FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Holmes, A AF Holmes, Andrew TI CHRONIC ALCOHOL VAPOR EXPOSURE ALTERS EXECUTIVE FUNCTIONS AND CORTICO-STRIATAL NEURONAL MORPHOLOGY IN MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 296A EP 296A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301635 ER PT J AU Heilig, M Schank, JR Thorsell, A Carroll, FI AF Heilig, M. Schank, J. R. Thorsell, A. Carroll, F. I. TI REVISITING KAPPA-OPIOID RECEPTORS AS A TARGET FOR TREATMENT OF ALCOHOLISM: SOME UNEXPECTED RESULTS USING JDTIC SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Heilig, M.; Schank, J. R.; Thorsell, A.] NIAAA, Bethesda, MD 20892 USA. [Carroll, F. I.] RTI Int, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 304A EP 304A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301669 ER PT J AU Zhou, Z Kimura, M Yuan, Q Goldman, D AF Zhou, Z. Kimura, M. Yuan, Q. Goldman, D. TI WHOLE GENOME-SEQUENCING-BASED ANALYSIS OF HIPPOCAMPAL GENE EXPRESSION AND DNA METHYLATION IN THE ALCOHOL-PREFERRING AND -NON-PREFERRING RAT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Zhou, Z.; Kimura, M.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 305A EP 305A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301673 ER PT J AU Ramchandani, VA Stangl, BL Vatsalya, V Cooke, ME Zametkin, M Zimmermann, US O'Connor, S Hommer, DW Heilig, M AF Ramchandani, V. A. Stangl, B. L. Vatsalya, V. Cooke, M. E. Zametkin, M. Zimmermann, U. S. O'Connor, S. Hommer, D. W. Heilig, M. TI DETERMINANTS OF INTRAVENOUS ALCOHOL SELF-ADMINISTRATION AND PHARMACODYNAMIC RESPONSES: HUMAN LABORATORY STUDIES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Ramchandani, V. A.; Stangl, B. L.; Vatsalya, V.; Cooke, M. E.; Zametkin, M.; Zimmermann, U. S.; O'Connor, S.; Hommer, D. W.; Heilig, M.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 307A EP 307A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301679 ER PT J AU Hingson, R Winter, M Heeren, T AF Hingson, R. Winter, M. Heeren, T. TI ALCOHOL AND DRUG USE IN FATALLY INJURED DRIVERS IN STATES THAT TEST MORE THAN 80% FOR BOTH ALCOHOL AND DRUGS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Hingson, R.; Winter, M.; Heeren, T.] NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 308A EP 308A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301685 ER PT J AU Barr, CS Yuan, Q Zhou, Z Lindell, SG Heilig, M Schwandt, ML Higley, JD Goldman, D AF Barr, C. S. Yuan, Q. Zhou, Z. Lindell, S. G. Heilig, M. Schwandt, M. L. Higley, J. D. Goldman, D. TI GENETIC VARIATION AND EPIGENETIC REGULATION IN RHESUS MACAQUE BRAIN - RELEVANCE TO HUMAN ALCOHOL USE AND RELATED PHENOTYPES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Barr, C. S.; Yuan, Q.; Zhou, Z.; Lindell, S. G.; Heilig, M.; Schwandt, M. L.; Higley, J. D.; Goldman, D.] NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 311A EP 311A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301696 ER PT J AU Carlson, VCC Gremel, CM Lovinger, DM AF Carlson, V. C. Cuzon Gremel, C. M. Lovinger, D. M. TI GESTATIONAL ETHANOL EXPOSURE CAUSES DYNAMIC CHANGES IN GABAERGIC NEUROTRANSMISSION OF THE DORSAL STRIATUM IN THE ADULT MOUSE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Carlson, V. C. Cuzon; Gremel, C. M.; Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 312A EP 312A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301698 ER PT J AU Heilig, M Thorsell, A AF Heilig, M. Thorsell, A. TI ETHANOL/OPIOID INTERACTIONS ON NEUROTRANSMITTER SYSTEMS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 34th Annual Scientific Meeting of the Research-Society-on-Alcoholism CY JUN 25-29, 2011 CL Atlanta, GA SP Res Soc Alcoholism C1 [Heilig, M.; Thorsell, A.] NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2011 VL 35 IS 6 SU S BP 314A EP 314A PG 1 WC Substance Abuse SC Substance Abuse GA 766RN UT WOS:000290804301707 ER PT J AU Serra-Pages, M Olivera, A Torres, R Picado, C De Mora, F Rivera, J AF Serra-Pages, M. Olivera, A. Torres, R. Picado, C. De Mora, F. Rivera, J. TI Prostaglandin E 2 receptor 2 mediates inhibition of mast cell activity and in vivo allergic responses SO ALLERGY LA English DT Meeting Abstract CT 30th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 11-15, 2011 CL Istanbul, TURKEY SP European Acad Allergy & Clin Immunol (EAACI) C1 [Serra-Pages, M.; De Mora, F.] Univ Autonoma Barcelona, Dept Pharmacol Therapeut & Toxicol, Bellaterra, Cerdanyola Del, Spain. [Olivera, A.; Rivera, J.] Natl Inst Arthrit Musculoskeletal & Skin, Immunogenet Mol Lab, NIH, Bethesda, MD USA. [Torres, R.; Picado, C.] Univ Barcelona, IDIBAPS, Hosp Clin, Dept Pneumol & Resp Allergy, Barcelona, Spain. RI Torres, Rosa/D-1189-2014; de Mora, Fernando/O-4636-2014 OI Torres, Rosa/0000-0002-9109-4035; de Mora, Fernando/0000-0002-3002-6004 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 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD JUN PY 2011 VL 66 SU 94 SI SI MA 144 BP 69 EP 69 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 286IS UT WOS:000329462200145 ER PT J AU Chang, Y Lee, H Kwon, H Kim, S Kang, H Park, H Cho, S Min, K Kim, Y AF Chang, Y. Lee, H. Kwon, H. Kim, S. Kang, H. Park, H. Cho, S. Min, K. Kim, Y. TI Immunomodulatory roles of thalidomide in an ovalbumin-induced murine asthma model SO ALLERGY LA English DT Meeting Abstract CT 30th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 11-15, 2011 CL Istanbul, TURKEY SP European Acad Allergy & Clin Immunol (EAACI) C1 [Chang, Y.; Kim, S.] Seoul Natl Univ, Dept Internal Med, Bundang Hosp, Songnam, South Korea. [Lee, H.] Seoul Natl Univ, Med Res Ctr, Inst Allergy & Clin Immunol, Seoul, South Korea. [Kwon, H.] NIAID, NIH, Bethesda, MD USA. [Kang, H.; Park, H.; Cho, S.; Min, K.] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Kim, Y.] Natl Med Ctr, Dept Internal Med, Seoul, South Korea. 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 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD JUN PY 2011 VL 66 SU 94 SI SI MA 1160 BP 446 EP 446 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 286IS UT WOS:000329462202341 ER PT J AU Weinberg, CR Shi, M Umbach, DM AF Weinberg, Clarice R. Shi, Min Umbach, David M. TI RE: "GENETIC ASSOCIATION AND GENE-ENVIRONMENT INTERACTION: A NEW METHOD FOR OVERCOMING THE LACK OF EXPOSURE INFORMATION IN CONTROLS" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 [Weinberg, Clarice R.; Shi, Min; Umbach, David M.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM weinber2@niehs.nih.gov NR 1 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 IS 11 BP 1346 EP U148 DI 10.1093/aje/kwr105 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 770AC UT WOS:000291058400020 PM 21558409 ER PT J AU Adgent, M Daniels, J Rogan, W Adair, L Edwards, L Westreich, D Maisonet, M Marcus, M AF Adgent, M. Daniels, J. Rogan, W. Adair, L. Edwards, L. Westreich, D. Maisonet, M. Marcus, M. TI EARLY LIFE SOY EXPOSURE AND TIME TO MENARCHE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Adgent, M.; Daniels, J.; Rogan, W.; Adair, L.; Edwards, L.; Westreich, D.; Maisonet, M.; Marcus, M.] NIEHS, Durham, NC USA. RI Marcus, Michele/J-2746-2015; Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S297 EP S297 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601449 ER PT J AU Barry, KH Koutros, S Berndt, SI Andreotti, G Hoppin, JA Sandler, DP Burdette, LA Yeager, M Freeman, LEB Lubin, JH Ma, X Zheng, T Alavanja, MCR AF Barry, K. H. Koutros, S. Berndt, S. I. Andreotti, G. Hoppin, J. A. Sandler, D. P. Burdette, L. A. Yeager, M. Freeman, L. E. Beane Lubin, J. H. Ma, X. Zheng, T. Alavanja, M. C. R. TI GENETIC VARIATION IN BASE EXCISION REPAIR PATHWAY GENES, PESTICIDE EXPOSURE, AND PROSTATE CANCER RISK SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Barry, K. H.; Koutros, S.; Berndt, S. I.; Andreotti, G.; Hoppin, J. A.; Sandler, D. P.; Burdette, L. A.; Yeager, M.; Freeman, L. E. Beane; Lubin, J. H.; Ma, X.; Zheng, T.; Alavanja, M. C. R.] NCI, DCEG, DHHS, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S162 EP S162 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600630 ER PT J AU Bowers, K Yeung, E Williams, M Tobias, D Qi, L Hu, F Zhang, CL AF Bowers, Katherine Yeung, Edwina Williams, Michelle Tobias, Deirdre Qi, Lu Hu, Frank Zhang, Cuilin TI A PROSPECTIVE STUDY OF PRE-PREGNANCY DIETARY IRON INTAKE AND RISK FOR GESTATIONAL DIABETES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Bowers, Katherine; Yeung, Edwina; Williams, Michelle; Tobias, Deirdre; Qi, Lu; Hu, Frank; Zhang, Cuilin] NICHD, NIH, Rockville, MD USA. RI Bowers, Katherine/N-5226-2015 NR 0 TC 0 Z9 0 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S42 EP S42 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600163 ER PT J AU Brenner, AV Neta, G Sturgis, EM Pfeiffer, RM Hutchinson, A Xu, L Balasubramaniam, S Wheeler, W Ron, E Tucker, MA Chanock, J Sigurdson, AJ AF Brenner, A. V. Neta, G. Sturgis, E. M. Pfeiffer, R. M. Hutchinson, A. Xu, L. Balasubramaniam, S. Wheeler, W. Ron, E. Tucker, M. A. Chanock, J. Sigurdson, A. J. TI COMMON GENETIC VARIANTS IN IMMUNE GENES AND RISK OF PAPILLARY THYROID CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Brenner, A. V.; Neta, G.; Sturgis, E. M.; Pfeiffer, R. M.; Hutchinson, A.; Xu, L.; Balasubramaniam, S.; Wheeler, W.; Ron, E.; Tucker, M. A.; Chanock, J.; Sigurdson, A. J.] NCI, Bethesda, MD 20892 USA. RI Pfeiffer, Ruth /F-4748-2011; Tucker, Margaret/B-4297-2015 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S16 EP S16 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600062 ER PT J AU Cupul-Uicab, LA Skjaerven, R Haug, K Longnecker, MP AF Cupul-Uicab, L. A. Skjaerven, R. Haug, K. Longnecker, M. P. TI IN UTERO EXPOSURE TO MATERNAL TOBACCO SMOKE AND SUBSEQUENT METABOLIC SYNDROME-RELATED OUTCOMES AMONG WOMEN IN THE MOBA COHORT SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Cupul-Uicab, L. A.; Skjaerven, R.; Haug, K.; Longnecker, M. P.] NIEHS, Epidemiol Branch, NIH DHHS USA, Res Triangle Pk, NC 27709 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S133 EP S133 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600519 ER PT J AU Dallal, C Brinton, L Matthews, C Peplonska, B Lissowska, J Gierach, G AF Dallal, C. Brinton, L. Matthews, C. Peplonska, B. Lissowska, J. Gierach, G. TI ACCELEROMETER MEASURES OF PHYSICAL ACTIVITY AND BREAST CANCER RISK: THE NCI POLISH BREAST CANCER STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Dallal, C.; Brinton, L.; Matthews, C.; Peplonska, B.; Lissowska, J.; Gierach, G.] NCI, Bethesda, MD 20852 USA. RI Peplonska, Beata/F-6004-2010; Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 NR 0 TC 0 Z9 0 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S91 EP S91 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600356 ER PT J AU de Gonzalez, AB AF de Gonzalez, A. Berrington TI TO SCAN OR NOT TO SCAN? THE PEDIATRIC CT DEBATE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [de Gonzalez, A. Berrington] NCI, Bethesda, MD 20892 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S85 EP S85 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600331 ER PT J AU Doria-Rose, VP Marcus, PM Prorok, PC Weiss, NS AF Doria-Rose, V. P. Marcus, P. M. Prorok, P. C. Weiss, N. S. TI THE RISK OF NON-LUNG CANCER CAUSES OF DEATH FOLLOWING SCREEN-DETECTED EARLY-STAGE LUNG CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Doria-Rose, V. P.; Marcus, P. M.; Prorok, P. C.; Weiss, N. S.] NCI, Bethesda, MD 20892 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S254 EP S254 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601289 ER PT J AU Doria-Rose, VP Klabunde, CN Riley, T Hickey, T Schoen, RE AF Doria-Rose, V. P. Klabunde, C. N. Riley, T. Hickey, T. Schoen, R. E. TI ACCURACY OF SELF-REPORT OF COLONOSCOPY FINDINGS. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Doria-Rose, V. P.; Klabunde, C. N.; Riley, T.; Hickey, T.; Schoen, R. E.] NCI, Bethesda, MD 20892 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S168 EP S168 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600655 ER PT J AU George, SM Alfano, CM Matthews, CE AF George, S. M. Alfano, C. M. Matthews, C. E. TI SEDENTARY BEHAVIOR AND PHYSICAL FUNCTIONING AMONG CANCER SURVIVORS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [George, S. M.; Alfano, C. M.; Matthews, C. E.] NCI, Bethesda, MD 20892 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S2 EP S2 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600007 ER PT J AU Gerstenblith, MR Rajaraman, P Khaykin, E Doody, MM Alexander, BH Linet, MS Freedman, DM AF Gerstenblith, M. R. Rajaraman, P. Khaykin, E. Doody, M. M. Alexander, B. H. Linet, M. S. Freedman, D. M. TI BASAL CELL CARCINOMA AND ANTHROPOMETRIC FACTORS IN THE US RADIOLOGIC TECHNOLOGISTS STUDY. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Gerstenblith, M. R.; Rajaraman, P.; Khaykin, E.; Doody, M. M.; Alexander, B. H.; Linet, M. S.; Freedman, D. M.] NCI, Bethesda, MD 20852 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S168 EP S168 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600656 ER PT J AU Gierach, G Johnson, J Geller, B Vacek, P Weaver, D Chicoine, R Shepherd, J Wang, J Herschorn, S Brinton, L Sherman, M AF Gierach, G. Johnson, J. Geller, B. Vacek, P. Weaver, D. Chicoine, R. Shepherd, J. Wang, J. Herschorn, S. Brinton, L. Sherman, M. TI RELATIONSHIP OF PERI-LESIONAL MAMMOGRAPHIC DENSITY TO PATHOLOGIC DIAGNOSIS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Gierach, G.; Johnson, J.; Geller, B.; Vacek, P.; Weaver, D.; Chicoine, R.; Shepherd, J.; Wang, J.; Herschorn, S.; Brinton, L.; Sherman, M.] NCI, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S67 EP S67 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600260 ER PT J AU Hartge, P AF Hartge, P. TI COMMUNICATING EPIDEMIOLOGY-THE CHANGING LAND SCAPE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Hartge, P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S77 EP S77 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600301 ER PT J AU Iglesias, LI Cooney, MA McLain, AC Lum, KJ Sundaram, R Louis, GMB AF Iglesias, L. I. Cooney, M. A. McLain, A. C. Lum, K. J. Sundaram, R. Louis, G. M. Buck TI POLYCHLORINATED BYPHENILS (PCBS) AND ORGANOCHLORINE PESTICIDES (OCPS) AND MENSTRUAL CYCLE LENGTH AMONG WOMEN IN THE NEW YORK STATE ANGLER PROSPECTIVE PREGNANCY STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Iglesias, L. I.; Cooney, M. A.; McLain, A. C.; Lum, K. J.; Sundaram, R.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S10 EP S10 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600037 ER PT J AU Khaykin, E Rajaraman, P Alexander, BH Doody, MM Linet, MS Freedman, DM AF Khaykin, E. Rajaraman, P. Alexander, B. H. Doody, M. M. Linet, M. S. Freedman, D. M. TI USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS AND RISK OF BASAL CELL CARCINOMA IN THE UNITED STATES RADIOLOGIC TECHNOLOGISTS STUDY. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Khaykin, E.; Rajaraman, P.; Alexander, B. H.; Doody, M. M.; Linet, M. S.; Freedman, D. M.] NCI, Bethesda, MD 20892 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S168 EP S168 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600654 ER PT J AU Kim, CJ Freedman, DM Curtis, RE de Gonzalez, AB Morton, LM AF Kim, C. J. Freedman, D. M. Curtis, R. E. de Gonzalez, A. Berrington Morton, L. M. TI RISK OF NON-HODGKIN LYMPHOMA AFTER RADIOTHERAPY FOR PRIMARY SOLID CANCERS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Kim, C. J.; Freedman, D. M.; Curtis, R. E.; de Gonzalez, A. Berrington; Morton, L. M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S249 EP S249 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601268 ER PT J AU Kleinerman, RA Yu, CL Little, M Tucker, M AF Kleinerman, R. A. Yu, C-L Little, M. Tucker, M. TI VARIATION OF SECOND CANCER RISK BY MUTATION TYPE AMONG LONG-TERM SURVIVORS OF RETINOBLASTOMA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Kleinerman, R. A.; Yu, C-L; Little, M.; Tucker, M.] NCI, Rockville, MD 20852 USA. RI Tucker, Margaret/B-4297-2015 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S254 EP S254 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601288 ER PT J AU Lin, SW Wheeler, D Park, Y Freedman, M Schatzkin, A Abnet, C AF Lin, S-W Wheeler, D. Park, Y. Freedman, M. Schatzkin, A. Abnet, C. TI UV EXPOSURE AND RISK OF CANCER AND MORTALITY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Lin, S-W; Wheeler, D.; Park, Y.; Freedman, M.; Schatzkin, A.; Abnet, C.] NCI, Bethesda, MD 20852 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S166 EP S166 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600647 ER PT J AU Lin, W AF Lin, W. TI TISSUE-BASED IMMUNE MARKERS AND CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Lin, W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S84 EP S84 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600327 ER PT J AU Major, J Cross, A Doubeni, C Park, Y Lian, M Hollenbeck, A Schatzkin, A Graubard, B Sinha, R AF Major, J. Cross, A. Doubeni, C. Park, Y. Lian, M. Hollenbeck, A. Schatzkin, A. Graubard, B. Sinha, R. TI MEAT AND MORTALITY: EXAMINATION OF AREA-BASED DEPRIVATION IN A LARGE US COHORT SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Major, J.; Cross, A.; Doubeni, C.; Park, Y.; Lian, M.; Hollenbeck, A.; Schatzkin, A.; Graubard, B.; Sinha, R.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S324 EP S324 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601556 ER PT J AU Matthews, CE AF Matthews, C. E. TI THE BIOLOGICAL MECHANISMS UNDERLYING THE LINKS BETWEEN SEDENTARY BEHAVIORS AND DISEASE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Matthews, C. E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S316 EP S316 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601524 ER PT J AU Myers, SL Hoppin, JA Sandler, DP Baird, DD AF Myers, S. L. Hoppin, J. A. Sandler, D. P. Baird, D. D. TI ORGANOPHOSPHATE PESTICIDE USE AND SELF-REPORTED INCIDENT UTERINE FIBROIDS IN THE AGRICULTURAL HEALTH STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Myers, S. L.; Hoppin, J. A.; Sandler, D. P.; Baird, D. D.] NIEHS, Res Triangle Pk, NC 27709 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S12 EP S12 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600045 ER PT J AU Neta, G Brenner, A Sturgis, EM Pfeiffer, RM Hutchinson, A Aschebrook-Kilfoy, B Xu, L Wheeler, W Abend, M Ron, E Tucker, M Chanock, S Sigurdson, AJ AF Neta, G. Brenner, A. Sturgis, E. M. Pfeiffer, R. M. Hutchinson, A. Aschebrook-Kilfoy, B. Xu, L. Wheeler, W. Abend, M. Ron, E. Tucker, M. Chanock, S. Sigurdson, A. J. TI COMMON GENETIC VARIANTS RELATED TO GENOMIC INTEGRITY AND RISK OF PAPILLARY THYROID CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Neta, G.; Brenner, A.; Sturgis, E. M.; Pfeiffer, R. M.; Hutchinson, A.; Aschebrook-Kilfoy, B.; Xu, L.; Wheeler, W.; Abend, M.; Ron, E.; Tucker, M.; Chanock, S.; Sigurdson, A. J.] NCI, DCEG, Rockville, MD USA. RI Aschebrook-Kilfoy, Briseis/A-2537-2012; Tucker, Margaret/B-4297-2015 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S164 EP S164 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600638 ER PT J AU Nyante, SJ Graubard, BI McQuillan, G Platz, EA Rohrmann, S Bradwin, G McGlynn, KA AF Nyante, S. J. Graubard, B. I. McQuillan, G. Platz, E. A. Rohrmann, S. Bradwin, G. McGlynn, K. A. TI TESTOSTERONE LEVELS IN US MALES IN THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY, 1988-1991 TO 1999-2004 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Nyante, S. J.; Graubard, B. I.; McQuillan, G.; Platz, E. A.; Rohrmann, S.; Bradwin, G.; McGlynn, K. A.] NCI, Bethesda, MD 20892 USA. RI Rohrmann, Sabine/D-2113-2012 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S107 EP S107 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600417 ER PT J AU Perkins, NJ Whitcomb, B Lyles, R AF Perkins, N. J. Whitcomb, B. Lyles, R. TI ANALYSIS OF RANDOMLY POOLED CASE-CONTROL DATA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Perkins, N. J.; Whitcomb, B.; Lyles, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S186 EP S186 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601021 ER PT J AU Persson, EC Evans, AA London, WT Weber, JP LeBlanc, A Chen, G Lin, WY McGlynn, KA AF Persson, E. C. Evans, A. A. London, W. T. Weber, J. P. LeBlanc, A. Chen, G. Lin, W. Y. McGlynn, K. A. TI DICHLORODIPHENYLTRICHLOROETHANE (DDT) AND RISK OF HEPATOCELLULAR CARCINOMA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Persson, E. C.; Evans, A. A.; London, W. T.; Weber, J. P.; LeBlanc, A.; Chen, G.; Lin, W. Y.; McGlynn, K. A.] NCI, Rockville, MD 20852 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S2 EP S2 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600005 ER PT J AU Pollack, AZ Schisterman, EF Goldman, LR Mumford, SL Perkins, NJ Bloom, MS Rudra, CB Browne, RW Wactawski-Wende, J AF Pollack, A. Z. Schisterman, E. F. Goldman, L. R. Mumford, S. L. Perkins, N. J. Bloom, M. S. Rudra, C. B. Browne, R. W. Wactawski-Wende, J. TI METALS AND LIPID PEROXIDATION IN WOMEN. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Pollack, A. Z.; Schisterman, E. F.; Goldman, L. R.; Mumford, S. L.; Perkins, N. J.; Bloom, M. S.; Rudra, C. B.; Browne, R. W.; Wactawski-Wende, J.] NICHD, NIH, Rockville, MD USA. RI Pollack, Anna/F-2021-2011; Goldman, Lynn/D-5372-2012 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S177 EP S177 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600689 ER PT J AU Rajaraman, P Simpson, J Neta, G de Gonzalez, AB Ansell, P Ron, E Roman, E AF Rajaraman, P. Simpson, J. Neta, G. de Gonzalez, A. Berrington Ansell, P. Ron, E. Roman, E. TI EARLY-LIFE EXPOSURE TO DIAGNOSTIC RADIATION AND ULTRASOUND SCANS AND RISK OF CHILDHOOD CANCER: A CASE-CONTROL STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Rajaraman, P.; Simpson, J.; Neta, G.; de Gonzalez, A. Berrington; Ansell, P.; Ron, E.; Roman, E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 3 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S69 EP S69 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600268 ER PT J AU Schebrook-Kilfoy, BA Neta, G Brenner, AV Feiffer, RP Hutchinson, A Sturgis, EM Xu, L Wheeler, W Ron, E Tucker, MA Chanock, SJ Sigurdson, AJ AF Schebrook-Kilfoy, B. A. Neta, G. Brenner, A. V. Feiffer, R. P. Hutchinson, A. Sturgis, E. M. Xu, L. Wheeler, W. Ron, E. Tucker, M. A. Chanock, S. J. Sigurdson, A. J. TI COMMON GENETIC VARIANTS IN METABOLISM AND DETOXIFICATION PATHWAY GENES AND RISK OF PAPILLARY THYROID CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Schebrook-Kilfoy, B. A.; Neta, G.; Brenner, A. V.; Feiffer, R. P.; Hutchinson, A.; Sturgis, E. M.; Xu, L.; Wheeler, W.; Ron, E.; Tucker, M. A.; Chanock, S. J.; Sigurdson, A. J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S15 EP S15 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600058 ER PT J AU Shiels, MS Chaturvedi, A Katki, H Gochuico, B Caporaso, N Engels, E AF Shiels, M. S. Chaturvedi, A. Katki, H. Gochuico, B. Caporaso, N. Engels, E. TI CIRCULATING MARKERS OF INTERSTITIAL LUNG DISEASE AND SUBSEQUENT RISK OF LUNG CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Shiels, M. S.; Chaturvedi, A.; Katki, H.; Gochuico, B.; Caporaso, N.; Engels, E.] NCI, Rockville, MD 20892 USA. RI Katki, Hormuzd/B-4003-2015 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S88 EP S88 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600344 ER PT J AU Trabert, B Graubard, BI Erickson, RL McGlynn, KA AF Trabert, B. Graubard, B. I. Erickson, R. L. McGlynn, K. A. TI MUMPS, ORCHITIS AND TESTICULAR GERM CELL TUMORS: A CAUSE FOR CONCERN? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Trabert, B.; Graubard, B. I.; Erickson, R. L.; McGlynn, K. A.] NCI, Rockville, MD 20852 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S165 EP S165 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600643 ER PT J AU Wang, Y Chen, A Dietrich, K Rogan, W AF Wang, Y. Chen, A. Dietrich, K. Rogan, W. TI POSTNATAL EXPOSURE TO METHYL MERCURY AND COGNITIVE DEVELOPMENT IN 7-YEAR-OLD CHILDREN. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA DE Mercury; IQ; behavior; diet C1 [Wang, Y.; Chen, A.; Dietrich, K.; Rogan, W.] NIEHS, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S221 EP S221 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601161 ER PT J AU Weinberg, CR Shi, M Umbach, DM AF Weinberg, C. R. Shi, M. Umbach, D. M. TI A SIBLING-AUGMENTED CASE-ONLY DESIGN FOR ASSESSING MULTIPLICATIVE GENE-ENVIRONMENT INTERACTION SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Weinberg, C. R.; Shi, M.; Umbach, D. M.] NIEHS, Res Triangle Pk, NC 27709 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S69 EP S69 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600270 ER PT J AU Fornage, M Debette, S Bis, JC Schmidt, H Ikram, MA Dufouil, C Sigurdsson, S Lumley, T DeStefano, AL Fazekas, F Vrooman, HA Shibata, DK Maillard, P Zijdenbos, A Smith, AV Gudnason, H de Boer, R Cushman, M Mazoyer, B Heiss, G Vernooij, MW Enzinger, C Glazer, NL Beiser, A Knopman, DS Cavalieri, M Niessen, WJ Harris, TB Petrovic, K Lopez, OL Au, R Lambert, JC Hofman, A Gottesman, RF Garcia, M Heckbert, SR Atwood, LD Catellier, DJ Uitterlinden, AG Yang, Q Smith, NL Aspelund, T Romero, JR Rice, K Taylor, KD Nalls, MA Rotter, JI Sharrett, R van Duijn, CM Amouyel, P Wolf, PA Gudnason, V van der Lugt, A Boerwinkle, E Psaty, BM Seshadri, S Tzourio, C Breteler, MMB Mosley, TH Schmidt, R Longstreth, WT DeCarli, C Launer, LJ AF Fornage, Myriam Debette, Stephanie Bis, Joshua C. Schmidt, Helena Ikram, M. Arfan Dufouil, Carole Sigurdsson, Sigurdur Lumley, Thomas DeStefano, Anita L. Fazekas, Franz Vrooman, Henri A. Shibata, Dean K. Maillard, Pauline Zijdenbos, Alex Smith, Albert V. Gudnason, Haukur de Boer, Renske Cushman, Mary Mazoyer, Bernard Heiss, Gerardo Vernooij, Meike W. Enzinger, Christian Glazer, Nicole L. Beiser, Alexa Knopman, David S. Cavalieri, Margherita Niessen, Wiro J. Harris, Tamara B. Petrovic, Katja Lopez, Oscar L. Au, Rhoda Lambert, Jean-Charles Hofman, Albert Gottesman, Rebecca F. Garcia, Melissa Heckbert, Susan R. Atwood, Larry D. Catellier, Diane J. Uitterlinden, Andre G. Yang, Qiong Smith, Nicholas L. Aspelund, Thor Romero, Jose R. Rice, Kenneth Taylor, Kent D. Nalls, Michael A. Rotter, Jerome I. Sharrett, Richey van Duijn, Cornelia M. Amouyel, Philippe Wolf, Philip A. Gudnason, Vilmundur van der Lugt, Aad Boerwinkle, Eric Psaty, Bruce M. Seshadri, Sudha Tzourio, Christophe Breteler, Monique M. B. Mosley, Thomas H. Schmidt, Reinhold Longstreth, W. T. DeCarli, Charles Launer, Lenore J. TI Genome-Wide Association Studies of Cerebral White Matter Lesion Burden: The CHARGE Consortium SO ANNALS OF NEUROLOGY LA English DT Article ID HYPERINTENSITY VOLUME; HYPERTENSIVE SIBSHIPS; GENE-EXPRESSION; BLOOD-PRESSURE; LEUKOARAIOSIS; DISEASE; PROTEIN; LOCI; HEART; SCANS AB Objective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. Methods: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. Results: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (p(discovery) = 4.0 x 10(-9); p(replication) = 1.3 x 10(-7); p(combined) = 4.0 x 10(-15)). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 x 10(-9)), rs11869977 (p = 5.7 x 10(-9)), rs936393 (p = 6.8 x 10(-9)), rs3744017 (p = 7.3 x 10(-9)), and rs1055129 (p = 4.1 x 10(-8)). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample). Interpretation: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH. ANN NEUROL 2011;69:928-939 C1 [Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX USA. [Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Div Epidemiol, Sch Publ Hlth, Houston, TX USA. [Debette, Stephanie; DeStefano, Anita L.; Beiser, Alexa; Au, Rhoda; Atwood, Larry D.; Romero, Jose R.; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Bis, Joshua C.; Glazer, Nicole L.; Psaty, Bruce M.; Longstreth, W. T.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bis, Joshua C.; Glazer, Nicole L.; Psaty, Bruce M.; Longstreth, W. T.] Univ Washington, Dept Med, Seattle, WA USA. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [Ikram, M. Arfan; Vrooman, Henri A.; de Boer, Renske; Vernooij, Meike W.; Hofman, Albert; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Breteler, Monique M. B.] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. Arfan; de Boer, Renske; Vernooij, Meike W.; van der Lugt, Aad] Erasmus MC Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Dufouil, Carole; Tzourio, Christophe] Hop La Pitie Salpetriere, INSERM, U708, Paris, France. [Dufouil, Carole; Tzourio, Christophe] Univ Paris 06, Paris, France. [Sigurdsson, Sigurdur; Smith, Albert V.; Gudnason, Haukur; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Lumley, Thomas; Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [DeStefano, Anita L.; Beiser, Alexa; Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Fazekas, Franz; Enzinger, Christian; Cavalieri, Margherita; Petrovic, Katja; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Vrooman, Henri A.; de Boer, Renske; Niessen, Wiro J.] Erasmus MC Univ Med Ctr, Dept Med Informat, Rotterdam, Netherlands. [Vrooman, Henri A.; de Boer, Renske; Niessen, Wiro J.] Erasmus MC Univ Med Ctr, Biomed Imaging Grp Rotterdam, Rotterdam, Netherlands. [Shibata, Dean K.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Maillard, Pauline; Mazoyer, Bernard] Univ Caen Basse Normandie, Caen, France. [Maillard, Pauline; Mazoyer, Bernard] Ctr Energie Atom, Ctr Natl Rech Sci, Grp Imagerie Neurofonct, Caen, France. [Zijdenbos, Alex] Biospective Inc, Montreal, PQ, Canada. [Zijdenbos, Alex] McGill Univ, Neurol Inst, Montreal, PQ, Canada. [Cushman, Mary] Univ Vermont, Dept Pathol & Med, Burlington, VT USA. [Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Knopman, David S.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Cavalieri, Margherita; Launer, Lenore J.] Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, I-44100 Ferrara, Italy. [Harris, Tamara B.; Garcia, Melissa] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Lopez, Oscar L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Lambert, Jean-Charles; Amouyel, Philippe] Inst Pasteur, INSERM, U744, F-59019 Lille, France. [Gottesman, Rebecca F.; Sharrett, Richey] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Heckbert, Susan R.; Smith, Nicholas L.; Psaty, Bruce M.; Longstreth, W. T.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Catellier, Diane J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Uitterlinden, Andre G.] Erasmus MC Univ Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Uitterlinden, Andre G.] Erasmus MC Univ Med Ctr, Dept Clin Chem, Rotterdam, Netherlands. [Smith, Nicholas L.] Dept Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med Geriatr, Jackson, MS 39216 USA. [Longstreth, W. T.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. [DeCarli, Charles] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. RP Fornage, M (reprint author), 2121 W Holcombe Blvd,Suite 1007A, Houston, TX 77030 USA. EM Myriam.Fornage@uth.tmc.edu RI Lambert, jean-charles/A-9553-2014; Mazoyer, Bernard/B-6303-2012; Aspelund, Thor/F-4826-2011; LICEND, CEMND/F-1296-2015; Breteler, Monique /J-5058-2014; Gudnason, Vilmundur/K-6885-2015; Vernooij, Meike/E-4061-2016; Smith, Albert/K-5150-2015; Aspelund, Thor/C-5983-2008; Cavalieri, Margherita/G-8053-2012; Dufouil, Carole/J-4968-2012; Rice, Kenneth/A-4150-2013; Yang, Qiong/G-5438-2014; Tzourio, christophe/B-4015-2009 OI Lambert, jean-charles/0000-0003-0829-7817; Maillard, Pauline/0000-0003-3516-6345; Seshadri, Sudha/0000-0001-6135-2622; Au, Rhoda/0000-0001-7742-4491; Ikram, Mohammad Arfan/0000-0003-0372-8585; Beiser, Alexa/0000-0001-8551-7778; Mazoyer, Bernard/0000-0003-0970-2837; Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Aspelund, Thor/0000-0002-7998-5433; Rice, Kenneth/0000-0001-5779-4495; Tzourio, christophe/0000-0002-6517-2984 FU Baxter; Forest, Janssen; University of Washington; Fondation Plan Alzheimer; National Research Agency; Ipsen; Servier; Pfizer; Alzheimer Foundation FX C. Dufouil: consultancy, Eisai Company; travel expenses, Lundbeck. A.Z.: consulting fee, Biospective Inc.; employment, Biospective Inc. D. S. K.: consultancy, Lilly; grants/grants pending, Baxter, Forest, Janssen. O.L.L., consultancy, Pfizer, Eisai. N.L.S.: grant/grants pending, University of Washington; travel support, University of Washington. P. A.: grants/grants pending, Fondation Plan Alzheimer, National Research Agency, Ipsen; board membership, Leducq Foundation; consultancy, Ipsen; employment, Institut Pasteur de Lille; speaking fees, Servier, Pfizer; patents, University Lille 2, Inserm, Institut Pasteur de Lille; stock/stock options, Genoscreen. C. T.: grants/grants pending, National Research Agency, Alzheimer Foundation. C. DeCarli, consultancy, Merck, Elan. NR 33 TC 82 Z9 82 U1 0 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2011 VL 69 IS 6 BP 928 EP 939 DI 10.1002/ana.22403 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 782JA UT WOS:000292003100006 PM 21681796 ER PT J AU Eberle, FC Jaffe, ES AF Eberle, Franziska C. Jaffe, Elaine S. TI Gray zone lymphomas: a biological experiment, and a challenge for diagnosis and management SO ANNALS OF ONCOLOGY LA English DT Editorial Material ID B-CELL LYMPHOMA; CLASSICAL HODGKINS LYMPHOMA; SIGNATURE; FEATURES; REVEALS; DISEASE C1 [Eberle, Franziska C.] Univ Tubingen, Dept Dermatol, Tubingen, Germany. [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Eberle, FC (reprint author), Univ Tubingen, Dept Dermatol, Tubingen, Germany. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 16 TC 3 Z9 3 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 64 EP 66 DI 10.1093/annonc/mdr178 PG 3 WC Oncology SC Oncology GA 782GK UT WOS:000291996300012 ER PT J AU Royo, C Navarro, A Clot, G Salaverria, I Wilson, W Wiestner, A Lopez-Guillermo, A Trim, N Colomer, D Erber, W Ott, G Rosenwald, A Siebert, R Bea, S Campo, E AF Royo, C. Navarro, A. Clot, G. Salaverria, I. Wilson, W. Wiestner, A. Lopez-Guillermo, A. Trim, N. Colomer, D. Erber, W. Ott, G. Rosenwald, A. Siebert, R. Bea, S. Campo, E. TI DIFFERENTIAL EXPRESSION OF SOX11, HDGFRP3, AND DBN1 IDENTIFIES TWO SUBGROUPS OF MCL WITH DIFFERENT CLINICAL OUTCOME AND GENETIC FEATURES SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Royo, C.; Navarro, A.; Clot, G.] Hosp Clin Barcelona, Fdn Clin, IDIBAPS, Barcelona, Spain. [Salaverria, I.] Christian Albrechts Univ Kiel, Inst Human Genet, Kiel, Germany. [Salaverria, I.] Univ Hosp Schleswig Holstein, Kiel, Germany. [Wilson, W.; Wiestner, A.] NIH, Hematol Branch, Bethesda, MD 20892 USA. [Lopez-Guillermo, A.] Hosp Clin Barcelona, Hematopathol Dept, Barcelona, Spain. [Trim, N.; Erber, W.] Addenbrookes Hosp, Dept Haematol, Cambridge CB2 2QQ, England. [Colomer, D.] Hosp Clin Barcelona, Hematopathol Dept, Barcelona, Spain. [Ott, G.] Robert Bosch Krankenhaus, Clin Pathol, Stuttgart, Germany. [Ott, G.] Inst Klin Pharmakol, Stuttgart, Germany. [Rosenwald, A.] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. [Siebert, R.] Christian Albrechts Univ Kiel, Inst Human Genet, Kiel, Germany. [Siebert, R.] Univ Hosp Schleswig Holstein, Kiel, Germany. [Campo, E.] Univ Barcelona, Dept Pathol, Hosp Clin, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 86 EP 86 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300032 ER PT J AU Dunleavy, K Pittaluga, S Wayne, AS Shovlin, M Johnson, JL Little, R Steinberg, S Cheson, BD Hsi, E Jaffe, ES Wilson, WH AF Dunleavy, K. Pittaluga, S. Wayne, A. S. Shovlin, M. Johnson, J. L. Little, R. Steinberg, S. Cheson, B. D. Hsi, E. Jaffe, E. S. Wilson, W. H. TI MYC+ AGGRESSIVE-B-CELL LYMPHOMAS: NOVEL THERAPY OF UNTREATED BURKITT LYMPHOMA (BL) AND MYC+ DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) WITH DA-EPOCH-R SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Dunleavy, K.; Pittaluga, S.; Wayne, A. S.; Shovlin, M.; Little, R.; Steinberg, S.; Jaffe, E. S.; Wilson, W. H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Johnson, J. L.] Duke Univ, Med Ctr, CALGB, Durham, NC 27706 USA. [Cheson, B. D.] Georgetown Univ Hosp, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Hsi, E.] Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 6 Z9 7 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 106 EP 106 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300083 ER PT J AU Dunleavy, K Pittaluga, S Shovlin, M Grant, N Grant, C Chen, C Wright, G Gascoyne, R Steinberg, S Staudt, L Jaffe, ES Wilson, WH AF Dunleavy, K. Pittaluga, S. Shovlin, M. Grant, N. Grant, C. Chen, C. Wright, G. Gascoyne, R. Steinberg, S. Staudt, L. Jaffe, E. S. Wilson, W. H. TI UNTREATED PRIMARY MEDIASTINAL B-CELL (PMBL) AND MEDIASTINAL GREY ZONE (MGZL) LYMPHOMAS: COMPARISON OF BIOLOGICAL FEATURES AND CLINICAL OUTCOME FOLLOWING DA-EPOCH-R WITHOUT RADIATION SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Dunleavy, K.; Pittaluga, S.; Shovlin, M.; Grant, N.; Grant, C.; Chen, C.; Wright, G.; Steinberg, S.; Staudt, L.; Jaffe, E. S.; Wilson, W. H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Gascoyne, R.] British Columbia Canc Agcy, Ctr Lymphoid Dis, Vancouver, BC V5Z 4E6, Canada. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 5 Z9 5 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 134 EP 134 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300162 ER PT J AU Rao, E Jiang, C Iqbal, J Lenz, G Staudt, LM Zhao, Y Mckeithan, TW Chan, WC Fu, K AF Rao, E. Jiang, C. Iqbal, J. Lenz, G. Staudt, L. M. Zhao, Y. Mckeithan, T. W. Chan, W. C. Fu, K. TI THE MIRNA-17 similar to 92 CLUSTER MEDIATES CHEMORESISTANCE AND ENHANCES TUMOR GROWTH IN MANTLE CELL LYMPHOMA VIA PI3K/AKT PATHWAY ACTIVATION SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Rao, E.; Jiang, C.; Iqbal, J.; Mckeithan, T. W.; Chan, W. C.; Fu, K.] Univ Nebraska Med Ctr, Omaha, NE USA. [Lenz, G.] Charite, Mol Krebsforschungszentrum, D-13353 Berlin, Germany. [Staudt, L. M.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zhao, Y.] Chinese Acad Sci, Inst Zool, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 145 EP 145 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300194 ER PT J AU Schmitz, R Jhavar, S Xiao, W Liu, X Powell, J Wright, GW Chan, WC Jaffe, ES Gascoyne, RD Campo, E Rosenwald, A Ott, G Delabie, J Rimsza, LM Staudt, LM AF Schmitz, R. Jhavar, S. Xiao, W. Liu, X. Powell, J. Wright, G. W. Chan, W. C. Jaffe, E. S. Gascoyne, R. D. Campo, E. Rosenwald, A. Ott, G. Delabie, J. Rimsza, L. M. Staudt, L. M. TI DISCOVERY OF RECURRENT ONCOGENIC MUTATIONS IN LYMPHOMA BY RNA-SEQ SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Schmitz, R.; Jhavar, S.; Staudt, L. M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Xiao, W.; Liu, X.; Powell, J.] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Wright, G. W.] NCI, Biometr Res Branch, DCTD, Bethesda, MD 20892 USA. [Chan, W. C.] Univ Nebraska, Dept Pathol, Omaha, NE 68182 USA. [Chan, W. C.] Univ Nebraska, Dept Microbiol, Omaha, NE 68182 USA. [Jaffe, E. S.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Gascoyne, R. D.; Rosenwald, A.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. [Campo, E.] Univ Barcelona, Hosp Clin, Barcelona, Spain. [Rosenwald, A.] Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. [Ott, G.] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany. [Ott, G.] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany. [Delabie, J.] Oslo Univ Hosp, Pathol Clin, Oslo, Norway. [Rimsza, L. M.] Univ Arizona, Dept Pathol, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 148 EP 148 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300202 ER PT J AU Steidl, C Shah, SP Woolcock, BW Rui, L Kawahara, M Farinha, P Telenius, A Ben Neriah, S Connors, JM Siebert, R Savage, KJ Jaffe, ES Staudt, LM Steidl, U Marra, MA Gascoyne, RD AF Steidl, C. Shah, S. P. Woolcock, B. W. Rui, L. Kawahara, M. Farinha, P. Telenius, A. Ben Neriah, S. Connors, J. M. Siebert, R. Savage, K. J. Jaffe, E. S. Staudt, L. M. Steidl, U. Marra, M. A. Gascoyne, R. D. TI DISCOVERY OF CIITA GENE FUSIONS IN B CELL LYMPHOMAS BY NEXT GENERATION SEQUENCING SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Marra, M. A.] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada. [Rui, L.; Staudt, L. M.] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. [Kawahara, M.; Steidl, U.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Siebert, R.] Univ Kiel, Kiel, Germany. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 0 Z9 0 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 148 EP 148 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300201 ER PT J AU Floisand, Y Brinch, L Kvalheim, G Holte, H Fowler, DA Kolstad, A AF Floisand, Y. Brinch, L. Kvalheim, G. Holte, H. Fowler, D. A. Kolstad, A. TI ALLOGENEIC STEM CELL TRANSPLANTATION IN MALIGNANT LYMPHOMA; THE NORWEGIAN EXPERIENCE SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 11th International Conference on Malignant Lymphoma CY JUN 15-18, 2011 CL Lugano, SWITZERLAND C1 [Floisand, Y.; Brinch, L.] Oslo Univ Hosp, Rikshosp, Oslo, Norway. [Kvalheim, G.; Holte, H.; Kolstad, A.] Oslo Univ Hosp, Radiumhosp, Oslo, Norway. [Fowler, D. A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2011 VL 22 SU 4 BP 233 EP 233 PG 1 WC Oncology SC Oncology GA 782GK UT WOS:000291996300475 ER PT J AU Cai, YY Berger, EA AF Cai, Yingyun Berger, Edward A. TI An immunotoxin targeting the gH glycoprotein of KSHV for selective killing of cells in the lytic phase of infection SO ANTIVIRAL RESEARCH LA English DT Article DE Kaposi's sarcoma-associated herpesvirus; Ganciclovir; Immunotoxin; Glycoprotein H; Multicentric Castleman's disease; Lytic infection ID MULTICENTRIC CASTLEMANS-DISEASE; SARCOMA-ASSOCIATED HERPESVIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMARY EFFUSION LYMPHOMA; KAPOSIS-SARCOMA; DNA-SEQUENCES; CD4-PSEUDOMONAS EXOTOXIN; ENVELOPE GLYCOPROTEIN; GENE-EXPRESSION; A-CHAIN AB Amongst the pathologies associated with infection by Kaposi's sarcoma-associated herpesvirus (KSHV), multicentric Castleman's disease is distinctive for involvement of the lytic phase of the virus replication cycle. This B cell lymphoproliferative disorder has shown clinical responsiveness not only to generalized immunotherapy and cytotoxic chemotherapy, but also to inhibitors of herpesvirus DNA replication, consistent with the involvement of lytic phase of replication. These findings suggest that selective killing of virus-producing cells might represent a novel therapeutic strategy. We designed an immunotoxin. YC15-PE38, containing a single chain variable region fragment of a monoclonal antibody against KSHV glycoprotein H (gH) linked to the effector domains of Pseudomonas aeruginosa exotoxin A. Purified YC15-PE38 displayed highly selective and potent killing of a gH-expressing transfectant cell line (subnanomolar IC(50)). The immunotoxin also strongly inhibited production of infectious KSHV virions from an induced chronically infected cell line, by virtue of selective killing of the virus-producing cells. Combination treatment studies indicated complementary activities between YC15-PE38 and the herpesviral DNA replication inhibitor ganciclovir. These results provide support for the development of anti-KSHV strategies based on targeted killing of infected cells expressing lytic phase genes. Published by Elsevier B.V. C1 [Cai, Yingyun; Berger, Edward A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM eberger@niaid.nih.gov FU NIH, NIAID; NCI, NIH FX We thank Deboeeta Chatterjee (NIAID, NIH) for helpful discussions and Virgilio Bundoc (NIAID, NIH) for excellent technical assistance. We extend our thanks to Joseph Newland (NIAID, NIH), Tapan Bera, John Weldon, Dawn Walker, and Ira Pastan (NCI, NIH) for technical advice and donation of PE-based immunotoxins. Jeffrey Vieira (U. Washington) kindly provided Vero-219 cells and the BacK-50 baculovirus. This research was funded in part by the Intramural Program of the NIH, NIAID. Y.C. and E.A.B. are co-inventors on an NIH-owned patent application on the YC15 hybridoma/mAb and the YC15-PE38 immunotoxin. NR 49 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2011 VL 90 IS 3 BP 143 EP 150 DI 10.1016/j.antiviral.2011.03.175 PG 8 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 781ED UT WOS:000291912500006 PM 21440007 ER PT J AU Estes, A Shaw, DWW Sparks, BF Friedman, S Giedd, JN Dawson, G Bryan, M Dager, SR AF Estes, Annette Shaw, Dennis W. W. Sparks, Bobbi F. Friedman, Seth Giedd, Jay N. Dawson, Geraldine Bryan, Matthew Dager, Stephen R. TI Basal Ganglia Morphometry and Repetitive Behavior in Young Children with Autism Spectrum Disorder SO AUTISM RESEARCH LA English DT Article DE neuroimaging; preschoolers < pediatrics; clinical psychology; repetitive behavior; autism spectrum disorders ID HIGH-FUNCTIONING AUTISM; CAUDATE-NUCLEUS; BRAIN SIZE; AGE; PATTERNS; VOLUME; INTERESTS; INFANCY; LIFE; MRI AB We investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3- to 4-year-old children with autism spectrum disorder (ASD; n = 77) and developmental delay without autism (DD; n = 34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n = 45), DD (n = 14), and a group of children with typical development (TD; n = 25) were also assessed by magnetic resonance imaging. Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus. Autism Res 2011,4:212-220. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc. C1 [Estes, Annette] Univ Washington, UW Autism Ctr, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. [Estes, Annette; Dager, Stephen R.] Univ Washington, Autism Ctr, Seattle, WA 98195 USA. [Shaw, Dennis W. W.; Sparks, Bobbi F.; Friedman, Seth; Dager, Stephen R.