMERIC VIRUS; ENVELOPE GLYCOPROTEIN; EFFICACY TRIAL; HETEROSEXUAL TRANSMISSION; INTEGRIN ALPHA(4)BETA(7); MONOCLONAL-ANTIBODIES; CANARYPOX VACCINE AB The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200-3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100-200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169-184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100-800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p = 0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100-3200) and 3570 (range: 200-12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition. C1 [Karasavvas, Nicos; Madnote, Sirinan; Arworn, Duangnapa; Ngauy, Viseth; de Souza, Mark S.] Armed Forces Res Inst Med Sci, US Army Med Component, Dept Retrovirol, Bangkok 10400, Thailand. [Billings, Erik; Currier, Jeffrey R.; Andrews, Charla; Robb, Merlin L.] Henry M Jackson Fdn Adv Mil Med, US Mil HIV Res Program MHRP, Rockville, MD USA. [Rao, Mangala; Paris, Robert; Michael, Nelson L.; Kim, Jerome H.] Walter Reed Army Inst Res, USMHRP, Silver Spring, MD USA. [Williams, Constance; Zolla-Pazner, Susan; Cardozo, Timothy J.] NYU, Sch Med, Dept Pathol, New York, NY USA. [Williams, Constance; Zolla-Pazner, Susan; Cardozo, Timothy J.] NYU, Sch Med, Dept Pharmacol, New York, NY USA. [Zolla-Pazner, Susan] Vet Affairs Harbor Healthcare Syst, New York, NY USA. [Bailer, Robert T.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Shen, Xiaoying; Tomaras, Georgia D.; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Jiang, Mike; Magaret, Craig; Gottardo, Raphael; Gilbert, Peter] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA. [Rerks-Ngarm, Supachai] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand. [Nitayaphan, Sorachai] Armed Forces Res Inst Med Sci, Royal Thai Army Component, Bangkok 10400, Thailand. [Pitisuttithum, Punnee] Mahidol Univ, Fac Trop Med, Vaccine Trial Ctr, Bangkok, Thailand. [Pitisuttithum, Punnee] Mahidol Univ, Fac Trop Med, Dept Clin Trop Med, Bangkok, Thailand. [Kaewkungwal, Jaranit] Mahidol Univ, Fac Trop Med, Ctr Excellence Biomed & Publ Hlth Informat BIOPHI, Bangkok, Thailand. [Paris, Robert] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Greene, Kelli; Gao, Hongmei; Montefiori, David C.; Mascola, John R.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Gurunathan, Sanjay; Tartaglia, Jim] Sanofi Pasteur, Swiftwater, PA USA. [Sinangil, Faruk] Global Solut Infect Dis, San Francisco, CA USA. [Korber, Bette T.] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA. RP Karasavvas, N (reprint author), Armed Forces Res Inst Med Sci, US Army Med Component, Dept Retrovirol, 315-6 Rajvithi Rd, Bangkok 10400, Thailand. EM karasavvan@afrims.org RI Tomaras, Georgia/J-5041-2016; OI Korber, Bette/0000-0002-2026-5757 FU U.S. Army Medical Research and Materiel Command (USAMRMC) [Y1-AI-2642-12]; National Institutes of Allergy and Infectious Diseases; Henry M. Jackson Foundation for the Advancement of Military Medicine [W81XWH-07-2-0067]; U.S. Department of Defense [W81XWH-07-2-0067]; U.S. National Institute of Allergy and Infectious Diseases; Bill and Melinda Gates Foundation [OPP38744]; NIH Vaccine Research Center; NIH [HL59725, AI084119]; Department of Veterans Affairs; Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery FX The authors thank SCHARP for assisting with the microarray analysis, James Swetnam for providing the biotinylated subtype B linear peptides, Kelly Soderberg for coordination of sample shipment and project management, Rob O'Connell for constructive reading of the manuscript, Robert Parks, Ryan Meyerhoff, and Krissey Lloyd for ELISA technical assistance, and Ellen Turk for performing the peptide microarray analysis. These studies were supported in part by an Interagency Agreement Y1-AI-2642-12 between U.S. Army Medical Research and Materiel Command (USAMRMC) and the National Institutes of Allergy and Infectious Diseases. In addition, this work was supported by a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Department of Defense. This research was funded, in part, by the U.S. National Institute of Allergy and Infectious Diseases. Peptide microarray work was funded by the Bill and Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery (OPP38744) and the NIH Vaccine Research Center. S.Z.P. and T.J.C. receive funding from NIH Grants HL59725 (S.Z.P.) and AI084119 (T.J.C.) and the Department of Veterans Affairs. Supported in part by grants from the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery to Dr. Haynes. NR 69 TC 82 Z9 82 U1 4 U2 16 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2012 VL 28 IS 11 BP 1444 EP 1457 DI 10.1089/aid.2012.0103 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 032XP UT WOS:000310754100009 PM 23035746 ER PT J AU Solomon, BD Muenke, M AF Solomon, Benjamin D. Muenke, Maximilian TI When to Suspect a Genetic Syndrome SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID FAMILY-HISTORY; DISORDERS; DISEASE; CARE; MALFORMATIONS; DIAGNOSIS AB Family physicians should be able to recognize findings on physical examination and history that suggest the presence of a genetic syndrome to aid in the diagnosis and treatment of potentially affected patients, as well as subspecialty referral. General themes that can alert family physicians to the presence of genetic conditions include dysmorphic features that are evident on physical examination; multiple anomalies in one patient; unexplained neurocognitive impairment; and a family history that is suggestive of a hereditary disease. The presence of one obvious malformation should not limit the full evaluation, because additional, subtler findings will often be important in the differential diagnosis. Taking an accurate three-generation family history is invaluable when considering a genetic syndrome. Important elements include the age and sex of family members; when family members were affected by disease or when they died; the ethnic background; and if there is consanguinity. Genetic subspecialists can assist family physicians in diagnosis, suggest additional testing and referrals if warranted, help direct medical care, and provide counseling for affected patients and their families. (Am Fam Physician. 2012;86(9):826-833. Copyright (C) 2012 American Academy of Family Physicians.) C1 [Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Muenke, Maximilian] NHGRI, Med Genet Residency Training Program, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, 35 Convent Dr,Room 1B203,MSC 3717, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, Md FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, Md. NR 33 TC 1 Z9 1 U1 0 U2 1 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD NOV 1 PY 2012 VL 86 IS 9 BP 826 EP 833 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 033TO UT WOS:000310824200008 PM 23113462 ER PT J AU Bilous, RW Gonzalez-Campoy, JM Fradkin, JE Mauer, M Molitch, ME Narva, AS Nelson, RG Sharma, K Tuttle, KR Rocco, MV Berns, JS Wilt, TJ Ishani, A Rector, TS Slinin, Y Fitzgerald, P Carlyle, M AF Bilous, Rudolf W. Gonzalez-Campoy, J. Michael Fradkin, Judith E. Mauer, Michael Molitch, Mark E. Narva, Andrew S. Nelson, Robert G. Sharma, Kumar Tuttle, Katherine R. Rocco, Michael V. Berns, Jeffrey S. Wilt, Timothy J. Ishani, Areef Rector, Thomas S. Slinin, Yelena Fitzgerald, Patrick Carlyle, Maureen TI KDOQI CLINICAL PRACTICE GUIDELINE FOR DIABETES AND CKD: 2012 UPDATE SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Albuminuria; chronic kidney disease; Clinical Practice Guideline; diabetes; dyslipidemia; evidence-based recommendation; KDOQI ID CHRONIC KIDNEY-DISEASE; BLOOD-GLUCOSE CONTROL; PLACEBO-CONTROLLED TRIAL; IMPAIRED RENAL-FUNCTION; CONVERTING ENZYME-INHIBITION; RANDOMIZED CONTROLLED-TRIAL; IMPROVING GLOBAL OUTCOMES; ALBUMIN EXCRETION RATE; GLYCEMIC CONTROL; SEVERE HYPOGLYCEMIA AB The 2012 update of the Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guideline for Diabetes and Chronic Kidney Disease (CKD) is intended to assist the practitioner caring for patients with diabetes and CKD. Substantial high-quality new evidence has emerged since the original 2007 KDOQI guideline that could significantly change recommendations for clinical practice. As such, revisions of prior guidelines are offered that specifically address hemoglobin A(1c) (HbA(1c)) targets, treatments to lower low-density lipoprotein cholesterol (LDL-C) levels, and use of angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) treatment in diabetic patients with and without albuminuria. Treatment approaches are addressed in each section and the stated guideline recommendations are based on systematic reviews of relevant trials. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Limitations of the evidence are discussed and specific suggestions are provided for future research. C1 [Bilous, Rudolf W.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Bilous, Rudolf W.] James Cook Univ Hosp, Middlesbrough, Cleveland, England. [Bilous, Rudolf W.] NIH, Metab Med Unit, Bethesda, MD 20892 USA. [Bilous, Rudolf W.] Univ Minnesota, JDRF, Minneapolis, MN 55455 USA. [Gonzalez-Campoy, J. Michael; Mauer, Michael] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Gonzalez-Campoy, J. Michael] NIDDK, Div Diabet Endocrinol & Metab Dis DEMD, NIH, Bethesda, MD 20892 USA. [Fradkin, Judith E.] Yale Univ, New Haven, CT 06520 USA. [Fradkin, Judith E.] Ctr Dis Control & Prevent, Natl Diabet Educ Program, Atlanta, GA USA. [Fradkin, Judith E.] Natl Naval Med Ctr, Bethesda, MD USA. [Molitch, Mark E.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Evanston, IL 60208 USA. [Molitch, Mark E.] Univ Calif Los Angeles, Harbor Gen Hosp, Los Angeles, CA 90024 USA. [Narva, Andrew S.] NIDDK, Natl Kidney Dis Educ Program, Bethesda, MD 20892 USA. [Nelson, Robert G.] NIDDK, Phoenix, AZ USA. [Sharma, Kumar] Univ Calif San Diego, Ctr Renal Translat Med, San Diego, CA 92103 USA. [Tuttle, Katherine R.] Providence Sacred Heart Med Ctr, Spokane, WA USA. [Tuttle, Katherine R.] Natl Diabet Educ Program NIH & CDC, Healthcare Profess Work Grp, Bethesda, MD 20892 USA. [Tuttle, Katherine R.] Inst Review Board, Spokane, WA USA. [Tuttle, Katherine R.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Tuttle, Katherine R.] Washington State Univ, Pullman, WA 99164 USA. [Rocco, Michael V.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Berns, Jeffrey S.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Berns, Jeffrey S.] Univ Penn, Sch Med, Penn Presbyterian Med Ctr Philadelphia, Philadelphia, PA 19104 USA. [Wilt, Timothy J.; Rector, Thomas S.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Ishani, Areef] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [Fitzgerald, Patrick] CCDOR, Minneapolis, MN USA. [Carlyle, Maureen] Minneapolis VA Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Carlyle, Maureen] Univ Minnesota, Minnesota Evidence Based Practice Ctr, Minneapolis, MN 55455 USA. NR 115 TC 0 Z9 0 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2012 VL 60 IS 5 BP 858 EP + PG 30 WC Urology & Nephrology SC Urology & Nephrology GA 029PO UT WOS:000310508100041 ER PT J AU Heselmeyer-Haddad, K Garcia, LYB Bradley, A Ortiz-Melendez, C Lee, WJ Christensen, R Prindiville, SA Calzone, KA Soballe, PW Hu, Y Chowdhury, SA Schwartz, R Schaffer, AA Ried, T AF Heselmeyer-Haddad, Kerstin Garcia, Lissa Y. Berroa Bradley, Amanda Ortiz-Melendez, Clarymar Lee, Woei-Jyh Christensen, Rebecca Prindiville, Sheila A. Calzone, Kathleen A. Soballe, Peter W. Hu, Yue Chowdhury, Salim A. Schwartz, Russell Schaeffer, Alejandro A. Ried, Thomas TI Single-Cell Genetic Analysis of Ductal Carcinoma in Situ and Invasive Breast Cancer Reveals Enormous Tumor Heterogeneity yet Conserved Genomic Imbalances and Gain of MYC during Progression SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COPY-NUMBER ALTERATION; EXPRESSION PROFILES; SERIAL ANALYSIS; HER2 STATUS; HYBRIDIZATION; AMPLIFICATION; METASTASIS; EVOLUTION; ADJACENT; INSTABILITY AB Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC. Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances. CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC. Four of 13 DCISs showed identical clonal imbalances in the IDCs. Six cases revealed a switch, and in four of those, the IDC had acquired a gain of MYC. In one case, the major clone in the MC was one of several clones in the DCIS, and in another case, the major clone in the DCIS became one of the two major clones in the IDC. Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum. (Am J Pathol 2012, 181: 1807-1822; http://dx.doi.org/10.1016/j.ajpath.2012.07.012) C1 [Heselmeyer-Haddad, Kerstin; Garcia, Lissa Y. Berroa; Bradley, Amanda; Ortiz-Melendez, Clarymar; Calzone, Kathleen A.; Hu, Yue; Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lee, Woei-Jyh; Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Christensen, Rebecca; Soballe, Peter W.] Natl Naval Med Ctr, Bethesda, MD USA. [Prindiville, Sheila A.] NCI, Coordinating Ctr Clin Trials, Rockville, MD USA. [Chowdhury, Salim A.] Carnegie Mellon Univ, Joint Carnegie Mellon Univ Pittsburgh PhD Program, Pittsburgh, PA 15213 USA. [Chowdhury, Salim A.; Schwartz, Russell] Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Schwartz, Russell] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. RP Heselmeyer-Haddad, K (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bldg 50,Room 1408,50 South Dr, Bethesda, MD 20892 USA. EM heselmek@mail.nih.gov RI Schwartz, Russell/A-1998-2016 OI Schwartz, Russell/0000-0002-4970-2252 FU NIH, National Cancer Institute; National Library of Medicine; NIH [1R01CA140214, 1R01AI076318] FX Supported in part by the Intramural Research Program of the NIH, National Cancer Institute, and National Library of Medicine and by NIH grants 1R01CA140214 (R.S. and S.A.C.) and 1R01AI076318 (R.S.). NR 63 TC 36 Z9 37 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 NOV PY 2012 VL 181 IS 5 BP 1807 EP 1822 DI 10.1016/j.ajpath.2012.07.012 PG 16 WC Pathology SC Pathology GA 031QK UT WOS:000310656800030 PM 23062488 ER PT J AU Brown, KS Ebihara, H Feldmann, H AF Brown, Kyle S. Ebihara, Hideki Feldmann, Heinz TI Development of a minigenome system for Andes virus, a New World hantavirus SO ARCHIVES OF VIROLOGY LA English DT Article ID HEMORRHAGIC-FEVER VIRUS; REVERSE GENETICS; L-PROTEIN; PULMONARY SYNDROME; TULA-HANTAVIRUS; L-POLYMERASE; RNA; TRANSCRIPTION; EXPRESSION; RESCUE AB The development of reverse genetics systems for negative-stranded RNA viruses is a rapidly evolving field that has greatly advanced the study of the many different aspects of the viral life cycle. Andes virus (ANDV) is a highly pathogenic hantavirus found in South America that causes hantavirus pulmonary syndrome but to date remains poorly characterized due to the lack of a reverse genetics system for genetic manipulation. Here, we describe the first successful minigenome system for a New World hantavirus, as well as many of the obstacles that still exist in the development of such a system. C1 [Ebihara, Hideki; Feldmann, Heinz] NIAID, Div Intramural Res, Virol Lab, NIH,Rocky Mt Labs, Hamilton, MT USA. [Brown, Kyle S.; Feldmann, Heinz] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada. [Brown, Kyle S.; Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. RP Feldmann, H (reprint author), NIAID, Div Intramural Res, Virol Lab, NIH,Rocky Mt Labs, Hamilton, MT USA. EM feldmannh@niaid.nih.gov FU National Microbiology Laboratory of the Public Health Agency of Canada FX This work funded by the National Microbiology Laboratory of the Public Health Agency of Canada. The work was part of the Ph.D. thesis of KSB. Thank you to Dr. Connie Schmaljohn, U.S Army Medical Research Institute of Infectious Diseases, Ft. Detrick, MD for providing the Andes virus, strain Chile 9717869. NR 29 TC 7 Z9 7 U1 1 U2 5 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD NOV PY 2012 VL 157 IS 11 BP 2227 EP 2233 DI 10.1007/s00705-012-1401-0 PG 7 WC Virology SC Virology GA 031AK UT WOS:000310611100021 PM 22821183 ER PT J AU Soto-Pantoja, DR Miller, TW Pendrak, ML DeGraff, WG Sullivan, C Ridnour, LA Abu-Asab, M Wink, DA Tsokos, M Roberts, DD AF Soto-Pantoja, David R. Miller, Thomas W. Pendrak, Michael L. DeGraff, William G. Sullivan, Camille Ridnour, Lisa A. Abu-Asab, Mones Wink, David A. Tsokos, Maria Roberts, David D. TI CD47 deficiency confers cell and tissue radioprotection by activation of autophagy SO AUTOPHAGY LA English DT Article DE CD47; autophagosome; ionizing radiation; MAP1A/1BLC3; ATG5; ATG7; p62; BECN1 ID INTEGRATED STRESS-RESPONSE; ISCHEMIA-REPERFUSION INJURY; RIBOSOME ENTRY SITE; BREAST-TUMOR CELLS; MESSENGER-RNA; CANCER-CELLS; THROMBOSPONDIN-1; RADIATION; APOPTOSIS; DEATH AB Accidental or therapeutic exposure to ionizing radiation has severe physiological consequences and can result in cell death. We previously demonstrated that deficiency or blockade of the ubiquitously expressed receptor CD47 results in remarkable cell and tissue protection against ischemic and radiation stress. Antagonists of CD47 or its ligand THBS1/thrombospondin 1 enhance cell survival and preserve their proliferative capacity. However the signaling pathways that mediate this cell-autonomous radioprotection are unclear. We now report a marked increase in autophagy in irradiated T-cells and endothelial cells lacking CD47. Irradiated T cells lacking CD47 exhibit significant increases in formation of autophagosomes comprising double-membrane vesicles visualized by electron microscopy and numbers of MAP1LC3A/B+ puncta. Moreover, we observed significant increases in BECN1, ATG5, ATG7 and a reduction in SQSTM1/p62 expression relative to irradiated wild-type T cells. We observed similar increases in autophagy gene expression in mice resulting from blockade of CD47 in combination with total body radiation. Pharmacological or siRNA-mediated inhibition of autophagy selectively sensitized CD47-deficient cells to radiation, indicating that enhanced autophagy is necessary for the prosurvival response to CD47 blockade. Moreover, re-expression of CD47 in CD47-deficient T cells sensitized these cells to death by ionizing radiation and reversed the increase in autophagic flux associated with survival. This study indicates that CD47 deficiency confers cell survival through the activation of autophagic flux and identifies CD47 blockade as a pharmacological route to modulate autophagy for protecting tissue from radiation injury. C1 [Soto-Pantoja, David R.; Miller, Thomas W.; Pendrak, Michael L.; Sullivan, Camille; Abu-Asab, Mones; Tsokos, Maria; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [DeGraff, William G.; Ridnour, Lisa A.; Wink, David A.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Abu-Asab, Mones] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Miller, Thomas/G-1215-2011; OI Roberts, David/0000-0002-2481-2981; Miller, Thomas/0000-0001-8645-2785; Abu-Asab, Mones/0000-0002-4047-1232 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; NCI FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research (D.D.R., D.A.W., M.T.) and an NCI Director's Career Development Innovation Award (D.R.S.-P.). NR 53 TC 29 Z9 30 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD NOV PY 2012 VL 8 IS 11 BP 1628 EP 1642 DI 10.4161/auto.21562 PG 15 WC Cell Biology SC Cell Biology GA 033WC UT WOS:000310831100006 PM 22874555 ER PT J AU Hsu, S Kim, M Hernandez, L Grajales, V Noonan, A Anver, M Davidson, B Annunziata, CM AF Hsu, Sarah Kim, Marianne Hernandez, Lidia Grajales, Valentina Noonan, Anne Anver, Miriam Davidson, Ben Annunziata, Christina M. TI IKK-epsilon Coordinates Invasion and Metastasis of Ovarian Cancer SO CANCER RESEARCH LA English DT Article ID NICOTINAMIDE N-METHYLTRANSFERASE; BREAST-CANCER; IN-VITRO; KAPPA-B; EXPRESSION; CARCINOMA; INHIBITOR; MIGRATION; ONCOGENE; IKBKE AB Inhibitor of I kappa B kinases (IKK) are key regulators of NF-kappa B signaling. Three IKK isoforms-alpha, beta, and epsilon-have been linked to oncogenesis, yet the precise components of NF-kappa B signaling in ovarian cancer have not yet been dissected. We surveyed 120 ovarian cancer specimens for IKK-epsilon expression. Notably, cytoplasmic expression was elevated in metastatic lesions relative to primary tumors (P=0.03). Therefore, we hypothesized that IKK-epsilon drives ovarian cancer metastasis. IKK-epsilon was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. We now define an ovarian cancer-specific IKK-epsilon-regulated gene expression signature using stably expressed short hairpin RNA targeting IKK-epsilon. Pathway analysis of the signature indicated that IKK-epsilon regulates expression of genes involved in cell motility and inflammation. We further showed that IKK-epsilon depletion in metastatic ovarian cancer cell lines decreased growth, adhesion, and invasion. Consistently, human xenografts depleted of IKK-epsilon in mice showed decreased aggressiveness, whereas overexpression of IKK-epsilon in a less invasive ovarian cancer cell line increased metastasis in vivo. Taken together, these data provide evidence that IKK-epsilon is a key coordinator of invasion and metastasis programs in ovarian cancer. Inhibition of IKK-epsilon signaling thus emerges as a viable therapeutic strategy in women whose ovarian cancer shows aberrant activation of this pathway. Cancer Res; 72(21); 5494-504. (C)2012 AACR. C1 [Annunziata, Christina M.] NCI, NIH, Med Oncol Branch, Bethesda, MD USA. [Anver, Miriam] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Vet Pathol Sect, Frederick, MD USA. [Davidson, Ben] Oslo Univ Hosp, Div Pathol, Oslo, Norway. RP Annunziata, CM (reprint author), NCI, NIH, Med Oncol Branch, 10 Ctr Dr,Room 12N226, Bethesda, MD USA. EM annunzic@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 FU Intramural Research Program, CCR, NCI; NIH [K99CA151746]; Norwegian Cancer Society and Health Region of South-Eastern Norway; NCI, NIH [HSN261200800001E] FX This work was supported by the Intramural Research Program, CCR, NCI (C. M. Annunziata), NIH Grant K99CA151746 (C. M. Annunziata), and the Norwegian Cancer Society and Health Region of South-Eastern Norway (to B. Davidson), and with Federal funds from the NCI, NIH, under contract number HSN261200800001E. NR 25 TC 15 Z9 16 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2012 VL 72 IS 21 BP 5494 EP 5504 DI 10.1158/0008-5472.CAN-11-3993 PG 11 WC Oncology SC Oncology GA 030PG UT WOS:000310582000008 PM 22942254 ER PT J AU Manzoor, AA Lindner, LH Landon, CD Park, JY Simnick, AJ Dreher, MR Das, S Hanna, G Park, W Chilkoti, A Koning, GA ten Hagen, TLM Needham, D Dewhirst, MW AF Manzoor, Ashley A. Lindner, Lars H. Landon, Chelsea D. Park, Ji-Young Simnick, Andrew J. Dreher, Matthew R. Das, Shiva Hanna, Gabi Park, Won Chilkoti, Ashutosh Koning, Gerben A. ten Hagen, Timo L. M. Needham, David Dewhirst, Mark W. TI Overcoming Limitations in Nanoparticle Drug Delivery: Triggered, Intravascular Release to Improve Drug Penetration into Tumors SO CANCER RESEARCH LA English DT Article ID TEMPERATURE-SENSITIVE LIPOSOMES; SOLID TUMORS; THERMOSENSITIVE LIPOSOMES; LOCAL HYPERTHERMIA; SELECTIVE DELIVERY; MILD HYPERTHERMIA; XENOGRAFT MODEL; BLOOD-VESSELS; MURINE TUMORS; IN-VITRO AB Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumors. The enhanced permeability and retention effect can permit passive accumulation into tumor interstitium. However, suboptimal delivery is achieved with most nanoparticles because of heterogeneities of vascular permeability, which limits nanoparticle penetration. Furthermore, slow drug release limits bioavailability. We developed a fast drug-releasing liposome triggered by local heat that has already shown substantial antitumor efficacy and is in human trials. Here, we show that thermally sensitive liposomes (Dox-TSL) release doxorubicin inside the tumor vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors in window chambers and histologic analysis of flank tumors illustrates that intravascular drug release increases free drug in the interstitial space. This increases both the time that tumor cells are exposed to maximum drug levels and the drug penetration distance, compared with free drug or traditional pegylated liposomes. These improvements in drug bioavailability establish a new paradigm in drug delivery: rapidly triggered drug release in the tumor bloodstream. Cancer Res; 72(21); 5566-75. (C)2012 AACR. C1 [Manzoor, Ashley A.; Landon, Chelsea D.; Park, Ji-Young; Das, Shiva; Hanna, Gabi; Park, Won; Dewhirst, Mark W.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. [Manzoor, Ashley A.; Das, Shiva; Dewhirst, Mark W.] Duke Univ, Med Phys Program, Durham, NC USA. [Simnick, Andrew J.; Chilkoti, Ashutosh; Needham, David; Dewhirst, Mark W.] Duke Univ, Dept Biomed Engn, Durham, NC USA. [Lindner, Lars H.; Koning, Gerben A.; ten Hagen, Timo L. M.] Erasmus MC, Dept Surg, Sect Surg Oncol, Lab Expt Surg Oncol, Rotterdam, Netherlands. [Lindner, Lars H.] Univ Munich, Univ Hosp Grosshadern, Dept Internal Med 3, Munich, Germany. [Lindner, Lars H.] German Res Ctr Environm Hlth, CCG Hyperthermia, Helmholtz Zentrum Munchen, Munich, Germany. [Dreher, Matthew R.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Dewhirst, MW (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3455,Med Sci Res Bldg,Rm 201, Durham, NC 27710 USA. EM mark.dewhirst@duke.edu RI Koning, Gerben/K-2326-2012; OI Koning, Gerben/0000-0003-3090-2403; Lindner, Lars/0000-0003-3708-8264 FU NIH/National Cancer Institute [CA42745-21, CA42745-22, CA42745-23]; NIH/National Center for Complementary and Alternative Medicine [1F31ATT006644-01]; Department of Defense [W81XWH-09-1-0115]; Center for Interventional Radiology, the intramural research program of the NIH; Dr. Mildred Scheel Stiftung fuer Krebsforschung (Deutsche Krebshilfe e.V.) FX This work was supported by funding provided by grants from the NIH/National Cancer Institute CA42745-21, 22, 23, NIH/National Center for Complementary and Alternative Medicine 1F31ATT006644-01, and Department of Defense W81XWH-09-1-0115. Financial support was also provided by the Center for Interventional Radiology, the intramural research program of the NIH, and by a research grant from the "Dr. Mildred Scheel Stiftung fuer Krebsforschung (Deutsche Krebshilfe e.V.)." NR 49 TC 136 Z9 138 U1 14 U2 134 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2012 VL 72 IS 21 BP 5566 EP 5575 DI 10.1158/0008-5472.CAN-12-1683 PG 10 WC Oncology SC Oncology GA 030PG UT WOS:000310582000015 PM 22952218 ER PT J AU Murai, J Huang, SYN Das, BB Renaud, A Zhang, YP Doroshow, JH Ji, JP Takeda, S Pommier, Y AF Murai, Junko Huang, Shar-yin N. Das, Benu Brata Renaud, Amelie Zhang, Yiping Doroshow, James H. Ji, Jiuping Takeda, Shunichi Pommier, Yves TI Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors SO CANCER RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE; DNA-DAMAGE; HOMOLOGOUS RECOMBINATION; EXCISION-REPAIR; CANCER-CELLS; STABILITY; PATHWAYS; TUMORS; XRCC1 AB Small-molecule inhibitors of PARP are thought to mediate their antitumor effects as catalytic inhibitors that block repair of DNA single-strand breaks (SSB). However, the mechanism of action of PARP inhibitors with regard to their effects in cancer cells is not fully understood. In this study, we show that PARP inhibitors trap the PARP1 and PARP2 enzymes at damaged DNA. Trapped PARP-DNA complexes were more cytotoxic than unrepaired SSBs caused by PARP inactivation, arguing that PARP inhibitors act in part as poisons that trap PARP enzyme on DNA. Moreover, the potency in trapping PARP differed markedly among inhibitors with niraparib (MK-4827) > olaparib (AZD-2281) >> veliparib (ABT-888), a pattern not correlated with the catalytic inhibitory properties for each drug. We also analyzed repair pathways for PARP-DNA complexes using 30 genetically altered avian DT40 cell lines with preestablished deletions in specific DNA repair genes. This analysis revealed that, in addition to homologous recombination, postreplication repair, the Fanconi anemia pathway, polymerase beta, and FEN1 are critical for repairing trapped PARP-DNA complexes. In summary, our study provides a new mechanistic foundation for the rational application of PARP inhibitors in cancer therapy. Cancer Res; 72(21); 5588-99. (C)2012 AACR. C1 [Murai, Junko; Huang, Shar-yin N.; Das, Benu Brata; Renaud, Amelie; Doroshow, James H.; Pommier, Yves] NCI, 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. [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, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Japan Society for the Promotion of Science (JSPS); Intramural Program of the National Cancer Institute, Center for Cancer Research; JSPS Core-to-Core Program FX J. Murai is a recipient of a fellowship from the Japan Society for the Promotion of Science (JSPS). This work was supported by the Intramural Program of the National Cancer Institute, Center for Cancer Research, and by the JSPS Core-to-Core Program. NR 50 TC 290 Z9 293 U1 11 U2 51 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2012 VL 72 IS 21 BP 5588 EP 5599 DI 10.1158/0008-5472.CAN-12-2753 PG 12 WC Oncology SC Oncology GA 030PG UT WOS:000310582000017 PM 23118055 ER PT J AU Stabile, LP Rothstein, ME Cunningham, DE Land, SR Dacic, S Keohavong, P Siegfried, JM AF Stabile, Laura P. Rothstein, Mary E. Cunningham, Diana E. Land, Stephanie R. Dacic, Sanja Keohavong, Phouthone Siegfried, Jill M. TI Prevention of tobacco carcinogen-induced lung cancer in female mice using antiestrogens SO CARCINOGENESIS LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; HORMONE REPLACEMENT THERAPY; HEPATOCYTE GROWTH-FACTOR; BREAST-CANCER; AROMATASE INHIBITORS; POSTMENOPAUSAL WOMEN; GENE-EXPRESSION; MACROPHAGES; SURVIVAL; BETA AB Increasing evidence shows that estrogens are involved in lung cancer proliferation and progression, and most human lung tumors express estrogen receptor beta (ER beta) as well as aromatase. To determine if the aromatase inhibitor anastrozole prevents development of lung tumors induced by a tobacco carcinogen, alone or in combination with the ER antagonist fulvestrant, ovariectomized female mice received treatments with the tobacco carcinogen 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) along with daily supplements of androstenedione, the substrate for aromatase. Placebo, anastrozole and/or fulvestrant were administered in both an initiation and a promotion protocol of lung tumorigenesis. The combination of fulvestrant and anastrozole given during NNK exposure resulted in significantly fewer NNK-induced lung tumors (mean = 0.5) compared with placebo (mean = 4.6, P < 0.001), fulvestrant alone (mean = 3.4, P < 0.001) or anastrozole alone (mean = 2.8, P = 0.002). A significantly lower Ki67 cell proliferation index was also observed compared with single agent and control treatment groups. Beginning antiestrogen treatment after NNK exposure, when preneoplastic lesions had already formed, also yielded maximum antitumor effects with the combination. Aromatase expression was found mainly in macrophages infiltrating preneoplastic and tumorous areas of the lungs, whereas ER beta was found in both macrophages and tumor cells. Antiestrogens, especially in combination, effectively inhibited tobacco carcinogen-induced murine lung tumorigenesis and may have application for lung cancer prevention. An important source of estrogen synthesis may be inflammatory cells that infiltrate the lungs in response to carcinogens, beginning early in the carcinogenesis process. ER beta expressed by inflammatory and neoplastic epithelial cells in the lung may signal in response to local estrogen production. C1 [Stabile, Laura P.; Rothstein, Mary E.; Siegfried, Jill M.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. [Cunningham, Diana E.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA. [Dacic, Sanja] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. [Keohavong, Phouthone] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Land, Stephanie R.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Stabile, LP (reprint author), Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. EM las22@pitt.edu OI Keohavong, Phouthone/0000-0001-7812-4925 FU SPORE in Lung Cancer [P50 CA090440]; Comprehensive Cancer Center award [P30CA047904]; [R21 CA129260] FX Supported by P50 CA090440, SPORE in Lung Cancer, to J.M.S. and R21 CA129260 to P.K.. This project used the UPCI Animal Facility and Tissue and Research Pathology Services Facility and was supported in part by the Comprehensive Cancer Center award P30CA047904. NR 49 TC 13 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2012 VL 33 IS 11 BP 2181 EP 2189 DI 10.1093/carcin/bgs260 PG 9 WC Oncology SC Oncology GA 031FL UT WOS:000310624400020 PM 22859269 ER PT J AU John, K Pratt, M Beland, FA Churchwell, MI McMullen, G Olivero, OA Pogribny, IP Poirier, MC AF John, Kaarthik Pratt, M. Margaret Beland, Frederick A. Churchwell, Mona I. McMullen, Gail Olivero, Ofelia A. Pogribny, Igor P. Poirier, Miriam C. TI Benzo[a]pyrene (BP) DNA adduct formation in DNA repair-deficient p53 haploinsufficient [Xpa(-/-)p53(+/-)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-A; METABOLIZING-ENZYMES; MASS-SPECTROMETRY; TUMOR-DEVELOPMENT; ULTRAVIOLET-B; MOUSE MODELS; XPA MICE; GENE XPA AB We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a] pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(-/-)p53(+/-) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N-2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(-/-) p53(+/-) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(-/-) p53(+/-) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(-/-) p53(+/-) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP-DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(-/-) p53(+/-) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH-DNA adduct levels consistently in human organs. C1 [John, Kaarthik; Pratt, M. Margaret; Olivero, Ofelia A.; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bethesda, MD 20892 USA. US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Beland, Frederick A.; Churchwell, Mona I.; Pogribny, Igor P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [McMullen, Gail] NCI, Off Director, NIH, Bethesda, MD 20892 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov FU Intramural Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD FX This study was funded by the Intramural Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 45 TC 2 Z9 4 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2012 VL 33 IS 11 BP 2236 EP 2241 DI 10.1093/carcin/bgs247 PG 6 WC Oncology SC Oncology GA 031FL UT WOS:000310624400026 PM 22828138 ER PT J AU Lao, HC Akunda, JK Chun, KS Flake, GP Yuspa, SH Langenbach, R AF Lao, Huei-Chen Akunda, Jacqueline K. Chun, Kyung-Soo Flake, Gordon P. Yuspa, Stuart H. Langenbach, Robert TI Genetic ablation of cyclooxygenase-2 in keratinocytes produces a cell-autonomous defect in tumor formation SO CARCINOGENESIS LA English DT Article ID GROWTH-FACTOR RECEPTOR; INDUCED SKIN CARCINOGENESIS; EPITHELIAL-CELLS; MOUSE SKIN; CANCER; INHIBITION; CHEMOPREVENTION; ANGIOGENESIS; EXPRESSION; CARCINOMA AB Using a mouse skin tumor model, we reported previously that cyclooxygenase-2 (COX-2) deficiency reduced papilloma formation. However, this model did not differentiate between the effects of systemic COX-2-deficiency and keratinocyte-specific COX-2 deficiency on tumor formation. To determine whether keratinocyte-specific COX-2 deficiency reduced papilloma formation, v-H-ras-transformed COX-2+/+ and COX-2-/- keratinocytes were grafted onto nude mice and tumor development was compared. Transformed COX-2+/+ and COX-2-/- keratinocytes expressed similar levels of H-ras, epidermal growth factor receptor and phospho-extracellular signal-regulated kinase1/2 in vitro; and COX-2-deficiency did not reduce uninfected or v-H-ras infected keratinocyte replication. In contrast, tumors arising from grafted transformed COX-2+/+ and COX-2-/- keratinocytes expressed similar levels of H-ras, but COX-2 deficiency reduced phospho-extracellular signal-regulated kinase 1/2 and epidermal growth factor receptor levels 50-60% and tumor volume by 80% at 3 weeks. Two factors appeared to account for the reduced papilloma size. First, papillomas derived from COX-2-/- keratinocytes showed about 70% decreased proliferation, as measured by bromodeoxyuridine incorporation, compared with papillomas derived from COX-2+/+ keratinocytes. Second, keratin 1 immunostaining of papillomas indicated that COX-2-/- keratinocytes prematurely initiated terminal differentiation. Differences in the levels of apoptosis and vascularization did not appear to be contributing factors as their levels were similar in tumors derived from COX-2-/- and COX-2+/+ keratinocytes. Overall, the data are in agreement with our previous observations that decreased papilloma number and size on COX-2-/- mice resulted from reduced keratinocyte proliferation and accelerated keratinocyte differentiation. Furthermore, the data indicate that deficiency/inhibition of COX-2 in the initiated keratinocyte is an important determinant of papilloma forming ability. C1 [Lao, Huei-Chen; Langenbach, Robert] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. [Akunda, Jacqueline K.] Eli Lilly & Co, Dept Oncol, Indianapolis, IN 46285 USA. [Chun, Kyung-Soo] Keimyung Univ, Coll Pharm, Taegu 704701, South Korea. [Flake, Gordon P.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Langenbach, R (reprint author), NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. EM langenb1@niehs.nih.gov FU National Institute of Environmental Health Sciences, National Institute of Health, Intramural Program FX This work was supported by the National Institute of Environmental Health Sciences, National Institute of Health, Intramural Program. NR 48 TC 5 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2012 VL 33 IS 11 BP 2293 EP 2300 DI 10.1093/carcin/bgs267 PG 8 WC Oncology SC Oncology GA 031FL UT WOS:000310624400033 PM 22902545 ER PT J AU Johnson, RA Uddin, T Aktar, A Mohasin, M Alam, MM Chowdhury, F Harris, JB LaRocque, RC Bufano, MK Yu, YA Wu-Freeman, Y Leung, DT Sarracino, D Krastins, B Charles, RC Xu, P Kovac, P Calderwood, SB Qadri, F Ryan, ET AF Johnson, Russell A. Uddin, Taher Aktar, Amena Mohasin, M. Alam, Mohammad Murshid Chowdhury, Fahima Harris, Jason B. LaRocque, Regina C. Bufano, Meagan Kelly Yu, Yanan Wu-Freeman, Ying Leung, Daniel T. Sarracino, David Krastins, Bryan Charles, Richelle C. Xu, Peng Kovac, Pavol Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. TI Comparison of Immune Responses to the O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi Adult Patients with Cholera SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID B-CELL RESPONSES; INFECTION-DERIVED IMMUNITY; CONJUGATE VACCINES; STRUCTURAL-ANALYSIS; HOUSEHOLD CONTACTS; SEROTYPE INABA; CORE REGION; ANTIBODY; TOXIN; PROTECTION AB Immunity against Vibrio cholerae O1 is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) part of lipopolysaccharide (LPS). Despite this, human immune responses to V. cholerae OSP have not previously been characterized. We assessed immune responses against V. cholerae OSP in adults with cholera caused by V. cholerae O1 El Tor serotype Inaba or Ogawa in Dhaka, Bangladesh, using O1 OSP-core-bovine serum albumin (OSPc:BSA) conjugates; responses targeted OSP in these conjugates. Responses of Inaba-infected patients to Inaba OSP and LPS increased significantly in IgG, IgM, and IgA isotypes from the acute to convalescent phases of illness, and the responses correlated well between OSP and LPS (R = 0.86, 0.73, and 0.91, respectively; P < 0.01). Plasma IgG, IgM, and IgA responses to Ogawa OSP and LPS in Ogawa-infected patients also correlated well with each other (R = 0.60, 0.60, and 0.92, respectively; P < 0.01). Plasma IgM responses to Inaba OSP and Ogawa OSP correlated with the respective serogroup-specific vibriocidal antibodies (R = 0.80 and 0.66, respectively; P < 0.001). Addition of either OSPc: BSA or LPS, but not BSA, to vibriocidal assays inhibited vibriocidal responses in a comparable and concentration-dependent manner. Mucosal IgA immune responses to OSP and LPS were also similar. Our study is the first to characterize anti-OSP immune responses in patients with cholera and suggests that responses targeting V. cholerae LPS, including vibriocidal responses that correlate with protection against cholera, predominantly target OSP. Induction of anti-OSP responses may be associated with protection against cholera, and our results may support the development of a vaccine targeting V. cholerae OSP. C1 [Harris, Jason B.; LaRocque, Regina C.; Bufano, Meagan Kelly; Yu, Yanan; Wu-Freeman, Ying; Leung, Daniel T.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Johnson, Russell A.; Uddin, Taher; Aktar, Amena; Mohasin, M.; Alam, Mohammad Murshid; Chowdhury, Fahima; Leung, Daniel T.; Qadri, Firdausi] ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh. [LaRocque, Regina C.; Yu, Yanan; Leung, Daniel T.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Sarracino, David; Krastins, Bryan] Thermo Fisher Sci, Cambridge, MA USA. [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM etryan@partners.org RI Xu, Peng/K-7036-2012; Kovac, Pavol/B-8813-2008; OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801 FU ICDDR,B; Intramural Research Program of the National Institutes of Health, NIDDK; National Institutes of Health, National Institute of Allergy and Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883, K08 AI100923, K08 AI089721]; Fogarty International Center, Training Grant in Vaccine Development and Public Health [TW005572]; American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases [TW05572]; Career Development Awards [K01 TW07409, TW07144]; Fogarty International Clinical Research Scholars Award [R24 TW007988]; Swedish International Development Cooperation Agency; Howard Hughes Medical Institute; American Society for Tropical Medicine & Hygiene-Burroughs Wellcome Fund; Harvard Institute for Global Health Postdoctoral Fellowship in Global Infectious Diseases FX This research was supported by the ICDDR,B and by the Intramural Research Program of the National Institutes of Health, NIDDK, and extramural grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 [S. B. C. and E. T. R.], R03 AI063079 [F. Q.], U01 AI077883 [E. T. R.], K08 AI100923 and K08 AI089721 [R. C. C.]), the Fogarty International Center, Training Grant in Vaccine Development and Public Health (TW005572 [T. U., M. M. A., and F. Q.]), an American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases (TW05572 [D. T. L.]), Career Development Awards (K01 TW07409 [J.B.H.] and TW07144 [R. C. L.]), and a Fogarty International Clinical Research Scholars Award (R24 TW007988 [R.A.J. and T. U.]), as well as by the Swedish International Development Cooperation Agency (F. Q.), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (R. C. L.), a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine & Hygiene-Burroughs Wellcome Fund (D. T. L.), and the Harvard Institute for Global Health Postdoctoral Fellowship in Global Infectious Diseases (D.T.L). NR 53 TC 19 Z9 19 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD NOV PY 2012 VL 19 IS 11 BP 1712 EP 1721 DI 10.1128/CVI.00321-12 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 030IF UT WOS:000310563700002 PM 22993410 ER PT J AU Ledgerwood, JE Hu, Z Gordon, IJ Yamshchikov, G Enama, ME Plummer, S Bailer, R Pearce, MB Tumpey, TM Koup, RA Mascola, JR Nabel, GJ Graham, BS AF Ledgerwood, J. E. Hu, Z. Gordon, I. J. Yamshchikov, G. Enama, M. E. Plummer, S. Bailer, R. Pearce, M. B. Tumpey, T. M. Koup, R. A. Mascola, J. R. Nabel, G. J. Graham, B. S. CA VRC 304 Study Team VRC 305 Study Team TI Influenza Virus H5 DNA Vaccination Is Immunogenic by Intramuscular and Intradermal Routes in Humans SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID I CLINICAL-TRIAL; HEALTHY-ADULTS; NEUTRALIZING ANTIBODY; CANDIDATE VACCINE; IMMUNE-RESPONSES; OPEN-LABEL; SAFETY; ANTIGENS AB Avian influenza virus causes outbreaks in domestic and wild birds around the world, and sporadic human infections have been reported. A DNA vaccine encoding hemagglutinin (HA) protein from the A/Indonesia/5/05 (H5N1) strain was initially tested in two randomized phase I clinical studies. Vaccine Research Center study 304 (VRC 304) was a double-blinded study with 45 subjects randomized to placebo, 1 mg of vaccine, or 4 mg of vaccine treatment groups (n = 15/group) by intramuscular (i.m.) Biojector injection. VRC 305 was an open-label study to evaluate route, with 44 subjects randomized to intradermal (i.d.) injections of 0.5 mg by needle/syringe or by Biojector or 1 mg delivered as two 0.5-mg Biojector injections in the same deltoid or as 0.5 mg in each deltoid (n = 11/group). Injections were administered at weeks 0, 4, and 8 in both studies. Antibody responses to H5 were assessed by hemagglutination inhibition (HAI) assay, enzyme-linked immunosorbent assay (ELISA), and neutralization assay, and the H5 T cell responses were assessed by enzyme-linked immunospot and intracellular cytokine staining assays. There were no vaccine-related serious adverse events, and the vaccine was well tolerated in all groups. At 1 mg, i.d. vaccination compared to i.m. vaccination induced a greater frequency and magnitude of response by ELISA, but there were no significant differences in the frequency or magnitude of response between the i.d. and i.m. routes in the HAI or neutralization assays. T cell responses were more common in subjects who received the 1- or 4-mg dose i.m. These studies demonstrated that the DNA vaccine encoding H5 is safe and immunogenic and served to define the proper dose and route for further studies. The i.d. injection route did not offer a significant advantage over the i.m. route, and no difference was detected by delivery to one site versus splitting the dose between two sites for i.d. vaccine administration. The 4-mg dose (i.m) was further investigated in prime-boost regimens. C1 [Ledgerwood, J. E.; Gordon, I. J.; Yamshchikov, G.; Enama, M. E.; Plummer, S.; Bailer, R.; Koup, R. A.; Mascola, J. R.; Nabel, G. J.; Graham, B. S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Hu, Z.] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Pearce, M. B.; Tumpey, T. M.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ledgerwood@mail.nih.gov FU NIAID FX This clinical trial was funded by the NIAID Intramural program. NR 22 TC 26 Z9 26 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD NOV PY 2012 VL 19 IS 11 BP 1792 EP 1797 DI 10.1128/CVI.05663-11 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 030IF UT WOS:000310563700011 PM 22956656 ER PT J AU Southern, T Bess, L Harmon, J Taylor, L Caldwell, H AF Southern, Timothy Bess, Leah Harmon, Jillian Taylor, Lacey Caldwell, Harlan TI Fluorometric High-Throughput Assay for Measuring Chlamydial Neutralizing Antibody SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; IN-VITRO NEUTRALIZATION; TRACHOMATIS; INFECTIONS; DISEASE AB Chlamydia trachomatis is an obligate intracellular mucosotropic pathogen that causes human infections of global importance. C. trachomatis causes trachoma, the leading cause of preventable blindness worldwide, and is the most common cause of bacterial sexually transmitted disease. Although oculogenital infections are treatable with antibiotics, a vaccine is needed to control C. trachomatis infection. Ideally, a vaccine would provide coverage against most, if not all, naturally occurring antigenically distinct serovariants. The development of a subunit vaccine to prevent oculogenital disease could be advanced by identifying chlamydial antigens that elicit pan-neutralizing antibodies, particularly among infected human populations of known risk factors. There is currently no objective high-throughput in vitro assay to screen human sera for neutralization to aid in identification of these antigens. This report describes an objective, high-throughput in vitro assay that measures C. trachomatis-neutralizing antibodies. Antibody-mediated neutralization of chlamydial infection was performed in a 96-well microtiter format, and neutralization was quantified by immunostaining fixed cells followed by automated fluorometric analysis. This report shows that fluorometric analysis of C. trachomatis infection directly correlates to labor-intensive manual inclusion counts. Furthermore, this report shows that fluorometry can be used to identify C. trachomatis serovar-and serocomplex-specific neutralization. This objective, high-throughput analysis of serum neutralization is amenable to epidemiological studies of human chlamydial infection, human clinical vaccine trials, and preclinical animal model experiments of Chlamydia infection. C1 [Southern, Timothy; Bess, Leah; Harmon, Jillian; Taylor, Lacey; Caldwell, Harlan] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Caldwell, H (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. EM hcaldwell@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, NIH FX This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. NR 19 TC 3 Z9 4 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD NOV PY 2012 VL 19 IS 11 BP 1864 EP 1869 DI 10.1128/CVI.00460-12 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 030IF UT WOS:000310563700022 PM 23015646 ER PT J AU Lora, CM Ricardo, AC Brecklin, CS Fischer, MJ Rosman, RT Carmona, E Lopez, A Balaram, M Nessel, L Tao, KX Xie, DW Kusek, JW Go, AS Lash, JP AF Lora, Claudia M. Ricardo, Ana C. Brecklin, Carolyn S. Fischer, Michael J. Rosman, Robert T. Carmona, Eunice Lopez, Amada Balaram, Manjunath Nessel, Lisa Tao, Kaixiang (Kelvin) Xie, Dawei Kusek, John W. Go, Alan S. Lash, James P. TI Recruitment of Hispanics into an observational study of chronic kidney disease: The Hispanic Chronic Renal Insufficiency Cohort Study experience SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Recruitment; Hispanics; CKD ID BASE-LINE CHARACTERISTICS; UNITED-STATES; TREATMENT TRIALS; POPULATIONS; STRATEGIES; PREVENTION; MINORITY; RETENTION; BARRIERS; ADULTS AB Despite the large burden of chronic kidney disease (CKD) in Hispanics, this population has been underrepresented in research studies. We describe the recruitment strategies employed by the Hispanic Chronic Renal Insufficiency Cohort Study, which led to the successful enrollment of a large population of Hispanic adults with CKD into a prospective observational cohort study. Recruitment efforts by bilingual staff focused on community clinics with Hispanic providers in high-density Hispanic neighborhoods in Chicago, academic medical centers, and private nephrology practices. Methods of publicizing the study included church meetings, local Hispanic print media, Spanish television and radio stations, and local health fairs. From October 2005 to July 2008, we recruited 327 Hispanics aged 21-74 years with mild-to-moderate CKD as determined by age-specific estimated glomerular filtration rate (eGFR). Of 716 individuals completing a screening visit, 49% did not meet eGFR inclusion criteria and 46% completed a baseline visit. The mean age at enrollment was 57.1 and 67.1% of participants were male. Approximately 75% of enrolled individuals were Mexican American, 15% Puerto Rican, and 10% had other Latin American ancestry. Eighty two percent of participants were Spanish-speakers. Community-based and academic primary care clinics yielded the highest percentage of participants screened (45.9% and 22.4%) and enrolled (38.2% and 24.5%). However, academic and community-based specialty clinics achieved the highest enrollment yield from individuals screened (61.9% to 71.4%). A strategy focused on primary care and nephrology clinics and the use of bilingual recruiters allowed us to overcome barriers to the recruitment of Hispanics with CKD. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lora, Claudia M.; Ricardo, Ana C.; Brecklin, Carolyn S.; Fischer, Michael J.; Rosman, Robert T.; Carmona, Eunice; Lopez, Amada; Lash, James P.] Univ Illinois, Chicago, IL USA. [Lora, Claudia M.; Ricardo, Ana C.; Fischer, Michael J.; Lash, James P.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Brecklin, Carolyn S.] John H Stroger Hosp, Chicago, IL USA. [Balaram, Manjunath; Nessel, Lisa; Tao, Kaixiang (Kelvin); Xie, Dawei] Univ Penn, Philadelphia, PA 19104 USA. [Kusek, John W.] NIDDK, Bethesda, MD USA. [Go, Alan S.] Kaiser Permanente No Calif, Oakland, CA USA. RP Lora, CM (reprint author), 820 S Wood St,M-C 793, Chicago, IL 60612 USA. EM clora1@uic.edu FU University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) from the National Center for Research Resources (NCRR) [UL1RR029879]; VA HSR&D Career Development Award; National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) [R01 DK072231]; Clinical Translational Science Awards; National Institutes of Health [M01 RR-013987-06] FX Dr. Lora's work is supported by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS), Award Number UL1RR029879 from the National Center for Research Resources (NCRR). Michael J. Fischer was supported by a VA HSR&D Career Development Award. The HCRIC Study is supported by the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) grant, Award Number R01 DK072231. This work was also supported in part by the Clinical Translational Science Awards and National Institutes of Health grant for the University of Illinois at Chicago Clinical Research Center, M01 RR-013987-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NCRR, NIDDK, National Institutes of Health, or the Department of Veterans Affairs or the United States government. NR 30 TC 4 Z9 4 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2012 VL 33 IS 6 BP 1238 EP 1244 DI 10.1016/j.cct.2012.07.012 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 033UA UT WOS:000310825400017 PM 22841929 ER PT J AU McDermott, MM Domanchuk, K Liu, K Guralnik, JM Tian, L Criqui, MH Ferrucci, L Kibbe, M Jones, DL Pearce, WH Zhao, LH Spring, B Rejeski, WJ AF McDermott, Mary M. Domanchuk, Kathryn Liu, Kiang Guralnik, Jack M. Tian, Lu Criqui, Michael H. Ferrucci, Luigi Kibbe, Melina Jones, Donald-Lloyd Pearce, William H. Zhao, Lihui Spring, Bonnie Rejeski, W. Jack TI The Group Oriented Arterial Leg Study (GOALS) to improve walking performance in patients with peripheral arterial disease SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Peripheral artery disease; Intermittent claudication; Clinical trial; Exercise ID COUNSELING TRIAL ACT; ANKLE BRACHIAL INDEX; PHYSICAL-ACTIVITY; INTERMITTENT CLAUDICATION; SUPERVISED EXERCISE; FUNCTIONAL DECLINE; TREADMILL WALKING; LOWER-EXTREMITY; OLDER-ADULTS; DAILY-LIFE AB People with lower extremity peripheral artery disease (PAD) have greater functional impairment and faster functional decline than those without PAD. We describe methods for the Group Oriented Arterial Leg Study (GOALS), an ongoing randomized controlled clinical trial designed to determine whether a Group-Mediated Cognitive Behavioral (GMCB) intervention improves functional performance in PAD participants, compared to a health education control condition. In GOALS, PAD participants were randomized to either an intervention or a health education control condition in a parallel design. Both conditions consist of weekly group sessions with other PAD participants. In the intervention, cognitive behavioral techniques are used to assist participants in setting and adhering to home-based walking exercise goals. Participants are encouraged to walk for exercise at home at least 5 days/week. In the control condition, participants receive lectures on health-related topics. After 6 months of on-site weekly sessions, participants are transitioned to telephone follow-up for another 6 months. Participants in the intervention are asked to continue home walking exercise. The primary outcome is change in six-minute walk performance between baseline and six-month follow-up. Secondary outcomes include change in six-minute walk performance at 12-month follow-up, and change in treadmill walking performance, the Walking Impairment Questionnaire, quality of life, and physical activity at six and 12-month follow-up. In conclusion, if our group-mediated cognitive behavioral intervention is associated with improved walking performance in individuals with PAD, results will have major public health implications for the large and growing number of people with PAD. (C) 2012 Elsevier Inc. All rights reserved. C1 [McDermott, Mary M.; Domanchuk, Kathryn] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Liu, Kiang; Jones, Donald-Lloyd; Zhao, Lihui; Spring, Bonnie] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Hlth Res & Policy, Baltimore, MD 21201 USA. [Tian, Lu] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA. [Kibbe, Melina] Jesse Brown Vet Affairs Med Center, Chicago, IL 60612 USA. [Rejeski, W. Jack] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA. RP McDermott, MM (reprint author), Northwestern Univ, Dept Med, Feinberg Sch Med, 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU National Heart Lung and Blood Institute [R01-HL088589]; National Institute on Aging FX This work is supported by the National Heart Lung and Blood Institute [grant number R01-HL088589] and by the National Institute on Aging. NR 42 TC 12 Z9 13 U1 3 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2012 VL 33 IS 6 BP 1311 EP 1320 DI 10.1016/j.cct.2012.08.001 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 033UA UT WOS:000310825400025 PM 23158112 ER PT J AU Annab, LA Bortner, CD Sifre, MI Collins, JM Shah, RR Dixon, D Kinyamu, HK Archer, TK AF Annab, Lois A. Bortner, Carl D. Sifre, Marie I. Collins, Jennifer M. Shah, Ruchir R. Dixon, Darlene Kinyamu, H. Karimi Archer, Trevor K. TI Differential responses to retinoic acid and endocrine disruptor compounds of subpopulations within human embryonic stem cell lines SO DIFFERENTIATION LA English DT Article DE Human embryonic stem cell; Heterogeneous population; Retinoic acid differentiation; Endocrine disruptor compounds; Notch signaling; Chromatin remodeling ID CHROMATIN-REMODELING COMPLEX; GENE-EXPRESSION; SELF-RENEWAL; BREAST-CANCER; ES CELLS; PLURIPOTENT; LSD1; CULTURE; COMMITMENT; RECEPTORS AB The heterogeneous nature of stem cells is an important issue in both research and therapeutic use in terms of directing cell lineage differentiation pathways, as well as self-renewal properties. Using flow cytometry we have identified two distinct subpopulations by size, large and small, within cultures of human embryonic stem (hES) cell lines. These two cell populations respond differentially to retinoic acid (RA) differentiation and several endocrine disruptor compounds (EDC). The large cell population responds to retinoic acid differentiation with greater than a 50% reduction in cell number and loss of Oct-4 expression, whereas the number of the small cell population does not change and Oct-4 protein expression is maintained. In addition, four estrogenic compounds altered SSEA-3 expression differentially between the two cell subpopulations changing their ratios relative to each other. Both populations express stem cell markers Oct-4, Nanog, Tra-1-60, Tra-1-80 and SSEA-4, but express low levels of differentiation markers common to the three germ layers. Cloning studies indicate that both populations can revive the parental population. Furthermore, whole genome microarray identified approximately 400 genes with significantly different expression between the two populations (p<0.01). We propose the differential response to RA in these populations is due to differential gene expression of Notch signaling members, CoupTF1 and CoupTF2, chromatin remodeling and histone modifying genes that render the small population resistant to RA differentiation. The findings that hES cells exist as heterogeneous populations with distinct responses to differentiation signals and environmental stimuli will be relevant for their use for drug discovery and disease therapy. Published by Elsevier B.V. on behalf of International Society of Differentiation C1 [Annab, Lois A.; Kinyamu, H. Karimi; Archer, Trevor K.] NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Bortner, Carl D.; Sifre, Marie I.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Collins, Jennifer M.] NIEHS, Microarray Facil, NIH, Res Triangle Pk, NC 27709 USA. [Shah, Ruchir R.] NIEHS, SRA Int Inc, NIH, Res Triangle Pk, NC 27709 USA. [Dixon, Darlene] NIEHS, Cellular & Mol Pathol Branch, NTP, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, MD D4-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov FU Intramural NIH HHS [ZIA ES071006-13, Z99 ES999999, ZIA ES071006-12]; NIEHS NIH HHS [Z01 ES071006, Z01ES071006-10] NR 69 TC 3 Z9 4 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD NOV PY 2012 VL 84 IS 4 BP 330 EP 343 DI 10.1016/j.diff.2012.07.006 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 030LR UT WOS:000310572700006 PM 22906706 ER PT J AU Quenet, D McNally, JG Dalal, Y AF Quenet, Delphine McNally, James G. Dalal, Yamini TI Through thick and thin: the conundrum of chromatin fibre folding in vivo SO EMBO REPORTS LA English DT Editorial Material ID CHROMOSOMES; MODEL; SITU C1 [Quenet, Delphine; McNally, James G.; Dalal, Yamini] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Quenet, D (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM dalaly@mail.nih.gov OI Dalal, Yamini/0000-0002-7655-6182 FU Intramural NIH HHS [ZIA BC011207-03, ZIA BC011207-04, ZIA BC011207-05, ZIA BC011207-06, ZIA BC011207-01, ZIA BC011207-02] NR 12 TC 10 Z9 10 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD NOV PY 2012 VL 13 IS 11 BP 943 EP 944 DI 10.1038/embor.2012.143 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 033DH UT WOS:000310773300003 PM 23041656 ER PT J AU Miguel-Aliaga, I Oliver, B Teleman, AA AF Miguel-Aliaga, Irene Oliver, Brian Teleman, Aurelio A. TI The flies of Icarus: science with wings in Crete SO EMBO REPORTS LA English DT Editorial Material C1 [Miguel-Aliaga, Irene] Univ Cambridge, Dept Zool, Cambridge, England. [Oliver, Brian] NIDDKD, Lab Cellular & Dev Biol, Bethesda, MD USA. [Teleman, Aurelio A.] German Canc Res Ctr, Heidelberg, Germany. RP Miguel-Aliaga, I (reprint author), Univ Cambridge, Dept Zool, Cambridge, England. EM im307@cam.ac.uk; briano@helix.nih.gov; a.teleman@dkfz-heidelberg.de RI Teleman, Aurelio/E-6864-2013 OI Teleman, Aurelio/0000-0002-4237-9368 FU Medical Research Council [MC_UP_1102/3] NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD NOV PY 2012 VL 13 IS 11 BP 945 EP 947 DI 10.1038/embor.2012.154 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 033DH UT WOS:000310773300004 PM 23059980 ER PT J AU Severson, PL Tokar, EJ Vrba, L Waalkes, MP Futscher, BW AF Severson, Paul L. Tokar, Erik J. Vrba, Lukas Waalkes, Michael P. Futscher, Bernard W. TI Agglomerates of aberrant DNA methylation are associated with toxicant-induced malignant transformation SO EPIGENETICS LA English DT Article DE epigenetics; arsenic; cadmium; DNA methylation; malignant transformation; long-range epigenetic silencing; agglomerative DNA methylation; H3K9me3; H3K27me3 ID PROSTATE EPITHELIAL-CELLS; UROTHELIAL CELLS; BREAST-CANCER; BLADDER; GENE; CARCINOMA; LINES; CARCINOGENESIS; EPIGENETICS; CHROMATIN AB Epigenetic dysfunction is a known contributor in carcinogenesis, and is emerging as a mechanism involved in toxicant-induced malignant transformation for environmental carcinogens such as arsenicals or cadmium. In addition to aberrant DNA methylation of single genes, another manifestation of epigenetic dysfunction in cancer is agglomerative DNA methylation, which can participate in long-range epigenetic silencing that targets many neighboring genes and has been shown to occur in several types of clinical cancers. Using in vitro model systems of toxicant-induced malignant transformation, we found hundreds of aberrant DNA methylation events that emerge during malignant transformation, some of which occur in an agglomerative fashion. In an arsenite-transformed prostate epithelial cell line, the protocadherin (PCDH), HOXC and HOXD gene family clusters are targeted for agglomerative DNA methylation. The agglomerative DNA methylation changes induced by arsenicals appear to be common and clinically relevant events, since they occur in other human cancer cell lines and models of malignant transformation, as well as clinical cancer specimens. Aberrant DNA methylation in general occurred more often within histone H3 lysine-27 trimethylation stem cell domains. We found a striking association between enrichment of histone H3 lysine-9 trimethylation stem cell domains and toxicant-induced agglomerative DNA methylation, suggesting these epigenetic modifications may become aberrantly linked during malignant transformation. In summary, we found an association between toxicant-induced malignant transformation and agglomerative DNA methylation, which lends further support to the hypothesis that epigenetic dysfunction plays an important role in toxicant-induced malignant transformation. C1 [Severson, Paul L.; Futscher, Bernard W.] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. [Tokar, Erik J.; Waalkes, Michael P.] Natl Inst Environm Hlth Sci, Natl Toxicol Program Lab, Res Triangle Pk, NC USA. [Vrba, Lukas] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Vrba, Lukas] Acad Sci Czech Republic, Inst Plant Mol Biol, Biol Ctr ASCR, CR-37005 Ceske Budejovice, Czech Republic. RP Futscher, BW (reprint author), Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA. EM bfutscher@azcc.arizona.edu RI Vrba, Lukas/J-9268-2015 OI Vrba, Lukas/0000-0003-3042-6275 FU National Institutes of Health [P42 ES04940, ES006694, CA23074, 5T32ES16652-3] FX This work was supported by the National Institutes of Health (P42 ES04940, ES006694, CA23074, 5T32ES16652-3 to P.S.). We thank the laboratory of Dr A. Jay Gandolfi for providing the URO-MSC52 and URO-MSC12+24(-) cell lines. We are grateful to the laboratory of Drs Donald and Mary Ann Sens for sharing UROtsa, URO-ASSC and URO-CDSC. We wish to thank Dr Petr Novak for contributing his time and insightful comments. The costs for publication of this article were deferred by the Southwest Environmental Health Sciences Center (ES006694). This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), however, the statements, opinions or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH or the US government. NR 60 TC 14 Z9 16 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD NOV PY 2012 VL 7 IS 11 BP 1238 EP 1248 DI 10.4161/epi.22163 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 030PO UT WOS:000310582800004 PM 22976526 ER PT J AU Sturgeon, SR Balasubramanian, R Schairer, C Muss, HB Ziegler, RG Arcaro, KF AF Sturgeon, Susan R. Balasubramanian, Raji Schairer, Catherine Muss, Hyman B. Ziegler, Regina G. Arcaro, Kathleen F. TI Detection of promoter methylation of tumor suppressor genes in serum DNA of breast cancer cases and benign breast disease controls SO EPIGENETICS LA English DT Article DE serum DNA; breast cancer; promoter methylation; early marker; pyrosequencing ID CELL-FREE DNA; HYPERMETHYLATION; BIOMARKER; PLASMA; CARCINOGENESIS; RISK AB Tumors are capable of shedding DNA into the blood stream. This shed DNA may be recovered from serum or plasma. The objective of this study was to evaluate whether pyrosequencing promoter DNA in a panel of 12 breast cancer-related genes (APC, BRCA1, CCND2, CDH1, ESR1, GSTP1, HIN1, P16, RAR beta, RASSF1, SFRP1 and TWIST) to measure the degree of methylation would lead to a useful serum-based marker of breast cancer. Serum was obtained from women who were about to undergo a breast biopsy or mastectomy at three hospitals from 1977 to 1987 in Grand Rapids, MI USA. We compared the methylation status of 12 genes in serum DNA obtained from three groups of postmenopausal women (mean age at blood collection: 63.0 y; SD 9.9; range 35-91): breast cancer cases with lymph node-positive disease (n = 241); breast cancer cases with lymph node-negative disease (n = 63); and benign breast disease control subjects (n = 234). Overall, median levels of promoter methylation were low, typically below 5%, for all genes in all study groups. For all genes, median levels of methylation were higher (by 3.3% to 47.6%) in lymph node-positive breast cancer cases than in the controls. Comparing mean methylation level between lymph-node positive cases and controls, the most statistically significant findings, after adjustment of the false-positive rate (q-value), were for TWIST (p = 0.04), SFRP1 (p = 0.16), ESR1 (p = 0.17), P16 (p = 0.19) and APC (p = 0.19). For two of these four genes (TWIST, P16), the median methylation level was also highest in lymph-node positive cases, intermediate in lymph node-negative cases and lowest in the controls. The percent of study subjects with mean methylation scores >= 5% was higher among lymph node-positive cases than controls for ten genes, and significantly higher for HIN1 and TWIST (22.0 vs. 12.2%, p = 0.04 and 37.9 vs. 24.5%, p = 0.004, respectively). Despite relatively consistent variation in methylation patterns among groups, these modest differences did not provide sufficient ability to distinguish between cases and controls in a clinical setting. C1 [Sturgeon, Susan R.; Balasubramanian, Raji] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Schairer, Catherine; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Muss, Hyman B.] UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Arcaro, Kathleen F.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. RP Sturgeon, SR (reprint author), Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA. EM ssturgeon@schoolph.umass.edu FU Susan G. Komen for the Cure FX This research was supported by a grant from Susan G. Komen for the Cure. NR 25 TC 25 Z9 27 U1 0 U2 14 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD NOV PY 2012 VL 7 IS 11 BP 1258 EP 1267 DI 10.4161/epi.22220 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 030PO UT WOS:000310582800006 PM 22986510 ER PT J AU Yang, CZ Matro, JC Huntoon, KM Ye, DY Huynh, TT Fliedner, SMJ Breza, J Zhuang, ZP Pacak, K AF Yang, Chunzhang Matro, Joey C. Huntoon, Kristin M. Ye, Donald Y. Huynh, Thanh T. Fliedner, Stephanie M. J. Breza, Jan Zhuang, Zhengping Pacak, Karel TI Missense mutations in the human SDHB gene increase protein degradation without altering intrinsic enzymatic function SO FASEB JOURNAL LA English DT Article DE pheochromocytoma; paraganglioma; succinate dehydrogenase subunit B; histone deacetylase inhibitor ID TUMOR-SUPPRESSOR GENE; SUCCINATE-DEHYDROGENASE; QUALITY-CONTROL; IN-VIVO; FAMILIAL PHEOCHROMOCYTOMA; HEREDITARY PARAGANGLIOMA; PROLYL HYDROXYLASE; OXIDATIVE STRESS; LINDAU-DISEASE; GERMLINE SDHB AB Mutations of succinate dehydrogenase subunit B (SDHB) play a crucial role in the pathogenesis of the most aggressive and metastatic pheochromocytomas (PHEOs) and paragangliomas (PGLs). Although a variety of missense mutations in the coding sequence of the SDHB gene have been found in PHEOs and PGLs, it has been unclear whether these mutations impair mRNA expression, protein stability, subcellular localization, or intrinsic protein function. RT-PCR and Western blot analysis of SDHB mRNA and protein expression from SDHB-related PHEOs and PGLs demonstrated intact mRNA expression but significantly reduced protein expression compared to non-SDHB PHEOs and PGLs. A pulse-chase assay of common SDHB missense mutations in transfected HeLa cell lines demonstrated that the loss of SDHB function was due to a reduction in mutant protein half-life, whereas colocalization of SDHB with mitochondria and immunoprecipitation with SDHA demonstrated intact subcellular localization and complex formation. The half-life of the SDHB protein increased after treatment with histone deacetylase inhibitors (HDACis), implicating the protein quality control machinery in the degradation of mutant SDHB protein. These findings provide the first direct mechanism of functional loss resulting from SDHBmutations and suggest that reducing protein degradation with HDACis may serve as a novel therapeutic paradigm for preventing the development of SDHB-related tumors.-Yang, C., Matro, J. C., Huntoon, K. M., Ye, D. Y., Huynh, T. T., Fliedner, S. M. J., Breza, J., Zhuang, Z., Pacak, K. Missense mutations in the human SDHB gene increase protein degradation without altering intrinsic enzymatic function. FASEB J. 26, 4506-4516 (2012). www.fasebj.org C1 [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bethesda, MD 20892 USA. [Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Breza, Jan] Comenius Univ, Sch Med, Dept Urol, Bratislava, Slovakia. RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bldg 10,Rm 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov; karel@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Neurological Disorders and Stroke at the U. S. National Institutes of Health FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke at the U. S. National Institutes of Health. NR 58 TC 21 Z9 21 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2012 VL 26 IS 11 BP 4506 EP 4516 DI 10.1096/fj.12-210146 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 030MG UT WOS:000310574200013 PM 22835832 ER PT J AU Roudier, E Forn, P Perry, ME Birot, O AF Roudier, Emilie Forn, Paul Perry, Mary Ellen Birot, Olivier TI Murine double minute-2 expression is required for capillary maintenance and exercise-induced angiogenesis in skeletal muscle SO FASEB JOURNAL LA English DT Article DE VEGF-A; endothelial cell; p53; physiology ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; GROWTH-FACTOR EXPRESSION; FACTOR MESSENGER-RNA; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; ISCHEMIC MUSCLE; CANCER-THERAPY; FACTOR 1-ALPHA; MDM2; P53 AB Exercise-induced angiogenesis is a key determinant of skeletal muscle function. Here, we investigated whether the E3 ubiquitin ligase murine double minute-2 (Mdm2) exerts a proangiogenic function in exercised skeletal muscle. Mdm2 hypomorphic (Mdm2(Puro/Delta 7-9)) mice have a 60% reduction in Mdm2 expression compared with that in wild-type animals. Capillary staining on muscle sections from Mdm2(Puro/Delta 7-9) sedentary mice with a wild-type or knockout background for p53 revealed that deficiency in Mdm2 resulted in 20% capillary regression independently of p53 status. In response to one bout of exercise, protein expression of the proangiogenic vascular endothelial growth factor-A (VEGF-A) was increased by 64% in muscle from wild-type animals, and endothelial cell outgrowth from exercised muscle biopsy samples cultured in a 3-dimensional collagen gel was enhanced by 37%. These proangiogenic responses to exercise were impaired in exercised Mdm2(Puro/Delta 7-9) mice. Prolonged exercise training resulted in increased Mdm2 protein expression (+49%) and capillarization (+24%) in wildtype muscles. However, exercise training-induced angiogenesis was abolished in Mdm2(Puro/Delta 7-9) mice. Finally, exercise training restored Mdm2, VEGF-A, and capillarization levels in skeletal muscles from obese Zucker diabetic fatty rats compared with those in healthy animals. Our results define Mdm2 as a crucial regulator of capillary maintenance and exercise-induced angiogenesis in skeletal muscle.