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Giedd, Jay N.] NIMH, Bethesda, MD 20892 USA. [Dawson, Geraldine] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Dawson, Geraldine] Autism Speaks, New York, NY USA. [Bryan, Matthew] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Estes, A (reprint author), Univ Washington, UW Autism Ctr, Dept Speech & Hearing Sci, Box 357920, Seattle, WA 98195 USA. EM estesa@u.washington.edu RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU National Institute of Child Health and Human Development; National Institute on Deafness and Communication Disorders [U19HD34565]; National Institute of Child Health and Human Development [P50HD55782]; National Institute of Child Health and Human Development which is part of the Autism Centers of Excellence (ACE) [P50HD55782] FX Grant sponsors: National Institute of Child Health and Human Development; National Institute on Deafness and Communication Disorders; Grant number: U19HD34565; Grant sponsor: National Institute of Child Health and Human Development; Grant number: P50HD55782.; This research was funded by a program project grant from the National Institute of Child Health and Human Development and the National Institute on Deafness and Communication Disorders (U19HD34565) which is part of the NICHD Collaborative Program of Excellence in Autism (CPEA) and a program project grant from the National Institute of Child Health and Human Development (P50HD55782) which is part of the Autism Centers of Excellence (ACE). NR 42 TC 42 Z9 43 U1 1 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-3792 J9 AUTISM RES JI Autism Res. PD JUN PY 2011 VL 4 IS 3 BP 212 EP 220 DI 10.1002/aur.193 PG 9 WC Behavioral Sciences; Psychology, Developmental SC Behavioral Sciences; Psychology GA 781CO UT WOS:000291908400005 PM 21480545 ER PT J AU Varmus, H AF Varmus, Harold TI Update from the Hill: Budget Battle SO CANCER DISCOVERY LA English DT Editorial Material C1 Natl Canc Inst, Bethesda, MD 20892 USA. RP Varmus, H (reprint author), Natl Canc Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JUN PY 2011 VL 1 IS 1 BP 7 EP 8 DI 10.1158/2159-8290.CD-ND11-01 PG 2 WC Oncology SC Oncology GA 832CY UT WOS:000295780300008 ER PT J AU Szabo, E AF Szabo, Eva TI Altered Histology Provides a Positive Clinical Signal in the Bronchial Epithelium SO CANCER PREVENTION RESEARCH LA English DT Article ID PHASE IIB TRIAL; INTRAEPITHELIAL NEOPLASIA; FORMER SMOKERS; LUNG-CANCER; DYSPLASIA; PREVENTION; CHEMOPREVENTION; BUDESONIDE; CARCINOMA; PLACEBO AB The history of lung cancer chemoprevention trials has been uniformly disappointing in that the large phase III studies showed no effect or harm in actively smoking participants, and smaller phase II studies have also been negative. In this issue of the journal (beginning on page 793), Keith and colleagues report their randomized, placebo-controlled trial of the oral prostacyclin analogue iloprost, the first trial to show an improvement in bronchial histology (i.e., regression), which occurred in former, but not current, smokers with sputum atypia. This Perspective discusses the strength of the clinical signal provided by this observation and its implications for further drug development. Cancer Prev Res; 4(6); 775-8. (C) 2011 AACR. C1 NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH,DHHS, Bethesda, MD 20892 USA. RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH,DHHS, 6130 Execut Blvd,Rm 2132, Bethesda, MD 20892 USA. EM szaboe@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 18 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUN PY 2011 VL 4 IS 6 BP 775 EP 778 DI 10.1158/1940-6207.CAPR-11-0214 PG 4 WC Oncology SC Oncology GA 771ZR UT WOS:000291199700001 PM 21636542 ER PT J AU Alguacil, J Kogevinas, M Silverman, DT Malats, N Real, FX Garcia-Closas, M Tardon, A Rivas, M Tora, M Garcia-Closas, R Serra, C Carrato, A Pfeiffer, RM Fortuny, J Samanic, C Rothman, N AF Alguacil, Juan Kogevinas, Manolis Silverman, Debra T. Malats, Nuria Real, Francisco X. Garcia-Closas, Montserrat Tardon, Adonina Rivas, Manuel Tora, Montserrat Garcia-Closas, Reina Serra, Consol Carrato, Alfredo Pfeiffer, Ruth M. Fortuny, Joan Samanic, Claudine Rothman, Nathaniel TI Urinary pH, cigarette smoking and bladder cancer risk SO CARCINOGENESIS LA English DT Article ID N-ACETYLBENZIDINE; GLUCURONIDATION; 4-AMINOBIPHENYL; METABOLISM; BENZIDINE; LIVER; DOG AB Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite can be rapidly hydrolyzed in acidic urine to undergo further metabolic activation and form DNA adducts in the urothelium. We conducted a large multicenter case-control study in Spain to explore the etiology of bladder cancer and evaluated the association between urine pH and bladder cancer risk, alone and in combination with cigarette smoking. In total, 712 incident urothelial cell carcinoma cases and 611 hospital controls directly measured their urine pH with dipsticks twice a day (first void in the morning and early in the evening) during four consecutive days 2 weeks after hospital discharge. We found that a consistently acidic urine pH <= 6.0 was associated with an increased risk of bladder cancer [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2-1.9] compared with all other subjects. Furthermore, risk estimates for smoking intensity and risk of bladder cancer among current smokers tended to be higher for those with a consistently acidic urine (OR = 8.8, 11.5 and 23.8) compared with those without (OR = 4.3, 7.7 and 5.8, respectively, for 1-19, 20-29 and 30+ cigarettes per day; P(interaction) for 30+ cigarettes per day = 0.024). These results suggest that urine pH, which is determined primarily by diet and body surface area, may be an important modifier of smoking and risk of bladder cancer. C1 [Alguacil, Juan; Silverman, Debra T.; Samanic, Claudine; Rothman, Nathaniel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA. [Alguacil, Juan] Univ Huelva, Ctr Invest Salud & Medio Ambiente CYSMA, E-21071 Huelva, Spain. [Kogevinas, Manolis; Fortuny, Joan] Inst Municipal Invest Med, Ctr Res Environm Epidemiol, E-08003 Barcelona, Spain. [Kogevinas, Manolis] Univ Crete, Sch Med, Iraklion 71003, Greece. [Malats, Nuria; Real, Francisco X.] Spanish Natl Canc Res Ctr, E-28029 Madrid, Spain. [Real, Francisco X.; Serra, Consol] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, E-08003 Barcelona, Spain. [Garcia-Closas, Montserrat] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA. [Tardon, Adonina; Rivas, Manuel] Univ Oviedo, E-33006 Oviedo, Spain. [Tora, Montserrat] Univ Autonoma Barcelona, E-08003 Barcelona, Spain. [Tora, Montserrat] Inst Municipal Invest Med, Inst Recerca, Hosp Mar, E-08003 Barcelona, Spain. [Garcia-Closas, Reina] Hosp Univ Canarias, E-38320 San Cristobal la Laguna, Spain. [Serra, Consol] Consorci Hosp Parc Tauli, E-08208 Sabadell, Spain. [Carrato, Alfredo] Hosp Gen Elche, E-03202 Elche, Spain. [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA. RP Alguacil, J (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA. EM alguacil@dbasp.uhu.es RI Pfeiffer, Ruth /F-4748-2011; Serra, C/E-6879-2014; Garcia-Closas, Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Real Arribas, Francisco/H-5275-2015; Kogevinas, Manolis/C-3918-2017 OI Serra, C/0000-0001-8337-8356; Garcia-Closas, Montserrat /0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; Real Arribas, Francisco/0000-0001-9501-498X; FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics [N02-CP-11015]; Fondo de Investigacion Sanitaria/Spain [98/1274, 00/0745, G03/174, G03/160, C03/09, C03/10] FX Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (including NCI Contract #N02-CP-11015); Fondo de Investigacion Sanitaria/Spain (98/1274, 00/0745, G03/174, G03/160, C03/09, C03/10). NR 18 TC 13 Z9 13 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2011 VL 32 IS 6 BP 843 EP 847 DI 10.1093/carcin/bgr048 PG 5 WC Oncology SC Oncology GA 782AG UT WOS:000291979200008 PM 21402590 ER PT J AU Gao, Y Hayes, RB Huang, WY Caporaso, NE Burdette, L Yeager, M Chanock, SJ Berndt, SI AF Gao, Ying Hayes, Richard B. Huang, Wen-Yi Caporaso, Neil E. Burdette, Laurie Yeager, Meredith Chanock, Stephen J. Berndt, Sonja I. TI DNA repair gene polymorphisms and tobacco smoking in the risk for colorectal adenomas SO CARCINOGENESIS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; CANCER SCREENING TRIAL; NON-SYNONYMOUS SNPS; LUNG-CANCER; EXO1 GENE; ATAXIA-TELANGIECTASIA; PROMOTER POLYMORPHISM; BREAST-CANCER; DIOL EPOXIDE AB DNA damage is thought to play a critical role in the development of colorectal adenoma. Variation in DNA repair genes may alter their capacity to correct endogenous and exogenous DNA damage. We explored the association between common single-nucleotide polymorphisms (SNPs) in DNA repair genes and adenoma risk with a case-control study nested in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 1338 left sided, advanced colorectal adenoma cases and 1503 matched controls free of left-sided polyps were included in the study. Using DNA extracted from blood, 3144 tag SNPs in 149 DNA repair genes were successfully genotyped. Among Caucasians, 30 SNPs were associated with adenoma risk at P < 0.01, with four SNPs remaining significant after gene-based adjustment for multiple testing. The most significant finding was for a non-synonymous SNP (rs9350) in Exonuclease-1 (EXO1) [odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.11-1.51, P = 0.001)], which was predicted to be damaging using bioinformatics methods. However, the association was limited to smokers with a strong risk for current smokers (OR = 2.15, 95% CI = 1.27-3.65) and an intermediate risk for former smokers (OR = 1.45, 95% CI = 1.14-1.82) and no association for never smokers (OR = 0.98, 95% CI = 0.76-1.25) (P(interaction) = 0.002). Among the top findings, an SNP (rs17503908) in ataxia telangiectasia mutated (ATM) was inversely related to adenoma risk (OR = 0.75, 95% CI = 0.63-0.91). The association was restricted to never smokers (OR = 0.55, 95% CI = 0.40-0.76) with no increased risk observed among smokers (OR = 0.89, 95% CI = 0.70-1.13) (P(interaction) = 0.006). This large comprehensive study, which evaluated all presently known DNA repair genes, suggests that polymorphisms in EXO1 and ATM may be associated with risk for advanced colorectal adenoma with the associations modified by tobacco-smoking status. C1 [Gao, Ying] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Gao, Y (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Bldg EPS,Room 7110, Bethesda, MD 20892 USA. EM gaoying@mail.nih.gov OI Hayes, Richard/0000-0002-0918-661X FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH) FX Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH). NR 56 TC 14 Z9 14 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2011 VL 32 IS 6 BP 882 EP 887 DI 10.1093/carcin/bgr071 PG 6 WC Oncology SC Oncology GA 782AG UT WOS:000291979200015 PM 21504893 ER PT J AU Bourdi, M Davies, JS Pohl, LR AF Bourdi, Mohammed Davies, John S. Pohl, Lance R. TI Mispairing C57BL/6 Substrains of Genetically Engineered Mice and Wild-Type Controls Can Lead to Confounding Results as It Did in Studies of JNK2 in Acetaminophen and Concanavalin A Liver Injury SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID TERMINAL KINASE; DIFFERENTIAL SUSCEPTIBILITY; BEHAVIORAL-DIFFERENCES; COPY NUMBER; KNOCKOUT AB C57BL/6 mice are widely used in biomedical research for the background of genetically engineered mice (GEM) and wild-type controls With the belief that the genetic background of GEM and control mice differ significantly by only one or more altered genes. This principle, however, does have limitations due in part to the existence of multiple substrains of C57BL/6 mice that should not be used interchangeably as they can differ both genetically and phenotypically. We show here that these mispairings do occur frequently and can lead to inaccurate and conflicting findings. C1 [Bourdi, Mohammed; Davies, John S.; Pohl, Lance R.] NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bourdi, M (reprint author), NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH,Dept Hlth & Human Serv, Bldg 10,Room 8N 110, Bethesda, MD 20892 USA. EM bourdim@nhlbi.nih.gov OI Davies, John/0000-0002-9482-1066 FU National Institutes of Health; National Heart, Lung, and Blood Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health and the National Heart, Lung, and Blood Institute. NR 22 TC 29 Z9 30 U1 0 U2 2 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 JUN PY 2011 VL 24 IS 6 BP 794 EP 796 DI 10.1021/tx200143x PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 780YG UT WOS:000291896700004 PM 21557537 ER PT J AU Weinstein, DH Childs, R Heller, T AF Weinstein, Douglas H. Childs, Richard Heller, Theo TI Giant Duodenal Ectasia SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID LESIONS C1 [Weinstein, Douglas H.; Childs, Richard; Heller, Theo] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, DH (reprint author), NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 DK999999]; NIDDK NIH HHS [ZIA DK075008] NR 4 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2011 VL 9 IS 6 BP XXVII EP XXVII DI 10.1016/j.cgh.2011.01.016 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 778HA UT WOS:000291693300002 PM 21277390 ER PT J AU Salit, RB Bishop, MR AF Salit, Rachel B. Bishop, Michael R. TI Reduced-intensity Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: A Concise Review SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Review DE Allogeneic stem cell transplant; Donor lymphocyte infusion; Immunomodulatory drugs; Multiple myeloma; Reduced intensity transplantation ID DONOR-LYMPHOCYTE INFUSION; AUTOLOGOUS TRANSPLANTATION; BONE-MARROW; REMISSION; AGENTS; IMMUNOTHERAPY; THALIDOMIDE; BORTEZOMIB; ALLOGRAFTS; AUTOGRAFT AB Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) can result in reliable donor engraftment, relatively low treatment-related mortality, and sustained remissions in the treatment of multiple myeloma. However, substantial cytoreduction pre-allografting is often necessary because of a variable graft-versus-myeloma effect. The use of RIC allogeneic HSCT immediately after autologous HSCT provides a temporal separation between tumor reduction by high-dose chemotherapy and the graft-versus-myeloma effect. There are currently a number of prospective trials attempting to address the issue of whether this strategy leads to decreases in relapse and/or improvement in overall survival as compared with double autologous transplants. Unfortunately, similar to autografting, relapse remains the major cause of treatment failure after RIC allogeneic HSCT. To improve treatment results with allografting, consideration should be given to incorporating immunomodulatory drugs and targeted treatments to enhance pretransplantation remission status, as posttransplantation maintenance therapy, or in combination with donor lymphocyte infusions for refractory or relapsed disease. Studies exploring these strategies are ongoing. Clinical Lymphoma, Myeloma & Leukemia, Vol. 11, No. 3, 247-52 (C) 2011 Elsevier Inc. All rights reserved. C1 [Salit, Rachel B.; Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Salit, Rachel B.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Salit, RB (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, 10 Ctr Dr,CRC Room 4-3152, Bethesda, MD 20892 USA. EM salitr@mail.nih.gov FU Center for Cancer Research, National Cancer Institute FX This work was supported by the Center for Cancer Research, National Cancer Institute, Intramural Research Program. NR 36 TC 7 Z9 8 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD JUN PY 2011 VL 11 IS 3 BP 247 EP 252 DI 10.1016/j.clml.2011.03.010 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 783ER UT WOS:000292064800001 PM 21658650 ER PT J AU Signore, C Landon, MB AF Signore, Caroline Landon, Mark B. TI Delivery After Previous Cesarean Preface SO CLINICS IN PERINATOLOGY LA English DT Editorial Material C1 [Signore, Caroline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA. [Landon, Mark B.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Columbus, OH 43210 USA. RP Signore, C (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA. EM signorec@mail.nih.gov; mark.landon@osumc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD JUN PY 2011 VL 38 IS 2 BP XV EP XVI DI 10.1016/j.clp.2011.03.014 PG 2 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 784PR UT WOS:000292169700002 PM 21645787 ER PT J AU Strenziok, M Pulaski, S Krueger, F Zamboni, G Clawson, D Grafman, J AF Strenziok, Maren Pulaski, Sarah Krueger, Frank Zamboni, Giovanna Clawson, Deborah Grafman, Jordan TI Regional Brain Atrophy and Impaired Decision Making on the Balloon Analog Risk Task in Behavioral Variant Frontotemporal Dementia SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Article DE decision making; stimulus-reinforcement learning; orbitofrontal cortex; BART; frontotemporal dementia ID HUMAN ORBITOFRONTAL CORTEX; CONSTRUCT-VALIDITY; PREFRONTAL CORTEX; TAKING PROPENSITY; BART; IMPULSIVITY; REWARD; REPRESENTATIONS; PERFORMANCE; ACTIVATION AB Objective: The goal of this study was 2-fold, first, to compare decision making in behavioral variant frontotemporal dementia (bvFTD) patients and healthy adults using the Balloon Analog Risk Task (BART), and, second, to identify the regions of gray matter atrophy associated with bvFTD patients' BART performance. Background: Stimulus-reinforcement learning is required to evaluate the results of previously chosen actions to improve future decisions. Although there is a well established literature suggesting altered decision making in FTD patients and data from lesion studies suggest orbitofrontal cortex (OFC) involvement in decision making, there is very little research looking at the brain correlates of decision making in FTD populations specifically. Method: Twenty-seven bvFTD patients and 19 age-matched and education-matched normal controls completed the BART. Voxel-based morphometry analysis was performed on the magnetic resonance imaging scans of a subset of patients. Results: Compared with healthy controls, the bvFTD patients did not learn and pumped less to inflate a balloon to receive a reward, indicating altered stimulus-reinforcement learning. The voxel-based morphometry analysis indicated that bvFTD patients' impaired BART performance was related to atrophy in the right lateral OFC. Conclusions: The right lateral OFC is crucial for stimulus-reinforcement learning required for the adjustment of behavior under changing reward contingencies. C1 [Grafman, Jordan] Kessler Fdn Res Ctr, Traumat Brain Injury Res Lab, W Orange, NJ 07052 USA. [Pulaski, Sarah; Clawson, Deborah] Catholic Univ Amer, Washington, DC 20064 USA. [Strenziok, Maren] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Krueger, Frank] George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22030 USA. [Krueger, Frank; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Zamboni, Giovanna] Univ Oxford, FMRIB Ctr, Oxford OX3 9DU, England. [Zamboni, Giovanna] Univ Oxford, Div Expt Med, NDM, Oxford OX3 9DU, England. RP Grafman, J (reprint author), Kessler Fdn Res Ctr, Traumat Brain Injury Res Lab, 1199 Pleasant Valley Way, W Orange, NJ 07052 USA. EM JGrafman@kesslerfoundation.org RI Zamboni, Giovanna/F-3583-2017; OI Zamboni, Giovanna/0000-0002-6133-3373; Grafman, Jordan H./0000-0001-8645-4457 FU National Institutes of Health, National Institute of Neurological Disorders and Stroke FX Supported by the intramural research program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. NR 45 TC 6 Z9 6 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD JUN PY 2011 VL 24 IS 2 BP 59 EP 67 DI 10.1097/WNN.0b013e3182255a7c PG 9 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 784VP UT WOS:000292186700003 PM 21697710 ER PT J AU Haas, DM Gallauresi, B Shields, K Zeitlin, D Clark, SM Hebert, MF Ren, ZX Nallani, SC Meslin, EM Feibus, KB Koren, G Goebel, WS Easterling, T Denne, SC Flockhart, DA Renbarger, JL AF Haas, David M. Gallauresi, Beverly Shields, Kristine Zeitlin, Deborah Clark, Shannon M. Hebert, Mary F. Ren, Zhaoxia Nallani, Srikanth C. Meslin, Eric M. Feibus, Karen B. Koren, Gideon Goebel, W. Scott Easterling, Thomas Denne, Scott C. Flockhart, David A. Renbarger, Jamie L. TI Pharmacotherapy and Pregnancy: Highlights from the Third International Conference for Individualized Pharmacotherapy in Pregnancy SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article ID PRESCRIPTION DRUG-USE; PRETERM LABOR; PHARMACOKINETICS; WOMEN; HYPERTENSION; ASSOCIATION; POSTPARTUM; MANAGEMENT; GLYBURIDE; METFORMIN AB To address provider struggles to provide evidence-based, rational drug therapy to pregnant women, this third Conference was convened to highlight the current progress and research in the field. Speakers from academic centers, industry, and governmental institutions spoke about: the Food and Drug Administration's role in pregnancy pharmacology and the new labeling initiative; drug registries in pregnancy; the pharmacist's role in medication use in pregnancy; therapeutic areas such as preterm labor, gestational diabetes, nausea and vomiting in pregnancy, and hypertension; breast-feeding and medications; ethical challenges for consent in pregnancy drug studies; the potential for cord blood banks; and concerns about the fetus when studying drugs in pregnancy. The Conference highlighted several areas of collaboration within the current Obstetrics Pharmacology Research Units Network and hoped to educate providers, researchers, and agencies with the common goal to improve the ability to safely and effectively use individualized pharmacotherapy in pregnancy. Clin Trans Sci 2011; Volume 4: 204-209 C1 [Haas, David M.; Meslin, Eric M.; Goebel, W. Scott; Denne, Scott C.; Flockhart, David A.; Renbarger, Jamie L.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Haas, David M.; Meslin, Eric M.; Denne, Scott C.; Flockhart, David A.; Renbarger, Jamie L.] Indiana Univ, Ctr Pharmacogenet & Therapeut Res Maternal & Chil, PREGMED, Indianapolis, IN 46204 USA. [Gallauresi, Beverly; Nallani, Srikanth C.; Feibus, Karen B.] US FDA, Silver Spring, MD USA. [Shields, Kristine] Merck & Co Inc, N Wales, PA USA. [Zeitlin, Deborah] Butler Univ, Indianapolis, IN 46208 USA. [Clark, Shannon M.] Univ Texas Med Branch, Galveston, TX USA. [Hebert, Mary F.; Easterling, Thomas] Univ Washington, Seattle, WA 98195 USA. [Ren, Zhaoxia] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Meslin, Eric M.] Indiana Univ, Ctr Bioeth, Indianapolis, IN 46204 USA. [Koren, Gideon] Sick Kids Hosp, Motherisk Program, Toronto, ON, Canada. RP Haas, DM (reprint author), Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. EM dahaas@iupui.edu FU Indiana University-Purdue University, Indianapolis Signature Center; Indiana University Center for Pharmacogenetics and Therapeutics Research in Maternal and Child Health; U.S. Food and Drug Administration, Office of Women's Health; National Institute for Child Health and Human Development, National Institutes of Health FX Funding for the conference was provided by an Indiana University-Purdue University, Indianapolis Signature Center Grant to PREGMED, the Indiana University Center for Pharmacogenetics and Therapeutics Research in Maternal and Child Health.; Speakers would like to acknowledge the U.S. Food and Drug Administration, Office of Women's Health and the National Institute for Child Health and Human Development, National Institutes of Health for providing travel funds for affiliated speakers. NR 31 TC 3 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD JUN PY 2011 VL 4 IS 3 BP 204 EP 209 DI 10.1111/j.1752-8062.2011.00280.x PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 783TR UT WOS:000292107400016 PM 21707952 ER PT J AU Driscoll, I Troncoso, J AF Driscoll, Ira Troncoso, Juan TI Brain Resilience and Plasticity in the Face of Alzheimer Pathology SO CURRENT ALZHEIMER RESEARCH LA English DT Editorial Material C1 [Driscoll, Ira] NIA, NIH, Baltimore, MD 21224 USA. [Troncoso, Juan] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Driscoll, I (reprint author), NIA, NIH, Baltimore, MD 21224 USA. FU NIA NIH HHS [P50 AG005146] NR 0 TC 0 Z9 0 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JUN PY 2011 VL 8 IS 4 BP 329 EP 329 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 783LB UT WOS:000292082800001 PM 21557722 ER PT J AU Driscoll, I Troncoso, J AF Driscoll, I. Troncoso, J. TI Asymptomatic Alzheimer's Disease: A Prodrome or a State of Resilience? SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Normal aging; MCI; AD; neuropathology; beta-amyloid; neuronal hypertrophy ID MILD COGNITIVE IMPAIRMENT; DEMENTED OLD PEOPLE; NEUROFIBRILLARY TANGLES; NONDEMENTED INDIVIDUALS; NEURONAL HYPERTROPHY; AMYLOID DEPOSITION; BETA-A4 DEPOSITS; UNITED-STATES; PLAQUES; NEUROPATHOLOGY AB Neuritic plaques and neurofibrillary tangles, the neuropathological hallmarks of AD, are not limited to individuals with dementia. These pathologic changes can also be present in the brains of cognitively normal older adults - a condition we defined as Asymptomatic AD (ASYMAD). Although it remains unclear whether these individuals would remain clinically normal with longer survival, they seem to be able to compensate for or delay the appearance of dementia symptoms. Here, we provide a historical background and highlight the combined clinical, pathologic and morphometric evidence related to ASYMAD. Understanding the nature of changes during this apparently asymptomatic state may shed light on the mechanisms that forestall the progression of the disease and allow for maintenance of cognitive health, an important area of research that has been understudied relative to the identification of risks and pathways to negative health outcomes. C1 [Driscoll, I.; Troncoso, J.] Johns Hopkins Univ, Sch Med, Dept Pathol Neuropathol, Baltimore, MD 21205 USA. [Driscoll, I.] NIA, NIH, Baltimore, MD 21224 USA. [Troncoso, J.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Driscoll, I (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol Neuropathol, Ross Bldg 558,720 Rutland Ave, Baltimore, MD 21205 USA. EM troncoso@jhmi.edu FU NIA NIH HHS [P50 AG005146-27, P50 AG005146] NR 79 TC 23 Z9 23 U1 2 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JUN PY 2011 VL 8 IS 4 BP 330 EP 335 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 783LB UT WOS:000292082800002 PM 21222594 ER PT J AU Beason-Held, LL AF Beason-Held, L. L. TI Dementia and the Default Mode SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Functional imaging; brain function; mild cognitive impairment; MCI; Alzheimer's disease; AD; age; PET; fMRI; human ID MILD COGNITIVE IMPAIRMENT; VOXEL-BASED MORPHOMETRY; RESTING-STATE NETWORKS; GRAY-MATTER LOSS; POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; BRAIN ACTIVITY; FUNCTIONAL MRI; MEMORY; DEACTIVATION AB Changes in regional activity levels and network connectivity occur across the lifespan within the default mode network (DMN) of resting brain function. Changes with age are noted in most components of the DMN, especially in medial frontal/anterior cingulate and posterior cingulate/precuneus regions. Individuals with age-related disease such as mild cognitive impairment (MCI) and Alzheimer's disease (AD) demonstrate additional default-related changes particularly in posterior cingulate/precuneus and hippocampal regions. As these regions are areas of known pathologic change in both normal aging and age-related disease, examining DMN activity may allow future studies to more fully assess the relationship between pathology and function in these regions. The ability to form this structure-function link could allow us to determine critical factors involved in the decline or preservation of function in the presence of age-related neuropathology. C1 NIA, NIH, Baltimore, MD 21224 USA. RP Beason-Held, LL (reprint author), NIA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM heldlo@mail.nih.gov FU NIH, National Institute on Aging; [N01-AG-3-2124] FX Dr. Beason-Held's work is supported by the Intramural Research Program of the NIH, National Institute on Aging and by Research and Development Contract N01-AG-3-2124. NR 69 TC 15 Z9 16 U1 1 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JUN PY 2011 VL 8 IS 4 BP 361 EP 365 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 783LB UT WOS:000292082800007 PM 21222595 ER PT J AU Sojkova, J Resnick, SM AF Sojkova, J. Resnick, S. M. TI In Vivo Human Amyloid Imaging SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE PiB; amyloid; aging; MCI; AD; cognition; MRI; FDG; pathology; human; brain ID PITTSBURGH COMPOUND-B; MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; PRECLINICAL ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID MARKERS; LATE-ONSET ALZHEIMERS; 2-YEAR FOLLOW-UP; A-BETA; APOLIPOPROTEIN-E; PIB-PET AB PET imaging agents such as Pittsburgh compound B (PiB) allow detection of fibrillar beta-amyloid (A beta) in vivo. In addition to quantification of A beta deposition in mild cognitive impairment and Alzheimer's disease, PiB has also increased our understanding of A beta deposition in older adults without cognitive impairment. In vivo A beta deposition has been studied in relation to genotype, structural and functional brain changes, as well as alterations in biomarker levels. To date, several studies have reported changes in A beta burden over time. This, together with investigation of the relationship between A beta deposition and cognition, sets the stage for elucidation of the temporal sequence of the neurobiological events leading to cognitive decline. Furthermore, correlation of A beta levels detected by PiB PET and those obtained from biopsy or postmortem specimens will allow more rigorous quantitative interpretation of PiB PET data in relation to neuropathological evaluation. Since the first human study in 2004, in vivo amyloid imaging has led to advances in our understanding of the role of A beta deposition in human aging and cognitive decline, as well as provided new tools for patient selection and therapeutic monitoring in clinical trials. C1 [Sojkova, J.; Resnick, S. M.] NIA, Lab Behav Neurosci, NIH, Biomed Res Ctr,IRP, Baltimore, MD 21224 USA. [Sojkova, J.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21218 USA. RP Resnick, SM (reprint author), NIA, Lab Behav Neurosci, NIH, Biomed Res Ctr,IRP, 251 Bayview Blvd,Room 4B317, Baltimore, MD 21224 USA. EM resnicks@grc.nia.nih.gov FU NIH, National Institute on Aging; [N01-AG-3-2124] FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging and N01-AG-3-2124. NR 84 TC 17 Z9 17 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JUN PY 2011 VL 8 IS 4 BP 366 EP 372 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 783LB UT WOS:000292082800008 PM 21222593 ER PT J AU Chaves, LF Hamer, GL Walker, ED Brown, WM Ruiz, MO Kitron, UD AF Chaves, Luis F. Hamer, Gabriel L. Walker, Edward D. Brown, William M. Ruiz, Marilyn O. Kitron, Uriel D. TI Climatic variability and landscape heterogeneity impact urban mosquito diversity and vector abundance and infection SO ECOSPHERE LA English DT Article DE Chicago; entomological risk; Filariasis; habitat gradient; metacommunity; nuisance; richness; Rift Valley fever; Schmalhausen's law; West Nile virus ID WEST-NILE-VIRUS; DROUGHT-INDUCED AMPLIFICATION; LOUIS-ENCEPHALITIS-VIRUS; BIODIVERSITY CONSERVATION; CULEX-QUINQUEFASCIATUS; COMMUNITY STRUCTURE; DIPTERA-CULICIDAE; CURRENT KNOWLEDGE; LARVAL MOSQUITOS; MALARIA CONTROL AB Urban habitat heterogeneity can modify interactions across species and lead to spatially fine grained differences in beta-diversity patterns and their associated ecosystem services. Here, we study the impacts of landscape heterogeneity and climatic variability on: (1) the richness and diversity patterns of mosquitoes (Diptera: Culicidae) and (2) the abundance and West Nile virus infection rate of the house mosquito, Culex pipiens, in Chicago, USA. We conducted a four year long study (2005-2008) in 8 sites that captured a gradient of urban heterogeneities. We found a total of 19 mosquito species, a representative sample of mosquito species richness in the area, according to both model estimation (Chao2 +/- S. E. = 20.50 +/- 2.29) and faunal records for Chicago. We found that heterogeneity in the landscape was the best predictor of both mosquito species richness and diversity, with the most heterogeneous landscapes harboring the largest number of species. In general there were no changes in species richness over the years that could be associated with weather patterns and climatic variability (WPCV). In contrast, changes in diversity were associated with WPCV. Our results also showed that WPCV had major impacts on house mosquito abundance and West Nile virus mosquito infection rate (MIR) patterns. Although MIR was independent of mosquito diversity, it was associated with overall mosquito abundance, which had a convex association with species richness (i.e., abundance increases to a point after which it decreases as function of species richness). Finally, our results highlight the importance of considering dominant vector species as part of a community of vectors, whose biodiversity patterns can directly or indirectly impact the risk of infectious disease transmission. C1 [Chaves, Luis F.; Kitron, Uriel D.] Emory Univ, Dept Environm Studies, Atlanta, GA 30322 USA. [Chaves, Luis F.] Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 060, Japan. [Chaves, Luis F.] Hokkaido Univ, Global Ctr Excellence Program Integrated Field En, Sapporo, Hokkaido, Japan. [Chaves, Luis F.] Univ Nacl, Escuela Med Vet, Programa Invest Enfermedades Trop, Heredia, Costa Rica. [Hamer, Gabriel L.] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA. [Hamer, Gabriel L.] Michigan State Univ, Dept Fisheries & Wildlife, Lansing, MI USA. [Walker, Edward D.] Michigan State Univ, Dept Entomol, Lansing, MI USA. [Walker, Edward D.] Michigan State Univ, Dept Microbiol & Mol Genet, Lansing, MI USA. [Brown, William M.; Ruiz, Marilyn O.] Univ Illinois, Dept Pathobiol, Urbana, IL 61801 USA. [Kitron, Uriel D.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Chaves, LF (reprint author), Emory Univ, Dept Environm Studies, Atlanta, GA 30322 USA. EM lfchave@emory.edu RI Chaves, Luis Fernando/F-3448-2010 OI Chaves, Luis Fernando/0000-0002-5301-2764 FU NSF Ecology of Infectious Disease [0429124, 0840403]; University of Illinois Adaptive Infrastructure Information Systems Initiative; Emory University; Research and Policy for Infectious Disease Dynamics (RAPIDD) mosquito-borne disease program of the Science and Technology Directorate; Fogarty International Center, National Institutes of Health; Gorgas Memorial Research Grant of the American Society of Tropical Medicine and Hygiene; Japan Society for the Promotion of Science (JSPS) FX We thank the municipalities and residents of Alsip, Oak Lawn, Chicago, Palos Hills and Evergreen Park for their cooperation with our study. For the mosquito field work we counted with the invaluable help of: T. Thompson, D. Gohde, M. Neville, M. Goshorn, B Pultorak, J. McClain, L. Abernathy, R. Atkins, J. Sidge, B. Bullard. Our study was funded by NSF Ecology of Infectious Disease Grants 0429124 (West Nile Virus: Eco-Epidemiology of Disease Emergence in Urban Areas) and 0840403 (Eco-epidemiology of Disease Emergence in Urban Areas II), the University of Illinois Adaptive Infrastructure Information Systems Initiative (WMB and MOR) and Emory University (LFC and UDK). LFC and UDK were also supported by Research and Policy for Infectious Disease Dynamics (RAPIDD) mosquito-borne disease program of the Science and Technology Directorate and the Fogarty International Center, National Institutes of Health. LFC was additionally supported by a Gorgas Memorial Research Grant of the American Society of Tropical Medicine and Hygiene and a Post-Doctoral Fellowship and Grant in Aid for research from Japan Society for the Promotion of Science (JSPS). NR 97 TC 8 Z9 9 U1 3 U2 23 PU ECOLOGICAL SOC AMER PI WASHINGTON PA 1990 M STREET NW, STE 700, WASHINGTON, DC 20036 USA SN 2150-8925 J9 ECOSPHERE JI Ecosphere PD JUN PY 2011 VL 2 IS 6 AR UNSP art70 DI 10.1890/ES11-00088.1 PG 21 WC Ecology SC Environmental Sciences & Ecology GA V30IW UT WOS:000208810700006 ER PT J AU Mazzone, L Reale, L Mannino, V Guarnera, M Vitiello, B AF Mazzone, Luigi Reale, Laura Mannino, Valeria Guarnera, Manuela Vitiello, Benedetto TI Atomoxetine for the treatment of attention-deficit/hyperactivity disorder symptoms in children with different cognitive abilities SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Meeting Abstract C1 [Mazzone, Luigi] Univ Catania, Pediat, I-95124 Catania, Italy. [Reale, Laura; Mannino, Valeria; Guarnera, Manuela] Univ Catania, I-95124 Catania, Italy. [Vitiello, Benedetto] NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1018-8827 EI 1435-165X J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD JUN PY 2011 VL 20 IS 1 SU S MA P01-27 BP S123 EP S123 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA V47CB UT WOS:000209928800375 ER PT J AU Catherino, WH AF Catherino, William H. TI Stress relief to augment fertility: the pressure mounts SO FERTILITY AND STERILITY LA English DT Editorial Material DE Infertility; stress response; alpha-amylase; psychological testing; psychological counseling ID IN-VITRO FERTILIZATION; OCCUPATIONAL PSYCHOLOGICAL STRESS; ASSISTED REPRODUCTIVE TECHNOLOGY; ENTERING IVF-TREATMENT; INVITRO FERTILIZATION; EMBRYO TRANSFER; INFERTILITY; WOMEN; SUPPORT; NOREPINEPHRINE AB Current studies have not conclusively demonstrated an objective and consistent marker of an aberrant stress response; an effect of such a stress response on reproductive outcome; or a benefit of counseling on reproductive outcome in such patients. (Fertil Steril (R) 2011; 95: 2462-3. (C) 2011 by American Society for Reproductive Medicine.) C1 [Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [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, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM catheriw@mail.nih.gov NR 36 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 2011 VL 95 IS 8 BP 2462 EP 2463 DI 10.1016/j.fertnstert.2011.05.067 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 782TI UT WOS:000292034100032 PM 21704209 ER PT J AU Ewens, KG Jones, MR Ankener, W Stewart, DR Urbanek, M Dunaif, A Legro, RS Chua, A Azziz, R Spielman, RS Goodarzi, MO Strauss, JF AF Ewens, Kathryn G. Jones, Michelle R. Ankener, Wendy Stewart, Douglas R. Urbanek, Margrit Dunaif, Andrea Legro, Richard S. Chua, Angela Azziz, Ricardo Spielman, Richard S. Goodarzi, Mark O. Strauss, Jerome F., III TI Type 2 diabetes susceptibility single-nucleotide polymorphisms are not associated with polycystic ovary syndrome SO FERTILITY AND STERILITY LA English DT Editorial Material DE Polycystic ovary syndrome (PCOS); transmission disequilibrium test (TDT); SNP ID GENOME-WIDE ASSOCIATION; GLUCOSE-INTOLERANCE; INSULIN-RESISTANCE; COMMON VARIANTS; SYNDROME PCOS; TCF7L2 GENE; RISK; WOMEN; LOCI; PREVALENCE AB Two cohorts of women with polycystic ovary syndrome (PCOS), comprising 400 probands and affected sisters in 365 families and a case-control group including 395 women with PCOS and 171 healthy women with regular menstrual cycles, were studied to determine whether single-nucleotide polymorphisms (SNPs) identified as susceptibility loci in genomewide association studies of type 2 diabetes are also associated with PCOS. None of the 18 allelic variants in 10 genes previously shown to be associated with type 2 diabetes were found to be associated with PCOS, but some were associated with indices of beta cell function. (Fertil Steril (R) 2011; 95: 2538-41. (C) 2011 by American Society for Reproductive Medicine.) C1 [Ewens, Kathryn G.; Ankener, Wendy; Spielman, Richard S.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Jones, Michelle R.; Chua, Angela; Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA. [Stewart, Douglas R.] NHGRI, NIH, Bethesda, MD 20892 USA. [Urbanek, Margrit; Dunaif, Andrea] Northwestern Univ, Div Endocrinol Metab & Mol Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Legro, Richard S.] Penn State Hershey Coll Med, Dept Obstet & Gynecol, Hershey, PA USA. [Azziz, Ricardo] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Los Angeles, CA 90048 USA. [Strauss, Jerome F., III] Virginia Commonwealth Univ, Dept Obstet & Gynecol, Richmond, VA 23298 USA. RP Strauss, JF (reprint author), Virginia Commonwealth Univ, Dept Obstet & Gynecol 7628, Richmond, VA 23298 USA. EM jfstrauss@vcu.edu RI Azziz, Ricardo/N-7229-2014 OI Azziz, Ricardo/0000-0002-3917-0483 FU National Institutes of Health (NIH) [U54HD034449]; Division of Intramural Research of the National Human Genome Research Institute [P50 HD44405, U54 HD34449, RR10732, C06 RR016499, M01 RR00048, M01 RR10732, M01 RR02635, R01-HD29364, K24-HD01346, R01-DK79888]; Division of Intramural Research of the National Human Genome Research Institute, NCCR [M01-RR00425]; Pennsylvania Department of Health [SAP 41-000-26343] FX Supported by National Institutes of Health (NIH) Grants U54HD034449 (to J.F.S. and R. S. S.); Division of Intramural Research of the National Human Genome Research Institute (D. R. S.); P50 HD44405 (A. D.); U54 HD34449 (to M. U. and A. D.); RR10732 and C06 RR016499 [to Pennsylvania State University General Clinical Research Center (GCRC)]; M01 RR00048 (to Northwestern University GCRC); M01 RR10732 and M01 RR02635 (to Brigham and Women's Hospital GCRC); R01-HD29364 and K24-HD01346 (to R. A.); R01-DK79888 (to M.O.G.); and M01-RR00425 (General Clinical Research Center Grant from the NCRR); the Winnick Clinical Scholars Award (to M.O.G.); and an endowment from the Helping Hand of Los Angeles, Inc. Funded in part under a grant with the Pennsylvania Department of Health using Tobacco Settlement Funds (R. S. L.-SAP 41-000-26343). The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. 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 29 TC 17 Z9 17 U1 0 U2 3 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 JUN PY 2011 VL 95 IS 8 BP 2538 EP U566 DI 10.1016/j.fertnstert.2011.02.050 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 782TI UT WOS:000292034100054 PM 21444075 ER PT J AU Michalakis, KG Mesen, TB Brayboy, L Yu, B Richter, KS Levy, M Widra, E Segars, JH AF Michalakis, Konstantinos G. Mesen, Tolga B. Brayboy, LynaeM. Yu, Bo Richter, Kevin S. Levy, Michael Widra, Eric Segars, James H. TI Subclinical elevations of thyroid-stimulating hormone and assisted reproductive technology outcomes SO FERTILITY AND STERILITY LA English DT Editorial Material DE TSH; autoimmunity; ART; subclinical hypothyroidism; diminished ovarian reserve ID IN-VITRO FERTILIZATION; INFERTILE WOMEN; PREGNANCY; HYPOTHYROIDISM; AUTOIMMUNITY; DISORDERS; RISK; TSH AB The prevalence of moderately elevated TSH levels consistent with subclinical hypothyroidism (2.5-4.0 mu IU/mL) was 23% in a cohort of 1,231 women pursuing assisted reproductive technologies. Preconception elevated levels of TSH were associated with diminished ovarian reserve but were not associated with adverse assisted reproductive technology or pregnancy outcomes. (Fertil Steril (R) 2011;95:2634-7. (C) 2011 by American Society for Reproductive Medicine.) C1 [Michalakis, Konstantinos G.; Mesen, Tolga B.; Brayboy, LynaeM.; Yu, Bo; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Mesen, Tolga B.] Carolinas Med Ctr, Dept Obstet & Gynecol, Charlotte, NC 28203 USA. [Brayboy, LynaeM.] Abington Mem Hosp, Dept Obstet & Gynecol, Abington, PA 19001 USA. [Richter, Kevin S.; Levy, Michael; Widra, Eric] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. RP Segars, JH (reprint author), CRC, Pediat & Reprod Endocrinol Branch, 10 Ctr Dr,1E-3140, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov FU Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX Supported in part by the intramural research program of the Program of Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 21 TC 18 Z9 22 U1 1 U2 4 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 JUN PY 2011 VL 95 IS 8 BP 2634 EP 2637 DI 10.1016/j.fertnstert.2011.02.056 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 782TI UT WOS:000292034100083 PM 21457968 ER PT J AU Shaw, CM Stanczyk, FZ Egleston, BL Kahle, LL Spittle, CS Godwin, AK Brinton, LA Dorgan, JF AF Shaw, Christiana M. Stanczyk, Frank Z. Egleston, Brian L. Kahle, L. L. Spittle, Cynthia S. Godwin, Andrew K. Brinton, Louise A. Dorgan, Joanne F. TI Serum antimullerian hormone in healthy premenopausal women SO FERTILITY AND STERILITY LA English DT Editorial Material DE Mullerian-inhibiting substance (MIS); antimullerian hormone (AMH); ovary; premenopausal; healthy ID ANTI-MULLERIAN HORMONE; POLYCYSTIC-OVARY-SYNDROME; LATE REPRODUCTIVE-AGE; SPONTANEOUS MENSTRUAL-CYCLE; INHIBITING SUBSTANCE; CONTRACEPTIVES; VARIABILITY; RESERVE AB Antimullerian hormone (AMH) is extensively studied in ovarian aging and pathology; however, little is known about correlates in healthy premenopausal women. We found that AMH levels are strongly inversely associated with age and differed significantly between oral contraceptive pill users and nonusers, whereas no significant associations were seen between AMH and other clinical, behavioral, and anthropometric characteristics and laboratory variables, making it an attractive hormone for clinical applications. (Fertil Steril (R) 2011;95:2718-21. (C)2011 by American Society for Reproductive Medicine.) C1 [Shaw, Christiana M.] Univ Florida, Dept Surg, Gainesville, FL 32610 USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Stanczyk, Frank Z.] Womens & Childrens Hosp, Los Angeles, CA USA. [Egleston, Brian L.; Dorgan, Joanne F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Kahle, L. L.] Informat Management Serv Inc, Rockville, MD USA. [Spittle, Cynthia S.] Mol MD Corp, Portland, OR USA. [Godwin, Andrew K.] Univ Kansas, Dept Pathol & Lab Med, Kansas City, KS USA. [Brinton, Louise A.] NCI, Rockville, MD USA. RP Shaw, CM (reprint author), Univ Florida, Dept Surg, 1600 SW Archer Rd,POB 100109, Gainesville, FL 32610 USA. EM christiana.shaw@surgery.ufl.edu RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU US Department of Defense [BC062367]; National Institutes of Health [P30CA006927]; US Department of Health and Human Services [T32CA103652] FX Supported by the US Department of Defense (grant no. BC062367), the National Institutes of Health (grant no. P30CA006927), the US Department of Health and Human Services (grant no. T32CA103652), and by the National Institutes of Health Intramural Research Program. NR 30 TC 21 Z9 22 U1 0 U2 1 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 JUN PY 2011 VL 95 IS 8 BP 2718 EP 2721 DI 10.1016/j.fertnstert.2011.05.051 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 782TI UT WOS:000292034100107 PM 21704216 ER PT J AU Smith, K Alnifaidy, R Wei, QX Nieman, LK AF Smith, Kathryn Alnifaidy, Redab Wei, Qingxiang Nieman, Lynnette K. TI Endometrial Indian hedgehog expression is decreased in women with endometriosis SO FERTILITY AND STERILITY LA English DT Editorial Material DE Indian hedgehog; endometriosis; endometrium; progesterone ID PROGESTERONE RESISTANCE; REDUCED EXPRESSION; MOUSE UTERUS; RECEPTOR-B; IMPLANTATION; INFERTILITY; TARGETS; FAILURE AB Nuclear and cytoplasmic endometrial expression of Indian hedgehog increased from the late proliferative to mid and late secretory phases in 26 healthy volunteers compared with 30 women with endometriosis. The abnormal expression of Indian hedgehog protein in women with endometriosis suggests a resistance to P action. (Fertil Steril (R) 2011;95:2738-41. (C)2011 by American Society for Reproductive Medicine.) C1 [Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bldg 10,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM niemanl@mail.nih.gov FU Intramural NIH HHS [Z01 HD000637-14] NR 22 TC 5 Z9 5 U1 1 U2 3 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 JUN PY 2011 VL 95 IS 8 BP 2738 EP + DI 10.1016/j.fertnstert.2011.05.018 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 782TI UT WOS:000292034100113 PM 21640343 ER PT J AU Yellaboina, S Zheng, XF Zaykin, D Hu, G Jothi, R AF Yellaboina, Sailu Zheng, Xiaofeng Zaykin, Dmitri Hu, Guang Jothi, Raja TI Integrating Genomic Datasets to Understand the Mechanisms of Embryonic Stem Cell Maintenance SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 [Yellaboina, Sailu; Zaykin, Dmitri; Jothi, Raja] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Zheng, Xiaofeng; Hu, Guang] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM yellaboinas@mail.nih.gov RI Hu, Guang/E-7474-2016 OI Hu, Guang/0000-0003-0437-4723 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JUN PY 2011 VL 47 SU 1 BP S4 EP S5 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 799IZ UT WOS:000293281700010 ER PT J AU Raam, MS Solomon, BD Muenke, M AF Raam, Manu S. Solomon, Benjamin D. Muenke, Maximilian TI Holoprosencephaly: A guide to diagnosis and clinical management SO INDIAN PEDIATRICS LA English DT Review DE Diagnosis; Genetics; Holoprosencephaly; Management; Review ID SONIC-HEDGEHOG GENE; HUMAN SIX3 GENE; PRENATAL-DIAGNOSIS; RISK-FACTORS; MUTATIONS; CHILDREN; PHENOTYPE; SPECTRUM; BRAIN; EPIDEMIOLOGY AB Holoprosencephaly affects 1 in 8,000 live births and is the most common structural anomaly of the developing forebrain, resulting in facial dysmorphism, neurologic impairment, and additional clinical sequelae. Given the increasing relative contribution of genetic diseases to perinatal morbidity and mortality in India, proper recognition and management of holoprosencephaly can improve care for a significant number of affected Indian children. We used the PubMed database (search terms: "holoprosencephaly," "HPE," "holoprosencephaly India") and cross-referenced articles regarding