-Roudier, E., Forn, P., Perry, M. E., Birot, O. Murine double minute-2 expression is required for capillary maintenance and exercise-induced angiogenesis in skeletal muscle. FASEB J. 26, 4530-4539 (2012). www.fasebj.org C1 [Birot, Olivier] York Univ, Fac Hlth, Norman Bethune Coll, Angiogenesis Res Grp, Toronto, ON M3J 1P3, Canada. [Roudier, Emilie; Birot, Olivier] Univ Montreal, Dept Kinesiol, Montreal, PQ, Canada. [Perry, Mary Ellen] NCI, Lab Prot Dynam & Signaling, US Natl Inst Hlth, Frederick, MD 21701 USA. RP Birot, O (reprint author), York Univ, Fac Hlth, Norman Bethune Coll, Angiogenesis Res Grp, Room 353,4700 Keele St, Toronto, ON M3J 1P3, Canada. EM birot@yorku.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC) [341258]; NIH, National Cancer Institute, Center for Cancer Research FX The authors thank Nicole Morris [National Cancer Institute, U.S. National Institutes of Health (NIH)] for maintaining the Mdm2puro/Delta 7-9 mice, and Dr. Raynald Bergeron (University of Montreal) for his help in the ZDF mouse conditioning. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC discovery grant 341258 to O.B.) and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (M. E. P.). E. R. and O.B. conceived the study; E. R., M. E. P., and O.B. designed experiments; E. R., P. F., and O.B. performed experiments and analyzed data; M. E. P. supplied Mdm2puro/Delta 7-9 mice; E. R., M. E. P., and O.B. participated in the redaction of the manuscript. NR 54 TC 15 Z9 15 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2012 VL 26 IS 11 BP 4530 EP 4539 DI 10.1096/fj.12-212720 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 030MG UT WOS:000310574200015 PM 22835827 ER PT J AU Tryndyak, V de Conti, A Kobets, T Kutanzi, K Koturbash, I Han, T Fuscoe, JC Latendresse, JR Melnyk, S Shymonyak, S Collins, L Ross, SA Rusyn, I Beland, FA Pogribny, IP AF Tryndyak, Volodymyr de Conti, Aline Kobets, Tetyana Kutanzi, Kristy Koturbash, Igor Han, Tao Fuscoe, James C. Latendresse, John R. Melnyk, Stepan Shymonyak, Svitlana Collins, Leonard Ross, Sharon A. Rusyn, Ivan Beland, Frederick A. Pogribny, Igor P. TI Interstrain differences in the severity of liver injury induced by a choline- and folate-deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism SO FASEB JOURNAL LA English DT Article DE nonalcoholic fatty liver; interindividual; oxidative stress ID ELEMENT-BINDING PROTEIN; NONALCOHOLIC STEATOHEPATITIS; OXIDATIVE STRESS; PPAR-ALPHA; HEPATIC STEATOSIS; EXPRESSION; DISEASE; PROGRESSION; CHREBP; CYTOCHROME-P450 AB Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and developed countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD. The goals of this study were to compare the magnitude of interindividual differences in the severity of liver injury induced by methyl-donor deficiency among individual inbred strains of mice and to investigate the underlying mechanisms associated with the variability. Feeding mice a choline-and folate-deficient diet for 12 wk caused liver injury similar to NAFLD. The magnitude of liver injury varied among the strains, with the order of sensitivity being A/J approximate to C57BL/6J approximate to C3H/HeJ < 129S1/SvImJ approximate to CAST/EiJ < PWK/PhJ < WSB/EiJ. The interstrain variability in severity of NAFLD liver damage was associated with dysregulation of genes involved in lipid metabolism, primarily with a down-regulation of the peroxisome proliferator receptor alpha (PPAR alpha)-regulated lipid catabolic pathway genes. Markers of oxidative stress and oxidative stress-induced DNA damage were also elevated in the livers but were not correlated with severity of liver damage. These findings suggest that the PPAR alpha-regulated metabolism network is one of the key mechanisms determining interstrain susceptibility and severity of NAFLD in mice.-Tryndyak, V., de Conti, A., Kobets, T., Kutanzi, K., Koturbash, I., Han, T., Fuscoe, J. C., Latendresse, J. R., Melnyk, S., Shymonyak, S., Collins, L., Ross, S. A., Rusyn, I., Beland, F. A., Pogribny, I. P. Interstrain differences in the severity of liver injury induced by a choline-and folate-deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism. FASEB J. 26, 4592-4602 (2012). www.fasebj.org C1 [Tryndyak, Volodymyr; Kobets, Tetyana; Kutanzi, Kristy; Koturbash, Igor; Beland, Frederick A.; Pogribny, Igor P.] US FDA, NCTR, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Han, Tao; Fuscoe, James C.] US FDA, NCTR, Div Syst Biol, Jefferson, AR 72079 USA. [Latendresse, John R.] US FDA, NCTR, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [de Conti, Aline] Univ Sao Paulo, Lab Diet Nutr & Canc, Sao Paulo, Brazil. [Kobets, Tetyana; Shymonyak, Svitlana; Collins, Leonard; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. [Melnyk, Stepan] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), US FDA, NCTR, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI de Conti, Aline/I-1666-2013; Rusyn, Ivan/S-2426-2016 FU NIEHS NIH HHS [P30 ES010126] NR 45 TC 15 Z9 15 U1 0 U2 12 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2012 VL 26 IS 11 BP 4592 EP 4602 DI 10.1096/fj.12-209569 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 030MG UT WOS:000310574200021 PM 22872676 ER PT J AU Ashkenazi, A Viard, M Unger, L Blumenthal, R Shai, Y AF Ashkenazi, Avraham Viard, Mathias Unger, Linor Blumenthal, Robert Shai, Yechiel TI Sphingopeptides: dihydrosphingosine-based fusion inhibitors against wild-type and enfuvirtide-resistant HIV-1 SO FASEB JOURNAL LA English DT Article DE viral envelope protein; sphingolipids ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL MEMBRANE-FUSION; CELL-CELL FUSION; ENVELOPE GLYCOPROTEIN; MEDIATED FUSION; LIPID RAFTS; COILED-COIL; GP41; PEPTIDE; CHOLESTEROL AB Understanding the structural organization of lipids in the cell and viral membranes is essential for elucidating mechanisms of viral fusion that lead to entry of enveloped viruses into their host cells. The HIV lipidome shows a remarkable enrichment in dihydrosphingomyelin, an unusual sphingolipid formed by a dihydrosphingosine backbone. Here we investigated the ability of dihydrosphingosine to incorporate into the site of membrane fusion mediated by the HIV envelope (Env) protein. Dihydrosphingosine as well as cholesterol, fatty acid, and tocopherol was conjugated to highly conserved, short HIV-1 Env-derived peptides with no antiviral activity otherwise. We showed that dihydrosphingosine exclusively endowed nanomolar antiviral activity to the peptides (IC50 as low as 120 nM) in HIV-1 infection on TZM-bl cells and on Jurkat T cells, as well as in the cell-cell fusion assay. These sphingopeptides were active against enfuvirtide-resistant and wild-type CXCR4 and CCR5 tropic HIV strains. The anti-HIV activity was determined by both the peptides and their dihydrosphingosine conjugate. Moreover, their mode of action involved accumulation in the cells and viruses and binding to membranes enriched in sphingomyelin and cholesterol. The data suggest that sphingopeptides are recruited to the HIV membrane fusion site and provide a general concept in developing inhibitors of sphingolipid-mediated biological systems.-Ashkenazi, A., Viard, M., Unger, L., Blumenthal, R., Shai, Y. Sphingopeptides: dihydrosphingosine-based fusion inhibitors against wild-type and enfuvirtide-resistant HIV-1. FASEB J. 26, 4628-4636 (2012). www.fasebj.org C1 [Ashkenazi, Avraham; Unger, Linor; Shai, Yechiel] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. [Viard, Mathias; Blumenthal, Robert] NCI, Nanobiol Program, Ctr Canc Res, Frederick Natl Lab, Frederick, MD 21701 USA. [Viard, Mathias] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, Frederick Natl Lab, Frederick, MD USA. RP Shai, Y (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. EM yechiel.shai@weizmann.ac.il FU Israel Science Foundation; Frederick National Laboratory; National Cancer Institute; U.S. National Institutes of Health [HHSN26120080001E] FX The authors thank Batya Zarmi for her valuable help with peptide purification and Winfried Weissenhorn for providing the recent 3-dimensional structure of gp41. This study was supported by the Israel Science Foundation (to Y. S.) and in part by federal funds (to R. B.) from the Frederick National Laboratory, National Cancer Institute, U.S. National Institutes of Health (contract HHSN26120080001E). The content of this publication does not necessarily reflect the views or policies of the U. S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. government. Y. S. is the incumbent of the Harold S. and Harriet B. Brady Professorial Chair in Cancer Research. NR 56 TC 14 Z9 14 U1 1 U2 12 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2012 VL 26 IS 11 BP 4628 EP 4636 DI 10.1096/fj.12-215111 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 030MG UT WOS:000310574200024 PM 22872679 ER PT J AU Linehan, WM AF Linehan, W. Marston TI Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics SO GENOME RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; HIPPEL-LINDAU-DISEASE; HOGG-DUBE-SYNDROME; TUMOR-SUPPRESSOR PROTEIN; PARENCHYMAL SPARING SURGERY; TUBEROUS SCLEROSIS COMPLEX; HEREDITARY LEIOMYOMATOSIS; FUMARATE-HYDRATASE; CHROMOSOME-TRANSLOCATION; GERMLINE MUTATIONS AB Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease. C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. EM linehanm@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The author thanks Tracey A. Rouault, M. D. for the manuscript review and Georgia Shaw for editorial and graphics support. NR 100 TC 38 Z9 43 U1 0 U2 27 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2012 VL 22 IS 11 BP 2089 EP 2100 DI 10.1101/gr.131110.111 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 030QE UT WOS:000310584400001 PM 23038766 ER PT J AU Burzynski, GM Reed, X Taher, L Stine, ZE Matsui, T Ovcharenko, I McCallion, AS AF Burzynski, Grzegorz M. Reed, Xylena Taher, Leila Stine, Zachary E. Matsui, Takeshi Ovcharenko, Ivan McCallion, Andrew S. TI Systematic elucidation and in vivo validation of sequences enriched in hindbrain transcriptional control SO GENOME RESEARCH LA English DT Article ID RECEPTOR-RELATED RECEPTORS; SUPPORT VECTOR MACHINES; CHIP-SEQ; EMBRYONIC-DEVELOPMENT; HEART ENHANCERS; NERVOUS-SYSTEM; 2008 UPDATE; ZEBRAFISH; EXPRESSION; GENOME AB Illuminating the primary sequence encryption of enhancers is central to understanding the regulatory architecture of genomes. We have developed a machine learning approach to decipher motif patterns of hindbrain enhancers and identify 40,000 sequences in the human genome that we predict display regulatory control that includes the hindbrain. Consistent with their roles in hindbrain patterning, MEIS1, NKX6-1, as well as HOX and POU family binding motifs contributed strongly to this enhancer model. Predicted hindbrain enhancers are overrepresented at genes expressed in hindbrain and associated with nervous system development, and primarily reside in the areas of open chromatin. In addition, 77 (0.2%) of these predictions are identified as hindbrain enhancers on the VISTA Enhancer Browser, and 26,000 (60%) overlap enhancer marks (H3K4me1 or H3K27ac). To validate these putative hindbrain enhancers, we selected 55 elements distributed throughout our predictions and six low scoring controls for evaluation in a zebrafish transgenic assay. When assayed in mosaic transgenic embryos, 51/55 elements directed expression in the central nervous system. Furthermore, 30/34 (88%) predicted enhancers analyzed in stable zebrafish transgenic lines directed expression in the larval zebrafish hindbrain. Subsequent analysis of sequence fragments selected based upon motif clustering further confirmed the critical role of the motifs contributing to the classifier. Our results demonstrate the existence of a primary sequence code characteristic to hindbrain enhancers. This code can be accurately extracted using machine-learning approaches and applied successfully for de novo identification of hindbrain enhancers. This study represents a critical step toward the dissection of regulatory control in specific neuronal subtypes. C1 [Taher, Leila; Ovcharenko, Ivan] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. [Burzynski, Grzegorz M.; Reed, Xylena; Stine, Zachary E.; Matsui, Takeshi; McCallion, Andrew S.] Johns Hopkins Univ, Dept Mol & Comparat Pathobiol, McKusick Nathans Inst Genet Med, Sch Med, Baltimore, MD 21205 USA. [Reed, Xylena] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, Baltimore, MD 21205 USA. RP Ovcharenko, I (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. EM ovcharen@nig.gov; andy@jhmi.edu FU National Institute of Neurological Disease and Stroke [NS062972]; NIH, National Library of Medicine; [GM07814] FX This work was funded in part by the National Institute of Neurological Disease and Stroke (NS062972) to A. S. M., the Intramural Research Program of the NIH, National Library of Medicine to I.O., and a predoctoral training grant (GM07814) to X.R. NR 63 TC 7 Z9 7 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 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2012 VL 22 IS 11 BP 2278 EP 2289 DI 10.1101/gr.139717.112 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 030QE UT WOS:000310584400020 PM 22759862 ER PT J AU Gorkin, DU Lee, D Reed, X Fletez-Brant, C Bessling, SL Loftus, SK Beer, MA Pavan, WJ McCallion, AS AF Gorkin, David U. Lee, Dongwon Reed, Xylena Fletez-Brant, Christopher Bessling, Seneca L. Loftus, Stacie K. Beer, Michael A. Pavan, William J. McCallion, Andrew S. TI Integration of ChIP-seq and machine learning reveals enhancers and a predictive regulatory sequence vocabulary in melanocytes SO GENOME RESEARCH LA English DT Article ID STEM-CELL DIFFERENTIATION; NEURAL CREST; GENE-EXPRESSION; HUMAN GENOME; TRANSCRIPTIONAL ENHANCERS; PROMOTER INTERACTIONS; MOUSE MELANOCYTES; MOTIF DISCOVERY; OPEN CHROMATIN; MELANOMA AB We take a comprehensive approach to the study of regulatory control of gene expression in melanocytes that proceeds from large-scale enhancer discovery facilitated by ChIP-seq; to rigorous validation in silico, in vitro, and in vivo; and finally to the use of machine learning to elucidate a regulatory vocabulary with genome-wide predictive power. We identify 2489 putative melanocyte enhancer loci in the mouse genome by ChIP-seq for EP300 and H3K4me1. We demonstrate that these putative enhancers are evolutionarily constrained, enriched for sequence motifs predicted to bind key melanocyte transcription factors, located near genes relevant to melanocyte biology, and capable of driving reporter gene expression in melanocytes in culture (86%; 43/50) and in transgenic zebrafish (70%; 7/10). Next, using the sequences of these putative enhancers as a training set for a supervised machine learning algorithm, we develop a vocabulary of 6-mers predictive of melanocyte enhancer function. Lastly, we demonstrate that this vocabulary has genome-wide predictive power in both the mouse and human genomes. This study provides deep insight into the regulation of gene expression in melanocytes and demonstrates a powerful approach to the investigation of regulatory sequences that can be applied to other cell types. C1 [Gorkin, David U.; Reed, Xylena; Fletez-Brant, Christopher; Bessling, Seneca L.; Beer, Michael A.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Gorkin, David U.; Reed, Xylena] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, Baltimore, MD 21205 USA. [Lee, Dongwon; Beer, Michael A.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21201 USA. [Loftus, Stacie K.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Beer, MA (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. EM mbeer@jhu.edu; bpavan@nhgri.nih.gov; andy@jhmi.edu FU National Institute of General Medical Sciences [GM071648]; National Institute of Neurological Disease and Stroke [NS062972]; National Human Genome Research Institute's (NHGRI) Intramural Research Program; NSF; Searle Scholars Program; [GM07814] FX We thank Barbara Migeon, Kirby Smith, Hongkai Ji, George Wu, Megana Prasad, Zachary Stine, Samantha Maragh, and Amanda Price for helpful comments and discussion. This work was funded in part by the National Institute of General Medical Sciences (GM071648) and the National Institute of Neurological Disease and Stroke (NS062972) to A. S. M., by the National Human Genome Research Institute's (NHGRI) Intramural Research Program (W.J.P., S. K. L.), by an NSF Graduate Research Fellowship to D. U. G., and by a predoctoral training grant (GM07814) to X. R. M. A. B. was supported by the Searle Scholars Program and in part by NS062972. NR 71 TC 33 Z9 34 U1 1 U2 8 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2012 VL 22 IS 11 BP 2290 EP 2301 DI 10.1101/gr.139360.112 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 030QE UT WOS:000310584400021 PM 23019145 ER PT J AU Hamasaki-Katagiri, N Salari, R Simhadri, VL Tseng, SC Needlman, E Edwards, NC Sauna, ZE Grigoryan, V Komar, AA Przytycka, TM Kimchi-Sarfaty, C AF Hamasaki-Katagiri, N. Salari, R. Simhadri, V. L. Tseng, S. C. Needlman, E. Edwards, N. C. Sauna, Z. E. Grigoryan, V. Komar, A. A. Przytycka, T. M. Kimchi-Sarfaty, C. TI Analysis of F9 point mutations and their correlation to severity of haemophilia B disease SO HAEMOPHILIA LA English DT Article DE coagulation factor IX; genotype-phenotype association; haemophilia B; in silico analysis; mRNA free energy; predictive tools ID FACTOR-IX; PROTEIN; GENE AB Haemophilia B is an X-linked recessive disorder caused by deficiency of functional coagulation factor IX, which results almost exclusively from mutations in the F9 gene. We sought to determine features, which could distinguish between mutations that cause severe disease symptoms from those that cause non-severe disease symptoms. Towards this objective, we have performed a statistical analysis of reported point mutations in F9. These include: potential local changes in mRNA free energy, codon usage, charge and type of mutated amino acid, location of the mutation with regard to protein secondary structure and functional domain and amino acids' evolutionary conservation scores. Wilcoxon signed-rank tests showed highly significant differences between severe and non-severe disease causing mutations in their effect on free energy of small mRNA fragments and evolutionarily conserved amino acids. Our results suggest that information at the mRNA level as well as conservation of the amino acid correlate well with disease severity. This study demonstrates that computational tools may be used to characterize the severity of haemophilia B associated with point mutations and suggests their utility in predicting the outcome of sequence changes in recombinant proteins. C1 [Hamasaki-Katagiri, N.; Simhadri, V. L.; Tseng, S. C.; Needlman, E.; Edwards, N. C.; Sauna, Z. E.; Kimchi-Sarfaty, C.] US FDA, Div Hematol, Lab Hemostasis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Salari, R.; Grigoryan, V.; Przytycka, T. M.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Komar, A. A.] Cleveland State Univ, Dept Biol Geol & Environm Sci, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA. RP Kimchi-Sarfaty, C (reprint author), US FDA, Div Hematol, Lab Hemostasis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM chava.kimchi-sarfaty@fda.hhs.gov FU Intramural Research Programme of the National Institutes of Health, National Library of Medicine FX The authors thank Ms. Nechama Nelson for her assistance with mfold. This study was supported in part by the Intramural Research Programme of the National Institutes of Health, National Library of Medicine. The authors declare no competing financial interests. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 19 TC 6 Z9 7 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD NOV PY 2012 VL 18 IS 6 BP 933 EP 940 DI 10.1111/j.1365-2516.2012.02848.x PG 8 WC Hematology SC Hematology GA 030EY UT WOS:000310553600030 PM 22639855 ER PT J AU Leiding, JW Holland, SM AF Leiding, Jennifer W. Holland, Steven M. TI Warts and all: Human papillomavirus in primary immunodeficiencies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Immunodeficiency; human papillomavirus; warts; squamous; carcinoma; dysplastic ID WISKOTT-ALDRICH-SYNDROME; CELL-MEDIATED-IMMUNITY; CERVICAL INTRAEPITHELIAL NEOPLASIA; ADENOSINE-DEAMINASE DEFICIENCY; LEUKOCYTE ADHESION DEFICIENCY; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; DOMINANT EPIDERMODYSPLASIA-VERRUCIFORMIS; HPV-16/18 AS04-ADJUVANTED VACCINE; IDIOPATHIC CD4+ LYMPHOCYTOPENIA AB Infection with human papillomavirus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and dedicator of cytokinesis 8 (DOCK8) are typically associated with extensive HPV infections, whereas several other primary immune defects result in severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them. (J Allergy Clin Immunol 2012;130:1030-48.) C1 [Leiding, Jennifer W.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Leiding, JW (reprint author), Univ S Florida, Childrens Reseach Inst, Dept Pediat, Div Allergy Immunol & Rheumatol, 140 7th Ave S Box 9680, St Petersburg, FL 33701 USA. EM jleiding@health.usf.edu; smh@nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX Supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 201 TC 35 Z9 36 U1 0 U2 20 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2012 VL 130 IS 5 BP 1030 EP 1048 DI 10.1016/j.jaci.2012.07.049 PG 19 WC Allergy; Immunology SC Allergy; Immunology GA 030LE UT WOS:000310571400002 PM 23036745 ER PT J AU Bousquet, J Schunemann, HJ Samolinski, B Demoly, P Baena-Cagnani, CE Bachert, C Bonini, S Boulet, LP Bousquet, PJ Brozek, JL Canonica, GW Casale, TB Cruz, AA Fokkens, WJ Fonseca, JA van Wijk, RG Grouse, L Haahtela, T Khaltaev, N Kuna, P Lockey, RF Carlsen, KCL Mullol, J Naclerio, R O'Hehir, RE Ohta, K Palkonen, S Papadopoulos, NG Passalacqua, G Pawankar, R Price, D Ryan, D Simons, FER Togias, A Williams, D Yorgancioglu, A Yusuf, OM Aberer, W Adachi, M Agache, I Ait-Khaled, N Akdis, CA Andrianarisoa, A Annesi-Maesano, I Ansotegui, IJ Baiardini, I Bateman, ED Bedbrook, A Beghe, B Beji, M Bel, EH Ben Kheder, A Bennoor, KS Bergmann, KC Berrissoul, F Bieber, T Jensen, CB Blaiss, MS Boner, AL Bouchard, J Braido, F Brightling, CE Bush, A Caballero, F Calderon, MA Calvo, MA Camargos, PAM Caraballo, LR Carlsen, KH Carr, W Cepeda, AM Cesario, A Chavannes, NH Chen, YZ Chiriac, AM Perez, TC Chkhartishvili, E Ciprandi, G Costa, DJ Cox, L Custovic, A Dahl, R Darsow, U De Blay, F Deleanu, D Denburg, JA Devillier, P Didi, T Dokic, D Dolen, WK Douagui, H Dubakiene, R Durham, SR Dykewicz, MS El-Gamal, Y El-Meziane, A Emuzyte, R Fiocchi, A Fletcher, M Fukuda, T Gamkrelidze, A Gereda, JE Diaz, SG Gotua, M Guzman, MA Hellings, PW Hellquist-Dahl, B Horak, F Hourihane, JO Howarth, P Humbert, M Ivancevich, JC Jackson, C Just, J Kalayci, O Kaliner, MA Kalyoncu, AF Keil, T Keith, PK Khayat, G Kim, YY N'Goran, BK Koppelman, GH Kowalski, ML Kull, I Kvedariene, V Larenas-Linnemann, D Le, LT Lemiere, C Li, J Lieberman, P Lipworth, B Mahboub, B Makela, MJ Martin, F Marshall, GD Martinez, FD Masjedi, MR Maurer, M Mavale-Manuel, S Mazon, A Melen, E Meltzer, EO Mendez, NH Merk, H Mihaltan, F Mohammad, Y Morais-Almeida, M Muraro, A Nafti, S Namazova-Baranova, L Nekam, K Neou, A Niggemann, B Nizankowska-Mogilnicka, E Nyembue, TD Okamoto, Y Okubo, K Orru, MP Ouedraogo, S Ozdemir, C Panzner, P Pali-Scholl, I Park, HS Pigearias, B Pohl, W Popov, TA Postma, DS Potter, P Rabe, KF Ratomaharo, J Reitamo, S Ring, J Roberts, R Rogala, B Romano, A Rodriguez, MR Rosado-Pinto, J Rosenwasser, L Rottem, M Sanchez-Borges, M Scadding, GK Schmid-Grendelmeier, P Sheikh, A Sisul, JC Sole, D Sooronbaev, T Spicak, V Spranger, O Stein, RT Stoloff, SW Sunyer, J Szczeklik, A Todo-Bom, A Toskala, E Tremblay, Y Valenta, R Valero, AL Valeyre, D Valiulis, A Valovirta, E Van Cauwenberge, P Vandenplas, O van Weel, C Vichyanond, P Viegi, G Wang, DY Wickman, M Wohrl, S Wright, J Yawn, BP Yiallouros, PK Zar, HJ Zernotti, ME Zhong, N Zidarn, M Zuberbier, T AF Bousquet, J. Schuenemann, H. J. Samolinski, B. Demoly, P. Baena-Cagnani, C. E. Bachert, C. Bonini, S. Boulet, L. P. Bousquet, P. J. Brozek, J. L. Canonica, G. W. Casale, T. B. Cruz, A. A. Fokkens, W. J. Fonseca, J. A. van Wijk, R. Gerth Grouse, L. Haahtela, T. Khaltaev, N. Kuna, P. Lockey, R. F. Carlsen, K. C. Lodrup Mullol, J. Naclerio, R. O'Hehir, R. E. Ohta, K. Palkonen, S. Papadopoulos, N. G. Passalacqua, G. Pawankar, R. Price, D. Ryan, D. Simons, F. E. R. Togias, A. Williams, D. Yorgancioglu, A. Yusuf, O. M. Aberer, W. Adachi, M. Agache, I. Ait-Khaled, N. Akdis, C. A. Andrianarisoa, A. Annesi-Maesano, I. Ansotegui, I. J. Baiardini, I. Bateman, E. D. Bedbrook, A. Beghe, B. Beji, M. Bel, E. H. Ben Kheder, A. Bennoor, K. S. Bergmann, K. C. Berrissoul, F. Bieber, T. Jensen, C. Bindslev Blaiss, M. S. Boner, A. L. Bouchard, J. Braido, F. Brightling, C. E. Bush, A. Caballero, F. Calderon, M. A. Calvo, M. A. Camargos, P. A. M. Caraballo, L. R. Carlsen, K. H. Carr, W. Cepeda, A. M. Cesario, A. Chavannes, N. H. Chen, Y. Z. Chiriac, A. M. Chivato Perez, T. Chkhartishvili, E. Ciprandi, G. Costa, D. J. Cox, L. Custovic, A. Dahl, R. Darsow, U. De Blay, F. Deleanu, D. Denburg, J. A. Devillier, P. Didi, T. Dokic, D. Dolen, W. K. Douagui, H. Dubakiene, R. Durham, S. R. Dykewicz, M. S. El-Gamal, Y. El-Meziane, A. Emuzyte, R. Fiocchi, A. Fletcher, M. Fukuda, T. Gamkrelidze, A. Gereda, J. E. Gonzalez Diaz, S. Gotua, M. Guzman, M. A. Hellings, P. W. Hellquist-Dahl, B. Horak, F. Hourihane, J. O'B. Howarth, P. Humbert, M. Ivancevich, J. C. Jackson, C. Just, J. Kalayci, O. Kaliner, M. A. Kalyoncu, A. F. Keil, T. Keith, P. K. Khayat, G. Kim, Y. Y. N'Goran, B. Koffi Koppelman, G. H. Kowalski, M. L. Kull, I. Kvedariene, V. Larenas-Linnemann, D. Le, L. T. Lemiere, C. Li, J. Lieberman, P. Lipworth, B. Mahboub, B. Makela, M. J. Martin, F. Marshall, G. D. Martinez, F. D. Masjedi, M. R. Maurer, M. Mavale-Manuel, S. Mazon, A. Melen, E. Meltzer, E. O. Mendez, N. H. Merk, H. Mihaltan, F. Mohammad, Y. Morais-Almeida, M. Muraro, A. Nafti, S. Namazova-Baranova, L. Nekam, K. Neou, A. Niggemann, B. Nizankowska-Mogilnicka, E. Nyembue, T. D. Okamoto, Y. Okubo, K. Orru, M. P. Ouedraogo, S. Ozdemir, C. Panzner, P. Pali-Schoell, I. Park, H. S. Pigearias, B. Pohl, W. Popov, T. A. Postma, D. S. Potter, P. Rabe, K. F. Ratomaharo, J. Reitamo, S. Ring, J. Roberts, R. Rogala, B. Romano, A. Rodriguez, M. Roman Rosado-Pinto, J. Rosenwasser, L. Rottem, M. Sanchez-Borges, M. Scadding, G. K. Schmid-Grendelmeier, P. Sheikh, A. Sisul, J. C. Sole, D. Sooronbaev, T. Spicak, V. Spranger, O. Stein, R. T. Stoloff, S. W. Sunyer, J. Szczeklik, A. Todo-Bom, A. Toskala, E. Tremblay, Y. Valenta, R. Valero, A. L. Valeyre, D. Valiulis, A. Valovirta, E. Van Cauwenberge, P. Vandenplas, O. van weel, C. Vichyanond, P. Viegi, G. Wang, D. Y. Wickman, M. Woehrl, S. Wright, J. Yawn, B. P. Yiallouros, P. K. Zar, H. J. Zernotti, M. E. Zhong, N. Zidarn, M. Zuberbier, T. CA World Hlth Org Collaborating Ctr TI Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Rhinitis; asthma; Allergic Rhinitis and its Impact on Asthma; allergy; GRADE ID QUALITY-OF-LIFE; WORLD-HEALTH-ORGANIZATION; PERSISTENT TYPES; CONTROLLED-TRIAL; EUROPEAN-UNION; PRIMARY-CARE; 2008 UPDATE; GUIDELINES; MANAGEMENT; CLASSIFICATION AB Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified ARas mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIAWorld Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children. (J Allergy Clin Immunol 2012;130:1049-62.) C1 [Bousquet, J.; Demoly, P.; Bousquet, P. J.] Hop Arnaud Villeneuve, Dept Resp Dis, Univ Hosp, Montpellier, France. [Bousquet, J.] INSERM, U1018, CESP Ctr Res Epidemiol & Populat Hlth, Resp & Environm Epidemiol Team, Villejuif, France. [Schuenemann, H. J.; Brozek, J. L.] McMaster Univ, Dept Clin Epidemiol & Biostat & Med, Hamilton, ON, Canada. [Samolinski, B.] Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland. [Demoly, P.] Univ Hosp Montpellier, Hop Arnaud Villeneuve, INSERM, U657, Montpellier, France. [Baena-Cagnani, C. E.] Catholic Univ, Fac Med, Res Ctr Resp Med CIMER, Cordoba, Argentina. [Baena-Cagnani, C. E.] Univ Genoa, Sch Specializat, Genoa, Italy. [Bachert, C.] Univ Ghent, Dept Otorhinolaryngol, Upper Airways Res Lab, B-9000 Ghent, Belgium. [Bonini, S.] CNR, Inst Translat Pharmacol, Rome, Italy. [Bonini, S.] Univ Naples 2, Naples, Italy. [Boulet, L. P.] Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada. [Canonica, G. W.; Passalacqua, G.; Baiardini, I.; Braido, F.] Univ Genoa, Dept Internal Med, DIMI, I-16126 Genoa, Italy. [Casale, T. B.] Creighton Univ, Dept Med, Div Allergy & Immunol, Omaha, NE 68178 USA. [Cruz, A. A.] Univ Fed Bahia, ProAR Nucleo Excelencia Asma, Salvador, BA, Brazil. [Cruz, A. A.] CNPq, Salvador, BA, Brazil. [Fokkens, W. J.] Univ Amsterdam, Dept Otorhinolaryngol, NL-1012 WX Amsterdam, Netherlands. [Fokkens, W. J.] Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, NL-1105 AZ Amsterdam, Netherlands. [Fonseca, J. A.] Univ Porto, Sch Med, Dept Hlth Informat & Decis Sci, P-4100 Oporto, Portugal. [Fonseca, J. A.] Univ Porto, Sch Med, CINTESIS, P-4100 Oporto, Portugal. [Fonseca, J. A.] Hosp S Joao & Inst, Dept Allergy, Oporto, Portugal. [Fonseca, J. A.] Hosp CUF Porto, Oporto, Portugal. [van Wijk, R. Gerth] Erasmus MC, Dept Internal Med, Sect Allergol, Rotterdam, Netherlands. [Grouse, L.] Univ Washington, Sch Med, Seattle, WA USA. [Haahtela, T.] Helsinki Univ Hosp, Dept Allergy, Skin & Allergy Hosp, Helsinki, Finland. [Khaltaev, N.] GARD ARIA Coordinator, Geneva, Switzerland. [Kuna, P.] Med Univ Lodz, Dept Internal Med Asthma & Allergy, Barlicki Univ Hosp, Lodz, Poland. [Lockey, R. F.] Univ S Florida, Coll Med, Dept Internal Med, Div Allergy & Immunol, Tampa, FL 33612 USA. [Lockey, R. F.] James A Haley Vet Hosp, Tampa, FL USA. [Carlsen, K. C. Lodrup; Carlsen, K. H.] Univ Oslo, Oslo Univ Hosp, Dept Paediat, Oslo, Norway. [Mullol, J.] CIBERES, IDIBAPS, Hosp Clin, Rhinol Unit,ENT Dept, Barcelona, Spain. [Mullol, J.] CIBERES, IDIBAPS, Hosp Clin, Smell Clin,ENT Dept, Barcelona, Spain. [Naclerio, R.] Univ Chicago, Dept Otolaryngol Head & Neck Surg, Chicago, IL 60637 USA. [O'Hehir, R. E.] Alfred Hosp, Dept Allergy Immunol & Resp Med, Melbourne, Vic, Australia. [O'Hehir, R. E.] Monash Univ, Melbourne, Vic 3004, Australia. [Ohta, K.] Teikyo Univ, Sch Med, Dept Med, Div Resp Med & Allergol, Tokyo 173, Japan. [Palkonen, S.] EFA European Federat Allergy & Airways Dis Patien, Brussels, Belgium. [Papadopoulos, N. G.] Univ Athens, Dept Allergy, Pediat Clin 2, Athens, Greece. [Pawankar, R.] Nippon Med Sch, Bunkyo Ku, Tokyo 113, Japan. [Price, D.] Univ Aberdeen, Dept Primary Care Resp Med, Aberdeen, Scotland. [Ryan, D.] Woodbrook Med Ctr, Loughborough, Leics, England. [Ryan, D.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Simons, F. E. R.] Univ Manitoba, Fac Med, Winnipeg, MB, Canada. [Togias, A.] NIAID, Bethesda, MD 20892 USA. [Williams, D.] Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. [Yorgancioglu, A.] Celal Bayar Univ, Sch Med, Dept Pulmonol, Manisa, Turkey. [Yusuf, O. M.] Allergy & Asthma Inst, Islamabad, Pakistan. [Aberer, W.] Med Univ Graz, Dept Dermatol, Graz, Austria. [Adachi, M.] Showa Univ, Sch Med, Div Allergol & Resp Med, Tokyo 142, Japan. [Agache, I.] Transylvania Univ, Fac Med, Brasov, Romania. [Ait-Khaled, N.] Int Union TB & Lung Dis Union, Paris, France. [Akdis, C. A.] Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Davos, Switzerland. [Andrianarisoa, A.] Minist Hlth, Publ Hosp Med Serv, Antananarivo, Madagascar. [Annesi-Maesano, I.] INSERM, EPAR U707, Paris, France. [Annesi-Maesano, I.] Univ Paris 06, EPAR, UMR S, Paris, France. [Ansotegui, I. J.] Hosp Quiron Bizkaia, Dept Allergy & Immunol, Erandio Bilbao, Spain. [Bateman, E. D.] Univ Cape Town, Dept Med, Fac Hlth Sci, Div Pulmonol, ZA-7925 Cape Town, South Africa. [Bedbrook, A.] WHO, Collaborating Ctr Asthma & Rhinitis, Montpellier, France. [Beghe, B.] Univ Modena & Reggio Emilia, Dept Oncol Hematol & Resp Dis, Modena, Italy. [Beji, M.] Ctr Hosp Univ Rabta, Serv Pneumol Allergol, Tunis, Tunisia. [Bel, E. H.] Univ Amsterdam, Acad Med Ctr, Dept Pulmonol, NL-1105 AZ Amsterdam, Netherlands. [Ben Kheder, A.] Hop Mami, Ariana, Tunisia. [Bennoor, K. S.] Bangladesh Lung Fdn, Dhaka, Bangladesh. [Bennoor, K. S.] Natl Inst Dis Chest & Hosp, Dhaka, Bangladesh. [Bergmann, K. C.] Charite, Dept Dermatol, Allergy Ctr Charite, D-13353 Berlin, Germany. [Bieber, T.] Univ Med Ctr, Dept Dermatol & Allergy, Bonn, Germany. [Jensen, C. Bindslev] Odense Univ Hosp, Dept Dermatol, DK-5000 Odense, Denmark. [Jensen, C. Bindslev] Odense Univ Hosp, Allergy Ctr, DK-5000 Odense, Denmark. [Blaiss, M. S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Boner, A. L.] Univ Verona, Dept Paediat, I-37100 Verona, Italy. [Bouchard, J.] Univ Laval, Fac Med, Quebec City, PQ G1K 7P4, Canada. [Bouchard, J.] Hop Malbaie, La Malbaie, PQ, Canada. [Brightling, C. E.] Univ Leicester, Inst Lung Hlth, Leicester LE1 7RH, Leics, England. [Bush, A.] Royal Brompton Hosp, Dept Paediat Resp Med, London SW3 6LY, England. [Calderon, M. A.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Sect Allergy & Clin Immunol, London, England. [Caballero, F.] Ctr Med Docente La Trinidad Caracas, Dept Immunol, Caracas, Venezuela. [Calvo, M. A.] Univ Austral Chile, Fac Med, Dept Pediat, Valdivia, Chile. [Camargos, P. A. M.] Univ Fed Sao Joao del Rei, Hlth Sci Ctr, Hlth Sci Postgrad Program, Divinopolis, Brazil. [Caraballo, L. R.] Univ Cartagena, Immunol Res Inst, Cartagena De Indias, Colombia. [Carr, W.] So Calif Res, Mission Viejo, CA USA. [Cepeda, A. M.] Metropolitan Univ Barranquilla, Allergy & Immunol Lab, Barranquilla, Colombia. [Cesario, A.] IRCCS San Raffaele Pisana, Rome, Italy. [Cesario, A.] Univ Cattolica Sacro Cuore, Dept Thorac Surg, Rome, Italy. [Chavannes, N. H.] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands. [Chen, Y. Z.] Capital Inst Pediat, Asthma Clin, Natl Cooperat Grp Pediat Res Asthma, Beijing, Peoples R China. [Chen, Y. Z.] Capital Inst Pediat, Educ Ctr, Beijing, Peoples R China. [Chen, Y. Z.] Ctr Asthma Res & Educ, Beijing, Peoples R China. [Chiriac, A. M.] Hop Arnaud Villeneuve, Univ Hosp, Allergy Unit, Montpellier, France. [Chivato Perez, T.] Univ Hosp, Dept Allergol, Sch Med CEU San Pablo Madrid, Madrid, Spain. [Chkhartishvili, E.] Georgian Natl Univ, AIETI Med Sch, SEU Clin, Med Ctr, Tbilisi, Rep of Georgia. [Ciprandi, G.] Univ Genoa, Dept Internal Med, IRCCS Azienda Osped Univ San Martino, I-16126 Genoa, Italy. [Costa, D. J.] Univ Montpellier I, Primary Care Dept, Montpellier, France. [Cox, L.] Nova SE Univ, Coll Osteopath Med, Davie, FL USA. [Custovic, A.] Univ Manchester, Manchester, Lancs, England. [Dahl, R.] Aarhus Univ Hosp, Dept Resp Dis, DK-8000 Aarhus, Denmark. [Darsow, U.] Tech Univ Munich, Dept Dermatol & Allergy Biederstein, Munich, Germany. [Darsow, U.] TUM, Div Environm Dermatol, Munich, Germany. [Darsow, U.] TUM, Allergy Helmholtz Ctr, Munich, Germany. [De Blay, F.] Univ Hosp Strasbourg, Chest Dis Dept, Div Pulmonol Asthma & Allergol, Strasbourg, France. [Deleanu, D.] Univ Med & Pharm Iuliu Hatieganu, Dept Allergy, Med Clin 3, Romanian Soc Allergy & Clin Immunol, Cluj Napoca, Romania. [Denburg, J. A.] McMaster Univ, AllerGen NCE, Dept Med, Hamilton, ON, Canada. [Denburg, J. A.] McMaster Univ, AllerGen NCE, Michael G DeGroote Sch Med, Div Clin Immunol & Allergy,Fac Hlth Sci, Hamilton, ON, Canada. [Devillier, P.] Univ Versailles St Quentin, Hop Foch, UPRES EA 220, Suresnes, France. [Didi, T.] Ctr Hosp Reg Annecy, Serv Pneumol, Annecy, France. [Dokic, D.] Univ Ss Cyril & Methodius, Univ Clin Pulmonol & Allergy, Skopje, Macedonia. [Dolen, W. K.] Georgia Hlth Sci Univ, Augusta, GA USA. [Douagui, H.] Ctr Hosp Univ Beni Messous, Serv Pneumoallergol, Algiers, Algeria. [Dubakiene, R.] Vilnius Univ, Fac Med, Collaborating Ctr GA2LEN, Vilnius, Lithuania. [Durham, S. R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Dykewicz, M. S.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [El-Gamal, Y.] Ain Shams Univ, Childrens Hosp, Pediat Allergy & Immunol Unit, Cairo, Egypt. [El-Gamal, Y.] Egyptian Soc Pediat Allergy & Immunol, Cairo, Egypt. [El-Meziane, A.] Soc Marocaine Malad Resp, Casablanca, Morocco. [El-Meziane, A.] Ctr Resp Dis & Allergy, Casablanca, Morocco. [Emuzyte, R.] Vilnius Univ, Fac Med, Vilnius, Lithuania. [Fiocchi, A.] Univ Milan, Sch Med, Melloni Hosp, Milan, Italy. [Fletcher, M.] Educ Hlth, Warwick, England. [Fukuda, T.] Dokkyo Med Univ, Mibu, Tochigi, Japan. [Gamkrelidze, A.] WHO, Country Off Georgia, Tbilisi, Rep of Georgia. [Gereda, J. E.] Clin Ricardo Palma, Lima, Peru. [Gonzalez Diaz, S.] Univ Nuevo Leon UANL, Hosp Univ, Fac Med, Monterrey, Mexico. [Gotua, M.] Ctr Allergy & Immunol, Tbilisi, Rep of Georgia. [Guzman, M. A.] Univ Chile, Clin Hosp, Dept Med, Immunol & Allergol Div, Santiago, Chile. [Hellings, P. W.] Univ Hosp Leuven, Dept Otorhinolaryngol Head & Neck Surg, Louvain, Belgium. [Hellquist-Dahl, B.] Cent Reg Denmark, Ctr Publ Hlth & Qual Improvement, Aarhus, Denmark. [Horak, F.] Allergy Ctr Vienna W, Vienna, Austria. [Hourihane, J. O'B.] Natl Univ Ireland Univ Coll Cork, Dept Paediat & Child Hlth, Cork, Ireland. [Howarth, P.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England. [Humbert, M.] Univ Paris 11, Serv Pneumol, Hop Antoine Beclere, AP HP,INSERM,U999, Clamart, France. [Ivancevich, J. C.] Salvador Univ, Sch Med, Dept Immunol, Buenos Aires, DF, Argentina. [Jackson, C.] Univ St Andrews, St Andrews, Fife, Scotland. [Just, J.] Univ Paris, APHP, Ctr Asthme & Allergies, Grp Hosp Trousseau La Roche Guyon, F-75252 Paris, France. [Kalayci, O.] Hacettepe Univ, Sch Med, Pediat Allergy & Asthma Unit, Ankara, Turkey. [Kaliner, M. A.] George Washington Univ, Sch Med, Washington, DC USA. [Kaliner, M. A.] Inst Asthma & Allergy, Chevy Chase, MD USA. [Kalyoncu, A. F.] Hacettepe Univ Hosp, Dept Chest Dis, Adult Allergy Unit, Ankara, Turkey. [Keil, T.] Charite, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany. [Keith, P. K.] McMaster Univ, Hamilton, ON, Canada. [Khayat, G.] Hotel Dieu France, Serv Pneumol & Reanimat Med, Beirut, Lebanon. [Khayat, G.] Univ St Joseph, Fac Med, Beirut, Lebanon. [Kim, Y. Y.] Natl Med Ctr, Seoul, South Korea. [Kim, Y. Y.] Seoul Natl Univ, Seoul, South Korea. [Kim, Y. Y.] Korea Asthma Allergy Fdn, Seoul, South Korea. [N'Goran, B. Koffi] Ctr Hosp Univ, Serv Malad Resp, Abidjan, Cote Ivoire. [Koppelman, G. H.] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Beatrix Childrens Hosp,Dept Pediat Pulmonol & Ped, Groningen, Netherlands. [Kowalski, M. L.] Med Univ Lodz, Dept Immunol Rheumatol & Allergy, Lodz, Poland. [Kull, I.] Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden. [Kull, I.] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden. [Kvedariene, V.] Vilnius Univ, Ctr Pulmonol & Allergol, Vilnius, Lithuania. [Kvedariene, V.] Vilnius Univ Hosp Santariskiu Klinikos, Vilnius, Lithuania. [Larenas-Linnemann, D.] Hosp Med Sur, Dept Allergy, Mexico City, DF, Mexico. [Le, L. T.] Univ Med & Pharm, Ho Chi Minh City, Vietnam. [Lemiere, C.] Hop Sacre Coeur Montreal, Montreal, PQ, Canada. [Lemiere, C.] Univ Montreal, Montreal, PQ, Canada. [Li, J.] Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China. [Lieberman, P.] Univ Tennessee, Coll Med, Memphis, TN USA. [Lipworth, B.] Univ Dundee, Ninewells Hosp, Asthma & Allergy Res Grp, Dundee, Scotland. [Mahboub, B.] Dubai Hlth Author, Sharjah, U Arab Emirates. [Mahboub, B.] Univ Sharjah, Sharjah, U Arab Emirates. [Makela, M. J.] Helsinki Univ Hosp, Dept Allergy, Skin & Allergy Hosp, Helsinki, Finland. [Marshall, G. D.] Univ Mississippi, Med Ctr, Div Clin Immunol & Allergy, Jackson, MS 39216 USA. [Martinez, F. D.] Univ Arizona, Coll Med, Arizona Resp Ctr, Tucson, AZ USA. [Martinez, F. D.] Univ Arizona, Inst BIO5, Tucson, AZ USA. [Masjedi, M. R.] Shahid Beheshti Univ Med Sci, NRITLD, Tehran, Iran. [Masjedi, M. R.] Shahid Beheshti Univ Med Sci, Chron Resp Dis Res Ctr, Tehran, Iran. [Maurer, M.] Charite, Dept Dermatol & Allergy, D-13353 Berlin, Germany. [Mavale-Manuel, S.] Maputo Cent Hosp, Dept Peadiat, Maputo, Mozambique. [Mavale-Manuel, S.] Eduardo Mondlane Univ, Fac Med, Maputo, Mozambique. [Mazon, A.] Childrens Hosp La Fe, Unit Pediat Allergy & Pneumol, Valencia, Spain. [Melen, E.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Melen, E.] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden. [Meltzer, E. O.] Univ Calif San Diego, Allergy & Asthma Med Grp, San Diego, CA 92103 USA. [Meltzer, E. O.] Univ Calif San Diego, Res Ctr, San Diego, CA 92103 USA. [Mendez, N. H.] IMSS, Dept Allergy & Clin Immunol, Ctr Med Nacl Siglo 21, Mexico City, DF, Mexico. [Merk, H.] Univ Aachen, Dept Dermatol, Aachen, Germany. [Mihaltan, F.] Inst Pneumol Marius Nasta, Bucharest, Romania. [Mohammad, Y.] Tishreen Univ, Sch Med, Dept Internal Med, WHO EMRO Collaborating Ctr Training & Res Chron R, Latakia, Syria. [Morais-Almeida, M.] CUF Descobertas Hosp, Immunoallergy Dept, Lisbon, Portugal. [Muraro, A.] Univ Padua, Dept Pediat, Food Allergy Referral Ctr Veneto Reg, Padua, Italy. [Nafti, S.] Mustapha Hosp, Algiers, Algeria. [Namazova-Baranova, L.] Sci Ctr Childrens Hlth RAMS, Moscow, Russia. [Nekam, K.] Hosp Hospitaller Bros Buda, Budapest, Hungary. [Neou, A.] Charite, Allergie Ctr Charite ECARF, Dept Dermatol Venerol & Allergy, D-13353 Berlin, Germany. [Niggemann, B.] German Red Cross Hosp Westend, Berlin, Germany. [Nizankowska-Mogilnicka, E.] Jagiellonian Univ, Sch Med, Dept Pulmonol, Krakow, Poland. [Nyembue, T. D.] Kinshasa Univ, ENT Dept, Kinshasa, Zaire. [Okamoto, Y.] Chiba Univ Hosp, Dept Otorhinolaryngol, Chiba, Japan. [Okubo, K.] Nippon Med Sch, Dept Otolaryngol, Bunkyo Ku, Tokyo 113, Japan. [Ouedraogo, S.] Ctr Hosp Univ Pediat Charles de Gaulle, Ouagadougou, Burkina Faso. [Ozdemir, C.] Marmara Univ, Div Pediat Allergy & Immunol, Istanbul, Turkey. [Ozdemir, C.] Mem Hlth Grp, Istanbul, Turkey. [Panzner, P.] Charles Univ Prague, Fac Med Plzen, Dept Immunol & Allergol, Prague, Czech Republic. [Pali-Schoell, I.] MESSERLI Res Inst, Vienna, Austria. [Pali-Schoell, I.] Med Univ Vienna, Univ Vet Med Vienna, Vienna, Austria. [Pali-Schoell, I.] Univ Vienna, Vienna, Austria. [Park, H. S.] Ajou Univ, Sch Med, Suwon 441749, South Korea. [Pigearias, B.] NICE, Paris, France. [Pigearias, B.] Soc Pneumol Langue Francaise, Paris, France. [Pohl, W.] Krankenhaus Hietzing, Karl Landsteiner Inst Expt & Clin Pneumol, Dept Pulm Med, Vienna, Austria. [Popov, T. A.] Alexanders Univ Hosp, Clin Allergy & Asthma, Sofia, Bulgaria. [Postma, D. S.] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Dept Pulmonol, Groningen, Netherlands. [Potter, P.] Univ Cape Town, Lung Inst, ZA-7925 Cape Town, South Africa. [Potter, P.] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Rabe, K. F.] Leiden Univ, Dept Pulmonol, Med Ctr, Leiden, Netherlands. [Rabe, K. F.] Grosshansdorf Clin, Grosshansdorf, Germany. [Ratomaharo, J.] Hop Prive Athis Mons, Serv Pneumol, Athis Mons, France. [Reitamo, S.] Helsinki Univ Hosp, Dept Dermatol, Skin & Allergy Hosp, Helsinki, Finland. [Ring, J.] Tech Univ Munich, CKCARE, Dept Dermatol Allergy Biederstein, Munich, Germany. [Roberts, R.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Rogala, B.] Med Univ Silesia, Dept & Clin Internal Dis Allergol & Clin Immunol, Katowice, Poland. [Romano, A.] Complesso Integrato Columbus, Allergy Unit, Rome, Italy. [Romano, A.] IRCCS Oasi Maria SS, Troina, Italy. [Rodriguez, M. Roman] Son Pisa Primary Care Ctr, IB Salut Balear Hlth Serv, Int Primary Care Resp Grp, Palma de Mallorca, Spain. [Rosado-Pinto, J.] Hosp Luz, Immunoallergy Dept, Lisbon, Portugal. [Rosenwasser, L.] Univ Missouri, Kansas City Sch Med, Kansas City, MO 64110 USA. [Rosenwasser, L.] Childrens Mercy Hosp, Kansas City, MO USA. [Rottem, M.] Emek Med Ctr, Afula, Israel. [Rottem, M.] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel. [Sanchez-Borges, M.] Ctr Med Docente La Trinidad, Dept Allergy & Clin Immunol, Caracas, Venezuela. [Scadding, G. K.] UCL, Royal Natl TNE Hosp, London, England. [Schmid-Grendelmeier, P.] Univ Zurich Hosp, Dept Dermatol, Allergy Unit, CH-8091 Zurich, Switzerland. [Sheikh, A.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Allergy & Resp Res Grp, Edinburgh, Midlothian, Scotland. [Sole, D.] Univ Fed Sao Paulo, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, Sao Paulo, Brazil. [Sooronbaev, T.] Natl Ctr Cardiol & Internal Med, Bishkek, Kyrgyzstan. [Spicak, V.] Ctr ACI Immunoflow, Czech Initiat Asthma, Prague, Czech Republic. [Spranger, O.] GAAPP, Vienna, Austria. [Stein, R. T.; Sunyer, J.] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Stein, R. T.] Pontificia Univ Catolica RGS, Sch Med, Porto Alegre, RS, Brazil. [Stoloff, S. W.] Univ Nevada, Sch Med, Reno, NV 89557 USA. [Sunyer, J.] Hosp Mar, Municipal Inst Med Res IMIM, Barcelona, Spain. [Sunyer, J.] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain. [Sunyer, J.] Univ Pompeu Fabra UPF, Barcelona, Spain. [Szczeklik, A.] Jagiellonian Univ, Coll Med, Krakow, Poland. [Todo-Bom, A.] Coimbra Univ Hosp, Immunoallergy Dept, Coimbra, Portugal. [Toskala, E.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Toskala, E.] Finnish Inst Occupat Hlth, Helsinki, Finland. [Tremblay, Y.] Univ Laval, Fac Med, Dept Obstet & Gynecol, Laval, PQ, Canada. [Valenta, R.] Med Univ Vienna, Christian Doppler Lab Allergy Res, Div Immunopathol, Dept Pathophysiol & Allergy Res,Ctr Pathophysiol, Vienna, Austria. [Valero, A. L.] Hosp Clin Barcelona, Dept Pneumol, Allergy Unit, Immunoallergia Resp Clin, Barcelona, Spain. [Valero, A. L.] IDIBAPS, Barcelona, Spain. [Valero, A. L.] CIBERES, Barcelona, Spain. [Valeyre, D.] Univ Paris 13, Bobigny, France. [Valeyre, D.] Avicenne Hosp, AP HP, Bobigny, France. [Valiulis, A.] Vilnius Univ, Fac Med, Dept Paediat, Vilnius, Lithuania. [Valiulis, A.] Lithuanian Natl Council Childs Hlth, Vilnius, Lithuania. [Valovirta, E.] Terveystalo Turku, Allergy Clin, Turku, Finland. [Valovirta, E.] Univ Turku, Dept Lung Dis & Clin Immunol, Turku, Finland. [Van Cauwenberge, P.] Univ Ghent, Dept Otorhinolaryngol, B-9000 Ghent, Belgium. [Vandenplas, O.] Catholic Univ Louvain, Univ Hosp Mt Godinne, Yvoir, Belgium. [van weel, C.] Radboud Univ Nijmegen, Med Ctr, Dept Primary & Community Care, NL-6525 ED Nijmegen, Netherlands. [Vichyanond, P.] Siriraj Hosp, Fac Med, Dept Pediat, Bangkok, Thailand. [Viegi, G.] CNR, IBIM, Palermo, Italy. [Viegi, G.] Clin Physiol IFC, Pisa, Italy. [Wang, D. Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore. [Wickman, M.] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden. [Wickman, M.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Woehrl, S.] Floridsdorf Allergy Ctr FAZ, Vienna, Austria. [Woehrl, S.] Med Univ Vienna, Dept Dermatol, DIAID, Vienna, Austria. [Wright, J.] Bradford Teaching Hosp Fdn Trust, Bradford Inst Hlth Res, Bradford, W Yorkshire, England. [Yawn, B. P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, B. P.] Univ Minnesota, Dept Family & Community Hlth, Rochester, MN USA. [Yiallouros, P. K.] Harvard Univ, Sch Publ Hlth, Cyprus Int Inst Environm & Publ Hlth Assoc, Limassol, Cyprus. [Yiallouros, P. K.] Cyprus Univ Technol, Limassol, Cyprus. [Zar, H. J.] Univ Cape Town, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, ZA-7925 Cape Town, South Africa. [Zernotti, M. E.] Catholic Univ Cordoba, Sch Med, Dept Otorhinolaryngol, Cordoba, Argentina. [Zhong, N.] Guangzhou Med Univ, Guangzhou Inst Resp Dis, Guangzhou, Guangdong, Peoples R China. Guangzhou Med Univ, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China. [Zidarn, M.] Univ Clin Resp & Allerg Dis, Golnik, Slovenia. [Zuberbier, T.] Charite, Dept Dermatol, Allergy Ctr Charite, D-13353 Berlin, Germany. [Zuberbier, T.] Charite, Network Excellence, Global Allergy & Asthma European Network GA2LEN, D-13353 Berlin, Germany. RP Bousquet, J (reprint author), CHU Montpellier, F-34295 Montpellier 05, France. EM jean.bousquet@inserm.fr RI Deleanu, Diana/G-3963-2015; Fonseca, Joao/B-7562-2008; Bindslev-Jensen, Carsten/H-1877-2011; CESARIO, Alfredo/O-4215-2015; Annesi-Maesano, Isabella/D-9173-2016; van Weel, Chris/D-4375-2009; Custovic, Adnan/A-2435-2012; Osborne, Nicholas/N-4915-2015; Sunyer, J/G-6909-2014; Wohrl, Stefan/B-6954-2013; Casale, Thomas/K-4334-2013; Stein, Renato/G-2975-2012; FMUP, CINTESIS/C-6631-2014; Chavannes, Niels/F-1148-2011; Wright, John/H-1624-2012; Sheikh, Aziz /D-2818-2009; Baigenjin, Abay/P-4137-2014; Stein, Renato/K-2568-2014; Kvedariene, Violeta /D-7730-2011; Namazova-Baranova, Leyla/D-4934-2013; Sole, Dirceu/D-7789-2013; Dahl, Ronahl/F-8170-2013; jackson, cathy/H-4869-2013; O'Hehir, Robyn/H-3627-2011; OI Mazon, Angel/0000-0001-5639-1037; Namazova-Baranova, Leyla/0000-0002-2209-7531; Terreehorst, Ingrid/0000-0002-3264-2740; Deleanu, Diana/0000-0002-8431-8352; Bonini, Sergio/0000-0003-0079-3031; Masjedi, Mohammadreza/0000-0003-4964-3851; Fonseca, Joao/0000-0002-0887-8796; Bindslev-Jensen, Carsten/0000-0002-8940-038X; CESARIO, Alfredo/0000-0003-4687-0709; van Weel, Chris/0000-0003-3653-4701; Custovic, Adnan/0000-0001-5218-7071; Osborne, Nicholas/0000-0002-6700-2284; Sunyer, J/0000-0002-2602-4110; Wohrl, Stefan/0000-0002-6324-0007; Papadopoulos, Nikolaos/0000-0002-2508-3872; Bousquet, Philippe Jean/0000-0002-0217-5483; Casale, Thomas/0000-0002-3149-7377; FMUP, CINTESIS/0000-0001-7248-2086; Chavannes, Niels/0000-0002-8607-9199; Wright, John/0000-0001-9572-7293; Sheikh, Aziz /0000-0001-7022-3056; Baigenjin, Abay/0000-0002-7703-5004; Romano, Antonino/0000-0001-9742-9898; Price, David/0000-0002-9728-9992; O'Hehir, Robyn/0000-0002-3489-7595; Fiocchi, Alessandro/0000-0002-2549-0523; Ryan, Dermot/0000-0002-4115-7376; Park, Hae-Sim/0000-0003-2614-0303; Popov, Todor/0000-0001-5052-5866; Kull, Inger/0000-0001-6096-3771; Makela, Mika/0000-0002-2933-3111; Panzner, Petr/0000-0002-1291-450X FU Stallergenes; ALK-Abello; European Academy of Allergy and Clinical Immunology (EAACI); MSD; Novartis; Nycomed/Takeda; PHADIA/Thermo Fischer; 3M; AstraZeneca; GlaxoSmithKline; Merck Frosst; Altair; Amgen; Asmacure; Boehringer-Ingelheim; Genentech; Pharmaxis; Schering; Wyeth; Ache; Brazilian Research Council; Fundacao de Amparo a Pesquisa da Bahia; Fundacao Ciencia e Tecnologia; Sociedade Portuguesa de Alergologia e Immunologia Clinica; Abdi Ibrahim; MSD; OrionPharma; Nasonebs; Merck; McNeal; Chiesi; Nycomed; Air Liquid Healthcare; Mundipharma; Almirall; Kyorin; Teva; UK National Health Service; Aerocrine; AKL Ltd; PREDICTA; Swiss National Science Foundation; MeDALL; Global Allergy and Asthma European Network (GA 2LEN); Christine Kuthe Center for Allergy Research and Education; Faes Farma; Bial; Johnson Johnson; Sanofi; HAD treasurer; Innovative Medicine Initiative (EU); Helse Sor-Ost RHF (Southern and Eastern Norway Regional Health Authority); MEDA; Alcon; ISTA; Thermo-Fisher; Airsonett; Medical Research Council; Moulton Charitable Trust; AB Science; Canadian Institutes for Health Research; AllerGen NCE; Merck/Schering-Plough; Circassia; University Hospital; Medical School of Universidad Autonoma de Nuevo Leon, Mexico; Children's Research Foundation (Ireland); Danone; Food Standards Agency (United Kingdom); European Union (EU); DTG; Netherlands Asthma Foundation; Merck-Sharp-Dohme, Mexico; Allerquim Mexico; Abbott; Apotex; HRA; MedImmune; Schering-Plough; Proctor Gamble; Sunovion (Sepracor); Phadia; Servier; CSC JohnsonJohnson; Oxygen Plus; New Medics; European Respiratory Society; Societe de Pneumologie de Langue Francaise Asthma; Ministry of Health, Welfare, and Labor; Altana; Takeda; UCB; Uriach advisory board; NAPP; Royal College of GPs Clinical Champion in Allergy; Agency for Healthcare Research and Quality (AHRQ); AnseII; Bayer Schering; OST; Fujisawa; IHAL; Henkel; Kryolan; Leti; MSO; Procter and Gamble; Sanofi-Aventis; Scientific Advisory Board for the German Society for Allergy and Clinical Immunology; German Federal Ministry of Consumer Protection; European Centre for Allergy Research Foundation (ECARF) FX J. Bousquet has received honoraria from Stallergenes, Actelion, Almirall, AstraZeneca, Chiesi, GlaxoSmithKline, Merck, Novartis, OM Pharma, Sanofi, Teva, and Uriach. P. Demoly is a speaker for and on the advisory board of Stallergenes and ALK-Abello; is a consultant for Therabel and Crucell; is a speaker for Merck/Schering- Plough, AstraZeneca, and GlaxoSmithKline; has received research support from Stallergenes and ALK-Abello; and is the Vice President of the European Academy of Allergy and Clinical Immunology (EAACI). S. Bonini has a scientific board member and speaker at Symposia sponsored by A. Menarini, MS&D, Novartis, Nycomed/Takeda, PHADIA/Thermo Fischer, and Stallergenes and is a member of the LIBRA (Italian Guidelines for Asthma, Rhinitis, and COPD) executive board. L. P. Boulet is on the advisory boards for AstraZeneca, GlaxoSmithKline, Merck Frosst, and Novartis; has received lecture fees from 3M, AstraZeneca, GlaxoSmithKline, Merck Frosst, and Novartis; has received research support from Altair, Amgen, Asmacure, AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Pharmaxis, Schering, Wyeth, and Merck Frosst; is chair for the Canadian Thoracic Society Respiratory Guidelines Committee and the Global Initiative for Asthma (GINA) Guidelines and Implementation Committee; is an organizational holder for the Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health; and is a member of the Knowledge Translation Canada. T. B. Casale is on the Stallergenes advisory board, is a consultant for Roche has received research support from Stallergenes and Roche, and is Executive Vice President for the American Academy of Allergy, Asthma & Immunology (AAAAI). A. A. Cruz is an advisor and lecturer for Merck and Mantecorp; is a lecturer for GlaxoSmithKline, Novartis, Chiesi, and Aventis; has received an educational grant from Ache; and has received research support from the Brazilian Research Council, Fundacao de Amparo a Pesquisa da Bahia, and GlaxoSmithKline. W. J. Fokkens has received research support from GlaxoSmithKline and provided legal consultation/expert witness testimony for Stallergenes. J. A. Fonseca has received lecture and consulting fees from Merck has received research support from the Fundacao Ciencia e Tecnologia and is Vice President of the Sociedade Portuguesa de Alergologia e Immunologia Clinica. L. Grouse has received funds from Novartis for personal services. T. Haahtela has received lecture fees from Abdi Ibrahim, GlaxoSmithKline, MSD, and OrionPharma and has received research support from Stallergenes. K. C. Lodrup Carlsen has received research support from MeDALL EU. R. Naclerio is on the speaker's bureau for Merck and Sunovion; is a consultant for Teva, Kalypsys, and Regeneron; and has received research support from Nasonebs, GlaxoSmithKline, Merck, and McNeal. K. Ohta has received lecture honoraria from MSD, Novartis, and GlaxoSmithKline. S. Palkonen's employer received grants from Novartis, GlaxoSmithKline, Boehringer-Ingelheim, Pfizer, Chiesi, ALK-Abello , Stallergenes, Nycomed, AstraZeneca, and Air Liquid Healthcare. N. G. Papadopoulos has received honoraria from Merck, AllergoPharma, Abbott, and Uriach. D.; r Price has received consultancy fees from Merck, Mundipharma, Novartis, GlaxoSmithKline, Almirall, Chiesi, Kyorin, and Teva; has received consultancy fees and grants from Pfizer, AstraZeneca, and Boehringer-Ingelheim; has received research support from the UK National Health Service, Aerocrine, and Nycomed; holds shares in AKL Ltd; and is director of Research in Real Life Ltd. D. Ryan is a consultant for Uriach and is Allergy Lead for the International Primary Care Respiratory Group. F. E. R. Simons is on the Rupatadine Medical Advisory Board. D. Williams's spouse is employed by GlaxoSmithKline. A. Yorgancioglu has received honoraria from MSD, GlaxoSmithKline, and Novartis and has received research support from Chiesi. O. M. Yosuf has received honoraria from and is director and chair of research for the International Primary Care Respiratory Group. C. A. Akdis has received research support from Novartis, PREDICTA, Swiss National Science Foundation, MeDALL, the Global Allergy and Asthma European Network (GA 2LEN), and the Christine Kuthe Center for Allergy Research and Education; has provided legal consultation/expert witness testimony on the topics of Actellion Th2-specific receptors, Aventis T-cell and B-cell regulation, Stallergenes allergen-specific immunotherapy, and Allergopharma allergen-specific immunotherapy; is a Fellow and interest group member of the AAAAI; is president of the EAACI; and is a GA 2LEN ex-com memberWPleader. I. J. Ansotegui has received consulting fees and honoraria from Faes Farma and Bial, has received consulting fees from Johnson & Johnson and Sanofi, and has received honoraria from AstraZeneca. E. D. Bateman is a consultant for and on the advisory board of Almirall; is on the advisory board of Forest, Novartis, Napp Pharma, and Actelion; has received lecture and consultancy fees and grants and is on the advisory board for Boehringer Ingelheim; has received lecture fees and is on the advisory board for GlaxoSmithKline, Nycomed, and AstraZeneca; is a consultant for ALK-Abello; and is the GINA chair of board. E. H. Bel has received research support from GlaxoSmithKline, Novartis, and Innovative Medicine Initiative (EU). M. S. Blaiss is a speaker for GlaxoSmithKline, Merck, AstraZeneca, Nycomed, Sunovion, and Genentech; is a consultant for Alcon, ISTA, Allergan, Proctor & Gamble, and Pfizer; has received research support from GlaxoSmithKline; and is HAD treasurer. M. A. Calderon is a speaker for ALK-Abello, Merck, and STG. K. H. Carlsen has received research support from Helse Sor-Ost RHF (Southern and Eastern Norway Regional Health Authority). W. Carr is a consultant for and has received research support from MEDA, Alcon, and ISTA. A. M. Cepeda is a speaker for MSD, AstraZeneca, and Novartis and has received research support from Novartis and Universidad Metropolitana. L. Cox is a speaker for Thermo-Fisher and ISTA and has received research support from Stallergenes and Teva. A. Custovic has received lecture fees from GlaxoSmithKline, Thermo-Fisher, MSD, and Airsonett; is on the advisory board for Novartis; and has received research support from the Medical Research Council and Moulton Charitable Trust. R. Dahl has received lecture fees from ALK-Abello and MSD, has received research support from ALK-Abello and Stallergenes, and is chair of the Danish Respiratory Society. U. Darsow is a consultant for Benoard. F. De Blay has received research support from Stallergenes, ALK-Abello, Novartis, GlaxoSmithKline, AB Science, and Amgen. J. A.; r Denburg has received research support from the Canadian Institutes for Health Research and AllerGen NCE. P. Devillier has received consultancy fees and honoraria from Stallergenes and has received consultancy fees from Merck/Schering-Plough, GlaxoSmithKline, and AstraZeneca. S. R. Durham is a consultant and speaker for ALK-Abello and Merck, is a speaker for GlaxoSmithKline, has received consultancy fees from Boehringer Ingelheim and Circassia, has received research support from ALK-Abello and Novartis, has provided legal consultation/expert witness testimony on the topic of topical corticosteroids and antihistamines in allergic rhinitis is on the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID) steering committee, and is on the British Society for Allergy and Clinical Immunology standards of care committee. M. S. Dykewicz is a consultant for Merck; is on the AAAAI Board of Directors, Needs Assessment Committee, Rhinitis/Sinusitis/Ocular Diseases Committee, and Web Site Oversight Committee; and is on the American College of Allergy, Asthma & Immunology (ACAAI) Program Directors Advisory Committee (chair), Annual Program Planning Committee, Publications Committee, Rhinitis-Sinusitis Committee, Occupational Health Committee, Ocular Allergy Committee. A. Fiocchi has received research support from Stallergenes. S. Gonzalez Diaz is a speaker for GlaxoSmithKline, MSD, and Takeda and has received research support from the University Hospital and Medical School of Universidad Autonoma de Nuevo Leon, Mexico. M. Gotua has received honoraria from GlaxoSmithKline and AstraZeneca. J. O'B. Hourihane has received research support from the Children's Research Foundation (Ireland), Danone, the Food Standards Agency (United Kingdom), and Stallergenes; in addition, his employer, University College Cork, holds a patent on challenge outcome predictor software. M. Humbert has received consultancy and lecture fees from AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Stallergenes, and Teva. J. C. Ivancevich is on the Faes Farma advisory board, is speaker for Laboratorios Casasco Argentina, and is Web editor for the World Allergy Organization and Interasma. O. Kalayci was the Uriach Pharma chairperson at the company sponsor symposium. M. A. Kaliner is a consultant for Ista and Alcon, has received research support from multiple allergy and asthma companies, and has provided legal consultation/expert witness testimony for Alcon. T. Keil has received research support from the European Union (EU) and DTG. P. K. Keith is a speaker for and has received research support from GlaxoSmithKline and Merck. B. Koffi N'Goran is a speaker for AstraZeneca and GlaxoSmithKline. G. H. Koppelman has received research support from the Netherlands Asthma Foundation and MeDALL. D. E. Larenas-Linnemann has received a speaker's fee and travel grant from Merck-Sharp-Dohme, Mexico; has received a speaker's fee from AstraZeneca; has received travel grants from Allerquim Mexico, ALK-Abello, and Stallergenes; has received research support from Allerquim Mexico, ALK-Abello, Stallergenes, and Greer Laboratories; and is chair of the IT committee for the AAAAI and Mexican College of Clinical Immunology and Allergy. L. T. Le has received honoraria from GlaxoSmithKline and AstraZeneca, has received research support and honoraria from MSD, and is chair of the Respiratory Society of Ho Chi Minh City, Vietnam. C. Lemiere is on the AstraZeneca advisory board. P. Lieberman is an advisor for the Allergy Foundation of America. B.; r Lipworth has provided legal consultation/expert witness testimony for Nycomed on the topic of nasal ciclesonide. B. Mahboub is employed by the Dubai Health Authority and the University of Sharjah. F. D. Martinez is a consultant for MedImmune and has received lecture honorarium and travel fees from Abbott. E. O. Meltzer is a consultant and on the advisory board for Alcon, AstraZeneca, Bausch + Lomb, Dey, Forest, Ista, Johnson & Johnson, Meda, Merck, ONO Pharma, OptiNose, Proctor& Gamble, Rady Children's Hospital, Rigel, Sanofi Aventis, Sepracor, Stallergenes, Teva, Alexza, Boehringer Ingelheim, Kalypsys, and Sunovion; is a speaker for the AAAAI, Alcon, Allergists for Israel, Dey, Florida Allergy Asthma Immunol Society, Ista, Sepracor, Teva, Merck, and Sunovion; has received research support from Amgen, Apotex, HRA, MedImmune, Schering-Plough, Alcon, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Proctor & Gamble, Sunovion (Sepracor), and Teva; has provided legal consultation/expert witness testimony for Aventis Pharmaceuticals and Sanofi Aventis in the USLLC v. Barr Laboratories Fexofenadine Litigation; and is a Fellow of the AAAAI, ACAAI, and World Allergy Organization (WAO). H. Merk has received research support from Phadia and has provided legal consultation/expert witness testimony for Novartis and ALK-Abello. F. Mihaltan has received consulting fees and honoraria from AstraZeneca, GlaxoSmithKline, MSD, Novartis, Nycomed, Boehringer Ingelheim, Servier, Sanofi, Pfizer, CSC Johnson&Johnson, Oxygen Plus, and New Medics. S. Nafti has received research support from the European Respiratory Society and the Societe de Pneumologie de Langue Francaise Asthma and has provided legal consultation/expert witness testimony for GlaxoSmithKline on the topics of asthma and chronic obstructive pulmonary disease. Y. Okamoto is a medical advisory for Taibo Pharmaceutical Co, Ono Pharmaceutical Co, and Meiji Nyugyo Co and has received research support from the Ministry of Health, Welfare, and Labor. D. S. Postma has received consultancy fees from Nycomed, GlaxoSmithKline, AstraZeneca, and Chiesi. K. F. Rabe has received research support from Altana, Novartis, AstraZeneca, and MSD and has provided legal consultation/expert witness testimony for AstraZeneca, Chiesi, Novartis, MSD, and GlaxoSmithKline. J. Ring has received research support from ALK-Abello, Allergopharma, Almirall-Hermal, Astellas, Bencard, Biogen-Idec, Gladerma, GlaxoSmithKline, Leo, MSD, Novartis, Phadia, PLS Design, and Stallergenes. R. Roberts is president of the World Organization of Family Doctors and the American Academy of Family Physicians Foundation and is Vice Chair of the Interstate Postgraduate Medical Association. B. Rogala has received lecture fees from Takeda, Nycomed, Teva, UCB, and Chiesi and is on the advisory board for MSD and AstraZeneca. G. K. Scadding has received research support from and is a speaker for ALK-Abello and GlaxoSmithKline, is on the Uriach advisory board, and is a speaker for Merck. A. Sheikh has received consultancy fees from Phadia and NAPP and is a Royal College of GPs Clinical Champion in Allergy. S. W. Stoloff is a consultant and on the advisory board for Teva and is a consultant for Aerocrine, Merck, and Sunovion. B. P. Yawn has received research support from the Agency for Healthcare Research and Quality (AHRQ) and the National Heart, Lung, and Blood Institute (NHLBI). T.; r Zuberbier has received consultancy fees, honoraria, and/or research support from AnseII, Bayer Schering, OST, Fujisawa, IHAL, Henkel, Kryolan, Leti, MSO, Novartis, Procter and Gamble, Sanofi-Aventis, Schering-Plough, Stallergenes, and UCB; is on the Scientific Advisory Board for the German Society for Allergy and Clinical Immunology; is on the Expert Commission "Novel Food'' of the German Federal Ministry of Consumer Protection; is Head of the European Centre for Allergy Research Foundation (ECARF); is a Committee member of the World Health Organization (WHO) Initiative Allergic Rhinitis and its Impact on Asthma (ARIA); is a Member or the WAO Communications Council; and is Secretary General of GA 2 LEN. The rest of the authors declare that they have no relevant conflicts of interest. NR 107 TC 181 Z9 201 U1 14 U2 160 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 NOV PY 2012 VL 130 IS 5 BP 1049 EP 1062 DI 10.1016/j.jaci.2012.07.053 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 030LE UT WOS:000310571400003 PM 23040884 ER PT J AU Wilson, S Rand, C Taggart, V AF Wilson, Sandra Rand, Cynthia Taggart, Virginia TI Guidance is also needed on how to choose from existing asthma-specific quality-of-life measures Reply SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 [Wilson, Sandra] Palo Alto Med Fdn, Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94301 USA. [Rand, Cynthia] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Taggart, Virginia] NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. RP Wilson, S (reprint author), Palo Alto Med Fdn, Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94301 USA. EM taggartv@nih.gov NR 4 TC 0 Z9 0 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2012 VL 130 IS 5 BP 1219 EP 1220 DI 10.1016/j.jaci.2012.08.035 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 030LE UT WOS:000310571400033 ER PT J AU Macvanin, M Edgar, R Cui, F Trostel, A Zhurkin, V Adhya, S AF Macvanin, Mirjana Edgar, Rotem Cui, Feng Trostel, Andrei Zhurkin, Victor Adhya, Sankar TI Noncoding RNAs Binding to the Nucleoid Protein HU in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MICROARRAY ANALYSIS; MESSENGER-RNAS; DNA-BINDING; RIBOSOMAL-RNA; IDENTIFICATION; TRANSLATION; COMPLEXES; GENOME; ARRAYS; IHF AB Some unidentified RNA molecules, together with the nucleoid protein HU, were suggested to be involved in the nucleoid structure of Escherichia coli. HU is a conserved protein known for its role in binding to DNA and maintaining negative supercoils in the latter. HU also binds to a few RNAs, but the full spectrum of its binding targets in the cell is not known. To understand any interaction of HU with RNA in the nucleoid structure, we immunoprecipitated potential HU-RNA complexes from cells and examined bound RNAs by hybridization to whole-genome tiling arrays. We identified associations between HU and 10 new intragenic and intergenic noncoding RNAs (ncRNAs), 2 of which are homologous to the annotated bacterial interspersed mosaic elements (BIMEs) and boxC DNA repeat elements. We confirmed direct binding of HU to BIME RNA in vitro. We also studied the nucleoid shape of HU and two of the ncRNA mutants (nc1 and nc5) by transmission electron microscopy and showed that both HU and the two ncRNAs play a role in nucleoid morphology. We propose that at least two of the ncRNA species complex with HU and help the formation or maintenance of the architecture of the E. coli chromosome. We also observed binding of HU with rRNA and tRNA segments, a few small RNAs, and a distinct small set of mRNAs, although the significance, if any, of these associations is not known. C1 [Macvanin, Mirjana; Edgar, Rotem; Trostel, Andrei; Adhya, Sankar] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cui, Feng; Zhurkin, Victor] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM adhyas@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 60 TC 13 Z9 13 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2012 VL 194 IS 22 BP 6046 EP 6055 DI 10.1128/JB.00961-12 PG 10 WC Microbiology SC Microbiology GA 030SB UT WOS:000310589300004 PM 22942248 ER PT J AU Varga, JJ Losada, L Zelazny, AM Brinkac, L Harkins, D Radune, D Hostetler, J Sampaio, EP Ronning, CM Nierman, WC Greenberg, DE Holland, SM Goldberg, JB AF Varga, John J. Losada, Liliana Zelazny, Adrian M. Brinkac, Lauren Harkins, Derek Radune, Diana Hostetler, Jessica Sampaio, Elizabeth P. Ronning, Catherine M. Nierman, William C. Greenberg, David E. Holland, Steven M. Goldberg, Joanna B. TI Draft Genome Sequence Determination for Cystic Fibrosis and Chronic Granulomatous Disease Burkholderia multivorans Isolates SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CEPACIA AB Burkholderia multivorans is a Gram-negative bacterium and a member of the Burkholderia cepacia complex, which is frequently associated with respiratory infections in people with cystic fibrosis (CF) and chronic granulomatous disease (CGD). We are reporting the genome sequences of 4 B. multivorans strains, 2 from CF patients and 2 from CGD patients. C1 [Varga, John J.; Goldberg, Joanna B.] Univ Virginia Hlth Syst, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA USA. [Varga, John J.; Losada, Liliana; Brinkac, Lauren; Harkins, Derek; Radune, Diana; Hostetler, Jessica; Ronning, Catherine M.; Nierman, William C.] J Craig Venter Inst, Rockville, MD USA. [Zelazny, Adrian M.] NIAID, Microbiol Serv, Dept Lab Med, Ctr Clin,NIH, Bethesda, MD 20892 USA. [Zelazny, Adrian M.; Sampaio, Elizabeth P.; Greenberg, David E.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Sampaio, Elizabeth P.] Fiocruz MS, Leprosy Lab, Inst Oswaldo Cruz, BR-21045900 Rio De Janeiro, Brazil. [Nierman, William C.] George Washington Univ, Washington, DC USA. [Greenberg, David E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Goldberg, JB (reprint author), Univ Virginia Hlth Syst, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA USA. EM jbg2b@virginia.edu RI Varga, John/I-8130-2012 OI Varga, John/0000-0002-4868-1971 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200900007C, N01-AI30071]; National Institutes of Health [5T32AI055432] FX This project has been funded in whole with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract numbers HHSN272200900007C and N01-AI30071. J.J.V. was supported by the National Institutes of Health grant 5T32AI055432, awarded to the University of Virginia. NR 6 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2012 VL 194 IS 22 BP 6356 EP 6357 DI 10.1128/JB.01306-12 PG 2 WC Microbiology SC Microbiology GA 030SB UT WOS:000310589300068 PM 23105085 ER PT J AU Hong, P Chen, K Huang, BH Liu, M Cui, M Rozenberg, I Chaqour, B Pan, XY Barton, ER Jiang, XC Siddiqui, MAQ AF Hong, Peng Chen, Kang Huang, Bihui Liu, Min Cui, Miao Rozenberg, Inna Chaqour, Brahim Pan, Xiaoyue Barton, Elisabeth R. Jiang, Xian-Cheng Siddiqui, M. A. Q. TI HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RNA-POLYMERASE-II; ELONGATION-FACTOR-B; P-TEFB; STEM-CELLS; TRANSCRIPTION-ELONGATION; SELF-RENEWAL; MUSCULAR-DYSTROPHY; CLP-1 GENE; ACTIVATION; PAX7 AB The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle regeneration after injury, we identified hexamethylene bisacetatnide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Hexim1-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subsequent activation of P-TEFb are required for satellite cell proliferation and the prevention of early myogenic differentiation. These findings suggest a crucial role for the HEXIM1/P-TEFb pathway in the regulation of satellite cell-mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degenerative muscular diseases. C1 [Hong, Peng; Rozenberg, Inna; Chaqour, Brahim; Pan, Xiaoyue; Jiang, Xian-Cheng; Siddiqui, M. A. Q.] Suny Downstate Med Ctr, Dept Cell Biol, New York, NY USA. [Hong, Peng; Chaqour, Brahim; Pan, Xiaoyue; Jiang, Xian-Cheng; Siddiqui, M. A. Q.] Suny Downstate Med Ctr, Ctr Cardiovasc & Muscle Res, New York, NY USA. [Chen, Kang] NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. [Chen, Kang] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Huang, Bihui] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY USA. [Liu, Min] Univ Penn, Dept Physiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cui, Miao] Mt Sinai Med Ctr, Dept Med, Div Clin Immunol, New York, NY 10029 USA. [Barton, Elisabeth R.] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. RP Siddiqui, MAQ (reprint author), 450 Clarkson Ave,Box 5, Brooklyn, NY 11203 USA. EM MAQ.Siddiqui@downstate.edu FU NIH [HL073399, AR052646]; intramural SUNY funds; Wayne State University School of Medicine FX We sincerely thank Katherine Hajjar and Gianna Ballon (Weill Cornell Medical College); Weifeng Xu, Meimei Shan, and Xiaodong Ge (Mount Sinai Medical Center); and Weijun Jin and Michael Wagner (SUNY Downstate Medical Center) for comments on experimental design and the article as well as Zhiqiang Li and Hui Jiang (SUNY Downstate Medical Center) for technical support. This work was supported in parr by NIH grants HL073399 (to M.A.Q. Siddiqui) and AR052646 (to E.R. Barton), intramural SUNY funds (to M.A.Q. Siddiqui), and a research grant from the Wayne State University School of Medicine (to K. Chen). NR 58 TC 5 Z9 5 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 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2012 VL 122 IS 11 BP 3873 EP 3887 DI 10.1172/JCI62818 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031WP UT WOS:000310673600018 PM 23023707 ER PT J AU Helft, J Manicassamy, B Guermonprez, P Hashimoto, D Silvin, A Agudo, J Brown, BD Schmolke, M Miller, JC Leboeuf, M Murphy, KM Garcia-Sastre, A Merad, M AF Helft, Julie Manicassamy, Balaji Guermonprez, Pierre Hashimoto, Daigo Silvin, Aymeric Agudo, Judith Brown, Brian D. Schmolke, Mirco Miller, Jennifer C. Leboeuf, Marylene Murphy, Kenneth M. Garcia-Sastre, Adolfo Merad, Miriam TI Cross-presenting CD103(+) dendritic cells are protected from influenza virus infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MHC CLASS-I; T-CELLS; LYMPH-NODE; ANTIGEN; SUBSETS; IMMUNITY; RESPONSES; VIVO; INNATE; INTERFERENCE AB CD8(+) cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of antigen cross-presentation by DCs to the induction of anti-viral cytotoxic T cells remains controversial. Here, we used a recombinant influenza virus expressing a nonstructural 1-GFP (NS1-GFP) reporter gene to visualize the route of antigen presentation by lung DCs upon viral infection in mice. We found that lung CD103(+) DCs were the only subset of cells that carried intact GFP protein to the draining LNs. Strikingly, lung migratory CD103(+) DCs were not productively infected by influenza virus and thus were able to induce virus-specific CD8(+) T cells through the cross-presentation of antigens from virally infected cells. We also observed that CD103(+) DC resistance to infection correlates with an increased anti-viral state in these cells that is dependent on the expression of type I IFN receptor. These results show that efficient cross-priming by migratory lung DCs is coupled to the acquisition of an anti-viral status, which is dependent on the type I IFN signaling pathway. C1 [Helft, Julie; Hashimoto, Daigo; Silvin, Aymeric; Miller, Jennifer C.; Leboeuf, Marylene; Merad, Miriam] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. [Helft, Julie; Hashimoto, Daigo; Silvin, Aymeric; Agudo, Judith; Brown, Brian D.; Miller, Jennifer C.; Leboeuf, Marylene; Merad, Miriam] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA. [Manicassamy, Balaji; Schmolke, Mirco; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. [Manicassamy, Balaji; Schmolke, Mirco; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA. [Guermonprez, Pierre] Kings Coll London, Ctr Mol & Cellular Biol Inflammat, London WC2R 2LS, England. [Guermonprez, Pierre] Kings Coll London, Div Immunol Infect & Inflammatory Dis, London WC2R 2LS, England. [Agudo, Judith; Brown, Brian D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Murphy, Kenneth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Murphy, Kenneth M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. [Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY 10029 USA. [Merad, Miriam] NIAID, Mucosal Immunol Studies Team, Portland, OR USA. RP Merad, M (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1425 Madison Ave, New York, NY USA. EM Miriam.merad@mssm.edu RI Hashimoto, Daigo/O-1013-2013 OI Hashimoto, Daigo/0000-0001-9489-9704 FU NIH [U01 AI10008, R01 HL086899, R01AI046954, P01AI058113, U19AI083025, 1K99AI095320-01]; Center for Research on Influenza Pathogenesis (CRIP), an National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance network [HHSN266200700010C]; Fulbright-Generalitat de Catalunya; Beatriu de Pinos postdoctoral fellowship; [JDRF-17-2010-770]; [DP2DK083052-01] FX M. Merad is supported by NIH grants U01 AI10008 and R01 HL086899. A. Garcia-Sastre is supported by NIH grants R01AI046954, P01AI058113, and U19AI083025, and by Center for Research on Influenza Pathogenesis (CRIP), an National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance network supported CRIP (contract number HHSN266200700010C). K.M. Murphy is an investigator of the Howard Hughes Medical Institute. B. Manicassamy is supported by NIH K99 Pathway to Independence award (1K99AI095320-01). B.D. Brown is supported by JDRF-17-2010-770 and DP2DK083052-01. J. Agudo is supported by a Fulbright-Generalitat de Catalunya postdoctoral fellowship and a Beatriu de Pinos postdoctoral fellowship. We thank C. Schindler for kindly providing the Stat2-/- mice. We thank C. Munoz-Fontela for providing the PR8-OTI influenza virus. NR 41 TC 79 Z9 82 U1 2 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2012 VL 122 IS 11 BP 4037 EP 4047 DI 10.1172/JCI60659 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031WP UT WOS:000310673600033 PM 23041628 ER PT J AU Noh, KH Kim, BW Song, KH Cho, H Lee, YH Kim, JH Chung, JY Kim, JH Hewitt, SM Seong, SY Mao, CP Wu, TC Kim, TW AF Noh, Kyung Hee Kim, Bo Wook Song, Kwon-Ho Cho, Hanbyoul Lee, Young-Ho Kim, Jin Hee Chung, Joon-Yong Kim, Jae-Hoon Hewitt, Stephen M. Seong, Seung-Yong Mao, Chih-Ping Wu, T. -C. Kim, Tae Woo TI Nanog signaling in cancer promotes stem-like phenotype and immune evasion SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; CELL-LIKE PROPERTIES; CERVICAL-CANCER; ANTITUMOR IMMUNITY; VACCINE POTENCY; SELF-RENEWAL; HIGH NUMBER; RESISTANCE; PATHWAY; AKT AB Adaptation of tumor cells to the host is a major cause of cancer progression, failure of therapy, and ultimately death. Immune selection drives this adaptation in human cancer by enriching tumor cells with a cancer stem cell-like (CSC-like) phenotype that makes them resistant to CTL-mediated apoptosis; however, the mechanisms that mediate CSC maintenance and proliferation are largely unknown. Here, we report that CTL-mediated immune selection drives the evolution of tumor cells toward a CSC-like phenotype and that the CSC-like phenotype arises through the Akt signaling pathway via transcriptional induction of Tcl1a by Nanog. Furthermore, we found that hyperactivation of the Nanog/Tcl1a/Akt signaling axis was conserved across multiple types of human cancer. Inhibition of Nanog in a murine model of colon cancer rendered tumor cells susceptible to immune-mediated clearance and led to successful, long-term control of the disease. Our fmdings establish a firm link among immune selection, disease progression, and the development of a stem-like tumor phenotype in human cancer and implicate the Nanog/Tcl1a/Akt pathway as a central molecular target in this process. C1 [Mao, Chih-Ping; Wu, T. -C.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21231 USA. [Wu, T. -C.] Johns Hopkins Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21231 USA. [Wu, T. -C.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21231 USA. [Wu, T. -C.] Johns Hopkins Sch Med, Dept Mol Microbiol & Immunol, Baltimore, MD 21231 USA. [Noh, Kyung Hee; Song, Kwon-Ho; Lee, Young-Ho; Kim, Jin Hee; Kim, Tae Woo] Korea Univ, Grad Sch Med, Div Infect & Immunol, Seoul 425707, South Korea. [Kim, Bo Wook; Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, NIH, Bethesda, MD 20892 USA. [Kim, Bo Wook; Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Cho, Hanbyoul; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul, South Korea. [Seong, Seung-Yong] Seoul Natl Univ, Coll Med, Dept Microbiol & Immunol, Seoul, South Korea. RP Wu, TC (reprint author), Johns Hopkins Sch Med, Dept Pathol, CRB 2 Room 309,1550 Orleans St, Baltimore, MD 21231 USA. EM wutc@jhmi.edu; twkim0421@korea.com RI Seong, Seung Yong /J-2764-2012; OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 FU National Research Foundation of Korea [2012-007527, 2011-0027588, 2011-0002608]; Korea Healthcare Technology RD Project [A062260]; United States National Cancer Institute [P50 CA098252, RO1 CA114425] FX This work was supported by funding from the National Research Foundation of Korea (2012-007527, 2011-0027588, and 2011-0002608), the Korea Healthcare Technology R&D Project (A062260), and the United States National Cancer Institute (P50 CA098252 and RO1 CA114425). The authors thank Katherine Liu for the preparation of the manuscript. NR 43 TC 62 Z9 64 U1 1 U2 14 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2012 VL 122 IS 11 BP 4077 EP 4093 DI 10.1172/JCI64057 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031WP UT WOS:000310673600036 PM 23093782 ER PT J AU Romond, EH Jeong, JH Rastogi, P Swain, SM Geyer, CE Ewer, MS Rathi, V Fehrenbacher, L Brufsky, A Azar, CA Flynn, PJ Zapas, JL Polikoff, J Gross, HM Biggs, DD Atkins, JN Tan-Chiu, E Zheng, P Yothers, G Mamounas, EP Wolmark, N AF Romond, Edward H. Jeong, Jong-Hyeon Rastogi, Priya Swain, Sandra M. Geyer, Charles E., Jr. Ewer, Michael S. Rathi, Vikas Fehrenbacher, Louis Brufsky, Adam Azar, Catherine A. Flynn, Patrick J. Zapas, John L. Polikoff, Jonathan Gross, Howard M. Biggs, David D. Atkins, James N. Tan-Chiu, Elizabeth Zheng, Ping Yothers, Greg Mamounas, Eleftherios P. Wolmark, Norman TI Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CUMULATIVE INCIDENCE; OLDER WOMEN; CHEMOTHERAPY; ANTHRACYCLINE; CARDIOTOXICITY; DYSFUNCTION; TESTS; N9831; RISK AB Purpose Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. Patients and Methods In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. Results At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. Conclusion The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab. J Clin Oncol 30:3792-3799. (C) 2012 by American Society of Clinical Oncology C1 [Romond, Edward H.; Jeong, Jong-Hyeon; Rastogi, Priya; Swain, Sandra M.; Geyer, Charles E., Jr.; Fehrenbacher, Louis; Brufsky, Adam; Azar, Catherine A.; Flynn, Patrick J.; Zapas, John L.; Polikoff, Jonathan; Gross, Howard M.; Biggs, David D.; Atkins, James N.; Zheng, Ping; Yothers, Greg; Mamounas, Eleftherios P.; Wolmark, Norman] Operat & Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Jeong, Jong-Hyeon; Zheng, Ping; Yothers, Greg] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Rastogi, Priya; Brufsky, Adam] Univ Pittsburgh, Magee Womens Hosp, Sch Med, UPMC, Pittsburgh, PA 15213 USA. [Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. [Romond, Edward H.] Univ Kentucky, Lucille Parker Markey Canc Ctr, Lexington, KY USA. [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. [Geyer, Charles E., Jr.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Ewer, Michael S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rathi, Vikas] Bon Secours Hlth Syst, Midlothian, VA USA. [Fehrenbacher, Louis] Kaiser Permanente No Calif, Vallejo, CA USA. [Polikoff, Jonathan] Kaiser Permanente, San Diego, CA USA. [Azar, Catherine A.] Colorado Canc Res Program, CCOP, Denver, CO USA. [Flynn, Patrick J.] CCOP, St Louis Pk, MN USA. [Zapas, John L.] Franklin Sq Hosp Ctr, Baltimore, MD USA. [Gross, Howard M.] CCOP, Dayton, OH USA. [Mamounas, Eleftherios P.] Aultman Hosp Canc Ctr, Canton, OH USA. [Biggs, David D.] Christiana Care Hlth Syst, CCOP, Newark, DE USA. [Atkins, James N.] CCOP SE Canc Control Consortium, Goldsboro, NC USA. [Tan-Chiu, Elizabeth] Florida Canc Res Inst, Plantation, FL USA. RP Rastogi, P (reprint author), Four Allegheny Ctr, Natl Surg Adjuvant Breast & Bowel Project, E Commons Profess Bldg,5th Floor, Pittsburgh, PA 15212 USA. EM rastogip@upmc.edu FU National Cancer Institute, Department of Health and Human Services, Public Health Service; Genentech; [U10-CA-12027]; [U10-CA-69651]; [U10-CA-37377]; [U10-CA-69974] FX Supported by Grants No. U10-CA-12027, U10-CA-69651, U10-CA-37377, and U10-CA-69974 from the National Cancer Institute, Department of Health and Human Services, Public Health Service, and by Genentech. NR 22 TC 146 Z9 147 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2012 VL 30 IS 31 BP 3792 EP 3799 DI 10.1200/JCO.2011.40.0010 PG 8 WC Oncology SC Oncology GA 030PT UT WOS:000310583300014 PM 22987084 ER PT J AU Kantarjian, H Thomas, D Wayne, AS O'Brien, S AF Kantarjian, Hagop Thomas, Deborah Wayne, Alan S. O'Brien, Susan TI Monoclonal Antibody-Based Therapies: A New Dawn in the Treatment of Acute Lymphoblastic Leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHILDRENS ONCOLOGY GROUP; MINIMAL RESIDUAL DISEASE; B-CELL MALIGNANCIES; INOTUZUMAB OZOGAMICIN; HYPER-CVAD; HEMATOLOGIC MALIGNANCIES; GEMTUZUMAB OZOGAMICIN; CYTOTOXIC ACTIVITY; PEDIATRIC-PATIENTS C1 [Kantarjian, Hagop] Univ Texas MD Anderson Canc Ctr, Leukemia Dept, Houston, TX 77030 USA. [Wayne, Alan S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kantarjian, H (reprint author), Univ Texas MD Anderson Canc Ctr, Leukemia Dept, 1515 Holcombe Blvd,Box 428, Houston, TX 77030 USA. EM hkantarj@mdanderson.org FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Institutes of Health [CA016672] FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and by National Institutes of Health Grant No. CA016672. NR 69 TC 42 Z9 42 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2012 VL 30 IS 31 BP 3876 EP 3883 DI 10.1200/JCO.2012.41.6768 PG 8 WC Oncology SC Oncology GA 030PT UT WOS:000310583300025 PM 22891271 ER PT J AU Ehler, M Filbir, F Mhaskar, HN AF Ehler, M. Filbir, F. Mhaskar, H. N. TI Locally Learning Biomedical Data Using Diffusion Frames SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE graphs and networks; machine learning ID NONLINEAR DIMENSIONALITY REDUCTION; MACULAR DEGENERATION; GEOMETRIC DIFFUSIONS; STRUCTURE DEFINITION; HARMONIC-ANALYSIS; LAPLACIAN; SPHERE; REPRESENTATION; EIGENFUNCTIONS; DIAGNOSIS AB Diffusion geometry techniques are useful to classify patterns and visualize high-dimensional datasets. Building upon ideas from diffusion geometry, we outline our mathematical foundations for learning a function on high-dimension biomedical data in a local fashion from training data. Our approach is based on a localized summation kernel, and we verify the computational performance by means of exact approximation rates. After these theoretical results, we apply our scheme to learn early disease stages in standard and new biomedical datasets. C1 [Ehler, M.; Filbir, F.] Helmholtz Zentrum Munchen, Inst Biomath & Biometry, D-85764 Neuherberg, Germany. [Ehler, M.] NICHD, NIH, Sect Med Biophys, Bethesda, MD USA. [Mhaskar, H. N.] CALTECH, Dept Math, Pasadena, CA 91125 USA. [Mhaskar, H. N.] Claremont Grad Univ, Dept Math, Claremont, CA USA. RP Ehler, M (reprint author), Helmholtz Zentrum Munchen, Inst Biomath & Biometry, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM martin.ehler@helmholtz-muenchen.de FU NIH/DFG Research Career Transition Awards Program [EH 405/1-1/575910]; Deutsche Forschungsgemeinschaft [FI 883/3-1]; National Science Foundation [DMS-0908037]; U.S. Army Research Office [W911NF-09-1-0465] FX M.E. was supported by the NIH/DFG Research Career Transition Awards Program (EH 405/1-1/575910). The research of F.F. was partially funded by Deutsche Forschungsgemeinschaft grant FI 883/3-1. H.N.M. was supported, in part, by grant DMS-0908037 from the National Science Foundation and grant W911NF-09-1-0465 from the U.S. Army Research Office. NR 51 TC 4 Z9 4 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD NOV PY 2012 VL 19 IS 11 BP 1251 EP 1264 DI 10.1089/cmb.2012.0187 PG 14 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 033YN UT WOS:000310837400004 PM 23101786 ER PT J AU Hildreth, RL Bullough, MD Zhang, AP Chen, HL Schwartz, PH Panchision, DM Colberg-Poley, AM AF Hildreth, Richard L. Bullough, Matthew D. Zhang, Aiping Chen, Hui-Ling Schwartz, Philip H. Panchision, David M. Colberg-Poley, Anamaris M. TI Viral mitochondria-localized inhibitor of apoptosis (UL37 exon 1 protein) does not protect human neural precursor cells from human cytomegalovirus-induced cell death SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; SUBVENTRICULAR ZONE; NERVOUS-SYSTEM; STEM-CELLS; NEURONAL DIFFERENTIATION; PROGENITOR CELLS; INFECTION; VIRUS; ASTROCYTES; BRAIN AB Congenital human cytomegalovirus (HCMV) infection can cause severe brain abnormalities. Apoptotic HCMV-infected brain cells have been detected in a congenitally infected infant. In biologically relevant human neural precursor cells (hNPCs), cultured in physiological oxygen tensions, HCMV infection (m.o.i. of 1 or 3) induced cell death within 3 days post-infection (p.i.) and increased thereafter. Surprisingly, its known anti-apoptotic genes, including the potent UL37 exon 1 protein (pUL37x1) or viral mitochondria-localized inhibitor of apoptosis (vMIA), which protects infected human fibroblasts (HFFs) from apoptosis and from caspase-independent, mitochondrial serine protease-mediated cell death, were expressed by 2 days p.i. Consistent with this finding, an HCMV UL37x1 mutant, BADsubstitutionUL37x1 (BADsubUL37x1) induced cell death in hNPCs (m.o.i.=1) to level which were indistinguishable from parental virus (BADwild-type)-infected hNPCs. Surprisingly, although BADsubUL37x1 is growth defective in permissive HFFs, it produced infectious progeny in hNPCs with similar kinetics and to levels comparable to BADwild-type-infected hNPCs (m.o.i.=1). While delayed at a lower multiplicity (m.o.i.=0.3), the BADsubUL37x1 mutant reached similar levels to revertant within 12 days, in contrast to its phenotype in HFFs. The inability of pUL37x1/vMIA to protect hNPCs from HCMV-induced cell death did not result from impaired trafficking as pUL37x1/vMIA trafficked efficiently to mitochondria in transfected hNPCs and in HCMV-infected hNPCs. These results establish that pUL37x1/vMIA, although protective in permissive HFFs, does not protect HCMV-infected hNPCs from cell death under physiologically relevant oxygen tensions. They further suggest that pUL37x1/vMIA is not essential for HCMV growth in hNPCs and has different cell type-specific roles. C1 [Hildreth, Richard L.; Bullough, Matthew D.; Zhang, Aiping; Colberg-Poley, Anamaris M.] Childrens Res Inst, Res Ctr Genet Med, Washington, DC 20010 USA. [Hildreth, Richard L.; Colberg-Poley, Anamaris M.] George Washington Univ, Mol Med Program, Washington, DC 20052 USA. [Chen, Hui-Ling] Childrens Res Inst, Ctr Neurosci Res, Washington, DC 20010 USA. [Chen, Hui-Ling] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. [Schwartz, Philip H.] Childrens Hosp Orange Cty, Res Inst, Orange, CA 92668 USA. [Panchision, David M.] NIMH, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA. [Colberg-Poley, Anamaris M.] George Washington Univ, Dept Biochem & Mol Biol, Washington, DC 20052 USA. [Colberg-Poley, Anamaris M.] George Washington Univ, Dept Integrat Syst Biol, Washington, DC 20052 USA. RP Colberg-Poley, AM (reprint author), Childrens Res Inst, Res Ctr Genet Med, Washington, DC 20010 USA. EM acolberg-poley@cnmcresearch.org FU NIH [R01 AI057906]; National Center for Research Resources [UL1RR031988]; Children's Research Institute funds; [1P30HD40677] FX The authors thank Dr Tom Shenk for the gift of the recombinant HCMV viruses BADwt, BADrev, BADsubUL37x1 and antibody mAb4B-6B, Dr Bill Britt for the gift of mAb28-4, mAb28-19 and mAb65-8. We are grateful to Drs Lina Chakrabarti and Chad Williamson for help in analysing the flow cytometry and quantifying the MetaMorph co-localization signals, respectively. The studies were supported by NIH R01 AI057906, National Center for Research Resources UL1RR031988 and Children's Research Institute funds to A.C.P. Confocal microscopy imaging was performed in the Cellular Imaging & Analysis Core at Children's Research Institute and was supported by a core grant to the Children's Intellectual and Developmental Disabilities Research Center (1P30HD40677). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. These studies were performed by R.L.H. in partial fulfilment of his doctoral studies in the Molecular Medicine Program at George Washington University Institute of Biomedical Sciences. NR 56 TC 2 Z9 2 U1 1 U2 8 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 2012 VL 93 BP 2436 EP 2446 DI 10.1099/vir.0.044784-0 PN 11 PG 11 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 033RW UT WOS:000310819600015 PM 22875256 ER PT J AU Yewdell, JW David, A AF Yewdell, Jonathan W. David, Alexandre TI Editorial: Proteostenosis: cancer's Achilles heel? SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material DE defective ribosomal products; multiple myeloma; proteasome; proteostasis; protein synthesis; rapidly degraded polypeptides; ubiquitin ID PROTEIN-SYNTHESIS; OXIDATIVE-STRESS; MAMMALIAN-CELLS; LIVED PROTEINS; DEGRADATION; PROTEASOME; IMMUNOPROTEASOME C1 [Yewdell, Jonathan W.; David, Alexandre] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33, Bethesda, MD 20892 USA. EM jyewdell@niaid.nih.gov OI David, Alexandre/0000-0003-3365-1339 FU Intramural NIH HHS NR 20 TC 1 Z9 1 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2012 VL 92 IS 5 BP 913 EP 915 DI 10.1189/jlb.0612272 PG 3 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 030QF UT WOS:000310584500001 PM 23118441 ER PT J AU Shen, J AF Shen, Jun TI Preserving the excitation profile of small flip angle RF pulses in the presence of rapid transverse relaxation SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE RF pulse design; Linear response theory; Relaxation effects ID SELECTIVE EXCITATION; ACCOMMODATE RELAXATION; DESIGN AB Degradation of excitation profile of selective RF pulses by rapid transverse relaxation has been a long-standing concern. In this report we demonstrate that transverse relaxation can be incorporated into small flip angle RF pulse design based on the linear response theory. Small flip angle pulses that were designed without considering transverse relaxation effects can be transformed for a predefined pulse duration/T-2 ratio. The transformed pulses, within the realm of the linear response theory, produce the same transverse frequency response as if there were no relaxation. Published by Elsevier Inc. C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU Intramural Research Program of the NIH, NIMH FX The author thanks the reviewers and the editor for their helpful comments. This work is supported by the Intramural Research Program of the NIH, NIMH. NR 20 TC 2 Z9 2 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 2012 VL 224 BP 8 EP 12 DI 10.1016/j.jmr.2012.08.012 PG 5 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 033AP UT WOS:000310765000002 PM 23000975 ER PT J AU Fujimura, KE Rauch, M Matsui, E Iwai, S Calatroni, A Lynn, H Mitchell, H Johnson, CC Gern, JE Togias, A Boushey, HA Kennedy, S Lynch, SV AF Fujimura, Kei E. Rauch, Marcus Matsui, Elizabeth Iwai, Shoko Calatroni, Agustin Lynn, Henry Mitchell, Herman Johnson, Christine C. Gern, James E. Togias, Alkis Boushey, Homer A. Kennedy, Suzanne Lynch, Susan V. TI Development of a standardized approach for environmental microbiota investigations related to asthma development in children SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Dust microbiome; Standardized sampling; Phylogenetic microarray; 454-Pyrosequencing ID 16S RIBOSOMAL-RNA; GUT MICROBIOME; DIVERSITY; BACTERIA; ALLERGY AB Standardized studies examining environmental microbial exposure in populations at risk for asthma are necessary to improve our understanding of the role this factor plays in disease development. Here we describe studies aimed at developing guidelines for high-resolution culture-independent microbiome profiling, using a phylogenetic microarray (PhyloChip), of house dust samples in a cohort collected as part of the NIH-funded Inner City Asthma Consortium (ICAC). We demonstrate that though extracted DNA concentrations varied across dust samples, the majority produced sufficient 16S rRNA to be profiled by the array. Comparison of array and 454-pyrosequencing performed in parallel on a subset of samples, illustrated that increasingly deeper sequencing efforts validated greater numbers of array-detected taxa. Community composition agreement across samples exhibited a hierarchy in concordance, with the highest level of agreement in replicate array profiles followed by samples collected from adjacent 1 x 1 m(2) sites in the same room, adjacent sites with different sized sampling quadrants (1 x 1 and 2 x 2 m(2)), different sites within homes (living and bedroom) to lowest in living room samples collected from different homes. The guidelines for sample collection and processing in this pilot study extend beyond PhyloChip based studies of house-associated microbiota, and bear relevance for other microbiome profiling approaches such as next-generation sequencing. (C) 2012 Elsevier B.V. All rights reserved. C1 [Fujimura, Kei E.; Rauch, Marcus; Iwai, Shoko; Lynch, Susan V.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. [Matsui, Elizabeth] Johns Hopkins Univ, Sch Med, Div Pediat Allergy & Immunol, Baltimore, MD 21287 USA. [Calatroni, Agustin; Lynn, Henry; Mitchell, Herman; Kennedy, Suzanne] Rho Fed Syst Div Inc, Chapel Hill, NC 27517 USA. [Johnson, Christine C.] Henry Ford Hlth Syst, Div Allergy & Immunol, Dept Publ Hlth Sci, Dept Internal Med, Detroit, MI 48202 USA. [Gern, James E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat & Med, Madison, WI 53792 USA. [Togias, Alkis] NIAID, Bethesda, MD 20814 USA. [Boushey, Homer A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Lynch, SV (reprint author), Univ Calif San Francisco, Div Gastroenterol, 513 Parnassus Ave, San Francisco, CA 94143 USA. EM susan.lynch@ucsf.edu OI Johnson, Christine Cole/0000-0002-6864-6604 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [NO1-AI-25496, NO1-AI-25482, HHSN272200900052C, HHSN2722010000521]; National Center for Research Resources, National Institutes of Health [RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, 5UL1RR024992-02] 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, HHSN272200900052C and HHSN2722010000521. Additional support was provided by the National Center for Research Resources, National Institutes of Health, under grants RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, and 5UL1RR024992-02. NR 32 TC 4 Z9 4 U1 1 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD NOV PY 2012 VL 91 IS 2 BP 231 EP 239 DI 10.1016/j.mimet.2012.08.016 PG 9 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 034HP UT WOS:000310863800003 PM 22975469 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD NOV PY 2012 VL 41 IS 11 BP 308 EP 308 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 031PG UT WOS:000310653800015 PM 23079911 ER PT J AU Peickert, S Waurig, J Dittfeld, C Dietrich, A Garbe, Y Kabus, L Baumann, M Grade, M Ried, T Kunz-Schughart, LA AF Peickert, Susann Waurig, Julia Dittfeld, Claudia Dietrich, Antje Garbe, Yvette Kabus, Lydia Baumann, Michael Grade, Marian Ried, Thomas Kunz-Schughart, Leoni A. TI Rapid re-expression of CD133 protein in colorectal cancer cell lines in vitro and in vivo SO LABORATORY INVESTIGATION LA English DT Article DE cancer stem cell hypothesis; CD133 protein; colorectal cancer cell line; 2-D culture; 3-D culture; radio-/chemotherapy; xenograft ID TUMOR-INITIATING CELLS; PLASMA-MEMBRANE PROTRUSIONS; HUMAN COLON-CANCER; STEM-CELLS; RECTAL-CANCER; PREOPERATIVE CHEMORADIOTHERAPY; GENE-EXPRESSION; MARKER CD133; SOLID TUMORS; HUMAN GLIOMA AB Studies related to the cancer stem cell hypothesis are challenging because of the imperfect tools to identify cell populations of interest and controversy on the usefulness of established cancer cell lines. We previously found CD133 to not be selective for a tumor-propagating or radioresistant population in a near-diploid, microsatellite-instable colorectal carcinoma (CRC) cell line. Because of discrepant literature data, we herein systematically analyzed the behavior of microsatellite-stable cell line subpopulations reflecting the more frequent carcinogenesis pathway in spontaneous CRC. CD133(+) and CD133(-/low) populations were isolated by fluorescence-activated cell sorting and further processed. HT29 and SW620 cells were studied in detail in monolayer and/or spheroid culture assays and upon subcutaneous injection in NMRI (nu/nu) mice using a limiting dilution approach. CD133(-/low) HT29 cells showed a significantly lower clonogenic survival and reduced spheroid formation capacity than their CD133+ counterparts. However, the cell populations neither differed in growth kinetics and response to treatment in vitro nor in tumor formation capacity when injecting as low as 10 cells. CD 133(-/low) HT29 cells rapidly re-expressed CD 133 protein in vitro and in vivo as shown by flow cytometry and/or western blot analyses, and they also showed a particular survival benefit under tissue normoxic conditions. In contrast, CD133 protein in the CD133(+) population was quite stable throughout culturing. The observation of CD133 re-expression and lack of difference in tumor take rate of subpopulations was confirmed in SW620 cells. Here, we found cell density to affect CD133 re-expression in the CD133(-)-sorted population. And even SW480 cells, classified as a CD133(-) cell line, presented some CD133 protein on their surface upon in vivo engraftment. We conclude that (i) CD133 protein expression shows high plasticity in CRC cell lines, and (ii) in vitro CD133 status on the cell surface neither determines tumorigenic potential nor CD133 profile in vivo. Laboratory Investigation (2012) 92, 1607-1622; doi:10.1038/labinvest.2012.124; published online 10 September 2012 C1 [Peickert, Susann; Waurig, Julia; Dittfeld, Claudia; Dietrich, Antje; Garbe, Yvette; Kabus, Lydia; Baumann, Michael; Kunz-Schughart, Leoni A.] Tech Univ Dresden, OncoRay Natl Ctr Radiat Res Oncol, Med Fac Carl Gustav Carus, D-01307 Dresden, Germany. [Baumann, Michael] Tech Univ Dresden, Dept Radiat Oncol, Fac Med, D-01307 Dresden, Germany. [Baumann, Michael] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, D-01307 Dresden, Germany. [Grade, Marian] Univ Med Gottingen, Dept Gen & Visceral Surg, Gottingen, Germany. [Ried, Thomas] NCI, NIH, Bethesda, MD 20892 USA. RP Kunz-Schughart, LA (reprint author), Tech Univ Dresden, OncoRay Natl Ctr Radiat Res Oncol, Med Fac Carl Gustav Carus, Fetscherstr 74,PF 86, D-01307 Dresden, Germany. EM leoni.kunz-schughart@oncoray.de FU German Research Foundation (DFG) [KU 971/7-1, GR 3376/2-1, KFO179]; BMBF in the program 'Center for Innovation Competence' FX We thank Mrs Marit Wondrak and Mrs Melanie Huether for excellent technical assistance. This work was supported by the German Research Foundation (DFG) through grants KU 971/7-1 and GR 3376/2-1, and the KFO179. OncoRay is funded by the BMBF in the program 'Center for Innovation Competence'. Disclaimer: The authors alone are responsible for the content and writing of the paper. NR 65 TC 12 Z9 12 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 2012 VL 92 IS 11 BP 1607 EP 1622 DI 10.1038/labinvest.2012.124 PG 16 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 032ZL UT WOS:000310761800009 PM 22964855 ER PT J AU Beral, V Bull, D Pirie, K Reeves, G Peto, R Skegg, D LaVecchia, C Magnusson, C Pike, MC Thomas, D Hamajima, N Hirose, K Tajima, K Rohan, T Friedenreich, CM Calle, EE Gapstur, SM Patel, AV Coates, RJ Liff, JM Talamini, R Chantarakul, N Koetsawang, S Rachawat, D Marcou, Y Kakouri, E Duffy, SW Morabia, A Schuman, L Stewart, W Szklo, M Coogan, PF Palmer, JR Rosenberg, L Band, P Coldman, AJ Gallagher, RP Hislop, TG Yang, P Cummings, SR Canfell, K Sitas, F Chao, P Lissowska, J Horn-Ross, PL John, EM Kolonel, LM Nomura, AMY Ghiasvand, R Hu, J Johnson, KC Mao, Y Callaghan, K Crossley, B Goodill, A Green, J Hermon, C Key, T Lindgard, I Liu, B Pirie, K Reeves, G Collins, R Doll, R Peto, R Bishop, T Fentiman, IS De Sanjose, S Gonzaler, CA Lee, N Marchbanks, P Ory, HW Peterson, HB Wingo, P Ebeling, K Kunde, D Nishan, P Hopper, JL Eliassen, H Gajalakshmi, V Martin, N Pardthaisong, T Silpisornkosol, S Theetranont, C Boosiri, B Chutivongse, S Jimakorn, P Virutamasen, P Wongsrichanalai, C Neugut, A Santella, R Baines, CJ Kreiger, N Miller, AB Wall, C Tjonneland, A Jorgensen, T Stahlberg, C Pedersen, AT Flesch-Janys, D Hakansson, N Cauley, J Heuch, I Adami, HO Persson, I Weiderpass, E Magnusson, C Chang-Claude, J Kaaks, R McCredie, M Paul, C Skegg, DCG Spears, GFS Iwasaki, M Tsugane, S Anderson, G Daling, JR Hampton, J Hutchinson, WB Li, CI Malone, K Mandelson, M Newcomb, P Noonan, EA Ray, RM Stanford, JL Tang, MTC Thomas, DB Weiss, NS White, E Izquierdo, A Viladiu, P Fourkala, EO Jacobs, I Menon, U Ryan, A Cuevas, HR Ontiveros, P Palet, A Salazar, SB Aristizabal, N Cuadros, A Tryggvadottir, L Tulinius, H Riboli, E Andrieu, N Bachelot, A Le, MG Bremond, A Gairard, B Lansac, J Piana, L Renaud, R Clavel-Chapelon, F Fournier, A Touillaud, M Mesrine, S Chabbert-Buffet, N Boutron-Ruault, MC Wolk, A Torres-Mejia, G Franceschi, S Romieu, I Boyle, P Lubin, F Modan, B Ron, E Wax, Y Friedman, GD Hiatt, RA Levi, F Kosmelj, K Primic-Zakelj, M Ravnihar, B Stare, J Ekbom, A Erlandsson, G Persson, I Beeson, WL Fraser, G Peto, J Hanson, RL Leske, MC Mahoney, MC Nasca, PC Varma, AO Weinstein, AL Hartman, ML Olsson, H Goldbohm, RA van den Brandt, PA Palli, D Teitelbaum, S Apelo, RA Baens, J de la Cruz, JR Javier, B Lacaya, LB Ngelangel, CA La Vecchia, C Negri, E Marubini, E Ferraroni, M Pike, MC Gerber, M Richardson, S Segala, C Gatei, D Kenya, P Kungu, A Mati, JG Brinton, LA Freedman, M Hoover, R Schairer, C Ziegler, R Banks, E Spirtas, R Lee, HP Rookus, MA van Leeuwen, FE Schoenberg, JA Graff-Iversen, S Selmer, R Jones, L McPherson, K Neil, A Vessey, M Yeates, D Mabuchi, K Preston, D Hannaford, P Kay, C McCann, SE Rosero-Bixby, L Gao, YT Jin, F Yuan, JM Wei, HY Yun, T Zhiheng, C Berry, G Booth, JC Jelihovsky, T MacLennan, R Shearman, R Hadjisavvas, A Kyriacou, K Loisidou, M Zhou, X Wang, QS Kawai, M Minami, Y Tsuji, I Lund, E Kumle, M Stalsberg, H Shu, XO Zheng, W Monninkhof, EM Onland-Moret, NC Peeters, PHM Katsouyanni, K Trichopoulou, A Trichopoulos, D Tzonou, A Baltzell, KA Dabancens, A Martinez, L Molina, R Salas, O Alexander, FE Anderson, K Folsom, AR Gammon, MD Hulka, BS Millikan, R Chilvers, CED Lumachi, F Bain, C Schofield, F Siskind, V Rebbeck, TR Bernstein, LR Enger, S Haile, RW Paganini-Hill, A Ross, RK Ursin, G Wu, AH Yu, MC Ewertz, DM Clarke, EA Bergkvist, L Anderson, GL Gass, M O'Sullivan, MJ Kalache, A Farley, TMM Holck, S Meirik, O Fukao, A AF Beral, V. Bull, D. Pirie, K. Reeves, G. Peto, R. Skegg, D. LaVecchia, C. Magnusson, C. Pike, M. C. Thomas, D. Hamajima, N. Hirose, K. Tajima, K. Rohan, T. Friedenreich, C. M. Calle, E. E. Gapstur, S. M. Patel, A. V. Coates, R. J. Liff, J. M. Talamini, R. Chantarakul, N. Koetsawang, S. Rachawat, D. Marcou, Y. Kakouri, E. Duffy, S. W. Morabia, A. Schuman, L. Stewart, W. Szklo, M. Coogan, P. F. Palmer, J. R. Rosenberg, L. Band, P. Coldman, A. J. Gallagher, R. P. Hislop, T. G. Yang, P. Cummings, S. R. Canfell, K. Sitas, F. Chao, P. Lissowska, J. Horn-Ross, P. L. John, E. M. Kolonel, L. M. Nomura, A. M. Y. Ghiasvand, R. Hu, J. Johnson, K. C. Mao, Y. Callaghan, K. Crossley, B. Goodill, A. Green, J. Hermon, C. Key, T. Lindgard, I. Liu, B. Pirie, K. Reeves, G. Collins, R. Doll, R. Peto, R. Bishop, T. Fentiman, I. S. De Sanjose, S. Gonzaler, C. A. Lee, N. Marchbanks, P. Ory, H. W. Peterson, H. B. Wingo, P. Ebeling, K. Kunde, D. Nishan, P. Hopper, J. L. Eliassen, H. Gajalakshmi, V. Martin, N. Pardthaisong, T. Silpisornkosol, S. Theetranont, C. Boosiri, B. Chutivongse, S. Jimakorn, P. Virutamasen, P. Wongsrichanalai, C. Neugut, A. Santella, R. Baines, C. J. Kreiger, N. Miller, A. B. Wall, C. Tjonneland, A. Jorgensen, T. Stahlberg, C. Pedersen, A. Tonnes Flesch-Janys, D. Hakansson, N. Cauley, J. Heuch, I. Adami, H. O. Persson, I. Weiderpass, E. Magnusson, C. Chang-Claude, J. Kaaks, R. McCredie, M. Paul, C. Skegg, D. C. G. Spears, G. F. S. Iwasaki, M. Tsugane, S. Anderson, G. Daling, J. R. Hampton, J. Hutchinson, W. B. Li, C. I. Malone, K. Mandelson, M. Newcomb, P. Noonan, E. A. Ray, R. M. Stanford, J. L. Tang, M. T. C. Thomas, D. B. Weiss, N. S. White, E. Izquierdo, A. Viladiu, P. Fourkala, E. O. Jacobs, I. Menon, U. Ryan, A. Cuevas, H. R. Ontiveros, P. Palet, A. Salazar, S. B. Aristizabal, N. Cuadros, A. Tryggvadottir, L. Tulinius, H. Riboli, E. Andrieu, N. Bachelot, A. Le, M. G. Bremond, A. Gairard, B. Lansac, J. Piana, L. Renaud, R. Clavel-Chapelon, F. Fournier, A. Touillaud, M. Mesrine, S. Chabbert-Buffet, N. Boutron-Ruault, M. C. Wolk, A. Torres-Mejia, G. Franceschi, S. Romieu, I. Boyle, P. Lubin, F. Modan, B. Ron, E. Wax, Y. Friedman, G. D. Hiatt, R. A. Levi, F. Kosmelj, K. Primic-Zakelj, M. Ravnihar, B. Stare, J. Ekbom, A. Erlandsson, G. Persson, I. Beeson, W. L. Fraser, G. Peto, J. Hanson, R. L. Leske, M. C. Mahoney, M. C. Nasca, P. C. Varma, A. O. Weinstein, A. L. Hartman, M. L. Olsson, H. Goldbohm, R. A. van den Brandt, P. A. Palli, D. Teitelbaum, S. Apelo, R. A. Baens, J. de la Cruz, J. R. Javier, B. Lacaya, L. B. Ngelangel, C. A. La Vecchia, C. Negri, E. Marubini, E. Ferraroni, M. Pike, M. C. Gerber, M. Richardson, S. Segala, C. Gatei, D. Kenya, P. Kungu, A. Mati, J. G. Brinton, L. A. Freedman, M. Hoover, R. Schairer, C. Ziegler, R. Banks, E. Spirtas, R. Lee, H. P. Rookus, M. A. van Leeuwen, F. E. Schoenberg, J. A. Graff-Iversen, S. Selmer, R. Jones, L. McPherson, K. Neil, A. Vessey, M. Yeates, D. Mabuchi, K. Preston, D. Hannaford, P. Kay, C. McCann, S. E. Rosero-Bixby, L. Gao, Y. T. Jin, F. Yuan, J-M Wei, H. Y. Yun, T. Zhiheng, C. Berry, G. Booth, J. Cooper Jelihovsky, T. MacLennan, R. Shearman, R. Hadjisavvas, A. Kyriacou, K. Loisidou, M. Zhou, X. Wang, Q-S Kawai, M. Minami, Y. Tsuji, I. Lund, E. Kumle, M. Stalsberg, H. Shu, X. O. Zheng, W. Monninkhof, E. M. Onland-Moret, N. C. Peeters, P. H. M. Katsouyanni, K. Trichopoulou, A. Trichopoulos, D. Tzonou, A. Baltzell, K. A. Dabancens, A. Martinez, L. Molina, R. Salas, O. Alexander, F. E. Anderson, K. Folsom, A. R. Gammon, M. D. Hulka, B. S. Millikan, R. Chilvers, C. E. D. Lumachi, F. Bain, C. Schofield, F. Siskind, V. Rebbeck, T. R. Bernstein, L. R. Enger, S. Haile, R. W. Paganini-Hill, A. Ross, R. K. Ursin, G. Wu, A. H. Yu, M. C. Ewertz, Denmark M. Clarke, E. A. Bergkvist, L. Anderson, G. L. Gass, M. O'Sullivan, M. J. Kalache, A. Farley, T. M. M. Holck, S. Meirik, O. Fukao, A. CA Collaborative Grp Hormonal Factors Collaborative Grp Hormonal Factors S Hankinson Nurses Hlth Study I II Res Grp TI Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies SO LANCET ONCOLOGY LA English DT Article ID REQUIRING PROLONGED OBSERVATION; COLLABORATIVE REANALYSIS; POSTMENOPAUSAL WOMEN; SEX-HORMONES; AGE; THERAPY; PATIENT; TRIALS; RECALL; REPRODUCIBILITY AB Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women. Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression. Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p < 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p < 0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p < 0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p < 0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p < 0.01 for both comparisons). Interpretation The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours. Funding Cancer Research UK. C1 [Beral, V.; Bull, D.; Pirie, K.; Reeves, G.] Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7LF, England. [Peto, R.] Univ Oxford, CRUK MRC BHF Clin Trial Serv Unit, Oxford OX3 7LF, England. [Peto, R.] Univ Oxford, Epidemiol Studies Unit, Oxford OX3 7LF, England. [Skegg, D.] Univ Otago, Dunedin, New Zealand. [LaVecchia, C.] Ist Mario Negri, Milan, Italy. [LaVecchia, C.] Univ Milan, Milan, Italy. [Magnusson, C.] Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden. [Pike, M. C.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Thomas, D.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Hamajima, N.; Hirose, K.; Tajima, K.] Aichi Canc Res Inst, Nagoya, Aichi, Japan. [Rohan, T.] Albert Einstein Coll Med, New York, NY USA. [Friedenreich, C. M.] Alberta Hlth Serv, Calgary, AB, Canada. [Calle, E. E.; Gapstur, S. M.; Patel, A. V.] Amer Canc Soc, Atlanta, GA USA. [Coates, R. J.; Liff, J. M.] Emory Univ, Atlanta, GA USA. [Talamini, R.] Aviano Canc Ctr, Pordenone, Italy. [Chantarakul, N.; Koetsawang, S.; Rachawat, D.] Mahidol Univ, Bangkok, Thailand. [Marcou, Y.; Kakouri, E.] Bank Cyprus Oncol Ctr, Nicosia, Cyprus. [Duffy, S. W.] Barts & London Queen Marys Sch Med & Dent, London, England. [Morabia, A.; Schuman, L.; Stewart, W.; Szklo, M.] Johns Hopkins Univ, Breast Tumor Collaborat Study, Baltimore, MD USA. [Coogan, P. F.; Palmer, J. R.; Rosenberg, L.] Boston Univ, Sloane Epidemiol Ctr, Boston, MA USA. [Band, P.; Coldman, A. J.; Gallagher, R. P.; Hislop, T. G.; Yang, P.] British Columbia Canc Agcy, Vancouver, BC, Canada. [Cummings, S. R.] Calif Pacific Med Ctr, San Francisco, CA USA. [Canfell, K.; Sitas, F.] Canc Council NSW, Sydney, NSW, Australia. [Chao, P.; Lissowska, J.] Canc Ctr & M Sklodowska Curie Inst Oncol, Warsaw, Poland. [Horn-Ross, P. L.; John, E. M.] Canc Prevent Inst Calif, Fremont, CA USA. [Kolonel, L. M.; Nomura, A. M. Y.] Univ Hawaii, Canc Res Ctr, Honolulu, HI USA. [Ghiasvand, R.] Univ Tehran, Inst Canc, Canc Res Ctr, Tehran, Iran. [Hu, J.; Johnson, K. C.; Mao, Y.] Canadian Canc Registries Epidemiol Res Grp, Ottawa, ON, Canada. [Beral, V.; Bull, D.; Callaghan, K.; Crossley, B.; Goodill, A.; Green, J.; Hermon, C.; Key, T.; Lindgard, I.; Liu, B.; Pirie, K.; Reeves, G.] Canc Res UK Epidemiol Unit, Oxford, England. [Collins, R.; Doll, R.; Peto, R.] Canc Res UK MRC BHF, Clin Trial Serv, Oxford, England. [Collins, R.; Doll, R.; Peto, R.] Canc Res UK MRC BHF, Epidemiol Studies Unit, Oxford, England. [Bishop, T.] Canc Res UK Genet Epidemiol Lab, Leeds, W Yorkshire, England. [Fentiman, I. S.] Canc Res UK, London, England. [De Sanjose, S.; Gonzaler, C. A.] Catalan Inst Oncol, Barcelona, Spain. [Lee, N.; Marchbanks, P.; Ory, H. W.; Peterson, H. B.; Wingo, P.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Ebeling, K.; Kunde, D.; Nishan, P.] Cent Inst Canc Res, Berlin, Germany. [Hopper, J. L.] Univ Melbourne, Ctr Genet Epidemiol, Melbourne, Vic, Australia. [Eliassen, H.; S Hankinson Nurses Hlth Study I II Res Grp] Harvard Med Sch, Brigham & Womens Hosp, Channing Lab, Boston, MA USA. [Gajalakshmi, V.] Chennai Canc Inst, Madras, Tamil Nadu, India. [Martin, N.; Pardthaisong, T.; Silpisornkosol, S.; Theetranont, C.] Chiang Mai Univ, Chiang Mai, Thailand. [Boosiri, B.; Chutivongse, S.; Jimakorn, P.; Virutamasen, P.; Wongsrichanalai, C.] Chulalongkorn Univ, Bangkok, Thailand. [Neugut, A.; Santella, R.] Columbia Univ, New York, NY 10027 USA. [Baines, C. J.; Kreiger, N.; Miller, A. B.; Wall, C.] Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Tjonneland, A.] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Jorgensen, T.; Stahlberg, C.; Pedersen, A. Tonnes] Res Ctr Prevent & Hlth, Danish Nurse Cohort Study, Capital Reg, Denmark. [Flesch-Janys, D.] Univ Canc Ctr Hamburg, Dept Canc Epidemiol Clin Canc Registry, Hamburg, Germany. [Hakansson, N.] Karolinska Inst, Dept Environm Med, Stockholm, Sweden. [Cauley, J.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Heuch, I.] Univ Bergen, Dept Math, N-5007 Bergen, Norway. [Adami, H. O.; Persson, I.; Weiderpass, E.] Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. [Magnusson, C.] Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden. [Chang-Claude, J.; Kaaks, R.] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [McCredie, M.; Paul, C.; Skegg, D. C. G.; Spears, G. F. S.] Univ Otago, Dunedin, New Zealand. [Iwasaki, M.; Tsugane, S.] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Epidemiol & Prevent Div, Tokyo 104, Japan. [Anderson, G.; Daling, J. R.; Hampton, J.; Hutchinson, W. B.; Li, C. I.; Malone, K.; Mandelson, M.; Newcomb, P.; Noonan, E. A.; Ray, R. M.; Stanford, J. L.; Tang, M. T. C.; Thomas, D. B.; Weiss, N. S.; White, E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Izquierdo, A.; Viladiu, P.] Girona Canc Registry, Girona, Spain. [Fourkala, E. O.; Jacobs, I.; Menon, U.; Ryan, A.] UCL, Dept Womens Canc, Inst Womens Hlth, Gynaecol Canc Res Ctr, London, England. [Cuevas, H. R.; Ontiveros, P.; Palet, A.; Salazar, S. B.] Hosp Gen Mexico City, Mexico City, DF, Mexico. [Aristizabal, N.; Cuadros, A.] Univ Hosp, Cali, Colombia. [Tryggvadottir, L.; Tulinius, H.] Iceland Canc Soc, Reykjavik, Iceland. [Riboli, E.] Univ London Imperial Coll Sci Technol & Med, London, England. [Andrieu, N.; Bachelot, A.; Le, M. G.; Bremond, A.; Gairard, B.; Lansac, J.; Piana, L.; Renaud, R.] Inst Gustave Roussy, Villejuif, France. [Clavel-Chapelon, F.; Fournier, A.; Touillaud, M.; Mesrine, S.; Chabbert-Buffet, N.; Boutron-Ruault, M. C.] Paris S Univ, INSERM, Inst Gustave Roussy, EPIC Grp E3N, Villejuif, France. [Wolk, A.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Torres-Mejia, G.] Inst Nacl Salud Publ, Morelos, Mexico. [Franceschi, S.; Romieu, I.] Int Agcy Res Canc, F-69372 Lyon, France. [Boyle, P.] Int Prevent Res Inst, Lyon, France. [Lubin, F.; Modan, B.; Ron, E.; Wax, Y.] Israel Chaim Sheba Med Ctr, Tel Hashomer, Israel. [Friedman, G. D.; Hiatt, R. A.] Kaiser Permanente, Oakland, CA USA. [Levi, F.] Inst Univ Med Sociale & Prevent, Lausanne, Switzerland. [Kosmelj, K.; Primic-Zakelj, M.; Ravnihar, B.; Stare, J.] Inst Oncol, Ljubljana, Slovenia. [Ekbom, A.; Erlandsson, G.; Persson, I.] Karolinska Inst, Stockholm, Sweden. [Beeson, W. L.; Fraser, G.] Loma Linda Univ, Loma Linda, CA 92350 USA. [Peto, J.] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. [Hanson, R. L.; Leske, M. C.; Mahoney, M. C.; Nasca, P. C.; Varma, A. O.; Weinstein, A. L.] Long Isl Breast Canc Study, Long Isl City, NY USA. [Hartman, M. L.; Olsson, H.] Univ Hosp, Lund, Sweden. [Goldbohm, R. A.; van den Brandt, P. A.] Maastricht Univ, Maastricht, Netherlands. [Palli, D.] ISPO, Mol & Nutrit Epidemiol Unit, Florence, Italy. [Teitelbaum, S.] Mt Sinai Sch Med, New York, NY 10029 USA. [Apelo, R. A.; Baens, J.; de la Cruz, J. R.; Javier, B.; Lacaya, L. B.; Ngelangel, C. A.] Univ Philippines, Manila, Philippines. [La Vecchia, C.; Negri, E.] Ist Mario Negri, Milan, Italy. [La Vecchia, C.; Negri, E.] Univ Milan, I-20122 Milan, Italy. [Marubini, E.] Ist Nazl Tumori, Div Stat Med & Biometria, Milan, Italy. [Ferraroni, M.] Ist Stat Med & Biometria, Milan, Italy. [Pike, M. C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gerber, M.; Richardson, S.; Segala, C.] Montpellier Canc Ctr, Montpellier, France. [Gerber, M.; Richardson, S.; Segala, C.] INSERM, Montpellier, France. [Gatei, D.; Kenya, P.; Kungu, A.; Mati, J. G.] Nairobi Ctr Res Reprod, Nairobi, Kenya. [Brinton, L. A.; Freedman, M.; Hoover, R.; Schairer, C.; Ziegler, R.] NCI, Bethesda, MD 20892 USA. [Banks, E.] Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia. [Spirtas, R.] NICHHD, Bethesda, MD 20892 USA. [Lee, H. P.] Natl Univ Singapore, Singapore 117548, Singapore. [Rookus, M. A.; van Leeuwen, F. E.] Netherlands Canc Inst, Amsterdam, Netherlands. [Schoenberg, J. A.] New Jersey State Dept Hlth, Trenton, NJ 08625 USA. [Graff-Iversen, S.; Selmer, R.] Norwegian Inst Publ Hlth, Oslo, Norway. [Jones, L.; McPherson, K.; Neil, A.; Vessey, M.; Yeates, D.] Dept Publ Hlth, Oxford, England. [Mabuchi, K.; Preston, D.] Radiat Effects Res Fdn, Hiroshima, Japan. [Hannaford, P.; Kay, C.] Royal Coll Gen Practitioners Oral Contracept Study, London, England. [McCann, S. E.] Roswell Pk Canc Inst, New York, NY USA. [Rosero-Bixby, L.] Univ Costa Rica, San Jose, Costa Rica. [Gao, Y. T.; Jin, F.; Yuan, J-M] Shanghai Canc Inst, Shanghai, Peoples R China. [Wei, H. Y.; Yun, T.; Zhiheng, C.] Shanghai Inst Planned Parenthood Res, Shanghai, Peoples R China. [Berry, G.; Booth, J. Cooper; Jelihovsky, T.; MacLennan, R.; Shearman, R.] Univ Sydney, Dept Publ Hlth, Sydney, NSW 2006, Australia. [Hadjisavvas, A.; Kyriacou, K.; Loisidou, M.] Cyprus Inst Neurol & Genet, Nicosia, Cyprus. [Zhou, X.] Wuhan Univ, Zhongman Hosp, Wuhan 430072, Peoples R China. [Wang, Q-S] Tianjin Canc Inst, Tianjin, Peoples R China. [Kawai, M.; Minami, Y.; Tsuji, I.] Tohoku Univ, Grad Sch Med, Sendai, Miyagi 980, Japan. [Lund, E.; Kumle, M.; Stalsberg, H.] Univ Tromso, Tromso, Norway. [Shu, X. O.; Zheng, W.] Vanderbilt Univ, Nashville, TN USA. [Monninkhof, E. M.; Onland-Moret, N. C.; Peeters, P. H. M.] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Katsouyanni, K.; Trichopoulou, A.; Trichopoulos, D.; Tzonou, A.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Baltzell, K. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dabancens, A.; Martinez, L.; Molina, R.; Salas, O.] Univ Chile, Santiago, Chile. [Alexander, F. E.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Anderson, K.; Folsom, A. R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Gammon, M. D.; Hulka, B. S.; Millikan, R.] Univ N Carolina Chapel Hill, Sch Publ Hlth, Chapel Hill, NC USA. [Chilvers, C. E. D.] Univ Nottingham, Nottingham NG7 2RD, England. [Lumachi, F.] Univ Padua, Sch Med, Padua, Italy. [Bain, C.; Schofield, F.; Siskind, V.] Univ Queensland, Brisbane, Qld, Australia. [Rebbeck, T. R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Bernstein, L. R.; Enger, S.; Haile, R. W.; Paganini-Hill, A.; Ross, R. K.; Ursin, G.; Wu, A. H.; Yu, M. C.] Univ So Calif, Los Angeles, CA USA. [Ewertz, Denmark M.] Univ So Denmark, Odense Univ Hosp, Dept Oncol, Odense, Denmark. [Clarke, E. A.] Univ Toronto, Toronto, ON, Canada. [Kalache, A.; Farley, T. M. M.; Holck, S.; Meirik, O.] World Hlth Org, World Bank Special Programme Res, UNDP, UNFPA, Geneva, Switzerland. [Fukao, A.] Yamagata Univ, Grad Sch Med, Yamagata 990, Japan. RP Beral, V (reprint author), Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg, Oxford OX3 7LF, England. RI Tsugane, Shocichiro/A-2424-2015; Heuch, Ivar/A-4510-2008; Negri, Eva/B-7244-2013; KAWAI, MASAAKI/B-3461-2008; Jacobs, Ian/F-1743-2013; Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Loizidou, Maria/C-6607-2009; Hakansson, Niclas/L-7913-2013; Clavel-Chapelon, Francoise/G-6733-2014; ANDRIEU, Nadine/H-4255-2014; de Sanjose Llongueras, Silvia/H-6339-2014; Hartman, Mikael/B-4324-2011; Boutron-Ruault, Marie-Christine/H-3936-2014; Brinton, Louise/G-7486-2015; Onland-Moret, N. Charlotte/G-9185-2011; Lumachi, Franco/K-9501-2015; Hamajima, Nobuyuki/I-7237-2014; IBIS, GENICA/O-1906-2015; Richardson, Sylvia/G-4691-2015; Weiderpass, Elisabete/M-4029-2016; Ferraroni, Monica/D-6548-2017; OI Heuch, Ivar/0000-0003-3386-9688; Negri, Eva/0000-0001-9712-8526; KAWAI, MASAAKI/0000-0003-1383-0487; Jacobs, Ian/0000-0002-8112-4624; Hakansson, Niclas/0000-0001-7673-5554; Lissowska, Jolanta/0000-0003-2695-5799; Sitas, Freddy/0000-0001-9679-1481; La Vecchia, Carlo/0000-0003-1441-897X; Yuan, Jian-Min/0000-0002-4620-3108; Bishop, Tim/0000-0002-8752-8785; PALLI, Domenico/0000-0002-5558-2437; Cauley, Jane A/0000-0003-0752-4408; Brinton, Louise/0000-0003-3853-8562; Lumachi, Franco/0000-0001-8349-631X; Richardson, Sylvia/0000-0003-1998-492X; Weiderpass, Elisabete/0000-0003-2237-0128; Ferraroni, Monica/0000-0002-4542-4996; Magnusson, Cecilia/0000-0002-8567-6725 FU Cancer Research UK FX Funding for this collaborative reanalysis of original data was provided by Cancer Research UK. Funding for the contributing studies is described in the publications of those studies. NR 25 TC 100 Z9 101 U1 2 U2 59 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2012 VL 13 IS 11 BP 1141 EP 1151 DI 10.1016/S1470-2045(12)70425-4 PG 11 WC Oncology SC Oncology GA 030KZ UT WOS:000310570900045 ER PT J AU Comenzo, RL Reece, D Palladini, G Seldin, D Sanchorawala, V Landau, H Falk, R Wells, K Solomon, A Wechalekar, A Zonder, J Dispenzieri, A Gertz, M Streicher, H Skinner, M Kyle, RA Merlini, G AF Comenzo, R. L. Reece, D. Palladini, G. Seldin, D. Sanchorawala, V. Landau, H. Falk, R. Wells, K. Solomon, A. Wechalekar, A. Zonder, J. Dispenzieri, A. Gertz, M. Streicher, H. Skinner, M. Kyle, R. A. Merlini, G. TI Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis SO LEUKEMIA LA English DT Review DE amyloidosis; free light chains; clinical trials; clinical research ID STEM-CELL TRANSPLANTATION; BRAIN NATRIURETIC PEPTIDE; HIGH-DOSE MELPHALAN; SERUM CARDIAC TROPONINS; TWICE-WEEKLY BORTEZOMIB; AL AMYLOIDOSIS; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHIES; INTRAVENOUS MELPHALAN; MOLECULAR-MECHANISMS AB This manuscript summarizes the recommendations that emerged from the first Roundtable on Clinical Research in Immunoglobulin Light-chain Amyloidosis (AL), a meeting sponsored by the Amyloidosis Foundation (Clarkston, MI, USA) to develop a consensus of experts on a modern framework for clinical trial design and drug development in AL. Recent diagnostic and technical advances in AL, and updated consensus guidelines for assessing hematologic and organ responses, enable us to define study populations, appropriate end points, and other criteria for all phases of clinical research. This manuscript provides a framework for the design and conduct of systematic collaborative clinical research in AL to encourage more rapid testing of therapies and to expedite new drug development and approval. C1 [Comenzo, R. L.] Tufts Med Ctr, Blood Bank, Div Hematol Oncol, Boston, MA 02111 USA. [Reece, D.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Palladini, G.; Merlini, G.] Univ Pavia, Fdn IRCCS Policlin San Matteo, I-27100 Pavia, Italy. [Seldin, D.; Sanchorawala, V.; Skinner, M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Landau, H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Falk, R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wells, K.; Solomon, A.] Univ Tennessee, Grad Sch Med, Knoxville, TN USA. [Wechalekar, A.] UCL, London, England. [Zonder, J.] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Dispenzieri, A.; Gertz, M.; Kyle, R. A.] Mayo Clin, Rochester, MN USA. [Streicher, H.] NCI, Washington, DC USA. RP Comenzo, RL (reprint author), Tufts Med Ctr, Blood Bank, Div Hematol Oncol, 800 Washington St, Boston, MA 02111 USA. EM rcomenzo@tuftsmedicalcenter.org RI Palladini, Giovanni/G-1763-2010; OI Palladini, Giovanni/0000-0001-5994-5138; Merlini, Giampaolo/0000-0001-7680-3254; Dispenzieri, Angela/0000-0001-8780-9512 NR 53 TC 59 Z9 64 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 2012 VL 26 IS 11 BP 2317 EP 2325 DI 10.1038/leu.2012.100 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 033JL UT WOS:000310791300003 PM 22475872 ER PT J AU O'Connor, FG Bergeron, MF Cantrell, J Connes, P Harmon, KG Ivy, E Kark, J Klossner, D Lisman, P Meyers, BK O'Brien, K Ohene-Frempong, K Thompson, AA Whitehead, J Deuster, PA AF O'Connor, Francis G. Bergeron, Michael F. Cantrell, Joyce Connes, Philippe Harmon, Kimberly G. Ivy, Edward Kark, John Klossner, Dave Lisman, Peter Meyers, Bryce K. O'Brien, Karen Ohene-Frempong, Kwaku Thompson, Alexis A. Whitehead, James Deuster, Patricia A. TI ACSM and CHAMP Summit on Sickle Cell Trait: Mitigating Risks for Warfighters and Athletes SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE ATHLETIC HEALTH; EXERCISE COLLAPSE; HEMOGLOBINOPATHIES; RISK MANAGEMENT ID SUDDEN-DEATH; ALPHA-THALASSEMIA; BLOOD RHEOLOGY; ADHESION MOLECULES; ARMED-FORCES; EXERTIONAL RHABDOMYOLYSIS; MALIGNANT HYPERTHERMIA; EXERCISE PERFORMANCE; ENDURANCE EXERCISE; STRENUOUS EXERCISE AB O'CONNOR, F. G., M. F. BERGERON, J. CANTRELL, P. CONNES, K. G. HARMON, E. IVY, J. KARK, D. KLOSSNER, P. LISMAN, B. K. MEYERS, K. 0 BRIEN, K. OHENE-FREMPONG, A. A. THOMPSON, J. WHITEHEAD, AND P. A. DEUSTER. ACSM and CHAMP Summit on Sickle Cell Trait: Mitigating Risks for Warfighters and Athletes. Med. Set. Sports Ererc., Vol. 44, No. 11, pp. 2045-2056, 2012. Introduction: An estimated 300 million people worldwide have sickle cell trait (SCT). Although largely benign, SCT has been associated with exertional rhabdomyolysis and exercise-related sudden death in warfighters/athletes (WA). The National Collegiate Athletic Association's policy to confirm a student athlete's SCT status during their preparticipation medical examination prompted reaction from some organizations regarding the rationale and ethical justification of the policy. Methods: On September 26 and 27, 2011, a summit, composed of military and civilian experts in sports medicine and SCT, was convened at the Uniformed Services University in Bethesda, MD. The expert panel was charged with two objectives: 1) to provide specific recommendations to further mitigate the apparent risk with strenuous exercise in WA with SCT and 2) to develop clinical guidelines to identify, treat, and return to duty/play WA suspected to have incurred nonfatal sickle cell collapse. Results: New terminology is introduced, areas of current controversy are explored, consensus recommendations for mitigating risk and managing the WA with SCT are reviewed, and important areas for future research are identified. Conclusion: Further research is needed before conclusions can be drawn regarding the etiology of the increased death rate observed in WA with SCT, and the possibility exists that SCT is a surrogate for as yet another contributing factor for the unexplained deaths. C1 [O'Connor, Francis G.; Lisman, Peter; Deuster, Patricia A.] Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. [Bergeron, Michael F.] Sanford USD Med Ctr, Natl Inst Athlet Hlth & Performance, Sioux Falls, SD USA. [Cantrell, Joyce] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Connes, Philippe] Univ Antilles Guyane, INSERM, UMR 665, Pointe A Pitre, Guadeloupe. [Harmon, Kimberly G.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Harmon, Kimberly G.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. [Ivy, Edward] NHLBI, Bethesda, MD 20892 USA. [Kark, John] Howard Univ Hosp, Div Hematol Oncol, Washington, DC USA. [Klossner, Dave] Natl Collegiate Athlet Assoc, Indianapolis, IN USA. [Meyers, Bryce K.] Walter Reed Army Inst Res, Div Prevent Med, Silver Spring, MD USA. [O'Brien, Karen] Madigan Army Med Ctr, Tacoma, WA 98431 USA. [Ohene-Frempong, Kwaku] Childrens Hosp Philadelphia, Ctr Comprehens Sickle Cell, Philadelphia, PA 19104 USA. [Thompson, Alexis A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Whitehead, James] Amer Coll Sports Med, Indianapolis, IN USA. RP O'Connor, FG (reprint author), Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM francis.oconnor@usuhs.edu RI Deuster, Patricia/G-3838-2015; OI Deuster, Patricia/0000-0002-7895-0888; Philippe, Connes/0000-0001-8449-7998 NR 100 TC 21 Z9 21 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 2012 VL 44 IS 11 BP 2045 EP 2056 DI 10.1249/MSS.0b013e31826851c2 PG 12 WC Sport Sciences SC Sport Sciences GA 024QD UT WOS:000310122800001 PM 22811029 ER PT J AU Gorbach, AM Ackerman, HC Liu, WM Meyer, JM Littel, PL Seamon, C Footman, E Chi, A Zorca, S Krajewski, ML Cuttica, MJ Machado, RF Cannon, RO Kato, GJ AF Gorbach, Alexander M. Ackerman, Hans C. Liu, Wei-Min Meyer, Joseph M. Littel, Patricia L. Seamon, Catherine Footman, Eleni Chi, Amy Zorca, Suzana Krajewski, Megan L. Cuttica, Michael J. Machado, Roberto F. Cannon, Richard O., III Kato, Gregory J. TI Infrared imaging of nitric oxide-mediated blood flow in human sickle cell disease SO MICROVASCULAR RESEARCH LA English DT Article ID PULMONARY-HYPERTENSION; ENDOTHELIAL DYSFUNCTION; TRANSCRANIAL DOPPLER; RISK-FACTORS; ANEMIA; VASODILATION; HEMOGLOBIN; CHILDREN; CATHETERIZATION; MORTALITY AB Vascular dysfunction is an important pathophysiologic manifestation of sickle cell disease (SCD), a condition that increases risk of pulmonary hypertension and stroke. We hypothesized that infrared (IR) imaging would detect changes in cutaneous bloodflow reflective of vascular function. We performed IR imaging and conventional strain gauge plethysmography in twenty-five adults with SCD at baseline and during intra-arterial infusions of an endothelium-dependent vasodilator acetylcholine (ACh), an endothelium-independent vasodilator sodium nitroprusside (SNP), and a NOS inhibitor L-NMMA. Skin temperature measured by IR imaging increased in a dose-dependent manner to graded infusions of ACh (+1.1 degrees C, p<0.0001) and SNP (+0.9 degrees C, p<0.0001), and correlated with dose-dependent increases in forearm blood flow (ACh: +19.9 mL/min/100 mL, p<0.0001; r(s)=0.57, p=0.003; SNP: +8.6 mL/min/100 mL, p<0.0001; r=0.70, p=0.0002). Although IR measurement of skin temperature accurately reflected agonist-induced increases in blood flow, it was less sensitive to decreases in blood flow caused by NOS inhibition. Baseline forearm skin temperature measured by IR imaging correlated significantly with baseline forearm blood flow (31.8 +/- 0.2 degrees C. 6.0 +/- 0.4 mL/min/100 mL; r=0.58, p=0.003), and appeared to represent a novel biomarker of vascular function. It predicted a blunted blood flow response to SNP (r=-0.61, p=0.002), and was independently associated with a marker of pulmonary artery pressure, as well as hemoglobin level, diastolic blood pressure, homocysteine, and cholesterol (R-2=0.84, p<0.0001 for the model). IR imaging of agonist-stimulated cutaneous blood flow represents a less cumbersome alternative to plethysmography methodology. Measurement of baseline skin temperature by IR imaging may be a useful new marker of vascular risk in adults with SCD. Published by Elsevier Inc. C1 [Ackerman, Hans C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Gorbach, Alexander M.; Liu, Wei-Min; Meyer, Joseph M.] Natl Inst Biomed Imaging & Bioengn, Infrared Imaging & Thermometry Unit, NIH, Bethesda, MD USA. [Littel, Patricia L.; Seamon, Catherine; Footman, Eleni; Chi, Amy; Zorca, Suzana; Krajewski, Megan L.; Cuttica, Michael J.; Machado, Roberto F.; Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, NIH, Bethesda, MD USA. [Cannon, Richard O., III] NHLBI, Clin Cardiol Sect, Cardiovasc & Pulm Branch, NIH, Bethesda, MD USA. [Ackerman, Hans C.; Cuttica, Michael J.; Machado, Roberto F.; Kato, Gregory J.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD USA. RP Ackerman, HC (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM hans.ackerman@nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Division of Intramural Research, National Heart, Lung and Blood Institute; National Institute of Biomedical Imaging and Bioengineering [1ZIAHL006017]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases FX The authors gratefully acknowledge the expert protocol management by Mary K. Hall, CIP. We thank Dr. E. Elster, Department of Surgery, National Naval Medical Center, for encouraging us to use infrared imaging in this study. This study was funded by the Division of Intramural Research, National Heart, Lung and Blood Institute and the National Institute of Biomedical Imaging and Bioengineering (1ZIAHL006017). HCA is supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. The authors thank the staff of the NIH Clinical Center Procedure Unit and the patients with sickle cell disease who participated in this study. NR 40 TC 9 Z9 9 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 EI 1095-9319 J9 MICROVASC RES JI Microvasc. Res. PD NOV PY 2012 VL 84 IS 3 BP 262 EP 269 DI 10.1016/j.mvr.2012.06.011 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 034GZ UT WOS:000310862200005 PM 22784510 ER PT J AU Rone, MB Midzak, AS Issop, L Rammouz, G Jagannathan, S Fan, JJ Ye, XY Blonder, J Veenstra, T Papadopoulos, V AF Rone, Malena B. Midzak, Andrew S. Issop, Leeyah Rammouz, Georges Jagannathan, Sathvika Fan, Jinjiang Ye, Xiaoying Blonder, Josip Veenstra, Timothy Papadopoulos, Vassilios TI Identification of a Dynamic Mitochondrial Protein Complex Driving Cholesterol Import, Trafficking, and Metabolism to Steroid Hormones SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ACUTE REGULATORY PROTEIN; SIDE-CHAIN CLEAVAGE; BENZODIAZEPINE-RECEPTOR; ENDOPLASMIC-RETICULUM; CELL-DEATH; IN-VITRO; STEROIDOGENESIS; BINDING; BIOSYNTHESIS; TRANSPORT AB Steroid hormones are critical for organismal development and health. The rate-limiting step in steroidogenesis is the transport of cholesterol from the outer mitochondrial membrane (OMM) to the cytochrome P450 enzyme CYP11A1 in the inner mitochondrial membrane (IMM). Cholesterol transfer occurs through a complex termed the "transduceosome," in which cytosolic steroidogenic acute regulatory protein interacts with OMM proteins translocator protein and voltage-dependent anion channel (VDAC) to assist with the transfer of cholesterol to OMM. It has been proposed that cholesterol transfer from OMM to IMM occurs at specialized contact sites bridging the two membranes composed of VDAC and IMM adenine nucleotide translocase (ANT). Blue native PAGE of Leydig cell mitochondria identified two protein complexes that were able to bind cholesterol at 66- and 800-kDa. Immunoblot and mass spectrometry analyses revealed that the 800-kDa complex contained the OMM translocator protein (18-kDa) and VDAC along with IMM CYP11A1, ATPase family AAA domain-containing protein 3A (ATAD3A), and optic atrophy type 1 proteins, but not ANT. Knockdown of ATAD3A, but not ANT or optic atrophy type 1, in Leydig cells resulted in a significant decrease in hormone-induced, but not 22R-hydroxycholesterol-supported, steroid production. Using a 22-phenoxazonoxy-5-cholene-3-beta-ol CYP11A1-specific probe, we further demonstrated that the 800-kDa complex offers the microenvironment needed for CYP11A1 activity. Addition of steroidogenic acute regulatory protein to the complex mobilized the cholesterol bound at the 800-kDa complex, leading to increased steroid formation. These results identify a bioactive, multimeric protein complex spanning the OMM and IMM unit that is responsible for the hormone-induced import, segregation, targeting, and metabolism of cholesterol. (Molecular Endocrinology 26: 1868-1882, 2012) C1 [Papadopoulos, Vassilios] McGill Univ, Ctr Hlth, Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada. [Rone, Malena B.; Midzak, Andrew S.; Issop, Leeyah; Rammouz, Georges; Jagannathan, Sathvika; Fan, Jinjiang; Papadopoulos, Vassilios] McGill Univ, Dept Med, Montreal, PQ H3G 1A4, Canada. [Rone, Malena B.; Midzak, Andrew S.; Issop, Leeyah; Rammouz, Georges; Jagannathan, Sathvika; Fan, Jinjiang; Papadopoulos, Vassilios] McGill Univ, Dept Biochem, Montreal, PQ H3G 1A4, Canada. [Rone, Malena B.; Midzak, Andrew S.; Issop, Leeyah; Rammouz, Georges; Jagannathan, Sathvika; Fan, Jinjiang; Papadopoulos, Vassilios] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1A4, Canada. [Ye, Xiaoying; Blonder, Josip; Veenstra, Timothy] SAIC Frederick Inc, NCI, Lab Prote & Analyt Technol, Ft Detrick, MD 21702 USA. RP Papadopoulos, V (reprint author), McGill Univ, Ctr Hlth, Montreal Gen Hosp, Res Inst, 1650 Cedar Ave,C10-148, Montreal, PQ H3G 1A4, Canada. EM vassilios.papadopoulos@mcgill.ca OI Papadopoulos, Vassilios/0000-0002-1183-8568 FU Canadian Institutes of Health Research [MOP102647, TGF36110]; Canada Research Chair in Biochemical Pharmacology; Research Institute of McGill University Health Center; Le Fonds de la recherche du Quebec-sante FX This work was supported by a grant from the Canadian Institutes of Health Research (MOP102647) and a Canada Research Chair in Biochemical Pharmacology (to V.P.). M.R. was supported in part by a postdoctoral fellowship from The Research Institute of McGill University Health Center. A.M. was supported by postdoctoral fellowships from the Canadian Institutes of Health Research (TGF36110) and Le Fonds de la recherche du Quebec-sante. The Research Institute of McGill University Health Center was supported by a Center grant from Le Fonds de la recherche du Quebec-sante. NR 38 TC 67 Z9 68 U1 1 U2 21 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 2012 VL 26 IS 11 BP 1868 EP 1882 DI 10.1210/me.2012-1159 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 030QJ UT WOS:000310584900008 PM 22973050 ER PT J AU Bouladoux, N Hall, JA Grainger, JR dos Santos, LM Kann, MG Nagarajan, V Verthelyi, D Belkaid, Y AF Bouladoux, N. Hall, J. A. Grainger, J. R. dos Santos, L. M. Kann, M. G. Nagarajan, V. Verthelyi, D. Belkaid, Y. TI Regulatory role of suppressive motifs from commensal DNA SO MUCOSAL IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL IMMUNE-RESPONSES; RETINOIC-ACID; T-CELLS; TOXOPLASMA-GONDII; IFN-GAMMA; DENDRITIC CELLS; BACTERIAL-DNA; CPG MOTIFS; OLIGODEOXYNUCLEOTIDES AB The microbiota contributes to the induction of both effector and regulatory responses in the gastrointestinal (GI) tract. However, the mechanisms controlling these distinct properties remain poorly understood. We previously showed that commensal DNA promotes intestinal immunity. Here, we find that the capacity of bacterial DNA to stimulate immune responses is species specific and correlated with the frequency of motifs known to exert immunosuppressive function. In particular, we show that the DNA of Lactobacillus species, including various probiotics, is enriched in suppressive motifs able to inhibit lamina propria dendritic cell activation. In addition, immunosuppressive oligonucleotides sustain T-reg cell conversion during inflammation and limit pathogen-induced immunopathology and colitis. Altogether, our findings identify DNA-suppressive motifs as a molecular ligand expressed by commensals and support the idea that a balance between stimulatory and regulatory DNA motifs contributes to the induction of controlled immune responses in the GI tract and gut immune homeostasis. Further, our findings suggest that the endogenous regulatory capacity of DNA motifs enriched in some commensal bacteria could be exploited for therapeutic purposes. C1 [Bouladoux, N.; Hall, J. A.; Grainger, J. R.; dos Santos, L. M.; Belkaid, Y.] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Hall, J. A.] NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY USA. [dos Santos, L. M.] Univ Fed Minas Gerais, Lab Gnotobiol & Immunol LAGI, Belo Horizonte, MG, Brazil. [Kann, M. G.] Univ Maryland, Baltimore, MD 21201 USA. [Nagarajan, V.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD USA. [Verthelyi, D.] Ctr Drug Evaluat & Res, Food & Drug Adm, Div Therapeut Proteins, Immunol Lab, Bethesda, MD USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov OI Grainger, John/0000-0002-4052-5923 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank C Eigsti and E Stregevsky from the NIAID sorting facility and K Beacht, V Wang, and T Peterson for technical assistance. We thank D Chou, M Molloy, S Naik, S Spencer, and E Wohlfert for their critical reading of the manuscript. NR 52 TC 23 Z9 23 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2012 VL 5 IS 6 BP 623 EP 634 DI 10.1038/mi.2012.36 PG 12 WC Immunology SC Immunology GA 030LS UT WOS:000310572800005 PM 22617839 ER PT J AU Klatt, NR Estes, JD Sun, X Ortiz, AM Barber, JS Harris, LD Cervasi, B Yokomizo, LK Pan, L Vinton, CL Tabb, B Canary, LA Dang, Q Hirsch, VM Alter, G Belkaid, Y Lifson, JD Silvestri, G Milner, JD Paiardini, M Haddad, EK Brenchley, JM AF Klatt, N. R. Estes, J. D. Sun, X. Ortiz, A. M. Barber, J. S. Harris, L. D. Cervasi, B. Yokomizo, L. K. Pan, L. Vinton, C. L. Tabb, B. Canary, L. A. Dang, Q. Hirsch, V. M. Alter, G. Belkaid, Y. Lifson, J. D. Silvestri, G. Milner, J. D. Paiardini, M. Haddad, E. K. Brenchley, J. M. TI Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection SO MUCOSAL IMMUNOLOGY LA English DT Article ID INNATE LYMPHOID-CELLS; NATURAL-KILLER-CELLS; REGULATORY T-CELLS; RETINOIC-ACID; MICROBIAL TRANSLOCATION; HIV-INFECTION; IMMUNE ACTIVATION; TH17 CELLS; GENE-EXPRESSION; DENDRITIC CELLS AB Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV) disease progression is associated with multifocal damage to the gastrointestinal tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation, but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of interleukin (IL)-17-producing lymphocytes, cells that microarray analysis showed expressed genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103+ dendritic cells (DCs) after SIV infection, which associated with the loss of IL-17- and IL-22-producing lymphocytes. CD103+ DCs expressed genes associated with promotion of IL-17/IL-22+ cells, and coculture of CD103+ DCs and naive T cells led to increased IL17A and RORc expression in differentiating T cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis. C1 [Klatt, N. R.; Harris, L. D.; Vinton, C. L.; Canary, L. A.; Dang, Q.; Hirsch, V. M.; Belkaid, Y.; Brenchley, J. M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Klatt, N. R.; Harris, L. D.; Vinton, C. L.; Canary, L. A.; Dang, Q.; Hirsch, V. M.; Belkaid, Y.; Brenchley, J. M.] NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA. [Estes, J. D.; Tabb, B.; Lifson, J. D.] Frederick Natl Lab Canc Res, SAIC Frederick, AIDS & Canc Virus Program, Frederick, MD USA. [Sun, X.; Pan, L.; Haddad, E. K.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA. [Ortiz, A. M.; Cervasi, B.; Silvestri, G.; Paiardini, M.] Emory Univ, Yerkes Natl Primate Res Ctr, Pathol & Lab Med, Atlanta, GA 30322 USA. [Ortiz, A. M.] Univ Penn, Sch Med, Cellular & Mol Biol Program, Philadelphia, PA 19104 USA. [Barber, J. S.; Yokomizo, L. K.; Milner, J. D.] NIAD, Lab Allerg Dis, NIH, Bethesda, MD USA. [Alter, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst, Boston, MA USA. [Belkaid, Y.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Brenchley, JM (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbrenchl@mail.nih.gov FU Intramural National Institute of Allergy and Infectious Diseases, US National Institutes of Health program; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health [R01 AI-084836] FX We would like to acknowledge Heather Cronise, JoAnne Swerczek, Richard Herbert, and all the veterinary staff at the NIH animal center. We would like to thank Tracy Meeker and Stephanie Ehnert, and the veterinary staff at YNPRC. We would like to thank the Cleveland Immunopathogenesis Consortium (BBC/CLIC) for advice and helpful discussions. We would like to thank Mark Cameron and Peter Wilkinson from the Genomics core at VGTI-FL for gene array consultation. Histology support was provided by the Pathology/Histotechnology Laboratory (PHL) core service located at the National Cancer Institute-Frederick, Frederick, MD, USA. These studies were supported by the Intramural National Institute of Allergy and Infectious Diseases, US National Institutes of Health program, and in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, and National Institutes of Health R01 AI-084836 under M Paiardini. 