holoprosencephaly, using our research group's extensive experience as a guide for identifying seminal papers in the field. Holoprosencephaly is classified into four types based on the nature of the brain malformations as seen on neuroimaging and/or pathologic examination, with typically recognizable craniofacial phenotypes. Despite the identification of several genetic loci and other etiologic agents involved in pathogenesis, additional causes are elusive. Moreover, satisfactory explanations for phenomena such as incomplete penetrance and variable expressivity are lacking. For each patient, pediatricians should follow a diagnostic protocol including dysmorphology examination, complete family history and ascertainment of risk factors, and neuroimaging. Many medical issues, including hypothalamic dysfunction, endocrinologic dysfunction, motor impairment, respiratory issues, seizures, and hydrocephalus should be prioritized in management. Pediatricians should work with genetic specialists to identify syndromic forms and to perform cytogenetic investigation, molecular screening, and genetic counseling in order to fully characterize prognosis and recurrence risk. C1 [Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Raam, Manu S.] Howard Hughes Med Inst, HHMI NIH Res Scholars Program, Chevy Chase, MD USA. RP Muenke, M (reprint author), Bldg 35,Room 1B-203,35 Convent Dr,MSC 3717, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov FU Division of Intramural Research at the National Human Genome Research Institute (National Institutes of Health, Department of Health and Human Services, United States of America) FX Funding: Support was provided in part by Division of Intramural Research at the National Human Genome Research Institute (National Institutes of Health, Department of Health and Human Services, United States of America). NR 46 TC 8 Z9 10 U1 1 U2 8 PU SPRINGER INDIA PI NEW DELHI PA BARAKHAMBA RD 906-907, AKASH DEEP BUILDING, NEW DELHI, 110 001, INDIA SN 0019-6061 J9 INDIAN PEDIATR JI Indian Pediatrics PD JUN PY 2011 VL 48 IS 6 BP 457 EP 466 DI 10.1007/s13312-011-0078-x PG 10 WC Pediatrics SC Pediatrics GA 782XE UT WOS:000292045300007 PM 21743112 ER PT J AU Baber, I Tamby, JP Manoukis, NC Sangare, D Doumbia, S Traore, SF Maiga, MS Dembele, D AF Baber, Ibrahima Tamby, Jean Philippe Manoukis, Nicholas C. Sangare, Djibril Doumbia, Seydou Traore, Sekou F. Maiga, Mohamed S. Dembele, Doulaye TI A python module to normalize microarray data by the quantile adjustment method SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Module; Quantile method; Python; Microarray; Normalization AB Microarray technology is widely used for gene expression research targeting the development of new drug treatments. In the case of a two-color microarray, the process starts with labeling DNA samples with fluorescent markers (cyanine 635 or Cy5 and cyanine 532 or Cy3), then mixing and hybridizing them on a chemically treated glass printed with probes, or fragments of genes. The level of hybridization between a strand of labeled DNA and a probe present on the array is measured by scanning the fluorescence of spots in order to quantify the expression based on the quality and number of pixels for each spot. The intensity data generated from these scans are subject to errors due to differences in fluorescence efficiency between Cy5 and Cy3, as well as variation in human handling and quality of the sample. Consequently, data have to be normalized to correct for variations which are not related to the biological phenomena under investigation. Among many existing normalization procedures, we have implemented the quantile adjustment method using the python computer language, and produced a module which can be run via an HTML dynamic form. This module is composed of different functions for data files reading, intensity and ratio computations and visualization. The current version of the HTML form allows the user to visualize the data before and after normalization. It also gives the option to subtract background noise before normalizing the data. The output results of this module are in agreement with the results of other normalization tools. Published by Elsevier B.V. C1 [Baber, Ibrahima; Sangare, Djibril; Doumbia, Seydou; Traore, Sekou F.] Univ Bamako, Fac Med Pharm & Odontostomatol, MRTC, Bamako, Mali. [Tamby, Jean Philippe] ERL CNRS 8196, Unite Rech Genom Vegetale URGV UMR INRA UEVE 1165, F-91057 Evry, France. [Manoukis, Nicholas C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Maiga, Mohamed S.] Univ Bamako, Fac Sci & Tech, Bamako, Mali. [Dembele, Doulaye] CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. RP Baber, I (reprint author), Univ Bamako, Fac Med Pharm & Odontostomatol, MRTC, Mali BP 1805, Bamako, Mali. EM baber@icermali.org; tamby@evry.inra.fr; manoukisn@niaid.nih.gov; dsangare@icermali.org; sdoumbi@icermali.org; cheick@icermali.org; mohmaiga@ml.refer.org; doulaye@igbmc.fr OI Manoukis, Nicholas/0000-0001-5062-7256; Dembele, Doulaye/0000-0003-3879-6940 FU NIH, NIAID; CNRS, France FX This research was supported in part by the Intramural Research Program of the NIH, NIAID. We thanks Dr. Olivier Gascuel and Dr. Chantal Pacteau from CNRS, France for their help in training grant funding, and Dr Cathrine Letondal from Pasteur Institute, Paris, France for training in python. I would like to thank the NIH, USA and TOKTEN (Transfer of Knowledge through Expatriate Nationals), Mali for technical support. NR 16 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JUN PY 2011 VL 11 IS 4 BP 765 EP 768 DI 10.1016/j.meegid.2010.10.008 PG 4 WC Infectious Diseases SC Infectious Diseases GA 785TW UT WOS:000292254200010 PM 20970526 ER PT J AU Bulua, AC Pelletier, M Myerowitz-Vanderhoek, S Kastner, D Siegel, RM AF Bulua, A. C. Pelletier, M. Myerowitz-Vanderhoek, S. Kastner, D. Siegel, R. M. TI MITOCHONDRIAL REACTIVE OXYGEN SPECIES PROMOTE PRODUCTION OF PRO-INFLAMMATORY CYTOKINES IN THE TNFR1-ASSOCIATED PERIODIC FEVER SYNDROME SO INFLAMMATION RESEARCH LA English DT Meeting Abstract CT 10th World Congress on Inflammation CY JUN 25-29, 2011 CL Paris, FRANCE SP Int Assoc Inflammation Soc, Grp Res & Study Mediators Inflammat C1 [Bulua, A. C.; Pelletier, M.; Myerowitz-Vanderhoek, S.; Kastner, D.; Siegel, R. M.] NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD JUN PY 2011 VL 60 SU 1 BP 79 EP 79 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 774CM UT WOS:000291358900201 ER PT J AU Arai, AE AF Arai, Andrew E. TI Gadolinium Can Depict Area at Risk and Myocardial Infarction A Double-Edged Sword? SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE acute myocardial infarction; area at risk; CMR; edema; gadolinium ID CARDIOVASCULAR MAGNETIC-RESONANCE; CONTRAST ENHANCEMENT; DELAYED ENHANCEMENT; IRREVERSIBLE INJURY; TRANSMURAL EXTENT; VISUALIZATION; SIZE; TIME C1 NHLBI, Cardiovasc & Pulm Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Room B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM araia@nih.gov FU Intramural NIH HHS [Z01 HL004607-09, ZIA HL004607-14, Z01 HL004607-10, ZIA HL006136-02, ZIA HL004607-12, ZIA HL006136-01] NR 23 TC 9 Z9 9 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 JUN PY 2011 VL 4 IS 6 BP 619 EP 621 DI 10.1016/j.jcmg.2011.04.006 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 782WH UT WOS:000292042900008 PM 21679896 ER PT J AU Aubin, S Bingen, K Carpentier, MY Ford, JS Jones, BL Quinn, GP Salsman, JM Victorson, D Smith, AW Zebrack, B AF Aubin, Sylvie Bingen, Kristin Carpentier, Melissa Y. Ford, Jennifer S. Jones, Barbara L. Quinn, Gwendolyn P. Salsman, John M. Victorson, David Smith, Ashley Wilder Zebrack, Brad TI Challenges Conducting Qualitative Psychosocial Research for Adolescent and Young Adult Patients and Survivors SO JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY LA English DT Article C1 [Aubin, Sylvie] Sir Mortimer B Davis Jewish Hosp, Montreal, PQ, Canada. [Bingen, Kristin] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Carpentier, Melissa Y.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Ford, Jennifer S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Jones, Barbara L.] Univ Texas Austin, Austin, TX 78712 USA. [Quinn, Gwendolyn P.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Quinn, Gwendolyn P.] Univ S Florida, Tampa, FL USA. [Salsman, John M.; Victorson, David] Northwestern Univ, Chicago, IL 60611 USA. [Smith, Ashley Wilder] NCI, Bethesda, MD 20892 USA. [Zebrack, Brad] Univ Michigan, Ann Arbor, MI 48109 USA. RP Aubin, S (reprint author), Sir Mortimer B Davis Jewish Hosp, Montreal, PQ, Canada. EM sylvie.aubin@mail.mcgill.ca; kbingen@mcw.edu; melissa.y.carpentier@uth.tmc.edu; fordj@mskcc.org; barbarajones@mail.utexas.edu; gwen.quinn@moffitt.org; j-salsman@northwestern.edu; d-victorson@northwestern.edu; smithas@mail.nih.gov; zebrack@umich.edu NR 2 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2156-5333 EI 2156-535X J9 J ADOLESC YOUNG ADUL JI J. Adolesc. Young Adult Oncol. PD JUN PY 2011 VL 1 IS 2 BP 71 EP 76 DI 10.1089/jayao.2011.1513 PG 6 WC Oncology SC Oncology GA V39IF UT WOS:000209404000002 ER PT J AU Bai, RL Nguyen, TL Burnett, JC Atasoylu, O Munro, MHG Pettit, GR Smith, AB Gussio, R Hamel, E AF Bai, Ruoli Tam Luong Nguyen Burnett, James C. Atasoylu, Onur Munro, Murray H. G. Pettit, George R. Smith, Amos B., III Gussio, Rick Hamel, Ernest TI Interactions of Halichondrin B and Eribulin with Tubulin SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article ID MACROCYCLIC KETONE ANALOGS; VINCA DOMAIN; DOLASTATIN 10; ANTINEOPLASTIC AGENTS; MARINE SPONGE; BINDING-SITE; E7389; INHIBITION; COLCHICINE; DISTINCT AB Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading to continuing efforts to identify new agents and improve the activity of established ones. Here, we demonstrate that [(3)H]-labeled halichondrin B (HB), a complex, sponge-derived natural product, is bound to and dissociated from tubulin rapidly at one binding site per alpha beta-heterodimer, with an apparent K(d) of 0.31 mu M. We found no HB-induced aggregation of tubulin by high-performance liquid chromatography, even following column equilibration with HB. Binding of [(3)H]HB was competitively inhibited by a newly approved clinical agent, the truncated HB analogue eribulin (apparent K(nu) 0.80 mu M) and noncompetitively by dolastatin 10 and vincristine (apparent K(i)'s, 0.35 and 5.4 mu M, respectively). Our earlier studies demonstrated that HB inhibits nucleotide exchange on beta-tubulin, and this, together with the results presented here, indicated the I-1B site is located on beta-tubulin. Using molecular dynamics simulations, we determined complementary conformations of HB and beta-tubulin that delineated in atomic detail binding interactions of HB with only beta-tubulin, with no involvement of the alpha-subunit in the binding interaction. Moreover, the HB model served as a template for an eribulin binding model that furthered our understanding of the properties of eribulin as a drug. Overall, these results established a mechanistic basis for the antimitotic activity of the halichondrin class of compounds. C1 [Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [Bai, Ruoli; Hamel, Ernest] NCI, Informat Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [Tam Luong Nguyen; Burnett, James C.] NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. [Atasoylu, Onur; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Munro, Murray H. G.] Univ Canterbury, Dept Chem, Christchurch 1, New Zealand. [Pettit, George R.] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. RP Hamel, E (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. EM hamele@mail.nih.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; Division of Cancer Treatment and Diagnosis of the National Cancer Institute FX This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. This research was supported in part by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. NR 43 TC 27 Z9 28 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD JUN PY 2011 VL 51 IS 6 BP 1393 EP 1404 DI 10.1021/ci200077t PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 782LG UT WOS:000292010100019 PM 21539396 ER PT J AU Pine, D AF Pine, Daniel TI Commentary: Diagnosis and classification: There must be something left about which to argue - reflections on Rutter (2011) SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Pine, D (reprint author), NIMH, 10 Ctr Dr,10-3N202, Bethesda, MD 20892 USA. EM pined@mail.nih.gov NR 4 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JUN PY 2011 VL 52 IS 6 BP 663 EP 664 DI 10.1111/j.1469-7610.2011.02382.x PG 2 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 765EG UT WOS:000290685600006 PM 21434916 ER PT J AU TrehanPati, N Kotillil, S Hissar, SS Shrivastava, S Khanam, A Sukriti, S Mishra, SK Sarin, SK AF TrehanPati, Nirupma Kotillil, Shyam Hissar, Syed S. Shrivastava, Shikha Khanam, Arshi Sukriti, Sukriti Mishra, Siddartha K. Sarin, Shiv Kumar TI Circulating Tregs Correlate with Viral Load Reduction in Chronic HBV-Treated Patients with Tenofovir Disoproxil Fumarate SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Hepatitis B; chronicity; Tregs; PBMCs; chronicity; PD-1 ID CHRONIC HEPATITIS-B; REGULATORY T-CELLS; ANTIVIRAL IMMUNE-RESPONSE; VIRUS-INFECTION; ADEFOVIR DIPIVOXIL; LAMIVUDINE TREATMENT; LIVER-DISEASE; THERAPY; INTERLEUKIN-12; REPLICATION AB Limited response to current hepatitis B virus (HBV) drugs is possibly due to inadequate host cytotoxic cellular responses. Circulating Tregs have been shown to be associated with chronicity of HBV infection, but their profile during antiviral therapy has not been studied. We analyzed the frequency and effect of Tregs on cellular immune responses against HBV in 35 chronic hepatitis B eAg-ve and eAg+ve patients treated with tenofovir 300 mg/day. Frequency of Tregs and their modulatory role in cytokine-secreting cells were determined after stimulation with HBsAg or HBcAg in the absence or presence of Tregs and after blockage of PD-1/PDL-1 in peripheral blood mononuclear cells (PBMCs). Prior to therapy, eAg-ve patients had lower HBV DNA levels, reduced CD8 T cells, increased Tregs, and T cells expressing PD1. After 12 weeks of therapy, > 2 log HBV viral reduction was observed in both groups, along with an increase frequencies of CD8 T cells in eAg-ve patients and increased expression of chemokine receptors/Toll-like receptors in both groups. PD-1 expression on CD8 cells in PBMCs was decreased in both groups during therapy but not on Tregs. In eAg-ve group, sustained increase of Tregs was observed till week 12, which declined at week 24. In both groups, after 24 weeks, depletion of CD4(+)CD25(+) Tregs from PBMCs enhanced HBV-specific T cell responses, and blockage of PD-1/PDL1 pathway did enhance pro-inflammatory cytokine production in eAg+ve patients but not in eAg-ve. We conclude that Tregs induced by HBV replication in vivo are expanded in eAg-ve patients more. Reduction in HBV DNA by tenofovir partially restored adaptive immune responses and also reduced the Tregs. Blockage of PD-1/PDL1, enhanced cytokine production in eAg+ve patients but not in eAg-ve, suggests that distinctly different immunologic mechanisms are involved in eAg+ve and eAg-ve patients. C1 [TrehanPati, Nirupma; Sarin, Shiv Kumar] Inst Liver & Biliary Sci ILBS, New Delhi 110070, India. [TrehanPati, Nirupma; Hissar, Syed S.; Shrivastava, Shikha; Khanam, Arshi; Sukriti, Sukriti; Mishra, Siddartha K.; Sarin, Shiv Kumar] GB Pant Hosp, Dept Gastroenterol, New Delhi, India. [Kotillil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP TrehanPati, N (reprint author), Inst Liver & Biliary Sci ILBS, D-1, New Delhi 110070, India. EM trehanpati@gmail.com; shivsarin@gmail.com FU Department of Biotechnology, Govt. of India, New Delhi, India [BT/PR10283/GBD/27/91/2007]; National Institute of Allergy and Infectious Diseases, National Institute of Health (USA) FX This study was in part supported by grant no. BT/PR10283/GBD/27/91/2007 received from Department of Biotechnology, Govt. of India, New Delhi, India and by the intramural program of the National Institute of Allergy and Infectious Diseases, National Institute of Health (USA). NR 55 TC 16 Z9 17 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JUN PY 2011 VL 31 IS 3 BP 509 EP 520 DI 10.1007/s10875-011-9509-7 PG 12 WC Immunology SC Immunology GA 789YQ UT WOS:000292556000024 PM 21305387 ER PT J AU Zhou, Q Yu, XM Shu, C Cai, YM Gong, W Wang, XM Wang, DM Hu, SN AF Zhou, Qing Yu, Xiaomin Shu, Chang Cai, Yimei Gong, Wei Wang, Xumin Wang, Duen-mei Hu, Songnian TI Analysis of CYP3A4 genetic polymorphisms in Han Chinese SO JOURNAL OF HUMAN GENETICS LA English DT Article DE CYP3A4; Han Chinese; genetic polymorphisms ID SINGLE NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; DNA POLYMORPHISM; CYP3A4-ASTERISK-18 ALLELE; HEPATOCELLULAR-CARCINOMA; DIFFERENTIAL EXPRESSION; CYTOCHROME-P450 3A4; STATISTICAL-METHOD; PROMOTER VARIANT; CANCER RISK AB Our study aimed to comprehensively investigate the genetic polymorphisms of CYP3A4 in Han Chinese. We sequenced the gene regions of CYP3A4, including its promoter, exons, surrounding introns and 3' untranslated region (3'UTR), from 100 unrelated-healthy Han Chinese individuals. We detected 11 SNPs, three of which are novel. According to in silico functional prediction of novel variants, 20148 A > G in exon 10, resulting in substitution of Tyr319 with Cys (CYP3A4*21), may induce dramatic alteration of protein conformation, and 26908 G > A in 3'UTR may disrupt post-transcriptional regulation. We identified five alleles in Han Chinese, the allele frequencies of CYP3A4*1, *5, *6, *18 and *21 are 97, 0.5, 1, 1 and 0.5%, respectively. Haplotype inference revealed 14 haplotypes, of which the major haplotype CYP3A4*1A constitutes 59% of the total chromosomes. We also examined the possible role of natural selection in shaping the variation of CYP3A4 and confirmed a trend, consistent with the action of positive selection. We systematically screened the genetic polymorphisms of CYP3A4 in Han Chinese, highlighted possible functional impairment of the novel allele and summarized the distinct allele and haplotype frequency distribution, with an emphasis on detecting the footprint of recent positive selection on the CYP3A4 gene in Han Chinese. Journal of Human Genetics (2011) 56, 415-422; doi:10.1038/jhg.2011.30; published online 17 March 2011 C1 [Zhou, Qing; Yu, Xiaomin; Shu, Chang; Cai, Yimei; Gong, Wei; Wang, Xumin; Wang, Duen-mei; Hu, Songnian] Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genome Sci & Informat, Beijing 100029, Peoples R China. [Yu, Xiaomin] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zhou, Q (reprint author), Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genome Sci & Informat, 7 Beitucheng W Rd, Beijing 100029, Peoples R China. EM zhouqingnwu@gmail.com; husn@big.ac.cn RI Yu, Xiaomin/I-6407-2016; OI Hu, Songnian/0000-0003-3966-3111 FU National Natural Science Foundation of China [81001472] FX We thank Dr Jun Yu (Beijing Institute of Genomics, Chinese Academy of Sciences) for his valuable contribution. This work is supported by National Natural Science Foundation of China (No. 81001472) awarded to Qing Zhou. NR 70 TC 10 Z9 13 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD JUN PY 2011 VL 56 IS 6 BP 415 EP 422 DI 10.1038/jhg.2011.30 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 782RO UT WOS:000292028000003 PM 21412247 ER PT J AU Kang, C Domingues, BS Sainz, E Domingues, CEF Drayna, D Moretti-Ferreira, D AF Kang, Changsoo Domingues, Bianca Santos Sainz, Eduardo Frigerio Domingues, Carlos Eduardo Drayna, Dennis Moretti-Ferreira, Danilo TI Evaluation of the association between polymorphisms at the DRD2 locus and stuttering SO JOURNAL OF HUMAN GENETICS LA English DT Letter C1 [Kang, Changsoo; Sainz, Eduardo; Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. [Domingues, Bianca Santos; Frigerio Domingues, Carlos Eduardo; Moretti-Ferreira, Danilo] Sao Paulo State Univ Unesp, Biosci Inst, Dept Genet, Botucatu, SP, Brazil. RP Kang, C (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. EM drayna@nidcd.nih.gov RI Moretti-Ferreira, Danilo/F-9565-2012; Domingues, Carlos Eduardo/B-5511-2013; OI Moretti-Ferreira, Danilo/0000-0002-9256-7623 FU Intramural NIH HHS [ZIA DC000046-12]; NIDCD NIH HHS [T32 DC000046, Z01 DC000046] NR 5 TC 4 Z9 4 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD JUN PY 2011 VL 56 IS 6 BP 472 EP 473 DI 10.1038/jhg.2011.29 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 782RO UT WOS:000292028000014 PM 21390039 ER PT J AU Udey, MC AF Udey, Mark C. TI Jonathan Carl Vogel, MD (1954-2010) IN MEMORIAM SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Biographical-Item C1 NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 2011 VL 131 IS 6 BP 1194 EP 1195 DI 10.1038/jid.2011.95 PG 2 WC Dermatology SC Dermatology GA 764GD UT WOS:000290616700007 ER PT J AU Fathi, AR Vortmeyer, A Holland, SM Pluta, RM AF Fathi, A. R. Vortmeyer, A. Holland, S. M. Pluta, R. M. TI Intracranial aneurysms associated with hyperimmunoglobulinaemia E (Job) syndrome: report of two cases SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Letter C1 [Fathi, A. R.; Vortmeyer, A.; Pluta, R. M.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Fathi, A. R.] Kantonsspital Aarau, Dept Neurosurg, Aarau, Switzerland. [Holland, S. M.