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 United States. NR 57 TC 75 Z9 75 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2012 VL 5 IS 6 BP 646 EP 657 DI 10.1038/mi.2012.38 PG 12 WC Immunology SC Immunology GA 030LS UT WOS:000310572800007 PM 22643849 ER PT J AU Sundaresan, NR Vasudevan, P Zhong, L Kim, G Samant, S Parekh, V Pillai, VB Ravindra, PV Gupta, M Jeevanandam, V Cunningham, JM Deng, CX Lombard, DB Mostoslavsky, R Gupta, MP AF Sundaresan, Nagalingam R. Vasudevan, Prabhakaran Zhong, Lei Kim, Gene Samant, Sadhana Parekh, Vishwas Pillai, Vinodkumar B. Ravindra, P. V. Gupta, Madhu Jeevanandam, Valluvan Cunningham, John M. Deng, Chu-Xia Lombard, David B. Mostoslavsky, Raul Gupta, Mahesh P. TI The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun SO NATURE MEDICINE LA English DT Article ID HEAVY-CHAIN EXPRESSION; FOCAL ADHESION KINASE; REGULATES LIFE-SPAN; CALORIE RESTRICTION; HISTONE DEACETYLASE; GENE-EXPRESSION; HEART-FAILURE; MICE; ACTIVATION; DISEASE AB Abnormal activation of insulin-like growth factor (IGF)-Akt signaling is implicated in the development of various diseases, including heart failure. However, the molecular mechanisms that regulate activation of this signaling pathway are not completely understood. Here we show that sirtuin 6 (SIRT6), a nuclear histone deacetylase, functions at the level of chromatin to directly attenuate IGF-Akt signaling. SIRT6-deficient mice developed cardiac hypertrophy and heart failure, whereas SIRT6 transgenic mice were protected from hypertrophic stimuli, indicating that SIRT6 acts as a negative regulator of cardiac hypertrophy. SIRT6-deficient mouse hearts showed hyperactivation of IGF signaling-related genes and their downstream targets. Mechanistically, SIRT6 binds to and suppresses the promoter of IGF signaling-related genes by interacting with c-Jun and deacetylating histone 3 at Lys9 (H3K9). We also found reduced SIRT6 expression in human failing hearts. These findings disclose a new link between SIRT6 and IGF-Akt signaling and implicate SIRT6 in the development of cardiac hypertrophy and failure. C1 [Sundaresan, Nagalingam R.; Samant, Sadhana; Pillai, Vinodkumar B.; Ravindra, P. V.; Jeevanandam, Valluvan; Gupta, Mahesh P.] Univ Chicago, Dept Surg, Comm Cellular & Mol Physiol, Chicago, IL 60637 USA. [Vasudevan, Prabhakaran; Parekh, Vishwas; Cunningham, John M.] Univ Chicago, Dept Pediat, Comm Dev Biol, Chicago, IL 60637 USA. [Zhong, Lei; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Kim, Gene] Univ Chicago, Cardiol Sect, Dept Med, Chicago, IL 60637 USA. [Gupta, Madhu] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60680 USA. [Deng, Chu-Xia] NIDDKD, US NIH, Bethesda, MD 20892 USA. [Lombard, David B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Lombard, David B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. RP Gupta, MP (reprint author), Univ Chicago, Dept Surg, Comm Cellular & Mol Physiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM mgupta@surgery.bsd.uchicago.edu RI Parekh, Vishwas/B-7162-2014; deng, chuxia/N-6713-2016; OI Parekh, Vishwas/0000-0003-3131-2958; Ravindra, P V/0000-0003-4228-1843 FU US National Institutes of Health [RO1 HL-117041, HL-83423, 111455]; American Heart Association FX We thank F. Alt, Harvard Medical School, for providing SIRT6 knockout mice, E. Verdin, University of California, San Francisco, for providing Flag-SIRT6 wild-type and mutant plasmids, F. VanGool, Institut de Biologie, Universite Libre de Bruxelles, Gosselies, Belgium, for providing mouse-SIRT6 expression plasmid and K. Chua, Stanford University, for providing SIRT6 retroviral vectors and SIRT6 knockout MEFs. The alpha-MHC promoter vector used to make cardiac-specific SIRT6 transgenic mice was provided by J. Robbins, University of Cincinnati. This study was supported by US National Institutes of Health grants RO1 HL-117041, HL-83423 and 111455 to M. P. G. N.R.S. was supported by a postdoctoral fellowship from the American Heart Association. NR 46 TC 119 Z9 124 U1 4 U2 39 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2012 VL 18 IS 11 BP 1643 EP + DI 10.1038/nm.2961 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 033YJ UT WOS:000310837000024 PM 23086477 ER PT J AU Fukazawa, Y Park, H Cameron, MJ Lefebvre, F Lum, R Coombes, N Mahyari, E Hagen, SI Bae, JY Delos Reyes, M Swanson, T Legasse, AW Sylwester, A Hansen, SG Smith, AT Stafova, P Shoemaker, R Li, Y Oswald, K Axthelm, MK McDermott, A Ferrari, G Montefiori, DC Edlefsen, PT Piatak, M Lifson, JD Sekaly, RP Picker, LJ AF Fukazawa, Yoshinori Park, Haesun Cameron, Mark J. Lefebvre, Francois Lum, Richard Coombes, Noel Mahyari, Eisa Hagen, Shoko I. Bae, Jin Young Delos Reyes, Marcelo, III Swanson, Tonya Legasse, Alfred W. Sylwester, Andrew Hansen, Scott G. Smith, Andrew T. Stafova, Petra Shoemaker, Rebecca Li, Yuan Oswald, Kelli Axthelm, Michael K. McDermott, Adrian Ferrari, Guido Montefiori, David C. Edlefsen, Paul T. Piatak, Michael, Jr. Lifson, Jeffrey D. Sekaly, Rafick P. Picker, Louis J. TI Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines SO NATURE MEDICINE LA English DT Article ID SIMIAN-IMMUNODEFICIENCY-VIRUS; FOLLICULAR HELPER; RHESUS-MONKEYS; CONTROL REPLICATION; ANTIBODY-RESPONSES; VIRAL LOAD; NEF GENE; MEMORY; PROTECTION; CHALLENGE AB Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in the lymph node but not with the responses of such T cells in the blood or with other cellular, humoral and innate immune parameters. We found that maintenance of protective T cell responses is associated with persistent LAV replication in the lymph node, which occurs almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wild-type SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection, an observation that provides a rationale for the development of safe, persistent vectors that can elicit and maintain such responses. C1 [Fukazawa, Yoshinori; Park, Haesun; Lum, Richard; Coombes, Noel; Mahyari, Eisa; Hagen, Shoko I.; Bae, Jin Young; Delos Reyes, Marcelo, III; Swanson, Tonya; Legasse, Alfred W.; Sylwester, Andrew; Hansen, Scott G.; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA. [Fukazawa, Yoshinori; Park, Haesun; Lum, Richard; Coombes, Noel; Mahyari, Eisa; Hagen, Shoko I.; Bae, Jin Young; Delos Reyes, Marcelo, III; Swanson, Tonya; Legasse, Alfred W.; Sylwester, Andrew; Hansen, Scott G.; Axthelm, Michael K.; Edlefsen, Paul T.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Cameron, Mark J.; Lefebvre, Francois; Smith, Andrew T.; Stafova, Petra; Sekaly, Rafick P.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA. [Shoemaker, Rebecca; Li, Yuan; Oswald, Kelli; Piatak, Michael, Jr.; Lifson, Jeffrey D.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA. [McDermott, Adrian] US NIAID, Vaccine Res Inst, Bethesda, MD USA. [Ferrari, Guido; Montefiori, David C.] Duke Univ, Med Ctr, Durham, NC USA. [Edlefsen, Paul T.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. RP Picker, LJ (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA. EM pickerl@ohsu.edu RI Ferrari, Guido/A-6088-2015; mahyari, eisa/L-2002-2016 OI mahyari, eisa/0000-0002-5613-3131 FU Bill and Melinda Gates Foundation [41185]; International AIDS Vaccine Initiative (IAVI); National Institute of Allergy and Infectious Diseases FX This work was supported by the Bill and Melinda Gates Foundation (grant #41185), the International AIDS Vaccine Initiative (IAVI), the National Institute of Allergy and Infectious Diseases (including the US National Institutes of Health (NIH) kits (Ambion). The microarray analysis was conducted using 750 ng of biotinylated complementary RNA hybridized to HumanHT-12_V4 BeadChips (Illumina) at 58 degrees C for 20 h. The arrays were scanned using Illumina's iSCAN and quantified using Genome Studio (Illumina). The analysis of the GenomeStudio output data was conducted using the R54 and Bioconductor55 software packages. Quantile normalization was applied, followed by a log2 transformation. The LIMMA package56 was used to fit a linear model to each probe and perform (moderated) t tests or F tests on the groups being compared. To control the expected proportions of false positives, the FDR for each unadjusted P value was calculated using the Benjamini and Hochberg method implemented in LIMMA. Multidimensional scaling was used as a dimensionality reduction method in R to generate plots for the evaluation of similarities or dissimilarities between datasets. Ingenuity Pathway Analysis software (IPA, Ingenuity Systems) was used to annotate genes and rank canonical pathways. An immune response gene filter, constructed from innate and adaptive immune response gene queries of Gene Ontology (http://www.geneontology.org/),T cell activation and complement pathway genes from IPA and our own IFN- and inflammasomeresponse gene lists57, was used where noted to reduce datasets for visualization before FDR estimation. The microarray data are available through the National Center for Biotechnology Information Gene Expression Omnibus (GEO superseries GSE40006). NR 57 TC 77 Z9 77 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2012 VL 18 IS 11 BP 1673 EP + DI 10.1038/nm.2934 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 033YJ UT WOS:000310837000028 PM 22961108 ER PT J AU Wilson, RH Maruoka, S Whitehead, GS Foley, JF Flake, GP Sever, ML Zeldin, DC Kraft, M Garantziotis, S Nakano, H Cook, DN AF Wilson, Rhonda H. Maruoka, Shuichiro Whitehead, Gregory S. Foley, Julie F. Flake, Gordon P. Sever, Michelle L. Zeldin, Darryl C. Kraft, Monica Garantziotis, Stavros Nakano, Hideki Cook, Donald N. TI The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens SO NATURE MEDICINE LA English DT Article ID IMMUNE-RESPONSES; ENDOTOXIN EXPOSURE; AIRWAY HYPERRESPONSIVENESS; BACTERIAL FLAGELLIN; BIRTH COHORT; CELLS; INNATE; INFLAMMATION; SALMONELLA; PROTEIN AB Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction(1). Exposure to indoor allergens is a risk factor for asthma, but this disease is also associated with high household levels of total and particularly Gram-negative bacteria(2). The ability of bacterial products to act as adjuvants(3) suggests they might promote asthma by priming allergic sensitization to inhaled allergens. In support of this idea, house dust extracts (HDEs) can activate antigen-presenting dendritic cells (DCs) in vitro and promote allergic sensitization to inhaled innocuous proteins in vivo(4). It is unknown which microbial products provide most of the adjuvant activity in HDEs. A screen for adjuvant activity of microbial products revealed that the bacterial protein flagellin (FLA) stimulated strong allergic airway responses to an innocuous inhaled protein, ovalbumin (OVA). Moreover, Toll-like receptor 5 (TLR5), the mammalian receptor for FLA(5,6), was required for priming strong allergic responses to natural indoor allergens present in HDEs. In addition, individuals with asthma have higher serum levels of FLA-specific antibodies as compared to nonasthmatic individuals. Together, these findings suggest that household FLA promotes the development of allergic asthma by TLR5-dependent priming of allergic responses to indoor allergens. C1 [Wilson, Rhonda H.; Maruoka, Shuichiro; Whitehead, Gregory S.; Foley, Julie F.; Flake, Gordon P.; Sever, Michelle L.; Zeldin, Darryl C.; Garantziotis, Stavros; Nakano, Hideki; Cook, Donald N.] NIEHS, Biol Res Lab, NIH, Res Triangle Pk, NC 27709 USA. [Maruoka, Shuichiro] Nihon Univ, Sch Med, Div Resp Med, Tokyo, Japan. [Kraft, Monica] Duke Univ, Med Ctr, Duke Asthma Allergy & Airway Ctr, Durham, NC USA. RP Cook, DN (reprint author), NIEHS, Biol Res Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM cookd@niehs.nih.gov RI Garantziotis, Stavros/A-6903-2009; OI Garantziotis, Stavros/0000-0003-4007-375X; Sever, Michelle/0000-0002-2435-1214 FU Intramural Research Program of the US National Institutes of Health NIEHS FX This work was supported by the Intramural Research Program of the US National Institutes of Health NIEHS. We thank the human subjects for their blood donations and B. Yingling, J. Marshburn and A. Rice of the NIEHS Clinical Research Unit and D. Beaver of Duke University for assistance with patient recruitment and serum isolation. J. Hollingsworth (Duke University) with permission from R. Medzhitov (Yale University) provided CD11c-Myd88 transgenic mice on a Myd88-/- background. S. Akira (Osaka University) provided Tlr2-/-, Tlr4-/- and Myd88-/- mice and J. Ting (University of North Carolina) provided Nlrc4-/- mice. D. Wozniak (Ohio State University) provided both strains of P. aeruginosa, F.-S. Shu (Wayne State University) provided purified FLA from P. aeruginosa and A. Gewirtz (Emory University) provided FLA from Escherichia coli. We also thank NIEHS members K. Nakano for genotyping, L. Perrow for mouse colony management, N. Flagler for histology, J. Aloor for measuring endotoxin levels in HDEs, M. Sifre and C. Bortner for help with FACS-based cell sorting, J. Ciencewicki for advice on airway epithelial cell culture and M. Fessler and S. London for suggestions on the manuscript. NR 41 TC 44 Z9 45 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2012 VL 18 IS 11 BP 1705 EP + DI 10.1038/nm.2920 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 033YJ UT WOS:000310837000033 PM 23064463 ER PT J AU Gavara, N Chadwick, RS AF Gavara, Nuria Chadwick, Richard S. TI Determination of the elastic moduli of thin samples and adherent cells using conical atomic force microscope tips SO NATURE NANOTECHNOLOGY LA English DT Article ID MECHANICAL-PROPERTIES; CANCER-DETECTION; AFM; APPLICABILITY; MICRORHEOLOGY AB The atomic force microscope can detect the mechanical fingerprints of normal and diseased cells at the single-cell level under physiological conditions(1,2). However, atomic force microscopy studies of cell mechanics are limited by the 'bottom effect' artefact that arises from the stiff substrates used to culture cells. Because cells adhered to substrates are very thin(3), this artefact makes cells appear stiffer than they really are(4). Here, we show an analytical correction that accounts for this artefact when conical tips are used for atomic force microscope measurements of thin samples. Our bottom effect cone correction (BECC) corrects the Sneddon's model(5), which is widely used to measure Young's modulus, E. Comparing the performance of BECC and Sneddon's model on thin polyacrylamide gels, we find that although Sneddon's model overestimates E, BECC yields E values that are thickness-independent and similar to those obtained on thick regions of the gel. The application of BECC to measurements on live adherent fibroblasts demonstrates a significant improvement on the estimation of their local mechanical properties. C1 [Gavara, Nuria; Chadwick, Richard S.] Natl Inst Deafness & Other Commun Disorders, Auditory Mech Sect, NIH, Bethesda, MD 20892 USA. RP Gavara, N (reprint author), Univ Gottingen, Drittes Phys Inst, Friedrich Hund Pl 1, D-37077 Gottingen, Germany. EM chadwick@helix.nih.gov FU US National Institute of Deafness and Other Communication Disorders FX The authors thank R. Sunyer, V. Luo and K. M. Yamada for critical input. This work was supported by the Intramural Program of the US National Institute of Deafness and Other Communication Disorders. NR 24 TC 72 Z9 74 U1 8 U2 103 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD NOV PY 2012 VL 7 IS 11 BP 733 EP 736 DI 10.1038/NNANO.2012.163 PG 4 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 033JQ UT WOS:000310791900013 PM 23023646 ER PT J AU Beers, J Gulbranson, DR George, N Siniscalchi, LI Jones, J Thomson, JA Chen, GK AF Beers, Jeanette Gulbranson, Daniel R. George, Nicole Siniscalchi, Lauren I. Jones, Jeffrey Thomson, James A. Chen, Guokai TI Passaging and colony expansion of human pluripotent stem cells by enzyme-free dissociation in chemically defined culture conditions SO NATURE PROTOCOLS LA English DT Article ID HUMAN ES CELLS; HUMAN BLASTOCYSTS; SELF-RENEWAL; DIFFERENTIATION; LINES; DERIVATION; SURVIVAL AB This protocol describes an EDTA-based passaging procedure to be used with chemically defined E8 medium that serves as a tool for basic and translational research into human pluripotent stem cells (PSCs). In this protocol, passaging one six-well or 10-cm plate of cells takes about 6-7 min. This enzyme-free protocol achieves maximum cell survival without enzyme neutralization, centrifugation or drug treatment. It also allows for higher throughput, requires minimal material and limits contamination. Here we describe how to produce a consistent E8 medium for routine maintenance and reprogramming and how to incorporate the EDTA-based passaging procedure into human induced PSC (iPSC) derivation, colony expansion, cryopreservation and teratoma formation. This protocol has been successful in routine cell expansion, and efficient for expanding large-volume cultures or a large number of cells with preferential dissociation of PSCs. Effective for all culture stages, this procedure provides a consistent and universal approach to passaging human PSCs in E8 medium. C1 [Beers, Jeanette; Siniscalchi, Lauren I.; Chen, Guokai] NHLBI, Ctr Mol Med, Bethesda, MD 20892 USA. [Gulbranson, Daniel R.; Thomson, James A.; Chen, Guokai] Morgridge Inst Res, Madison, WI USA. [Gulbranson, Daniel R.; Thomson, James A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, Madison, WI USA. [George, Nicole; Jones, Jeffrey] WiCell Inst, Madison, WI USA. [Jones, Jeffrey] Univ Wisconsin, Dept Obstet & Gynecol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Thomson, James A.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. RP Chen, GK (reprint author), NHLBI, Ctr Mol Med, Bldg 10, Bethesda, MD 20892 USA. EM guokai.chen@nih.gov FU NHLBI, NIH Common Fund through the Center for Regenerative Medicine; Charlotte Geyer Foundation; Morgridge Institute for Research, NIH grant [UO1ES017166]; NIH [RR-05-19, HHSN309200582085C]; Wisconsin Alumni Research Foundation FX This work was supported by NHLBI, NIH Common Fund through the Center for Regenerative Medicine (to G.C. and J.B.), the Charlotte Geyer Foundation, the Morgridge Institute for Research, NIH grant UO1ES017166 (to J.A.T.), NIH contract RR-05-19 (to J.A.T.), NIH contract no. HHSN309200582085C (to J.J.) and private funds from the Wisconsin Alumni Research Foundation (to J.J.). We thank M. Boehm, T. Finkel and M. Rao for their suggestions. We thank K. Eastman for editorial assistance. NR 20 TC 67 Z9 67 U1 3 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD NOV PY 2012 VL 7 IS 11 BP 2029 EP 2040 DI 10.1038/nprot.2012.130 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 030QM UT WOS:000310585200011 PM 23099485 ER PT J AU Fischer, RS Myers, KA Gardel, ML Waterman, CM AF Fischer, Robert S. Myers, Kenneth A. Gardel, Margaret L. Waterman, Clare M. TI Stiffness-controlled three-dimensional extracellular matrices for high-resolution imaging of cell behavior SO NATURE PROTOCOLS LA English DT Article ID BRANCHING MORPHOGENESIS; FOCAL ADHESIONS; GROWTH CONES; STEM-CELLS; IN-VITRO; SUBSTRATE; COLLAGEN; MIGRATION; CULTURE; ANGIOGENESIS AB Regulation of cell functions by the physical properties of the extracellular matrix (ECM) has emerged as a crucial contributor to development and disease. Two specific physical properties of the ECM, stiffness and dimensionality, each influence cell signaling and function. As these ECM physical properties are linked to other properties that also regulate cell behavior, e. g., integrin ligand density, parsing the specific contributions of ECM stiffness and dimensionality has proven difficult. Here we detail a simple protocol, which can be completed in 1-2 d, for combining three-dimensional (3D) ECM engagement with controlled underlying ECM stiffness. In these 'sandwich gels', cells are sandwiched between a 3D fibrillar ECM and an ECM-coupled polyacrylamide gel of defined compliance, allowing the study of the specific effects of ECM compliance on cell function in physiologically relevant 3D ECMs. This type of system enables high-resolution time-lapse imaging and is suitable for a wide range of cell types and molecular perturbations. C1 [Fischer, Robert S.; Waterman, Clare M.] Natl Heart Lung & Blood Inst NHBLI, Cell Biol & Physiol Ctr, US Natl Inst Hlth NIH, Bethesda, MD USA. [Myers, Kenneth A.] Univ Sci, Dept Biol Sci, Philadelphia, PA USA. [Gardel, Margaret L.] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA. [Gardel, Margaret L.] Inst Biophys Dynam, Chicago, IL USA. [Gardel, Margaret L.] Univ Chicago, Dept Phys, Chicago, IL 60637 USA. RP Waterman, CM (reprint author), Natl Heart Lung & Blood Inst NHBLI, Cell Biol & Physiol Ctr, US Natl Inst Hlth NIH, Bethesda, MD USA. EM fischerr2@nhlbi.nih.gov; watermancm@nhlbi.nih.gov OI Waterman, Clare/0000-0001-6142-6775 FU NHLBI Intramural Research Program; NIH Director's Pioneer Award [DP10D00354] FX R.S.F., K.A.M. and C.M.W. are supported by the NHLBI Intramural Research Program. M.L.G. is supported by the NIH Director's Pioneer Award (DP10D00354). We thank Sergey Plotnikov for insightful discussion. We also acknowledge members of the NIH Electron Microscopy Core Facility and are grateful for the particularly excellent technical skills of M. Daniels and P. Connelly. NR 76 TC 45 Z9 46 U1 5 U2 91 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 NOV PY 2012 VL 7 IS 11 BP 2056 EP 2066 DI 10.1038/nprot.2012.127 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 030QM UT WOS:000310585200013 PM 23099487 ER PT J AU Chio, A Calvo, A Mazzini, L Cantello, R Mora, G Moglia, C Corrado, L D'Alfonso, S Majounie, E Renton, A Pisano, F Ossola, I Brunetti, M Traynor, BJ Restagno, G AF Chio, Adriano Calvo, Andrea Mazzini, Letizia Cantello, Roberto Mora, Gabriele Moglia, Cristina Corrado, Lucia D'Alfonso, Sandra Majounie, Elisa Renton, Alan Pisano, Fabrizio Ossola, Irene Brunetti, Maura Traynor, Bryan J. Restagno, Gabriella CA PARALS TI Extensive genetics of ALS A population-based study in Italy SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; HEXANUCLEOTIDE REPEAT EXPANSION; CLINICAL CHARACTERISTICS; SOD1 MUTATIONS; FUS MUTATIONS; ANG GENE; C9ORF72; TARDBP; EPIDEMIOLOGY; DIAGNOSIS AB Objective: To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases. Methods: The study population includes all ALS cases diagnosed in Piemonte, Italy, from January 2007 to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, and C9ORF72 have been assessed. Results: Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p = 0.001), and age at onset <= 54 years (odds ratio 1.79; p = 0.012). Conclusions: We have found that similar to 11% of patients with ALS carry a genetic mutation, with C9ORF72 being the commonest genetic alteration. Comorbid FTD or a young age at onset are strong indicators of a possible genetic origin of the disease. Neurology (R) 2012;79:1983-1989 C1 [Chio, Adriano; Calvo, Andrea; Moglia, Cristina] Univ Turin, Dept Neurosci, ALS Ctr, Turin, Italy. AOU San Giovanni Battista Torino, Turin, Italy. [Mazzini, Letizia; Cantello, Roberto] Amedeo Avogadro Univ, Dept Neurol, ALS Ctr, Novara, Italy. AOU Maggiore della Carita, Novara, Italy. [Corrado, Lucia; D'Alfonso, Sandra] A Avogadro Univ, IRCAD, Dept Med Sci, Novara, Italy. [Mora, Gabriele] Sci Inst Milano, Milan, Italy. [Majounie, Elisa; Renton, Alan; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Pisano, Fabrizio] IRCCS, Salvatore Maugeri Fdn, Dept Neurol, Pavia, Italy. [Pisano, Fabrizio] IRCCS, Salvatore Maugeri Fdn, Dept Neurorehab, Pavia, Italy. [Pisano, Fabrizio] Sci Inst Veruno, Veruno, Italy. [Ossola, Irene; Restagno, Gabriella] AO OIRM St Anna, Mol Genet Lab, Turin, Italy. RP Chio, A (reprint author), Univ Turin, Dept Neurosci, ALS Ctr, Turin, Italy. EM achio@usa.net RI Traynor, Bryan/G-5690-2010; D'Alfonso, Sandra/K-7295-2014; Calvo, Andrea/K-4141-2016; Cantello, Roberto/L-3786-2016; Moglia, Cristina/K-4142-2016; OI D'Alfonso, Sandra/0000-0002-3983-9925; Calvo, Andrea/0000-0002-5122-7243; Cantello, Roberto/0000-0001-6999-5729; Moglia, Cristina/0000-0001-7377-7222; Chio, Adriano/0000-0001-9579-5341 FU Federazione Italiana Giuoco Calcio; Fondazione Vialli e Mauro per la Sclerosi Laterale Amiotrofica onlus; Ministero della Salute (Ricerca Sanitaria Finalizzata); Regione Piemonte (Progetti Finalizzati); Associazione Amico Canobio; Fondazione Cariplo [2010-0728]; PRIN; European Community [259867, 278611]; NIH, National Institute on Aging [Z01-AG000949-02]; Italian Ministry of Health (Ricerca Finalizzata); Regione Piemonte (Ricerca Finalizzata); University of Torino; Fondazione Vialli e Mauro onlus; European Commission (Health Seventh Framework Programme); Compagnia di San Paolo; Fondazione Borgonovo; Fondazione Cariplo FX This work was funded in part by Federazione Italiana Giuoco Calcio, Fondazione Vialli e Mauro per la Sclerosi Laterale Amiotrofica onlus, Ministero della Salute (Ricerca Sanitaria Finalizzata, 2007), Regione Piemonte (Progetti Finalizzati 2003 and 2004), Associazione Amico Canobio, Fondazione Cariplo (no. 2010-0728), and PRIN 2008. The research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013) (grant agreements no. 259867 and 278611). This work was supported in part by the Intramural Research Programs of the NIH, National Institute on Aging (Z01-AG000949-02).; A. Chio has received research support from Italian Ministry of Health (Ricerca Finalizzata), Regione Piemonte (Ricerca Finalizzata), University of Torino, Federazione Italiana Giuoco Calcio, Fondazione Vialli e Mauro onlus, and European Commission (Health Seventh Framework Programme), and serves on a scientific advisory board for Biogen Idec and Cytokinetics. A. Calvo has received research support from Regione Piemonte (Ricerca Finalizzata) and Compagnia di San Paolo. L. Mazzini has received research support from Fondazione Borgonovo. R. Cantello reports no disclosures. G. Mora has received research support from Italian Ministry of Health (Ricerca Finalizzata). C. Moglia and L. Corrado report no disclosures. S. D'Alfonso has received research support from Fondazione Cariplo. E. Majunie, A. Renton, F. Pisano, I. Ossola, M. Brunetti, and B. Traynor report no disclosures. G. Restagno reports has received research support from Italian Ministry of Health (Ricerca Finalizzata) and Regione Piemonte (Ricerca Finalizzata). Go to Neurology.org for full disclosures. NR 40 TC 64 Z9 66 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 2012 VL 79 IS 19 BP 1983 EP 1989 DI 10.1212/WNL.0b013e3182735d36 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 032US UT WOS:000310745200013 PM 23100398 ER PT J AU Ratchford, JN Costello, K Reich, DS Calabresi, PA AF Ratchford, John N. Costello, Kathleen Reich, Daniel S. Calabresi, Peter A. TI VARICELLA-ZOSTER VIRUS ENCEPHALITIS AND VASCULOPATHY IN A PATIENT TREATED WITH FINGOLIMOD SO NEUROLOGY LA English DT Editorial Material ID RELAPSING MULTIPLE-SCLEROSIS; ORAL FINGOLIMOD C1 [Ratchford, John N.; Costello, Kathleen; Reich, Daniel S.; Calabresi, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Reich, Daniel S.] Natl Inst Neurol Disorders & Stroke, Translat Neuroradiol Unit, Neuroimmunol Branch, Bethesda, MD USA. RP Ratchford, JN (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. EM jratchf1@jhmi.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU Intramural NIH HHS NR 5 TC 39 Z9 39 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 2012 VL 79 IS 19 BP 2002 EP 2004 DI 10.1212/WNL.0b013e3182735d00 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 032US UT WOS:000310745200017 PM 23035072 ER PT J AU Bao, XF Lu, SY Liow, JS Morse, CL Anderson, KB Zoghbi, SS Innis, RB Pike, VW AF Bao, Xiaofeng Lu, Shuiyu Liow, Jeih-San Morse, Cheryl L. Anderson, Kacey B. Zoghbi, Sami S. Innis, Robert B. Pike, Victor W. TI [C-11]Rhodamine-123: Synthesis and biodistribution in rodents SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE [C-11]Rhodamine-123; P-gp substrate; Organic cation transporter; Synthesis; Carbon-11; PET ID P-GLYCOPROTEIN; IN-VIVO; CYCLOSPORINE-A; FREE-FRACTION; RHODAMINE-123; BRAIN; RAT; RESISTANCE; PET; INHIBITION AB Introduction: Rhodamine-123 is a known substrate for the efflux transporter, P-glycoprotein (P-gp). We wished to assess whether rhodamine-123 might serve as a useful substrate for developing probes for imaging efflux transporters in vivo with positron emission tomography (PET). For this purpose, we aimed to label rhodamine-123 with carbon-11 (t(1/2)=20.4 min) and to study its biodistribution in rodents. Methods: [C-11]Rhodamine-123 was prepared by treating rhodamine-110 (desmethyl-rhodamine-123) with [C-11]methyl iodide. The biodistribution of this radiotracer was studied with PET in wild-type mice and rats, in efflux transporter knockout mice, in wild-type rats pretreated with DCPQ (an inhibitor of P-gp) or with cimetidine (an inhibitor of organic cation transporters: OCT), and in P-gp knockout mice pretreated with cimetidine. Unchanged radiotracer in forebrain, plasma and peripheral tissues was also measured ex vivo at 30 min after radiotracer administration to wild-type and efflux transporter knockout rodents. Results: [C-11]Rhodamine-123 was obtained in 4.4% decay-corrected radiochemical yield from cyclotron-produced [C-11]carbon dioxide. After intravenous administration of [C-11]rhodamine-123 to wild-type rodents, PET and ex vivo measurements showed radioactivity uptake was very low in brain, but relatively high in some other organs such as heart, and especially liver and kidney. Inhibition of P-gp increased uptake in brain, heart, kidney and liver, but only by up to twofold. Secretion of radioactivity from kidney was markedly reduced by OCT knockout or pretreatment with cimetidine. Conclusions: [C-11]Rhodamine-123 was unpromising as a PET probe for P-gp function and appears to be a strong substrate of OCT in kidney. Cimetidine appears effective for blocking OCT in kidney in vivo. Published by Elsevier Inc. C1 [Bao, Xiaofeng; Lu, Shuiyu; Liow, Jeih-San; Morse, Cheryl L.; Anderson, Kacey B.; Zoghbi, Sami S.; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM pikev@mail.nih.gov RI Bao, Xiaofeng/K-5278-2013; OI Lu, Shuiyu/0000-0003-0310-4318 FU National Institutes of Health (NIMH) FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIMH). We are grateful to the NIH Clinical PET Center (Chief: Dr. Peter Herscovitch) for cyclotron production of carbon-11. NR 43 TC 6 Z9 7 U1 1 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 2012 VL 39 IS 8 BP 1128 EP 1136 DI 10.1016/j.nucmedbio.2012.06.013 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 031VZ UT WOS:000310672000005 PM 22898316 ER PT J AU Lago, CU Nowinski, SM Rundhaug, JE Pfeiffer, ME Kiguchi, K Hirasaka, K Yang, X Abramson, EM Bratton, SB Rho, O Colavitti, R Kenaston, MA Nikawa, T Trempus, C DiGiovanni, J Fischer, SM Mills, EM AF Lago, C. U. Nowinski, S. M. Rundhaug, J. E. Pfeiffer, M. E. Kiguchi, K. Hirasaka, K. Yang, X. Abramson, E. M. Bratton, S. B. Rho, O. Colavitti, R. Kenaston, M. A. Nikawa, T. Trempus, C. DiGiovanni, J. Fischer, S. M. Mills, E. M. TI Mitochondrial respiratory uncoupling promotes keratinocyte differentiation and blocks skin carcinogenesis SO ONCOGENE LA English DT Article DE mitochondria; uncoupling proteins; skin; carcinogenesis; differentiation ID STEM-CELLS; HAIR FOLLICLE; SKELETAL-MUSCLE; CANCER-CELLS; MICE; EXPRESSION; PARAGANGLIOMA; MUTATIONS; PROTEIN-2; METABOLISM AB Decreased mitochondrial oxidative metabolism is a hallmark bioenergetic characteristic of malignancy that may have an adaptive role in carcinogenesis. By stimulating proton leak, mitochondrial uncoupling proteins (UCP1-3) increase mitochondrial respiration and may thereby oppose cancer development. To test this idea, we generated a mouse model that expresses an epidermal-targeted keratin-5-UCP3 (K5-UCP3) transgene and exhibits significantly increased cutaneous mitochondrial respiration compared with wild type (FVB/N). Remarkably, we observed that mitochondrial uncoupling drove keratinocyte/epidermal differentiation both in vitro and in vivo. This increase in epidermal differentiation corresponded to the loss of markers of the quiescent bulge stem cell population, and an increase in epidermal turnover measured using a bromodeoxyuridine (BrdU)-based transit assay. Interestingly, these changes in K5-UCP3 skin were associated with a nearly complete resistance to chemically-mediated multistage skin carcinogenesis. These data suggest that targeting mitochondrial respiration is a promising novel avenue for cancer prevention and treatment. C1 [Lago, C. U.; Abramson, E. M.; Bratton, S. B.; Mills, E. M.] Univ Texas Austin, Coll Pharm, Div Pharmacol & Toxicol, Inst Cellular & Mol Biol, Austin, TX 78712 USA. [Lago, C. U.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA. [Rundhaug, J. E.; Fischer, S. M.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX USA. [Yang, X.] Fudan Univ, Shanghai 200433, Peoples R China. [Colavitti, R.] Stanford Univ, Div Radiat & Canc Biol, Stanford, CA 94305 USA. [Nikawa, T.] Univ Tokushima, Inst Hlth Biosci, Dept Nutr Physiol, Tokushima 770, Japan. [Trempus, C.] NIEHS, Matrix Biol Grp, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. RP Mills, EM (reprint author), Univ Texas Austin, Coll Pharm, Div Pharmacol & Toxicol, Inst Cellular & Mol Biol, Austin, TX 78712 USA. EM ted_mills@mail.utexas.edu FU National Institutes of Health [DK089224, T32ES07247] FX EMM was supported by the National Institutes of Health grant # DK089224. SMN was supported by the National Institutes of Health Toxicology Training grant T32ES07247. NR 42 TC 7 Z9 7 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 2012 VL 31 IS 44 BP 4725 EP 4731 DI 10.1038/onc.2011.630 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 032MW UT WOS:000310724400008 PM 22266853 ER PT J AU Chew, EY Clemons, T SanGiovanni, JP Danis, R Domalpally, A McBee, W Sperduto, R Ferris, FL AF Chew, Emily Y. Clemons, Traci SanGiovanni, John Paul Danis, Ronald Domalpally, Amitha McBee, Wendy Sperduto, Robert Ferris, Frederick L. CA AREDS2 Res Grp TI The Age-related Eye Disease Study 2 (AREDS2) Study Design and Baseline Characteristics (AREDS2 Report Number 1) SO OPHTHALMOLOGY LA English DT Article ID HIGH-DOSE SUPPLEMENTATION; FATTY-ACID INTAKE; MACULAR DEGENERATION; VITAMIN-C; BETA-CAROTENE; UNITED-STATES; ANTIOXIDANT INTAKE; VISUAL IMPAIRMENT; ALPHA-TOCOPHEROL; FISH CONSUMPTION AB Purpose: The Age-Related Eye Disease Study (AREDS) demonstrated beneficial effects of oral supplementation with antioxidant vitamins and minerals on the development of advanced age-related macular degeneration (AMD) in persons with at least intermediate AMD (bilateral large drusen with or without pigment changes). Observational data suggest that other oral nutrient supplements might further reduce the risk of progression to advanced AMD. The primary purpose of the Age-Related Eye Disease Study 2 (AREDS2) is to evaluate the efficacy and safety of lutein plus zeaxanthin (L + Z) and/or omega-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation in reducing the risk of developing advanced AMD. The study also assesses the reduction in zinc and the omission of beta-carotene from original AREDS formulation. Design: Multicenter, phase III, randomized, controlled clinical trial. Participants: Persons aged 50 to 85 with bilateral intermediate AMD or advanced AMD in 1 eye. Methods: All participants were randomly assigned to placebo (n = 1012), L + Z (10 mg/2 mg; n = 1044), omega-3 LCPUFAs (eicosapentaenoic acid + docosahexaenoic acid [650 mg/350 mg]; n = 1069), or the combination of L + Z and omega-3 LCPUFAs (n = 1078). All participants were offered a secondary randomization to 1 of 4 variations of the original AREDS formulation keeping vitamins C (500 mg) and E (400 IU) and copper (2 mg) unchanged while varying zinc and beta-carotene as follows: Zinc remains at the original level (80 mg), lower only zinc to 25 mg, omit beta-carotene only, or lower zinc to 25 mg and omit beta-carotene. Main Outcome Measures: Progression to advanced AMD determined by centralized grading of annual fundus photographs. Results: We enrolled 4203 participants at 82 clinical centers located in the United States. Population characteristics at baseline were as follows: Mean age, 74 years; 57% female; 97% white; 7% current smokers; 19% with prior cardiovascular disease; and 44% and 50% taking statin-class cholesterol-lowering drugs and aspirin, respectively. Ocular characteristics include 59% with bilateral large drusen, 32% with advanced AMD in 1 eye and mean visual acuity of 20/32 in eyes without advanced AMD. Conclusions: This report presents the AREDS2 study design and the participants' baseline demographic and ocular characteristics. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:2282-2289 (C) 2012 by the American Academy of Ophthalmology. C1 [Chew, Emily Y.; SanGiovanni, John Paul; Ferris, Frederick L.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Clemons, Traci; McBee, Wendy; Sperduto, Robert] EMMES Corp, Rockville, MD USA. [Danis, Ronald; Domalpally, Amitha] Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI USA. RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov RI Domalpally, Amitha/B-2367-2015 FU National Eye Institute/National Institutes of Health (NEI/NIH), Department of Health and Human Services, Bethesda, MD [HHS-N-260-2005-00007-C]; ADB Contract [N01-EY-5-0007]; NIH, Office of Dietary Supplements (ODS); NIH, National Center for Complementary and Alternative Medicine (NCCAM); NIH, National Institute on Aging (NIA); NIH, National Heart, Lung and Blood Institute (NHLBI); NIH, National Institute of Neurological Disorders and Stroke (NINDS) FX This study is supported by the intramural program funds and contracts from the National Eye Institute/National Institutes of Health (NEI/NIH), Department of Health and Human Services, Bethesda, MD, Contract No. HHS-N-260-2005-00007-C and ADB Contract No. N01-EY-5-0007. Funds were generously contributed to these contracts by the following NIH institutes: Office of Dietary Supplements (ODS), National Center for Complementary and Alternative Medicine (NCCAM), National Institute on Aging (NIA), National Heart, Lung and Blood Institute (NHLBI), and National Institute of Neurological Disorders and Stroke (NINDS). NR 45 TC 54 Z9 55 U1 2 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2012 VL 119 IS 11 BP 2282 EP 2289 DI 10.1016/j.ophtha.2012.05.027 PG 8 WC Ophthalmology SC Ophthalmology GA 030OH UT WOS:000310579500014 ER PT J AU Elman, MJ Qin, HJ Aiello, LP Beck, RW Bressler, NM Ferris, FL Glassman, AR Maturi, RK Melia, M AF Elman, Michael J. Qin, Haijing Aiello, Lloyd Paul Beck, Roy W. Bressler, Neil M. Ferris, Frederick L., III Glassman, Adam R. Maturi, Raj K. Melia, Michele CA Diabetic Retinopathy Clinical Res TI Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment Three-Year Randomized Trial Results SO OPHTHALMOLOGY LA English DT Article ID PLUS PROMPT AB Objective: To report the 3-year follow-up results within a previously reported randomized trial evaluating prompt versus deferred (for >= 24 weeks) focal/grid laser treatment in eyes treated with intravitreal 0.5 mg ranibizumab for diabetic macular edema (DME). Design: Multicenter, randomized clinical trial. Participants: Three hundred sixty-one participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea. Methods: Ranibizumab every 4 weeks until no longer improving (with resumption if worsening) and random assignment to prompt or deferred (>= 24 weeks) focal/grid laser treatment. Main Outcome Measures: Best-corrected visual acuity and safety at the 156-week (3-year) visit. Results: The estimated mean change in visual acuity letter score from baseline through the 3-year visit was 2.9 letters more (9.7 vs. 6.8 letters; mean difference, 2.9 letters; 95% confidence interval, 0.4-5.4 letters; P = 0.02) in the deferral group compared with the prompt laser treatment group. In the prompt laser treatment group and deferral group, respectively, the percentage of eyes with a >= 10-letter gain/loss was 42% and 56% (P = 0.02), whereas the respective percentage of eyes with a >= 10-letter gain/loss was 10% and 5% (P = 0.12). Up to the 3-year visit, the median numbers of injections were 12 and 15 in the prompt and deferral groups, respectively (P = 0.007), including 1 and 2 injections, respectively, from the 2-year up to the 3-year visit. At the 3-year visit, the percentages of eyes with central subfield thickness of 250 mu m or more on time-domain optical coherence tomography were 36% in both groups (P = 0.90). In the deferral group, 54% did not receive laser treatment during the trial. Systemic adverse events seemed to be similar in the 2 groups. Conclusions: These 3-year results suggest that focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better, and possibly worse, for vision outcomes than deferring laser treatment for 24 weeks or more in eyes with DME involving the fovea and with vision impairment. Some of the observed differences in visual acuity at 3 years may be related to fewer cumulative ranibizumab injections during follow-up in the prompt laser treatment group. Follow-up through 5 years continues. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:2312-2318 (C) 2012 by the American Academy of Ophthalmology. C1 [Qin, Haijing; Beck, Roy W.; Glassman, Adam R.; Melia, Michele] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Elman, Michael J.] Elman Retina Grp, Baltimore, MD USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA. [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA. RP Qin, HJ (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat3@jaeb.org FU National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland [EY14231, EY14229, EY18817]; Genentech; Office of Research Administration; Abbott Medical Optics; Allergan; Bausch Lomb; Bristol-Meyer-Squibb; Carl Zeiss Meditec; EMMES Corporation; ForSight Labs; LLC Genentech; Genzyme Corporation; Lumenis; Notal Vision; Novartis; Regeneron FX Supported through cooperative agreements from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (grant nos.: EY14231, EY14229, and EY18817).; The funding organization (National Institutes of Health) participated in oversight of the conduct of the study and review of the manuscript, but not directly in the design or conduct of the study; nor in the collection, management, analysis, or interpretation of the data; nor in the preparation of the manuscript. Genentech provided the ranibizumab for the study. In addition, Genentech provided funds to DRCR.net to defray the study's clinical site costs. As described in the Diabetic Retinopathy Clinical Research Network (DRCR.net) Industry Collaboration Guidelines (available at www.drcr.net), the DRCR.net had complete control over the design of the protocol, ownership of the data, and all editorial content of presentations and publications related to the protocol. A complete list of all DRCR.net investigator financial disclosures can be found at www.drcr.net. Writing Committee financial disclosures: Neil M. Bressler: Grants to investigators at The Johns Hopkins University are negotiated and administered by the institution (such as the School of Medicine), which receives the grants, typically through the Office of Research Administration. Individual investigators who participate in the sponsored project(s) are not compensated directly by the sponsor, but may receive salary or other support from the institution to support their effort on the projects(s). Neil M. Bressler is the principal investigator of grants at The Johns Hopkins University sponsored by the following entities (not including the National Institutes of Health): Abbott Medical Optics, Allergan, Bausch & Lomb, Bristol-Meyer-Squibb, Carl Zeiss Meditec, EMMES Corporation, ForSight Labs, LLC Genentech, Genzyme Corporation, Lumenis, Notal Vision, Novartis, and Regeneron. A complete list of all DRCR. net investigator financial disclosures can be found at www.drcr.net. NR 4 TC 121 Z9 126 U1 0 U2 10 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 NOV PY 2012 VL 119 IS 11 BP 2312 EP 2318 DI 10.1016/j.ophtha.2012.08.022 PG 7 WC Ophthalmology SC Ophthalmology GA 030OH UT WOS:000310579500018 ER PT J AU Daniel, E Pistilli, M Pujari, SS Kacmaz, RO Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Foster, CS Jabs, DA Levy-Clarke, GA Kempen, JH AF Daniel, Ebenezer Pistilli, Maxwell Pujari, Siddharth S. Kacmaz, R. Oktay Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Jabs, Douglas A. Levy-Clarke, Grace A. Kempen, John H. TI Risk of Hypotony in Noninfectious Uveitis SO OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR-LENS IMPLANTATION; OCULAR COMPLICATIONS; CYTOMEGALOVIRUS RETINITIS; ULTRASOUND BIOMICROSCOPY; CYCLODIALYSIS CLEFT; CATARACT-SURGERY; PHACOEMULSIFICATION; PRESSURE; MACULOPATHY; VITRECTOMY AB Objective: We sought to describe the risk and risk factors for hypotony in a noninfectious uveitis cohort. Design: Retrospective cohort study. Participants: Patients with noninfectious uveitis seen between 1979 and 2007 at 4 academic ocular inflammation specialty clinics. Methods: Data were collected from medical records by trained, certified, expert reviewers. Main Outcome Measures: Hypotony (<5 mmHg) and low intraocular pressure (<8 mmHg), each sustained for >= 2 visits spanning >= 30 days. Results: During follow-up, 126 of 6785 patients (1.86%) developed hypotony at the rate of 0.61% (95% confidence interval [CI], 0.50-0.75%) per eye-year. Cataract surgery was associated with a 7.5-fold risk (adjusted hazard ratio [aHR], 7.51; 95% CI, 3.97-14.23) of incident hypotony. Phacoemulsification, the type of cataract surgery associated with the least hypotony risk still was associated with nearly 5-fold higher hypotony incidence (aHR, 4.87; 95% CI, 2.25-10.55). Increased risk was observed in children (aHR, 2.92; 95% CI, 1.20-7.10) with respect to young adults, and duration of uveitis of >5 years (aHR, 3.08; 95% CI, 1.30-7.31) with respect to uveitis of <6 month duration. Band keratopathy, >= 3+ vitreous cells, exudative retinal detachment, posterior synechia, and a history of pars plana vitrectomy also were associated with greater hypotony incidence. With respect to anterior uveitis, intermediate uveitis (aHR, 0.17; 95% CI, 0.05-0.56) and posterior uveitis (aHR, 0.11; 95% CI, 0.03-0.45) were associated with lower hypotony risk, whereas panuveitis (aHR, 1.25; 95% CI, 0.67-2.35) was similar. Approximately five-sixths (84.1%) of eyes presenting with hypotony had a visual acuity of <20/200 (aOR for visual acuity <20/200, 13.85; 95% CI, 7.23-26.53). Risk factors for prevalent hypotony were similar. Conclusions: The risk of hypotony is low among eyes with noninfectious uveitis, but is more frequently observed in cases with anterior segment inflammation. Signs of present or past inflammation were associated with greater risk, suggesting excellent inflammatory control may reduce the risk of hypotony. Prior ocular surgery also was associated with higher risk; cataract surgery in particular was associated with much higher risk of hypotony. Lower risk of hypotony with phacoemulsification than with alternative cataract surgery approaches suggests the phacoemulsification approach is preferable. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012; 119: 2377-2385 (C) 2012 by the American Academy of Ophthalmology. C1 [Daniel, Ebenezer; Pistilli, Maxwell; Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Daniel, Ebenezer; Pistilli, Maxwell; Kempen, John H.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Pujari, Siddharth S.; Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Pujari, Siddharth S.] Lions Nab Eye Hosp, Miraj, Maharashtra, India. [Kacmaz, R. Oktay] Allergan Pharmaceut Inc, Irvine, CA USA. [Nussenblatt, Robert B.; Levy-Clarke, Grace A.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Daniel, Ebenezer/0000-0002-2027-2316; Pistilli, Maxwell/0000-0002-4266-4150 FU National Eye Institute [EY014943]; Research to Prevent Blindness (RPB); Paul and Evanina Mackall Foundation FX This study was supported primarily by National Eye Institute Grant EY014943 (J.H.K.). Additional support was provided by Research to Prevent Blindness (RPB) and the Paul and Evanina Mackall Foundation. J.H.K. was an RPB James S. Adams Special Scholar Award recipient, J.E.T. was an RPB Harrington Special Scholar Award recipient, and D.A.J. and J.T.R. were Research to Prevent Blindness Senior Scientific Investigator Award recipients during the course of the study. G. A. L.-C. was previously supported by and R.B.N. continues to be supported by intramural funds of the National Eye Institute. E. B. S. receives support from the Department of Veterans' Affairs. None of the sponsors had any role in the design and conduct of the report; collection, management, analysis, and interpretation of the data; or in the preparation, review, and approval of this manuscript. NR 25 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2012 VL 119 IS 11 BP 2377 EP 2385 DI 10.1016/j.ophtha.2012.05.032 PG 9 WC Ophthalmology SC Ophthalmology GA 030OH UT WOS:000310579500027 PM 22796306 ER PT J AU Nelson, KB Bingham, P Edwards, EM Horbar, JD Kenny, MJ Inder, T Pfister, RH Raju, T Soll, RF AF Nelson, Karin B. Bingham, Peter Edwards, Erika M. Horbar, Jeffrey D. Kenny, Michael J. Inder, Terrie Pfister, Robert H. Raju, Tonse Soll, Roger F. TI Antecedents of Neonatal Encephalopathy in the Vermont Oxford Network Encephalopathy Registry SO PEDIATRICS LA English DT Article DE asphyxia; encephalopathy; newborn; perinatal factors; registries ID CEREBRAL-PALSY; NEWBORN ENCEPHALOPATHY; RISK-FACTORS; TERM INFANTS; SEIZURE DISORDERS; BIRTH-WEIGHT; BRAIN-INJURY; CHORIOAMNIONITIS; FEVER; ISCHEMIA AB BACKGROUND: Neonatal encephalopathy (NE) is a major predictor of death and long-term neurologic disability, but there are few studies of antecedents of NE. OBJECTIVES: To identify antecedents in a large registry of infants who had NE. METHODS: This was a maternal and infant record review of 4165 singleton neonates, gestational age of <= 36 weeks, meeting criteria for inclusion in the Vermont Oxford Network Neonatal Encephalopathy Registry. RESULTS: Clinically recognized seizures were the most prevalent condition (60%); 49% had a 5-minute Apgar score of >= 3 and 18% had a reduced level of consciousness. An abnormal maternal or fetal condition predated labor in 46%; maternal hypertension (16%) or small for gestational age (16%) were the most frequent risk factors. In 8%, birth defects were identified. The most prevalent birth complication was elevated maternal temperature in labor of >= 37.5 degrees C in 27% of mothers with documented temperatures compared with 2% to 3.2% in controls in population-based studies. Clinical chorioamnionitis, prolonged membrane rupture, and maternal hypothyroidism exceeded rates in published controls. Acute asphyxial indicators were reported in 15% (in 35% if fetal bradycardia included) and inflammatory indicators in 24%. Almost one-half had neither asphyxial nor inflammatory indicators. Although most infants with NE were observably ill since the first minutes of life, only 54% of placentas were submitted for examination. CONCLUSIONS: Clinically recognized asphyxial birth events, indicators of intrauterine exposure to inflammation, fetal growth restriction, and birth defects were each observed in term infants with NE, but much of NE in this large registry remained unexplained. Pediatrics 2012;130:878-886 C1 [Nelson, Karin B.; Pfister, Robert H.; Soll, Roger F.] Childrens Hosp, Natl Med Ctr, Washington, DC 20010 USA. [Nelson, Karin B.] NINDS, Bethesda, MD 20892 USA. [Bingham, Peter; Edwards, Erika M.; Horbar, Jeffrey D.; Pfister, Robert H.; Soll, Roger F.] Univ Vermont, Dept Pediat, Burlington, VT USA. [Edwards, Erika M.] Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA. [Kenny, Michael J.] Univ Vermont, Dept Med Biostat, Burlington, VT 05405 USA. [Horbar, Jeffrey D.; Kenny, Michael J.; Pfister, Robert H.; Soll, Roger F.] Vermont Oxford Network, Burlington, VT USA. [Inder, Terrie] Washington Univ, Dept Pediat, St Louis, MO 63130 USA. [Raju, Tonse] NICHHD, Bethesda, MD 20892 USA. RP Nelson, KB (reprint author), 5524 Charles St, Bethesda, MD 20892 USA. EM nelsonk@ninds.nih.gov RI Kenny, Michael/N-3244-2013 OI Kenny, Michael/0000-0002-7750-654X NR 42 TC 13 Z9 13 U1 0 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2012 VL 130 IS 5 BP 878 EP 886 DI 10.1542/peds.2012-0714 PG 9 WC Pediatrics SC Pediatrics GA 029OT UT WOS:000310505900057 PM 23071210 ER PT J AU Wiener, L Zadeh, S Battles, H Baird, K Ballard, E Osherow, J Pao, M AF Wiener, Lori Zadeh, Sima Battles, Haven Baird, Kristin Ballard, Elizabeth Osherow, Janet Pao, Maryland TI Allowing Adolescents and Young Adults to Plan Their End-of-Life Care SO PEDIATRICS LA English DT Article DE adolescents; end-of-life; advance care planning; decision-making; young adults; cancer; HIV ID PEDIATRIC PALLIATIVE CARE; DECISION-MAKING; CHILDREN; CANCER; ILLNESS; PERCEPTIONS; DOCUMENT; PARENTS AB OBJECTIVE: The objective of this study was to assess and compare the usefulness, helpfulness, and stress associated with reviewing a previously adapted advance care planning guide, My Thoughts, My Wishes, My Voice, in comparison with the widely used adult document Five Wishes by adolescents and young adults (AYAs) living with a serious illness. METHODS: Fifty-two participants (age 16-28) living with metastatic or recurrent cancer or HIV infection (acquired at birth or early in life) were presented pages randomly from My Thoughts, My Wishes, My Voice and, Five Wishes, and asked to rank 25 items on several factors, including how likely they would be to complete each statement. Participant opinion on suggested changes in content, design, format, and style was obtained and resulted in development of a new document. RESULTS: AYAs living with a life-threatening illness want to be able to choose and record (1) the kind of medical treatment they want and do not want, (2) how they would liked to be cared for, (3) information for their family and friends to know, and (4) how they would like to be remembered. CONCLUSIONS: AYA views of what should be included in an advance care planning guide were incorporated into a new document, Voicing My Choices, that provides youth, families and providers an opportunity to reduce the silence around the dying process by allowing an opportunity to share one's voice. We provide guidance on how to incorporate this tool into care. Pediatrics 2012;130:897-905 C1 [Wiener, Lori] NCI, Psychosocial Support & Res Program, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Ballard, Elizabeth] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA. [Ballard, Elizabeth; Pao, Maryland] NIMH, Off Clin Director, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Osherow, Janet] Georgetown Univ, Pediat Infect Dis Dept, Washington, DC USA. RP Wiener, L (reprint author), NCI, Psychosocial Support & Res Program, Pediat Oncol Branch, Ctr Canc Res,NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU Intramural Research Programs of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Institute of Mental Health; National Institutes of Health (NIH) FX Supported in part by the Intramural Research Programs of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and the National Institute of Mental Health. Funded by the National Institutes of Health (NIH). NR 32 TC 45 Z9 45 U1 3 U2 28 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2012 VL 130 IS 5 BP 897 EP 905 DI 10.1542/peds.2012-0663 PG 9 WC Pediatrics SC Pediatrics GA 029OT UT WOS:000310505900059 PM 23045560 ER PT J AU Korzeniewski, SJ Grigorescu, V Kleyn, M Young, W Birbeck, GL Todem, D Romero, R Chaiworapongsa, T Paneth, N AF Korzeniewski, Steven J. Grigorescu, Violanda Kleyn, Mary Young, William Birbeck, Gretchen L. Todem, David Romero, Roberto Chaiworapongsa, Tinnakorn Paneth, Nigel TI Performance Metrics After Changes in Screening Protocol for Congenital Hypothyroidism SO PEDIATRICS LA English DT Article DE newborn screening; performance evaluation; congenital hypothyroidism ID LOW-BIRTH-WEIGHT; TRANSIENT HYPOTHYROXINEMIA; THYROID-FUNCTION; PRETERM INFANTS; UNITED-STATES; NEONATAL HYPERTHYROTROPINEMIA; DIAGNOSTIC EFFECTIVENESS; WEEKS GESTATION; NEWBORN; THYROXINE AB OBJECTIVE: To evaluate Michigan newborn screening for congenital hypothyroidism (CH) protocol changes. METHODS: This population-based study includes infants born and screened in Michigan (January 1, 1994-June 30, 2010). Screening performance is compared across 4 periods defined by the dried blood spot testing method: (1) thyroxine (T4) with backup thyrotropin, (2) tandem T4 and thyrotropin, (3) primary thyrotropin testing without serial testing, and (4) primary thyrotropin plus serial testing for births weighing,1800 g. Logistic regression is used to test for differences across periods. RESULTS: Thyrotropin testing exhibited greater specificity overall and greater likelihood of detection with serial testing relative to primary T4 testing. Tandem T4 and thyrotropin testing appeared more sensitive relative to other protocols, yet it produced significantly more false-positives, and detection may have been affected by overdiagnosis and misclassification. Central CH was no longer detected once T4 testing ceased. CONCLUSIONS: Primary thyrotropin plus serial testing for infants at risk for later rising thyrotropin outperformed other newborn screening strategies for classic CH, although 2 false-negatives occurred among normal birth weight infants admitted to the NICU during this testing period. Tandem T4 and thyrotropin screening outperformed other strategies for detection of both classic and central CH combined, although it is associated with increased operating costs. Additional research is necessary to weigh the benefits of increased sensitivity against additional program operating costs. Pediatrics 2012;130:e1252-e1260 C1 [Korzeniewski, Steven J.; Romero, Roberto; Chaiworapongsa, Tinnakorn] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. [Korzeniewski, Steven J.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Grigorescu, Violanda; Kleyn, Mary; Young, William] Michigan Dept Community Hlth, Lansing, MI USA. [Birbeck, Gretchen L.; Todem, David; Paneth, Nigel] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. RP Korzeniewski, SJ (reprint author), Wayne State Univ, Hutzel Womens Hosp, Sch Med, Dept Obstet & Gynecol, 4 Brush Off 4817,3990 John R St, Detroit, MI 48201 USA. EM sKorzeni@med.wayne.edu FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services; National Institutes of Health (NIH) FX This research was supported in part by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. Funded by the National Institutes of Health (NIH). NR 51 TC 1 Z9 1 U1 0 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 NOV PY 2012 VL 130 IS 5 BP E1252 EP E1260 DI 10.1542/peds.2011-3340 PG 9 WC Pediatrics SC Pediatrics GA 029OT UT WOS:000310505900025 PM 23045555 ER PT J AU Wu, LM Austin, J Hamilton, JG Valdimarsdottir, H Isola, L Rowley, S Warbet, R Winkel, G Redd, WH Rini, C AF Wu, Lisa M. Austin, Jane Hamilton, Jada G. Valdimarsdottir, Heiddis Isola, Luis Rowley, Scott Warbet, Rachel Winkel, Gary Redd, William H. Rini, Christine TI Self-efficacy beliefs mediate the relationship between subjective cognitive functioning and physical and mental well-being after hematopoietic stem cell transplant SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; cognitive functioning; self-efficacy; quality of life; distress ID QUALITY-OF-LIFE; TRAUMATIC BRAIN-INJURY; BONE-MARROW-TRANSPLANTATION; CANCER-PATIENTS; MARITAL-STATUS; SOCIAL SUPPORT; BREAST-CANCER; THERAPY; REHABILITATION; SCALE AB Objective Cognitive problems are commonly reported by hematopoietic stem cell transplant (HSCT) survivors and are associated with poorer physical and mental well-being. It was hypothesized that adverse effects of subjective cognitive impairment occur because cognitive difficulties reduce survivors' confidence that they can manage HSCT-related symptomsthat is, self-efficacy for symptom management. Methods Hematopoietic stem cell transplant survivors (n=245), 9 months to 3 years post-HSCT, completed measures of subjective cognitive functioning, self-efficacy for symptom management, and clinically important outcomes: depressed mood, anxiety, and quality of life. Mediation analyses using bootstrapping were conducted to investigate whether effects of subjective cognitive impairment on these outcomes were mediated by self-efficacy for cognitive, emotional (SE-Emotional), social (SE-Social), and physical (SE-Physical) symptom management. Results Self-efficacy mediated relations between subjective cognitive impairment and depressed mood (total indirect effect=-0.0064 and 95% CI -0.0097 to -0.0036), anxiety (total indirect effect=-0.0045, CI -0.0072 to -0.0021), and quality of life (total indirect effect=0.0952, CI 0.0901 to 0.2642). SE-Emotional was a unique mediator when the outcome was depressed mood and anxiety. SE-Social, SE-Physical, and SE-Emotional were specific mediators when outcome was quality of life. Conclusions Findings support the conclusion that subjective cognitive impairment reduces HSCT survivors' confidence in their ability to manage common post-HSCT symptoms, with implications for physical and mental well-being. Interventions that help enhance survivors' self-efficacy, particularly self-efficacy for the management of emotional symptoms, are likely to benefit HSCT survivors who report subjective cognitive impairment. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Wu, Lisa M.; Valdimarsdottir, Heiddis; Winkel, Gary; Redd, William H.; Rini, Christine] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Austin, Jane] William Paterson Univ, Dept Psychol, Wayne, NJ USA. [Hamilton, Jada G.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Isola, Luis] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Rowley, Scott] Hackensack Univ, John Theurer Canc Ctr, Med Ctr, Hackensack, NJ USA. [Warbet, Rachel] Mt Sinai Hosp, New York, NY 10029 USA. [Rini, Christine] Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. [Valdimarsdottir, Heiddis] Reykjavik Univ, Dept Psychol, Reykjavik, Iceland. RP Wu, LM (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl,Box 1130, New York, NY 10029 USA. EM lisa.wu@mssm.edu FU American Cancer Society [RSGPB-07-285-01-CPPB]; National Cancer Institute [2R25CA081137-11A1] FX We wish to thank Katie Basmajian, MA, AnnaMarie Vu, BA, and Jennifer Chee-Chait, BA, for their assistance in data collection for this project. This research was supported by funding from the American Cancer Society (PI: Rini; grant #RSGPB-07-285-01-CPPB) and the National Cancer Institute (grant #2R25CA081137-11A1). The authors have no financial interests to disclose. NR 45 TC 10 Z9 10 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD NOV PY 2012 VL 21 IS 11 BP 1175 EP 1184 DI 10.1002/pon.2012 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 032RE UT WOS:000310735900006 PM 21739524 ER PT J AU Sutin, AR Zonderman, AB AF Sutin, A. R. Zonderman, A. B. TI Depressive symptoms are associated with weight gain among women SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Body mass index; depressed affect; depressive symptoms; longitudinal; weight gain ID BODY-MASS INDEX; SCALE CES-D; QUALITY-OF-LIFE; GENERAL-POPULATION; GENDER-DIFFERENCES; PSYCHIATRIC-DISORDERS; LONGITUDINAL DATA; OLDER-ADULTS; BIRTH COHORT; RISK-FACTOR AB Background. Many studies have linked depression and obesity; few have more than two assessments of depressive symptoms and adiposity to address the potential bidirectional relationship between adiposity and depressive symptoms from young adulthood through old age. We tested whether baseline depressive symptoms are associated with changes in weight, whether baseline adiposity is associated with changes in depressive symptoms, and whether these associations vary by sex. Method. Participants (n = 2251; 47% female) were from the Baltimore Longitudinal Study of Aging (BLSA). Using hierarchical linear modeling (HLM) on 30 years of data, the trajectory of adiposity and depressive symptoms over adulthood was estimated from >10 000 observations (mean = 4.5 assessments per participant) of body mass index (BMI; kg/m(2)), waist circumference and hip circumference and >10 000 observations (mean = 4.5 assessments per participant) of the Center for Epidemiological Studies Depression Scale (CES-D). Baseline depressive symptoms and adiposity were then tested as predictors of the trajectory of adiposity and depressive symptoms respectively. Additional analyses tested for sex-specific associations. Results. Sex moderated the association between depressive symptoms and weight gain such that women who experienced depressed affect had greater increases in BMI (b(interaction) = 0.12, S.E. = 0.04), waist (b(interaction) = 0.22, S.E. = 0.10) and hip circumference (b(interaction) = 0.20, S.E. = 0.07) across the adult lifespan, controlling for relevant demographic and behavioral covariates. Baseline adiposity was unrelated to the trajectory of depressive symptoms (median b = 0.00) for both sexes. Conclusions. Women who experience symptoms of depression tend to gain more weight across adulthood than men who experience such symptoms. Whether an individual was normal weight or overweight was unrelated to changes in depressive symptoms across adulthood. C1 [Sutin, A. R.; Zonderman, A. B.] NIA, NIH, DHHS, Baltimore, MD 21224 USA. RP Sutin, AR (reprint author), NIA, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sutina@mail.nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institutes of Health (NIH), National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the National Institutes of Health (NIH), National Institute on Aging. Dr A. R. Sutin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The funder had no role in the design and conduct of the study; in the collection, analysis and interpretation of the data; or in the preparation, review or the decision to submit. NR 71 TC 17 Z9 17 U1 2 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 2012 VL 42 IS 11 BP 2351 EP 2360 DI 10.1017/S0033291712000566 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 031HI UT WOS:000310629600010 PM 22475128 ER PT J AU Smallridge, RC Ain, KB Asa, SL Bible, KC Brierley, JD Burman, KD Kebebew, E Lee, NY Nikiforov, YE Rosenthal, MS Shah, MH Shaha, AR Tuttle, RM AF Smallridge, Robert C. Ain, Kenneth B. Asa, Sylvia L. Bible, Keith C. Brierley, James D. Burman, Kenneth D. Kebebew, Electron Lee, Nancy Y. Nikiforov, Yuri E. Rosenthal, M. Sara Shah, Manisha H. Shaha, Ashok R. Tuttle, R. Michael CA Amer Thyroid Assoc Anaplastic Thyr TI American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer SO THYROID LA English DT Article ID SQUAMOUS-CELL CARCINOMA; INTENSITY-MODULATED RADIOTHERAPY; PHASE-II TRIAL; HYPERFRACTIONATED ACCELERATED RADIOTHERAPY; COMPARATIVE GENOMIC HYBRIDIZATION; CLINICAL-PRACTICE GUIDELINE; COLONY-STIMULATING FACTOR; FINE-NEEDLE ASPIRATION; IN-SITU HYBRIDIZATION; PROGNOSTIC-FACTORS AB Background: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Rapid evaluation and establishment of treatment goals are imperative for optimum patient management and require a multi-disciplinary team approach. Here we present guidelines for the management of ATC. The development of these guidelines was supported by the American Thyroid Association (ATA), which requested the authors, members the ATA Taskforce for ATC, to independently develop guidelines for ATC. Methods: Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The quality and strength of recommendations were adapted from the Clinical Guidelines Committee of the American College of Physicians, which in turn was developed by the Grading of Recommendations Assessment, Development and Evaluation workshop. Results: The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues including end of life. The guidelines include 65 recommendations. Conclusions: These are the first comprehensive guidelines for ATC and provide recommendations for management of this extremely aggressive malignancy. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach (surgery, radiation, systemic therapy) is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for a clinical trial or hospice/palliative care, depending upon their preference. C1 [Smallridge, Robert C.] Mayo Clin, Jacksonville, FL 32224 USA. [Ain, Kenneth B.] Vet Affairs Med Ctr, Lexington, KY USA. [Asa, Sylvia L.] Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada. [Asa, Sylvia L.; Brierley, James D.] Univ Toronto, Toronto, ON, Canada. [Bible, Keith C.] Mayo Clin, Rochester, MN USA. [Burman, Kenneth D.] Washington Hosp Ctr, Washington, DC 20010 USA. [Kebebew, Electron] NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA. [Lee, Nancy Y.; Shaha, Ashok R.; Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Nikiforov, Yuri E.] Univ Pittsburgh, Pittsburgh, PA USA. [Rosenthal, M. Sara] Univ Kentucky, Program Bioeth, Lexington, KY USA. [Shah, Manisha H.] Ohio State Univ, Columbus, OH 43210 USA. RP Smallridge, RC (reprint author), Mayo Clin, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM smallridge.robert@mayo.edu FU Thyroid Cancer Survivors Association; Joan Shey of the Light of Life Foundation; Pfizer, Inc. (New York, NY); Eisei Inc. (Woodcliff Lake, NJ); Amgen Inc. (Thousand Oaks, CA); Genzyme Corp. (Cambridge, MA); Daiichi Sankyo, Inc. (Parsippany, NJ); Daiichi Sankyo; Genzyme FX We wish to thank Ms. Kathleen Norton (Mayo Clinic, Jacksonville, FL) for her invaluable editorial assistance in preparation of this document. We gratefully acknowledge financial contributions to this project from the Thyroid Cancer Survivors Association and from Joan Shey of the Light of Life Foundation.; J.D.B. is a consultant for OXiGENE, Inc. (South San Francisco, CA). K. D. B. is a consultant for UpToDate, Inc. (Waltham, MA) and Medscape WebMD LLC (New York, NY), and received clinical research support from Pfizer, Inc. (New York, NY), Eisei Inc. (Woodcliff Lake, NJ), Amgen Inc. (Thousand Oaks, CA), and Genzyme Corp. (Cambridge, MA). M.H.S. received clinical research support from Daiichi Sankyo, Inc. (Parsippany, NJ). R.C.S. received research support from Daiichi Sankyo for a clinical trial. R.M.T. received research support from Genzyme and is a consultant for Novo Nordisk (Princeton, NJ), AstraZeneca (Waltham, MA), Veracyte (South San Francisco, CA), and Genzyme. K.B.A., S.L.A., K.C.B., E.K., N.L., Y.E.N., M.S.R., and A.R.S. have no financial disclosures. NR 235 TC 141 Z9 144 U1 1 U2 16 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD NOV PY 2012 VL 22 IS 11 BP 1104 EP 1139 DI 10.1089/thy.2012.0302 PG 36 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 033KK UT WOS:000310794400004 PM 23130564 ER PT J AU Tsang, V Fry, RC Niculescu, MD Rager, JE Saunders, J Paul, DS Zeisel, SH Waalkes, MP Styblo, M Drobna, Z AF Tsang, Verne Fry, Rebecca C. Niculescu, Mihai D. Rager, Julia E. Saunders, Jesse Paul, David S. Zeisel, Steven H. Waalkes, Michael P. Styblo, Miroslav Drobna, Zuzana TI The epigenetic effects of a high prenatal folate intake in male mouse fetuses exposed in utero to arsenic SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Arsenic; Folate; Epigenetics; DNA methylation; Transplacental exposure; CD1 mice ID LOW-BIRTH-WEIGHT; FOLIC-ACID-SUPPLEMENTATION; INDUCED SKIN-LESIONS; DRINKING-WATER; HEPATOCELLULAR-CARCINOMA; CD1 MICE; POSTNATAL DIETHYLSTILBESTROL; CARDIOVASCULAR-DISEASE; METHYLATION CAPACITY; PLACENTAL EXPRESSION AB Inorganic arsenic (iAs) is a complete transplacental carcinogen in mice. Previous studies have demonstrated that in utero exposure to iAs promotes cancer in adult mouse offspring, possibly acting through epigenetic mechanisms. Humans and rodents enzymatically convert iAs to its methylated metabolites. This reaction requires S-adenosylmethionine (SAM) as methyl group donor. SAM is also required for DNA methylation. Supplementation with folate, a major dietary source of methyl groups for SAM synthesis, has been shown to modify iAs metabolism and the adverse effects of iAs exposure. However, effects of gestational folate supplementation on iAs metabolism and fetal DNA methylation have never been thoroughly examined. In the present study, pregnant CD1 mice were fed control (i.e. normal folate, or 2.2 mg/kg) or high folate diet (11 mg/kg) from gestational day (GD) 5 to 18 and drank water with 0 or 85 ppm of As (as arsenite) from GD8 to 18. The exposure to iAs significantly decreased body weight of GD18 fetuses and increased both SAM and S-adenosylhomocysteine (SAH) concentrations in fetal livers. High folate intake lowered the burden of total arsenic in maternal livers but did not prevent the effects of iAs exposure on fetal weight or hepatic SAM and SAH concentrations. In fact, combined folate-iAs exposure caused further significant body weight reduction. Notably, iAs exposure alone had little effect on DNA methylation in fetal livers. In contrast, the combined folate-iAs exposure changed the CpG island methylation in 2,931 genes, including genes known to be imprinted. Most of these genes were associated with neurodevelopment, cancer, cell cycle, and signaling networks. The canonical Wnt-signaling pathway, which regulates fetal development, was among the most affected biological pathways. Taken together, our results suggest that a combined in utero exposure to iAs and a high folate intake may adversely influence DNA methylation profiles and weight of fetuses, compromising fetal development and possibly increasing the risk for early-onset of disease in offspring. (c) 2012 Elsevier Inc. All rights reserved. C1 [Drobna, Zuzana] Univ N Carolina, Dept Nutr, Michael Hooker Res Ctr 2003, Chapel Hill, NC 27599 USA. [Fry, Rebecca C.; Rager, Julia E.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Niculescu, Mihai D.; Zeisel, Steven H.] Univ N Carolina, Dept Nutr, UNC Nutr Res Inst, Chapel Hill, NC 27599 USA. [Waalkes, Michael P.