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Room 3D20,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM rysiek@helix.nih.gov FU Intramural NIH HHS NR 5 TC 1 Z9 1 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUN PY 2011 VL 82 IS 6 BP 704 EP 706 DI 10.1136/jnnp.2009.198283 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 760CD UT WOS:000290298600030 PM 20861064 ER PT J AU Shin, EJ Bach, JH Lee, SY Kim, JM Lee, J Hong, JS Nabeshima, T Kim, HC AF Shin, Eun-Joo Bach, Jae-Hyung Lee, Sung Youl Kim, Jeong Min Lee, Jinhwa Hong, Jau-Shyong Nabeshima, Toshitaka Kim, Hyoung-Chun TI Neuropsychotoxic and Neuroprotective Potentials of Dextromethorphan and Its Analogs SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Review DE dextromethorphan; dimemorfan; 3-hydroxymorphinan; neuroprotection; neuropsychotoxicity; neurodegenerative disorder ID METHYL-D-ASPARTATE; NMDA RECEPTOR ANTAGONISTS; EXCITATORY AMINO-ACIDS; LONG-TERM POTENTIATION; SIGMA-BINDING-SITES; KAINIC ACID; RAT-BRAIN; PSEUDOBULBAR AFFECT; PARKINSONS-DISEASE; POSTOPERATIVE PAIN AB Dextromethorphan (3-methoxy-17-methylmorphinan) has complex pharmacologic effects on the central nervous system. Although some of these effects are neuropsychotoxic, this review focuses on the neuroprotective effects of dextromethorphan and its analogs. Some of these analogs, particularly dimemorfan (3-methyl-17-methylmorphinan) and 3-hydroxymorphinan, have promising neuroprotective properties with negligible neuropsychotoxic effects. Their neuroprotective effects, the mechanisms underlying these effects, and their therapeutic potential for the treatment of diverse neurodegenerative disorders are discussed. C1 [Shin, Eun-Joo; Bach, Jae-Hyung; Lee, Sung Youl; Kim, Hyoung-Chun] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea. [Kim, Jeong Min; Lee, Jinhwa] Green Cross Co, Cent Res Ctr, Yongin 446799, South Korea. [Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Nabeshima, Toshitaka] Meijo Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Nagoya, Aichi 4688503, Japan. RP Kim, HC (reprint author), Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea. EM kimhc@kangwon.ac.kr FU Ministry of Science and Technology, Republic of Korea; Ministry of Health & Welfare, Republic of Korea [A101069]; National Research Foundation of Korea, Republic of Korea [E00025]; BK 21 program; Research on Risk of Chemical Substances, Ministry of Health Labour, and Welfare; Ministry of Education, Culture, Sports, Science, and Technology, Japan FX This study was supported by a grant from the Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea; by a grant (#A101069) of the Korea Healthcare Technology R&D project, Ministry of Health & Welfare, Republic of Korea; and by a grant (#E00025) of the Korea-Japan Joint Research Program, National Research Foundation of Korea, Republic of Korea. Jae-Hyung Bach was supported by the BK 21 program. This work was, in part, supported by grants of the Research on Risk of Chemical Substances, Ministry of Health Labour, and Welfare and the Academic Frontier Project for Private Universities, Ministry of Education, Culture, Sports, Science, and Technology, Japan. NR 100 TC 13 Z9 14 U1 2 U2 8 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 EI 1347-8648 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD JUN PY 2011 VL 116 IS 2 BP 137 EP 148 DI 10.1254/jphs.11R02CR PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 783GB UT WOS:000292068400001 PM 21606622 ER PT J AU Dutta, A Henley, W Lang, I Llewellyn, D Guralnik, J Wallace, RB Melzer, D AF Dutta, Ambarish Henley, William Lang, Iain Llewellyn, David Guralnik, Jack Wallace, Robert B. Melzer, David TI Predictors of Extraordinary Survival in the Iowa Established Populations for Epidemiologic Study of the Elderly: Cohort Follow-Up to "Extinction" SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE extraordinary survivor; oldest old; predictors; heritable ID OLDER-ADULTS; EXTREME LONGEVITY; RISK-FACTORS; MORTALITY; CENTENARIANS; HEALTH; LIFE; MEN; MORBIDITY; TRAJECTORIES AB OBJECTIVES: To identify predictors of extraordinary survival. DESIGN: Longitudinal study of a cohort of elderly people followed up until almost all have died. SETTING: Two counties in Iowa; a part of the Established Populations for Epidemiologic Study of the Elderly. PARTICIPANTS: Two thousand eight hundred ninety community-dwelling citizens aged 65 to 85 at baseline and surviving at least 3 years. MEASUREMENTS: Data relating to age, sex, birth order, parental longevity, marital status, education, family income, social support, self-reported health, chronic diseases, blood pressure, body mass index, physical ability, exercise, life attitude and mental health were obtained. Extraordinary survivors (ESs) were defined to include approximately 10% of the longest survivors in their sex group. RESULTS: The 253 ESs were far more likely never to have smoked. In models adjusted for age, sex, and smoking, the earlier-life factors such as parental longevity, being earlier in the birth order (in women only), and body mass index at age 50 were associated with extraordinary survival. In similar models for predictors at age 65 to 85, extraordinary survival was associated with excellent self-reported health, fewer chronic diseases, better physical mobility and memory, and positive attitude toward life, but it was not associated with depression, anxiety, or sleep quality. In multivariable models, attitude toward life was not an independent predictor. Women in the top third of a cumulative score of independent predictors were 9.3 (95% confidence interval = 4.4-19.6, P<.001) times as likely to reach extraordinary survival as those in the bottom third. CONCLUSION: ESs had fewer "classical" risk factors and were in better health than their contemporaneous controls. Possibly genetic factors such as parental longevity and birth order appear to be less predictive in men than in women. J Am Geriatr Soc 59:963-971, 2011. C1 [Dutta, Ambarish; Henley, William; Lang, Iain; Llewellyn, David; Melzer, David] Univ Exeter, Peninsula Med Sch, Epidemiol & Publ Hlth Grp, Exeter EX2 5DW, Devon, England. [Guralnik, Jack] NIA, NIH, Bethesda, MD 20892 USA. [Wallace, Robert B.] Univ Iowa, Coll Publ Hlth, Ctr Aging, Dept Epidemiol, Iowa City, IA 52242 USA. RP Melzer, D (reprint author), Univ Exeter, Peninsula Med Sch, Epidemiol & Publ Hlth Grp, Barrack Rd, Exeter EX2 5DW, Devon, England. EM david.melzer@pms.ac.uk OI Lang, Iain/0000-0002-8473-2350; Melzer, David/0000-0002-0170-3838; Dutta, Ambarish/0000-0002-4019-7472 FU Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, Maryland FX The authors acknowledge support received from the Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, Maryland. NR 35 TC 13 Z9 13 U1 5 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2011 VL 59 IS 6 BP 963 EP 971 DI 10.1111/j.1532-5415.2011.03451.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 781ZZ UT WOS:000291978300001 PM 21649635 ER PT J AU Helzner, EP Patel, AS Pratt, S Sutton-Tyrrell, K Cauley, JA Talbott, E Kenyon, E Harris, TB Satterfield, S Ding, JZ Newman, AB AF Helzner, Elizabeth P. Patel, Ami S. Pratt, Sheila Sutton-Tyrrell, Kim Cauley, Jane A. Talbott, Evelyn Kenyon, Emily Harris, Tamara B. Satterfield, Suzanne Ding, Jingzhong Newman, Anne B. TI Hearing Sensitivity in Older Adults: Associations with Cardiovascular Risk Factors in the Health, Aging and Body Composition Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hearing; presbycusis; race; cardiovascular disease; pulse-wave velocity ID BLUE-MOUNTAINS HEARING; QUALITY-OF-LIFE; ALCOHOL-CONSUMPTION; ELDERLY POPULATION; DIABETES-MELLITUS; AGE; IMPAIRMENT; SMOKING; DISEASE; EPIDEMIOLOGY AB OBJECTIVES: To examine the association between cardiovascular disease (CVD) and its risk factors and age-associated hearing loss in a cohort of older black and white adults. DESIGN: Cross-sectional cohort study. SETTING: The Health, Aging, and Body Composition (Health ABC) Study, a community-based cohort study of older adults from Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Two thousand forty-nine well-functioning adults (mean age 77.5; 37% black). MEASUREMENTS: Pure-tone audiometry measurement and history of clinical CVD were obtained at the fourth annual follow-up visit. Pure-tone averages in decibels reflecting low (250, 500, and 1,000 Hz), middle (500, 1,000, and 2,000 Hz), and high (2,000, 4,000, and 8,000 Hz) frequencies were calculated for each ear. CVD risk factors, aortic pulse-wave velocity (PWV), and ankle-arm index (AAI) were obtained at study baseline. RESULTS: In sex-stratified models, after adjustment for age, race, study site, and occupational noise exposure, risk factors associated with poorer hearing sensitivity in men included high triglyceride levels, high resting heart rate, and history of smoking. In women, poor hearing sensitivity was associated with high body mass index, high resting heart rate, fast PWV, and low AAI. CONCLUSION: Modifiable risk factors for CVD may play a role in the development of age- related hearing loss. J Am Geriatr Soc 59:972-979, 2011. C1 [Helzner, Elizabeth P.] Suny Downstate Med Ctr, Dept Epidemiol & Biostat, Brooklyn, NY 11203 USA. [Patel, Ami S.; Sutton-Tyrrell, Kim; Cauley, Jane A.; Talbott, Evelyn; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Pratt, Sheila] Univ Pittsburgh, Dept Commun & Speech Disorders, Pittsburgh, PA 15261 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. [Pratt, Sheila] Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Kenyon, Emily] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demography & Biometry, Bethesda, MD 20892 USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Ding, Jingzhong] Wake Forest Univ, Dept Internal Med, Div Geriatr, Winston Salem, NC 27109 USA. RP Helzner, EP (reprint author), 450 Clarkson Ave,Box 43, Brooklyn, NY 11203 USA. EM Elizabeth.Helzner@downstate.edu RI Pratt, Sheila/H-7139-2013; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Talbott, Evelyn/0000-0002-5198-7939; Cauley, Jane A/0000-0003-0752-4408 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX This work was supported through National Institute on Aging Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. NR 43 TC 28 Z9 29 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2011 VL 59 IS 6 BP 972 EP 979 DI 10.1111/j.1532-5415.2011.03444.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 781ZZ UT WOS:000291978300002 PM 21649629 ER PT J AU Matsuno, RK Costantino, JP Ziegler, RG Anderson, GL Li, HL Pee, D Gail, MH AF Matsuno, Rayna K. Costantino, Joseph P. Ziegler, Regina G. Anderson, Garnet L. Li, Huilin Pee, David Gail, Mitchell H. TI Projecting Individualized Absolute Invasive Breast Cancer Risk in Asian and Pacific Islander American Women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ATTRIBUTABLE RISK; VALIDATION; PATTERNS; MODEL AB Background The Breast Cancer Risk Assessment Tool (BCRAT) of the National Cancer Institute is widely used for estimating absolute risk of invasive breast cancer. However, the absolute risk estimates for Asian and Pacific Islander American (APA) women are based on data from white women. We developed a model for projecting absolute invasive breast cancer risk in APA women and compared its projections to those from BCRAT. Methods Data from 589 women with breast cancer (case patients) and 952 women without breast cancer (control subjects) in the Asian American Breast Cancer Study were used to compute relative and attributable risks based on the age at menarche, number of affected mothers, sisters, and daughters, and number of previous benign biopsies. Absolute risks were obtained by combining this information with ethnicity-specific data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and with US ethnicity-specific mortality data to create the Asian American Breast Cancer Study model (AABCS model). Independent data from APA women in the Women's Health Initiative (WHI) were used to check the calibration and discriminatory accuracy of the AABCS model. Results The AABCS model estimated absolute risk separately for Chinese, Japanese, Filipino, Hawaiian, Other Pacific Islander, and Other Asian women. Relative and attributable risks for APA women were comparable to those in BCRAT, but the AABCS model usually estimated lower-risk projections than BCRAT in Chinese and Filipino, but not in Hawaiian women, and not in every age and ethnic subgroup. The AABCS model underestimated absolute risk by 17% (95% confidence interval = 1% to 38%) in independent data from WHI, but APA women in the WHI had incidence rates approximately 18% higher than those estimated from the SEER program. Conclusions The AABCS model was calibrated to ethnicity-specific incidence rates from the SEER program for projecting absolute invasive breast cancer risk and is preferable to BCRAT for counseling APA women. C1 [Matsuno, Rayna K.; Ziegler, Regina G.; Li, Huilin; Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Matsuno, Rayna K.; Li, Huilin; Gail, Mitchell H.] NCI, Biostat Branch, Bethesda, MD 20892 USA. [Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. [Matsuno, Rayna K.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Costantino, Joseph P.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Anderson, Garnet L.] Fred Hutchinson Canc Res Ctr, Womens Hlth Initiat Clin Coordinating Ctr, Seattle, WA 98104 USA. [Anderson, Garnet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Pee, David] Informat Management Serv Inc, Rockville, MD USA. RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, EPS Rm 8032, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov FU Division of Cancer Epidemiology and Genetics, National Cancer Institute; Public Health Service [U10-CA069651, U10-CA069974]; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-, 19, 32122, 42107-26, 42129-32, 44221] FX This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute and by Public Health Service (U10-CA069651 and U10-CA069974) to the National Surgical Breast and Bowel Project (J.P.C.). The Women's Health Initiative program (G.L.A.) is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-, 19, 32122, 42107-26, 42129-32, and 44221. NR 19 TC 40 Z9 41 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 JUN PY 2011 VL 103 IS 12 BP 951 EP 961 DI 10.1093/jnci/djr154 PG 11 WC Oncology SC Oncology GA 784ZP UT WOS:000292197500009 PM 21562243 ER PT J AU Grohar, PJ Woldemichael, GM Griffin, LB Mendoza, A Chen, QR Yeung, C Currier, DG Davis, S Khanna, C Khan, J McMahon, JB Helman, LJ AF Grohar, Patrick J. Woldemichael, Girma M. Griffin, Laurie B. Mendoza, Arnulfo Chen, Qing-Rong Yeung, Choh Currier, Duane G. Davis, Sean Khanna, Chand Khan, Javed McMahon, James B. Helman, Lee J. TI Identification of an Inhibitor of the EWS-FLI1 Oncogenic Transcription Factor by High-Throughput Screening SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; EWINGS-SARCOMA; FUSION PROTEIN; DNA-BINDING; GENE-EXPRESSION; BREAST-CANCER; MITHRAMYCIN-A; TUMOR-CELLS; PHASE-II; GROWTH AB Background Chromosomal translocations generating oncogenic transcription factors are the hallmark of a variety of tumors, including many sarcomas. Ewing sarcoma family of tumors (ESFTs) are characterized by the t(11;22)(q24;q12) translocation that generates the Ewing sarcoma breakpoint region 1 and Friend leukemia virus integration 1 (EWS-FLI1) fusion transcription factor responsible for the highly malignant phenotype of this tumor. Although continued expression of EWS-FLI1 is believed to be critical for ESFT cell survival, a clinically effective small-molecule inhibitor remains elusive likely because EWS-FLI1 is a transcription factor and therefore widely felt to be "undruggable." Methods We developed a high-throughput screen to evaluate more than 50 000 compounds for inhibition of EWS-FLI1 activity in TC32 ESFT cells. We used a TC32 cell-based luciferase reporter screen using the EWS-FLI1 downstream target NR0B1 promoter and a gene signature secondary screen to sort and prioritize the compounds. We characterized the lead compound, mithramycin, based on its ability to inhibit EWS-FLI1 activity in vitro using microarray expression profiling, quantitative reverse transcription-polymerase chain reaction, and immunoblot analysis, and in vivo using immunohistochemistry. We studied the impact of this inhibition on cell viability in vitro and on tumor growth in ESFT xenograft models in vivo (n = 15-20 mice per group). All statistical tests were two-sided. Results Mithramycin inhibited expression of EWS-FLI1 downstream targets at the mRNA and protein levels and decreased the growth of ESFT cells at half maximal inhibitory concentrations between 10 (95% confidence interval [CI] = 8 to 13 nM) and 15 nM (95% CI = 13 to 19 nM). Mithramycin suppressed the growth of two different ESFT xenograft tumors and prolonged the survival of ESFT xenograft-bearing mice by causing a decrease in mean tumor volume. For example, in the TC32 xenograft model, on day 15 of treatment, the mean tumor volume for the mithramycin-treated mice was approximately 3% of the tumor volume observed in the control mice (mithramycin vs control: 69 vs 2388 mm(3), difference = 2319 mm(3), 95% CI = 1766 to 2872 mm(3), P < .001). Conclusion Mithramycin inhibits EWS-FLI1 activity and demonstrates ESFT antitumor activity both in vitro and in vivo. C1 [Grohar, Patrick J.; Griffin, Laurie B.; Yeung, Choh; Helman, Lee J.] NCI, Mol Oncol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Mendoza, Arnulfo; Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Chen, Qing-Rong; Khan, Javed] NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Woldemichael, Girma M.] NCI, Mol Targets Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Currier, Duane G.] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. [Davis, Sean] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [McMahon, James B.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Grohar, PJ (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, 10 Ctr Dr,MSC 1104,10 CRC 1W-3816, Bethesda, MD 20892 USA. EM groharp@mail.nih.gov RI Khan, Javed/P-9157-2014; OI Khan, Javed/0000-0002-5858-0488; Davis, Sean/0000-0002-8991-6458 FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; NIH, National Cancer Institute, Center for Cancer Research; Sarcoma Alliance FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Grant support received from the Sarcoma Alliance for Research through Collaboration Career Development Award (to P.J.G.). NR 69 TC 79 Z9 83 U1 2 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN PY 2011 VL 103 IS 12 BP 962 EP 978 DI 10.1093/jnci/djr156 PG 17 WC Oncology SC Oncology GA 784ZP UT WOS:000292197500010 PM 21653923 ER PT J AU Belani, CP Nemunaitis, JJ Chachoua, A Eisenberg, PD Raez, LE Cuevas, JD Mather, CB Benner, RJ Meech, SJ AF Belani, Chandra P. Nemunaitis, John J. Chachoua, Abraham Eisenberg, Peter D. Raez, Luis E. Cuevas, Juan D. Mather, Cecile B. Benner, Rebecca J. Meech, Sandra J. TI RANDOMIZED PHASE II TRIAL OF ERLOTINIB WITH OR WITHOUT PF-3512676 (CPG 7909, A TOLL-LIKE RECEPTOR 9 [TLR9] AGONIST) IN PATIENTS WITH ADVANCED RECURRENT EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR)-POSITIVE NON-SMALL CELL LUNG CANCER (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE PF-3512676; erlotinib; Non-small cell lung cancer; immunotherapy C1 [Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA. [Nemunaitis, John J.] Mary Crowley Med Res Ctr, Dallas, TX USA. [Chachoua, Abraham] NYU, Sch Med, New York, NY 10003 USA. [Chachoua, Abraham] Natl Canc Inst, Ctr Canc, Bethesda, MD USA. [Raez, Luis E.] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. [Cuevas, Juan D.] St Louis Canc Care Llp, St Louis, MO 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S1218 EP S1219 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769801044 ER PT J AU Campbell, AK Boyer, M Giaccone, G Janne, PA Kim, DW Park, K Ramalingam, S Reckamp, KL Mundayat, R Letrent, SP O'Connell, J Lacouture, ME AF Campbell, Alicyn K. Boyer, Michael Giaccone, Giuseppe Janne, Pasi A. Kim, Dong-Wan Park, Keunchil Ramalingam, Suresh Reckamp, Karen L. Mundayat, Rajiv Letrent, Stephen P. O'Connell, Joseph Lacouture, Mario E. TI DERMATOLOGIC ADVERSE EVENTS OF THE PAN-HER TYROSINE KINASE INHIBITOR (TKI) PF299804: ASSESSMENT BY PATIENT-REPORTED OUTCOMES IN 2ND/3RD-LINE AND REFRACTORY NON-SMALL CELL LUNG CANCER (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE PF-00299804; Dermatologic Toxicity; Patient Reported Outcomes; EGFR TKI C1 [Campbell, Alicyn K.; Letrent, Stephen P.] Pfizer Oncol, Clin Dev & Med Affairs, New York, NY USA. [Boyer, Michael] Sydney Canc Ctr, Sydney, NSW, Australia. [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA USA. [Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul, South Korea. [Park, Keunchil] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med,Div Hem Onc, Seoul, South Korea. [Ramalingam, Suresh] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Reckamp, Karen L.] City Hope Natl Med Ctr, Med Oncol, Duarte, CA USA. [Mundayat, Rajiv] Pfizer Oncol, Specialty Care Business Unit, Stat, New York, NY USA. [O'Connell, Joseph] Pfizer Oncol, Oncol, New York, NY USA. [Lacouture, Mario E.] Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S1185 EP S1186 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769800398 ER PT J AU Gadgeel, S Ruckdeschel, J Wozniak, A Hackstock, D Chen, W Galasso, C Burger, A Lorusso, P Ivy, P Edelman, MJ AF Gadgeel, Shirish Ruckdeschel, John Wozniak, Antoinette Hackstock, Deborah Chen, Wei Galasso, Cathy Burger, Angelika Lorusso, Patricia Ivy, Percy Edelman, Martin J. TI CEDIRANIB, A VEGF RECEPTOR 1, 2 AND 3 INHIBITOR, AND PEMETREXED IN PATIENTS (PTS) WITH RECURRENT NON-SMALL CELL LUNG CANCER (NSCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE cediranib; Pemetrexed; recurrent NSCLC C1 [Gadgeel, Shirish; Wozniak, Antoinette; Hackstock, Deborah; Chen, Wei; Galasso, Cathy; Burger, Angelika; Lorusso, Patricia] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. [Ruckdeschel, John] Nevada Canc Inst, Las Vegas, NV USA. [Ivy, Percy] NCI, Bethesda, MD 20892 USA. [Edelman, Martin J.] Univ Maryland, Ctr Canc, College Pk, MD 20742 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S553 EP S554 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855802308 ER PT J AU Gandara, DR Van Dyke, TA Ohler, ZW Li, TH Lara, PN Mack, P Calhoun, RF Gandour-Edwards, R Danenberg, K White, RD Goodwin, N AF Gandara, David R. Van Dyke, Terry A. Ohler, Zoe Weaver Li, Tianhong Lara, Primo N. Mack, Phillip Calhoun, Royce F. Gandour-Edwards, Regina Danenberg, Kathleen White, Ralph Devere Goodwin, Neal TI ENHANCING EGFR-DIRECTED THERAPIES THROUGH A NOVEL RESEARCH PLATFORM INTEGRATING DATA FROM GENETICALLY ENGINEERED MICE, PATIENT DERIVED XENOGRAFTS AND CLINICAL TRIALS (IGXT) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE research platform C1 [Gandara, David R.; Li, Tianhong; Lara, Primo N.; Mack, Phillip; Calhoun, Royce F.; White, Ralph Devere] Univ Calif Davis, Ctr Canc, Davis, CA USA. [Van Dyke, Terry A.; Ohler, Zoe Weaver] NCI, Ctr Adv Preclin Res Capr, Bethesda, MD 20892 USA. [Gandour-Edwards, Regina] Univ Calif Davis, Dept Pathol & Lab Med, Davis, CA USA. [Goodwin, Neal] Jackson Lab, Bar Harbor, ME 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S418 EP S419 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855802137 ER PT J AU Giaccone, G Petrini, I Wang, YS AF Giaccone, Giuseppe Petrini, Iacopo Wang, Yisong TI BIOLOGY SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Thymoma; biology; mediastinum; genome C1 [Giaccone, Giuseppe; Petrini, Iacopo; Wang, Yisong] NCI, Med 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S122 EP S122 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855801075 ER PT J AU Johnson, BE Kris, MG Kwiatkowski, D Iafrate, AJ Wistuba, II Shyr, Y Engelman, J Khuri, FR Dubinett, S Pao, W Rudin, C Schiller, J Haura, EB Blumenschein, G Simon, G Giaccone, G Koehler, E Kugler, K Minna, JD Bunn, P AF Johnson, Bruce E. Kris, Mark G. Kwiatkowski, David Iafrate, A. J. Wistuba, Ignacio I. Shyr, Yu Engelman, Jeff Khuri, Fadlo R. Dubinett, Steven Pao, William Rudin, Charles Schiller, Joan Haura, Eric B. Blumenschein, George Simon, George Giaccone, Giuseppe Koehler, Elizabeth Kugler, Kelly Minna, John D. Bunn, Paul TI CLINICAL CHARACTERISTICS OF PLANNED 1000 PATIENTS WITH ADENOCARCINOMA OF LUNG (ACL) UNDERGOING GENOMIC CHARACTERIZATION IN THE US LUNG CANCER MUTATION CONSORTIUM (LCMC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE lung neoplasm; genomic changes; Epidermal growth factor receptor; EML4-ALK C1 [Johnson, Bruce E.; Kwiatkowski, David] Dana Farber Canc Inst, Boston, MA USA. [Kris, Mark G.