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Drobna, Z (reprint author), Univ N Carolina, Dept Nutr, Michael Hooker Res Ctr 2003, CB 7461, Chapel Hill, NC 27599 USA. EM drobnazu@med.unc.edu FU National Institutes of Health Grant [DK056350]; National Institute of Environmental Health Sciences [P30ES010126]; American Institute for Cancer Research/World Cancer Research Fund (AICR/WCRF); National Toxicology Program and National Institute of Environmental Health Sciences (NIEHS) FX We acknowledge Laurie Bennie and Mrs. Felecia Walton for their assistance during the mice dissection. This work has been supported in part by National Institutes of Health Grant DK056350 to the University of North Carolina at Chapel Hill's Nutrition Obesity Research Center, by a grant from the National Institute of Environmental Health Sciences (P30ES010126), and by the American Institute for Cancer Research/World Cancer Research Fund (AICR/WCRF) to Z.D. This research was supported by the National Toxicology Program and National Institute of Environmental Health Sciences (NIEHS). This article may be the work product of an employee or a group of employees of the NIEHS, NIH: however, the statements contained herein do not necessarily represent the statements, opinions or conclusions of the NIEHS, NIH or the United States Government. The content of this publication does not necessarily reflect the views or the 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 123 TC 18 Z9 19 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2012 VL 264 IS 3 BP 439 EP 450 DI 10.1016/j.taap.2012.08.022 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 031VG UT WOS:000310670000016 PM 22959928 ER PT J AU Adjemian, J Weber, IB McQuiston, J Griffith, KS Mead, PS Nicholson, W Roche, A Schriefer, M Fischer, M Kosoy, O Laven, JJ Stoddard, RA Hoffmaster, AR Smith, T Bui, D Wilkins, PP Jones, JL Gupton, PN Quinn, CP Messonnier, N Higgins, C Wong, D AF Adjemian, Jennifer Weber, Ingrid B. McQuiston, Jennifer Griffith, Kevin S. Mead, Paul S. Nicholson, William Roche, Aubree Schriefer, Martin Fischer, Marc Kosoy, Olga Laven, Janeen J. Stoddard, Robyn A. Hoffmaster, Alex R. Smith, Theresa Bui, Duy Wilkins, Patricia P. Jones, Jeffery L. Gupton, Paige N. Quinn, Conrad P. Messonnier, Nancy Higgins, Charles Wong, David TI Zoonotic Infections Among Employees from Great Smoky Mountains and Rocky Mountain National Parks, 2008-2009 SO VECTOR-BORNE AND ZOONOTIC DISEASES LA English DT Article DE Incidence; National Park Service; Prevalence; Vector-borne; Zoonoses ID BORNE RELAPSING FEVER; WEST-NILE-VIRUS; TOXOPLASMA-GONDII INFECTION; LINKED-IMMUNOSORBENT-ASSAY; UNITED-STATES; SPOTTED-FEVER; IMMUNOGLOBULIN-G; INTERSTATE OUTBREAK; PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS AB U.S. National Park Service employees may have prolonged exposure to wildlife and arthropods, placing them at increased risk of infection with endemic zoonoses. To evaluate possible zoonotic risks present at both Great Smoky Mountains (GRSM) and Rocky Mountain (ROMO) National Parks, we assessed park employees for baseline seroprevalence to specific zoonotic pathogens, followed by evaluation of incident infections over a 1-year study period. Park personnel showed evidence of prior infection with a variety of zoonotic agents, including California serogroup bunyaviruses (31.9%), Bartonella henselae (26.7%), spotted fever group rickettsiae (22.2%), Toxoplasma gondii (11.1%), Anaplasma phagocytophilum (8.1%), Brucella spp. (8.9%), flaviviruses (2.2%), and Bacillus anthracis (1.5%). Over a 1-year study period, we detected incident infections with leptospirosis (5.7%), B. henselae (5.7%), spotted fever group rickettsiae (1.5%), T. gondii (1.5%), B. anthracis (1.5%), and La Crosse virus (1.5%) in staff members at GRSM, and with spotted fever group rickettsiae (8.5%) and B. henselae (4.3%) in staff at ROMO. The risk of any incident infection was greater for employees who worked as resource managers (OR 7.4; 95% CI 1.4,37.5; p = 0.02), and as law enforcement rangers/rescue crew (OR 6.5; 95% CI 1.1,36.5; p = 0.03), relative to those who worked primarily in administration or management. The results of this study increase our understanding of the pathogens circulating within both parks, and can be used to inform the development of effective guidelines and interventions to increase visitor and staff awareness and help prevent exposure to zoonotic agents. C1 [Adjemian, Jennifer; Weber, Ingrid B.] Ctr Dis Control & Prevent CDC, Epidem Intelligence Serv, Off Workforce & Career Dev, Atlanta, GA USA. [Adjemian, Jennifer; McQuiston, Jennifer; Nicholson, William; Roche, Aubree] CDC, Rickettsial Zoonoses Branch, Div Vector Borne Dis, Atlanta, GA 30333 USA. [Weber, Ingrid B.; Griffith, Kevin S.; Mead, Paul S.; Schriefer, Martin] CDC, Bacterial Dis Branch, Div Vector Borne Dis, Ft Collins, CO USA. [Weber, Ingrid B.; Fischer, Marc; Kosoy, Olga; Laven, Janeen J.] CDC, Arboviral Dis Branch, Div Vector Borne Dis, Ft Collins, CO USA. [Stoddard, Robyn A.; Hoffmaster, Alex R.; Smith, Theresa; Bui, Duy] CDC, Bacterial Special Pathogens Branch, Div High Consequence Pathogens & Pathol, Atlanta, GA 30333 USA. [Wilkins, Patricia P.; Jones, Jeffery L.; Gupton, Paige N.] CDC, Parasit Dis Branch, Div Parasit Dis, Atlanta, GA 30333 USA. [Quinn, Conrad P.; Messonnier, Nancy] CDC, Meningitis & Vaccine Preventable Dis Branch, Div Bacterial Dis, Atlanta, GA 30333 USA. [Higgins, Charles; Wong, David] Natl Pk Serv, Off Publ Hlth, Washington, DC USA. [Higgins, Charles; Wong, David] Natl Pk Serv, Off Publ Hlth, Albuquerque, NM USA. RP Adjemian, J (reprint author), NIAID, Epidem Intelligence Serv, Lab Clin Infect Dis, Quarters 15 B-1,8 West Dr,MSC 2665, Bethesda, MD 20892 USA. EM Jennifer.adjemian@nih.gov NR 60 TC 10 Z9 11 U1 0 U2 13 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-3667 EI 1557-7759 J9 VECTOR-BORNE ZOONOT JI Vector-Borne Zoonotic Dis. PD NOV PY 2012 VL 12 IS 11 BP 922 EP 931 DI 10.1089/vbz.2011.0917 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 033FW UT WOS:000310780600002 PM 22835153 ER PT J AU Kashiwakura, JI Okayama, Y Furue, M Kabashima, K Shimada, S Ra, C Siraganian, RP Kawakami, Y Kawakami, T AF Kashiwakura, Jun-ichi Okayama, Yoshimichi Furue, Masutaka Kabashima, Kenji Shimada, Shinji Ra, Chisei Siraganian, Reuben P. Kawakami, Yuko Kawakami, Toshiaki TI Most Highly Cytokinergic IgEs Have Polyreactivity to Autoantigens SO ALLERGY ASTHMA & IMMUNOLOGY RESEARCH LA English DT Article DE Atopic dermatitis; mast cell; cytokine; IgE; autoantigen; histamine-releasing factor ID FC-EPSILON-RI; MAST-CELL SURVIVAL; RECALCITRANT ATOPIC-DERMATITIS; IMMUNOGLOBULIN-E; HIGH-AFFINITY; MEDIATED AUTOIMMUNITY; ASPERGILLUS-FUMIGATUS; NC/NGA MICE; OMALIZUMAB; INDUCTION AB Purpose: Monomeric IgE molecules, when bound to the high-affinity receptor, exhibit a vast heterogeneity in their ability to induce survival promotion and cytokine production in mast cells. At one end of this spectrum, highly cytokinergic IgEs can induce potent survival promotion, degranulation, cytokine production, migration, etc., whereas at the other end, poorly cytokinergic (PC) IgEs can do so inefficiently. In this study, we investigated whether IgEs recognize autoantigens and whether IgEs' binding of autoantigens correlates with difference s in HC versus PC properties. Methods: Enzyme-linked immunosorbent assays were performed to test whether IgEs bind antigens. Histamine-releasing factor in human sera was quantified by western blotting. Cultured mast cells derived from human cord blood were used to test the effects of human sera on cytokine production. Results: Most (7/8) of mouse monoclonal HC IgEs exhibited polyreactivity to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), beta-galactosidase, thyroglobulin and/or histamine-releasing factor. By contrast mouse PC IgEs failed to react with these antigens. A human monoclonal HC IgE also showed polyreactivity to histamine-releasing factor, dsDNA and ssDNA. Interestingly, sera from atopic dermatitis patients showed increased reactivity to ssDNA and beta-galactosidase and increased levels of histamine-releasing factor. Some atopic dermatitis patients, but not healthy individuals, had substantial serum levels of HRF-reactive IgE. Sera from atopic dermatitis patients with high titers of DNA-reactive IgE could induce several fold more IL-8 secretion in human mast cells than sera from healthy individuals. Conclusions: The results show that most HC, but not PC, IgEs exhibit polyreactivity to autoantigens, supporting the autoimmune mechanism in the pathogenesis of atopic dermatitis. C1 [Kashiwakura, Jun-ichi; Kawakami, Yuko; Kawakami, Toshiaki] La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA. [Kashiwakura, Jun-ichi; Okayama, Yoshimichi; Ra, Chisei] Nihon Univ, Grad Sch Med Sci, Adv Med Res Ctr, Div Mol Cell Immunol & Allergol,Itabashi Ku, Tokyo, Japan. [Furue, Masutaka] Kyushu Univ, Dept Dermatol, Fukuoka 812, Japan. [Kabashima, Kenji] Univ Occupat & Environm Hlth, Dept Dermatol, Kitakyushu, Fukuoka 807, Japan. [Shimada, Shinji] Univ Yamanashi, Dept Dermatol, Yamanashi, Japan. [Siraganian, Reuben P.] NIDR, Receptors & Signal Transduct Sect, OIIB, NIH, Bethesda, MD USA. RP Kawakami, T (reprint author), La Jolla Inst Allergy & Immunol, Div Cell Biol, 9420 Athena Circle, La Jolla, CA 92037 USA. EM toshi@liai.org RI Kabashima, Kenji/G-2521-2014; Kawakami, Toshiaki/O-1616-2015 OI Kabashima, Kenji/0000-0002-0773-0554; FU NIH [R01 AI050209]; Intramural Research Program of the National Institutes of Health, NIDCR FX The authors thank Drs. Shane Crotty and Rachel Soloff for providing normal sera. This study was funded in part by an NIH grant R01 AI050209 (T.K.). RPS was supported by the Intramural Research Program of the National Institutes of Health, NIDCR. This is Publication No. 1465 from the La Jolla Institute for Allergy and Immunology. NR 50 TC 18 Z9 19 U1 0 U2 3 PU KOREAN ACAD ASTHMA ALLERGY & CLINICAL IMMUNOLOGY PI JONGNO-GU PA RM 1705, KUMHO BLDG 327-2, CHANGSINDONG, JONGNO-GU, SEOUL 110-540, SOUTH KOREA SN 2092-7355 J9 ALLERGY ASTHMA IMMUN JI Allergy Asthma Immunol. Res. PD NOV PY 2012 VL 4 IS 6 BP 332 EP 340 DI 10.4168/aair.2012.4.6.332 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 028ED UT WOS:000310404700004 PM 23115729 ER PT J AU Ben Mortenson, W Demers, L Fuhrer, MJ Jutai, JW Lenker, J DeRuyter, F AF Ben Mortenson, W. Demers, Louise Fuhrer, Marcus J. Jutai, Jeffrey W. Lenker, James DeRuyter, Frank TI How Assistive Technology Use by Individuals with Disabilities Impacts Their Caregivers A Systematic Review of the Research Evidence SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Review DE Self-Help Devices; Caregivers; Outcomes Assessment; Review ID LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIALS; QUALITATIVE RESEARCH; OUTCOMES RESEARCH; PERSONAL CARE; OLDER PERSONS; HOME; DEVICES; INTERVENTIONS; MOBILITY AB Mortenson WB, Demers L, Fuhrer MJ, Jutai JW, Lenker J, DeRuyter F: How assistive technology use by individuals with disabilities impacts their caregivers: a systematic review of the research evidence. Am J Phys Med Rehabil 2012;91:984-998. Informal caregivers are a critical yet frequently unacknowledged part of the healthcare system. It is commonly presumed that providing assistive technology will decrease the burden of their care provision; however, no review has evaluated the evidence behind this assumption. Therefore, a systematic review was undertaken to evaluate evidence of the impact of assistive technology use by care recipients on their informal caregivers. Data sources included EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Web of Science, PsychINFO, PubMed, and active researchers in this area. Twenty-two studies met the specified inclusion criteria. Collectively, the findings suggest that assistive technology use helps caregivers by diminishing some of the physical and emotional effort entailed in supporting individuals with disability. However, confidence in this causal connection is limited because of the study designs that were used. This undermines the understanding of the impacts of assistive technology use on the users' informal caregivers. C1 [Ben Mortenson, W.] Simon Fraser Univ, Gerontol Res Ctr, Harbour Ctr 2800, Vancouver, BC V6B 5K3, Canada. [Ben Mortenson, W.; Demers, Louise] Inst Univ Geriatr Montreal, Ctr Rech, Montreal, PQ, Canada. [Fuhrer, Marcus J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Demers, Louise] Univ Montreal, Ecole Readaptat, Montreal, PQ, Canada. [Jutai, Jeffrey W.] Univ Ottawa, Interdisciplinary Sch Hlth Sci, Ottawa, ON, Canada. [Jutai, Jeffrey W.] Bruyere Res Inst, Ottawa, ON, Canada. [Lenker, James] SUNY Buffalo, Dept Rehabil Sci, Buffalo, NY 14260 USA. [DeRuyter, Frank] Duke Univ, Dept Surg, Div Speech Pathol & Audiol, Durham, NC USA. RP Ben Mortenson, W (reprint author), Simon Fraser Univ, Gerontol Res Ctr, Harbour Ctr 2800, 515 W Hastings St, Vancouver, BC V6B 5K3, Canada. RI Mortenson, William/L-7441-2013 OI Mortenson, William/0000-0002-0183-6163 FU National Institute on Disability and Rehabilitation Research [H133A060062]; Canadian Institutes of Health Research (CIHR) [232262] FX Supported by the National Institute on Disability and Rehabilitation Research (grant no. H133A060062) and the Canadian Institutes of Health Research (CIHR) (grant no. 232262). Personal financial support for Dr Mortenson was provided by a CIHR postdoctoral fellowship in the area of Aging and Mobility from the Institute of Aging. Presented at the American Congress of Rehabilitation Medicine-American Society of Neurorehabilitation Conference, October, Montreal, PQ (Mortenson WB, Demers L, Jutai J, Fuhrer MJ, Lenker J, DeRuyter F: Impacts of assistive technology interventions on informal caregivers of adults with chronic physical impairments: A systematic review. 2010) and at the 2011 Disability, Aging and Technology, Disability, Aging and Technology, June, Toronto, ON (Mortenson WB, Demers L, Jutai J, Fuhrer MJ, Lenker J, DeRuyter F: Impacts of assistive technology interventions on informal caregivers. 2011) (portions of the findings). NR 64 TC 0 Z9 0 U1 1 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD NOV PY 2012 VL 91 IS 11 BP 984 EP 998 DI 10.1097/PHM.0b013e318269eceb PG 15 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 027NR UT WOS:000310359900009 ER PT J AU Kiley, JP Senior, RM AF Kiley, James P. Senior, Robert M. TI Pulmonary research in 2013 and beyond: a National Heart, Lung, and Blood Institute perspective SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Editorial Material ID CARDIOVASCULAR HEALTH; VIRAL-INFECTION; INNATE IMMUNE; LYMPHANGIOLEIOMYOMATOSIS; ACTIVATION; MORTALITY; FIBROSIS; CELLS; GENE; DISEASE C1 [Kiley, James P.] NHLBI, Div Lung Dis, NIH, Rockledge Ctr 2, Bethesda, MD 20892 USA. [Senior, Robert M.] Washington Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, St Louis, MO 63110 USA. RP Kiley, JP (reprint author), NHLBI, Div Lung Dis, NIH, Rockledge Ctr 2, Suite 10042,6701 Rockledge Dr,MSC 7952, Bethesda, MD 20892 USA. EM kileyj@nhlbi.nih.gov NR 34 TC 1 Z9 1 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 2012 VL 303 IS 9 BP L729 EP L732 DI 10.1152/ajplung.00305.2012 PG 4 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 031MT UT WOS:000310646200001 PM 22962017 ER PT J AU Tripp, A Oh, H Guilloux, JP Martinowich, K Lewis, DA Sibille, E AF Tripp, Adam Oh, Hyunjung Guilloux, Jean-Philippe Martinowich, Keri Lewis, David A. Sibille, Etienne TI Brain-Derived Neurotrophic Factor Signaling and Subgenual Anterior Cingulate Cortex Dysfunction in Major Depressive Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DRIVEN BDNF TRANSCRIPTION; PREFRONTAL CORTEX; SUICIDE SUBJECTS; GENE-EXPRESSION; SCHIZOPHRENIA; BEHAVIOR; AMYGDALA; CIRCUITRY; FEATURES; STRESS AB Objective: The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known. Method: Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdrif(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results. Results: Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and COR7) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex. Conclusions: These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features. C1 [Sibille, Etienne] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. Univ Paris Sud, Fac Pharm, Chatenay Malabry, France. NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Lieber Inst Brain Dev, Baltimore, MD USA. RP Sibille, E (reprint author), Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. EM sibilleel@upmc.edu RI Lewis, David/G-4053-2014; Guilloux, Jean-Philippe/B-3726-2015; Martinowich, Keri/F-9841-2012; OI Lewis, David/0000-0002-3225-6778; Guilloux, Jean-Philippe/0000-0003-0982-3751; Martinowich, Keri/0000-0002-5237-0789 FU NIMH [MH-084060, MH-085111, M-H084053]; Bristol-Myers Squibb; Bristol-Myers Squibb Foundation; Curridium, Ltd.; Pfizer FX Supported by NIMH grants MH-084060 and MH-085111 to Dr. Sibille and grant M-H084053 to Dr. Lewis.; Dr. Lewis currently receives investigator-initiated research support from Bristol-Myers Squibb, the Bristol-Myers Squibb Foundation, Curridium, Ltd., and Pfizer; he has also previously served as a consultant to Bristol-Myers Squibb in the areas of target identification and validation and new compound development. The other authors report no financial relationships with commercial interest. NR 40 TC 46 Z9 48 U1 4 U2 18 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2012 VL 169 IS 11 BP 1194 EP 1202 DI 10.1176/appi.ajp.2012.12020248 PG 9 WC Psychiatry SC Psychiatry GA 031RA UT WOS:000310658400012 PM 23128924 ER PT J AU Kulik, LM Fisher, RA Rodrigo, DR Brown, RS Freise, CE Shaked, A Everhart, JE Everson, GT Hong, JC Hayashi, PH Berg, CL Lok, ASF AF Kulik, L. M. Fisher, R. A. Rodrigo, D. R. Brown, R. S., Jr. Freise, C. E. Shaked, A. Everhart, J. E. Everson, G. T. Hong, J. C. Hayashi, P. H. Berg, C. L. Lok, A. S. F. CA A2ALL Study Grp TI Outcomes of Living and Deceased Donor Liver Transplant Recipients With Hepatocellular Carcinoma: Results of the A2ALL Cohort SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE HCC; loco-regional therapy; MELD score; Milan criteria; recurrence; survival ID SURVIVAL; RECURRENCE; CRITERION; EXPANSION; PRIORITY; THERAPY AB Hepatocellular carcinoma (HCC) represents an increasing fraction of liver transplant indications; the role of living donor liver transplant (LDLT) remains unclear. In the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, patients with HCC and an LDLT or deceased donor liver transplant (DDLT) for which at least one potential living donor had been evaluated were compared for recurrence and posttransplant mortality rates. Mortality from date of evaluation of each recipient's first potential living donor was also analyzed. Unadjusted 5-year HCC recurrence was significantly higher after LDLT (38%) than DDLT (11%), (p = 0.0004). After adjustment for tumor characteristics, HCC recurrence remained significantly different between LDLT and DDLT recipients (hazard ratio (HR) = 2.35; p = 0.04) for the overall cohort but not for recipients transplanted following the introduction of MELD prioritization. Five-year posttransplant survival was similar in LDLT and DDLT recipients from time of transplant (HR = 1.32; p = 0.27) and from date of LDLT evaluation (HR = 0.73; p = 0.36). We conclude that the higher recurrence observed after LDLT is likely due to differences in tumor characteristics, pretransplant HCC management and waiting time. C1 [Fisher, R. A.] Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Surg, Richmond, VA 23284 USA. [Kulik, L. M.] Northwestern Univ, Dept Med & Surg, Chicago, IL 60611 USA. [Rodrigo, D. R.] Univ Michigan, Dept Surg, Ann Arbor, MI USA. [Brown, R. S., Jr.] Columbia Univ Coll Phys & Surg, Dept Med & Surg, New York, NY 10032 USA. [Freise, C. E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Shaked, A.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Everhart, J. E.] Univ Colorado, Dept Med, Denver, CO USA. [Everson, G. T.] NIDDKD, Bethesda, MD 20892 USA. [Hong, J. C.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Hayashi, P. H.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Berg, C. L.] Univ Virginia, Dept Med, Charlottesville, VA USA. [Lok, A. S. F.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Fisher, RA (reprint author), Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Surg, Richmond, VA 23284 USA. EM rafisher@vcu.edu OI Yang, Shuman/0000-0002-9638-0890 FU Bayer/Onyx; Speaking and Teaching: Bayer/Onyx; Bristol-Myers Squibb; GlaxoSmithKline; Schering-Plough; Roche; Gilead; Hep C Connection; Pharmassett; Vertex; GSK; Tibotec; Human Genome Sciences/Novartis; GlobeImmune; OrthoBiotech; Medtronic; Pfizer; Eisai; Abbott; Conatus; ZymoGenetics; PSC Partners FX Laura M. Kulik-Advisory Committees: Bayer/Onyx; Grant/Research Support: Bayer/Onyx; Speaking and Teaching: Bayer/Onyx.; Anna S. Lok-Consulting: Roche, Gilead, Bristol-Myers Squibb, Bayer; Grant/Research Support: Bristol-Myers Squibb, GlaxoSmithKline, Schering-Plough, Roche, Gilead.; Greg T. Everson-Advisory Committee or Review Panels: Roche, Merck, Three Rivers, Hep C Connection; Board membership: HepQuant LLC, PSC partners; Consulting: Genentech; Grant/Research Support: Roche, Pharmassett, Vertex, GSK, Schering-Plough, Bristol-Myers Squibb, Tibotec, Human Genome Sciences/Novartis, GlobeImmune, OrthoBiotech, Medtronic, Pfizer, Eisai, Abbott, Conatus, ZymoGenetics, PSC Partners; Management Position: HepQuant LLC; Patent Held/Filed: University of Colorado. NR 33 TC 38 Z9 39 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2012 VL 12 IS 11 BP 2997 EP 3007 DI 10.1111/j.1600-6143.2012.04272.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 029EW UT WOS:000310478600018 PM 22994906 ER PT J AU Charafeddine, AH Kim, EJ Maynard, DM Yi, H Weaver, TA Gunay-Aygun, M Russell, M Gahl, WA Kirk, AD AF Charafeddine, A. H. Kim, E. J. Maynard, D. M. Yi, H. Weaver, T. A. Gunay-Aygun, M. Russell, M. Gahl, W. A. Kirk, A. D. TI Platelet-Derived CD154: Ultrastructural Localization and Clinical Correlation in Organ Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Costimulation; platelets; trauma ID SOLUBLE CD40 LIGAND; RENAL-ALLOGRAFT REJECTION; ACUTE CORONARY SYNDROMES; ACTIVATED T-CELLS; ALPHA-GRANULES; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; SAMPLE TYPE; PLASMA; EXOCYTOSIS AB CD154 is an immunostimulatory ligand for CD40 that markedly influences alloimmunity. Its presence in platelets suggests that its release and subsequent immune effects are driven by trauma and thus could be relevant following organ transplantation. However, the release of platelet derived CD154 and its consequences have not been investigated in a clinical transplant setting. To better characterize the relationship between platelet activation and CD154 release, we investigated CD154 release by platelets obtained from normal individuals, and patients with two genetic defects that influence platelet granule development. Using these unique patient populations and immune-electron microscopy, we confirmed that CD154 was an alpha granule and not a cell surface protein, and thereafter optimized the methods for its in vivo measurement in humans. We then investigated plasma CD154 levels in kidney and liver transplant recipients and found no evidence that CD154 levels fluctuated systemically as a result of kidney or liver transplant procedures. Paradoxically, we found that kidney transplant patients had significantly lower systemic CD154 levels during episodes of rejection. These data suggest that the immune effects of CD154 are likely mediated through local and not systemic mechanisms, and discourage the use of CD154 as a peripheral biomarker in organ transplantation. C1 [Charafeddine, A. H.; Kim, E. J.; Yi, H.; Weaver, T. A.; Russell, M.; Kirk, A. D.] Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA. [Gunay-Aygun, M.] NIH, Intramural Off Rare Dis, Off Director, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA. EM adkirk@emory.edu FU Intramural Research Program of the National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; Georgia Research Alliance; McKelvey Foundation FX The authors gratefully acknowledge Marquita Kilgore, Sumeet Bahl, Shine Thomas, Ewa Turner and Sean Crawford for their expert technical assistance. This work was funded in part by the Intramural Research Program of the National Human Genome Research Institute and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. ADK is supported by the Georgia Research Alliance and by the McKelvey Foundation. NR 34 TC 8 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2012 VL 12 IS 11 BP 3143 EP 3151 DI 10.1111/j.1600-6143.2012.04241.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 029EW UT WOS:000310478600034 PM 22947105 ER PT J AU Duell, EJ Lucenteforte, E Olson, SH Bracci, PM Li, D Risch, HA Silverman, DT Ji, BT Gallinger, S Holly, EA Fontham, EH Maisonneuve, P Bueno-de-Mesquita, HB Ghadirian, P Kurtz, RC Ludwig, E Yu, H Lowenfels, AB Seminara, D Petersen, GM La Vecchia, C Boffetta, P AF Duell, E. J. Lucenteforte, E. Olson, S. H. Bracci, P. M. Li, D. Risch, H. A. Silverman, D. T. Ji, B. T. Gallinger, S. Holly, E. A. Fontham, E. H. Maisonneuve, P. Bueno-de-Mesquita, H. B. Ghadirian, P. Kurtz, R. C. Ludwig, E. Yu, H. Lowenfels, A. B. Seminara, D. Petersen, G. M. La Vecchia, C. Boffetta, P. TI Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4) SO ANNALS OF ONCOLOGY LA English DT Article DE case-control studies; pancreatitis; pancreatic cancer; pooled analysis; risk factors ID ABO BLOOD-GROUP; HEREDITARY PANCREATITIS; ALCOHOL-CONSUMPTION; CIGARETTE-SMOKING; HISTORY; TOBACCO; INFLAMMATION; MECHANISMS; ALLERGIES; ONSET AB Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction. A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10 947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4). The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of > 2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of < 2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (< 65 years) pancreatic cancer cases showed stronger associations with previous (> 2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (>= 65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006). Despite a moderately strong association between pancreatitis (diagnosed before > 2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented. C1 [Duell, E. J.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Canc Epidemiol Res Program, Barcelona 08907, Spain. [Lucenteforte, E.; La Vecchia, C.] Inst Pharmacol Res Mario Negri, Dept Epidemiol, Milan, Italy. [Lucenteforte, E.] Univ Florence, Dept Preclin & Clin Pharmacol Mario Aiazzi Mancin, Florence, Italy. [Olson, S. H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Bracci, P. M.; Holly, E. A.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. [Li, D.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Risch, H. A.; Yu, H.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, New Haven, CT 06510 USA. [Silverman, D. T.; Ji, B. T.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Gallinger, S.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Fontham, E. H.] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA. [Maisonneuve, P.] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy. [Bueno-de-Mesquita, H. B.] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Bueno-de-Mesquita, H. B.] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Ghadirian, P.] Univ Montreal Hosp Ctr CRCHUM, Res Ctr, Epidemiol Res Unit, Montreal, PQ, Canada. [Kurtz, R. C.; Ludwig, E.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Yu, H.] Univ Hawaii, Canc Res Ctr Hawaii, Canc Epidemiol Program, Honolulu, HI 96813 USA. [Lowenfels, A. B.] New York Med Coll, Dept Surg, Valhalla, NY 10595 USA. [Seminara, D.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Petersen, G. M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Petersen, G. M.] Mayo Clin, Coll Med, Dept Gastroenterol, Rochester, MN USA. [Petersen, G. M.] Mayo Clin, Coll Med, Dept Med Genet, Rochester, MN USA. [La Vecchia, C.] Univ Milan, Dept Occupat Hlth, Milan, Italy. [Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, P.] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA. RP Duell, EJ (reprint author), Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Canc Epidemiol Res Program, Avda Gran Via 199-203, Barcelona 08907, Spain. EM eduell@iconcologia.net RI Gallinger, Steven/E-4575-2013; OI Duell, Eric J/0000-0001-5256-0163; La Vecchia, Carlo/0000-0003-1441-897X; Lucenteforte, Ersilia/0000-0001-5608-5902; Maisonneuve, Patrick/0000-0002-5309-4704 FU National Cancer Institute (NCI); Prevention, Control and Population Research Goldstein Award; society of MSKCC; Geoffrey Beene Cancer Research Fund; National Institutes of Health [5R01CA098870, CA59706, CA108370, CA109767, CA89726, CA121846]; Stamford Hospital; National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics; Rombauer Pancreatic Cancer Research Fund; California Department of Public Health; National Cancer Institute's Surveillance, Epidemiology, and End Results Program [N01-PC-35136]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U55/CCR921930-02]; Italian Association for Cancer Research (AIRC) [10068]; Ministry of Health, Welfare, and Sports (formerly Ministry of Welfare, Health, and Culture) of the Netherlands; Commission of the European Communities; Fonds de recerche du Quebec - Sante (FRSQ); U.S. National Institutes of Health [CA98380]; CD Smithers Foundation; Spanish Ministry of Health [ISCIII RETICC RD06/0020] FX The PanC4 consortium gratefully acknowledges the National Cancer Institute (NCI) for partial support for its annual meetings.; The Pancreatic Cancer Family Registry at MSKCC was supported by the Prevention, Control and Population Research Goldstein Award; the society of MSKCC; and the Geoffrey Beene Cancer Research Fund. The Yale study was supported in part by National Institutes of Health grant 5R01CA098870; the cooperation of 30 Connecticut hospitals, including Stamford Hospital, in allowing patient access, is gratefully acknowledged. The Yale study was approved by the State of Connecticut Department of Public Health Human Investigation Committee. Certain data used in the Yale study were obtained from the Connecticut Tumor Registry in the Connecticut Department of Public Health. The NCI study was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The UCSF study was supported in part by National Institutes of Health grants (CA59706, CA108370, CA109767, CA89726, and CA121846) and by the Rombauer Pancreatic Cancer Research Fund. The collection of cancer incidence data for the UCSF study was supported by the California Department of Public Health as part of the statewide cancer reporting program; the National Cancer Institute's Surveillance, Epidemiology, and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The Milan study was supported by the Italian Association for Cancer Research (AIRC, Project no. 10068). The SEARCH study and the investigators were partially supported by The Ministry of Health, Welfare, and Sports (formerly Ministry of Welfare, Health, and Culture) of the Netherlands and the 'Europe against Cancer' program of the Commission of the European Communities; and Fonds de recerche du Quebec - Sante (FRSQ). The MD Anderson study was supported by the U.S. National Institutes of Health (CA98380). Financial support for ABL from the CD Smithers Foundation. EJD supported by the Spanish Ministry of Health (ISCIII RETICC RD06/0020). The authors assume sole responsibility for analyses and interpretation of these data. NR 30 TC 54 Z9 54 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2012 VL 23 IS 11 BP 2964 EP 2970 DI 10.1093/annonc/mds140 PG 7 WC Oncology SC Oncology GA 027SG UT WOS:000310373100031 PM 22767586 ER PT J AU Wang, JB Jiang, Y Liang, H Li, P Xiao, HJ Ji, J Xiang, W Shi, JF Fan, YG Li, L Wang, D Deng, SS Chen, WQ Wei, WQ Qiao, YL Boffetta, P AF Wang, J. B. Jiang, Y. Liang, H. Li, P. Xiao, H. J. Ji, J. Xiang, W. Shi, J. F. Fan, Y. G. Li, L. Wang, D. Deng, S. S. Chen, W. Q. Wei, W. Q. Qiao, Y. L. Boffetta, P. TI Attributable causes of cancer in China SO ANNALS OF ONCOLOGY LA English DT Article DE cancer; modifiable risk factors; population attributable fraction; China ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; EMERGING TOBACCO HAZARDS; RISK-FACTORS; ALCOHOL-DRINKING; REPRODUCTIVE FACTORS; BREAST-CANCER; LIFE-STYLE; MORTALITY; SMOKING; BURDEN AB Most cancers are due to modifiable lifestyle and environmental risk factors, and are potentially preventable. No studies have provided a systematic quantitative assessment of the burden of cancer mortality and incidence attributable to known risk factors in China. We calculated the proportions of cancer deaths and new cases attributable to known risk factors in China, based on the prevalence of exposure around 1990 and national data on cancer mortality and incidence for the year 2005. Chronic infection is the main risk factor for cancer in China, accounting for 29.4% of cancer deaths (31.7% in men and 25.3% in women), followed by tobacco smoking (22.6% with 32.7% in men and 5.0% in women), low fruit intake (13.0%), alcohol drinking (4.4%), low vegetable intake (3.6%) and occupational exposures (2.7%). The remaining factors, including environmental agents, physical inactivity, the use of exogenous hormones and reproductive factors are each responsible for < 1.0%. Modifiable risk factors explain nearly 60% of cancer deaths in China, with a predominant role of chronic infection and tobacco smoking. Our findings could provide a basis for cancer prevention and control programs aimed at reducing cancer risk in other developing countries. C1 [Wang, J. B.; Jiang, Y.; Liang, H.; Shi, J. F.; Wang, D.; Wei, W. Q.; Qiao, Y. L.] Chinese Acad Med Sci, Canc Inst Hosp, Dept Canc Epidemiol, Beijing 100021, Peoples R China. [Wang, J. B.; Jiang, Y.; Liang, H.; Shi, J. F.; Wang, D.; Chen, W. Q.; Wei, W. Q.; Qiao, Y. L.] Peking Union Med Coll, Beijing 100021, Peoples R China. [Wang, J. B.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Li, P.] Chongqing Med Univ, Sch Publ Hlth, Dept Occupat Hlth, Chongqing, Peoples R China. [Li, P.] Chongqing Med Univ, Sch Publ Hlth, Dept Environm Hlth, Chongqing, Peoples R China. [Xiao, H. J.; Deng, S. S.] Sichuan Univ, Sch Publ Hlth, Chengdu 610064, Peoples R China. [Ji, J.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Xiang, W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Shi, J. F.] NSW Canc Council, Canc Epidemiol Res Unit, Woolloomooloo, NSW, Australia. [Fan, Y. G.] Tianjin Med Univ, Gen Hosp, Tianjin Lung Canc Inst, Tianjin, Peoples R China. [Li, L.] Xinjiang Med Univ, Peoples Hosp Xinjiang Prov, Dept Gynecol, Urumqi, Peoples R China. [Chen, W. Q.] Chinese Acad Med Sci, Canc Inst Hosp, Natl Off Canc Prevent & Control, Beijing 100021, Peoples R China. [Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, P.] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA. [Boffetta, P.] Int Prevent Res Inst, Lyon, France. RP Qiao, YL (reprint author), Chinese Acad Med Sci, Canc Inst Hosp, Dept Canc Epidemiol, 17 S Pan Jia Yuan Lane, Beijing 100021, Peoples R China. EM qiaoy@cicams.ac.cn RI Qiao, You-Lin/B-4139-2012; Jiang, Yong/B-4103-2012 OI Qiao, You-Lin/0000-0001-6380-0871; Jiang, Yong/0000-0002-1892-1196 FU International Agency for Research on Cancer (Lyon, France) [GEE/08/19]; Cancer Institute, Chinese Academy of Medical Sciences (Beijing, China) [JK2011B19] FX International Agency for Research on Cancer (Lyon, France; Grant number: CRA No GEE/08/19) and Cancer Institute, Chinese Academy of Medical Sciences (Beijing, China; Grant number: JK2011B19). The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, decision to publish or preparation of the manuscript. NR 40 TC 22 Z9 23 U1 0 U2 14 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 NOV PY 2012 VL 23 IS 11 BP 2983 EP 2989 DI 10.1093/annonc/mds139 PG 7 WC Oncology SC Oncology GA 027SG UT WOS:000310373100034 PM 22689178 ER PT J AU Byzova, NA Zherdev, AV Eskendirova, SZ Baltin, KK Unysheva, GB Mukanov, KK Ramankulov, EM Dzantiev, BB AF Byzova, N. A. Zherdev, A. V. Eskendirova, S. Z. Baltin, K. K. Unysheva, G. B. Mukanov, K. K. Ramankulov, E. M. Dzantiev, B. B. TI Development of immunochromatographic test system for rapid detection of the lipopolysaccharide antigen and cells of the causative agent of bovine brucellosis SO APPLIED BIOCHEMISTRY AND MICROBIOLOGY LA English DT Article ID PROTEIN-G; MONOCLONAL-ANTIBODIES; SEROLOGICAL DIAGNOSIS; ASSAY; ABORTUS; CONJUGATE; MILK AB A rapid method for detection of the surface lipopolysaccharide antigen and the cells of the causative agent of bovine brucellosis was developed. The method represents a sandwich format immunochromatographic assay. The contact between the sample and the test strip with immobilized immunoreagents initiates the fluid movement along the membrane components of the test strip, immunochemical reactions, and the formation of colored bands. The novel method requires 10 minutes to determine the lipopolysaccharide antigen of the cell wall of the brucellosis causative agent at concentrations down to 10 ng/mL and the Brucella abortus cells at concentrations down to 10(6) cells/mL (5 x 10(4) cells in the sample). The specificity of the immunodetection was confirmed. The designed test system can be used for the rapid field diagnosis of brucellosis in cattle. C1 [Byzova, N. A.; Zherdev, A. V.; Dzantiev, B. B.] Russian Acad Sci, Bach Inst Biochem, Moscow 119071, Russia. [Eskendirova, S. Z.; Baltin, K. K.; Unysheva, G. B.; Mukanov, K. K.; Ramankulov, E. M.] Natl Ctr Biotechnol Republ Kazakhstan, Astana, Kazakhstan. RP Byzova, NA (reprint author), Russian Acad Sci, Bach Inst Biochem, Moscow 119071, Russia. EM nbyzova@inbi.ras.ru RI Ramanculov, Erlan/E-2823-2013; Zherdev, Anatoly/G-2916-2013; Dzantiev, Boris/C-6125-2014 OI Zherdev, Anatoly/0000-0003-3008-2839; NR 36 TC 0 Z9 0 U1 0 U2 12 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0003-6838 EI 1573-8183 J9 APPL BIOCHEM MICRO+ JI Appl. Biochem. Microbiol. PD NOV PY 2012 VL 48 IS 6 BP 590 EP 597 DI 10.1134/S0003683812060026 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 025ZN UT WOS:000310237200010 ER PT J AU Cheng, TJ Wang, YL Bryant, SH AF Cheng, Tiejun Wang, Yanli Bryant, Stephen H. TI FSelector: a Ruby gem for feature selection SO BIOINFORMATICS LA English DT Article ID BIOINFORMATICS AB The FSelector package contains a comprehensive list of feature selection algorithms for supporting bioinformatics and machine learning research. FSelector primarily collects and implements the filter type of feature selection techniques, which are computationally efficient for mining large datasets. In particular, FSelector allows ensemble feature selection that takes advantage of multiple feature selection algorithms to yield more robust results. FSelector also provides many useful auxiliary tools, including normalization, discretization and missing data imputation. C1 [Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Wang, YL (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov RI Cheng, Tiejun/A-5344-2010 OI Cheng, Tiejun/0000-0002-4486-3356 FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 8 TC 4 Z9 4 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2012 VL 28 IS 21 BP 2851 EP 2852 DI 10.1093/bioinformatics/bts528 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 025AR UT WOS:000310155300022 PM 22942017 ER PT J AU Kaur, JS Coe, K Rowland, J Braun, KL Conde, FA Burhansstipanov, L Heiney, S Kagawa-Singer, M Lu, Q Witte, C AF Kaur, Judith S. Coe, Kathryn Rowland, Julia Braun, Kathryn L. Conde, Francisco A. Burhansstipanov, Linda Heiney, Sue Kagawa-Singer, Marjorie Lu, Qian Witte, Catherine TI Enhancing life after cancer in diverse communities SO CANCER LA English DT Article DE community networks; cancer; quality of life; health disparities; palliative care; comprehensive cancer care; spirituality ID QUALITY-OF-LIFE; BREAST-CANCER; AFRICAN-AMERICANS; MENTAL-HEALTH; SURVIVORS; CARE; POPULATION; ETHNICITY; BELIEFS; PAIN AB BACKGROUND: Although large numbers of cancer survivors exist in every community, including minority communities, there is a significant gap in knowledge about best practices for these patients. METHODS: The Community Networks Program, funded by the National Cancer Institute Center to Reduce Cancer Health Disparities, has developed and tested unique services for these communities. These programs have used community-based participatory research techniques under a framework of diffusion of innovation and communications theory. RESULTS: This article describes some specifically tailored interventions that may be useful to a wide range of providers working with the underserved. CONCLUSIONS: Enhancing life after cancer can be achieved in underserved communities by supplementing local resources. Cancer 2012. (c) 2012 American Cancer Society. C1 [Kaur, Judith S.] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA. [Coe, Kathryn] Indiana Univ Purdue Univ, Dept Publ Hlth, Indianapolis, IN 46202 USA. [Rowland, Julia] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,US Dept HHS, Bethesda, MD 20892 USA. [Braun, Kathryn L.] Univ Hawaii, Honolulu, HI 96822 USA. [Conde, Francisco A.] Queens Med Ctr, Honolulu, HI USA. [Burhansstipanov, Linda] Native Amer Canc Res, Pine, CO USA. [Heiney, Sue] Univ S Carolina, Coll Nursing, Columbia, SC 29208 USA. [Kagawa-Singer, Marjorie] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Kagawa-Singer, Marjorie] Univ Calif Los Angeles, Dept Asian Amer Studies, Los Angeles, CA USA. [Lu, Qian] Univ Houston, Dept Psychol, Houston, TX USA. [Witte, Catherine] Phoenix Indian Med Ctr, Oncol Ctr Excellence, Phoenix, AZ USA. RP Kaur, JS (reprint author), Mayo Clin, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM kaur.judith@mayo.edu RI Coe, Mary Kasthryn/F-3636-2014 OI Coe, Mary Kasthryn/0000-0003-1284-3841 FU National Institutes of Health (NIH) [U01 CA114630]; NIH [U01 CA114609, U01 CA11469]; Susan G. Komen for the Cure [POP0202135, POP0503920]; NCI [R25 CA 101938, NCI U01 CA 114609] FX 'Imi Hale-Native Hawaiian Cancer Network is funded by National Institutes of Health (NIH) grant U01 CA114630. Mayo Clinic's Spirit of EAGLES Community Network Program is funded by NIH grant U01 CA114609. Southwest American Indian Collaborative Network is funded by NIH grant U01 CA11469. Native American Cancer Education for Survivors is supported by Susan G. Komen for the Cure (POP0202135 and POP0503920) and NCI (R25 CA 101938 and NCI U01 CA 114609). NR 50 TC 4 Z9 4 U1 4 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 1 PY 2012 VL 118 IS 21 BP 5366 EP 5373 DI 10.1002/cncr.27491 PG 8 WC Oncology SC Oncology GA 024BQ UT WOS:000310083000022 PM 22434384 ER PT J AU Glaros, TG Stockwin, LH Mullendore, ME Smith, B Morrison, BL Newton, DL AF Glaros, Trevor G. Stockwin, Luke H. Mullendore, Michael E. Smith, Brian Morrison, Bethanie L. Newton, Dianne L. TI The "survivin suppressants" NSC 80467 and YM155 induce a DNA damage response (vol 70, pg 207, 2012) SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Correction C1 [Glaros, Trevor G.; Stockwin, Luke H.; Mullendore, Michael E.; Smith, Brian; Morrison, Bethanie L.; Newton, Dianne L.] NCI, Biol Testing Branch, Dev Therapeut Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Newton, DL (reprint author), NCI, Biol Testing Branch, Dev Therapeut Program, SAIC Frederick Inc, Bldg 320,Room 9, Frederick, MD 21702 USA. EM newtondianne@mail.nih.gov NR 1 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2012 VL 70 IS 5 BP 763 EP 764 DI 10.1007/s00280-012-1971-2 PG 2 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 029ZO UT WOS:000310537600016 ER PT J AU Covo, S Ma, WJ Westmoreland, JW Gordenin, DA Resnick, MA AF Covo, Shay Ma, Wenjian Westmoreland, James W. Gordenin, Dmitry A. Resnick, Michael A. TI Understanding the origins of UV-induced recombination through manipulation of sister chromatid cohesion SO CELL CYCLE LA English DT Article DE UV; recombination; cohesin; double-strand breaks ID DOUBLE-STRAND BREAKS; MITOTIC GENE CONVERSION; DNA-DAMAGE RESPONSE; HOMOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; YEAST-CELLS; PYRIMIDINE DIMERS; ULTRAVIOLET-LIGHT; GAMMA-RAYS; X-RAYS AB Ultraviolet light (UV) can provoke genome instability, partly through its ability to induce homologous recombination (HR). However, the mechanism(s) of UV-induced recombination is poorly understood. Although double-strand breaks (DSBs) have been invoked, there is little evidence for their generation by UV. Alternatively, single-strand DNA lesions that stall replication forks could provoke recombination. Recent findings suggest efficient initiation of UV-induced recombination in G(1) through processing of closely spaced single-strand lesions to DSBs. However, other scenarios are possible, since the recombination initiated in G(1) can be completed in the following stages of the cell cycle. We developed a system that could address UV-induced recombination events that start and finish in G(2) by manipulating the activity of the sister chromatid cohesion complex. Here we show that sister-chromatid cohesion suppresses UV-induced recombination events that are initiated and resolved in G(2). By comparing recombination frequencies and survival between UV and ionizing radiation, we conclude that a substantial portion of UV-induced recombination occurs through DSBs. This notion is supported by a direct physical observation of UV-induced DSBs that are dependent on nucleotide excision repair. However, a significant role of nonDSB intermediates in UV-induced recombination cannot be excluded. C1 [Covo, Shay; Ma, Wenjian; Westmoreland, James W.; Gordenin, Dmitry A.; Resnick, Michael A.] NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Covo, S (reprint author), NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM covos@niehs.nih.gov OI Gordenin, Dmitry/0000-0002-8399-1836 FU NIEHS (NIH, DHHS) [1Z01ES065073] FX We thank Drs. Steve Roberts and Kin Chan for critically evaluating this manuscript. This work was supported by the Intramural Research Program of the NIEHS (NIH, DHHS) under project 1Z01ES065073 to M.A.R. NR 49 TC 3 Z9 3 U1 1 U2 31 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2012 VL 11 IS 21 BP 3937 EP 3944 DI 10.4161/cc.21945 PG 8 WC Cell Biology SC Cell Biology GA 030PV UT WOS:000310583500014 PM 22987150 ER PT J AU Konforte, D Diamandis, EP van Venrooij, WJ Lories, R Ward, MM AF Konforte, Danijela Diamandis, Eleftherios P. van Venrooij, Walther J. Lories, Rik Ward, Michael M. TI Autoimmune Diseases: Early Diagnosis and New Treatment Strategies SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Diamandis, Eleftherios P.] Mt Sinai Hosp, Joseph & Wolf Lebovic Ctr, Dept Pathol & Lab Med, Toronto, ON M5T 3L9, Canada. [Konforte, Danijela; Diamandis, Eleftherios P.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Diamandis, Eleftherios P.] Univ Hlth Network, Dept Clin Biochem, Toronto, ON, Canada. [van Venrooij, Walther J.] Radbound Univ, Nijmegen Ctr Mol Life Sci, Nijmegen, Netherlands. [Lories, Rik] Katholieke Univ Leuven, Dept Rheumatol, Louvain, Belgium. [Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Diamandis, EP (reprint author), Mt Sinai Hosp, Joseph & Wolf Lebovic Ctr, Dept Pathol & Lab Med, 60 Murray St,Box 32,Flr 6,Rm L6-201, Toronto, ON M5T 3L9, Canada. EM ediamandis@mtsinai.on.ca OI Diamandis, Eleftherios/0000-0002-1589-820X NR 0 TC 2 Z9 2 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2012 VL 58 IS 11 BP 1510 EP 1514 DI 10.1373/clinchem.2012.189480 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 029IS UT WOS:000310489300003 PM 22761474 ER PT J AU Ho, JE Mahajan, A Chen, MH Larson, MG McCabe, EL Ghorbani, A Cheng, S Johnson, AD Lindgren, CM Kempf, T Lind, L Ingelsson, E Vasan, RS Januzzi, J Wollert, KC Morris, AP Wang, TJ AF Ho, Jennifer E. Mahajan, Anubha Chen, Ming-Huei Larson, Martin G. McCabe, Elizabeth L. Ghorbani, Anahita Cheng, Susan Johnson, Andrew D. Lindgren, Cecilia M. Kempf, Tibor Lind, Lars Ingelsson, Erik Vasan, Ramachandran S. Januzzi, James Wollert, Kai C. Morris, Andrew P. Wang, Thomas J. TI Clinical and Genetic Correlates of Growth Differentiation Factor 15 in the Community SO CLINICAL CHEMISTRY LA English DT Article ID ACUTE CORONARY SYNDROME; MACROPHAGE INHIBITORY CYTOKINE-1; CHRONIC HEART-FAILURE; RISK STRATIFICATION; MYOCARDIAL-INFARCTION; DISEASE; PREDICTION; MARKER; ASSOCIATION; ACTIVATION AB BACKGROUND: Growth differentiation factor 15 (GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively. METHODS: Plasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of GDF15 were examined in multivariable analyses. We then conducted a genomewide association study of the GDF15 concentration that included participants in the Framingham Offspring Study and participants in the PIVUS (Prospective Investigation of the Vasctilature in Uppsala Seniors) study. RESULTS: GDF15 was positively associated with age, smoking, antihypertensive treatment, diabetes, worse kidney function, and use of nonsteroidal anti-inflammatory drugs (NSAIDs), but it was negatively associated with total cholesterol and HDL cholesterol. Clinical correlates accounted for 38% of interindividual variation in the circulating GDF15 concentration, whereas genetic factors accounted for up to 38% of the residual variability (h(2) = 0.38; P = 2.5 X 10(-11)). We identified 1 locus of genomewide significance. This locus, which is on chromosome 19p13.11 and includes the GDF15 gene, is associated with GDF15 concentration (smallest P = 2.74 X 10(-32) for rs888663). Conditional analyses revealed 2 independent association signals at this locus (rs888663 and rs1054564), which were associated with altered cis gene expression in blood cell lines. CONCLUSIONS: In ambulatory individuals, both cardio-metabolic risk factors and genetic factors play important roles in determining circulating GDF15 concentrations and contribute similarly to the overall variation. (C) 2012 American Association for Clinical Chemistry C1 [Ho, Jennifer E.; Ghorbani, Anahita; Januzzi, James; Wang, Thomas J.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Ho, Jennifer E.; Chen, Ming-Huei; Larson, Martin G.; Cheng, Susan; Johnson, Andrew D.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Ho, Jennifer E.; Johnson, Andrew D.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Mahajan, Anubha; Lindgren, Cecilia M.; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Chen, Ming-Huei; McCabe, Elizabeth L.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Dept Med, Boston, MA 02215 USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Kempf, Tibor; Wollert, Kai C.] Hannover Med Sch, Dept Cardiol & Angiol, D-3000 Hannover, Germany. [Lind, Lars] Uppsala Univ, Dept Med, Uppsala, Sweden. [Lind, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Vasan, Ramachandran S.] Boston Univ, Dept Med, Div Cardiol & Prevent Med, Boston, MA 02215 USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. RP Wang, TJ (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org RI Johnson, Andrew/G-6520-2013; OI Larson, Martin/0000-0002-9631-1254; Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970 FU E. Ingelsson; Swedish Research Council; Swedish Heart and Lung Foundation; Swedish Foundation for Strategic Research; Royal Swedish Academy of Sciences; Swedish Diabetes Foundation; Swedish Society of Medicine; Novo Nordisk Fonden; J. Januzzi, Roche; Siemens; BG Medicine; Thermo Fisher Scientific; K.C. Wollert; Roche Diagnostics; A.P. Morris, Wellcome Trust [WT081682, WT064890, WT090532] FX E. Ingelsson, Swedish Research Council, Swedish Heart and Lung Foundation, Swedish Foundation for Strategic Research, Royal Swedish Academy of Sciences, Swedish Diabetes Foundation, Swedish Society of Medicine, and Novo Nordisk Fonden; J. Januzzi, Roche, Siemens, BG Medicine, and Thermo Fisher Scientific; K.C. Wollert, GDF15 test kits from Roche Diagnostics; A.P. Morris, Wellcome Trust (WT081682, WT064890, and WT090532). NR 40 TC 19 Z9 21 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2012 VL 58 IS 11 BP 1582 EP 1591 DI 10.1373/clinchem.2012.190322 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 029IS UT WOS:000310489300014 PM 22997280 ER PT J AU Chen, WY Xu, Z Merke, DP McDonnell, NB AF Chen, Wuyan Xu, Zhi Merke, Deborah P. McDonnell, Nazli B. TI CH-8 Phenotype in Steroid 21-Hydroxylase Deficiency: Fact or Fancy? Reply SO CLINICAL CHEMISTRY LA English DT Letter ID RCCX MODULE; GENES C1 [McDonnell, Nazli B.] NIA, Clin Invest Lab, Biomed Res Ctr, Baltimore, MD 21224 USA. [Merke, Deborah P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Dev Endocrinol & Genet PDEGEN, Bethesda, MD USA. [McDonnell, Nazli B.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP McDonnell, NB (reprint author), NIA, Clin Invest Lab, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2012 VL 58 IS 11 BP 1601 EP 1603 DI 10.1373/clinchem.2012.194118 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 029IS UT WOS:000310489300019 ER PT J AU Deeken, JF Tjen-A-Looi, A Rudek, MA Okuliar, C Young, M Little, RF Dezube, BJ AF Deeken, John F. Tjen-A-Looi, Angelique Rudek, Michelle A. Okuliar, Catherine Young, Mary Little, Richard F. Dezube, Bruce J. TI The Rising Challenge of Non-AIDS-Defining Cancers in HIV-Infected Patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SQUAMOUS-CELL CARCINOMA; WOMENS INTERAGENCY HIV; HEPATITIS-C VIRUS; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; POSITIVE PATIENTS; HODGKIN-LYMPHOMA AB Since the advent of HAART, patients with HIV infection have seen a significant improvement in their morbidity, mortality, and life expectancy. The incidence of AIDS-defining illnesses, including AIDS-defining malignancies, has been on the decline. However, deaths due to non-AIDS-defining illnesses have been on the rise. These so-called non-AIDS-defining cancers (NADCs) include cancers of the lung, liver, kidney, anus, head and neck, and skin, as well as Hodgkin's lymphoma. It is poorly understood why this higher rate of NADCs is occurring. The key challenge facing oncologists is how to administer chemotherapy effectively and safely to patients on antiretroviral therapy. The challenge to clinicians caring for HIV-infected patients is to develop and implement effective means to screen, treat, and prevent NADCs in the future. This review presents data on the epidemiology and etiology of NADCs, as well as ongoing research into this evolving aspect of the HIV epidemic. C1 [Deeken, John F.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hematol Oncol, Washington, DC 20007 USA. [Tjen-A-Looi, Angelique; Young, Mary] Georgetown Univ, Med Ctr, Div Infect Dis, Washington, DC 20007 USA. [Okuliar, Catherine] Georgetown Univ, Med Ctr, Div Internal Med, Washington, DC 20007 USA. [Rudek, Michelle A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Little, Richard F.] NCI, Clin Invest Branch CTEP, Bethesda, MD 20892 USA. [Dezube, Bruce J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med Hematol Oncol, Boston, MA 02215 USA. RP Deeken, JF (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hematol Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM john.deeken@gunet.georgetown.edu FU National Cancer Institute [U01CA121947]; National Institute of Allergy and Infectious Disease [U01AI34994] FX This work was supported in part by grant number U01CA121947 from the National Cancer Institute to the AIDS Malignancy Clinical Trials Consortium (J. D., M. A. R.), as well as grant number U01AI34994 from the National Institute of Allergy and Infectious Disease to the Women's Interagency HIV Study (M. Y.). NR 88 TC 68 Z9 72 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2012 VL 55 IS 9 BP 1228 EP 1235 DI 10.1093/cid/cis613 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 021IF UT WOS:000309877800015 PM 22776851 ER PT J AU Kang, SY Hallett, M Sohn, YH AF Kang, Suk Y. Hallett, Mark Sohn, Young H. TI Synchronized finger exercise reduces surround inhibition SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Surround inhibition; Dystonia; Motor-evoked potentials; TMS ID FOCAL HAND DYSTONIA; HUMAN MOTOR CORTEX; PRIMARY SOMATOSENSORY CORTEX; INTRACORTICAL INHIBITION; ORGANIZATION; MUSCLE; CONNECTIONS; MODULATION; ACTIVATION; ATTENTION AB Objective: To investigate whether hand muscle repetitive use reduces surround inhibition (SI) as observed in patients with focal hand dystonia, we performed a transcranial magnetic stimulation (TMS) study in 15 healthy right-handed volunteers. Methods: TMS was set to be triggered by self-initiated flexion of the index finger at 3 ms after movement onset. Motor evoked potentials (MEPs) of the abductor digiti minimi (ADM) were measured before and at 0, 10, 20 and 30 min after 'single' (little finger abduction) and 'dual' (both index finger flexion and little finger abduction) exercise at 0.5 Hz for 30 min. SI was calculated as (mean control MEP - mean self-triggered MEP) x 100/mean control MEP. Results: Compared to single exercise, dual exercise produced significantly larger and longer-lasting enhancements of self-triggered MEPs, and greater reduction in calculated SIs. Conclusions: This result demonstrates that synchronized finger exercise can reduce SI between the involved muscles possibly due either to the strengthening of the excitatory connections or to the weakening of the inhibitory connections between them, and may illustrate the association between hand muscle repetitive use and disturbed SI observed in FHD. Significance: The operation of surround inhibition can be reduced by practicing synchronous movements. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Kang, Suk Y.; Sohn, Young H.] Yonsei Univ, Coll Med, Dept Neurol, Seoul 120752, South Korea. [Kang, Suk Y.; Sohn, Young H.] Yonsei Univ, Coll Med, Brain Res Inst, Seoul 120752, South Korea. [Kang, Suk Y.] Hallym Univ, Coll Med, Dept Neurol, Kangnam Sacred Heart Hosp, Seoul, South Korea. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Sohn, YH (reprint author), Yonsei Univ, Coll Med, Dept Neurol, 250 Seongsanno, Seoul 120752, South Korea. EM yhsohn62@yuhs.ac FU Brain Korea 21 Project for Medical Science, Yonsei University; NINDS Intramural Program FX This work was supported by the Brain Korea 21 Project for Medical Science, Yonsei University. Dr. Hallett is supported by the NINDS Intramural Program. The authors report no conflict of interest. NR 25 TC 10 Z9 10 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2012 VL 123 IS 11 BP 2227 EP 2231 DI 10.1016/j.clinph.2012.04.019 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 016VB UT WOS:000309546600017 PM 22608486 ER PT J AU Lancaster, CS Bruun, GH Peer, CJ Mikkelsen, TS Corydon, TJ Gibson, AA Hu, S Orwick, SJ Mathijssen, RHJ Figg, WD Baker, SD Sparreboom, A AF Lancaster, C. S. Bruun, G. H. Peer, C. J. Mikkelsen, T. S. Corydon, T. J. Gibson, A. A. Hu, S. Orwick, S. J. Mathijssen, R. H. J. Figg, W. D. Baker, S. D. Sparreboom, A. TI OATP1B1 Polymorphism as a Determinant of Erythromycin Disposition SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CYTOCHROME-P450 3A ACTIVITY; BREATH TEST; IN-VIVO; POPULATION PHARMACOKINETICS; WEEKLY DOCETAXEL; CYP3A4 ACTIVITY; CANCER-PATIENTS; METABOLISM; INHIBITION; VARIANTS AB Previous studies have demonstrated that the pharmacokinetic profile of erythromycin, a probe for CYP3A4 activity, is affected by inhibitors or inducers of hepatic solute carriers. We hypothesized that these interactions are mediated by OATP1B1 (gene symbol, SLCO1B1), a polypeptide expressed on the basolateral surface of hepatocytes. Using stably transfected Flp-In T-Rex293 cells, erythromycin was found to be a substrate for OATP1B1*1A (wild type) with a Michaelis-Menten constant of similar to 13 mu mol/l, and that its transport was reduced by similar to 50% in cells expressing OATP1B1*5 (V174A). Deficiency of the ortholog transporter Oatp1b2 in mice was associated with a 52% decrease in the metabolic rate of erythromycin (P = 0.000043). In line with these observations, in humans the c.521T > C variant in SLCO1B1 (rs4149056), encoding OATP1B1*5, was associated with a decline in erythromycin metabolism (P = 0.0072). These results suggest that impairment of OATP1B1 function can alter erythromycin metabolism, independent of changes in CYP3A4 activity. C1 [Lancaster, C. S.; Gibson, A. A.; Hu, S.; Orwick, S. J.; Baker, S. D.; Sparreboom, A.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Bruun, G. H.; Corydon, T. J.] Aarhus Univ, Dept Biomed, Aarhus, Denmark. [Peer, C. J.; Figg, W. D.] NCI, Clin Pharmacol Program, Off Clin Director, Bethesda, MD 20892 USA. [Mikkelsen, T. S.] Aarhus Univ Hosp, Dept Pediat Oncol & Hematol, DK-8000 Aarhus, Denmark. [Mathijssen, R. H. J.] Erasmus MC Daniel den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. RP Sparreboom, A (reprint author), St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 332 N Lauderdale St, Memphis, TN 38105 USA. EM alex.sparreboom@stjude.org RI Figg Sr, William/M-2411-2016; OI Corydon, Thomas Juhl/0000-0003-3588-6350 FU American Lebanese Syrian Associated Charities; National Cancer Institute grant [5R01CA151633-01]; ASCPT's 2012 David J. Goldstein Trainee Award; US Public Health Service Cancer Center Support [3P30CA021765] FX We thank Richard Kim and Jeffrey Stock for providing the Oatp1b2(-/-) mice and Lubin Lan and Erin Schuetz for their assistance with carrying out the erythromycin breath tests in mice. This work was supported in part by the American Lebanese Syrian Associated Charities, US Public Health Service Cancer Center Support grant 3P30CA021765 (to S.D.B.), and National Cancer Institute grant 5R01CA151633-01 (to A.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. This work was previously presented, in part, at the 113th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics (ASCPT), held 14-17 March 2012 in National Harbor, MD. C.S.L. was a recipient of ASCPT's 2012 David J. Goldstein Trainee Award in connection with this study. NR 43 TC 10 Z9 10 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2012 VL 92 IS 5 BP 642 EP 650 DI 10.1038/clpt.2012.106 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 027QF UT WOS:000310367400032 PM 22990751 ER PT J AU Sissung, TM Reece, KM Spencer, S Figg, WD AF Sissung, T. M. Reece, K. M. Spencer, S. Figg, W. D. TI Contribution of the OATP1B Subfamily to Cancer Biology and Treatment SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID TRANSPORT; TISSUES AB The organic anion transporter 1B (OATP1B) subfamily consists of OATP1B1 and OATP1B3.(1) These transporters have generally been considered liver-specific; however, recent evidence demonstrates that they are also expressed in extrahepatic tissues and in some tumors. This review discusses the potential influence of extrahepatic OATP1B expression on homeostasis and pathophysiology and its implications for pharmacotherapy in general. C1 [Sissung, T. M.; Spencer, S.; Figg, W. D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Reece, K. M.; Figg, W. D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 5 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2012 VL 92 IS 5 BP 658 EP 660 DI 10.1038/clpt.2012.127 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 027QF UT WOS:000310367400034 PM 23010650 ER PT J AU Lerner, I Bentin, S Shriki, O AF Lerner, Itamar Bentin, Shlomo Shriki, Oren TI Spreading Activation in an Attractor Network With Latching Dynamics: Automatic Semantic Priming Revisited SO COGNITIVE SCIENCE LA English DT Article DE Word recognition; Semantic priming; Neural networks; Distributed representations; Latching dynamics ID STIMULUS-ONSET ASYNCHRONY; PRIMED-LEXICAL DECISION; VISUAL WORD RECOGNITION; NEURAL-NETWORKS; MODEL; MEMORY; ASSOCIATION; BRAIN; ATTENTION; RETRIEVAL AB Localist models of spreading activation (SA) and models assuming distributed representations offer very different takes on semantic priming, a widely investigated paradigm in word recognition and semantic memory research. In this study, we implemented SA in an attractor neural network model with distributed representations and created a unified framework for the two approaches. Our models assume a synaptic depression mechanism leading to autonomous transitions between encoded memory patterns (latching dynamics), which account for the major characteristics of automatic semantic priming in humans. Using computer simulations, we demonstrated how findings that challenged attractor-based networks in the past, such as mediated and asymmetric priming, are a natural consequence of our present models dynamics. Puzzling results regarding backward priming were also given a straightforward explanation. In addition, the current model addresses some of the differences between semantic and associative relatedness and explains how these differences interact with stimulus onset asynchrony in priming experiments. C1 [Shriki, Oren] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. [Lerner, Itamar; Bentin, Shlomo] Hebrew Univ Jerusalem, Interdisciplinary Ctr Neural Computat, IL-91905 Jerusalem, Israel. [Bentin, Shlomo] Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. RP Shriki, O (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. EM oren70@gmail.com OI Shriki, Oren/0000-0003-1129-4799 FU Intramural NIH HHS [Z99 MH999999] NR 89 TC 8 Z9 8 U1 6 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-0213 J9 COGNITIVE SCI JI Cogn. Sci. PD NOV-DEC PY 2012 VL 36 IS 8 BP 1339 EP 1382 DI 10.1111/cogs.12007 PG 44 WC Psychology, Experimental SC Psychology GA 030XI UT WOS:000310603000001 PM 23094718 ER PT J AU Pia, L Neppi-Modona, M Cremasco, L Gindri, P Dal Monte, O Folegatti, A AF Pia, Lorenzo Neppi-Modona, Marco Cremasco, Luigi Gindri, Patrizia Dal Monte, Olga Folegatti, Alessia TI Functional independence between numerical and visual space: Evidence from right brain-damaged patients SO CORTEX LA English DT Article DE Visual line bisection; Mental number line; Unilateral neglect; Visual space; Numerical space ID MENTAL NUMBER LINE; SPATIAL REPRESENTATION; UNILATERAL NEGLECT; BISECTION; SEQUENCES AB What is the relationship between numerical and visual space? Here we tried to shed new light on this debated issue investigating whether and how the two forms of representation are associated or dissociated when co-activated. We carried out a series of visual-numerical bisection experiments on a large group of right brain-damaged patients (N = 32) with and without left neglect. We examined (a) the degree of association between the pathological rightward error in the bisection of numerical intervals and left neglect (Experiment 1); (b) if the size of the numerical interval modulates spatial errors in bisection tasks in which numerical and visual space representations are co-activated (Experiment 2). The results showed that (a) numerical bisection error and left spatial neglect are doubly dissociated and that, when both are present, they are not correlated; (b) the size of the numerical interval did not affect the spatial bisection error but influenced the numerical bisection error. These data suggest that attentional processes involved in the navigation along visual space and numerical internal representations are independent neurocognitive operations. We must emphasize that our findings should be taken with caution because they are based mainly on negative results. (C) 2012 Elsevier Srl. All rights reserved. C1 [Pia, Lorenzo; Neppi-Modona, Marco; Dal Monte, Olga; Folegatti, Alessia] Univ Turin, Dept Psychol, I-10123 Turin, Italy. [Pia, Lorenzo; Neppi-Modona, Marco] Univ Turin, NIT, I-10123 Turin, Italy. [Cremasco, Luigi] Fdn Don Carlo Gnocchi, Turin, Italy. [Cremasco, Luigi] Ctr Santa Maria Ai Colli, Turin, Italy. [Gindri, Patrizia] Sanit Garrison San Camillo, Turin, Italy. [Dal Monte, Olga] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Dal Monte, Olga] Uniformed Serv Univ Hlth Sci, Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Rockville, MD USA. RP Pia, L (reprint author), Univ Turin, Dept Psychol, Via Po 14, I-10123 Turin, Italy. EM lorenzo.pia@unito.it OI dal monte, olga/0000-0002-7823-4769; Pia, Lorenzo/0000-0002-0360-3152 FU PRIN grant FX These works was in part supported by a PRIN grant to Lorenzo Pia, Marco Neppi-Modona and Alessia Folegatti. NR 27 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD NOV-DEC PY 2012 VL 48 IS 10 BP 1351 EP 1358 DI 10.1016/j.cortex.2012.04.005 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 028IV UT WOS:000310416900009 PM 22608781 ER PT J AU Ryall, JG AF Ryall, James G. TI The role of sirtuins in the regulation of metabolic homeostasis in skeletal muscle SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Review DE hypertrophy; nicotinamide adenine dinucleotide; satellite cells; SirT1; NAD ID DEPENDENT GENE-EXPRESSION; ACTIVATED PROTEIN-KINASE; CALORIE RESTRICTION; TRANSCRIPTION FACTORS; SIRT1 ACTIVATION; HISTONE H3; LIFE-SPAN; ACETYLATION; DEACETYLASE; INTERACTS AB Purpose of review To discuss recent findings regarding the role of the histone deacetylase sirtuin SirT1 in anabolic and catabolic signaling pathways in skeletal muscle. Recent findings Since its discovery as a regulator of peroxisome proliferator-activated receptor g-coactivator 1 alpha transcriptional activity, SirT1 has received much attention for its role in the regulation of tissue-specific and whole body regulation of metabolic processes. Although these early seminal discoveries identified SirT1 as a central player in metabolism, it is only more recently that we have begun to understand the complexities of SirT1 signaling. In addition to peroxisome proliferator-activated receptorgamma-coactivator 1 alpha, SirT1 has been found to regulate the activity and/or transcription of protein kinase B, mammalian target of rapamycin, forkhead box O 1 and 3a and myogenic determination factor, all of which are central players in the regulation of energy status in skeletal muscle, via actions on catabolic and anabolic signaling. Summary SirT1-mediated regulation of skeletal muscle metabolism (and indeed, whole body metabolism) likely occurs at numerous levels, from cell membrane receptors to transcription factors and histones. The end result of these regulatory actions of SirT1 is to maintain cellular homeostasis. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Ryall, JG (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM jgryall@gmail.com OI Ryall, James/0000-0003-4702-1143 FU Overseas Biomedical Research Fellowship from the National Health and Medical Research Council of Australia (NHMRC); Intramural Research Program of the National Institute of Arthritis, and Musculoskeletal, and Skin diseases (NIAMS) at the National Institutes of Health FX J.G.R. is supported by an Overseas Biomedical Research Fellowship from the National Health and Medical Research Council of Australia (NH&MRC) and the Intramural Research Program of the National Institute of Arthritis, and Musculoskeletal, and Skin diseases (NIAMS) at the National Institutes of Health. NR 47 TC 9 Z9 9 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD NOV PY 2012 VL 15 IS 6 BP 561 EP 566 DI 10.1097/MCO.0b013e3283590914 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 027OI UT WOS:000310362000007 PM 23075935 ER PT J AU Mahnke, YD Beddall, MH Roederer, M AF Mahnke, Yolanda D. Beddall, Margaret H. Roederer, Mario TI OMIP-013: Differentiation of human T-cells SO CYTOMETRY PART A LA English DT Article ID EXPRESSION C1 [Mahnke, Yolanda D.; Beddall, Margaret H.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mahnke, YD (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5608, Bethesda, MD 20892 USA. EM mahnkey@mail.nih.gov NR 8 TC 5 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD NOV PY 2012 VL 81A IS 11 BP 935 EP 936 DI 10.1002/cyto.a.22201 PG 2 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 027WV UT WOS:000310385700003 PM 23027685 ER PT J AU Jeong, J Cesario, J Zhao, YG Burns, L Westphal, H Rubenstein, JLR AF Jeong, Juhee Cesario, Jeffry Zhao, Yangu Burns, Lorel Westphal, Heiner Rubenstein, John L. R. TI Cleft palate defect of Dlx1/2-/- mutant mice is caused by lack of vertical outgrowth in the posterior palate SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Dlx; cleft palate; palatogenesis; craniofacial development; mice ID CRANIAL NEURAL CREST; SECONDARY PALATE; HOMEOBOX GENES; MOUSE EMBRYOS; DOWN-SYNDROME; DLX GENES; EXPRESSION; MORPHOGENESIS; FOREBRAIN; GROWTH AB Background: Mice lacking the activities of Dlx1 and Dlx2 (Dlx1/2-/-) exhibit cleft palate, one of the most common human congenital defects, but the etiology behind this phenotype has been unknown. Therefore, we analyzed the morphological, cellular, and molecular changes caused by inactivation of Dlx1 and Dlx2 as related to palate development. Results: Dlx1/2-/- mutants exhibited lack of vertical growth in the posterior palate during the earliest stage of palatogenesis. We attributed this growth deficiency to reduced cell proliferation. Expression of a cell cycle regulator Ccnd1 was specifically down-regulated in the same region. Previous studies established that the epithelial-mesenchymal signaling loop involving Shh, Bmp4, and Fgf10 is important for cell proliferation and tissue growth during palate development. This signaling loop was disrupted in Dlx1/2-/- palate. Interestingly, however, the decreases in Ccnd1 expression and mitosis in Dlx1/2-/- mutants were independent of this signaling loop. Finally, Dlx1/2 activity was required for normal expression of several transcription factor genes whose mutation results in palate defects. Conclusions: The functions of Dlx1 and Dlx2 are crucial for the initial formation of the posterior palatal shelves, and that the Dlx genes lie upstream of multiple signaling molecules and transcription factors important for later stages of palatogenesis. Developmental Dynamics 241:17571769, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Jeong, Juhee; Cesario, Jeffry; Burns, Lorel] NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY 10010 USA. [Zhao, Yangu; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, Program Genom Differentiat, Bethesda, MD USA. [Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94158 USA. RP Jeong, J (reprint author), NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, 345 E 24 th St,Room 902D, New York, NY 10010 USA. EM jj78@nyu.edu; john.rubenstein@ucsf.edu FU NIH/NIDCD [R01 DC05667]; March of Dimes; NIH/NIDCR [K99/R00 DE019486]; NIH/NICHD intramural research program; Weston Havens Foundation; Hillblom Foundation; Nina Ireland; NIH [NIDCD R01 DC05667, NIDCR K99/R00 DE019486]; NICHD intramural research program FX Grant sponsor: NIH/NIDCD; Grant number: R01 DC05667; Grant sponsor: March of Dimes; Grant sponsor: NIH/NIDCR; Grant number: K99/R00 DE019486; Grant sponsor: NIH/NICHD intramural research program; Grant sponsor: Weston Havens Foundation; Grant sponsor: Hillblom Foundation; Grant sponsor: Nina Ireland.; We thank Regeneron for Lhx6 mutant mice (MAID #406); Purvi Patel for genotyping mice and embryos; Hideyo Ohuchi, Joy Yang, and Jun Aruga for in situ hybridization probes; Jason Long, Jeremy Cholfin, Inma Cobos, Greg Potter, and Andrea Faedo for sharing reagents and ideas; and Gail Martin, Ophir Klein, Ross Metzger, Maria Barna, and the members of Rubenstein lab and Martin lab for helpful discussions. This work was funded by grants from NIH (NIDCD R01 DC05667), March of Dimes, Weston Havens Foundation, Hillblom Foundation and Nina Ireland to J.L.R.R., a grant from NIH (NIDCR K99/R00 DE019486) to J.J., and by funds from the NICHD intramural research program to H.W. NR 59 TC 7 Z9 8 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2012 VL 241 IS 11 BP 1757 EP 1769 DI 10.1002/dvdy.23867 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 026NF UT WOS:000310285300010 PM 22972697 ER PT J AU Ren, RQ Oakley, RH Cruz-Topete, D Cidlowski, JA AF Ren, Rongqin Oakley, Robert H. Cruz-Topete, Diana Cidlowski, John A. TI Dual Role for Glucocorticoids in Cardiomyocyte Hypertrophy and Apoptosis SO ENDOCRINOLOGY LA English DT Article ID HUMAN MINERALOCORTICOID RECEPTOR; INDUCED MYOCARDIAL APOPTOSIS; CONGESTIVE-HEART-FAILURE; RAT VENTRICULAR MYOCYTES; NECROSIS-FACTOR-ALPHA; CARDIAC CELL-DEATH; GENE-EXPRESSION; CARDIOVASCULAR-DISEASE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; NUCLEAR RECEPTORS AB Glucocorticoids and their synthetic derivatives are known to alter cardiac function in vivo; however, the nature of these effects and whether glucocorticoids act directly on cardiomyocytes are poorly understood. To explore the role of glucocorticoid signaling in the heart, we used rat embryonic H9C2 cardiomyocytes and primary cardiomyocytes as model systems. Dexamethasone (100 nM) treatment of cardiomyocytes caused a significant increase in cell size and up-regulated the expression of cardiac hypertrophic markers, including atrial natriuretic factor, beta-myosin heavy chain, and skeletal muscle alpha-actin. In contrast, serum deprivation and TNF alpha exposure triggered cardiomyocyte apoptosis, and these apoptotic effects were inhibited by dexamethasone. Both the hypertrophic and anti-apoptotic actions of glucocorticoids were abolished by the glucocorticoid receptor (GR) antagonist RU486 and by short hairpin RNA-mediated GR depletion. Blocking the activity of the mineralocorticoid receptor had no effect on these glucocorticoid-dependent cardiomyocyte responses. Aldosterone (1 mu M) activation of GR also promoted cardiomyocyte hypertrophy and cell survival. To elucidate the mechanism of the dual glucocorticoid actions, a genome-wide microarray was performed on H9C2 cardiomyocytes treated with vehicle or dexamethasone in the absence or presence of serum. Serum dramatically influenced the transcriptome regulated by GR, revealing potential glucocorticoid signaling mediators in both cardiomyocyte hypertrophy and apoptosis. These studies reveal a direct and dynamic role for glucocorticoids and GR signaling in the modulation of cardiomyocyte function. (Endocrinology 153:5346-5360, 2012) C1 [Ren, Rongqin; Oakley, Robert H.; Cruz-Topete, Diana; Cidlowski, John A.] NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, POB 12233,MD F3-07, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU National Institutes of Health, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 79 TC 33 Z9 35 U1 0 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2012 VL 153 IS 11 BP 5346 EP 5360 DI 10.1210/en.2012-1563 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 027NL UT WOS:000310359300023 PM 22989630 ER PT J AU Galperin, MY Mekhedov, SL Puigbo, P Smirnov, S Wolf, YI Rigden, DJ AF Galperin, Michael Y. Mekhedov, Sergei L. Puigbo, Pere Smirnov, Sergey Wolf, Yuri I. Rigden, Daniel J. TI Genomic determinants of sporulation in Bacilli and Clostridia: towards the minimal set of sporulation-specific genes SO ENVIRONMENTAL MICROBIOLOGY LA English DT Review ID SUBTILIS SPORE COAT; SEGMENTED FILAMENTOUS BACTERIA; RESPONSE REGULATOR SPO0A; SP-NOV.; ANAEROBIC BACTERIUM; ENDOSPORE FORMATION; COG DATABASE; TRANSCRIPTIONAL PROGRAM; LIFE-CYCLE; FAM. NOV AB Three classes of low-G+C Gram-positive bacteria (Firmicutes), Bacilli, Clostridia and Negativicutes, include numerous members that are capable of producing heat-resistant endospores. Spore-forming firmicutes include many environmentally important organisms, such as insect pathogens and cellulose-degrading industrial strains, as well as human pathogens responsible for such diseases as anthrax, botulism, gas gangrene and tetanus. In the best-studied model organism Bacillus subtilis, sporulation involves over 500 genes, many of which are conserved among other bacilli and clostridia. This work aimed to define the genomic requirements for sporulation through an analysis of the presence of sporulation genes in various firmicutes, including those with smaller genomes than B. subtilis. Cultivable spore-formers were found to have genomes larger than 2300 kb and encompass over 2150 protein-coding genes of which 60 are orthologues of genes that are apparently essential for sporulation in B. subtilis. Clostridial spore-formers lack, among others, spoIIB, sda, spoVID and safA genes and have non-orthologous displacements of spoIIQ and spoIVFA, suggesting substantial differences between bacilli and clostridia in the engulfment and spore coat formation steps. Many B. subtilis sporulation genes, particularly those encoding small acid-soluble spore proteins and spore coat proteins, were found only in the family Bacillaceae, or even in a subset of Bacillus spp. Phylogenetic profiles of sporulation genes, compiled in this work, confirm the presence of a common sporulation gene core, but also illuminate the diversity of the sporulation processes within various lineages. These profiles should help further experimental studies of uncharacterized widespread sporulation genes, which would ultimately allow delineation of the minimal set(s) of sporulation-specific genes in Bacilli and Clostridia. C1 [Galperin, Michael Y.; Mekhedov, Sergei L.; Puigbo, Pere; Smirnov, Sergey; Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Rigden, Daniel J.] Univ Liverpool, Inst Integrat Biol, Liverpool L69 7ZB, Merseyside, England. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Rigden, Daniel/0000-0002-7565-8937 FU National Institutes of Health at the National Library of Medicine FX We are grateful to Eugene Koonin for guidance throughout this project, Boris Belitsky (Tufts University), Tatiana Gaidenko (UC Davis) and Vladimir Levdikov (University of York) for critical comments and to Natalya Yutin for providing the ribosomal protein tree used in Fig. S2. This work was supported by the Intramural Research Program of the National Institutes of Health at the National Library of Medicine. NR 146 TC 71 Z9 71 U1 3 U2 71 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD NOV PY 2012 VL 14 IS 11 BP 2870 EP 2890 DI 10.1111/j.1462-2920.2012.02841.x PG 21 WC Microbiology SC Microbiology GA 029DR UT WOS:000310475500002 PM 22882546 ER PT J AU Loverdo, C Park, M Schreiber, SJ Lloyd-Smith, JO AF Loverdo, Claude Park, Miran Schreiber, Sebastian J. Lloyd-Smith, James O. TI INFLUENCE OF VIRAL REPLICATION MECHANISMS ON WITHIN-HOST EVOLUTIONARY DYNAMICS SO EVOLUTION LA English DT Article DE Models; simulations; mutations; reproductive strategies ID RNA-POLYMERASE-II; RETROVIRAL MUTATION-RATES; IN-VIVO; REVERSE-TRANSCRIPTASE; POPULATION-GENETICS; LETHAL MUTAGENESIS; RHESUS MACAQUES; MOSAIC-VIRUS; BURST SIZE; EMERGENCE AB Viruses replicate their genomes using a variety of mechanisms, leading to different distributions of mutations among their progeny. Yet, models of viral evolution often only consider the mean mutation rate. To investigate when and how replication mechanisms impact viral evolution, we analyze the early dynamics of within-host infection for two idealized cases: when all offspring virions from an infected cell carry the same genotype, mutated or not; and when mutations occur independently across offspring virions. Other replication life histories fall between these extremes. Using branching process models, we study the probability that viral infection becomes established when mutations are lethal, and in the more general case of two strains of different fitness. For a given mean mutation rate, we show that a lineage of viruses with correlated mutations is less likely to survive than with independent mutations, but when it survives, the viral population grows faster. While this holds true for all parameter regimes, replication life history has a quantitatively significant influence on viral dynamics when stochastic effects are important and when mutations are crucial for survival-conditions typical of evolutionary escape situations. C1 [Loverdo, Claude; Park, Miran; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [Schreiber, Sebastian J.] Univ Calif Davis, Dept Evolut & Ecol, Davis, CA 95616 USA. [Schreiber, Sebastian J.] Univ Calif Davis, Ctr Populat Biol, Davis, CA 95616 USA. [Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Loverdo, C (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. EM loverdo@ucla.edu RI Lloyd-Smith, James/K-4080-2012; OI Lloyd-Smith, James/0000-0001-7941-502X; Loverdo, Claude/0000-0002-0888-1717 FU National Science Foundation [EF-0928690, EF-0928987]; De Logi Chair in Biological Sciences; RAPIDD program of the Science & Technology Directorate; Department of Homeland Security; Fogarty International Center, National Institutes of Health FX The authors thank S. Blumberg, C. Strelioff, and R. Ke for providing useful comments on earlier drafts of this manuscript. All authors are supported by the National Science Foundation grants EF-0928690 and EF-0928987. JLS is grateful for the support of the De Logi Chair in Biological Sciences, and the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. NR 56 TC 8 Z9 8 U1 1 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-3820 J9 EVOLUTION JI Evolution PD NOV PY 2012 VL 66 IS 11 BP 3462 EP 3471 DI 10.1111/j.1558-5646.2012.01687.x PG 10 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 029EM UT WOS:000310477600012 PM 23106710 ER PT J AU Pepper, JW AF Pepper, John W. TI Drugs that target pathogen public goods are robust against evolved drug resistance SO EVOLUTIONARY APPLICATIONS LA English DT Article DE biomedicine; cancer medicine; contemporary evolution; disease biology; evolutionary medicine; evolutionary theory; experimental evolution; microbial biology; natural selection ID DIGITAL EVOLUTION; GROUP SELECTION; MECHANISMS; COVARIANCE AB Pathogen drug resistance is a central problem in medicine and public health. It arises through somatic evolution, by mutation and selection among pathogen cells within a host. Here, we examine the hypothesis that evolution of drug resistance could be reduced by developing drugs that target the secreted metabolites produced by pathogen cells instead of directly targeting the cells themselves. Using an agent-based computational model of an evolving population of pathogen cells, we test this hypothesis and find support for it. We also use our model to explain this effect within the framework of standard evolutionary theory. We find that in our model, the drugs most robust against evolved drug resistance are those that target the most widely shared external products, or public goods, of pathogen cells. We also show that these drugs exert a weak selective pressure for resistance because they create only a weak correlation between drug resistance and cell fitness. The same principles apply to design of vaccines that are robust against vaccine escape. Because our theoretical results have crucial practical implications, they should be tested by empirical experiments. C1 [Pepper, John W.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Pepper, John W.] Santa Fe Inst, Santa Fe, NM 87501 USA. RP Pepper, JW (reprint author), NCI, Canc Prevent Div, 6130 Execut Blvd,MSC 7315, Bethesda, MD 20892 USA. EM pepperjw@mail.nih.gov RI Pepper, John/O-1662-2013 OI Pepper, John/0000-0001-9888-0437 FU NSF DDIG [1010669] FX My doctoral student William W. Driscoll chose not to be listed as co-author on this paper, but was fully qualified to be. He wrote most of the software, carried out simulation experiments, collected results, and contributed substantially to writing. He was supported by NSF DDIG #1010669. NR 18 TC 18 Z9 22 U1 2 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-4571 J9 EVOL APPL JI Evol. Appl. PD NOV PY 2012 VL 5 IS 7 BP 757 EP 761 DI 10.1111/j.1752-4571.2012.00254.x PG 5 WC Evolutionary Biology SC Evolutionary Biology GA 030BW UT WOS:000310543800009 PM 23144661 ER PT J AU Beall, S DeCherney, AH AF Beall, Stephanie DeCherney, Alan H. TI Management of tubal ectopic pregnancy: methotrexate and salpingostomy are preferred to preserve fertility SO FERTILITY AND STERILITY LA English DT Editorial Material ID SYSTEMIC METHOTREXATE; EXPECTANT MANAGEMENT C1 [Beall, Stephanie; DeCherney, Alan H.] NIH, Bethesda, MD 20892 USA. RP Beall, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2012 VL 98 IS 5 BP 1118 EP 1120 DI 10.1016/j.fertnstert.2012.07.1115 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 028TW UT WOS:000310447300014 PM 22884016 ER PT J AU Ferrell, RJ Rodriguez, G Holman, D O'Connor, K Wood, JW Weinstein, M AF Ferrell, Rebecca J. Rodriguez, German Holman, Darryl O'Connor, Kathleen Wood, James W. Weinstein, Maxine TI Hypoestrogenic "inactive phases'' at the start of the menstrual cycle: changes with age and reproductive stage, and relationship to follicular depletion SO FERTILITY AND STERILITY LA English DT Article DE Follicular depletion; hypoestrogenic; inactive phase; female reproductive aging; perimenopause ID MENOPAUSAL TRANSITION; OVARIAN-FOLLICLES; WOMEN; OVULATION; PATTERNS; PERIMENOPAUSE; VARIABILITY; ESTRADIOL; FREEDOM; LENGTH AB Objective: To investigate hypoestrogenic "inactive phases'' (IP) in the follicular phase of the menstrual cycle, with respect to age, reproductive stage, and follicular depletion. Design: Analysis of prospectively collected menstrual bleed and estrone-3-glucuronide data. Setting: Center for Population and Health, Georgetown University. Patient(s): White women (n = 88, aged 25-59 years, mean = 44.7 years) from the population-based Biodemographic Models of Reproductive Aging (BIMORA) project. Intervention(s): None. Main Outcome Measure(s): The IP durations by age and reproductive stage. Estimated follicular depletion rate based on IP durations. Result(s): Mean IP duration and variability decreased and then increased with age/reproductive stage. The proportion of very short (<= 1 day) IP durations increased and then decreased with age/stage. Long IPs occurred most, but not exclusively, in the oldest age/latest stage. Follicular depletion rate estimates were a plausible 2%-4% per year of age, but these models were a poor fit because IP durations did not consistently increase across ages/stages. Conclusion(s): Follicular depletion models alone do not explain the observed pattern of IPs. Our data suggest that IPs reflect both follicular depletion and hyperstimulation in premenopausal and perimenopausal women. Knowledge of underlying IP patterns in the menstrual cycle could inform decisions about hormone sampling and contraception during the perimenopause. (Fertil Steril (R) 2012;98:1246-53. (C)2012 by American Society for Reproductive Medicine.) C1 [Ferrell, Rebecca J.] NIA, NIH, Bethesda, MD 20892 USA. [Rodriguez, German] Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA. [Holman, Darryl; O'Connor, Kathleen] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [Holman, Darryl; O'Connor, Kathleen] Univ Washington, Ctr Studies Demog & Ecol, Seattle, WA 98195 USA. [Wood, James W.] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. [Wood, James W.] Penn State Univ, Populat Res Inst, University Pk, PA 16802 USA. [Weinstein, Maxine] Georgetown Univ, Ctr Populat & Hlth, Washington, DC USA. RP Ferrell, RJ (reprint author), NIA, NIH, 7201 Wisconsin Ave,Room 2C212, Bethesda, MD 20892 USA. EM rebecca.ferrell@nih.gov FU [NIH R01AG015141]; [NIH R01HD034159]; [NIH F32HD007994]; [NIH R24HD042828] FX Supported by grants NIH R01AG015141, NIH R01HD034159, NIH F32HD007994, and NIH R24HD042828. NR 43 TC 2 Z9 2 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2012 VL 98 IS 5 BP 1246 EP + DI 10.1016/j.fertnstert.2012.07.1101 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 028TW UT WOS:000310447300035 PM 22901850 ER PT J AU Britten, JL Malik, M Levy, G Mendoza, M Catherino, WH AF Britten, Joy Lynne Malik, Minnie Levy, Gary Mendoza, Mirian Catherino, William H. TI Gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate and GnRH antagonist cetrorelix acetate directly inhibit leiomyoma extracellular matrix production SO FERTILITY AND STERILITY LA English DT Article DE Leiomyoma; leuprolide acetate; cetrorelix acetate; collagen 1A1; versican; fibronectin ID MESSENGER-RIBONUCLEIC-ACID; UTERINE LEIOMYOMAS; DOUBLE-BLIND; HUMAN MYOMETRIUM; GENE-EXPRESSION; IN-VITRO; FIBROIDS; GROWTH; CELLS; VERSICAN AB Objective: To determine the direct effect that GnRH analogues leuprolide acetate and cetrorelix acetate have on extracellular matrix in human leiomyoma and patient-matched myometrial cells. Design: Laboratory study. Setting: University hospital. Patient(s): None. Intervention(s): Cell culture, proliferation studies, and messenger RNA and protein analysis. Main Outcome Measure(s): Expression of GnRHR1, COL1A1, fibronectin, and versican variant V0 in treated leiomyoma cells and patient-matched myometrial cells. Result(s): Leiomyoma cells were treated with GnRH analogues for 6, 24, and 120 hours. Leuprolide treatment for 6 hours resulted in an increase in expression of GnRHR1 (4.02 +/- 0.12-fold), COL1A1 (6.41 +/- 0.29-fold), fibronectin (9.69 +/- 0.18-fold), and versican variant V0 (7.58 +/- 0.43-fold). Leiomyoma cells treated with cetrorelix for 6 hours showed a decreased expression of GnRHR1 (0.5 +/- 0.15-fold), COL1A1 (3.79 +/- 0.7-fold), fibronectin (0.92 +/- 0.09-fold), and versican variant V0 (0.14 +/- 0.07-fold). Leuprolide treatment of leiomyoma cells at high concentrations (10(-5) M) did not result in an increase in protein production. Cetrorelix treatment of leiomyoma cells for 6 hours showed an increase in fibronectin protein production (3.14 +/- 0.09-fold). Protein production of leiomyoma cells treated with cetrorelix for 120 hours demonstrated a decrease in GnRHR1 (0.51 +/- 0.07-fold), COL1A1 (0.35 +/- 0.07-fold), fibronectin (1.94 +/- 0.08-fold), and versican variant V0 (0.77 +/- 0.19-fold). Conclusion(s): Our findings demonstrate that GnRH analogue treatment directly regulated COL1A1, fibronectin, and matrix proteoglycan production. The reduction in versican variant V0 gene expression caused by cetrorelix treatment, and its association with the osmotic regulation of leiomyomas, presents a new and innovative approach to therapy for this disease. (Fertil Steril (R) 2012; 98: 1299-307. (C)2012 by American Society for Reproductive Medicine.) C1 [Britten, Joy Lynne; Malik, Minnie; Levy, Gary; Mendoza, Mirian; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Levy, Gary; Catherino, William H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM william.catherino@usuhs.edu OI Malik, Minnie/0000-0003-1129-6575 FU EMD Serono Pharmaceutical; Ferring Pharmaceutical FX This work was made possible by generous grants from EMD Serono and Ferring Pharmaceuticals. NR 48 TC 10 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2012 VL 98 IS 5 BP 1299 EP 1307 DI 10.1016/j.fertnstert.2012.07.1123 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 028TW UT WOS:000310447300043 PM 22901846 ER PT J AU Zheng, G Wu, CO Kwak, M Jiang, WH Joo, J Lima, JAC AF Zheng, Gang Wu, Colin O. Kwak, Minjung Jiang, Wenhua Joo, Jungnam Lima, Joao A. C. TI Joint Analysis of Binary and Quantitative Traits With Data Sharing and Outcome-Dependent Sampling (vol 36, pg 263, 2012) SO GENETIC EPIDEMIOLOGY LA English DT Correction ID RHEUMATOID-ARTHRITIS; POLYMORPHISM; ASSOCIATION; SEVERITY C1 [Zheng, Gang; Wu, Colin O.; Kwak, Minjung] NHLBI, Bethesda, MD 20892 USA. [Jiang, Wenhua; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Joo, Jungnam] Natl Canc Ctr, Geonggi Do, South Korea. RP Zheng, G (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 BP 717 EP 719 DI 10.1002/gepi.21666 PG 3 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200005 ER PT J AU Liu, CY Dupuis, J Larson, MG Levy, D AF Liu, Chunyu Dupuis, Josee Larson, Martin G. Levy, Daniel TI Association Testing of Mitochondrial Genome Using Pedigree Data SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Liu, Chunyu; Levy, Daniel] Framingham Heart Study NHLBI, Framingham, MA USA. [Dupuis, Josee; Larson, Martin G.] Boston Univ, Boston, MA 02215 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 16 BP 724 EP 724 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200022 ER PT J AU Edwards, TL Edwards, DRV Papanicolaou, GJ North, KE AF Edwards, Todd L. Edwards, Digna R. Velez Papanicolaou, George J. North, Kari E. CA African Amer BMI GWAS Consortium TI Evidence of Recent Positive Selection in Africans at Known and Novel BMI Loci SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Edwards, Todd L.; Edwards, Digna R. Velez] Vanderbilt Univ, Nashville, TN 37212 USA. [Papanicolaou, George J.] NHLBI, Bethesda, MD 20892 USA. [North, Kari E.] Univ N Carolina, Chapel Hill, NC 27515 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 19 BP 725 EP 725 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200025 ER PT J AU Liu, JH Chen, GK Blot, WJ Strom, SS Berndt, SI Kittles, RA Rybicki, BA Isaacs, W Ingles, SA Stanford, JL Diver, WR Witte, JS Hsing, AW Nemesure, B Rebbeck, TR Cooney, KA Xu, JF Kibel, AS Hu, JJ John, EM Gueye, SM Watya, S Signorello, LB Hayes, RB Wang, ZM Chu, L Klein, EA Goodman, P Yeboah, E Tettey, Y Cai, QY Kolb, S Ostrander, EA Zeigler-Johnson, C Yamamura, Y Neslund-Dudas, C Haslag-Minoff, J Wu, W Thomas, V Allen, GO Murphy, A Chang, BL Zheng, SL Leske, MC Wu, SY Ray, AM Hennis, AJM Thun, MJ Carpten, J Casey, G Chanock, SJ Stram, DO Henderson, BE Haiman, CA Conti, DV AF Liu, Jinghua Chen, Gary K. Blot, William J. Strom, Sara S. Berndt, Sonja I. Kittles, Rick A. Rybicki, Benjamin A. Isaacs, William Ingles, Sue A. Stanford, Janet L. Diver, W. Ryan Witte, John S. Hsing, Ann W. Nemesure, Barbara Rebbeck, Timothy R. Cooney, Kathleen A. Xu, Jianfeng Kibel, Adam S. Hu, Jennifer J. John, Esther M. Gueye, Serigne M. Watya, Stephen Signorello, Lisa B. Hayes, Richard B. Wang, Zhaoming Chu, Lisa Klein, Eric A. Goodman, Phyllis Yeboah, Edward Tettey, Yao Cai, Qiuyin Kolb, Suzanne Ostrander, Elaine A. Zeigler-Johnson, Charnita Yamamura, Yuko Neslund-Dudas, Christine Haslag-Minoff, Jennifer Wu, William Thomas, Venetta Allen, Glenn O. Murphy, Adma Chang, Bao-Li Zheng, S. Lilly Leske, M. Cristina Wu, Suh-Yuh Ray, Anna M. Hennis, Anselm J. M. Thun, Michael J. Carpten, John Casey, Graham Chanock, Stephen J. Stram, Daniel O. Henderson, Brian E. Haiman, Christopher A. Conti, David V. TI Models for Admixture Mapping in a Regression Framework SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Liu, Jinghua; Chen, Gary K.; Ingles, Sue A.; Casey, Graham; Stram, Daniel O.; Henderson, Brian E.; Haiman, Christopher A.; Conti, David V.] Univ So Calif, Los Angeles, CA 90089 USA. [Blot, William J.; Signorello, Lisa B.; Cai, Qiuyin] Vanderbilt Univ, Nashville, TN USA. [Strom, Sara S.; Yamamura, Yuko] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Hsing, Ann W.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kittles, Rick A.] Univ Illinois, Chicago, IL USA. [Rybicki, Benjamin A.; Neslund-Dudas, Christine] Henry Ford Hosp, Detroit, MI USA. [Stanford, Janet L.; Kolb, Suzanne] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Witte, John S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Nemesure, Barbara; Leske, M. Cristina; Wu, Suh-Yuh; Hennis, Anselm J. M.] SUNY Stony Brook, Stony Brook, NY USA. [Rebbeck, Timothy R.; Zeigler-Johnson, Charnita; Chang, Bao-Li] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.; Zeigler-Johnson, Charnita; Chang, Bao-Li] Abramson Canc Ctr, Philadelphia, PA USA. [Cooney, Kathleen A.; Ray, Anna M.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Xu, Jianfeng; Zheng, S. Lilly] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Kibel, Adam S.; Haslag-Minoff, Jennifer; Wu, William] Washington Univ, St Louis, MO 63130 USA. [Hu, Jennifer J.; Thomas, Venetta; Allen, Glenn O.] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [John, Esther M.; Chu, Lisa] Canc Prevent Inst Calif, Fremont, CA USA. [Gueye, Serigne M.] Hop Gen Grand Yoff, Dakar, Senegal. [Watya, Stephen] Makerere Univ, Mulago Hosp, Dept Surg, Urol Unit, Kampala, Uganda. [Hayes, Richard B.] NYU, Langone Med Ctr, New York, NY 10003 USA. [Wang, Zhaoming] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH USA. [Goodman, Phyllis] Fred Hutch Canc Ctr, Seattle, WA USA. [Yeboah, Edward; Tettey, Yao] Univ Ghana, Sch Med, Legon, Ghana. [Cai, Qiuyin] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, Bethesda, MD USA. [Murphy, Adma] Northwestern Univ, Evanston, IL 60208 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 26 BP 727 EP 727 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200032 ER PT J AU Peng, B Racine, B Chen, HS Mechanic, L Clarke, L Gillanders, E Feuer, E AF Peng, Bo Racine, Ben Chen, Huann-Sheng Mechanic, Leah Clarke, Lauren Gillanders, Elizabeth Feuer, Eric TI Genetic Simulation Resources (GSR): A Website for the Registration and Discovery of Genetic Data Simulators SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Peng, Bo] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Chen, Huann-Sheng; Mechanic, Leah; Gillanders, Elizabeth; Feuer, Eric] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RI Chen, Huann-Sheng/D-6328-2013 OI Chen, Huann-Sheng/0000-0002-5905-8050 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 49 BP 733 EP 734 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200055 ER PT J AU He, J Chen, GK Blot, WJ Strom, SS Berndt, SI Kitties, RA Rybicki, BA Isaacs, W Ingles, SA Stanford, JL Diver, RW Witte, JS Hsing, AW Nemesure, B Rebbeck, TR Cooney, KA Xu, JF Kibel, AS Hu, JJ John, EM Gueye, SM Watya, S Signorello, LB Hayes, RB Wang, ZM Chu, LW Klein, EA Goodman, P Yeboah, E Tettey, Y Cai, QY Kolb, S Ostrander, EA Zeigler-Johnson, C Yamamura, Y Neslund-Dudas, C Haslag-Minoff, J Wu, W Thomas, V Allen, GO Murphy, A Chang, BL Zheng, LS Leske, CM Wu, SY Ray, AM Hennis, AJM Thun, MJ Carpten, J Casey, G Chanock, SJ Henderson, BE Haiman, CA Stram, DO AF He, Jing Chen, Gary K. Blot, William J. Strom, Sara S. Berndt, Sonja I. Kitties, Rick A. Rybicki, Benjamin A. Isaacs, William Ingles, Sue A. Stanford, Janet L. Diver, Ryan W. Witte, John S. Hsing, Ann W. Nemesure, Barbara Rebbeck, Timothy R. Cooney, Kathleen A. Xu, Jianfeng Kibel, Adam S. Hu, Jennifer J. John, Esther M. Gueye, Serigne M. Watya, Stephen Signorello, Lisa B. Hayes, Richard B. Wang, Zhaoming Chu, Lisa W. Klein, Eric A. Goodman, Phyllis Yeboah, Edward Tettey, Yao Cai, Qiuyin Kolb, Suzanne Ostrander, Elaine A. Zeigler-Johnson, Charnita Yamamura, Yuko Neslund-Dudas, Christine Haslag-Minoff, Jennifer Wu, William Thomas, Venetta Allen, Glenn O. Murphy, Adam Chang, Bao-Li Zheng, Lilly S. Leske, Cristina M. Wu, Suh-Yuh Ray, Anna M. Hennis, Anselm J. M. Thun, Michael J. Carpten, John Casey, Graham Chanock, Stephen J. Henderson, Brian E. Haiman, Christopher A. Stram, Daniel O. TI Polygenes and Estimated Heritability of Prostate Cancer in an African American Sample Using GWAS Data SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [He, Jing; Chen, Gary K.; Ingles, Sue A.; Casey, Graham; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD USA. [Strom, Sara S.; Yamamura, Yuko] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Berndt, Sonja I.; Hsing, Ann W.; Wang, Zhaoming; Chu, Lisa W.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kitties, Rick A.] Univ Illinois, Dept Med, Chicago, IL USA. [Rybicki, Benjamin A.; Neslund-Dudas, Christine] Henry Ford Hosp, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. [Isaacs, William] Johns Hopkins Hosp & Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD USA. [Stanford, Janet L.; Kolb, Suzanne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Diver, Ryan W.; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94143 USA. [Witte, John S.] Univ Calif San Francisco, Dept Urol, Inst Human Genet, San Francisco, CA USA. [Nemesure, Barbara; Leske, Cristina M.; Wu, Suh-Yuh; Hennis, Anselm J. M.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Rebbeck, Timothy R.; Zeigler-Johnson, Charnita; Chang, Bao-Li] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.; Zeigler-Johnson, Charnita; Chang, Bao-Li] Abramson Canc Ctr, Philadelphia, PA USA. [Cooney, Kathleen A.; Ray, Anna M.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Xu, Jianfeng; Zheng, Lilly S.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA. [Kibel, Adam S.; Haslag-Minoff, Jennifer; Wu, William] Washington Univ, Dept Surg, Div Urol, St Louis, MO USA. [Hu, Jennifer J.; Thomas, Venetta; Allen, Glenn O.] Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Coral Gables, FL 33124 USA. [Hu, Jennifer J.; Thomas, Venetta; Allen, Glenn O.] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Coral Gables, FL 33124 USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [Gueye, Serigne M.] Hop Gen Grand Yoff, Dakar, Senegal. [Watya, Stephen] Makerere Univ, Mulago Hosp, Dept Surg, Urol Unit, Kampala, Uganda. [Hayes, Richard B.] NYU, Dept Environm Med, Langone Med Ctr, Div Epidemiol, New York, NY 10016 USA. [Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA. [Yeboah, Edward; Tettey, Yao] Univ Ghana, Sch Med, Legon, Ghana. [Cai, Qiuyin] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Med, Div Epidemiol, Nashville, TN 37235 USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Murphy, Adam] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA. [Carpten, John] Translat Genom Res Inst, Phoenix, AZ 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 58 BP 736 EP 736 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200064 ER PT J AU Bailey-Wilson, JE Parker, MM Szymczak, S Li, Q Cropp, CD Nothen, MM Hetmanski, JB Ling, H Pugh, EW Duggal, P Taub, MA Ruczinski, I Scott, AF Marazita, ML Murray, JC Mangold, E Beaty, TH AF Bailey-Wilson, Joan E. Parker, Margaret M. Szymczak, Silke Li, Qing Cropp, Cheryl D. Nothen, Markus M. Hetmanski, Jacqueline B. Ling, Hua Pugh, Elizabeth W. Duggal, Priya Taub, Margaret A. Ruczinski, Ingo Scott, Alan F. Marazita, Mary L. Murray, Jeffrey C. Mangold, Elisabeth Beaty, Terri H. TI Using Whole Exome Sequencing to Identify Rare Causal Variants for Oral Clefts in Multiplex Families with a Focus on Syrian Families SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Bailey-Wilson, Joan E.; Szymczak, Silke; Li, Qing; Cropp, Cheryl D.] NHGRI, NIH, Bethesda, MD 20892 USA. [Parker, Margaret M.; Hetmanski, Jacqueline B.; Duggal, Priya; Taub, Margaret A.; Ruczinski, Ingo; Beaty, Terri H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Nothen, Markus M.; Mangold, Elisabeth] Univ Bonn, Inst Human Genet, Bonn, Germany. [Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Pittsburgh, PA 15260 USA. [Murray, Jeffrey C.] Univ Iowa, Childrens Hosp, Iowa City, IA 52242 USA. RI Szymczak, Silke/C-6625-2013 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 66 BP 738 EP 739 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200072 ER PT J AU Yang, XH Jacobs, K Cullen, M Boland, J Burdett, L Malasky, M Rotunno, M Yeager, M Chanock, S Tucker, M Goldstein, A AF Yang, Xiaohong Jacobs, Kevin Cullen, Michael Boland, Joseph Burdett, Laurie Malasky, Michael Rotunno, Melissa Yeager, Meredith Chanock, Stephen Tucker, Margaret Goldstein, Alisa TI Characterization of Rare Variants in Melanoma-associated Genes in Melanoma-prone Families without CDKN2A/CDK4 Mutations using Exome Sequencing Data SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Yang, Xiaohong; Jacobs, Kevin; Cullen, Michael; Boland, Joseph; Burdett, Laurie; Malasky, Michael; Rotunno, Melissa; Yeager, Meredith; Chanock, Stephen; Tucker, Margaret; Goldstein, Alisa] NIH, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 67 BP 739 EP 739 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200073 ER PT J AU Ritchie, MD Setia, SZ Armstrong, GD Armstrong, L Bradford, Y Crawford, DC Crosslin, DR de Andrade, M Doheny, KF Hayes, MG Jarvik, GP Kullo, I Li, RL McCarty, CA Mirel, D Olson, L Purcell, S Pugh, EW Tromp, G Kuivaniemi, H Lotay, V Gottesman, O Haines, JL AF Ritchie, Marylyn D. Setia, Shefali Z. Armstrong, Gretta D. Armstrong, Loren Bradford, Yuki Crawford, Dana C. Crosslin, David R. de Andrade, Mariza Doheny, Kimberly F. Hayes, M. Geoffrey Jarvik, Gail P. Kullo, Iftiklhar Li, Rongling McCarty, Cathy A. Mirel, Daniel Olson, Lana Purcell, Shaun Pugh, Elizabeth W. Tromp, Gerard Kuivaniemi, Helena Lotay, Vaneet Gottesman, Omri Haines, Jonathan L. TI Merging Genomic Data for Research in the Electronic MEdical Records and GEnomics Network: Lessons Learned in eMERGE SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Ritchie, Marylyn D.; Setia, Shefali Z.; Armstrong, Gretta D.] Penn State Univ, University Pk, PA 16802 USA. [Armstrong, Loren; Hayes, M. Geoffrey] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Bradford, Yuki; Crawford, Dana C.; Olson, Lana; Haines, Jonathan L.] Vanderbilt Univ, Nashville, TN USA. [Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Seattle, WA 98195 USA. [de Andrade, Mariza; Kullo, Iftiklhar] Mayo Clin, Rochester, MN USA. [Doheny, Kimberly F.; Pugh, Elizabeth W.] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21218 USA. [Li, Rongling] NHGRI, NIH, Bethesda, MD USA. [McCarty, Cathy A.] Essentia Rural Hlth, Duluth, MN USA. [Purcell, Shaun; Lotay, Vaneet; Gottesman, Omri] Mt Sinai Sch Med, New York, NY USA. RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 71 BP 740 EP 740 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200077 ER PT J AU Mandal, DM Haskins, M Bencaz, A Hutchinson, J Chambliss, J Rothschild, H Bailey-Wilson, JE AF Mandal, Diptasri M. Haskins, Matthew Bencaz, Angelle Hutchinson, Jill Chambliss, Jessica Rothschild, Henry Bailey-Wilson, Joan E. TI Histologic Types and Risk Factors in Familial Lung Cancer Cases from Southern Louisiana SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Mandal, Diptasri M.; Haskins, Matthew; Bencaz, Angelle; Hutchinson, Jill; Chambliss, Jessica; Rothschild, Henry] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA USA. [Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 81 BP 743 EP 743 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200087 ER PT J AU Zaitlen, N Lindstrom, S Pasaniuc, B Cornelis, M Genovese, G Pollack, S Barton, A Bowden, DW Eyre, S Freedman, BI Field, JK Groop, L Haugen, A Henderson, BE Hicks, PJ Hocking, LJ Kolonel, LN Landi, MT Langefeld, CD Le Marchand, L Meister, M Morgan, AW Raji, OY Risch, A Scherf, D Steer, S Walshaw, M Waters, KM Wilson, AG Wordsworth, P Zienolddiny, S Tchetgen, ET Haiman, C Hunter, DJ Plenge, RM Worthington, J Christiani, DC Schaumberg, DA Chasman, DI Altshuler, D Voight, B Kraft, P Patterson, N Price, AL AF Zaitlen, Noah Lindstrom, Sara Pasaniuc, Bogdan Cornelis, Marilyn Genovese, Giulio Pollack, Samuela Barton, Anne Bowden, Donald W. Eyre, Steve Freedman, Barry I. Field, John K. Groop, Leif Haugen, Aage Henderson, Brian E. Hicks, Pamela J. Hocking, Lynne J. Kolonel, Laurence N. Landi, Maria Teresa Langefeld, Carl D. Le Marchand, Loic Meister, Michael Morgan, Ann W. Raji, Olaide Y. Risch, Angela Scherf, David Steer, Sophia Walshaw, Martin Waters, Kevin M. Wilson, Anthony G. Wordsworth, Paul Zienolddiny, Shanbeh Tchetgen, Eric Tchetgen Haiman, Christopher Hunter, David J. Plenge, Robert M. Worthington, Jane Christiani, David C. Schaumberg, Debra A. Chasman, Daniel I. Altshuler, David Voight, Benjamin Kraft, Peter Patterson, Nick Price, Alkes L. TI Informed Conditioning on Clinical Covariates Increases Power in Case-control Association Studies SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Zaitlen, Noah; Lindstrom, Sara; Pasaniuc, Bogdan; Cornelis, Marilyn; Pollack, Samuela; Tchetgen, Eric Tchetgen; Hunter, David J.; Christiani, David C.; Schaumberg, Debra A.; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Genovese, Giulio; Plenge, Robert M.; Chasman, Daniel I.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Barton, Anne; Eyre, Steve; Worthington, Jane] Univ Manchester, Manchester M13 9PL, Lancs, England. [Field, John K.; Raji, Olaide Y.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Henderson, Brian E.; Waters, Kevin M.; Haiman, Christopher] Univ So Calif, Los Angeles, CA 90089 USA. [Hicks, Pamela J.; Langefeld, Carl D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hocking, Lynne J.] Univ Aberdeen, Aberdeen AB9 1FX, Scotland. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Honolulu, HI 96822 USA. [Landi, Maria Teresa] NIH, Bethesda, MD USA. [Steer, Sophia] Kings Coll London, London, England. [Wilson, Anthony G.] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. RI Altshuler, David/A-4476-2009; Barton, Anne/N-2053-2014; Zienolddiny, Shanbeh/O-7392-2015 OI Altshuler, David/0000-0002-7250-4107; Barton, Anne/0000-0003-3316-2527; NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 88 BP 745 EP 745 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200094 ER PT J AU Cropp, CD Simpson, CL Wahlfors, T George, A Jones, MS Harper, U Ponciano-Jackson, D Tammela, T Schleutker, J Bailey-Wilson, JE AF Cropp, Cheryl D. Simpson, Claire L. Wahlfors, Tiina George, Asha Jones, MaryPat S. Harper, Ursula Ponciano-Jackson, Damaris Tammela, Teuvo Schleutker, Johanna Bailey-Wilson, Joan E. TI Unraveling Phenotype Heterogeneity in Prostate Cancer Susceptibility in Finland Utilizing Covariate-Based Analysis SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Cropp, Cheryl D.; Simpson, Claire L.; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [Wahlfors, Tiina] Univ Tampere, Inst Biomed Technol, BioMediTech, FIN-33101 Tampere, Finland. [George, Asha] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Jones, MaryPat S.; Harper, Ursula; Ponciano-Jackson, Damaris] NHGRI, Genom Core, Genome Technol Branch, NIH, Rockville, MD USA. [Tammela, Teuvo] Univ Tampere, Tampere Univ Hosp, Dept Urol, FIN-33101 Tampere, Finland. [Schleutker, Johanna] Univ Turku, Dept Med Biochem & Genet, Turku, Finland. 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 93 BP 746 EP 747 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200099 ER PT J AU Szymczak, S Li, Q Kim, Y Dasgupta, A Malley, JD Bailey-Wilson, JE AF Szymczak, Silke Li, Qing Kim, Yoonhee Dasgupta, Abhijit Malley, James D. Bailey-Wilson, Joan E. TI A Two-stage Random Forest Approach to Identify Genetic Variants Using Recombination Hotspot Information SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Szymczak, Silke; Li, Qing; Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Kim, Yoonhee] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Dasgupta, Abhijit] NIH, Clin Sci Sect, Inst Arthrit & Musculoskeletal & Skin Dis, Bethesda, MD 20892 USA. [Malley, James D.] NIH, Ctr Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RI Szymczak, Silke/C-6625-2013 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 115 BP 752 EP 753 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200120 ER PT J AU Lu, C Latourelle, J O'Connor, GT Dupuis, J Kolaczyk, ED AF Lu, Chen Latourelle, Jeanne O'Connor, George T. Dupuis, Josee Kolaczyk, Eric D. TI Network-guided Sparse Regression Modeling for Detection of Gene by Gene Interactions SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Lu, Chen] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Latourelle, Jeanne; O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02215 USA. [Latourelle, Jeanne] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Latourelle, Jeanne; O'Connor, George T.; Dupuis, Josee] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. [Dupuis, Josee] Boston U, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee] Boston U, Program Bioinformat, Boston, MA USA. [Kolaczyk, Eric D.] Boston Univ, Dept Math & Stat, Program Bioinformat, Boston, MA 02215 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 117 BP 753 EP 753 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200122 ER PT J AU Li, Q Szymczak, S Bailey-Wilson, JE AF Li, Qing Szymczak, Silke Bailey-Wilson, Joan E. TI Test for Two-SNP Interaction Adjusting for Long Range Linkage Disequilibrium SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Li, Qing; Szymczak, Silke; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, Bethesda, MD USA. RI Szymczak, Silke/C-6625-2013 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 124 BP 755 EP 755 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200129 ER PT J AU Buck, K Hein, R Haeberle, L Garcia-Closas, M Chatterjee, N Chang-Claude, J AF Buck, Katharina Hein, Rebecca Haeberle, Lothar Garcia-Closas, Montserrat Chatterjee, Nilanjan Chang-Claude, Jenny TI Empirical-Bayes Approach to Investigate Gene-environment Interactions in Large Consortia SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Buck, Katharina; Chang-Claude, Jenny] German Canc Res Ctr, Heidelberg, Germany. [Hein, Rebecca] Univ Cologne, Cologne, Germany. [Haeberle, Lothar] Univ Hosp Erlangen, Erlangen, Germany. [Garcia-Closas, Montserrat] Inst Canc Res, London, England. [Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, London, England. [Chatterjee, Nilanjan] NCI, 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 129 BP 756 EP 757 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200134 ER PT J AU Nickels, S Truong, T Hein, R Stevens, K Buck, K Gaudet, MM Haeberle, L Spurdle, A Behrens, S Eilber, U Figueora, J Dunning, AM Chenevix-Trench, G Pharoah, P Easton, DF Hall, P Schmidt, M Garcia-Closas, M Milne, RL Chang-Claude, J AF Nickels, Stefan Truong, Therese Hein, Rebecca Stevens, Kristen Buck, Katharina Gaudet, Mia M. Haeberle, Lothar Spurdle, Amanda Behrens, Sabine Eilber, Ursula Figueora, Jonine Dunning, Alison M. Chenevix-Trench, Georgia Pharoah, Paul Easton, Douglas F. Hall, Per Schmidt, Marjanka Garcia-Closas, Montserrat Milne, Roger L. Chang-Claude, Jenny TI Evidence of Gene-environment Interaction Between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Nickels, Stefan; Behrens, Sabine; Eilber, Ursula; Chang-Claude, Jenny] Univ Cologne, German Canc Res Ctr DKFZ, Div Canc Epidemiol, Cologne, Germany. [Truong, Therese] Univ Cologne, INSERM, Natl Inst Hlth & Med Res, CESP Ctr Res Epidemiol & Populat Hlth, Cologne, Germany. [Hein, Rebecca] Univ Cologne, PMV Res Grp, Dept Child & Adolescent Psychiat & Psychotherapy, Cologne, Germany. [Stevens, Kristen] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Haeberle, Lothar] Erlangen Univ Hosp, Dept Obstet & Gynecol, Erlangen, Germany. [Chenevix-Trench, Georgia] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia. [Figueora, Jonine] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Dunning, Alison M.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB2 1TN, England. [Hall, Per] Karolinska Inst, Stockholm, Sweden. [Schmidt, Marjanka] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England. 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 127 BP 756 EP 756 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200132 ER PT J AU Franceschini, N Dreisbach, A Kao, WL North, KE Nalls, M Fox, C Cupp, A AF Franceschini, Nora Dreisbach, Albert Kao, W. Linda North, Kari E. Nalls, Michael Fox, Caroline Cupp, Adrienne TI Gene-by-Smoking Interaction Analyses of Kidney Traits in the NHLBI Candidate-gene Association Resources CARe Cohorts SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Franceschini, Nora; North, Kari E.] Univ N Carolina, Chapel Hill, NC 39216 USA. [Dreisbach, Albert] Univ Mississippi, Jackson, MS USA. [Kao, W. Linda] Johns Hopkins Univ, Baltimore, MD 20892 USA. [Nalls, Michael] NIA, Neurogenet Lab, NIH, Bethesda, MD 02115 USA. [Fox, Caroline] Harvard Univ, NHLBI, Framingham Heart Study & Ctr Populat Studies & En, Sch Med, Boston, MA USA. [Cupp, Adrienne] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Cupp, Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 135 BP 758 EP 759 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200140 ER PT J AU Joshi, AD Lindstrom, S Ziegler, RG Figueroa, JD Gapstur, SM Haiman, CA Riboli, E Kraft, P Gaudet, MM AF Joshi, Amit D. Lindstrom, Sara Ziegler, Regina G. Figueroa, Jonine D. Gapstur, Susan M. Haiman, Christopher A. Riboli, Elio Kraft, Peter Gaudet, Mia M. TI A Comparison of Approaches for Genome-wide Gene-environment Interaction Analyses in the Risk of Estrogen Receptor (ER)-Negative Breast Cancer SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Joshi, Amit D.; Lindstrom, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Ziegler, Regina G.; Figueroa, Jonine D.] NCI, Bethesda, MD 20892 USA. [Gapstur, Susan M.; Gaudet, Mia M.] Amer Canc Soc, Atlanta, GA 30329 USA. [Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. [Riboli, Elio] Imperial Coll London, Sch Publ Hlth, London, England. 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 137 BP 759 EP 759 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200142 ER PT J AU Lobach, I Fan, RZ AF Lobach, Iryna Fan, Ruzong TI Genotype-based Bayesian Analysis of Gene-Environment Interactions with Multiple Genetic Markers and Misclassification in Environmental Factors SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Lobach, Iryna] NYU, Sch Med, New York, NY 10003 USA. [Fan, Ruzong] NICHD, 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 153 BP 764 EP 764 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200158 ER PT J AU Wang, ZM Jacobs, KB Yeager, M Hutchinson, A Sampson, J Tucker, M Chanock, SJ AF Wang, Zhaoming Jacobs, Kevin B. Yeager, Meredith Hutchinson, Amy Sampson, Joshua Tucker, Margaret Chanock, Stephen J. TI Second Generation DCEG Reference Set Improves Performance of Genotype Imputation SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Wang, Zhaoming; Jacobs, Kevin B.; Yeager, Meredith; Hutchinson, Amy] NCI, SAIC Frederick, DCEG, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 162 BP 766 EP 766 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200167 ER PT J AU Hiraki, LT Joshi, A Lindstrom, S Chan, AT Chanock, S Kraft, P AF Hiraki, Linda T. Joshi, Amit Lindstrom, Sara Chan, Andrew T. Chanock, Stephen Kraft, Peter TI Building and Assessing Protein-Protein Interaction Networks from Genome Wide Association Results in Cancer SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Hiraki, Linda T.; Joshi, Amit; Lindstrom, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chanock, Stephen] NCI, 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 178 BP 771 EP 771 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200183 ER PT J AU Chen, H Meigs, JB Dupuis, J AF Chen, Han Meigs, James B. Dupuis, Josee TI Sequence Kernel Association Test in Family Data SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Meigs, James B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Cambridge, MA 02138 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 181 BP 772 EP 772 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200186 ER PT J AU Simpson, CL Green, T Doan, B Amos, CI Pinney, SM Kupert, EY de Andrade, M Yang, P Schwartz, AG Fain, PR Gazdar, A Minna, J Wiest, JS Rothschild, H Mandal, D You, M Coons, TA Gaba, C Anderson, MW Bailey-Wilson, JE AF Simpson, Claire L. Green, Tiffany Doan, Betty Amos, Christopher I. Pinney, Susan M. Kupert, Elena Y. de Andrade, Mariza Yang, Ping Schwartz, Ann G. Fain, Pam R. Gazdar, Adi Minna, John Wiest, Jonathan S. Rothschild, Henry Mandal, Diptasri You, Ming Coons, Theresa A. Gaba, Colette Anderson, Marshall W. Bailey-Wilson, Joan E. TI Fine-Mapping in a Covariate-based Genomewide Linkage Scan of Lung Cancer Susceptibility SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Simpson, Claire L.; Green, Tiffany; Doan, Betty; Bailey-Wilson, Joan E.] NHGRI, NIH, Bethesda, MD 20892 USA. [Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA. [Pinney, Susan M.; Kupert, Elena Y.; You, Ming; Anderson, Marshall W.] Med Coll Wisconsin, Milwaukee, WI USA. [de Andrade, Mariza; Yang, Ping] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. [Fain, Pam R.] Univ Colorado, Boulder, CO 80309 USA. [Wiest, Jonathan S.] NCI, NIH, Bethesda, MD 20892 USA. [Rothschild, Henry; Mandal, Diptasri] Louisiana State Univ, Hlth Sci Ctr, Baton Rouge, LA 70803 USA. [Gaba, Colette] Univ Toledo, Toledo, OH 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 191 BP 774 EP 775 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200196 ER PT J AU Holz, LE Yoon, JC Raghuraman, S Moir, S Sneller, MC Rehermann, B AF Holz, Lauren E. Yoon, Joo Chun Raghuraman, Sukanya Moir, Susan Sneller, Michael C. Rehermann, Barbara TI B Cell Homeostasis in Chronic Hepatitis C Virus-Related Mixed Cryoglobulinemia Is Maintained Through Naive B Cell Apoptosis SO HEPATOLOGY LA English DT Article ID MONONUCLEAR-CELLS; ANTIVIRAL THERAPY; INFECTION; RECEPTOR; ACTIVATION; VASCULITIS; PROTEIN; DISORDERS; RITUXIMAB; ANTIBODY AB Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of chronic hepatitis C virus (HCV) infection. Although the formation of inflammation-triggering immune complexes is driven by clonal expansions of autoreactive B cells, we found total B cell numbers paradoxically reduced in HCV-infected patients with MC. HCV patients with MC (n = 17) also displayed a reduced number and a reduced frequency of naive B cells compared with HCV-infected patients without MC (n = 19), hepatitis B virusinfected patients (n = 10), and uninfected controls (n = 50). This was due to an increased sensitivity of naive B cells to apoptosis resulting in a reduction in the size of the naive B cell subset. In addition, 4-fold expansion and skewing (lower T1/T2-ratio) of the immature B cell subset was noted in MC patients, suggesting that apoptosis of naive B cells triggered the release of B cell precursors from bone marrow in an attempt to maintain normal B cell numbers. Following treatment of MC with the B celldepleting antibody rituximab, the size of all B cell subsets, the T1/T2-ratio, and the cyroglobulin levels all normalized. Cryoglobulin levels correlated with in vivo proliferation of T2 B cells, suggesting a link between the skewing of the T1/T2 ratio and the formation of immune complexes. Conclusion: This study provides insight into the mechanisms maintaining B cell homeostasis in HCV-induced MC and the ability of rituximab therapy to restore normal B cell compartments. (HEPATOLOGY 2012;56:16021610) C1 [Holz, Lauren E.; Yoon, Joo Chun; Raghuraman, Sukanya; Rehermann, Barbara] NIDDKD, Immunol Sect, Liver Dis Branch, Bethesda, MD 20892 USA. [Moir, Susan; Sneller, Michael C.] NIAID, Immunoregulat Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA. EM rehermann@nih.gov RI Yoon, Joo Chun/D-3675-2012 OI Yoon, Joo Chun/0000-0001-9395-8418 FU National Institutes of Health intramural research program FX Supported by the National Institutes of Health intramural research program (National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases). NR 24 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2012 VL 56 IS 5 BP 1602 EP 1610 DI 10.1002/hep.25821 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030BR UT WOS:000310543100005 PM 22556016 ER PT J AU Sarkar, M Bacchetti, P French, AL Tien, P Glesby, MJ Nowicki, M Plankey, M Gange, S Sharp, G Minkoff, H Peters, MG AF Sarkar, Monika Bacchetti, Peter French, Audrey L. Tien, Phyllis Glesby, Marshall J. Nowicki, Marek Plankey, Michael Gange, Stephen Sharp, Gerald Minkoff, Howard Peters, Marion G. CA WIHS TI Lower liver-related death in African-American women with human immunodeficiency virus/hepatitis C virus coinfection, compared to Caucasian and Hispanic women SO HEPATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; UNITED-STATES; FIBROSIS PROGRESSION; GENETIC-VARIATION; MORTALITY; INFECTION; HIV AB Among individuals with and without concurrent human immunodeficiency virus (HIV), racial/ethnic differences in the natural history of hepatitis C virus (HCV) have been described. African Americans have lower spontaneous HCV clearance than Caucasians, yet slower rates of liver fibrosis once chronically infected. It is not clear how these differences in the natural history of hepatitis C affect mortality, in either HIV-positive or -negative individuals. We conducted a cohort study of HIV/HCV coinfected women followed in the multicenter Women's Interagency HIV Study to determine the association of self-reported race/ethnicity with all-cause and liver-related mortality. Survival analyses were performed using Cox's proportional hazards models. The eligible cohort (n = 794) included 140 Caucasians, 159 Hispanics, and 495 African Americans. There were 438 deaths and 49 liver-related deaths during a median follow-up of 8.9 years and maximum follow-up of 16 years. African-American coinfected women had significantly lower liver-related mortality, compared to Caucasian (hazard ratio [HR], 0.41; 95% confidence interval [CI]: 0.19-0.88; P = 0.022) and Hispanic coinfected women (HR, 0.38; 95% CI: 0.19-0.76; P = 0.006). All-cause mortality was similar between racial/ethnic groups (HRs for all comparisons: 0.82-1.03; log-rank test: P = 0.8). Conclusions: African-American coinfected women were much less likely to die from liver disease, as compared to Caucasians and Hispanics, independent of other causes of death. Future studies are needed to investigate the reasons for this marked racial/ethnic discrepancy in liver-related mortality. (HEPATOLOGY 2012;56:16991705) C1 [Sarkar, Monika; Peters, Marion G.] Univ Calif San Francisco, Dept Med, Div Gastroenterol & Hepatol, San Francisco, CA 94143 USA. [Bacchetti, Peter] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [French, Audrey L.] John H Stroger Jr Hosp Cook Cty, Dept Med, CORE Center, Chicago, IL USA. [Tien, Phyllis] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA. [Glesby, Marshall J.] Weill Cornell Med Coll, Dept Med, Div Infect Dis, New York, NY USA. [Nowicki, Marek] Univ So Calif, Dept Med, Los Angeles, CA USA. [Plankey, Michael] Georgetown Univ, Dept Med, Div Infect Dis, Washington, DC USA. [Gange, Stephen] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Sharp, Gerald] NIAID, Epidemiol Branch, NIH, Div Acquired Immune Deficiency Syndrome, Bethesda, MD 20892 USA. [Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. RP Sarkar, M (reprint author), Univ Calif San Francisco, Dept Med, Div Gastroenterol & Hepatol, 513 Parnassus Ave,Room S-357, San Francisco, CA 94143 USA. EM monika.sarkar@ucsf.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Institutes of Health [T32 DK060414] FX The Women's Interagency HIV Study is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Additional support was received through the National Institutes of Health (T32 DK060414; to M.S.). NR 25 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2012 VL 56 IS 5 BP 1699 EP 1705 DI 10.1002/hep.25859 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030BR UT WOS:000310543100015 PM 22618868 ER PT J AU Lee, YM Jun, HS Pan, CJ Lin, SR Wilson, LH Mansfield, BC Chou, JY AF Lee, Young Mok Jun, Hyun Sik Pan, Chi-Jiunn Lin, Su Ru Wilson, Lane H. Mansfield, Brian C. Chou, Janice Y. TI Prevention of hepatocellular adenoma and correction of metabolic abnormalities in murine glycogen storage disease type Ia by gene therapy SO HEPATOLOGY LA English DT Article ID MOUSE; CARCINOMA; LIVER; GLUCOSE-6-PHOSPHATASE; DEFICIENCY; MANAGEMENT; TRANSPORT; SERIES; MICE AB Glycogen storage disease type Ia (GSD-Ia), which is characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA), is caused by deficiencies in the endoplasmic reticulum (ER)-associated glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC) that hydrolyzes glucose-6-phosphate (G6P) to glucose. G6Pase-alpha activity depends on the G6P transporter (G6PT) that translocates G6P from the cytoplasm into the ER lumen. The functional coupling of G6Pase-alpha and G6PT maintains interprandial glucose homeostasis. We have shown previously that gene therapy mediated by AAV-GPE, an adeno-associated virus (AAV) vector expressing G6Pase-alpha directed by the human G6PC promoter/enhancer (GPE), completely normalizes hepatic G6Pase-alpha deficiency in GSD-Ia (G6pc(-/-)) mice for at least 24 weeks. However, a recent study showed that within 78 weeks of gene deletion, all mice lacking G6Pase-alpha in the liver develop HCA. We now show that gene therapy mediated by AAV-GPE maintains efficacy for at least 70-90 weeks for mice expressing more than 3% of wild-type hepatic G6Pase-alpha activity. The treated mice displayed normal hepatic fat storage, had normal blood metabolite and glucose tolerance profiles, had reduced fasting blood insulin levels, maintained normoglycemia over a 24-hour fast, and had no evidence of hepatic abnormalities. After a 24-hour fast, hepatic G6PT messenger RNA levels in G6pc(-/-) mice receiving gene therapy were markedly increased. Because G6PT transport is the rate-limiting step in microsomal G6P metabolism, this may explain why the treated G6pc(-/-) mice could sustain prolonged fasts. The low fasting blood insulin levels and lack of hepatic steatosis may explain the absence of HCA. Conclusion: These results confirm that AAV-GPEmediated gene transfer corrects hepatic G6Pase-alpha deficiency in murine GSD-Ia and prevents chronic HCA formation. (HEPATOLOGY 2012;56:17191729) C1 [Lee, Young Mok; Jun, Hyun Sik; Pan, Chi-Jiunn; Lin, Su Ru; Wilson, Lane H.; Mansfield, Brian C.; Chou, Janice Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Mansfield, Brian C.] Fdn Fighting Blindness, Columbia, MD 21046 USA. RP Chou, JY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov RI Jun, Hyun Sik/C-6799-2013; OI Mansfield, Brian/0000-0002-8533-2789 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Children's Fund for Glycogen Storage Disease Research FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and The Children's Fund for Glycogen Storage Disease Research. NR 27 TC 16 Z9 16 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2012 VL 56 IS 5 BP 1719 EP 1729 DI 10.1002/hep.25717 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030BR UT WOS:000310543100017 PM 22422504 ER PT J AU Oishi, N Kumar, MR Roessler, S Ji, JF Forgues, M Budhu, A Zhao, XL Andersen, JB Ye, QH Jia, HL Qin, LX Yamashita, T Woo, HG Kim, YJ Kaneko, S Tang, ZY Thorgeirsson, SS Wang, XW AF Oishi, Naoki Kumar, Mia R. Roessler, Stephanie Ji, Junfang Forgues, Marshonna Budhu, Anuradha Zhao, Xuelian Andersen, Jesper B. Ye, Qing-Hai Jia, Hu-Liang Qin, Lun-Xiu Yamashita, Taro Woo, Hyun Goo Kim, Yoon Jun Kaneko, Shuichi Tang, Zhao-You Thorgeirsson, Snorri S. Wang, Xin Wei TI Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma SO HEPATOLOGY LA English DT Article ID HUMAN LIVER-CANCER; HEPATOCELLULAR-CARCINOMA; TUMOR-METASTASIS; E-CADHERIN; MICRO-RNA; TGF-BETA; CELLS; IDENTIFICATION; EXPRESSION; EPCAM AB Intrahepatic cholangiocellular carcinoma (ICC) is the second most common type of primary liver cancer. However, its tumor heterogeneity and molecular characteristics are largely unknown. In this study, we conducted transcriptomic profiling of 23 ICC and combined hepatocellular cholangiocarcinoma tumor specimens from Asian patients using Affymetrix messenger RNA (mRNA) and NanoString microRNA microarrays to search for unique gene signatures linked to tumor subtypes and patient prognosis. We validated the signatures in an additional 68 ICC cases derived from Caucasian patients. We found that both mRNA and microRNA expression profiles could independently classify Asian ICC cases into two main subgroups, one of which shared gene expression signatures with previously identified hepatocellular carcinoma (HCC) with stem cell gene expression traits. ICC-specific gene signatures could predict survival in Asian HCC cases and independently in Caucasian ICC cases. Integrative analyses of the ICC-specific mRNA and microRNA expression profiles revealed that a common signaling pathway linking miR-200c signaling to epithelial-mesenchymal transition (EMT) was preferentially activated in ICC with stem cell gene expression traits. Inactivation of miR-200c resulted in an induction of EMT, whereas activation of miR-200c led to a reduction of EMT including a reduced cell migration and invasion in ICC cells. We also found that miR-200c and neural cell adhesion molecule 1 (NCAM1) expression were negatively correlated and their expression levels were predictive of survival in ICC samples. NCAM1, a known hepatic stem/progenitor cell marker, was experimentally demonstrated to be a direct target of miR-200c. Conclusion: Our results indicate that ICC and HCC share common stem-like molecular characteristics and poor prognosis. We suggest that the specific components of EMT may be exploited as critical biomarkers and clinically relevant therapeutic targets for an aggressive form of stem cell-like ICC. (HEPATOLOGY 2012;56:17921803) C1 [Oishi, Naoki; Kumar, Mia R.; Roessler, Stephanie; Ji, Junfang; Forgues, Marshonna; Budhu, Anuradha; Zhao, Xuelian; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Andersen, Jesper B.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ye, Qing-Hai; Jia, Hu-Liang; Qin, Lun-Xiu; Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. [Yamashita, Taro; Kaneko, Shuichi] Kanazawa Univ, Liver Dis Ctr, Kanazawa, Ishikawa, Japan. [Yamashita, Taro; Kaneko, Shuichi] Kanazawa Univ, Kanazawa Univ Hosp, Kanazawa, Ishikawa, Japan. [Woo, Hyun Goo] Ajou Univ, Dept Physiol, Sch Med, Suwon 441749, South Korea. [Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul, South Korea. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Rm 3044A, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Kim, Yoon Jun/J-2746-2012; Wang, Xin/B-6162-2009; OI Andersen , Jesper B/0000-0003-1760-5244 FU Intramural Research Program of the center for Cancer Research, the U.S. National Cancer Institute [Z01 BC 010313, Z01 BC 010876] FX Supported in part by the Intramural Research Program of the center for Cancer Research, the U.S. National Cancer Institute (Z01 BC 010313 and Z01 BC 010876). NR 52 TC 84 Z9 87 U1 3 U2 27 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 NOV PY 2012 VL 56 IS 5 BP 1792 EP 1803 DI 10.1002/hep.25890 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030BR UT WOS:000310543100024 PM 22707408 ER PT J AU Tanaka, N Gonzalez, FJ AF Tanaka, Naoki Gonzalez, Frank J. TI Bile Acids in Nonalcoholic Steatohepatitis: Inserting Nuclear Receptors Into the Reply SO HEPATOLOGY LA English DT Letter C1 [Tanaka, Naoki; Gonzalez, Frank J.] Natl Canc Inst, Natl Inst Hlth, Lab Metab, Bethesda, MD USA. RP Tanaka, N (reprint author), Natl Canc Inst, Natl Inst Hlth, Lab Metab, Bethesda, MD USA. FU Intramural NIH HHS [ZIA BC005708-19] NR 1 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 J9 HEPATOLOGY JI Hepatology PD NOV PY 2012 VL 56 IS 5 BP 2009 EP 2009 DI 10.1002/hep.25811 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030BR UT WOS:000310543100052 PM 23115012 ER PT J AU Kahn, JA Burk, RD Squires, KE Kapogiannis, BG Rudy, B Xu, JH Gonin, R Liu, N Worrell, C Wilson, CM AF Kahn, Jessica A. Burk, Robert D. Squires, Kathleen E. Kapogiannis, Bill G. Rudy, Bret Xu, Jiahong Gonin, Rene Liu, Nancy Worrell, Carol Wilson, Craig M. TI Prevalence and Risk Factors for HPV in HIV-Positive Young Women Receiving Their First HPV Vaccination SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE human papillomavirus; vaccine; epidemiology; women; HIV ID HUMAN-PAPILLOMAVIRUS INFECTION; CERVICAL INTRAEPITHELIAL NEOPLASIA; HUMAN-IMMUNODEFICIENCY-VIRUS; PARTICLE VACCINE; NATURAL-HISTORY; ADOLESCENT GIRLS; AFRICAN WOMEN; DNA DETECTION; CANCER; LESIONS AB Background: The objectives of this study were to describe the prevalence and risk factors for HPV infection among HIV-infected young women receiving their first quadrivalent HPV (HPV-6, -11, -16, and -18) vaccine dose. Methods: We recruited 16- to 23-year-old women from 14 sites for an HPV vaccine trial. At the first visit, they completed a questionnaire and were tested for cervicovaginal HPV DNA (41 types) and HPV serology (4 vaccine types). Factors associated with any HPV, type-specific HPV, and high-risk (cancer-associated) HPV infections were identified using univariate and multivariable logistic regression. Results: The mean age of participants (N = 99) was 21.4 years, 30.3% were on antiretroviral therapy, 74.7% were positive for >= 1 HPV DNA type, 53.5% for >1 high-risk type, 12.1% for HPV-16, and 5.1% for HPV-18. Most were HPV DNA negative and seronegative for HPV-16 (55.6%) and HPV-18 (73.7%); 45.5% were HPV DNA negative and seronegative for both HPV-16 and -18. Three variables were associated with high-risk HPV DNA in multivariable analysis: non-Hispanic black versus Hispanic ethnicity (adjusted odds ratio [AOR]: 7.06, 95% CI: 1.63 to 30.5), HIV viral load >= 400 versus <400 copies/mL (AOR: 3.47, 95% CI: 1.28 to 9.43), and frequency of vaginal sex in the past 90 days (AOR: 5.82, 95% CI: 1.30 to 26.11 for >= 6 vs 0 times). Conclusions: The prevalence of >= 1 HPV type was high in these young women, demonstrating the importance of vaccinating before sexual initiation. However, most women were HPV DNA negative and seronegative for high-risk vaccine-type HPV infection, supporting vaccination of sexually experienced HIV-positive young women. C1 [Kahn, Jessica A.] Cincinnati Childrens Hosp Med Ctr, Div Adolescent Med, MLC 4000, Dept Pediat, Cincinnati, OH 45229 USA. [Kahn, Jessica A.] Univ Cincinnati Coll Med, Cincinnati, OH USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Squires, Kathleen E.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA. [Kapogiannis, Bill G.; Worrell, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. [Rudy, Bret] New York Univ Sch Med, Dept Pediat, New York, NY USA. [Xu, Jiahong; Gonin, Rene; Liu, Nancy] WESTAT Corp, Rockville, MD 20850 USA. [Wilson, Craig M.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. RP Kahn, JA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Adolescent Med, MLC 4000, Dept Pediat, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM jessica.kahn@cchmc.org FU Adolescent Trials Network for HIV/AIDS Interventions from the National Institutes of Health (NIH) through the National Institute of Child Health and Human Development [U01 HD 040533, U01 HD 040474]; NIH [AI-51519]; Einstein Cancer Research Center from the National Cancer Institute [P30CA013330]; General Clinical Research Center Program of the National Center for Research Resources, NIH, Department of Health and Human Services; Children's National Medical Center [M01RR020359]; University of Pennsylvania/Children's Hospital of Philadelphia [NCRRUL1-RR-024134]; Louisiana Board of Regents RC/EEP [RC/EEP-06] FX Supported by The Adolescent Trials Network for HIV/AIDS Interventions from the National Institutes of Health (NIH) Grants U01 HD 040533 and U01 HD 040474 through the National Institute of Child Health and Human Development (B. G. Kapogiannis and C. Worrell). Vaccine and HPV Mean Geometric Titers were provided through the Investigator-Initiated Studies Program of Merck & Co, Inc. In addition, R. D. Burk used core facilities of the Einstein-Montefiore Center for AIDS supported by the NIH Grant AI-51519 and the Einstein Cancer Research Center Grant P30CA013330 from the National Cancer Institute. Two of the sites used their General Clinical Research Center/Pediatric Clinical Research Center for the study. The centers were supported by grants from the General Clinical Research Center Program of the National Center for Research Resources, NIH, Department of Health and Human Services as follows: Children's National Medical Center Grant M01RR020359 and University of Pennsylvania/Children's Hospital of Philadelphia Grant NCRRUL1-RR-024134. The site at Tulane University Health Sciences Center used its Clinical and Transnational Research Center for the study; the center was supported in whole or in part by funds provided through the Louisiana Board of Regents RC/EEP (RC/EEP-06). NR 55 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2012 VL 61 IS 3 BP 390 EP 399 DI 10.1097/QAI.0b013e3182676fe3 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 029TR UT WOS:000310519300023 PM 22820809 ER PT J AU Nostramo, R Tillinger, A Saavedra, JM Kumar, A Pandey, V Serova, L Kvetnansky, R Sabban, EL AF Nostramo, Regina Tillinger, Andrej Saavedra, Juan M. Kumar, Ashok Pandey, Varunkumar Serova, Lidia Kvetnansky, Richard Sabban, Esther L. TI Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID PHENYLETHANOLAMINE N-METHYLTRANSFERASE; CATECHOLAMINE BIOSYNTHETIC-ENZYMES; DOPAMINE BETA-HYDROXYLASE; MESSENGER-RNA LEVELS; TYROSINE-HYDROXYLASE; AT(2) RECEPTORS; PC12 CELLS; DIFFERENTIAL REGULATION; CHROMAFFIN CELLS; AT(1) RECEPTORS AB While the renin-angiotensin system is important for adrenomedullary responses to stress, the involvement of specific angiotensin II (Ang II) receptor subtypes is unclear. We examined gene expression changes of angiotensin II type 1A (AT(1A)) and type 2 (AT(2)) receptors in rat adrenal medulla in response to immobilization stress (IMO). AT(2) receptor mRNA levels decreased immediately after a single 2-h IMO. Repeated IMO also decreased AT(2) receptor mRNA levels, but the decline was more transient. AT(1A) receptor mRNA levels were unaltered with either single or repeated IMO, although binding was increased following repeated IMO. These effects of stress on Ang II receptor expression may alter catecholamine biosynthesis, as tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels in PC12 cells are decreased with Ang II treatment in the presence of ZD7155 (AT(1) receptor antagonist) or with CGP42112 (AT(2) receptor agonist) treatment. Involvement of stress-triggered activation of the hypothalamic-pituitary-adrenocortical or sympathoadrenal axis in AT(2) receptor downregulation was examined. Cultured cells treated with the synthetic glucocorticoid dexamethasone displayed a transcriptionally mediated decrease in AT(2) receptor mRNA levels. However, glucocorticoids are not required for the immediate stress-triggered decrease in AT(2) receptor gene expression, as demonstrated in corticotropin-releasing hormone knockout (Crh KO) mice and hypophysectomized rats, although they can regulate basal gene expression. cAMP and pituitary adenylate cyclase-activating polypeptide also reduced AT(2) receptor gene expression and may mediate this response. Overall, the effects of stress on adrenomedullary AT(1A) and AT(2) receptor expression may contribute to allostatic changes, such as regulation of catecholamine biosynthesis. Journal of Endocrinology (2012) 215, 291-301 C1 [Nostramo, Regina; Tillinger, Andrej; Serova, Lidia; Sabban, Esther L.] New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA. [Saavedra, Juan M.] NIMH, Pharmacol Sect, DIRP, NIH, Bethesda, MD 20892 USA. [Kumar, Ashok; Pandey, Varunkumar] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. [Kvetnansky, Richard] Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia. RP Sabban, EL (reprint author), New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA. EM esther_sabban@nymc.edu FU American Heart Association [10GRNT442001, APVV-0088-10]; VEGA [2/0036/11] FX This work was supported by the American Heart Association (grant no. 10GRNT442001) to E L S and grant nos APVV-0088-10 and VEGA 2/0036/11 to R K. NR 55 TC 5 Z9 5 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 2012 VL 215 IS 2 BP 291 EP 301 DI 10.1530/JOE-12-0181 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 025UR UT WOS:000310221200009 PM 22911895 ER PT J AU Sarkar, S Jiang, Z Evon, DM Wahed, AS Hoofnagle, JH AF Sarkar, Souvik Jiang, Zhen Evon, Donna M. Wahed, Abdus S. Hoofnagle, Jay H. TI Fatigue before, during and after antiviral therapy of chronic hepatitis C: Results from the Virahep-C study SO JOURNAL OF HEPATOLOGY LA English DT Article DE Liver; Anti-viral therapy; Tiredness; Cirrhosis; Peginterferon; Ribavirin; Side-effects ID QUALITY-OF-LIFE; GENOTYPE 1 INFECTION; CAUCASIAN AMERICAN PATIENTS; ALPHA-2A PLUS RIBAVIRIN; VISUAL ANALOG SCALES; VIRUS-INFECTION; COMBINATION THERAPY; AFRICAN-AMERICAN; PEGINTERFERON; IMPACT AB Background Si Aims: Fatigue is the most frequent and often debilitating symptom of chronic hepatitis C. It is unclear whether successful therapy of hepatitis C leads to its clinical improvement. In the Virahep-C study, patients with hepatitis C virus (HCV) genotype 1 infection were treated with peginterferon alfa-2a and ribavirin for up to 48 weeks while undergoing assessment of viral kinetics and clinical symptoms. Methods: Fatigue measurements were conducted, before, during and after therapy, as 'presence' (yes/no) and 'severity' (visual analog scale: 0-100 mm). The clinical, histologic, and virologic features that correlated with the presence and degree of fatigue were assessed focusing upon changes associated with sustained virological response (SVR). Results: At baseline, 52% (n = 401) of participants reported having fatigue, which was more common in women than men (59% vs. 48%, p = 0.02) and slightly more severe (30 vs. 22 mm, p = 0.056). Fatigue was frequent and worse in cirrhotics versus those with lesser fibrosis (66% vs. 49%; 34 vs. 24 mm). Fatigue did not correlate with other parameters. The proportion of patients and median fatigue scores increased on treatment (52-78%; 25-40 mm, p <0.0001) with higher fatigue noted amongst those who ultimately achieved SVR (p <0.0001). On achieving SVR, there was a significant decrease in both frequency and severity of fatigue compared to their baseline (53-33%; 27-13 mm, both p <0.0001). Conclusions: Fatigue is common in patients with chronic hepatitis C but is poorly associated with biochemical parameters. Sustained response is accompanied by substantial improvement of fatigue. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Hoofnagle, Jay H.] NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Sarkar, Souvik] NIDDKD, Liver Dis Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Jiang, Zhen; Wahed, Abdus S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Evon, Donna M.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Room 9A27,Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA. EM Hoofnaglej@extra.niddk.nih.gov OI Sarkar, Souvik/0000-0002-9358-4257; Wahed, Abdus/0000-0001-6911-7221 FU Roche/Genentech; NIDDK; Roche Pharmaceutics through Roche; Roche Pharmaceutics through NIDDK; K23 award [Evon: K23-DK089004] FX D.M.E. had grant funding from Roche/Genentech and served as advisor for Vertex in the last 12 months. The other authors have no conflicts of interest to report.; The Virahep-C Study was funded as a cooperative agreement by NIDDK. Peginterferon, ribavirin, HCV RNA detection assays and funds for ancillary studies were provided by Roche Pharmaceutics through a Cooperative Research and Development Agreement (CRADA) between Roche and NIDDK. (See Acknowledgements) NCT Trial Number: NCT00038974. Further support for this study was from the Intramural Program of NIDDK and a K23 award (Evon: K23-DK089004). NR 40 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD NOV PY 2012 VL 57 IS 5 BP 946 EP 952 DI 10.1016/j.jhep.2012.06.030 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 028IW UT WOS:000310417000005 PM 22760009 ER PT J AU Pandiyan, P Yang, XP Saravanamuthu, SS Zheng, LX Ishihara, S O'Shea, JJ Lenardo, MJ AF Pandiyan, Pushpa Yang, Xiang-Ping Saravanamuthu, Senthil S. Zheng, Lixin Ishihara, Satoru O'Shea, John J. Lenardo, Michael J. TI The Role of IL-15 in Activating STAT5 and Fine-Tuning IL-17A Production in CD4 T Lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REMITTING MULTIPLE-SCLEROSIS; HELPER-CELL DIFFERENTIATION; TH17 CELLS; RHEUMATOID-ARTHRITIS; LYMPHOID HOMEOSTASIS; FAMILY CYTOKINES; TRANSGENIC MICE; GROWTH-FACTOR; GM-CSF AB IL-15 is an important IL-2-related cytokine whose role in Th17 cell biology has not been fully elucidated. In this study, we show that exogenous IL-15 decreased IL-17A production in Th17 cultures. Neutralization of IL-15 using an Ab led to increases in IL17A production in Th17 cultures. Both Il15(-/-) and Il15r(-/-) T cell cultures displayed higher frequency of IL-17A producers and higher amounts of IL-17A in the supernatants compared with those of wild-type (WT) cells in vitro. IL-15 down-modulated IL-17A production independently of retinoic acid-related orphan receptor-gamma t, Foxp3, and IFN-gamma expression. Both Th17 cells and APCs produced IL-15, which induced binding of STAT5, an apparent repressor to the Il17 locus in CD4 T cells. Also, in a model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), Il15(-/-) mice displayed exacerbated inflammation-correlating with increased IL-17A production by their CD4(+) T cells-compared with WT controls. Exogenous IL-15 administration and IL-17A neutralization reduced the severity of EAE in Il15(-/-) mice. Taken together, these data indicate that IL-15 has a negative regulatory role in fine-tuning of IL-17A production and Th17-mediated inflammation. The Journal of Immunology, 2012, 189: 4237-4246. C1 [Pandiyan, Pushpa; Zheng, Lixin; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Pandiyan, Pushpa] Case Western Reserve Univ, Sch Dent Med, Dept Biol Sci, Cleveland, OH 44106 USA. [Yang, Xiang-Ping; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Saravanamuthu, Senthil S.] NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Ishihara, Satoru] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11N246, Bethesda, MD 20892 USA. EM pxp226@case.edu; lenardo@nih.gov FU intramural research program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Research Council, National Academy of Sciences FX This work was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. P. P. was partially supported by a fellowship from the National Research Council, National Academy of Sciences. NR 56 TC 25 Z9 26 U1 2 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2012 VL 189 IS 9 BP 4237 EP 4246 DI 10.4049/jimmunol.1201476 PG 10 WC Immunology SC Immunology GA 025OO UT WOS:000310200600009 PM 22993203 ER PT J AU Maloveste, SM Chen, D Gostick, E Vivian, JP Plishka, RJ Iyengar, R Kruthers, RL Buckler-White, A Brooks, AG Rossjohn, J Price, DA Lafont, BAP AF Maloveste, Sebastien M. Chen, Dan Gostick, Emma Vivian, Julian P. Plishka, Ronald J. Iyengar, Ranjini Kruthers, Robin L. Buckler-White, Alicia Brooks, Andrew G. Rossjohn, Jamie Price, David A. Lafont, Bernard A. P. TI Degenerate Recognition of MHC Class I Molecules with Bw4 and Bw6 Motifs by a Killer Cell Ig-like Receptor 3DL Expressed by Macaque NK Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN-LIKE RECEPTOR; SIMIAN IMMUNODEFICIENCY; HLA-B; RHESUS MACAQUES; INHIBITORY RECEPTOR; CYNOMOLGUS MACAQUES; CRYSTAL-STRUCTURE; VIRUS-INFECTION; KIR HAPLOTYPES; COMPLEX AB The killer cell Ig-like receptors (KIRs) expressed on the surface of NK cells recognize specific MHC class I (MHC-I) molecules and regulate NK cell activities against pathogen-infected cells and neoplasia. In HIV infection, survival is linked to host KIR and MHC-I genotypes. In the SIV macaque model, however, the role of NK cells is unclear due to the lack of information on KIR-MHC interactions. In this study, we describe, to our knowledge, the first in-depth characterization of KIR- MHC interactions in pigtailed macaques (Macaca nemestrina). Initially, we identified three distinct subsets of macaque NK cells that stained ex vivo with macaque MHC-I tetramers loaded with SIV peptides. We then cloned cDNAs corresponding to 15 distinct KIR3D alleles. One of these, KIR049-4, was an inhibitory KIR3DL that bound MHC-I tetramers and prevented activation, degranulation, and cytokine production by macaque NK cells after engagement with specific MHC-I molecules on the surface of target cells. Furthermore, KIR049-4 recognized a broad range of MHC-I molecules carrying not only the Bw4 motif, but also Bw6 and non-Bw4/Bw6 motifs. This degenerate, yet peptide-dependent, MHC reactivity differs markedly from the fine specificity of human KIRs. The Journal of Immunology, 2012, 189: 4338-4348. C1 [Maloveste, Sebastien M.; Chen, Dan; Lafont, Bernard A. P.] NIAID, Nonhuman Primate Immunogenet & Cellular Immunol U, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales. [Vivian, Julian P.; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. [Plishka, Ronald J.; Iyengar, Ranjini; Kruthers, Robin L.; Buckler-White, Alicia] NIAID, Lab Mol Microbiol Core, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Brooks, Andrew G.