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY USA. [Iafrate, A. J.; Engelman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Wistuba, Ignacio I.; Blumenschein, George] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Shyr, Yu; Koehler, Elizabeth] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA. [Khuri, Fadlo R.] Emory Univ, Atlanta, GA 30322 USA. [Dubinett, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care, Los Angeles, CA 90095 USA. [Pao, William] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Rudin, Charles] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21218 USA. [Schiller, Joan] Univ Texas Southwestern Med Ctr, Div Hematol Oncol, Dallas, TX USA. [Haura, Eric B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Simon, George] Med Univ S Carolina, Charleston, SC USA. [Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. [Kugler, Kelly] Univ Colorado, Ctr Canc, Div Med Oncol, Boulder, CO 80309 USA. [Minna, John D.] Univ Texas Southwestern Med Ctr, Dallas, TX USA. [Bunn, Paul] Univ Colorado, Denver Sch Med, Div Med Oncol, Boulder, CO 80309 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S344 EP S345 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855802041 ER PT J AU Kelly, RJ Rajan, A Chun, G Lopez-Chavez, A Giaccone, G AF Kelly, Ronan J. Rajan, Arun Chun, Guinevere Lopez-Chavez, Ariel Giaccone, Giuseppe TI A PHASE I STUDY OF PACLITAXEL, CARBOPLATIN AND YM155 (SURVIVIN SUPPRESSOR) IN SUBJECTS WITH SOLID TUMORS SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE survivin C1 [Kelly, Ronan J.] NCI, Thorac 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S1194 EP S1195 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769801012 ER PT J AU Lee, DH Lai, CH Wang, YS Giaccone, G AF Lee, Dae Ho Lai, Chien-Hao Wang, Yisong Giaccone, Giuseppe TI MECHANISM(S) OF ACTION AND POTENCY OF HSP90 INHIBITOR GANETESPIB IN SMALL CELL LUNG CARCINOMA CELLS SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Ganetespib; Hsp90 inhibitor; SCLC C1 [Lee, Dae Ho; Lai, Chien-Hao; Wang, Yisong; Giaccone, Giuseppe] NCI, 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S936 EP S937 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769800054 ER PT J AU Linnoila, I Wang, XY Keefe, KM Jensen-Taubman, SM Demelash, A AF Linnoila, Ilona Wang, Xiaoyang Keefe, Kathleen M. Jensen-Taubman, Sandra M. Demelash, Abeba TI PRONEURAL TRANSCRIPTION FACTOR ACHAETE-SCUTE HOMOLOG 1 REGULATES STEMNESS IN THE AIRWAY EPITHELIUM THROUGH ACTIVATION OF THE WNT/beta-CATENIN PATHWAY SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Ascl1; stem cell; Wnt; premalignant C1 [Linnoila, Ilona] NCI, Exp Pathol Sect, CCBB, NIH, Bethesda, MD 20892 USA. [Wang, Xiaoyang; Keefe, Kathleen M.; Jensen-Taubman, Sandra M.; Demelash, Abeba] NCI, 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S680 EP S681 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855803091 ER PT J AU Linnoila, I Li, Y AF Linnoila, Ilona Li, Yan TI NEUROENDOCRINE TRANSCRIPTION FACTOR ASCL1 DEFINES MULTIPLE PROGENITORS IN THE LUNG DURING THE DEVELOPMENT AND REPAIR SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Ascl1; progenitor; lung; Neuroendocrine C1 [Linnoila, Ilona] NCI, Exp Pathol Sect, Ccbb, NIH, Bethesda, MD 20892 USA. [Li, Yan] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S372 EP S373 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855802079 ER PT J AU Lubet, RA Szabo, E Grubbs, CJ AF Lubet, Ronald A. Szabo, Eva Grubbs, Clinton J. TI ALTERNATIVE DOSING REGIMENS WITH TARCEVA IN A PRECLINCAL BREAST CANCER MODEL: EFFECTS ON EFFICACY AND POTENTIAL EFFECTS ON TOXICITY. IMPLICATIONS FOR LUNG CANCER TREATMENT SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE EGFr Inhibitors; Prevention; Altered Dosing C1 [Lubet, Ronald A.; Szabo, Eva] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Grubbs, Clinton J.] Univ Alabama, Dept Surg, Birmingham, AL 35294 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S942 EP S943 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769800062 ER PT J AU Luo, J AF Luo, Ji TI SYNTHETIC LETHAL APPROACHES TO TACKLE RAS MUTANT NSCLC SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE ras; synthetic lethality; RNAi; genetic screen C1 [Luo, Ji] NCI, Med 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S62 EP S62 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855801015 ER PT J AU Pelosi, G AF Pelosi, Giuseppe TI EPITHELIAL-MESENCHYMAL TRANSITION: FROM DIAGNOSIS TO THERAPY SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Pelosi, Giuseppe] NCI, Dept Pathol & Lab Med, Bethesda, MD 20892 USA. [Pelosi, Giuseppe] Univ Milan, Sch Med, I-20122 Milan, Italy. 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S75 EP S76 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855801029 ER PT J AU Petrini, I Wang, YS Pineda, M Davis, S Giaccone, G AF Petrini, Iacopo Wang, Yisong Pineda, Marbin Davis, Sean Giaccone, Giuseppe TI COMPLETE GENOME SEQUENCING OF A HUMAN B3 THYMOMA SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Thymoma; Next generation sequening; Whole genome sequencing; CGH C1 [Petrini, Iacopo; Wang, Yisong; Pineda, Marbin; Davis, Sean; Giaccone, Giuseppe] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S452 EP S453 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855802178 ER PT J AU Pikor, LA Thu, K Chari, R Wilson, IM Macaulay, CE English, JC Tsao, MS Gazdar, AF Lam, S Lockwood, WW Lam, W AF Pikor, Larissa A. Thu, Kelsie Chari, Raj Wilson, Ian M. Macaulay, Calum E. English, John C. Tsao, Ming S. Gazdar, Adi F. Lam, Stephen Lockwood, William W. Lam, Wan TI KEAP1/CULLIN-3/RING BOX PROTEIN-1 E3 UBIQUITIN LIGASE COMPLEX DISRUPTION IS A NOVEL GENETIC MECHANISM OF NF-kappa B ACTIVATION IN LUNG CANCER SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE NFkB signaling; IKBKB; KEAP1/CUL3/RBX1 E3 Ubiquitin ligase; genetic disruption C1 [Pikor, Larissa A.; Thu, Kelsie; Wilson, Ian M.; Macaulay, Calum E.; Lam, Stephen; Lam, Wan] BC Canc Res Ctr, Vancouver, BC, Canada. [Chari, Raj] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [English, John C.] Vancouver Gen Hosp, Vancouver, BC, Canada. [Tsao, Ming S.] Princess Margaret Hosp, Toronto, ON, Canada. [Gazdar, Adi F.] Univ Texas, Hamon Ctr Therapeut Oncol Res, Austin, TX USA. [Lockwood, William W.] NHGRI, NIH, Bethesda, MD 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S342 EP S343 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855802039 ER PT J AU Rudin, C Garon, EB De Oliveira, MR Bonomi, P Camidge, RD Chu, Q Giaccone, G Khaira, D Ramalingam, S Ranson, M Hann, C Mckeegan, E Chyla, B Dowell, BL Chakravartty, A Nolan, C Busman, T Mabry, M Krivoshik, A Humerickhouse, R Shapiro, G Gandhi, L AF Rudin, Charles Garon, Edward B. De Oliveira, Moacyr Ribeiro Bonomi, Philip Camidge, Ross D. Chu, Quincy Giaccone, Giuseppe Khaira, Divis Ramalingam, Suresh Ranson, Malcolm Hann, Christine Mckeegan, Evelyn Chyla, Brenda Dowell, Barry L. Chakravartty, Arunava Nolan, Catherine Busman, Todd Mabry, Mack Krivoshik, Andrew Humerickhouse, Rod Shapiro, Geoffrey Gandhi, Leena TI PATIENT OUTCOME AND EXPLORATORY ANALYSIS FROM A PHASE 2A STUDY OF NAVITOCLAX (ABT-263) IN PATIENTS WITH ADVANCED/RELAPSED SMALL CELL LUNG CANCER (SCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Navitoclax; Phase 2 Trial; SCLC; apoptosis C1 [Rudin, Charles] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21218 USA. [Garon, Edward B.] Univ Calif Los Angeles, Johnsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [De Oliveira, Moacyr Ribeiro] Northwest Med Specialties Pllc, Oncol, Tacoma, WA USA. [Bonomi, Philip] Rush Univ, Med Ctr, Chicago, IL USA. [Camidge, Ross D.] Univ Calif Davis, Ctr Canc, Davis, CA 95616 USA. [Chu, Quincy] Alberta Hlth Serv, Calgary, AB, Canada. [Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. [Khaira, Divis] Sunterra Oncol Associates, Peoria, IL USA. [Ramalingam, Suresh] Emory Univ, Atlanta, GA 30322 USA. [Ranson, Malcolm] Christie NHS Fdn Trust, Cambridge, England. [Hann, Christine] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Mckeegan, Evelyn; Chyla, Brenda; Dowell, Barry L.; Chakravartty, Arunava; Nolan, Catherine; Busman, Todd; Mabry, Mack; Krivoshik, Andrew; Humerickhouse, Rod] Abbott, Abbott Pk, IL USA. [Shapiro, Geoffrey; Gandhi, Leena] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S644 EP S645 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855803045 ER PT J AU Schrump, DS Zhang, M Mathur, A Rao, M Xi, S Zhang, YW Hong, JA Kemp, C Ripley, RT Liu, F Weigand, G Avital, I AF Schrump, David S. Zhang, Mary Mathur, Aarti Rao, Mahadev Xi, Sichaun Zhang, Yuwei Hong, Julie A. Kemp, Clinton Ripley, R. Taylor Liu, Fang Weigand, Gordon Avital, Itzak TI CIGARETTE SMOKE ENHANCES THE MALIGNANT PHENOTYPE OF LUNG CANCER CELLS VIA INDUCTION OF THE PUTATIVE STEM CELL MARKER ABCG2 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Schrump, David S.; Zhang, Mary; Mathur, Aarti; Rao, Mahadev; Xi, Sichaun; Zhang, Yuwei; Hong, Julie A.; Kemp, Clinton; Ripley, R. Taylor; Liu, Fang; Weigand, Gordon; Avital, Itzak] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S749 EP S750 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855803189 ER PT J AU Schrump, DS Xi, SC Xu, H Shan, JG Tao, YG Zhang, M Inchauste, S Mercedes, L Hong, JA AF Schrump, David S. Xi, Sichaun Xu, Hong Shan, Jigui Tao, Yongguang Zhang, Mary Inchauste, Suzanne Mercedes, Leandro Hong, Julie A. TI CIGARETTE SMOKE ENHANCES POLYCOMB EXPRESSION AND ACTIVATES WNT SIGNALING IN NORMAL RESPIRATORY EPITHELIA AND LUNG CANCER CELLS VIA EPIGENETIC REPRESSION OF MIR-487B SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Schrump, David S.; Xi, Sichaun; Zhang, Mary; Inchauste, Suzanne; Mercedes, Leandro; Hong, Julie A.] NCI, Bethesda, MD 20892 USA. [Xu, Hong; Tao, Yongguang] NCI, Lab Canc Prevent, Bethesda, MD 20892 USA. [Shan, Jigui] NCI, Adv Biomed Comp Ctr, 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 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S681 EP S681 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855803092 ER PT J AU Stewart, GL Pikor, LA Wilson, IM Coe, BP Chari, R Thu, K Yee, J English, JC Murray, N Tsao, MS Minna, JD Gazdar, AF Macaulay, CE Lam, S Lam, W Lockwood, WW AF Stewart, Greg L. Pikor, Larissa A. Wilson, Ian M. Coe, Bradley P. Chari, Raj Thu, Kelsie Yee, John English, John C. Murray, Nevin Tsao, Ming S. Minna, John D. Gazdar, Adi F. Macaulay, Calum E. Lam, Stephen Lam, Wan Lockwood, William W. TI DIVERGENT GENOMIC AND EPIGENOMIC LANDSCAPES OF LUNG CANCER SUBTYPES UNDERSCORE THE SELECTION OF DIFFERENT ONCOGENIC PATHWAYS SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Subtype; Genomics; squamous cell carcinoma; Adenocarcinoma C1 [Stewart, Greg L.; Pikor, Larissa A.; Wilson, Ian M.; Coe, Bradley P.; Chari, Raj; Thu, Kelsie; Macaulay, Calum E.; Lam, Stephen; Lam, Wan] British Columbia Canc Res Ctr, Vancouver, BC, Canada. [Yee, John; English, John C.] Vancouver Gen Hosp, Vancouver, BC, Canada. [Murray, Nevin] British Columbia Canc Agcy, Vancouver, BC, Canada. [Tsao, Ming S.] Princess Margaret Hosp, Univ Hlth Network, Dept Pathol, Toronto, ON, Canada. [Tsao, Ming S.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Minna, John D.; Gazdar, Adi F.] Univ Texas Southwestern Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. [Lockwood, William W.] NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU 2 BP S300 EP S301 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA V31AF UT WOS:000208855801250 ER PT J AU Wang, YA Lubet, RA You, M AF Wang, Yian Lubet, Ronald A. You, Ming TI EFFICACY OF THE RXR AGONIST BEXAROTENE IN PRECLINICAL MODELS OF ADENOCARCINOMA OF THE LUNG AND SMALL CELL LUNG CANCER SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract DE Small cell lung cancer; transgenic model; RXR agonist (Bexarotene) C1 [Wang, Yian] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63130 USA. [Lubet, Ronald A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [You, Ming] Med Coll Wisconsin, Ctr Canc, Milwaukee, WI 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 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2011 VL 6 IS 6 SU S BP S943 EP S943 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 779HX UT WOS:000291769800063 ER PT J AU Sanders, JL Iannaccone, A Boudreau, RM Conley, YP Opresko, PL Hsueh, WC Cummings, SR Cawthon, RM Harris, TB Nalls, MA Kritchevsky, SB Newman, AB AF Sanders, Jason L. Iannaccone, Alessandro Boudreau, Robert M. Conley, Yvette P. Opresko, Patricia L. Hsueh, Wen-Chi Cummings, Steven R. Cawthon, Richard M. Harris, Tamara B. Nalls, Michael A. Kritchevsky, Steven B. Newman, Anne B. CA Hlth ABC Study TI The Association of Cataract With Leukocyte Telomere Length in Older Adults: Defining a New Marker of Aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Lens transparency; Cataract; Leukocyte telomere length; Aging; Biomarker ID AGE-RELATED CATARACT; SLIT-LAMP CAMERA; HUMAN LENS; CARDIOVASCULAR HEALTH; EYE; CHAPERONES; CRYSTALLIN; DISEASE; POPULATION; EXPRESSION AB Lens transparency, or the magnitude of cataract severity, is a potential in vivo marker of aging distinguishable from diagnosed cataract. To explore lens transparency as a marker of aging, we determined its association with leukocyte telomere length (LTL) measured with quantitative polymerase chain reaction. Cataract severity was directly measured in 259 participants, and prevalent cataract and incident cataract surgery were ascertained in 2,750 participants of the Health. Aging, and Body Composition Study. LTL was unassociated with clinical cataract outcomes. Six of 259 had successfully aged lenses and a mean LTL of 5,700 bp, whereas 253/259 with poorly aged lenses had a mean LTL of 4,770 bp. Participants with a 1,000 bp greater mean LTL had nearly half the odds of any cataract (odds ratio = 0.47,95% confidence interval 0.22-1.02) after adjustment. Lens transparency might be associated with longer LTL in community-dwelling older adults and should be investigated further as a possible biomarker of aging. C1 [Sanders, Jason L.; Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Sanders, Jason L.] Univ Pittsburgh, Med Scientist Training Program, Sch Med, Pittsburgh, PA 15213 USA. [Iannaccone, Alessandro] Univ Tennessee, Ctr Hlth Sci, Retinal Degenerat & Ophthalm Genet Serv, Hamilton Eye Inst,Dept Ophthalmol, Memphis, TN 38163 USA. [Conley, Yvette P.] Univ Pittsburgh, Grad Sch Publ Hlth, Sch Nursing, Dept Hlth Promot & Dev, Pittsburgh, PA 15213 USA. [Opresko, Patricia L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Environm & Occupat Hlth, Pittsburgh, PA 15213 USA. [Hsueh, Wen-Chi] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Hsueh, Wen-Chi] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Cummings, Steven R.] Univ Calif San Francisco, San Francisco Coordinating Ctr, CPMC Res Inst, San Francisco, CA 94143 USA. [Cawthon, Richard M.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA. [Harris, Tamara B.; Nalls, Michael A.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Kritchevsky, Steven B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. [Kritchevsky, Steven B.] J Paul Sticht Ctr Aging, Winston Salem, NC USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. RP Sanders, JL (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Bellefield Profess Bldg,4th Floor,130 N Bellefiel, Pittsburgh, PA 15213 USA. EM sanders.jason@medstudent.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Opresko, Patricia/0000-0002-6470-2189; Boudreau, Robert/0000-0003-0162-5187 FU National Institutes of Health (NIH), National Institute on Aging (NIA); NIH, Bethesda, MD [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Eye Institute [K23 EY000409, N01 AG62101, N01 AG62103, N01 AG62106]; International Retinal Research Foundation, Birmingham, AL; Macular Degeneration Research, American Health Assistance Foundation, Clarksburg, MD; Research to Prevent Blindness; Longevity Consortium [5U19AG023122-05] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute on Aging (NIA). The Health ABC study is funded by contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 from the NIH, Bethesda, MD. The ARMA study is supported by National Eye Institute Grant K23 EY000409; Contracts NO I AG62101, N01 AG62103, and N01 AG62106 and the Intramural NIA Research Program; the International Retinal Research Foundation, Birmingham, AL; Macular Degeneration Research, American Health Assistance Foundation, Clarksburg, MD; and a Career Development Award (A.I.) and an unrestricted grant to the UTHSC Department of Ophthalmology from Research to Prevent Blindness. Telomere length measurement was supported by grant 5U19AG023122-05 (S.R.C.) from the Longevity Consortium. NR 39 TC 8 Z9 9 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2011 VL 66 IS 6 BP 639 EP 645 DI 10.1093/gerona/glr034 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 780XA UT WOS:000291892900004 PM 21382885 ER PT J AU Baigent, C Landray, MJ Reith, C Emberson, J Wheeler, DC Tomson, C Wanner, C Krane, V Cass, A Craig, J Neal, B Jiang, LX Hooi, LS Levin, A Agodoa, L Gaziano, M Kasiske, B Walker, R Massy, ZA Feldt-Rasmussen, B Krairittichai, U Ophascharoensuk, V Fellstrom, B Holdaas, H Tesar, V Wiecek, A Grobbee, D de Zeeuw, D Gronhagen-Riska, C Dasgupta, T Lewis, D Herrington, W Mafham, M Majoni, W Wallendszus, K Grimm, R Pedersen, T Tobert, J Armitage, J Baxter, A Bray, C Chen, YP Chen, ZM Hill, M Knott, C Parish, S Simpson, D Sleight, P Young, A Collins, R AF Baigent, Colin Landray, Martin J. Reith, Christina Emberson, Jonathan Wheeler, David C. Tomson, Charles Wanner, Christoph Krane, Vera Cass, Alan Craig, Jonathan Neal, Bruce Jiang, Lixin Hooi, Lai Seong Levin, Adeera Agodoa, Lawrence Gaziano, Mike Kasiske, Bertram Walker, Robert Massy, Ziad A. Feldt-Rasmussen, Bo Krairittichai, Udom Ophascharoensuk, Vuddidhej Fellstrom, Bengt Holdaas, Hallvard Tesar, Vladimir Wiecek, Andrzej Grobbee, Diederick de Zeeuw, Dick Gronhagen-Riska, Carola Dasgupta, Tanaji Lewis, David Herrington, William Mafham, Marion Majoni, William Wallendszus, Karl Grimm, Richard Pedersen, Terje Tobert, Jonathan Armitage, Jane Baxter, Alex Bray, Christopher Chen, Yiping Chen, Zhengming Hill, Michael Knott, Carol Parish, Sarah Simpson, David Sleight, Peter Young, Alan Collins, Rory CA SHARP Investigators TI The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial SO LANCET LA English DT Article ID REQUIRING PROLONGED OBSERVATION; UNITED-KINGDOM HEART; CARDIOVASCULAR EVENTS; EFFICACY; SAFETY; METAANALYSIS; DESIGN; PARTICIPANTS; HEMODIALYSIS; OUTCOMES AB Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and I SRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0.85 mmol/L (SE 0.02; with about two-thirds compliance) during a median follow-up of 4.9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11.3%] simvastatin plus ezetimibe vs 619 [13.4%] placebo; rate ratio [RR] 0.83, 95% CI 0.74-0.94; log-rank p=0.0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4.6%] vs 230 [5.0%]; RR 0.92,95% CI 0.76-1.11; p=0.37) and there were significant reductions in non-haemorrhagic stroke (131 [2.8%] vs 174 [3.8%]; RR 0.75,95% CI 0.60-0.94; p=0.01) and arterial revascularisation procedures (284 [6.1%] vs 352 [7.6%]; RR 0.79, 95% CI 0.68-0.93; p=0.0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0.2%] vs 5 [0.1%]). There was no evidence of excess risks of hepatitis (21 [0.5%] vs 18 [0.4%]), gallstones (106 [2.3%] vs 106 [2.3%]), or cancer (438 [9.4%] vs 439 [9.5%], p=0.89) and there was no significant excess of death from any non-vascular cause (668 [14.4%] vs 612 [13.2%], p=0.13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease. C1 [Baigent, Colin; Landray, Martin J.; Reith, Christina; Emberson, Jonathan; Lewis, David; Herrington, William; Mafham, Marion; Wallendszus, Karl; Armitage, Jane; Baxter, Alex; Bray, Christopher; Chen, Yiping; Chen, Zhengming; Hill, Michael; Knott, Carol; Parish, Sarah; Simpson, David; Young, Alan; Collins, Rory] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England. [Wheeler, David C.] UCL, London, England. [Tomson, Charles] N Bristol NHS Trust, Bristol, Avon, England. [Wanner, Christoph; Krane, Vera] Univ Wurzburg, Dept Med 1, Div Nephrol, Wurzburg, Germany. [Cass, Alan; Neal, Bruce] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Craig, Jonathan] Univ Sydney, Childrens Hosp Westmead, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia. [Jiang, Lixin] Fuwai Hosp, China Oxford Ctr Int Hlth Res, Beijing, Peoples R China. [Jiang, Lixin] Chinese Acad Med Sci, Beijing, Peoples R China. [Jiang, Lixin] Peking Union Med Coll, Beijing, Peoples R China. [Hooi, Lai Seong] Sultanah Aminah Hosp, Dept Med, Johor Baharu, Malaysia. [Hooi, Lai Seong] Sultanah Aminah Hosp, Haemodialysis Unit, Johor Baharu, Malaysia. [Levin, Adeera] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Agodoa, Lawrence] NIDDK, NIH, Bethesda, MD USA. [Gaziano, Mike] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston, Boston, MA 02115 USA. [Kasiske, Bertram] Univ Minnesota, Minneapolis, MN USA. [Walker, Robert] Univ Otago, Dunedin Sch Med, Otago, New Zealand. [Massy, Ziad A.] Amiens Univ Hosp, Div Clin Pharmacol, Amiens, France. [Massy, Ziad A.] Amiens Univ Hosp, Div Nephrol, Amiens, France. [Massy, Ziad A.] Univ Picardie Jules Verne, INSERM, ERI 12, Amiens, France. [Feldt-Rasmussen, Bo] Univ Copenhagen, Rigshosp, DK-2100 Copenhagen, Denmark. [Krairittichai, Udom] Rajavithi Hosp, Dept Med, Div Nephrol, Bangkok, Thailand. [Ophascharoensuk, Vuddidhej] Chiang Mai Univ, Fac Med, Dept Internal Med, Div Renal, Chiang Mai 50000, Thailand. [Fellstrom, Bengt] Univ Uppsala Hosp, Uppsala, Sweden. [Holdaas, Hallvard] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Organ Transplantat,Renal Sect, N-0027 Oslo, Norway. [Tesar, Vladimir] Charles Univ Prague, Sch Med 1, Dept Nephrol, Prague, Czech Republic. [Tesar, Vladimir] Charles Univ Prague, Gen Univ Hosp, Prague, Czech Republic. [Wiecek, Andrzej] Med Univ Silesia, Dept Nephrol Endocrinol & Metab Dis, Katowice, Poland. [Grobbee, Diederick] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [de Zeeuw, Dick] Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharmacol, NL-9713 AV Groningen, Netherlands. [Gronhagen-Riska, Carola] Helsinki Univ Hosp, Helsinki, Finland. [Dasgupta, Tanaji] Oxford Radcliffe Hosp NHS Trust, Oxford, England. [Majoni, William] Royal Darwin Hosp, Darwin, NT, Australia. [Grimm, Richard] Univ Minnesota, Hennepin Cty Med Ctr, Berman Ctr Outcomes & Clin Res, Minneapolis, MN 55415 USA. [Pedersen, Terje] Univ Oslo, Oslo, Norway. [Pedersen, Terje] Univ Oslo, Ulleval Hosp, Ctr Prevent Med, Oslo, Norway. [Tobert, Jonathan] Tobert Med Consulting LLC, Warren, NJ USA. [Sleight, Peter] John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. RP Baigent, C (reprint author), Univ Oxford, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England. EM sharpclinical@ctsu.ox.ac.uk RI Aldigier, Jean /O-8551-2016; Maxwell, Patrick/C-5557-2008; Johnson, David/F-2897-2011; Fassett, Robert/F-1752-2010; Walker, Robert /B-1498-2010; Colquhoun, David/F-9078-2013; Grobbee, Diederick/C-7651-2014; Craig, Jonathan/E-2813-2013; Mudge, David/C-1438-2011; de Zeeuw, Dick/E-9080-2014; HEALY, Helen/G-2686-2010; Combe, Christian/N-3726-2015; Rahimi, Kazem/Q-1279-2015 OI Aldigier, Jean /0000-0002-1804-981X; Fahal, Ibrahim/0000-0003-4897-6427; Mount, Peter/0000-0001-7637-3661; Emberson, Jonathan/0000-0001-7792-9422; Ferrari, Paolo/0000-0002-9619-3104; Herrington, Will/0000-0003-1172-8243; Landray, Martin/0000-0001-6646-827X; Maxwell, Alexander P./0000-0002-6110-7253; Beige, Joachim/0000-0002-1907-825X; Gray, Nicholas/0000-0001-9112-0304; Maxwell, Patrick/0000-0002-0338-2679; Johnson, David/0000-0001-5491-3460; Fassett, Robert/0000-0002-5318-6940; Grobbee, Diederick/0000-0003-4472-4468; Craig, Jonathan/0000-0002-2548-4035; Mudge, David/0000-0002-4112-5550; de Zeeuw, Dick/0000-0003-3434-7777; HEALY, Helen/0000-0003-4342-5300; Combe, Christian/0000-0002-0360-573X; Rahimi, Kazem/0000-0002-4807-4610 FU Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council; Merck/Schering-Plough Pharmaceuticals (North Wales, PA, USA); British Heart Foundation Centre of Research Excellence (Oxford, UK) [RE/08/04] FX Funding Merck/Schering-Plough Pharmaceuticals; Australian National Health and Medical Research Council; British Heart Foundation; UK Medical Research Council.; We thank the participants in SHARP and the local clinical centre staff, regional and national coordinators, steering committee, and data monitoring committee. The study was funded by Merck/Schering-Plough Pharmaceuticals (North Wales, PA, USA), with additional support from the Australian National Health Medical Research Council, the British Heart Foundation, and the UK Medical Research Council. JE acknowledges support from the British Heart Foundation Centre of Research Excellence (Oxford, UK; RE/08/04). NR 26 TC 855 Z9 904 U1 52 U2 195 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUN-JUL PY 2011 VL 377 IS 9784 BP 2181 EP 2192 DI 10.1016/S0140-6736(11)60739-3 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 786XI UT WOS:000292340800031 PM 21663949 ER PT J AU Kasprzak, W Bindewald, E Kim, TJ Jaeger, L Shapiro, BA AF Kasprzak, Wojciech Bindewald, Eckart Kim, Tae-Jin Jaeger, Luc Shapiro, Bruce A. TI Use of RNA structure flexibility data in nanostructure modeling SO METHODS LA English DT Review DE RNA; Nanostructure; Design; Modeling; Flexibility; Molecular dynamics ID POTENTIAL PARTS; CANCER-CELLS; GENOMIC RNA; IN-VITRO; NANOTECHNOLOGY; DYNAMICS; DESIGN; CONSTRUCTION; DIMERIZATION; MOTOR AB In the emerging field of RNA-based nanotechnology there is a need for automation of the structure design process. Our goal is to develop computer methods for aiding in this process. Towards that end, we created the RNAJunction database, which is a repository of RNA junctions, i.e. internal, multi-branch and kissing loops with emanating stem stubs, extracted from the larger RNA structures stored in the PDB database. These junctions can be used as building blocks for nanostructures. Two programs developed in our laboratory, NanoTiler and RNA2D3D, can combine such building blocks with idealized fragments of A-form helices to produce desired 3D nanostructures. Initially, the building blocks are treated as rigid objects and the resulting geometry is tested against the design objectives. Experimental data, however, shows that RNA accommodates its shape to the constraints of larger structural contexts. Therefore we are adding analysis of the flexibility of our building blocks to the full design process. Here we present an example of RNA-based nanostructure design, putting emphasis on the need to characterize the structural flexibility of the building blocks to induce ring closure in the automated exploration. We focus on the use of kissing loops (KL) in nanostructure design, since they have been shown to play an important role in RNA self-assembly. By using an experimentally proven system, the RNA tectosquare, we show that considering the flexibility of the KLs as well as distortions of helical regions may be necessary to achieve a realistic design. (C) 2011 Published by Elsevier Inc. C1 [Kim, Tae-Jin; Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Kasprzak, Wojciech; Bindewald, Eckart] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Jaeger, Luc] Univ Calif Santa Barbara, Dept Chem & Biochem, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA. RP Shapiro, BA (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM shapirbr@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH [RO1GM079604]; NIH, National Cancer Institute, Center for Cancer Research FX This publication has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E (to WK and EB). This research was supported in part by NIH RO1GM079604 (to LJ). This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (to TJK and BAS). 