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia. RP Lafont, BAP (reprint author), NIAID, Nonhuman Primate Immunogenet & Cellular Immunol U, Mol Microbiol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. EM blafont@niaid.nih.gov RI Rossjohn, Jamie/F-9032-2013; Lafont, Bernard/B-7236-2014; Price, David/C-7876-2013; OI Rossjohn, Jamie/0000-0002-2020-7522; Price, David/0000-0001-9416-2737; Brooks, Andrew/0000-0002-4085-9683 FU Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Health and Medical Research Council of Australia (NHMRC); Association for International Cancer Research; NHMRC Australia Fellowship FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, the National Health and Medical Research Council of Australia (NHMRC), and the Association for International Cancer Research (J.R. and A.G.B.); J.R. is supported by an NHMRC Australia Fellowship. NR 56 TC 10 Z9 10 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2012 VL 189 IS 9 BP 4338 EP 4348 DI 10.4049/jimmunol.1201360 PG 11 WC Immunology SC Immunology GA 025OO UT WOS:000310200600020 PM 23041569 ER PT J AU Gern, JE Pappas, T Visness, CM Jaffee, KF Lemanske, RF Togias, A Bloomberg, GR Cruikshank, WW Lamm, C Tuzova, M Wood, RA Lee, WM AF Gern, James E. Pappas, Tressa Visness, Cynthia M. Jaffee, Katy F. Lemanske, Robert F. Togias, Alkis Bloomberg, Gordon R. Cruikshank, William W. Lamm, Carin Tuzova, Marina Wood, Robert A. Lee, Wai Ming TI Comparison of the Etiology of Viral Respiratory Illnesses in Inner-City and Suburban Infants SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CHILDHOOD ASTHMA; RHINOVIRUS ILLNESSES; YOUNG-CHILDREN; BIRTH COHORT; VIRUSES; LIFE; INFECTIONS; PATHOGENS; SENSITIZATION; BRONCHIOLITIS AB Background. The risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. Since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct. Methods. We compared the viral etiology of respiratory illnesses in 2 groups: a cohort of 515 infants from 4 inner-city areas and a cohort of 285 infants from mainly suburban Madison, Wisconsin. Nasal secretions were sampled during periods of respiratory illness and at 1 year of age and were analyzed for viral pathogens by multiplex polymerase chain reaction. Results. Overall, inner-city infants had lower rates of viral detection. Considering specific viruses, sick urban infants had lower rates of detectable rhinovirus or respiratory syncytial virus infection and higher rates of adenovirus infection. Every urban site had a higher proportion of adenovirus-positive samples associated with illnesses (10%-21%), compared with Madison (6%). Conclusions. These findings provide evidence that inner-city babies have different patterns of viral respiratory illnesses than babies who grow up in a more suburban location. These findings raise important questions about the etiology of virus-negative illnesses in urban infants and the possibility of long-term consequences of early life infections with adenovirus in this population. C1 [Gern, James E.; Pappas, Tressa; Lemanske, Robert F.; Lee, Wai Ming] Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA. [Gern, James E.; Lemanske, Robert F.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Visness, Cynthia M.; Jaffee, Katy F.] Rho, Chapel Hill, NC USA. [Togias, Alkis] NIAID, NIH, Bethesda, MD 20892 USA. [Bloomberg, Gordon R.] Washington Univ, Sch Med, St Louis, MO USA. [Cruikshank, William W.; Tuzova, Marina] Boston Univ, Med Ctr, Boston, MA 02215 USA. [Lamm, Carin] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Gern, JE (reprint author), K4-918 CSC,600 Highland Ave, Madison, WI 53792 USA. EM gern@medicine.wisc.edu FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) [NO1-AI-25496, NO1-AI-25482]; National Center for Research Resources, NIH [RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, 5UL1RR024992-02]; Merck; Astra Zeneca; GlaxoSmithKline FX This work was supported in whole or in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH; contract numbers NO1-AI-25496 and NO1-AI-25482); and by the National Center for Research Resources, NIH (grants RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, and 5UL1RR024992-02).; J. E. G is a consultant for GlaxoSmithKline, Biota, Centocor, Boehringer Ingelheim, MedImmune, Gilead, Theraclone, Synairgen, and Pulmatrix; has research funding from Merck, Astra Zeneca, and GlaxoSmithKline; and holds stock options in 3V BioSciences. R. A. W is a consultant to the Asthma and Allergy Foundation of America. All other authors report no potential conflicts. NR 26 TC 5 Z9 5 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2012 VL 206 IS 9 BP 1342 EP 1349 DI 10.1093/infdis/jis504 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 022BT UT WOS:000309930700005 PM 23014674 ER PT J AU Lederman, ER Davidson, W Groff, HL Smith, SK Warkentien, T Li, Y Wilkins, KA Karem, KL Akondy, RS Ahmed, R Frace, M Shieh, WJ Zaki, S Hruby, DE Painter, WP Bergman, KL Cohen, JI Damon, IK AF Lederman, Edith R. Davidson, Whitni Groff, Harold L. Smith, Scott K. Warkentien, Tyler Li, Yu Wilkins, Kimberly A. Karem, Kevin L. Akondy, Rama S. Ahmed, Rafi Frace, Michael Shieh, Wun-Ju Zaki, Sherif Hruby, Dennis E. Painter, Wendy P. Bergman, Kimberly L. Cohen, Jeffrey I. Damon, Inger K. TI Progressive Vaccinia: Case Description and Laboratory-Guided Therapy With Vaccinia Immune Globulin, ST-246, and CMX001 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL RESPONSES; SMALLPOX VACCINATION; MONKEYPOX; VIRUS; INFECTION; CHALLENGE; CONTACT; MICE AB Progressive vaccinia (PV) is a rare but potentially lethal complication that develops in smallpox vaccine recipients with severely impaired cellular immunity. We describe a patient with PV who required treatment with vaccinia immune globulin and who received 2 investigational agents, ST-246 and CMX001. We describe the various molecular, pharmacokinetic, and immunologic studies that provided guidance to escalate and then successfully discontinue therapy. Despite development of resistance to ST-246 during treatment, the patient had resolution of PV. This case demonstrates the need for continued development of novel anti-orthopoxvirus pharmaceuticals and the importance of both intensive and timely clinical and laboratory support in management of PV. C1 [Lederman, Edith R.; Davidson, Whitni; Smith, Scott K.; Li, Yu; Wilkins, Kimberly A.; Karem, Kevin L.; Frace, Michael; Shieh, Wun-Ju; Zaki, Sherif; Damon, Inger K.] Ctr Dis Control & Prevent, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA USA. [Warkentien, Tyler; Akondy, Rama S.; Ahmed, Rafi] Emory Univ, Sch Med, Vaccine Ctr, Atlanta, GA USA. [Lederman, Edith R.; Groff, Harold L.] USN, Div Infect Dis, San Diego Med Ctr, San Diego, CA USA. [Hruby, Dennis E.] Siga Technol, Corvallis, OR USA. [Painter, Wendy P.] Chimerix, Durham, NC USA. [Bergman, Kimberly L.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Cohen, Jeffrey I.] Natl Inst Allergy & Immunol, NIH, Bethesda, MD USA. RP Lederman, ER (reprint author), San Diego State Univ, Grad Sch Publ Hlth, Hardy Tower 119,5500 Campanile Dr, San Diego, CA 92182 USA. EM erlederman@yahoo.com OI Akondy, Rama/0000-0003-4737-5240 FU National Institute of Allergy and Infectious Diseases FX This work was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases (to J. I. C.). NR 22 TC 18 Z9 18 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2012 VL 206 IS 9 BP 1372 EP 1385 DI 10.1093/infdis/jis510 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 022BT UT WOS:000309930700009 PM 22904336 ER PT J AU Redd, AD Collinson-Streng, AN Chatziandreou, N Mullis, CE Laeyendecker, O Martens, C Ricklefs, S Kiwanuka, N Nyein, PH Lutalo, T Grabowski, MK Kong, XR Manucci, J Sewankambo, N Wawer, MJ Gray, RH Porcella, SF Fauci, AS Sagar, M Serwadda, D Quinn, TC AF Redd, Andrew D. Collinson-Streng, Aleisha N. Chatziandreou, Nikolaos Mullis, Caroline E. Laeyendecker, Oliver Martens, Craig Ricklefs, Stacy Kiwanuka, Noah Nyein, Phyu Hninn Lutalo, Tom Grabowski, Mary K. Kong, Xiangrong Manucci, Jordyn Sewankambo, Nelson Wawer, Maria J. Gray, Ronald H. Porcella, Stephen F. Fauci, Anthony S. Sagar, Manish Serwadda, David Quinn, Thomas C. TI Previously Transmitted HIV-1 Strains Are Preferentially Selected During Subsequent Sexual Transmissions SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENETIC DIVERSITY; HETEROSEXUAL TRANSMISSION; INFECTION; VARIANTS; UGANDA; RAKAI; IDENTIFICATION; SUBTYPES; COUPLES AB Background. A genetic bottleneck is known to exist for human immunodeficiency virus (HIV) at the point of sexual transmission. However, the nature of this bottleneck and its effect on viral diversity over time is unclear. Methods. Interhost and intrahost HIV diversity was analyzed in a stable population in Rakai, Uganda, from 1994 to 2002. HIV-1 envelope sequences from both individuals in initially HIV-discordant relationships in which transmission occurred later were examined using Sanger sequencing of bulk polymerase chain reaction (PCR) products (for 22 couples), clonal analysis (for 3), and next-generation deep sequencing (for 9). Results. Intrahost viral diversity was significantly higher than changes in interhost diversity (P < .01). The majority of HIV-1-discordant couples examined via bulk PCR (16 of 22 couples), clonal analysis (3 of 3), and next-generation deep sequencing (6 of 9) demonstrated that the viral populations present in the newly infected recipient were more closely related to the donor partner's HIV-1 variants found earlier during infection as compared to those circulating near the estimated time of transmission (P = .03). Conclusions. These findings suggest that sexual transmission constrains viral diversity at the population level, partially because of the preferential transmission of ancestral as opposed to contemporary strains circulating in the transmitting partner. Future successful vaccine strategies may need to target these transmitted ancestral strains. C1 [Redd, Andrew D.; Collinson-Streng, Aleisha N.; Laeyendecker, Oliver; Fauci, Anthony S.; Quinn, Thomas C.] NIAID, Lab Immunoregulat, DIR, NIH, Bethesda, MD 20892 USA. [Mullis, Caroline E.; Laeyendecker, Oliver; Manucci, Jordyn; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Grabowski, Mary K.; Kong, Xiangrong; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Chatziandreou, Nikolaos; Nyein, Phyu Hninn; Sagar, Manish] Harvard Univ, Sch Med, Brigham & Women Hosp, Boston, MA 02115 USA. [Martens, Craig; Ricklefs, Stacy; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,DIR,NIH, Hamilton, MT USA. [Kiwanuka, Noah; Lutalo, Tom; Sewankambo, Nelson; Serwadda, David] Rakai Hlth Sci Program, Entebbe, Uganda. [Lutalo, Tom] Uganda Virus Res Inst, Entebbe, Uganda. [Sewankambo, Nelson] Makerere Univ, Coll Hlth Sci, Kampala, Uganda. [Kiwanuka, Noah; Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. RP Quinn, TC (reprint author), NIAID, Rangos Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21205 USA. EM tquinn2@jhmi.edu RI Laeyendecker, Oliver/B-9331-2009; OI Sagar, Manish/0000-0001-9803-6594; Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker, Oliver/0000-0002-6429-4760 FU Division of Intramural Research, National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health; NIAID [R01 A134826, R01 A134265, R01 AI077473]; Eunice Kennedy Shriver National Institute of Child Health & Human Development [5P30HD06826]; World Bank STI Project, Uganda; Henry M. Jackson Foundation; Fogarty Foundation [5D43TW00010]; Bill and Melinda Gates Institute for Population and Reproductive Health at the Bloomberg School of Public Health, Johns Hopkins University FX This work was supported in part by funding from the Division of Intramural Research, National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health; the NIAID (grants R01 A134826, R01 A134265 and R01 AI077473 to M. S.); the Eunice Kennedy Shriver National Institute of Child Health & Human Development (grant 5P30HD06826); the World Bank STI Project, Uganda; the Henry M. Jackson Foundation; the Fogarty Foundation (grant 5D43TW00010); and the Bill and Melinda Gates Institute for Population and Reproductive Health at the Bloomberg School of Public Health, Johns Hopkins University. NR 39 TC 35 Z9 36 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2012 VL 206 IS 9 BP 1433 EP 1442 DI 10.1093/infdis/jis503 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 022BT UT WOS:000309930700016 PM 22997233 ER PT J AU Gandhi, M Greenblatt, RM Bacchetti, P Jin, CS Huang, Y Anastos, K Cohen, M DeHovitz, JA Sharp, GB Gange, SJ Liu, CL Hanson, SC Aouizerat, B AF Gandhi, Monica Greenblatt, Ruth M. Bacchetti, Peter Jin, Chengshi Huang, Yong Anastos, Kathryn Cohen, Mardge DeHovitz, Jack A. Sharp, Gerald B. Gange, Stephen J. Liu, Chenglong Hanson, Susan C. Aouizerat, Bradley CA Women's Interagency HIV Study TI A Single-Nucleotide Polymorphism in CYP2B6 Leads to > 3-Fold Increases in Efavirenz Concentrations in Plasma and Hair Among HIV-Infected Women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NONNUCLEOSIDE REVERSE-TRANSCRIPTASE; TANDEM MASS-SPECTROMETRY; ROUTINE CLINICAL-PRACTICE; HIV-1-INFECTED INDIVIDUALS; LIQUID-CHROMATOGRAPHY; CONTAINING REGIMENS; POPULATION PHARMACOKINETICS; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; UNSELECTED COHORT AB Background. Efavirenz exhibits marked interindividual variability in plasma levels and toxicities. Prior pharmacogenetic studies usually measure exposure via single plasma levels, examine limited numbers of polymorphisms, and rarely model multiple contributors. We analyzed numerous genetic and nongenetic factors impacting short-term and long-term exposure in a large heterogeneous population of human immunodeficiency virus (HIV)-infected women. Methods. We performed 24-hour intensive pharmacokinetic studies in 111 women receiving efavirenz under actual-use conditions and calculated the area-under-the-concentration-time curve (AUC) to assess short-term exposure; the efavirenz concentration in hair was measured to estimate long-term exposure. A total of 182 single-nucleotide polymorphisms (SNPs) and 45 haplotypes in 9 genes were analyzed in relationship to exposure by use of multivariate models that included a number of nongenetic factors. Results. Efavirenz AUCs increased 1.26-fold per doubling of the alanine aminotransferase level and 1.23-fold with orange and/or orange juice consumption. Individuals with the CYP2B6 516TT genotype displayed 3.5-fold increases in AUCs and 3.2-fold increases in hair concentrations, compared with individuals with the TG/GG genotype. Another SNP in CYP2B6 (983TT) and a p-glycoprotein haplotype affected AUCs without substantially altering long-term exposure. Conclusions. This comprehensive pharmacogenomics study showed that individuals with the CYP2B6 516TT genotype displayed >3-fold increases in both short-term and long-term efavirenz exposure, signifying durable effects. Pharmacogenetic testing combined with monitoring of hair levels may improve efavirenz outcomes and reduce toxicities. C1 [Gandhi, Monica] Univ Calif San Francisco, Div HIV AIDS, Dept Med, San Francisco, CA 94122 USA. [Greenblatt, Ruth M.; Huang, Yong] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94122 USA. [Greenblatt, Ruth M.; Bacchetti, Peter; Jin, Chengshi] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94122 USA. [Anastos, Kathryn] Albert Einstein Univ, Dept Med, Bronx, NY USA. [DeHovitz, Jack A.] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. [Cohen, Mardge] Rush Univ, Dept Med, Chicago, IL 60612 USA. [Sharp, Gerald B.] NIAID, NIH, Bethesda, MD 20892 USA. [Gange, Stephen J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Liu, Chenglong] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Hanson, Susan C.; Aouizerat, Bradley] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94122 USA. [Aouizerat, Bradley] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94122 USA. RP Gandhi, M (reprint author), Univ Calif San Francisco, Div HIV AIDS, Dept Med, 405 Irving St,2nd Fl, San Francisco, CA 94122 USA. EM monica.gandhi@ucsf.edu OI Gange, Stephen/0000-0001-7842-512X FU National Institute of Allergy and Infectious Diseases (NIAID) [K23 A1067065, R01 AI 65233, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Center for Research Resources via the University of California San Francisco Clinical and Translational Science Institute [UL1 RR024131]; NIH Roadmap for Medical Research [KL2 RR024130]; 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 and Other Communication Disorders FX This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID; K23 A1067065 to M. G. and R01 AI 65233 to R. M. G.). Additional funding was also provided by the National Center for Research Resources via the University of California San Francisco Clinical and Translational Science Institute (UL1 RR024131) and by the NIH Roadmap for Medical Research (KL2 RR024130 to B. A.).; The WIHS is funded by the NIAID (UO1-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 cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. NR 48 TC 18 Z9 20 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2012 VL 206 IS 9 BP 1453 EP 1461 DI 10.1093/infdis/jis508 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 022BT UT WOS:000309930700018 PM 22927450 ER PT J AU Venkatesh, BA Lima, JAC Bluemke, DA Lai, SH Steenbergen, C Liu, CY AF Venkatesh, Bharath Ambale Lima, Joao A. C. Bluemke, David A. Lai, Shenghan Steenbergen, Charles Liu, Chia-Ying TI MR proton spectroscopy for myocardial lipid deposition quantification: A quantitative comparison between 1.5T and 3T SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE myocardial fat; proton spectroscopy; fat fraction ID MAGNETIC-RESONANCE-SPECTROSCOPY; TO-NOISE RATIO; FREQUENCY-DOMAIN METHODS; TRIGLYCERIDE CONTENT; FAT QUANTIFICATION; DIABETES-MELLITUS; HUMAN BRAIN; REPRODUCIBILITY; RESOLUTION; STEATOSIS AB Purpose: To evaluate 3T magnetic resonance spectroscopy (MRS)-derived myocardial fat-signal fractions in comparison with those from 1.5T MRS. Materials and Methods: We conducted phantom, ex vivo and in vivo myocardial specimen evaluations at both 1.5T and 3T using 1H-MRS. A phantom with nine fat-water emulsions was constructed to assess the accuracy of the spectroscopy measurements. Ex vivo spectroscopy data were acquired in 70 segments from 21 autopsy heart slices. In vivo spectroscopy data were acquired in the interventricular septum from 22 human volunteers. Results: Phantom experiments demonstrated that 1.5T and 3T measurements were highly correlated with the reference values (r = 0.78, P < 0.05). The ex vivo and in vivo experiments demonstrated an increase in signal-to-noise ratio (SNR) of 45 +/- 73% and 76 +/- 72% at 3T compared to 1.5T (P < 0.05). The mean fat-signal fraction was similar at 3T and 1.5T (1.11 +/- 1.18 vs. 1.00 +/- 1.09, respectively, P = NS) in ex vivo studies but were significantly different in the in vivo studies (2.47 +/- 1.46 vs. 1.56 +/- 1.34, P < 0.05). The fat-signal fractions from 3T and 1.5T correlated fairly well in all experiments. Conclusion: 3T MRS has significantly greater SNR and could potentially be more accurate as compared to 1.5T for quantification of myocardial fat fraction in in vivo studies. J. Magn. Reson. Imaging 2012;36:12221230. (c) 2012 Wiley Periodicals, Inc. C1 [Venkatesh, Bharath Ambale; Lima, Joao A. C.; Bluemke, David A.; Liu, Chia-Ying] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. [Lai, Shenghan; Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Liu, CY (reprint author), Johns Hopkins Univ Hosp, Dept Radiol, MRI Room 110,600 N Wolfe St, Baltimore, MD 21287 USA. EM Cliu51@jhmi.edu RI Ambale Venkatesh, Bharath/F-4941-2016; OI Ambale Venkatesh, Bharath/0000-0002-2330-2373; Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health (NIH) [R21HL098827] FX Contract grant sponsor: National Institutes of Health (NIH); Contract grant number: R21HL098827. NR 33 TC 11 Z9 11 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2012 VL 36 IS 5 BP 1222 EP 1230 DI 10.1002/jmri.23761 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 027ZO UT WOS:000310392800024 PM 22826193 ER PT J AU Fernandez-Duenas, V Gomez-Soler, M Jacobson, KA Kumar, ST Fuxe, K Borroto-Escuela, DO Ciruela, F AF Fernandez-Duenas, Victor Gomez-Soler, Maricel Jacobson, Kenneth A. Kumar, Santhosh T. Fuxe, Kjell Borroto-Escuela, Dasiel O. Ciruela, Francisco TI Molecular determinants of A2AR-D2R allosterism: role of the intracellular loop 3 of the D2R SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE A2AR; D2R; FRET; oligomerization; allosterism; fluorescent agonist ID ADENOSINE A(2A) RECEPTORS; GLUTAMATE TYPE-1-ALPHA RECEPTOR; HAMSTER OVARY CELLS; DOPAMINE-D-2 RECEPTORS; ELECTROSTATIC INTERACTION; BASAL GANGLIA; LIVING CELLS; AGONIST; HETEROMERIZATION; INTERNALIZATION AB In the CNS, an antagonistic interaction has been shown between adenosine A2A and dopamine D2 receptors (A2ARs and D2Rs) that may be relevant both in normal and pathological conditions (i.e., Parkinson's disease). Thus, the molecular determinants mediating this receptorreceptor interaction have recently been explored, as the fine tuning of this target (namely the A2AR/D2R oligomer) could possibly improve the treatment of certain CNS diseases. Here, we used a fluorescence resonance energy transfer-based approach to examine the allosteric modulation of the D2R within the A2AR/D2R oligomer and the dependence of this receptorreceptor interaction on two regions rich in positive charges on intracellular loop 3 of the D2R. Interestingly, we observed a negative allosteric effect of the D2R agonist quinpirole on A2AR ligand binding and activation. However, these allosteric effects were abolished upon mutation of specific arginine residues (217222 and 267269) on intracellular loop 3 of the D2R, thus demonstrating a major role of these positively charged residues in mediating the observed receptorreceptor interaction. Overall, these results provide structural insights to better understand the functioning of the A2AR/D2R oligomer in living cells. C1 [Fernandez-Duenas, Victor; Gomez-Soler, Maricel; Ciruela, Francisco] Univ Barcelona, Unitat Farmacol, Fac Med, Dept Patol & Terapeut Expt, Barcelona 08907, Spain. [Jacobson, Kenneth A.; Kumar, Santhosh T.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Fuxe, Kjell; Borroto-Escuela, Dasiel O.] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Ciruela, F (reprint author), Univ Barcelona, Unitat Farmacol, Fac Med, Dept Patol & Terapeut Expt, Barcelona 08907, Spain. EM fciruela@ub.edu RI Jacobson, Kenneth/A-1530-2009; Borroto-Escuela, Dasiel/F-3627-2014; Ciruela, Francisco/A-5096-2013 OI Fernandez Duenas, Victor/0000-0001-7834-2965; Jacobson, Kenneth/0000-0001-8104-1493; Borroto-Escuela, Dasiel/0000-0002-5736-373X; Ciruela, Francisco/0000-0003-0832-3739 FU Ministerio de Ciencia e Innovacion [SAF2011-24779, CSD2008-00005]; ICREA Academia from the Catalan Institution for Research and Advanced Studies; NIDDK Intramural Research Program of the National Institutes of Health, Bethesda, MD, USA FX This work was supported by grants SAF2011-24779 and Consolider-Ingenio CSD2008-00005 from Ministerio de Ciencia e Innovacion and ICREA Academia-2010 from the Catalan Institution for Research and Advanced Studies to FC. Also, VF-D, MG-S, and FC belong to the "Neuropharmacology and Pain" accredited research group (Generalitat de Catalunya, 2009 SGR 232). Support to KAJ and TSK from the NIDDK Intramural Research Program of the National Institutes of Health, Bethesda, MD, USA is acknowledged. We also thank Esther Castano, Eva Julia, and Benjamin Torrejon, from the Scientific and Technical Services (SCT)-Bellvitge Campus of the University of Barcelona for the technical assistance. NR 31 TC 19 Z9 19 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2012 VL 123 IS 3 BP 373 EP 384 DI 10.1111/j.1471-4159.2012.07956.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 019MJ UT WOS:000309743600006 PM 22924752 ER PT J AU Ye, DY Bakhtian, KD Asthagiri, AR Lonser, RR AF Ye, Donald Y. Bakhtian, Kamran D. Asthagiri, Ashok R. Lonser, Russell R. TI Von Hippel-Lindau disease and pregnancy Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material ID CEREBELLAR HEMANGIOBLASTOMA C1 [Ye, Donald Y.; Bakhtian, Kamran D.; Asthagiri, Ashok R.; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Ye, DY (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2012 VL 117 IS 5 BP 816 EP 817 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 027UW UT WOS:000310380300005 ER PT J AU Ye, DY Bakhtian, KD Asthagiri, AR Lonser, RR AF Ye, Donald Y. Bakhtian, Kamran D. Asthagiri, Ashok R. Lonser, Russell R. TI Effect of pregnancy on hemangioblastoma development and progression in von Hippel-Lindau disease Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE hemangioblastoma; pregnancy; von Hippel-Lindau disease; tumor growth; oncology ID CENTRAL-NERVOUS-SYSTEM; CEREBELLAR HEMANGIOBLASTOMA; SURGICAL-MANAGEMENT; NATURAL-HISTORY AB Object. Prior cases suggest that pregnancy increases the development and progression of CNS hemangioblastomas and/or peritumoral cysts. To determine the effect of pregnancy on CNS hemangioblastomas and peritumoral cysts, the authors prospectively evaluated serial clinical and imaging findings in patients with von Hippel-Lindau (VHL) disease who became pregnant and compared findings during pregnancy to findings in the same patients when they were not pregnant as well as to findings from a cohort of VHL patients who did not become pregnant. Methods. Female VHL disease patients enrolled in a prospective natural history study who were of reproductive age (16-35 years at study entrance) were included. Analysis of serial clinical and imaging findings was performed. Results. Thirty-six consecutive female VHL disease patients harboring 177 hemangioblastomas were included (mean follow-up [+/- SD] 7.5 +/- 2.3 years). Nine patients (25%) became pregnant (pregnancy cohort). The mean rates of development of new hemangioblastomas and peritumoral cysts in these women during pregnancy (0.4 +/- 0.4 tumors/year; 0.1 +/- 0.2 cysts/year) did not differ significantly (p > 0.05) from the mean rates in the same group during nonpregnant periods (0.3 +/- 0.4 tumors/year: 0.1 +/- -0.1 cysts/year) or from the rate in the 27 patients who did not become pregnant (the no-pregnancy cohort: 0.3 +/- 0.5 tumors/year; 0.1 0.2 cysts/year). Hemangioblastoma growth rates were similar (p > 0.05) during pregnancy (mean 29.8% +/- 42.7% increase in volume per year) compared with during nonpregnant periods (41.4% +/- 51.4%) in the pregnancy cohort and the no-pregnancy cohort (34.3% +/- 55.3%). Peritumoral cyst growth rates during pregnancy (571.0% +/- 887.4%) were similar (p > 0.05) to those of the no-pregnancy cohort (483.9% +/- 493.9%), but the rates were significantly higher for women in the pregnancy cohort during nonpregnant periods (2373.6% +/- 3392.9%; p < 0.05 for comparison with no-pregnancy cohort). There was no significant difference (p > 0.05) in the need for resection or the mean age at resection between the pregnancy (28% of hemangioblastomas in cohort; mean patient age at resection 30.2 +/- 2.6 years) and no-pregnancy cohorts (19%; 32.3 +/- 5.6 years). Conclusions. Pregnancy is not associated with increased hemangioblastoma or peritumoral cyst development or progression in patients with VHL disease. (http://thejns.org/doi/abs/10.3171/2012.7.JNS12367) C1 [Ye, Donald Y.; Bakhtian, Kamran D.; Asthagiri, Ashok R.; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3D20, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke at the National Institutes of Health FX This research was supported by the intramural program at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. NR 27 TC 12 Z9 12 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2012 VL 117 IS 5 BP 818 EP 824 DI 10.3171/2012.7.JNS12367 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 027UW UT WOS:000310380300006 PM 22937928 ER PT J AU Heiss, JD Suffredini, G Bakhtian, KD Sarntinoranont, M Oldfield, EH AF Heiss, John D. Suffredini, Giancarlo Bakhtian, Kamran D. Sarntinoranont, Malisa Oldfield, Edward H. TI Normalization of hindbrain morphology after decompression of Chiari malformation Type I Clinical article SO JOURNAL OF NEUROSURGERY LA English DT Article DE Chiari malformation Type I; syringomyelia; decompression; magnetic resonance imaging; surgical ID CEREBELLAR TONSILS; SYRINGOMYELIA; PATHOPHYSIOLOGY AB Object. Chiari malformation Type I (CM-I) is characterized by hindbrain deformity. We investigated the effects of craniocervical decompression surgery on the anatomical features of hindbrain deformity with a prospective MRI study of patients with CM-I. Methods. A prospective longitudinal study was conducted in 48 patients with CM-I (39 with syringomyelia) treated with craniocervical decompression. Clinical examinations and cervical MRI were performed before surgery and 1 week, 3-6 months, and annually after surgery. Hindbrain deformity was defined by tonsillar ectopia, pointed cerebellar tonsils, and/or cervicomedullary protuberance. The length of the clivus, basiocciput (sphenooccipital synchondrosis to basion), supraocciput (internal occipital protuberance to opisthion), and anteroposterior (AP) width of CSF pathways at the foramen magnum were measured and compared with those from 18 healthy volunteers (control group). Results. Before surgery, the patients' posterior fossa bones were short and their CSF pathways were narrow. All patients had tonsillar ectopia (mean [+/-SD] 12.3 +/- 5.1 mm; normal 0.3 +/- 1.0). The majority of patients had pointed tonsils and more than two-thirds exhibited a cervicomedullary protuberance. Clivus and basiocciput lengths were significantly shorter than the values obtained in the control group. However, the supraocciput length did not differ significantly from control measurements. The mean bulbopontine sulcus distance superior to the basion was 9.5 +/- 2.6 mm (vs 13.6 +/- 2.8 mm in controls; p < 0.0001). The AP widths of the CSF pathways at the level of the foramen magnum were significantly narrowed. After surgery, CSF pathways significantly expanded both ventrally and dorsally. By 3-6 months after surgery, pointed tonsils became round, cervicomedullary protuberance disappeared, and tonsillar ectopia diminished by 51% (to 6.0 +/- 3.3 mm; p < 0.0001). Conclusions. The cerebellar tonsils and brainstem assumed a normal appearance within 6 months after craniocervical decompression. These findings support the concept that the CM-I is not a congenital malformation of the neural elements but rather an acquired malformation that arises from pulsatile impaction of the cerebellar tonsils into the foramen magnum. Clinical trial registration no.: NCT00001327. (http://thejns.org/doi/abs/10.3171/2012.8.JNS111476) C1 [Heiss, John D.; Suffredini, Giancarlo; Bakhtian, Kamran D.; Oldfield, Edward H.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Sarntinoranont, Malisa] Univ Florida, Soft Tissue Mech & Drug Delivery Lab, Gainesville, FL USA. [Oldfield, Edward H.] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA. RP Heiss, JD (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 10 Ctr Dr,10-3D20,MSC-1414, Bethesda, MD 20892 USA. EM heissj@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke at the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. NR 8 TC 14 Z9 15 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2012 VL 117 IS 5 BP 942 EP 946 DI 10.3171/2012.8.JNS111476 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 027UW UT WOS:000310380300029 PM 22978540 ER PT J AU Heiss, JD Snyder, K Peterson, MM Patronas, NJ Butman, JA Smith, RK DeVroom, HL Sansur, CA Eskioglu, E Kammerer, WA Oldfield, EH AF Heiss, John D. Snyder, Kendall Peterson, Matthew M. Patronas, Nicholas J. Butman, John A. Smith, Rene K. DeVroom, Hetty L. Sansur, Charles A. Eskioglu, Eric Kammerer, William A. Oldfield, Edward H. TI Pathophysiology of primary spinal syringomyelia Clinical article SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE syringomyelia; physiology; ultrasonography; surgery; cerebrospinal fluid; magnetic resonance imaging; myelography ID CEREBROSPINAL-FLUID FLOW; CT METRIZAMIDE MYELOGRAPHY; CHIARI I MALFORMATION; POSTTRAUMATIC SYRINGOMYELIA; THECOPERITONEAL SHUNT; CORD-INJURY; IDIOPATHIC SYRINGOMYELIA; CERVICAL SPONDYLOSIS; CRITICAL-APPRAISAL; ARACHNOID CYST AB Object. The pathogenesis of syringomyelia in patients with an associated spinal lesion is incompletely understood. The authors hypothesized that in primary spinal syringomyelia, a subarachnoid block effectively shortens the length of the spinal subarachnoid space (SAS), reducing compliance and the ability of the spinal theca to dampen the subarachnoid CSF pressure waves produced by brain expansion during cardiac systole. This creates exaggerated spinal subarachnoid pressure waves during every heartbeat that act on the spinal cord above the block to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed, enlarged subarachnoid pressure waves compress the external surface of the spinal cord, propel the syrinx fluid, and promote syrinx progression. Methods. To elucidate the pathophysiology, the authors prospectively studied 36 adult patients with spinal lesions obstructing the spinal SAS. Testing before surgery included clinical examination; evaluation of anatomy on T1-weighted MRI; measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest, during Valsalva maneuver, during jugular compression, and after removal of CSF (CSF compliance measurement); and evaluation with CT myelography. During surgery, pressure measurements from the SAS above the level of the lesion and the lumbar intrathecal space below the lesion were obtained, and cardiac-gated ultrasonography was performed. One week after surgery, CT myelography was repeated. Three months after surgery, clinical examination, T1-weighted MRI, and CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination and MRI studies were repeated annually thereafter. Findings in patients were compared with those obtained in a group of 18 healthy individuals who had already undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid pressure testing. Results. In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure was increased (2.7 +/- 1.2 vs 1.6 +/- 0.6 mm Hg, respectively; p = 0.004), pressure transmission to the theca] sac below the block was reduced, and spinal CSF compliance was decreased. Intraoperative ultrasonography confirmed that pulse pressure waves compressed the outer surface of the spinal cord superior to regions of obstruction of the subarachnoid space. Conclusions. These findings are consistent with the theory that a spinal subarachnoid block increases spinal subarachnoid pulse pressure above the block, producing a pressure differential across the obstructed segment of the SAS, which results in syrinx formation and progression. These findings are similar to the results of the authors' previous studies that examined the pathophysiology of syringomyelia associated with obstruction of the SAS at the foramen magnum in the Chiari Type I malformation and indicate that a common mechanism, rather than different, separate mechanisms, underlies syrinx formation in these two entities. Clinical trial registration no.: NCT00011245. (http://thejns.org/doi/abs/10.3171/2012.8.SPINE111059) C1 [Heiss, John D.; Smith, Rene K.; DeVroom, Hetty L.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Kammerer, William A.] NIH, Dept Anesthesia, Bethesda, MD 20892 USA. [Snyder, Kendall] George Washington Univ, Sch Med, Washington, DC USA. [Peterson, Matthew M.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Sansur, Charles A.] Univ Maryland, Dept Neurosurg, Baltimore, MD 21201 USA. [Eskioglu, Eric] Phys Reg Healthcare Syst, NeuroVasc & Stroke Inst, Naples, Italy. [Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA. RP Heiss, JD (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,l0-5D37,MSC-1414, Bethesda, MD 20892 USA. EM heissj@ninds.nih.gov RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU Intramural Research Program of the NINDS at the NIH FX This research was supported by the Intramural Research Program of the NINDS at the NIH. NR 75 TC 32 Z9 32 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD NOV PY 2012 VL 17 IS 5 BP 367 EP 380 DI 10.3171/2012.8.SPINE111059 PG 14 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 027VD UT WOS:000310381100001 PM 22958075 ER PT J AU Bennett, NJ Tabarani, CM Bartholoma, NM Wang, DL Huang, DN Riddell, SW Kiska, DL Hingre, R Rosenberg, HF Domachowske, JB AF Bennett, Nicholas J. Tabarani, Christy M. Bartholoma, Nadine M. Wang, Dongliang Huang, Danning Riddell, Scott W. Kiska, Deanna L. Hingre, Robert Rosenberg, Helene F. Domachowske, Joseph B. TI Unrecognized Viral Respiratory Tract Infections in Premature Infants during their Birth Hospitalization: A Prospective Surveillance Study in Two Neonatal Intensive Care Units SO JOURNAL OF PEDIATRICS LA English DT Article ID SYNCYTIAL VIRUS; BRONCHOPULMONARY DYSPLASIA; PRETERM INFANTS; OUTBREAK; EPIDEMIOLOGY; CYTOKINES; NURSERY AB Objective To determine the frequency and effects of nosocomial respiratory viral infections (RVIs) in premature neonates, including those who may be asymptomatic. Study design We performed a year-long surveillance for RVIs in infants < 33 weeks gestational age admitted to 2 Syracuse neonatal intensive care units. Infants were enrolled within 3 days of neonatal intensive care unit admission and were sampled for RVIs until discharge using a multiplex polymerase chain reaction assay capable of detecting 17 different respiratory viruses or subtypes. Results Twenty-six of 50 prematurely born infants (52%) tested positive for a respiratory virus at least once during their birth hospitalization. Testing positive for a respiratory virus was significantly associated with longer length of stay (70 days vs 35 days, P = .002) and prolonged ventilatory support (51 vs 13 days, P = .002). Infants who tested positive for a respiratory virus during their birth hospitalization had more than twice the rate of developing bronchopulmonary dysplasia (P < .05). Conclusion Nosocomial RVIs were frequent in our study population, despite the absence of clinical indicators of illness. Length of hospital stay was significantly longer and a diagnosis of bronchopulmonary dysplasia was more common in infants who had respiratory viruses detected. (J Pediatr 2012;161:814-8). C1 [Bartholoma, Nadine M.; Riddell, Scott W.; Kiska, Deanna L.] Upstate Golisano Childrens Hosp, Dept Clin Pathol, Syracuse, NY USA. [Bennett, Nicholas J.; Tabarani, Christy M.; Hingre, Robert; Domachowske, Joseph B.] Upstate Golisano Childrens Hosp, Dept Pediat, Syracuse, NY USA. [Wang, Dongliang] SUNY Upstate Med Univ, Dept Publ Hlth & Prevent Med, Syracuse, NY USA. [Huang, Danning] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA. [Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Bennett, NJ (reprint author), CT Childrens Med Ctr, Div Infect Dis, 282 Washington St, Hartford, CT 06106 USA. EM njb35@cantab.net FU Children's Miracle Network of New York; National Institute of Allergy and Infectious Diseases, Division of Intramural Research [Z01-AI000943] FX Funded by the Children's Miracle Network of New York (to J.D. and N.B.) and the National Institute of Allergy and Infectious Diseases, Division of Intramural Research (Z01-AI000943 to H.R.). The authors declare no conflicts of interest. NR 15 TC 20 Z9 23 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2012 VL 161 IS 5 BP 814 EP + DI 10.1016/j.jpeds.2012.05.001 PG 8 WC Pediatrics SC Pediatrics GA 027RJ UT WOS:000310370600012 PM 22694859 ER PT J AU Bailey, RL Fulgoni, VL Keast, DR Lentino, CV Dwyer, JT AF Bailey, Regan L. Fulgoni, Victor L., III Keast, Debra R. Lentino, Cindy V. Dwyer, Johanna T. TI Do Dietary Supplements Improve Micronutrient Sufficiency in Children and Adolescents? SO JOURNAL OF PEDIATRICS LA English DT Article ID MULTIVITAMIN-MULTIMINERAL SUPPLEMENTS; NUTRIENT INTAKE; ADULTS; NONUSERS; USERS; NUTRITION; MINERALS; ENERGY; HEALTH AB Objective To examine if children use supplements to fill gaps in nutritionally inadequate diets or whether supplements contribute to already adequate or excessive micronutrient intakes from foods. Study design Data were analyzed for children (2-18 years) from the National Health and Nutrition Examination Survey 2003-2006, a nationally representative, cross-sectional survey (n = 7250). Diet was assessed using two 24-hour recalls, and dietary supplement use was assessed with a 30-day questionnaire. Results Prevalence of supplements use was 21% (<2 years) and 42% (2-8 years). Supplement users had higher micronutrient intakes than nonusers. Calcium and vitamin D intakes were low for all children. Inadequate intakes of phosphorus, copper, selenium, folate, and vitamins B-6 and B-12 were minimal from foods alone among 2-8 year olds. However, among 9-18 year olds, a higher prevalence of inadequate intakes of magnesium, phosphorus, and vitamins A, C, and E were observed. Supplement use increased the likelihood of intakes above the upper tolerable intake level for iron, zinc, copper, selenium, folic acid, and vitamins A and C. Conclusions Even with the use of supplements, more than a one-third of children failed to meet calcium and vitamin D recommendations. Children 2-8 years old had nutritionally adequate diets regardless of supplement use. However, in children older than 8 years, dietary supplements added micronutrients to diets that would have otherwise been inadequate for magnesium, phosphorus, vitamins A, C, and E. Supplement use contributed to the potential for excess intakes of some nutrients. These findings may have implications for reformulating dietary supplements for children. (J Pediatr 2012;161:837-42). C1 [Bailey, Regan L.; Lentino, Cindy V.; Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Fulgoni, Victor L., III] Nutr Impact LLC, Battle Creek, MI USA. [Keast, Debra R.] Food & Nutr Database Res Inc, Okemos, MI USA. [Dwyer, Johanna T.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Dwyer, Johanna T.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Dwyer, Johanna T.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. RP Bailey, RL (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Rm 3B01, Bethesda, MD 20892 USA. EM baileyr@mail.nih.gov OI Dwyer, Johanna/0000-0002-0783-1769 FU United States Department of Agriculture Research Service [58-1950-7-707]; Office of Dietary Supplements at the National Institutes of Health; Fortification Committee of the International Life Sciences Institute, North American Branch FX Supported in part by the United States Department of Agriculture Research Service (agreement 58-1950-7-707) and the Office of Dietary Supplements at the National Institutes of Health. Data generation was funded by the Fortification Committee of the International Life Sciences Institute, North American Branch. The authors declare no conflicts of interest. NR 29 TC 26 Z9 26 U1 1 U2 30 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2012 VL 161 IS 5 BP 837 EP + DI 10.1016/j.jpeds.2012.05.009 PG 9 WC Pediatrics SC Pediatrics GA 027RJ UT WOS:000310370600016 PM 22717218 ER PT J AU Freimuth, RR Freund, ET Schick, L Sharma, MK Stafford, GA Suzek, BE Hernandez, J Hipp, J Kelley, JM Rokicki, K Pan, S Buckler, A Stokes, TH Fernandez, A Fore, I Buetow, KH Klemm, JD AF Freimuth, Robert R. Freund, Elaine T. Schick, Lisa Sharma, Mukesh K. Stafford, Grace A. Suzek, Baris E. Hernandez, Joyce Hipp, Jason Kelley, Jenny M. Rokicki, Konrad Pan, Sue Buckler, Andrew Stokes, Todd H. Fernandez, Anna Fore, Ian Buetow, Kenneth H. Klemm, Juli D. TI Life sciences domain analysis model SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB Objective Meaningful exchange of information is a fundamental challenge in collaborative biomedical research. To help address this, the authors developed the Life Sciences Domain Analysis Model (LS DAM), an information model that provides a framework for communication among domain experts and technical teams developing information systems to support biomedical research. The LS DAM is harmonized with the Biomedical Research Integrated Domain Group (BRIDG) model of protocol-driven clinical research. Together, these models can facilitate data exchange for translational research. Materials and methods The content of the LS DAM was driven by analysis of life sciences and translational research scenarios and the concepts in the model are derived from existing information models, reference models and data exchange formats. The model is represented in the Unified Modeling Language and uses ISO 21090 data types. Results The LS DAM v2.2.1 is comprised of 130 classes and covers several core areas including Experiment, Molecular Biology, Molecular Databases and Specimen. Nearly half of these classes originate from the BRIDG model, emphasizing the semantic harmonization between these models. Validation of the LS DAM against independently derived information models, research scenarios and reference databases supports its general applicability to represent life sciences research. Discussion The LS DAM provides unambiguous definitions for concepts required to describe life sciences research. The processes established to achieve consensus among domain experts will be applied in future iterations and may be broadly applicable to other standardization efforts. Conclusions The LS DAM provides common semantics for life sciences research. Through harmonization with BRIDG, it promotes interoperability in translational science. C1 [Fore, Ian; Buetow, Kenneth H.; Klemm, Juli D.] NCI CBIIT, Rockville, MD 20852 USA. [Fernandez, Anna] Booz Allen Hamilton, Rockville, MD USA. [Stokes, Todd H.] Emory Univ, Atlanta, GA 30322 USA. [Stokes, Todd H.] Georgia Tech, Dept Biomed Engn, Atlanta, GA USA. [Buckler, Andrew] BBMSC, Wenham, MA USA. [Rokicki, Konrad; Pan, Sue] SAIC Inc, Mclean, VA USA. [Kelley, Jenny M.] NCI, Lab Populat Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Hipp, Jason] Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI USA. [Hernandez, Joyce] Merck Sharp & Dohme Corp, Global Clin Data External Stand, Whitehouse Stn, NJ USA. [Suzek, Baris E.] Georgetown Univ, Dept Biochem & Mol Biol, Washington, DC USA. [Stafford, Grace A.] Jackson Lab, Bar Harbor, ME 04609 USA. [Sharma, Mukesh K.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Schick, Lisa] ScenPro Inc, Richardson, TX USA. [Freund, Elaine T.] 3rd Millennium Inc, Waltham, MA USA. [Freimuth, Robert R.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA. RP Klemm, JD (reprint author), NCI CBIIT, 2115 E Jefferson St, Rockville, MD 20852 USA. EM klemmj@mail.nih.gov OI Buckler, Andrew/0000-0002-0786-4835; Fore, Ian/0000-0002-2926-9324 FU National Cancer Institute FX This work was supported by contracts from Booz Allen Hamilton and SAIC-Frederick on behalf of the National Cancer Institute as part of the caBIG (R) Integrative Cancer Research Workspace. NR 35 TC 2 Z9 2 U1 3 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV PY 2012 VL 19 IS 6 BP 1095 EP 1102 DI 10.1136/amiajnl-2011-000763 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 028FP UT WOS:000310408500026 PM 22744959 ER PT J AU Shaikh, Q Kamal, AK AF Shaikh, Quratulain Kamal, Ayeesha Kamran TI Sarpogrelate- another new antiplatelet agent? SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PREVENTION; INFARCTION; ASPIRIN; TRIAL; RISK C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Programme, Fogarty Int Ctr, Karachi, Pakistan. Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan. RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Programme, Fogarty Int Ctr, Karachi, Pakistan. EM ayeesha.kamal@aku.edu FU FIC NIH HHS [D43TW008660, D43 TW008660] NR 3 TC 0 Z9 0 U1 0 U2 0 PU PAKISTAN MEDICAL ASSOC PI KARACHI PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN SN 0030-9982 J9 J PAK MED ASSOC JI J. Pak. Med. Assoc. PD NOV PY 2012 VL 62 IS 11 BP 1253 EP 1253 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 024RP UT WOS:000310126600031 PM 23866425 ER PT J AU Kong, R Li, H Georgiev, I Changela, A Bibollet-Ruche, F Decker, JM Rowland-Jones, SL Jaye, A Guan, YJ Lewis, GK Langedijk, JPM Hahn, BH Kwong, PD Robinson, JE Shaw, GM AF Kong, Rui Li, Hui Georgiev, Ivelin Changela, Anita Bibollet-Ruche, Frederic Decker, Julie M. Rowland-Jones, Sarah L. Jaye, Assan Guan, Yongjun Lewis, George K. Langedijk, Johannes P. M. Hahn, Beatrice H. Kwong, Peter D. Robinson, James E. Shaw, George M. TI Epitope Mapping of Broadly Neutralizing HIV-2 Human Monoclonal Antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP120 ENVELOPE GLYCOPROTEIN; PROXIMAL EXTERNAL REGION; MEMORY B-CELLS; MEDIATED NEUTRALIZATION; V3-SPECIFIC ANTIBODIES; POTENT NEUTRALIZATION; ANTIGENIC STRUCTURE; CORECEPTOR USAGE; CONSERVED REGION AB Recent studies have shown that natural infection by HIV-2 leads to the elicitation of high titers of broadly neutralizing antibodies (NAbs) against primary HIV-2 strains (T. I. de Silva, et al., J. Virol. 86: 930-946, 2012; R. Kong, et al., J. Virol. 86:947-960, 2012; G. Ozkaya Sahin, et al., J. Virol. 86:961-971, 2012). Here, we describe the envelope (Env) binding and neutralization properties of 15 anti-HIV-2 human monoclonal antibodies (MAbs), 14 of which were newly generated from 9 chronically infected subjects. All 15 MAbs bound specifically to HIV-2 gp120 monomers and neutralized heterologous primary virus strains HIV-2(7312A) and HIV-2(ST). Ten of 15 MAbs neutralized a third heterologous primary virus strain, HIV-2(UC1). The median 50% inhibitory concentrations (IC(50)s) for these MAbs were surprisingly low, ranging from 0.007 to 0.028 mu g/ml. Competitive Env binding studies revealed three MAb competition groups: CG-I, CG-II, and CG-III. Using peptide scanning, site-directed mutagenesis, chimeric Env constructions, and single-cycle virus neutralization assays, we mapped the epitope of CG-I antibodies to a linear region in variable loop 3 (V3), the epitope of CG-II antibodies to a conformational region centered on the carboxy terminus of V4, and the epitope(s) of CG-III antibodies to conformational regions associated with CD4- and coreceptor-binding sites. HIV-2 Env is thus highly immunogenic in vivo and elicits antibodies having diverse epitope specificities, high potency, and wide breadth. In contrast to the HIV-1 Env trimer, which is generally well shielded from antibody binding and neutralization, HIV-2 is surprisingly vulnerable to broadly reactive NAbs. The availability of 15 human MAbs targeting diverse HIV-2 Env epitopes can facilitate comparative studies of HIV/SIV Env structure, function, antigenicity, and immunogenicity. C1 [Kong, Rui; Li, Hui; Bibollet-Ruche, Frederic; Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kong, Rui; Decker, Julie M.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Kong, Rui; Decker, Julie M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Georgiev, Ivelin; Changela, Anita; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. [Rowland-Jones, Sarah L.] John Radcliffe Hosp, Med Res Council, Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, England. [Jaye, Assan] Med Res Council United Kingdom Labs, Fajara, Gambia. [Guan, Yongjun; Lewis, George K.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Langedijk, Johannes P. M.] Pepscan Therapeut, Lelystad, Netherlands. [Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA. RP Shaw, GM (reprint author), Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. EM shawg@upenn.edu FU NIH [AI67854, AI88564, AI87383]; Bill and Melinda Gates Foundation FX This work was supported by intramural funding to the Vaccine Research Center, NIAID, and by grants from the NIH (AI67854, AI88564, AI87383), and grants from the Bill and Melinda Gates Foundation. NR 85 TC 17 Z9 17 U1 1 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2012 VL 86 IS 22 BP 12115 EP 12128 DI 10.1128/JVI.01632-12 PG 14 WC Virology SC Virology GA 027MK UT WOS:000310356400014 PM 22933274 ER PT J AU Cardone, G Brecher, M Fontana, J Winkler, DC Butan, C White, JM Stevena, AC AF Cardone, Giovanni Brecher, Matthew Fontana, Juan Winkler, Dennis C. Butan, Carmen White, Judith M. Stevena, Alasdair C. TI Visualization of the Two-Step Fusion Process of the Retrovirus Avian Sarcoma/Leukosis Virus by Cryo-Electron Tomography SO JOURNAL OF VIROLOGY LA English DT Article ID INDUCED CONFORMATIONAL-CHANGES; VIRAL MEMBRANE-FUSION; LIPID MIXING STAGE; ENVELOPE GLYCOPROTEIN; LOW PH; RECEPTOR-BINDING; INFLUENZA-VIRUS; SARCOMA-VIRUS; IMMUNODEFICIENCY-VIRUS; ELECTRON-MICROSCOPY AB Retrovirus infection starts with the binding of envelope glycoproteins to host cell receptors. Subsequently, conformational changes in the glycoproteins trigger fusion of the viral and cellular membranes. Some retroviruses, such as avian sarcoma/leukosis virus (ASLV), employ a two-step mechanism in which receptor binding precedes low-pH activation and fusion. We used cryoelectron tomography to study virion/receptor/liposome complexes that simulate the interactions of ASLV virions with cells. Binding the soluble receptor at neutral pH resulted in virions capable of binding liposomes tightly enough to alter their curvature. At virion-liposome interfaces, the glycoproteins are similar to 3-fold more concentrated than elsewhere in the viral envelope, indicating specific recruitment to these sites. Subtomogram averaging showed that the oblate globular domain in the prehairpin intermediate (presumably the receptor-binding domain) is connected to both the target and the viral membrane by 2.5-nm-long stalks and is partially disordered, compared with its native conformation. Upon lowering the pH, fusion took place. Fusion is a stochastic process that, once initiated, must be rapid, as only final (postfusion) products were observed. These fusion products showed glycoprotein spikes on their surface, with their interiors occupied by patches of dense material but without capsids, implying their disassembly. In addition, some of the products presented a density layer underlying and resolved from the viral membrane, which may represent detachment of the matrix protein to facilitate the fusion process. C1 [Cardone, Giovanni; Fontana, Juan; Winkler, Dennis C.; Butan, Carmen; Stevena, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. [Brecher, Matthew; White, Judith M.] Univ Virginia, Dept Cell Biol, Charlottesville, VA USA. [Brecher, Matthew; White, Judith M.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. RP Stevena, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM jw7g@virginia.edu; stevena@mail.nih.gov RI Fontana, Juan/A-9138-2009 OI Fontana, Juan/0000-0002-9084-2927 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; NIH [AI22470]; NIAID [5T32 AI07046-27] FX This research was supported in part by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Work in the White laboratory was supported by NIH AI22470. M.B. was supported in part by an Infectious Disease Training Grant (5T32 AI07046-27) from the NIAID. NR 55 TC 13 Z9 13 U1 0 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2012 VL 86 IS 22 BP 12129 EP 12137 DI 10.1128/JVI.01880-12 PG 9 WC Virology SC Virology GA 027MK UT WOS:000310356400015 PM 22933285 ER PT J AU Verma, S Dimitrova, M Munjal, A Fontana, J Crevar, CJ Carter, DM Ross, TM Khurana, S Golding, H AF Verma, Swati Dimitrova, Milena Munjal, Ashok Fontana, Juan Crevar, Corey J. Carter, Donald M. Ross, Ted M. Khurana, Surender Golding, Hana TI Oligomeric Recombinant H5 HA1 Vaccine Produced in Bacteria Protects Ferrets from Homologous and Heterologous Wild-Type H5N1 Influenza Challenge and Controls Viral Loads Better than Subunit H5N1 Vaccine by Eliciting High-Affinity Antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLE; BROAD CROSS-PROTECTION; NEUTRALIZING ANTIBODIES; HEMAGGLUTININ PROTEINS; ELECTRON-MICROSCOPY; IMMUNE-RESPONSES; GLOBULAR HEAD; YOUNG-ADULTS; INSECT CELLS; A VIRUS AB Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission. C1 [Verma, Swati; Dimitrova, Milena; Khurana, Surender; Golding, Hana] Food & Drug Adm, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. [Verma, Swati; Munjal, Ashok] Banasthali Vidyapith, Dept Biosci & Biotechnol, Banasthali, Rajasthan, India. [Fontana, Juan] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. [Crevar, Corey J.; Carter, Donald M.; Ross, Ted M.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA. RP Khurana, S (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. EM surender.khurana@fda.hhs.gov; hana.golding@fda.hhs.gov RI Fontana, Juan/A-9138-2009 OI Fontana, Juan/0000-0002-9084-2927 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health; NIH/NIAID [U01AI077771] FX This work was partly supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health to J.F. and NIH/NIAID award U01AI077771 to T.M.R. NR 55 TC 13 Z9 13 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2012 VL 86 IS 22 BP 12283 EP 12293 DI 10.1128/JVI.01596-12 PG 11 WC Virology SC Virology GA 027MK UT WOS:000310356400029 PM 22951833 ER PT J AU Shi, M Jagger, BW Wise, HM Digard, P Holmes, EC Taubenberger, JK AF Shi, Mang Jagger, Brett W. Wise, Helen M. Digard, Paul Holmes, Edward C. Taubenberger, Jeffery K. TI Evolutionary Conservation of the PA-X Open Reading Frame in Segment 3 of Influenza A Virus SO JOURNAL OF VIROLOGY LA English DT Article ID CRYSTAL-STRUCTURE; ENDONUCLEASE AB PA-X is a fusion protein of influenza A virus encoded in part from a +1 frameshifted X open reading frame (X-ORF) in segment 3. We show that the X-ORFs of diverse influenza A viruses can be divided into two groups that differ in selection pressure and likely function, reflected in the presence of an internal stop codon and a change in synonymous diversity. Notably, truncated forms of PA-X evolved convergently in swine and dogs, suggesting a strong species-specific effect. C1 [Jagger, Brett W.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Shi, Mang; Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. [Wise, Helen M.; Digard, Paul] Univ Edinburgh, Roslin Inst, Edinburgh EH8 9YL, Midlothian, Scotland. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov RI Digard, Paul/B-7717-2008; Shi, Mang/D-5118-2013; OI Digard, Paul/0000-0002-0872-9440; Holmes, Edward/0000-0001-9596-3552 FU Medical Research Council [G0700815] NR 10 TC 38 Z9 40 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2012 VL 86 IS 22 BP 12411 EP 12413 DI 10.1128/JVI.01677-12 PG 3 WC Virology SC Virology GA 027MK UT WOS:000310356400043 PM 22951836 ER PT J AU Traylor, M Farrall, M Holliday, EG Sudlow, C Hopewell, JC Cheng, YC Fomage, M Ikram, MA Malik, R Bevan, S Thorsteinsdottir, U Nalls, MA Longstreth, WT Wiggins, KL Yadav, S Parati, EA DeStefano, AL Worrall, BB Kittner, S Khan, MS Reiner, AP Helgadottir, A Achterberg, S Fernandez-Cadenas, I Abboud, S Schmidt, R Walters, M Chen, WM Ringelstein, EB O'Donnell, M Ho, WK Pera, J Lemmens, R Norrving, B Higgins, P Benn, M Sale, M Kuhlenbaumer, G Doney, ASF Vicente, AM Delavaran, H Algra, A Davies, G Oliveira, SA Palmer, CNA Deary, I Schmidt, H Pandolfo, M Montaner, J Carty, C de Bakker, PIW Kostulas, K Ferro, JM van Zuydam, NR Valdimarsson, E Nordestgaard, BG Lindgren, A Thijs, V Slowik, A Saleheen, D Pare, G Berger, K Thorleifsson, G Hofman, A Mosley, TH Mitchell, BD Furie, K Clarke, R Levi, C Seshadri, S Gschwendtner, A Boncoraglio, GB Sharma, P Bis, JC Gretarsdottir, S Psaty, BM Rothwell, PM Rosand, J Meschia, JF Stefansson, K Dichgans, M Markus, HS AF Traylor, Matthew Farrall, Martin Holliday, Elizabeth G. Sudlow, Cathie Hopewell, Jemma C. Cheng, Yu-Ching Fomage, Myriam Ikram, M. Arfan Malik, Rainer Bevan, Steve Thorsteinsdottir, Unnur Nalls, Mike A. Longstreth, W. T. Wiggins, Kerri L. Yadav, Sunaina Parati, Eugenio A. DeStefano, Anita L. Worrall, Bradford B. Kittner, Steven Khan, Muhammad Saleem Reiner, Alex P. Helgadottir, Anna Achterberg, Sefanja Fernandez-Cadenas, Israel Abboud, Sherine Schmidt, Reinhold Walters, Matthew Chen, Wei-Min Ringelstein, E. Bernd O'Donnell, Martin Ho, Weang Kee Pera, Joanna Lemmens, Robin Norrving, Bo Higgins, Peter Benn, Marianne Sale, Michele Kuhlenbaeumer, Gregor Doney, Alexander S. F. Vicente, Astrid M. Delavaran, Hossein Algra, Ale Davies, Gail Oliveira, Sofia A. Palmer, Colin N. A. Deary, Ian Schmidt, Helena Pandolfo, Massimo Montaner, Joan Carty, Cara de Bakker, Paul I. W. Kostulas, Konstantinos Ferro, Jose M. van Zuydam, Natalie R. Valdimarsson, Einar Nordestgaard, Borge G. Lindgren, Ame Thijs, Vincent Slowik, Agnieszka Saleheen, Danish Pare, Guillaume Berger, Klaus Thorleifsson, Gudmar Hofman, Albert Mosley, Thomas H. Mitchell, Braxton D. Furie, Karen Clarke, Robert Levi, Christopher Seshadri, Sudha Gschwendtner, Andreas Boncoraglio, Giorgio B. Sharma, Pankaj Bis, Joshua C. Gretarsdottir, Solveig Psaty, Bruce M. Rothwell, Peter M. Rosand, Jonathan Meschia, James F. Stefansson, Kan Dichgans, Martin Markus, Hugh S. CA Australian Stroke Genetics Collabo WTCCC 2 Int Stroke Genetics Consortium TI Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies SO LANCET NEUROLOGY LA English DT Article ID SEQUENCE VARIANTS; LOCI; POPULATION; INFARCTION; DISEASES; COMMON; PRKCH; MAP AB Background Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. Methods We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nudeotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls. Findings We verified previous associations for cardioembolic stroke near PITX2 (p=2.8x10(-16)) and ZFHX3 (p=2.28x10(-8)), and for large-vessel stroke at a 9p21 locus (p=3.32x10(-5)) and HDAC9 (p=2.03x10(-12)). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5x10(-6). However, we were unable to replicate any of these novel associations in the replication cohort. Interpretation Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes. C1 [Traylor, Matthew; Bevan, Steve; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London SW17 0RE, England. [Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Farrall, Martin; Helgadottir, Anna] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [Holliday, Elizabeth G.] Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Callaghan, NSW 2308, Australia. [Holliday, Elizabeth G.] Hunter Med Res Inst, Ctr Bioinformat Biomarker Discovery & Informat Ba, Sydney, NSW, Australia. [Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Hopewell, Jemma C.; Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Hopewell, Jemma C.; Clarke, Robert] Univ Oxford, Epidemiol Studies Unit, Oxford, England. [Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Fomage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Ikram, M. Arfan; Hofman, Albert] Erasmus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus MC Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus MC Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Ikram, M. Arfan; Hofman, Albert] Consortium Healthy Ageing, Leiden, Netherlands. [Malik, Rainer; Gschwendtner, Andreas; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Malik, Rainer; Gschwendtner, Andreas; Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Thorsteinsdottir, Unnur; Helgadottir, Anna; Thorleifsson, Gudmar; Gretarsdottir, Solveig; Stefansson, Kan] DeCODE Genet, Reykjavik, Iceland. [Thorsteinsdottir, Unnur; Helgadottir, Anna; Stefansson, Kan] Univ Iceland, Fac Med, Reykjavik, Iceland. [Nalls, Mike A.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Longstreth, W. T.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Longstreth, W. T.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Wiggins, Kerri L.; Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Yadav, Sunaina; Khan, Muhammad Saleem; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, Cerebrovasc Res Unit ICCRU, London, England. [Parati, Eugenio A.; Boncoraglio, Giorgio B.] Ist Neurol Carlo Besta, Fdn Ist Ricovero Cura Carattere Sci IRCCS, Dept Cereberovasc Dis, Milan, Italy. [DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.; Chen, Wei-Min] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Kittner, Steven] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MA USA. [Kittner, Steven] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Reiner, Alex P.; Carty, Cara] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Achterberg, Sefanja; Algra, Ale] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Utrecht Stroke Ctr, Dept Neurol & Neurosurg, Utrecht, Netherlands. [Fernandez-Cadenas, Israel; Montaner, Joan] Univ Autonoma Barcelona, Neurovasc Res Lab, Dept Neurol, E-08193 Barcelona, Spain. [Fernandez-Cadenas, Israel; Montaner, Joan] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain. [Fernandez-Cadenas, Israel; Montaner, Joan] Vall dHebron Hosp, Inst Res, Barcelona, Spain. [Abboud, Sherine; Pandolfo, Massimo] Lab Expt Neurol, Brussels, Belgium. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Div Neurogeriatr, Graz, Austria. [Higgins, Peter] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Chen, Wei-Min; Sale, Michele] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Ringelstein, E. Bernd] Univ Munster, Dept Neurol, D-4400 Munster, Germany. [O'Donnell, Martin] Natl Univ Ireland Galway, Galway, Ireland. [Ho, Weang Kee; Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Dept Neurol, Krakow, Poland. [Lemmens, Robin; Thijs, Vincent] VIB, Vesalius Res Ctr, Neurobiol Lab, Louvain, Belgium. [Lemmens, Robin; Thijs, Vincent] Univ Leuven KU Leuven, Expt Neurol & Leuven Res Inst Neurodegenerat Dis, Louvain, Belgium. [Lemmens, Robin; Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium. [Norrving, Bo; Delavaran, Hossein; Lindgren, Ame] Skane Univ Hosp, Dept Neurol, Lund, Sweden. [Norrving, Bo; Delavaran, Hossein; Lindgren, Ame] Lund Univ, Dept Clin Sci Lund, Lund, Sweden. [Benn, Marianne; Nordestgaard, Borge G.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Benn, Marianne; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Dept Clin Biochem, Copenhagen, Denmark. [Benn, Marianne; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark. [Sale, Michele] Univ Virginia, Dept Internal Med, Div Cardiovasc Med, Charlottesville, VA USA. [Kuhlenbaeumer, Gregor] Univ Kiel, Inst Expt Med, D-24098 Kiel, Germany. [Doney, Alexander S. F.; Palmer, Colin N. A.; van Zuydam, Natalie R.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland. [Vicente, Astrid M.] Inst Natl Sande Dr Ricardo Jorge, Dept Promocao Saude Doencas Cron, Lisbon, Portugal. [Algra, Ale] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Davies, Gail; Deary, Ian] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Davies, Gail; Deary, Ian] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Oliveira, Sofia A.] Univ Lisbon, Fac Med, Inst Med Mol, P-1699 Lisbon, Portugal. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.; Rosand, Jonathan] MIT, Cambridge, MA 02139 USA. [de Bakker, Paul I. W.; Rosand, Jonathan] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Kostulas, Konstantinos] Karolinska Univ Hosp, Karolinska Inst, Dept Neurol, Huddinge, Sweden. [Ferro, Jose M.] Hosp Santa Maria, Ctr Estudos Egas Moniz, Serv Neurol, Lisbon, Portugal. [Valdimarsson, Einar] Univ Hosp, Landspitali, Reykjavik, Iceland. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Bispebjerg Hosp, Copenhagen City Heart Study, Copenhagen, Denmark. [Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan. [Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Pare, Guillaume] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany. [Mosley, Thomas H.; Rosand, Jonathan] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Furie, Karen] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Levi, Christopher] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth Res, New Lambton, NSW, Australia. [Levi, Christopher] Hunter Med Res Inst, New Lambton, NSW, Australia. [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Seattle, Grp Hlth Res Inst, Seattle, WA USA. [Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford, England. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. RP Markus, HS (reprint author), St Georges Univ London, Stroke & Dementia Res Ctr, Cranmer Terrace, London SW17 0RE, England. EM hmarkus@sgul.ac.uk RI Palmer, Colin/C-7053-2008; Vicente, Astrid/F-8692-2014; Thijs, Vincent/C-3647-2009; Carty, Cara/B-8683-2013; Deary, Ian/C-6297-2009; de Bakker, Paul/B-8730-2009; Boncoraglio, Giorgio/B-8647-2011; Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015; Study, GoDARTS/K-9448-2016; OI O'Donnell, Martin/0000-0002-7347-7761; Norrving, Bo/0000-0002-8024-5096; HO, WEANG KEE/0000-0002-8269-7344; Ikram, Mohammad Arfan/0000-0003-0372-8585; Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Ferro, Jose/0000-0002-2343-9097; Mitchell, Braxton/0000-0003-4920-4744; Seshadri, Sudha/0000-0001-6135-2622; Palmer, Colin/0000-0002-6415-6560; Vicente, Astrid/0000-0001-7134-8037; Thijs, Vincent/0000-0002-6614-8417; de Bakker, Paul/0000-0001-7735-7858; Oliveira, Sofia A/0000-0001-7919-4191; Benn, Marianne/0000-0002-1701-595X FU Wellcome Trust; UK Medical Research Council (MRC); Australian National and Medical Health Research Council; National Institutes of Health (NIH) including National Heart, Lung and Blood Institute (NHLBI); National Institute on Aging (NIA); National Human Genome Research Institute (NHGRI); National Institute of Neurological Disorders and Stroke (NINDS); National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health (NIH) [HHSN268200625226C]; NHLBI [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01-HL087641, U01 HL096917, R01-HL093029, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129]; NIH Roadmap for Medical Research [UL1RR025005]; METASTROKE project [HL-093029]; University of Newcastle; Australian National and Medical Health Research Council (NHMRC) [569257]; Australian National Heart Foundation (NHF) [G 04S 1623]; Gladys M Brawn Fellowship; Vincent Fairfax Family Foundation in Australia; Australian NHMRC Fellowship; Department of Health (UK); Henry Smith Charity; UK-India Education Research Institutive (UKIERI) from the British Council; National Institute on Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058]; National Center of Advancing Translational Technologies CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; European Community [HEALTH-F4-2007-201413]; Framingham Heart Study; NHLBI's Framingham Heart Study [N01-HC-25195, N02-HL-6-4278]; NINDS [NS17950]; NIA [AG033193]; NIH Genes; Almirall; Astra Zeneca; Berlin Chemie; Boehringer; Boots Health Care; Glaxo-Smith-Kline; Janssen Cilag; McNeil Pharma; MSD Sharp Dohme; Pfizer; Portuguese Fundacao para a Ciencia e a Tecnologia; Jagiellonian University, Krakow Poland [K/ZDS/002848]; Netherlands Heart Foundation [2005B031]; United States National Human Genome Research Institute (NHGRI) as part of the Genomics and Randomized Trials Network (GARNET) [U01 HG005160]; NIH; GARNET Coordinating Center [U01 HG005157]; United States Public Health Service, NINDS, Bethesda, Maryland [R01 NS34447]; United States National Center for Biotechnology Information, US National Library of Medicine; WHI-GARNET through the NHGRI GARNET [U01 HG005152]; NIH Genes, Environment, and Health Initiative [U01 HG004424]; National Heart, Lung and Blood Institute [N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, HL087652, HL105756, HL93029]; [PTDC/SAU-GMG/64426/2006] FX Funding Wellcome Trust, UK Medical Research Council (MRC), Australian National and Medical Health Research Council, National Institutes of Health (NIH) including National Heart, Lung and Blood Institute (NHLBI), the National Institute on Aging (NIA), the National Human Genome Research Institute (NHGRI), and the National Institute of Neurological Disorders and Stroke (NINDS).; Atherosclerosis Risk in Communities Study (ARIC) is a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; National Institutes of Health (NIH) contract HHSN268200625226C; and NHLBI contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, and grants R01-HL087641, U01 HL096917 (T H Mosley), and R01-HL093029 (M Fornage). Infrastructure was partly supported by Grant Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. ARIC analyses performed as part of the METASTROKE project were supported by grant HL-093029 to M Fornage. Australian Stroke Genetics Collaboration (ASGC) Australian population control data were derived from the Hunter Community Study. We also thank the University of Newcastle for funding and the men and women of the Hunter region who participated in this study. This research was funded by grants from the Australian National and Medical Health Research Council (NHMRC Project Grant ID: 569257), the Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623), the University of Newcastle, the Gladys M Brawn Fellowship scheme, and the Vincent Fairfax Family Foundation in Australia. Elizabeth G Holliday is supported by the Australian NHMRC Fellowship scheme. Bio-Repository of DNA in Stroke (BRAINS) is partly funded by a Senior Fellowship from the Department of Health (UK) to P Sharma, the Henry Smith Charity and the UK-India Education Research Institutive (UKIERI) from the British Council. Cardiovascular Health Study (CHS) research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through 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 the National Institute of Neurological Diseases and Stroke (NINDS). Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging (NIA). DNA handling and genotyping was supported in part by National Center of Advancing Translational Technologies CTSI grant UL1TR000124 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. deCODE Genetics Work performed at deCODE was funded in part through a grant from the European Community's Seventh Framework Programme (FP7/2007-2013), the ENGAGE project grant agreement HEALTH-F4-2007-201413. Framingham Heart Study (FHS) This work was supported by the dedication of the Framingham Heart Study participants, the NHLBI's Framingham Heart Study (Contract Nos. N01-HC-25195 and N02-HL-6-4278), and by grants from the NINDS (NS17950), the NHLBI (HL93029), and the NIA (AG033193). Genetics of Early Onset Stroke (GEOS) Study, Baltimore, USA was supported by the NIH Genes, grants of equal share from Almirall, Astra Zeneca, Berlin Chemie, Boehringer, Boots Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp & Dohme, and Pfizer to the University of Muenster. Portugal SAO, JMF, and AMV are deeply grateful to all study participants, to the genotyping unit at the Instituto Gulbenkian de Ciencia, and to the Portuguese study neurologists and nurses for their contributions.; This work was supported by the PTDC/SAU-GMG/64426/2006 grant, a Cilencia 2008 contract (SAO) and doctoral fellowships from the Portuguese Fundacao para a Ciencia e a Tecnologia. Poland: Krakow The study was supported by the grant from the Jagiellonian University, Krakow Poland: K/ZDS/002848. SMART-study the Netherlands Genotyping in the SMART Study was made possible, in part, by a Complementation Grant to P I W de Bakker from the Biobanking and Biomolecular Research Infrastructure in the Netherlands (BBMRI-NL). S Achterberg is working in part on a grant from the Netherlands Heart Foundation, No. 2005B031. VISP The GWAS component of the VISP study was supported by the United States National Human Genome Research Institute (NHGRI), Grant U01 HG005160 (PI Michele Sale & Bradford Worrell), as part of the Genomics and Randomized Trials Network (GARNET). Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to the Johns Hopkins University. Assistance with data cleaning was provided by the GARNET Coordinating Center (U01 HG005157; PI Bruce S Weir). Study recruitment and collection of datasets for the VISP clinical trial were supported by an investigator-initiated research grant (R01 NS34447; PI James Toole) from the United States Public Health Service, NINDS, Bethesda, Maryland. Control data obtained through the database of genotypes and phenotypes (dbGAP) maintained and supported by the United States National Center for Biotechnology Information, US National Library of Medicine. W H I Funding support for WHI-GARNET was provided through the NHGRI GARNET (Grant Number U01 HG005152). Assistance with phenotype harmonisation and genotype cleaning, as well as with general study coordination, was provided by the GARNET Coordinating Center (U01 HG005157). Funding support for genotyping, which was performed at the Broad Institute of MIT and Harvard, was provided by the NIH Genes, Environment, and Health Initiative (GEI; U01 HG004424). NR 31 TC 179 Z9 189 U1 3 U2 37 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2012 VL 11 IS 11 BP 951 EP 962 DI 10.1016/S1474-4422(12)70234-X PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 028KW UT WOS:000310422200011 PM 23041239 ER PT J AU Sidransky, E Lopez, G AF Sidransky, Ellen Lopez, Grisel TI The link between the GBA gene and parkinsonism SO LANCET NEUROLOGY LA English DT Review ID GENOME-WIDE ASSOCIATION; LEWY BODY DISORDERS; PRECEDING CLINICAL-MANIFESTATION; GLUCOCEREBROSIDASE N370S ALLELE; NEURONOPATHIC GAUCHER-DISEASE; MULTIPLE SYSTEM ATROPHY; ALPHA-SYNUCLEIN; EARLY-ONSET; RISK-FACTOR; COGNITIVE IMPAIRMENT AB Mutations in the glucocerebrosidase (GBA) gene, which encodes the lysosomal enzyme that is deficient in Gaucher's disease, are important and common risk factors for Parkinson's disease and related disorders. This association was first recognised in the clinic, where parkinsonism was noted, albeit rarely, in patients with Gaucher's disease and more frequently in relatives who were obligate carriers. Subsequently, findings from large studies showed that patients with Parkinson's disease and associated Lewy body disorders had an increased frequency of GBA mutations when compared with control individuals. Patients with GBA-associated parkinsonism exhibit varying parkinsonian phenotypes but tend to have an earlier age of onset and more associated cognitive changes than patients with parkinsonism without GBA mutations. Hypotheses proposed to explain this association include a gain-of-function due to mutations in glucocerebrosidase that promotes alpha-synuclein aggregation; substrate accumulation due to enzymatic loss-of-function, which affects a-synuclein processing and clearance; and a bidirectional feedback loop. Identification of the pathological mechanisms underlying GBA-associated parkinsonism will improve our understanding of the genetics, pathophysiology, and treatment for both rare and common neurological diseases. C1 [Sidransky, Ellen; Lopez, Grisel] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov FU National Human Genome Research Institute; National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Human Genome Research Institute and the National Institutes of Health. We thank Julia Fekecs, Wendy Westbroek, and Darryl Leja for their assistance with the preparation of the figures. NR 106 TC 100 Z9 102 U1 0 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2012 VL 11 IS 11 BP 986 EP 998 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 028KW UT WOS:000310422200014 PM 23079555 ER PT J AU Lin, YH Loewke, JD Hyun, DY Leazer, J Hibbeln, JR AF Lin, Yu Hong Loewke, James D. Hyun, Duk Y. Leazer, Jay Hibbeln, Joseph R. TI Fast Transmethylation of Serum Lipids Using Microwave Irradiation SO LIPIDS LA English DT Article DE Lepage & Roy; Acetyl chloride; In situ; Transesterification; GC; Fatty acid profile ID ACID METHYL-ESTERS; CHROMATOGRAPHY-MASS-SPECTROMETRY; FATTY-ACID; RAPID TRANSESTERIFICATION; OMEGA-3-FATTY-ACIDS; PHOSPHOLIPIDS; DISEASE; BRAIN AB Microwave irradiation as the energy source for one-step direct transesterification of fatty acids in human serum lipids was examined in a solvent system of methanol: hexane: acetyl chloride based on a Lepage & Roy assay. Innovative and explosion proof single-mode or multimode microwave accelerated reaction system was employed. Recoveries were calculated as the percentage of fatty acid concentrations measured by microwave assay to those by the reference method of the Lepage & Roy assay that utilized conductive heating at 100 A degrees C for 60 min. Under conditions of 100 A degrees C for 1 min in Single-mode (S4-100 x 1), or 125 A degrees C for 5 min in Multimode (M5-125 x 5), the recoveries were 100-103 % for the total fatty acids and 96-106 % for each categorized fatty acid, including saturates, monounsaturates, n-6 PUFA, and n-3 PUFA. For individual PUFA, the mean recoveries were 102-105 % for 18:2n-6 and 18:3n-3; 99, 109, and 95 % for 20:4n-6, 20:5n-3, and 22:6n-3, respectively. Thus, fatty acid concentrations determined by microwave fatty acid assay were accurate to those results by the reference method, when the microwave conditions were optimal. In summary, the microwave irradiation could replace conductive heating in one-step direct transesterification, and reduce the duration from 60 min to 5 min or less. This methodology may be applied in both the absolute and relative quantification of serum total fatty acids. C1 [Lin, Yu Hong; Loewke, James D.; Hyun, Duk Y.; Hibbeln, Joseph R.] NIAAA, Lab Membrane Biochem & Biophys, Sect Nutr Neurosci, NIH, Bethesda, MD 20892 USA. [Leazer, Jay] CEM Corp, Mathews, NC USA. RP Lin, YH (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Sect Nutr Neurosci, NIH, Bethesda, MD 20892 USA. EM yulin@mail.nih.gov FU National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health FX The authors wish to acknowledge Drs. Norman Salem Jr., Charlie Serhan, and William E. M. Lands for the valuable advice and encouragement on the method development. Thanks to Ms. Keller Barnhardt for set-up of the microwave reaction systems and to Ms. Cindy Clark from the NIH Library Writing Center for assistance with manuscript editing. This project was funded by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. NR 24 TC 4 Z9 4 U1 3 U2 15 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 J9 LIPIDS JI Lipids PD NOV PY 2012 VL 47 IS 11 BP 1109 EP 1117 DI 10.1007/s11745-012-3714-x PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 025XD UT WOS:000310229400009 PM 23015312 ER PT J AU Adeva, MM Souto, G Blanco, N Donapetry, C AF Adeva, Maria M. Souto, Gema Blanco, Natalia Donapetry, Cristobal TI Ammonium metabolism in humans SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Review DE Metabolic alkalosis; Glutamate dehydrogenase; Glutamine synthetase; Glutaminase; Hyperammonemia ID N-ACETYLGLUTAMATE-SYNTHASE; FULMINANT HEPATIC-FAILURE; UREA CYCLE DISORDERS; ACUTE LIVER-FAILURE; LYSINURIC PROTEIN INTOLERANCE; PHOSPHATE SYNTHETASE-I; INDUCED HYPERAMMONEMIC ENCEPHALOPATHY; ACYLCARNITINE TRANSLOCASE DEFICIENCY; HUMAN GLUTAMATE-DEHYDROGENASES; PROGRESSIVE SPASTIC DIPLEGIA AB Free ammonium ions are produced and consumed during cell metabolism. Glutamine synthetase utilizes free ammonium ions to produce glutamine in the cytosol whereas glutaminase and glutamate dehydrogenase generate free ammonium ions in the mitochondria from glutamine and glutamate, respectively. Ammonia and bicarbonate are condensed in the liver mitochondria to yield carbamoylphosphate initiating the urea cycle, the major mechanism of ammonium removal in humans. Healthy kidney produces ammonium which may be released into the systemic circulation or excreted into the urine depending predominantly on acid-base status, so that metabolic acidosis increases urinary ammonium excretion while metabolic alkalosis induces the opposite effect. Brain and skeletal muscle neither remove nor produce ammonium in normal conditions, but they are able to seize ammonium during hyperammonemia, releasing glutamine. Ammonia in gas phase has been detected in exhaled breath and skin, denoting that these organs may participate in nitrogen elimination. Ammonium homeostasis is profoundly altered in liver failure resulting in hyperammonemia due to the deficient ammonium clearance by the diseased liver and to the development of portal collateral circulation that diverts portal blood with high ammonium content to the systemic blood stream. Although blood ammonium concentration is usually elevated in liver disease, a substantial role of ammonium causing hepatic encephalopathy has not been demonstrated in human clinical studies. Hyperammonemia is also produced in urea cycle disorders and other situations leading to either defective ammonium removal or overproduction of ammonium that overcomes liver clearance capacity. Most diseases resulting in hyperammonemia and cerebral edema are preceded by hyperventilation and respiratory alkalosis of unclear origin that may be caused by the intracellular acidosis occurring in these conditions. (C) 2012 Elsevier Inc. All rights reserved. C1 [Adeva, Maria M.; Donapetry, Cristobal] Hosp Gen Juan Cardona, La Coruna 15406, Spain. [Souto, Gema] NIH, Ctr Clin, Bethesda, MD USA. [Blanco, Natalia] United Surg Partners, La Coruna, Spain. RP Adeva, MM (reprint author), Hosp Gen Juan Cardona, C Pardo Bazar S-N, La Coruna 15406, Spain. EM madevaa@yahoo.com NR 183 TC 60 Z9 60 U1 10 U2 96 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 2012 VL 61 IS 11 BP 1495 EP 1511 DI 10.1016/j.metabol.2012.07.007 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 030GD UT WOS:000310557900001 PM 22921946 ER PT J AU Cho, H Kamenyeva, O Yung, S Gao, JL Hwang, IY Park, C Murphy, PM Neubig, RR Kehrl, JH AF Cho, Hyeseon Kamenyeva, Olena Yung, Sunny Gao, Ji-Liang Hwang, Il-Young Park, Chung Murphy, Philip M. Neubig, Richard R. Kehrl, John H. TI The Loss of RGS Protein-G alpha(i2) Interactions Results in Markedly Impaired Mouse Neutrophil Trafficking to Inflammatory Sites SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STAPHYLOCOCCUS-AUREUS; CHEMOKINE RECEPTORS; SIGNAL-TRANSDUCTION; BONE-MARROW; PROTEIN; CXCR2; INFECTION; MIGRATION; MICE; DESENSITIZATION AB Neutrophils are first responders rapidly mobilized to inflammatory sites by a tightly regulated, nonredundant hierarchy of chemoattractants. These chemoattractants engage neutrophil cell surface receptors triggering heterotrimeric G-protein G alpha(i) subunits to exchange GDP for GTP. By limiting the duration that G alpha(i) subunits remain GTP bound, RGS proteins modulate chemoattractant receptor signaling. Here, we show that neutrophils with a genomic knock in of a mutation that disables regulator of G-protein signaling (RGS)-G alpha(i2) interactions accumulate in the bone marrow and mobilize poorly to inflammatory sites. These defects are attributable to enhanced sensitivity to background signals, prolonged chemoattractant receptor signaling, and inappropriate CXCR2 downregulation. Intravital imaging revealed a failure of the mutant neutrophils to accumulate at and stabilize sites of sterile inflammation. Furthermore, these mice could not control a nonlethal Staphylococcus aureus infection. Neutrophil RGS proteins establish a threshold for G alpha(i) activation, helping to coordinate desensitization mechanisms. Their loss renders neutrophils functionally incompetent. C1 [Cho, Hyeseon; Kamenyeva, Olena; Hwang, Il-Young; Park, Chung; Kehrl, John H.] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Yung, Sunny; Gao, Ji-Liang; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Neubig, Richard R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. RP Cho, H (reprint author), NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hcho@niaid.nih.gov; jkehrl@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases FX This research was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases. NR 45 TC 17 Z9 17 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2012 VL 32 IS 22 BP 4561 EP 4571 DI 10.1128/MCB.00651-12 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 029ZA UT WOS:000310536000006 PM 22966200 ER PT J AU Chrousos, GP Licinio, J Gold, PW AF Chrousos, G. P. Licinio, J. Gold, P. W. TI In memoriam: Wylie Walker Vale, Jr SO MOLECULAR PSYCHIATRY LA English DT Biographical-Item C1 [Chrousos, G. P.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Chrousos, G. P.] Aghia Sophia Childrens Hosp, Athens, Greece. [Chrousos, G. P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Licinio, J.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia. [Gold, P. W.] NIMH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), Univ Athens, Sch Med, GR-11527 Athens, Greece. EM chrousge@med.uoa.gr RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 1 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2012 VL 17 IS 11 BP 1052 EP 1053 DI 10.1038/mp.2012.132 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 030DQ UT WOS:000310549600001 PM 23096955 ER PT J AU French, CA Jin, X Campbell, TG Gerfen, E Groszer, M Fisher, SE Costa, RM AF French, C. A. Jin, X. Campbell, T. G. Gerfen, E. Groszer, M. Fisher, S. E. Costa, R. M. TI An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning SO MOLECULAR PSYCHIATRY LA English DT Article DE Foxp2; in vivo recording; KE family; motor-skill learning; speech and language; striatum ID LANGUAGE DISORDER; INHERITED SPEECH; BASAL GANGLIA; HUMAN BRAIN; GENE; EXPRESSION; MICE; IDENTIFICATION; ABNORMALITIES; IMPAIRMENT AB Mutations in the human FOXP2 gene cause impaired speech development and linguistic deficits, which have been best characterised in a large pedigree called the KE family. The encoded protein is highly conserved in many vertebrates and is expressed in homologous brain regions required for sensorimotor integration and motor-skill learning, in particular corticostriatal circuits. Independent studies in multiple species suggest that the striatum is a key site of FOXP2 action. Here, we used in vivo recordings in awake-behaving mice to investigate the effects of the KE-family mutation on the function of striatal circuits during motor-skill learning. We uncovered abnormally high ongoing striatal activity in mice carrying an identical mutation to that of the KE family. Furthermore, there were dramatic alterations in striatal plasticity during the acquisition of a motor skill, with most neurons in mutants showing negative modulation of firing rate, starkly contrasting with the predominantly positive modulation seen in control animals. We also observed striking changes in the temporal coordination of striatal firing during motor-skill learning in mutants. Our results indicate that FOXP2 is critical for the function of striatal circuits in vivo, which are important not only for speech but also for other striatal-dependent skills. Molecular Psychiatry (2012) 17, 1077-1085; doi: 10.1038/mp.2011.105; published online 30 August 2011 C1 [French, C. A.; Costa, R. M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, P-2780901 Oeiras, Portugal. [French, C. A.; Campbell, T. G.; Fisher, S. E.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Jin, X.; Gerfen, E.; Costa, R. M.] NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Bethesda, MD USA. [Groszer, M.] Univ Paris 06, INSERM, UMR S839, Inst Fer Moulin, Paris, France. [Fisher, S. E.] Max Planck Inst Psycholinguist, Dept Language & Genet, Nijmegen, Netherlands. RP Costa, RM (reprint author), Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, Rua Quinta Grande 6, P-2780901 Oeiras, Portugal. EM ruicosta@fchampalimaud.org RI Fisher, Simon/E-9130-2012; Campbell, Thomas/A-6964-2014; Campbell, Thomas/C-2498-2014; OI Fisher, Simon/0000-0002-3132-1996; Campbell, Thomas/0000-0002-4508-0089; Campbell, Thomas/0000-0002-4508-0089; French, Catherine/0000-0003-2072-8413; Costa, Rui/0000-0003-0495-8374 FU Human Frontier Science Program short-term fellowship; Royal Society Research Fellowship; Wellcome Trust [075491/Z/04, 080971]; Division of Intramural Clinical and Basic Research of the National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health; Champalimaud Neuroscience Programme; European Research Council [STG 243393]; Max Planck Society FX We thank Sonali Darbar, Rathi Puliyadi, Terrell D Holloway and Amber Luo for excellent technical assistance; John Burkhardt and Shih-Chieh Lin for help with Matlab; Emma Doran for running the operant learning task; and the staffs of the British Heart Foundation Functional Genetics Facility and the NIAAA vivarium for mouse husbandry. This work was supported by a Human Frontier Science Program short-term fellowship (to CAF); a Royal Society Research Fellowship (to SEF); the Wellcome Trust (075491/Z/04; 080971); the Division of Intramural Clinical and Basic Research of the National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health; the Champalimaud Neuroscience Programme; the European Research Council (STG 243393); and the Max Planck Society. NR 35 TC 36 Z9 36 U1 3 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2012 VL 17 IS 11 BP 1077 EP 1085 DI 10.1038/mp.2011.105 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 030DQ UT WOS:000310549600004 PM 21876543 ER PT J AU Nguyen, LS Jolly, L Shoubridge, C Chan, WK Huang, L Laumonnier, F Raynaud, M Hackett, A Field, M Rodriguez, J Srivastava, AK Lee, Y Long, R Addington, AM Rapoport, JL Suren, S Hahn, CN Gamble, J Wilkinson, MF Corbett, MA Gecz, J AF Nguyen, L. S. Jolly, L. Shoubridge, C. Chan, W. K. Huang, L. Laumonnier, F. Raynaud, M. Hackett, A. Field, M. Rodriguez, J. Srivastava, A. K. Lee, Y. Long, R. Addington, A. M. Rapoport, J. L. Suren, S. Hahn, C. N. Gamble, J. Wilkinson, M. F. Corbett, M. A. Gecz, J. TI Transcriptome profiling of UPF3B/NMD-deficient lymphoblastoid cells from patients with various forms of intellectual disability SO MOLECULAR PSYCHIATRY LA English DT Article DE intellectual disability; Nonsense-mediated mRNA decay; RNA-SEQ; UPF3A; UPF3B ID MESSENGER-RNA DECAY; EXON-JUNCTION COMPLEX; MENTAL-RETARDATION; GENE-EXPRESSION; FILAMIN-A; MUTATIONS; UPF1; NMD; SURVEILLANCE; COMPONENTS AB The nonsense-mediated mRNA decay (NMD) pathway was originally discovered by virtue of its ability to rapidly degrade aberrant mRNAs with premature termination codons. More recently, it was shown that NMD also directly regulates subsets of normal transcripts, suggesting that NMD has roles in normal biological processes. Indeed, several NMD factors have been shown to regulate neurological events (for example, neurogenesis and synaptic plasticity) in numerous vertebrate species. In man, mutations in the NMD factor gene UPF3B, which disrupts a branch of the NMD pathway, cause various forms of intellectual disability (ID). Using Epstein Barr virus-immortalized B cells, also known as lymphoblastoid cell lines (LCLs), from ID patients that have loss-of-function mutations in UPF3B, we investigated the genome-wide consequences of compromised NMD and the role of NMD in neuronal development and function. We found that similar to 5% of the human transcriptome is impacted in UPF3B patients. The UPF3B paralog, UPF3A, is stabilized in all UPF3B patients, and partially compensates for the loss of UPF3B function. Interestingly, UPF3A protein, but not mRNA, was stabilised in a quantitative manner that inversely correlated with the severity of patients' phenotype. This suggested that the ability to stabilize the UPF3A protein is a crucial modifier of the neurological symptoms due to loss of UPF3B. We also identified ARHGAP24, which encodes a GTPase-activating protein, as a canonical target of NMD, and we provide evidence that deregulation of this gene inhibits axon and dendrite outgrowth and branching. Our results demonstrate that the UPF3B-dependent NMD pathway is a major regulator of the transcriptome and that its targets have important roles in neuronal cells. Molecular Psychiatry (2012) 17, 1103-1115; doi: 10.1038/mp.2011.163; published online 20 December 2011 C1 [Nguyen, L. S.; Jolly, L.; Shoubridge, C.; Corbett, M. A.; Gecz, J.] SA Pathol, Dept Med Genet, Adelaide, SA, Australia. [Nguyen, L. S.; Shoubridge, C.; Gecz, J.] Univ Adelaide, Dept Paediat, Adelaide, SA, Australia. [Chan, W. K.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Huang, L.; Wilkinson, M. F.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA. [Laumonnier, F.; Raynaud, M.] INSERM, U930, Tours, France. [Laumonnier, F.] CNRS, ERL3106, Tours, France. [Laumonnier, F.; Raynaud, M.] Univ Tours, UMR Imaging & Brain, Tours, France. [Raynaud, M.] CHRU Tours, Serv Genet, Tours, France. [Hackett, A.; Field, M.] GOLD Serv, Newcastle, NSW, Australia. [Rodriguez, J.; Srivastava, A. K.] Greenwood Genet Ctr, JC Self Res Inst, Greenwood, SC 29646 USA. [Lee, Y.; Long, R.; Addington, A. M.; Rapoport, J. L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Suren, S.] UCL Inst Child Hlth, Neural Dev Unit, London, England. [Hahn, C. N.] SA Pathol, Dept Mol Pathol, Ctr Canc Biol, Adelaide, SA, Australia. [Gamble, J.] Univ Sydney, Centenary Inst Canc Med & Cell Biol, Sydney, NSW 2006, Australia. RP Gecz, J (reprint author), Womens & Childrens Hosp, Dept Genet Med, SA Pathol, 72 King William Rd, Adelaide, SA 5006, Australia. EM jozef.gecz@adelaide.edu.au RI Jolly, Lachlan/B-5892-2015; Shoubridge, Cheryl/A-1571-2016; Laumonnier, Frederic/N-1165-2016 OI Jolly, Lachlan/0000-0003-4538-2658; Gecz, Jozef/0000-0002-7884-6861; Shoubridge, Cheryl/0000-0002-0157-3084; Laumonnier, Frederic/0000-0003-2567-0708 FU Australian NHMRC Project [453457]; Women's and Children's Hospital Foundation; NH&MRC Principal Research Fellowship; MS McLeod Foundation FX We thank the members of the families studied for participation and Brigitte Jauffrion and Lucianne Vandeleur for help with cell culture. This work was supported by grants from the Australian NH&MRC Project Grant 453457 to JoG, and the Women's and Children's Hospital Foundation Grant to LJ and JoG. JoG is supported by NH&MRC Principal Research Fellowship. LSN's PhD scholarship was supported by the MS McLeod Foundation. NR 62 TC 28 Z9 28 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2012 VL 17 IS 11 BP 1103 EP 1115 DI 10.1038/mp.2011.163 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 030DQ UT WOS:000310549600007 PM 22182939 ER PT J AU Amin, N Byrne, E Johnson, J Chenevix-Trench, G Walter, S Nolte, IM Vink, JM Rawal, R Mangino, M Teumer, A Keers, JC Verwoert, G Baumeister, S Biffar, R Petersmann, A Dahmen, N Doering, A Isaacs, A Broer, L Wray, NR Montgomery, GW Levy, D Psaty, BM Gudnason, V Chakravarti, A Sulem, P Gudbjartsson, DF Kiemeney, LA Thorsteinsdottir, U Stefansson, K Van Rooij, FJA Aulchenko, YS Hottenga, JJ Rivadeneira, FR Hofman, A Uitterlinden, AG Hammond, CJ Shin, SY Ikram, A Witteman, JCM Janssens, ACJW Snieder, H Tiemeier, H Wolfenbuttel, BHR Oostra, BA Heath, AC Wichmann, E Spector, TD Grabe, HJ Boomsma, DI Martin, NG Van Duijn, CM AF Amin, N. Byrne, E. Johnson, J. Chenevix-Trench, G. Walter, S. Nolte, I. M. Vink, J. M. Rawal, R. Mangino, M. Teumer, A. Keers, J. C. Verwoert, G. Baumeister, S. Biffar, R. Petersmann, A. Dahmen, N. Doering, A. Isaacs, A. Broer, L. Wray, N. R. Montgomery, G. W. Levy, D. Psaty, B. M. Gudnason, V. Chakravarti, A. Sulem, P. Gudbjartsson, D. F. Kiemeney, L. A. Thorsteinsdottir, U. Stefansson, K. Van Rooij, F. J. A. Aulchenko, Y. S. Hottenga, J. J. Rivadeneira, F. R. Hofman, A. Uitterlinden, A. G. Hammond, C. J. Shin, S-Y Ikram, A. Witteman, J. C. M. Janssens, A. C. J. W. Snieder, H. Tiemeier, H. Wolfenbuttel, B. H. R. Oostra, B. A. Heath, A. C. Wichmann, E. Spector, T. D. Grabe, H. J. Boomsma, D. I. Martin, N. G. Van Duijn, C. M. CA kConFab Investigators TI Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM SO MOLECULAR PSYCHIATRY LA English DT Article DE coffee; P450; NRCAM; CAB39L; Parkinson's disease; CYP1A1/CYP1A2 ID TYPE-2 DIABETES-MELLITUS; AGED FINNISH MEN; PSYCHOMOTOR PERFORMANCE; PARKINSONS-DISEASE; CYP1A2 GENOTYPE; GENE-EXPRESSION; BLOOD-PRESSURE; MESSENGER-RNA; HUMAN BRAIN; CAFFEINE CONSUMPTION AB Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N = 18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values = 1.6 x 10(-11) and 2.7 x 10(-11)), which were also in strong linkage disequilibrium (r(2) = 0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value = 3.9 x 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value = 7.1 x 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value = 2.2 x 10(-05)) and Parkinson's disease pathways (P-value = 3.6 x 10(-05)). Molecular Psychiatry (2012) 17, 1116-1129; doi: 10.1038/mp.2011.101; published online 30 August 2011 C1 [Amin, N.; Isaacs, A.; Broer, L.; Aulchenko, Y. S.; Oostra, B. A.; Van Duijn, C. M.] Erasmus MC, Dept Epidemiol, Unit Genet Epidemiol, NL-3015 GE Rotterdam, Netherlands. [Byrne, E.; Johnson, J.; Chenevix-Trench, G.; Wray, N. R.; Montgomery, G. W.; Martin, N. G.] Queensland Inst Med Res, Dept Genet, Brisbane, Qld 4006, Australia. [Walter, S.; Van Rooij, F. J. A.] Erasmus MC, Dept Publ Hlth, NL-3015 GE Rotterdam, Netherlands. [Nolte, I. M.; Snieder, H.] Univ Groningen, Univ Med Ctr Groningen, Unit Genet Epidemiol & Bioinformat, Dept Epidemiol, Groningen, Netherlands. [kConFab Investigators] Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. [Vink, J. M.; Hottenga, J. J.; Boomsma, D. I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Rawal, R.; Doering, A.; Wichmann, E.] Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Mangino, M.; Spector, T. D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Teumer, A.] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany. [Keers, J. C.; Snieder, H.; Wolfenbuttel, B. H. R.] Univ Med Ctr Groningen, Univ Groningen, LifeLines Cohort Study, Groningen, Netherlands. [Keers, J. C.; Snieder, H.; Wolfenbuttel, B. H. R.] Univ Med Ctr Groningen, Univ Groningen, Biobank, Groningen, Netherlands. [Baumeister, S.] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Biffar, R.] Ernst Moritz Arndt Univ Greifswald, Ctr Oral Hlth, Dept Prosthodont Gerodontol & Dent Mat, Greifswald, Germany. [Petersmann, A.] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Dahmen, N.] Johannes Gutenberg Univ Mainz, Dept Psychiat, D-6500 Mainz, Germany. [Levy, D.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Levy, D.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Psaty, B. M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, B. M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, B. M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA. [Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Chakravarti, A.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Chakravarti, A.] Johns Hopkins Univ, Dept Epidemiol & Med, Baltimore, MD USA. [Sulem, P.; Gudbjartsson, D. F.; Thorsteinsdottir, U.; Stefansson, K.] deCODE Genet, Reykjavik, Iceland. [Kiemeney, L. A.] Radboud Univ Nijmegen, Dept Urol, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, L. A.] Radboud Univ Nijmegen, Dept Endocrinol, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, L. A.] BG Nijmegen, Comprehens Canc Ctr E, Nijmegen, Netherlands. [Thorsteinsdottir, U.; Stefansson, K.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Rivadeneira, F. R.; Uitterlinden, A. G.] Erasmus Univ, Dept Internal Med, Med Ctr, Rotterdam, Netherlands. [Hammond, C. J.; Shin, S-Y] Wellcome Trust Sanger Inst, Hinxton, England. [Tiemeier, H.] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Wolfenbuttel, B. H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands. [Oostra, B. A.] Erasmus Univ, Dept Clin Studies, Med Ctr, Rotterdam, Netherlands. [Heath, A. C.] Washington Univ, Dept Psychiat, St Louis, MI USA. [Wichmann, E.] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany. [Grabe, H. J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Stralsund, Germany. [Van Duijn, C. M.] Netherlands Consortium Hlth Aging, Ctr Med Syst Biol, Leiden, Netherlands. [Van Duijn, C. M.] Natl Genom Initiat, The Hague, Netherlands. RP Van Duijn, CM (reprint author), Erasmus MC, Dept Epidemiol, Unit Genet Epidemiol, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. EM c.vanduijn@erasmusmc.nl RI Wolffenbuttel, Bruce/A-8419-2011; Aulchenko, Yurii/M-8270-2013; Kiemeney, Lambertus/D-3357-2009; Wray, Naomi/C-8639-2015; Gudnason, Vilmundur/K-6885-2015; janssens, cecile/L-1075-2015; Montgomery, Grant/B-7148-2008; mangino, massimo/F-5134-2011; OI Ikram, Mohammad Arfan/0000-0003-0372-8585; Tiemeier, Henning/0000-0002-4395-1397; Rivadeneira, Fernando/0000-0001-9435-9441; Hammond, Christopher/0000-0002-3227-2620; Martin, Nicholas/0000-0003-4069-8020; Wolffenbuttel, Bruce/0000-0001-9262-6921; Aulchenko, Yurii/0000-0002-7899-1575; Kiemeney, Lambertus/0000-0002-2368-1326; Wray, Naomi/0000-0001-7421-3357; Gudnason, Vilmundur/0000-0001-5696-0084; Montgomery, Grant/0000-0002-4140-8139; mangino, massimo/0000-0002-2167-7470; Janssens, A Cecile/0000-0002-6153-4976 FU EUROSPAN (European Special Populations Research Network); European Commission [018947, LSHG-CT-2006-01947]; Netherlands Organization for Scientific Research; Erasmus MC; Centre for Medical Systems Biology (CMSB); Netherlands Brain Foundation (HersenStichting Nederland); Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany; German Federal Ministry of Education and Research (BMBF); German National Genome Research Network (NGFN); Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; Genetic basis of anxiety and depression [904-61-090]; Twin-family database for behavior genomics studies [480-04-004]; ZonMW [31160008]; Center for Medical Systems Biology (NWO Genomics); Spinozapremie [SPI 56-464-14192]; Neuroscience campus Amsterdam (NCA-VU); Genetics of Mental Illness [ERC 230374]; Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health; NWO [VENI 451-06-004]; National Breast Cancer Foundation and Cancer Australia [628333]; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498]; Australian Research Council [A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; US National Institutes of Health (NIH) [AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206]; Netherlands Scientific Organization [NWO 480-05-003]; Cancer Council Queensland; Erasmus Medical Center and Erasmus University Rotterdam; Netherlands Organization for Scientific Research (NWO); Netherlands Organization for Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Netherlands Genomics Initiative; Ministry of Education, Culture and Science; Ministry of Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; Internationaal Parkinson Fonds; Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs; Social Ministry of the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg, West Pomerania; German Research Foundation; Federal Ministry of Education and Research Germany; JanssenCilag; Lundbeck; Eli Lilly; Novartis; AstraZeneca; SALUS-Institute for Trend-Research and Therapy Evaluation in Mental Health; Wellcome Trust; European Community [HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413]; Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre; Biotechnology and Biological Sciences Research Council (BBSRC) [G20234]; National Eye Institute through an NIH/CIDR; Netherlands Organization of Scientific Research NWO [175.010.2007.006]; Economic Structure Enhancing Fund (FES) of the Dutch government; Ministry of Economic Affairs; Ministry for Health, Welfare and Sports; Northern Netherlands Collaboration of Provinces (SNN); Province of Groningen; University Medical Center Groningen; University of Groningen; Dutch Kidney Foundation; Dutch Diabetes Research Foundation FX ERF: The genotyping for the ERF study was supported by EUROSPAN (European Special Populations Research Network) and the European Commission FP6 STRP grant (018947; LSHG-CT-2006-01947). The ERF study was further supported by grants from the Netherlands Organization for Scientific Research, Erasmus MC, the Centre for Medical Systems Biology (CMSB) and the Netherlands Brain Foundation (HersenStichting Nederland). We are grateful to all patients and their relatives, general practitioners and neurologists for their contributions and to P Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work and P Snijders for his help in data collection. We acknowledge Internationale Stichting Alzheimer Onderzoek (ISAO) and Hersenstichting Netherlands. KORA: The KORA Augsburg studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF). Part of this work was financed by the German National Genome Research Network (NGFN). Our research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. Netherlands Twin Register(NTR): We acknowledge support from: Genetic basis of anxiety and depression (904-61-090); Twin-family database for behavior genomics studies (480-04-004); Genetic determinants of risk behavior in relation to alcohol use and alcohol use disorder: a developmental perspective (ZonMW Addiction 31160008), Center for Medical Systems Biology (NWO Genomics); Spinozapremie (SPI 56-464-14192); Neuroscience campus Amsterdam (NCA-VU); and Genetics of Mental Illness (ERC 230374). Genotyping was funded in part by the Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health. JMV is financially supported by NWO (VENI 451-06-004). QIMR: We thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, as well as the Clinical Follow-Up Study (funded 2001-2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia no. 628333) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. We thank the twins and their families for their participation. We also thank Ann Eldridge, Marlene Grace, Kerrie McAloney (sample collection); Lisa Bowdler, Steven Crooks (DNA processing); Dale Nyholt, Sarah Medland and Scott Gordon (imputation and genotyping QC); Allan McRae and Peter Visscher for helpful advice and input. Funding was provided by the Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498), the Australian Research Council (A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921), the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254) and the US National Institutes of Health (NIH grants AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206).; A portion of the genotyping on which this study was based (Illumina 370K scans on 4300 individuals) was carried out at the Center for Inherited Disease Research, Baltimore (CIDR), through an access award to our late colleague Dr Richard Todd (Psychiatry, Washington University School of Medicine, St Louis). Statistical analyses were carried out on the Genetic Cluster Computer, which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003). GWM and GCTare supported by the National Health and Medical Research Council (NHMRC) Fellowship Scheme. JJ was financially supported by the Cancer Council Queensland. Rotterdam Study (RS-I and RS-II): The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research (NWO), The Netherlands Organization for Health Research and Development (ZonMw), The Research Institute for Diseases in the Elderly (RIDE), The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. The contribution of inhabitants, general practitioners and pharmacists of the Ommoord district to the Rotterdam Study is gratefully acknowledged. AI was financially supported by the Internationaal Parkinson Fonds. The Study of Health in Pomerania (SHIP): SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants nos 01ZZ9603, 01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs, as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany, and the Federal State of Mecklenburg, West Pomerania. The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG. HJG was supported by the German Research Foundation; the Federal Ministry of Education and Research Germany; speakers honoraria from Bristol-Myers Squibb, Eli Lilly, Novartis, Eisai, Wyeth, Pfizer, Boehringer Ingelheim, Servier and travel funds from JanssenCilag, Lundbeck, Eli Lilly, Novartis, AstraZeneca and SALUS-Institute for Trend-Research and Therapy Evaluation in Mental Health. Twins UK: The study was funded by the Wellcome Trust; European Community's Seventh Framework Programme (FP7/20072013)/grant agreement HEALTH-F2-2008-201865-GEFOS and (FP7/2007-2013), ENGAGE project grant agreement HEALTH-F4-2007-201413 and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254). The study also receives support from the Department of Health through the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London. TDS is an NIHR senior Investigator. The project also received support from a Biotechnology and Biological Sciences Research Council (BBSRC) project grant. (G20234). We acknowledge the funding and support of the National Eye Institute through an NIH/CIDR genotyping project (PI: Terri Young)'.; We thank the staff from the Genotyping Facilities at the Wellcome Trust Sanger Institute for sample preparation, Quality Control and Genotyping led by Leena Peltonen and Panos Deloukas; Le Centre National de Genotypage, France, led by Mark Lathrop, for genotyping; Duke University, NC, USA, led by David Goldstein, for genotyping; and the Finnish Institute of Molecular Medicine, Finnish Genome Center, University of Helsinki, led by Aarno Palotie. LifeLines: The LifeLines Cohort Study, and generation and management of GWAS genotype data for the LifeLines Cohort Study is supported by the Netherlands Organization of Scientific Research NWO (grant 175.010.2007.006), the Economic Structure Enhancing Fund (FES) of the Dutch government, the Ministry of Economic Affairs, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the Northern Netherlands Collaboration of Provinces (SNN), the Province of Groningen, University Medical Center Groningen, the University of Groningen, Dutch Kidney Foundation and Dutch Diabetes Research Foundation. We thank Behrooz Alizadeh, Annemieke Boesjes, Marcel Bruinenberg, Noortje Festen, Ilja Nolte, Lude Franke and Mitra Valimohammadi for their help in creating the GWAS database, and Rob Bieringa, Joost Keers, Rene Oostergo, Rosalie Visser and Judith Vonk for their work related to data-collection and validation. We are grateful to the study participants, the staff from the LifeLines Cohort Study and Medical Biobank Northern Netherlands, and the participating general practitioners and pharmacists. NR 101 TC 26 Z9 29 U1 2 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2012 VL 17 IS 11 BP 1116 EP 1129 DI 10.1038/mp.2011.101 PG 14 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 030DQ UT WOS:000310549600008 PM 21876539 ER PT J AU Guilloux, JP Douillard-Guilloux, G Kota, R Wang, X Gardier, AM Martinowich, K Tseng, GC Lewis, DA Sibille, E AF Guilloux, J-P Douillard-Guilloux, G. Kota, R. Wang, X. Gardier, A. M. Martinowich, K. Tseng, G. C. Lewis, D. A. Sibille, E. TI Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression SO MOLECULAR PSYCHIATRY LA English DT Article DE major depression; female; amygdala; BDNF; GABA; somatostatin; neurotrophic hypothesis ID NEUROTROPHIC FACTOR EXPRESSION; DORSOLATERAL PREFRONTAL CORTEX; GAMMA-AMINOBUTYRIC-ACID; GENE-EXPRESSION; ANTIDEPRESSANT MEDICATIONS; HIPPOCAMPAL VOLUME; GENDER-DIFFERENCES; BIPOLAR DISORDER; SUICIDE SUBJECTS; MOOD DISORDERS AB Women are twice as likely as men to develop major depressive disorder (MDD) and are more prone to recurring episodes. Hence, we tested the hypothesis that the illness may associate with robust molecular changes in female subjects, and investigated large-scale gene expression in the post-mortem brain of MDD subjects paired with matched controls (n = 21 pairs). We focused on the lateral/basolateral/basomedian complex of the amygdala as a neural hub of mood regulation affected in MDD. Among the most robust findings were downregulated transcripts for genes coding for gamma-aminobutyric acid (GABA) interneuron-related peptides, including somatostatin (SST), tachykinin, neuropeptide Y (NPY) and cortistatin, in a pattern reminiscent to that previously reported in mice with low brain-derived neurotrophic factor (BDNF). Changes were confirmed by quantitative PCR and not explained by demographic, technical or known clinical parameters. BDNF itself was significantly downregulated at the RNA and protein levels in MDD subjects. Investigating putative mechanisms, we show that this core MDD-related gene profile (including SST, NPY, TAC1, RGS4 and CORT) is recapitulated by complementary patterns in mice with constitutive (BDNF-heterozygous) or activity-dependent (exon IV knockout) decreases in BDNF function, with a common effect on SST and NPY. Together, these results provide both direct (low RNA/protein) and indirect (low BDNF-dependent gene pattern) evidence for reduced BDNF function in the amygdala of female subjects with MDD. Supporting studies in mutant mice models suggest a complex mechanism of low constitutive and activity-dependent BDNF function in MDD, particularly affecting SST/NPY-related GABA neurons, thus linking the neurotrophic and GABA hypotheses of depression. Molecular Psychiatry (2012) 17, 1130-1142; doi: 10.1038/mp.2011.113; published online 13 September 2011 C1 [Guilloux, J-P; Douillard-Guilloux, G.; Kota, R.; Lewis, D. A.; Sibille, E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15312 USA. [Guilloux, J-P; Gardier, A. M.] Univ Paris Sud, EA 3544, Fac Pharm, Chatenay Malabry, France. [Wang, X.; Tseng, G. C.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15312 USA. [Martinowich, K.] NIMH, Genes Cognit & Psychosis Program GCAP, Bethesda, MD 20892 USA. [Lewis, D. A.; Sibille, E.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15312 USA. RP Sibille, E (reprint author), Univ Pittsburgh, Dept Psychiat, 3811 OHara St,BST W1643, Pittsburgh, PA 15312 USA. EM sibilleel@upmc.edu RI Lewis, David/G-4053-2014; Guilloux, Jean-Philippe/B-3726-2015; Martinowich, Keri/F-9841-2012; OI Lewis, David/0000-0002-3225-6778; Guilloux, Jean-Philippe/0000-0003-0982-3751; Martinowich, Keri/0000-0002-5237-0789 FU BMS Foundation; Bristol-Myers Squibb; Curridium; Pfizer; National Institute of Mental Health (NIMH) [MH084060, MH085111, MH084053] FX David A Lewis currently receives investigator-initiated research support from the BMS Foundation, Bristol-Myers Squibb, Curridium and Pfizer and in 2008-2010 served as a consultant in the areas of target identification and validation and new compound development to AstraZeneca, BioLine RX, Bristol-Myers Squibb, Merck, Neurogen and SK Life Science.; This work was supported by National Institute of Mental Health (NIMH) MH084060 (ES), MH085111 (ES) and MH084053 (DAL). The funding agency had no role in the study design, data collection and analysis, decision to publish and preparation of the paper. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH or the National Institutes of Health. NR 78 TC 70 Z9 74 U1 4 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2012 VL 17 IS 11 BP 1130 EP 1142 DI 10.1038/mp.2011.113 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 030DQ UT WOS:000310549600009 PM 21912391 ER PT J AU Riazuddin, S Belyantseva, IA Giese, APJ Lee, K Indzhykulian, AA Nandamuri, P Yousaf, R Sinha, GP Lee, S Terrell, D Hegde, RS Ali, RA Anwar, S Andrade-Elizondo, PB Sirmaci, A Parise, LV Basit, S Wali, A Ayub, M Ansar, M Ahmad, W Khan, SN Akram, J Tekin, M Riazuddin, S Cook, T Buschbeck, EK Frolenkov, GI Leal, SM Friedman, TB Ahmed, ZM AF Riazuddin, Saima Belyantseva, Inna A. Giese, Arnaud P. J. Lee, Kwanghyuk Indzhykulian, Artur A. Nandamuri, Pratima Yousaf, Rizwan Sinha, Ghanshyam P. Lee, Sue Terrell, David Hegde, Rashmi S. Ali, Rana A. Anwar, Saima Andrade-Elizondo, Paula B. Sirmaci, Asli Parise, Leslie V. Basit, Sulman Wali, Abdul Ayub, Muhammad Ansar, Muhammad Ahmad, Wasim Khan, Shaheen N. Akram, Javed Tekin, Mustafa Riazuddin, Sheikh Cook, Tiffany Buschbeck, Elke K. Frolenkov, Gregory I. Leal, Suzanne M. Friedman, Thomas B. Ahmed, Zubair M. TI Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48 SO NATURE GENETICS LA English DT Article ID OUTER HAIR-CELLS; CA2+ RELEASE; BULLFROGS SACCULUS; BUFFERING PROTEINS; LOCALIZATION; STEREOCILIA; ADAPTATION; DROSOPHILA; ZEBRAFISH; CHANNELS AB Sensorineural hearing loss is genetically heterogeneous. Here, we report that mutations in CIB2, which encodes a calcium- and integrin-binding protein, are associated with nonsyndromic deafness (DFNB48) and Usher syndrome type 11 (USH1J). One mutation in CIB2 is a prevalent cause of deafness DFNB48 in Pakistan; other CIB2 mutations contribute to deafness elsewhere in the world. In mice, CIB2 is localized to the mechanosensory stereocilia of inner ear hair cells and to retinal photoreceptor and pigmented epithelium cells. Consistent with molecular modeling predictions of calcium binding, CIB2 significantly decreased the ATP-induced calcium responses in heterologous cells, whereas mutations in deafness DFNB48 altered CIB2 effects on calcium responses. Furthermore, in zebrafish and Drosophila melanogaster, CIB2 is essential for the function and proper development of hair cells and retinal photoreceptor cells. We also show that CIB2 is a new member of the vertebrate Usher interactome. C1 [Riazuddin, Saima; Giese, Arnaud P. J.; Yousaf, Rizwan; Ahmed, Zubair M.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH USA. [Riazuddin, Saima; Giese, Arnaud P. J.; Terrell, David; Cook, Tiffany; Ahmed, Zubair M.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Ophthalmol, Cincinnati, OH USA. [Riazuddin, Saima; Ahmed, Zubair M.] Univ Cincinnati, Coll Med, Dept Otolaryngol, Cincinnati, OH USA. [Riazuddin, Saima; Cook, Tiffany; Ahmed, Zubair M.] Univ Cincinnati, Coll Med, Dept Ophthalmol, Cincinnati, OH USA. [Belyantseva, Inna A.; Lee, Sue; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Rockville, MD USA. [Lee, Kwanghyuk; Andrade-Elizondo, Paula B.; Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Indzhykulian, Artur A.; Sinha, Ghanshyam P.; Frolenkov, Gregory I.] Univ Kentucky, Dept Physiol, Lexington, KY USA. [Nandamuri, Pratima; Buschbeck, Elke K.] Univ Cincinnati, Dept Biol Sci, McMicken Coll Arts & Sci, Cincinnati, OH 45221 USA. [Yousaf, Rizwan; Ali, Rana A.; Anwar, Saima; Khan, Shaheen N.] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. [Hegde, Rashmi S.; Cook, Tiffany] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH USA. [Sirmaci, Asli; Tekin, Mustafa] Univ Miami, Miller Sch Med, Dept Human Genet, Miami, FL 33136 USA. [Parise, Leslie V.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. [Basit, Sulman; Ansar, Muhammad; Ahmad, Wasim] Quaid I Azam Univ, Fac Biol Sci, Dept Biochem, Islamabad, Pakistan. [Wali, Abdul] Baluchistan Univ Informat Technol, Inst Biotechnol, Quetta, Pakistan. [Ayub, Muhammad] Univ Baluchistan, Inst Biochem, Quetta, Pakistan. [Akram, Javed; Riazuddin, Sheikh] Allama Iqbal Med Coll, Lahore, Pakistan. [Riazuddin, Sheikh] Univ Lahore, Lahore, Pakistan. [Ahmed, Zubair M.] Bahauddin Zakariya Univ, Inst Mol Biol & Biotechnol, Multan, Pakistan. RP Ahmed, ZM (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH USA. EM zubair.ahmed@cchmc.org RI Basit, Sulman/B-2947-2013; Nasim Khan, Shaheen/F-2135-2015; Ansar, Muhammad/F-4808-2015; Ahmad, Wasim/E-9713-2015; Basit, Sulman/F-6395-2015; Anwar, Saima/C-7477-2016; Ansar, Muhammad/H-5967-2011; OI Ansar, Muhammad/0000-0001-5891-7063; Indzhykulian, Artur/0000-0002-2076-6818; Lee, Kwanghyuk/0000-0001-7781-9696; Cook, Tiffany/0000-0002-3100-5248; Frolenkov, Gregory/0000-0002-9810-5024; Basit, Sulman/0000-0003-4294-6825 FU US National Institutes of Health (NIH) [N01-HG-65403]; Research to Prevent Blindness; Higher Education Commission (Islamabad, Pakistan); Ministry of Science and Technology (Islamabad, Pakistan); International Center for Genetic Engineering and Biotechnology (Trieste, Italy) [08/009]; Cincinnati Children's Hospital Research Foundation (CCHMC); National Science Foundation [IOS-1050754]; US National Institute on Deafness and Other Communication Disorders (NIDCD/NIH) [R01 DC03594, DC011651, R01 HL092544, R01 DC009645, R01 DC008861, R01 DC012564, R00 DC009287, R01 DC011803, R01 DC011748]; NIDCD [DC000039-15] FX We thank the families for their participation and cooperation. We also thank G.N. Sarangdhar, R. Rachel, T. Jaworek, V. Ponferrada and K. Gul for technical assistance and R.J. Morell, J. Schultz, D. Drayna, A. Swaroop and A.J. Griffith for critique of the manuscript. We thank T.M. Leisner (University of North Carolina at Chapel Hill) for the generous gift of antibodies to CIB. Genotyping services were provided to S.M.L. by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract (N01-HG-65403) from the US National Institutes of Health (NIH) to Johns Hopkins University. Z.M.A. is a recipient of a Research to Prevent Blindness Career Development Award. This work was also supported by funding from the Higher Education Commission and the Ministry of Science and Technology (Islamabad, Pakistan) to Sheikh Riazuddin and W.A., the International Center for Genetic Engineering and Biotechnology (Trieste, Italy) under project CRP/PAK08-01 contract 08/009 to Sheikh Riazuddin, the Cincinnati Children's Hospital Research Foundation (CCHMC) Intramural Research Funds to Saima Riazuddin and Z.M.A., a National Science Foundation grant (IOS-1050754) to E.K.B., US National Institute on Deafness and Other Communication Disorders (NIDCD/NIH) research grants R01 DC03594 and DC011651 to S.M.L., R01 HL092544 to L.V.P., R01 DC009645 to M.T., R01 DC008861 to G.I.F., R01 DC012564 and R00 DC009287 to Z.M.A., and R01 DC011803 and R01 DC011748 to Saima Riazuddin, and intramural funds from the NIDCD (DC000039-15) to T.B.F. NR 52 TC 71 Z9 77 U1 4 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2012 VL 44 IS 11 BP 1265 EP 1271 DI 10.1038/ng.2426 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 029KZ UT WOS:000310495800021 PM 23023331 ER PT J AU Lovinger, DM AF Lovinger, David M. TI New twist on orphan receptor GPR88 function SO NATURE NEUROSCIENCE LA English DT Editorial Material ID EXPRESSION; NEURONS AB Ligands for G protein coupled receptor 88 (GPR88) have not yet been found. A new study finds that GPR88 is important in the physiology of dorsal striatal projection neurons, as well as in behaviors involving this brain region. C1 NIAAA, Lab Integrat Neurosci, Bethesda, MD USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Bethesda, MD USA. EM lovindav@mail.nih.gov FU Intramural NIH HHS [Z01 AA000407-06] NR 15 TC 1 Z9 1 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2012 VL 15 IS 11 BP 1469 EP 1470 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 028LX UT WOS:000310424900002 PM 23103990 ER PT J AU Lai, KO Wong, ASL Cheung, MC Xu, P Liang, ZY Lok, KC Xie, H Palko, ME Yung, WH Tessarollo, L Cheung, ZH Ip, NY AF Lai, Kwok-On Wong, Alan S. L. Cheung, Man-Chun Xu, Pei Liang, Zhuoyi Lok, Ka-Chun Xie, Hui Palko, Mary E. Yung, Wing-Ho Tessarollo, Lino Cheung, Zelda H. Ip, Nancy Y. TI TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory SO NATURE NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; SINGLE DENDRITIC SPINES; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; PROTEIN-SYNTHESIS; SIGNAL-TRANSDUCTION; NMDA RECEPTORS; BDNF; LTP; ROLES AB The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB participate in diverse neuronal functions, including activity-dependent synaptic plasticity that is crucial for learning and memory. On binding to BDNF, TrkB is not only autophosphorylated at tyrosine residues but also undergoes serine phosphorylation at S478 by the serine/threonine kinase cyclin-dependent kinase 5 (Cdk5). However, the in vivo function of this serine phosphorylation remains unknown. We generated knock-in mice lacking this serine phosphorylation (Trkb(S478A/S478A) mice) and found that the TrkB phosphorylation deficient mice displayed impaired spatial memory and compromised hippocampal long-term potentiation (LIP). S478 phosphorylation of TrkB regulates its interaction with the Rac1-specific guanine nucleotide exchange factor TIAM1, leading to activation of Rac1 and phosphorylation of S6 ribosomal protein during activity-dependent dendritic spine remodeling. These findings reveal the importance of Cdk5-mediated S478 phosphorylation of TrkB in activity-dependent structural plasticity, which is crucial for LIP and spatial memory formation. C1 [Lai, Kwok-On; Wong, Alan S. L.; Cheung, Man-Chun; Xu, Pei; Liang, Zhuoyi; Lok, Ka-Chun; Cheung, Zelda H.; Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China. [Lai, Kwok-On; Wong, Alan S. L.; Cheung, Man-Chun; Xu, Pei; Liang, Zhuoyi; Lok, Ka-Chun; Cheung, Zelda H.; Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Mol Neurosci Ctr, Hong Kong, Hong Kong, Peoples R China. [Lai, Kwok-On; Wong, Alan S. L.; Cheung, Man-Chun; Xu, Pei; Liang, Zhuoyi; Lok, Ka-Chun; Cheung, Zelda H.; Ip, Nancy Y.] Hong Kong Univ Sci & Technol, State Key Lab Mol Neurosci, Hong Kong, Hong Kong, Peoples R China. [Xie, Hui; Yung, Wing-Ho] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. [Palko, Mary E.; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Ip, NY (reprint author), Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China. EM boip@ust.hk OI Liang, Zhuoyi/0000-0003-1622-524X FU Research Grants Council of Hong Kong [HKUST 661109, 661309, 660810, 661010, 661111]; University Grants Committee [AoE/B-15/01]; S.H. Ho Foundation; Croucher Foundation; National Cancer Institute, Center for Cancer Research, US National Institutes of Health FX We are grateful to A. Kulkarni (National Institutes of Health) and T. Curran (University of Pennsylvania) for the Cdk5-/- mice, L.-H. Tsai (Massachusetts Institute of Technology) for the p35-/- mice, M. Greenberg (Harvard Medical School) for the phospho-TIAM1 and phospho-PAK antibodies, W Mobley (University of California, San Diego) for TIAM1 expression constructs, and L. Reichardt (University of California, San Francisco) for the chicken antibody to TrkB. We thank C. Kwong, B. Lai, P. Sun, B. Butt, Y. Liang, H. Chuang, Y. Dai and K. Ho for their excellent technical assistance, Amy Fu and Ada Fu for critical reading of the manuscript, and members of the Ip laboratory for many helpful discussions. This study was supported in part by the Research Grants Council of Hong Kong (HKUST 661109,661309, 660810, 661010 and 661111), the Area of Excellence Scheme of the University Grants Committee (AoE/B-15/01) and the S.H. Ho Foundation. N.Y.I. was the recipient of Croucher Foundation Senior Research Fellowship, and K.-O.L. and Z.H.C. were the recipients of Croucher Foundation Research Fellowship. M.E.P. and L.T. were supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, US National Institutes of Health. NR 50 TC 53 Z9 55 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2012 VL 15 IS 11 BP 1506 EP 1515 DI 10.1038/nn.3237 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 028LX UT WOS:000310424900010 PM 23064382 ER PT J AU Koya, E Cruz, FC Ator, R Golden, SA Hoffman, AF Lupica, CR Hope, BT AF Koya, Eisuke Cruz, Fabio C. Ator, Robert Golden, Sam A. Hoffman, Alexander F. Lupica, Carl R. Hope, Bruce T. TI Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization SO NATURE NEUROSCIENCE LA English DT Article ID LONG-TERM DEPRESSION; CONTEXT-SPECIFIC SENSITIZATION; RECEPTOR SUBUNIT COMPOSITION; INDUCED LOCOMOTOR-ACTIVITY; VENTRAL TEGMENTAL AREA; SYNAPTIC PLASTICITY; IN-VIVO; DOPAMINE NEURONS; BEHAVIORAL SENSITIZATION; GLUTAMATE TRANSMISSION AB Cocaine-induced alterations in synaptic glutamate function in nucleus accumbens are thought to mediate drug-related behaviors such as psychomotor sensitization. However, previous studies have examined global alterations in randomly selected accumbens neurons regardless of their activation state during cocaine-induced behavior. We recently found that a minority of strongly activated Fos-expressing accumbens neurons are necessary for cocaine-induced psychomotor sensitization, whereas the majority of accumbens neurons are less directly involved. We assessed synaptic alterations in these strongly activated accumbens neurons in Fos-GFP mice, which express a fusion protein of Fos and GFP in strongly activated neurons, and compared these alterations with those in surrounding non-activated neurons. Cocaine sensitization produced higher levels of 'silent synapses', which contained functional NMDA receptors and nonfunctional AMPA receptors only in GFP-positive neurons, 6-11 d after sensitization. Thus, distinct synaptic alterations are induced in the most strongly activated accumbens neurons that mediate psychomotor sensitization. C1 [Koya, Eisuke; Cruz, Fabio C.; Ator, Robert; Golden, Sam A.; Hope, Bruce T.] NIDA, Behav Neurosci Branch, Intramural Res Program, US NIH,US Dept HHS, Baltimore, MD USA. [Hoffman, Alexander F.; Lupica, Carl R.] NIDA, Electrophysiol Res Sect, Intramural Res Program, US NIH,US Dept HHS, Baltimore, MD USA. RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, US NIH,US Dept HHS, Baltimore, MD USA. EM bhope@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; Cruz, Fabio/K-1497-2013; Hoffman, Alexander/H-3035-2012; OI Hope, Bruce/0000-0001-5804-7061; Hoffman, Alexander/0000-0002-2676-0628; Golden, Sam/0000-0002-2104-2272 FU National Institute on Drug Abuse FX We thank A. Barth for providing the first line of Fos-GFP mice, K. Knestaut and J. Hug for breeding the Fos-GFP mice, and E. Goldart and R. Ator for genotyping assistance. We thank S. Hall and T. Shippenberg for the use of their locomotor activity chambers. We thank S. Kourrich for many fruitful discussions regarding synaptic plasticity in the nucleus accumbens. This research was supported by the National Institute on Drug Abuse, Intramural Research Program. NR 46 TC 32 Z9 33 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2012 VL 15 IS 11 BP 1556 EP 1562 DI 10.1038/nn.3232 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 028LX UT WOS:000310424900016 PM 23023294 ER PT J AU Friedl, P Sahai, E Weiss, S Yamada, KM AF Friedl, Peter Sahai, Erik Weiss, Stephen Yamada, Kenneth M. TI New dimensions in cell migration SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX; LEUKOCYTE MIGRATION; CANCER; INVASION; MORPHOGENESIS; COLLAGEN; TISSUE; 3D; PLASTICITY; MODEL AB Studies of cell migration in three-dimensional (3D) cell culture systems and in vivo have revealed several differences when compared with cell migration in two dimensions, including their morphology and mechanical and signalling control. Here, researchers assess the contribution of 3D models to our understanding of cell migration, both in terms of the mechanisms used to drive single cell and collective cell migration and how migrating cells respond to a changing environment in vivo. C1 [Friedl, Peter] Radboud Univ Nijmegen, Med Ctr, NL-6500 HC Nijmegen, Netherlands. [Friedl, Peter] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sahai, Erik] Canc Res UK, London Res Inst, London WC2A 3LY, England. [Weiss, Stephen] Univ Michigan, Ann Arbor, MI 48109 USA. [Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Friedl, P (reprint author), Radboud Univ Nijmegen, Med Ctr, NL-6500 HC Nijmegen, Netherlands. EM p.friedl@ncmls.ru.nl; erik.sahai@cancer.org.uk; sjweiss@med.umich.edu; kenneth.yamada@nih.gov RI Friedl, Peter/A-8961-2010; OI Yamada, Kenneth/0000-0003-1512-6805; Sahai, Erik/0000-0002-3932-5086 FU Intramural NIH HHS NR 30 TC 83 Z9 84 U1 6 U2 97 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD NOV PY 2012 VL 13 IS 11 BP 743 EP 747 DI 10.1038/nrm3459 PG 5 WC Cell Biology SC Cell Biology GA 028PQ UT WOS:000310435000015 PM 23072889 ER PT J AU Braganza, MZ Kitahara, CM de Gonzalez, AB Inskip, PD Johnson, KJ Rajaraman, P AF Braganza, Melissa Z. Kitahara, Cari M. de Gonzalez, Amy Berrington Inskip, Peter D. Johnson, Kimberly J. Rajaraman, Preetha TI Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review SO NEURO-ONCOLOGY LA English DT Review DE brain cancer; brain tumors; glioma; ionizing radiation; meningioma ID ATOMIC-BOMB SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD-CANCER SURVIVOR; DENTAL X-RAYS; SKIN HEMANGIOMA; INTRACRANIAL MENINGIOMA; TINEA-CAPITIS; FOLLOW-UP; EPIDEMIOLOGY; RADIOTHERAPY AB Although exposure to moderate-to-high doses of ionizing radiation is the only established environmental risk factor for brain and CNS tumors, it is not clear whether this relationship differs across tumor subtypes, by sex or age at exposure, or at the low-to-moderate range of exposure. This systematic review summarizes the epidemiologic evidence on the association between ionizing radiation exposure and risk of brain/CNS tumors. Articles included in this review estimated radiation exposure doses to the brain and reported excess relative risk (ERR) estimates for brain/CNS tumors. Eight cohorts were eligible for inclusion in the analysis. Average age at exposure ranged from 8 months to 26 years. Mean dose to the brain ranged from 0.07 to 10 Gy. Elevated risks for brain/CNS tumors were consistently observed in relation to ionizing radiation exposure, but the strength of this association varied across cohorts. Generally, ionizing radiation was more strongly associated with risk for meningioma compared with glioma. The positive association between ionizing radiation exposure and risk for glioma was stronger for younger vs older ages at exposure. We did not observe an effect modification on the risk for meningioma by sex, age at exposure, time since exposure, or attained age. The etiologic role of ionizing radiation in the development of brain/CNS tumors needs to be clarified further through additional studies that quantify the association between ionizing radiation and risk for brain/CNS tumors at low-to-moderate doses, examine risks across tumor subtypes, and account for potential effect modifiers. C1 [Braganza, Melissa Z.; Kitahara, Cari M.; de Gonzalez, Amy Berrington; Inskip, Peter D.; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Braganza, Melissa Z.; Johnson, Kimberly J.] Washington Univ, St Louis, MO USA. RP Braganza, MZ (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM melissa.braganza@nih.gov RI Kitahara, Cari/R-8267-2016 FU National Cancer Institute, National Institutes of Health FX This work was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 40 TC 37 Z9 37 U1 0 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2012 VL 14 IS 11 BP 1316 EP 1324 DI 10.1093/neuonc/nos208 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 027SN UT WOS:000310373800002 PM 22952197 ER PT J AU Proescholdt, MA Merrill, MJ Stoerr, EM Lohmeier, A Pohl, F Brawanski, A AF Proescholdt, Martin A. Merrill, Marsha J. Stoerr, Eva-Maria Lohmeier, Annette Pohl, Fabian Brawanski, Alexander TI Function of carbonic anhydrase IX in glioblastoma multiforme SO NEURO-ONCOLOGY LA English DT Article DE apoptosis; CAIX; hypoxia; invasion; pH ID TUMOR-CELL GROWTH; BRAIN-TUMORS; CA-IX; EXTRACELLULAR PH; POOR-PROGNOSIS; GLIOMA-CELLS; IN-VIVO; HYPOXIA; EXPRESSION; SURVIVAL AB Carbonic anhydrase (CA) IX is over-expressed in glioblastoma; however, its functions in this context are unknown. Metabolically, glioblastomas are highly glycolytic, leading to a significant lactic acid load. Paradoxically, the intracellular pH is alkaline. We hypothesized that CAIX contributes to the extrusion of hydrogen ions into the extracellular space, thereby moderating intra- and extracellular pH and creating an environment conductive to enhanced invasion. We investigated the role of CAIX as a prognostic marker in patients with glioblastoma and its biological function in vitro. CAIX expression was analyzed in 59 patients with glioblastoma by immunohistochemistry. The expression levels were correlated to overall survival. In vitro, U251 and Ln 18 glioblastoma cells were incubated under hypoxia to induce CAIX expression, and RNA interference (RNAi) was used to examine the function of CAIX on cell attachment, invasion, intracellular energy transfer, and susceptibility to adjuvant treatment. High CAIX expression was identified as an independent factor for poor survival in patients with glioblastoma. In vitro, cell attachment and invasion were strongly reduced after knockdown of CAIX. Finally, the effects of radiation and chemotherapy were strongly augmented after CAIX interference and were accompanied by a higher rate of apoptotic cell death. CAIX is an independent prognostic factor for poor outcome in patients with glioblastoma. Cell attachment, invasion, and survival during adjuvant treatment are significantly influenced by high CAIX expression. These results indicate that inhibition of CAIX is a potential metabolic target for the treatment of patients with glioblastoma. C1 [Proescholdt, Martin A.; Stoerr, Eva-Maria; Lohmeier, Annette; Brawanski, Alexander] Univ Regensburg, Med Ctr, Dept Neurosurg, D-93053 Regensburg, Germany. [Merrill, Marsha J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Pohl, Fabian] Univ Regensburg, Med Ctr, Dept Radiat Oncol, D-93053 Regensburg, Germany. RP Proescholdt, MA (reprint author), Univ Regensburg, Med Ctr, Dept Neurosurg, Franz Josef Str Allee 11, D-93053 Regensburg, Germany. EM martin.proescholdt@klinik.uni-regensburg.de NR 42 TC 29 Z9 29 U1 2 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2012 VL 14 IS 11 BP 1357 EP 1366 DI 10.1093/neuonc/nos216 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 027SN UT WOS:000310373800006 PM 23074198 ER PT J AU Yakel, JL AF Yakel, Jerrel L. TI Nicotinic ACh Receptors in the Hippocampus: Role in Excitability and Plasticity SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID LONG-TERM POTENTIATION; AMYLOID-BETA-PEPTIDE; STRATUM-ORIENS INTERNEURONS; CENTRAL CHOLINERGIC SYSTEM; CENTRAL-NERVOUS-SYSTEM; RAT ENTORHINAL CORTEX; ACETYLCHOLINE-RECEPTOR; SYNAPTIC PLASTICITY; ALZHEIMERS-DISEASE; DENTATE GYRUS AB The nicotinic ACh receptors (nAChRs) are in the cys-loop family of ligand-gated ion channels. They are widely expressed throughout the brain, including in the hippocampus where they are thought to be involved in regulating excitability, plasticity, and cognitive function. In addition, dysfunction in hippocampal nAChRs has been linked to a variety of neurological disorders and diseases, including Alzheimer's disease, schizophrenia, and epilepsy. In order to understand how to treat nAChR-related disorders and diseases, it is critical to understand how these receptors participate in normal brain function; this entails not only understanding the biophysical properties of ion channel function and their pattern of expression but also how these receptors are regulating excitability and circuit behavior. The primary cholinergic input to the hippocampus comes from the medial septum and diagonal band of Broca; however, the mechanistic details are unknown of how activation of cholinergic receptors, either through exogenous nAChR ligands or the activation of endogenous acetylcholine release, regulates hippocampal network activity. This entails direct study of the excitatory and inhibitory neuronal networks, as well as the role of nonneuronal cells, in regulating hippocampal function. Here, I will review the latest work from my laboratory in which we have attempted to do just that, with the overall goal of learning more about the role of the hippocampal nAChR in synaptic plasticity. C1 NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233,Mail Drop F2-08, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 114 TC 21 Z9 21 U1 0 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD NOV PY 2012 VL 14 IS 11 BP 1249 EP 1257 DI 10.1093/ntr/nts091 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 027TN UT WOS:000310376600001 PM 22472168 ER PT J AU Berggren, EK Mele, L Landon, MB Spong, CY Ramin, SM Casey, B Wapner, RJ Varner, MW Rouse, DJ Sciscione, A Catalano, P Harper, M Saade, G Caritis, SN Sorokin, Y Peaceman, AM Tolosa, JE AF Berggren, Erica K. Mele, Lisa Landon, Mark B. Spong, Catherine Y. Ramin, Susan M. Casey, Brian Wapner, Ronald J. Varner, Michael W. Rouse, Dwight J. Sciscione, Anthony Catalano, Patrick Harper, Margaret Saade, George Caritis, Steve N. Sorokin, Yoram Peaceman, Alan M. Tolosa, Jorge E. CA Eunice Kennedy Shriver Natl Inst TI Perinatal Outcomes in Hispanic and Non-Hispanic White Women With Mild Gestational Diabetes SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LOW-BIRTH-WEIGHT; EPIDEMIOLOGIC PARADOX; PREGNANCY OUTCOMES; MELLITUS; DISPARITIES; PREVALENCE AB OBJECTIVE: To compare perinatal outcomes between self-identified Hispanic and non-Hispanic white women with mild gestational diabetes mellitus (GDM) or glucose intolerance. METHODS: In a secondary analysis of a mild GDM treatment trial, we compared perinatal outcomes by race and ethnicity for 767 women with glucose intolerance (abnormal 50-g 1-hour screen, normal 100-g 3-hour oral glucose tolerance test), 371 women with mild GDM assigned to usual prenatal care, and 397 women with mild GDM assigned to treatment. Outcomes included: composite adverse perinatal outcome (neonatal death, hypoglycemia, hyperbilirubinemia, hyperinsulinemia, stillbirth, birth trauma), gestational age at delivery, birth weight, and hypertensive disorders of pregnancy. Adjusted regression models included: 100-g 3-hour oral glucose tolerance test results, parity, gestational age, body mass index, maternal age at enrollment, and current tobacco use. RESULTS: The sample of 1,535 women was 68.3% Hispanic and 31.7% non-Hispanic white. Among women with glucose intolerance, Hispanic women had more frequent composite outcome (37% compared with 27%, adjusted odds ratio [OR] 1.62, 95% confidence interval [CI] 1.10-2.37) with more neonatal elevated C-cord peptide (19% compared with 13%, adjusted OR 1.79, 95% CI 1.04-3.08) and neonatal hypoglycemia (21% compared with 13%, adjusted OR 2.04, 95% CI 1.18-3.53). Among women with untreated mild GDM, outcomes were similar by race and ethnicity. Among Hispanic women with treated mild GDM, composite outcome was similar to non-Hispanic white women (35% compared with 25%, adjusted OR 1.62, 95% CI 0.92-2.86), but Hispanic neonates had more frequent hyperinsulinemia (21% compared with 10%, adjusted OR 2.96, 95% CI 1.33-6.60). CONCLUSION: Individual components of some neonatal outcomes were more frequent in Hispanic neonates, but most perinatal outcomes were similar between Hispanic and non-Hispanic ethnic groups. (Obstet Gynecol 2012; 120: 1099-1104) DOI: http://10.1097/AOG.0b013e31827049a5 C1 Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Texas Hlth Sci Ctr Houston, Dept Obstet & Gynecol, Houston, TX USA. Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA. Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA. Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. George Washington Univ, Dept Obstet & Gynecol, Biostat Ctr, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Obstet & Gynecol, Bethesda, MD USA. RP Berggren, EK (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Obstet & Gynecol, Div Maternal Fetal Med, 834 Chestnut St,Suite 400, Philadelphia, PA 19107 USA. EM erica.berggren@gmail.com RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118, HD36801]; General Clinical Research Centers [M01-RR00034]; National Center for Research Resources [UL1-RR024989, M01-RR00080, UL1-RR025764, C06-RR11234] FX The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118, HD36801), General Clinical Research Centers Grant (M01-RR00034), and the National Center for Research Resources (UL1-RR024989, M01-RR00080, UL1-RR025764, C06-RR11234) and does not necessarily represent the official views of the NICHD or the National Institutes of Health (NIH). NR 24 TC 3 Z9 3 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2012 VL 120 IS 5 BP 1099 EP 1104 DI 10.1097/AOG.0b013e31827049a5 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 029RF UT WOS:000310512500017 PM 23090528 ER PT J AU Spong, CY Berghella, V Wenstrom, KD Mercer, BM Saade, GR AF Spong, Catherine Y. Berghella, Vincenzo Wenstrom, Katharine D. Mercer, Brian M. Saade, George R. TI Preventing the First Cesarean Delivery Summary of a Joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists Workshop SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ASSISTED VAGINAL DELIVERY; POSTTERM PREGNANCY; NULLIPAROUS WOMEN; LABOR; INDUCTION; OUTCOMES; FORCEPS; RATES; ANALGESIA AB With more than one third of pregnancies in the United States being delivered by cesarean and the growing knowledge of morbidities associated with repeat cesarean deliveries, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists convened a workshop to address the concept of preventing the first cesarean delivery. The available information on maternal and fetal factors, labor management and induction, and nonmedical factors leading to the first cesarean delivery was reviewed as well as the implications of the first cesarean delivery on future reproductive health. Key points were identified to assist with reduction in cesarean delivery rates including that labor induction should be performed primarily for medical indication; if done for nonmedical indications, the gestational age should be at least 39 weeks or more and the cervix should be favorable, especially in the nulliparous patient. Review of the current literature demonstrates the importance of adhering to appropriate definitions for failed induction and arrest of labor progress. The diagnosis of "failed induction" should only be made after an adequate attempt. Adequate time for normal latent and active phases of the first stage, and for the second stage, should be allowed as long as the maternal and fetal conditions permit. The adequate time for each of these stages appears to be longer than traditionally estimated. Operative vaginal delivery is an acceptable birth method when indicated and can safely prevent cesarean delivery. Given the progressively declining use, it is critical that training and experience in operative vaginal delivery are facilitated and encouraged. When discussing the first cesarean delivery with a patient, counseling should include its effect on future reproductive health. (Obstet Gynecol 2012; 120: 1181-93) DOI: http://10.1097/AOG.0b013e3182704880 C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Obstet & Gynecol, Div Maternal Fetal Med, Philadelphia, PA 19107 USA. Brown Univ, Women & Infants Hosp, Brown Alpert Sch Med, Dept Obstet & Gynecol,Div Maternal Fetal Med, Providence, RI USA. Case Western Reserve Univ, MetroHealth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Univ Texas Med Branch, Div Maternal Fetal Med, Dept Obstet & Gynecol, Galveston, TX USA. Soc Maternal Fetal Med, Publicat & Execut Comm, Washington, DC USA. RP Spong, CY (reprint author), NICHD, Pregnancy & Perinatol Branch, NIH, 6100 Executive Blvd,Room 4B03 MSC 7510, Bethesda, MD 20892 USA. EM spongc@mail.nih.gov OI Berghella, Vincenzo/0000-0003-2854-0239 FU Intramural NIH HHS [Z99 HD999999] NR 39 TC 159 Z9 175 U1 1 U2 14 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 NOV PY 2012 VL 120 IS 5 BP 1181 EP 1193 DI 10.1097/AOG.0b013e3182704880 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 029RF UT WOS:000310512500026 PM 23090537 ER EF