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 16 Z9 16 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD JUN PY 2011 VL 54 IS 2 BP 239 EP 250 DI 10.1016/j.ymeth.2010.12.010 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 782MG UT WOS:000292013200005 PM 21163354 ER PT J AU Edwards, AN Patterson-Fortin, LM Vakulskas, CA Mercante, JW Potrykus, K Vinella, D Camacho, MI Fields, JA Thompson, SA Georgellis, D Cashel, M Babitzke, P Romeo, T AF Edwards, Adrianne N. Patterson-Fortin, Laura M. Vakulskas, Christopher A. Mercante, Jeffrey W. Potrykus, Katarzyna Vinella, Daniel Camacho, Martha I. Fields, Joshua A. Thompson, Stuart A. Georgellis, Dimitris Cashel, Michael Babitzke, Paul Romeo, Tony TI Circuitry linking the Csr and stringent response global regulatory systems SO MOLECULAR MICROBIOLOGY LA English DT Article ID RNA-BINDING PROTEIN; SPOT-DEPENDENT ACCUMULATION; ESCHERICHIA-COLI GENE; BARA SENSOR KINASE; GLYCOGEN BIOSYNTHESIS; TRANSCRIPTION INITIATION; PSEUDOMONAS-AERUGINOSA; TRANSLATION INITIATION; BACILLUS-SUBTILIS; SALMONELLA-TYPHIMURIUM AB CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p) ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. C1 [Edwards, Adrianne N.; Mercante, Jeffrey W.; Romeo, Tony] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Patterson-Fortin, Laura M.; Vakulskas, Christopher A.; Romeo, Tony] Univ Florida, Dept Microbiol & Cell Sci, Gainesville, FL 32611 USA. [Potrykus, Katarzyna; Vinella, Daniel; Cashel, Michael] NICHD, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. [Camacho, Martha I.; Georgellis, Dimitris] Univ Nacl Autonoma Mexico, Dept Genet Mol, Inst Fisiol Celular, Mexico City 04510, DF, Mexico. [Fields, Joshua A.; Thompson, Stuart A.] Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. [Babitzke, Paul] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. RP Romeo, T (reprint author), Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. EM tromeo@ufl.edu RI vinella, daniel/G-5504-2012 FU NIH [GM059969, GM066794, AI084160, AI058284]; University of Florida CRIS [FLA-MCS-004949]; Emory University; DGAPA-PAPIIT of UNAM [IN219709-3]; International Centre for Genetic Engineering and Biotechnology (ICGEB) [CRP/MEX08-02]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX This work was supported by NIH grants GM059969 (T.R. and P.B.) and GM066794 (T.R.); FLA-MCS-004949 from University of Florida CRIS project (T.R.); George W. Woodruff Fellowship from Emory University (A.N.E.); NIH grants AI084160 and AI058284 (S.A.T.); by grants IN219709-3 from DGAPA-PAPIIT of UNAM and CRP/MEX08-02 from the International Centre for Genetic Engineering and Biotechnology (ICGEB) (D.G.); and in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural program of the NIH (M.C.). We also thank Helen Murphy for pHM1684. We would like to express our gratitude to William Farmerie at the University of Florida ICBR for 454 Sequencing of cDNA from CsrA-bound RNA. NR 83 TC 80 Z9 82 U1 1 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 2011 VL 80 IS 6 BP 1561 EP 1580 DI 10.1111/j.1365-2958.2011.07663.x PG 20 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 783TE UT WOS:000292106100012 PM 21488981 ER PT J AU Jin, SH Lin, P Auh, S Hallett, M AF Jin, Seung-Hyun Lin, Peter Auh, Sungyoung Hallett, Mark TI Abnormal Functional Connectivity in Focal Hand Dystonia: Mutual Information Analysis in EEG SO MOVEMENT DISORDERS LA English DT Article DE focal hand dystonia; mutual information; functional connectivity; sensorimotor integration ID SCIENTIFIC HYPOTHESIS GENERATION; PRIMARY SOMATOSENSORY CORTEX; WRITERS CRAMP; SENSORIMOTOR INTEGRATION; OSCILLATORY SYNCHRONY; BRAIN; MOTOR; RESPONSES; TASK; STIMULATION AB The aim of the present study was to investigate functional connectivity in focal hand dystonia patients to understand the pathophysiology underlying their abnormality in movement. We recorded EEGs from 58 electrodes in 15 focal hand dystonia patients and 15 healthy volunteers during rest and a simple finger- tapping task that did not induce any dystonic symptoms. We investigated mutual information, which provides a quantitative measure of linear and nonlinear coupling, in the alpha, beta, and gamma bands. Mean mutual information of all 58 channels and mean of the channels of interest representative of regional functional connectivity over sensorimotor areas (C3, CP3, C4, CP4, FCz, and Cz) were evaluated. For both groups, we found enhanced mutual information during the task compared with the rest condition, specifically in the beta and gamma bands for mean mutual information of all channels, and in all bands for mean mutual information of channels of interest. Comparing the focal hand dystonia patients with the healthy volunteers for both rest and task, there was reduced mutual information in the beta band for both mean mutual information of all channels and mean mutual information of channels of interest. Regarding the properties of the connectivity in the beta band, we found that the majority of the mutual information differences were from linear connectivity. The abnormal beta-band functional connectivity in focal hand dystonia patients suggests deficient brain connectivity. (C) 2011 Movement Disorder Society C1 [Jin, Seung-Hyun; Lin, Peter; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Auh, Sungyoung] Natl Inst Neurol Disorders & Stroke, Clin Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, 10 Ctr Dr,MSC 1428,Bldg 10,Room 7D37, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 54 TC 19 Z9 19 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN PY 2011 VL 26 IS 7 BP 1274 EP 1281 DI 10.1002/mds.23675 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 780NF UT WOS:000291863600017 PM 21506166 ER PT J AU Kobayashi, K Lang, AE Hallett, M Lenz, FA AF Kobayashi, Kazutaka Lang, Anthony E. Hallett, Mark Lenz, Frederick A. TI Thalamic Neuronal and EMG Activity in Psychogenic Dystonia Compared with Organic Dystonia SO MOVEMENT DISORDERS LA English DT Article DE psychogenic dystonia; organic dystonia; human thalamus; neuronal activity; plasticity; dystonia-related activity ID SENSORY NUCLEUS; REORGANIZATION; MONKEYS; REPRESENTATION; PLASTICITY; COHERENCE; CORTEX; TREMOR; HAND AB Background: This is a retrospective analysis of thalamic neuronal and electromyogram activities between subjects with organic dystonia and a subject with psychogenic dystonia in whom a thalamotomy was carried out before the diagnosis of psychogenic dystonia was made. Results: The signal-to-noise ratio in the lowest frequency band (dystonia frequency < 0.76 Hz) in the electromyogram was not significantly different by diagnosis or muscle. The coherence at dystonia frequency for wrist flexors X biceps electromyograms was significantly higher in organic dystonia, whereas the phase was not apparently different from zero for either diagnosis. In a thalamic pallidal relay nucleus (ventral oral posterior), neuronal firing rates were not apparently different between psychogenic and organic dystonia. The neuronal signal-to-noise ratio in ventral oral posterior was significantly higher in organic dystonia than in psychogenic dystonia, whereas both were greater than in controls with chronic pain. Spike X electromyogram coherence apparently was not different between psychogenic and organic dystonia. The proportion of thalamic cells responding to joint movements was higher in the cerebellar relay nucleus (ventral intermediate) of psychogenic dystonia than in organic dystonia. Conclusions: These results suggest that some features, such as firing rates and thalamic reorganization, are similar in psychogenic and organic dystonia. Other features differ, such as the coherence between the electromyograms from different muscles and the thalamic neuronal signal-to-noise ratio, which may reflect pathophysiological factors in organic dystonia. (C) 2011 Movement Disorder Society C1 [Kobayashi, Kazutaka; Lenz, Frederick A.] Johns Hopkins Univ Hosp, Dept Neurosurg, Baltimore, MD 21287 USA. [Kobayashi, Kazutaka] Nihon Univ, Sch Med, Dept Neurol Surg, Tokyo 173, Japan. [Kobayashi, Kazutaka] Nihon Univ, Sch Med, Dept Adv Med Sci, Div Appl Syst Neurosci, Tokyo, Japan. [Lang, Anthony E.] Univ Hlth Network, Div Neurol, Toronto, ON, Canada. [Lang, Anthony E.] Univ Toronto, Toronto, ON, Canada. [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Lenz, FA (reprint author), Johns Hopkins Univ Hosp, Dept Neurosurg, Meyer Bldg 8-181,600 N Wolfe St, Baltimore, MD 21287 USA. EM flenz1@jhmi.edu FU National Institutes of Health-National Institute of Neurological Disorders [RO1 NS38493, ROL NS40059] FX This work was supported by the National Institutes of Health-National Institute of Neurological Disorders and Stroke Intramural and Extramural Programs (RO1 NS38493 and ROL NS40059 to F.A.L.). NR 25 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN PY 2011 VL 26 IS 7 BP 1348 EP 1352 DI 10.1002/mds.23565 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 780NF UT WOS:000291863600029 PM 21500279 ER PT J AU Gaur, AB Holbeck, SL Colburn, NH Israel, MA AF Gaur, Arti B. Holbeck, Susan L. Colburn, Nancy H. Israel, Mark A. TI Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; mir-21; Pdcd4; tumor inhibition ID TUMOR-SUPPRESSOR PDCD4; BREAST-CANCER CELLS; MICRORNA-21 TARGETS; GENE-EXPRESSION; DEATH 4; TRANSLATION; INVASION; TRANSFORMATION; GROWTH; GLIOMA AB MicroRNAs (miRNAs) are small, noncoding RNAs that play a critical role in developmental and physiological processes and are implicated in the pathogenesis of several human diseases, including cancer. They function by regulating target gene expression post-transcriptionally. In this study, we examined the role of oncogenic mir-21 in the pathogenesis of glioblastoma, the most aggressive form of primary brain tumor. We have previously reported that mir-21 is expressed at higher levels in primary glioblastoma-tissue and glioblastoma-derived cell lines than in normal brain tissue. We demonstrate that downregulation of mir-21 in glioblastoma-derived cell lines results in increased expression of its target, programmed cell death 4 (Pdcd4), a known tumor-suppressor gene. In addition, our data indicate that either downregulation of mir-21 or overexpression of its target, Pdcd4, in glioblastoma-derived cell lines leads to decreased proliferation, increased apoptosis, and decreased colony formation in soft agar. Using a glioblastoma xenograft model in immune-deficient nude mice, we observe that glioblastoma-derived cell lines in which mir-21 levels are downregulated or Pdcd4 is over-expressed exhibit decreased tumor formation and growth. Significantly, tumors grow when the glioblastoma-derived cell lines are transfected with anti-mir-21 and siRNA to Pdcd4, confirming that the tumor growth is specifically regulated by Pdcd4. These critical in vivo findings demonstrate an important functional linkage between mir-21 and Pdcd4 and further elucidate the molecular mechanisms by which the known high level of mir-21 expression in glioblastoma can attribute to tumorigenesis namely, inhibition of Pdcd4 and its tumor-suppressive functions. C1 [Gaur, Arti B.; Israel, Mark A.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Dept Pediat, Hanover, NH 03755 USA. [Israel, Mark A.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Dept Genet, Hanover, NH 03755 USA. [Holbeck, Susan L.] NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. [Colburn, Nancy H.] NCI, Lab Canc Prevent, Bethesda, MD 20892 USA. RP Gaur, AB (reprint author), Dartmouth Med Sch, Norris Cotton Canc Ctr, Dept Pediat, Hanover, NH 03755 USA. EM arti.gaur@dartmouth.edu FU Theodora Betz foundation; National Cancer Institute, National Institutes of Health FX This work was supported by a grant from the Theodora Betz foundation to M.A.I. and by federal funds from the National Cancer Institute, National Institutes of Health (S.L.H. and N.H.C.). NR 50 TC 72 Z9 76 U1 0 U2 7 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 JUN PY 2011 VL 13 IS 6 BP 580 EP 590 DI 10.1093/neuonc/nor033 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 781FS UT WOS:000291916600003 PM 21636706 ER PT J AU Gursel, DB Connell-Albert, YS Tuskan, RG Anastassiadis, T Walrath, JC Hawes, JJ Amlin-Van Schaick, JC Reilly, KM AF Guersel, Demirkan B. Connell-Albert, Yvette S. Tuskan, Robert G. Anastassiadis, Theonie Walrath, Jessica C. Hawes, Jessica J. Amlin-Van Schaick, Jessica C. Reilly, Karlyne M. TI Control of proliferation in astrocytoma cells by the receptor tyrosine kinase/PI3K/AKT signaling axis and the use of PI-103 and TCN as potential anti-astrocytoma therapies SO NEURO-ONCOLOGY LA English DT Article DE Akt; astrocytoma; EGFR; Nf1; p53 ID TRICYCLIC NUCLEOSIDE PHOSPHATE; GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; RAPAMYCIN PATHWAY; MAMMALIAN TARGET; CANCER-THERAPY; IN-VIVO; GLIOBLASTOMA; GLIOMA; INHIBITORS AB A growing body of work suggests that astrocytomas and glioblastoma multiforme will require carefully tailored, molecularly targeted therapy for successful treatment. Recent efforts to comprehensively identify mutations and gene expression changes in glioblastoma have shown that mutation of NF1 is a common alteration in human glioblastoma. We have developed and characterized a panel of 14 tumor lines from grades H through IV astrocytomas developed from our Nf1-/+; Trp53-/+ cis mouse model and have used this panel to characterize signal transduction pathways and inhibitors that are candidate therapeutic targets for astrocytoma and glioblastoma. We show that these tumors express platelet-derived growth factor receptor-alpha, epidermal growth factor receptor, and their respective ligands to-varying degrees. We find that both the MEK and PI3K signaling pathways downstream of epidermal growth factor receptor and platelet-derived growth factor receptor-alpha are necessary for full proliferation of astrocytoma cells; however, inhibition of the PI3K pathway is more effective than inhibition of MEK at blocking cell growth. We have examined inhibitors of the PI3K/Akt/mTOR signaling pathway and find that PI-103 and TCN show particular promise for inhibiting growth in Nf1 and TrpS3 mutant astrocytoma cells. C1 [Guersel, Demirkan B.; Connell-Albert, Yvette S.; Tuskan, Robert G.; Anastassiadis, Theonie; Walrath, Jessica C.; Hawes, Jessica J.; Amlin-Van Schaick, Jessica C.; Reilly, Karlyne M.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. [Connell-Albert, Yvette S.] George Mason Univ, Fairfax, VA 22030 USA. RP Reilly, KM (reprint author), W 7th St & Ft Detrick,POB B, Frederick, MD 21702 USA. EM kreilly@ncifcrf.gov FU NIH, NCI FX This research was supported by the Intramural Program of the NIH, NCI. NR 31 TC 13 Z9 15 U1 1 U2 4 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 JUN PY 2011 VL 13 IS 6 BP 610 EP 621 DI 10.1093/neuonc/nor035 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 781FS UT WOS:000291916600006 PM 21636709 ER PT J AU Woicik, PA Urban, C Alia-Klein, N Henry, A Maloney, T Telang, F Wang, GJ Volkow, ND Goldstein, RZ AF Woicik, Patricia A. Urban, Catherine Alia-Klein, Nelly Henry, Ashley Maloney, Thomas Telang, Frank Wang, Gene-Jack Volkow, Nora D. Goldstein, Rita Z. TI A pattern of perseveration in cocaine addiction may reveal neurocognitive processes implicit in the Wisconsin Card Sorting Test SO NEUROPSYCHOLOGIA LA English DT Article DE Perseveration; Memory; Prefrontal cortex; Task switching; Cocaine; Drug addiction ID DORSOLATERAL PREFRONTAL CORTEX; SET-SHIFTING TASK; WORKING-MEMORY; COGNITIVE INFLEXIBILITY; FRONTAL-CORTEX; EXECUTIVE DYSFUNCTION; IMPULSIVITY PREDICTS; DOPAMINE MODULATION; SEROTONIN DEPLETION; INTRAVENOUS COCAINE AB The ability to adapt behavior in a changing environment is necessary for humans to achieve their goals and can be measured in the lab with tests of rule-based switching. Disease models, such as cocaine addiction, have revealed that alterations in dopamine interfere with adaptive set switching, culminating in perseveration. We explore perseverative behavior in individuals with cocaine use disorders (CUD) and healthy controls (CON) during performance of the Wisconsin Card Sorting Test (WCST) (N = 107 in each group). By examining perseverative errors within each of the 6 blocks of the WCST, we uniquely test two forms of set switching that are differentiated by either the presence (extradimensional set shifting (EDS) - first 3 blocks) or absence (task-set switching - last 3 blocks) of new contingency learning. We also explore relationships between perseveration and select cognitive and drug use factors including verbal learning and memory, trait inhibitory control, motivational state, and urine status for cocaine (in CUD). Results indicate greater impairment for CUD than CON on the WCST, even in higher performing CUD who completed all 6 blocks of the WCST. Block by block analysis conducted on completers' scores indicate a tendency for greater perseveration in CUD than CON but only during the first task-set switch; no such deficits were observed during EDS. This task-set switching impairment was modestly associated with two indices of immediate recall (r = -.32, -.29) and urine status for cocaine [t(134)=2.3, p<.03]. By distinguishing these two forms of switching on the WCST, the current study reveals a neurocognitive context (i.e. initial stage of task-set switching) implicit in the WCST that possibly relies upon intact dopaminergic function, but that is impaired in CUD, as associated with worse recall and possibly withdrawal from cocaine. Future studies should investigate whether dopaminergically innervated pathways alone, or in combination with other monoamines, underlie this implicit neurocognitive processes in the WCST. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Woicik, Patricia A.] Brookhaven Natl Lab, Neuropsychoimaging Grp, Dept Med, Upton, NY 11973 USA. [Urban, Catherine] SUNY Stony Brook, Sch Med, Stony Brook, NY 11790 USA. [Henry, Ashley] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Woicik, PA (reprint author), Brookhaven Natl Lab, Neuropsychoimaging Grp, Dept Med, Bldg 490, Upton, NY 11973 USA. EM pwoicik@bnl.gov; rgoldstein@bnl.gov FU National Institute on Drug Abuse [1R01DA023579, R21DA02062]; General Clinical Research Center [5-MO1-RR-10710]; U.S. Department of Energy [DE-AC02-98CHI-886] FX This study was supported by grants from the National Institute on Drug Abuse (to RZG: 1R01DA023579; R21DA02062) and General Clinical Research Center (5-MO1-RR-10710).; This manuscript 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. NR 92 TC 22 Z9 22 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUN PY 2011 VL 49 IS 7 BP 1660 EP 1669 DI 10.1016/j.neuropsychologia.2011.02.037 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 782LA UT WOS:000292009400003 PM 21392517 ER PT J AU Terao, Y Fukuda, H Yugeta, A Hikosaka, O Nomura, Y Segawa, M Hanajima, R Tsuji, S Ugawa, Y AF Terao, Yasuo Fukuda, Hideki Yugeta, Akihiro Hikosaka, Okihide Nomura, Yoshiko Segawa, Masaya Hanajima, Ritsuko Tsuji, Shoji Ugawa, Yoshikazu TI Initiation and inhibitory control of saccades with the progression of Parkinson's disease - Changes in three major drives converging on the superior colliculus SO NEUROPSYCHOLOGIA LA English DT Article DE Parkinson's disease; Saccades; Superior colliculus; Inhibition; Basal ganglia ID NIGRA PARS RETICULATA; POSITRON-EMISSION-TOMOGRAPHY; PRIMATE SUBTHALAMIC NUCLEUS; VISUALLY GUIDED SACCADES; LOCAL DOPAMINE DEPLETION; GABA-RELATED SUBSTANCES; EYE-MOVEMENT CONTROL; HUMAN BASAL GANGLIA; VOLUNTARY SACCADES; GLOBUS-PALLIDUS AB The cardinal pathophysiology of Parkinson's disease (PD) is considered to be the increase in the activities of basal ganglia (BC) output nuclei, which excessively inhibits the thalamus and superior colliculus (SC) and causes preferential impairment of internal over external movements. Here we recorded saccade performance in 66 patients with PD and 87 age-matched controls, and studied how the abnormality changed with disease progression. PD patients were impaired not only in memory guided saccades, but also in visually guided saccades, beginning in the relatively early stages of the disease. On the other hand, they were impaired in suppressing reflexive saccades (saccades to cue). All these changes deteriorated with disease progression. The frequency of reflexive saccades showed a negative correlation with the latency of visually guided saccades and Unified Parkinson's Disease Rating Scale motor subscores reflecting dopaminergic function. We suggest that three major drives converging on SC determine the saccade abnormalities in PD. The impairment in visually and memory guided saccades may be caused by the excessive inhibition of the SC due to the increased BC output and the decreased activity of the frontal cortex-BC circuit. The impaired suppression of reflexive saccades may be explained if the excessive inhibition of SC is "leaky." Changes in saccade parameters suggest that frontal cortex-BC circuit activity decreases with disease progression, whereas SC inhibition stays relatively mild in comparison throughout the course of the disease. Finally, SC disinhibition due to leaky suppression may represent functional compensation from neural structures outside BG, leading to hyper-reflexivity of saccades and milder clinical symptoms. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Terao, Yasuo; Yugeta, Akihiro; Hanajima, Ritsuko; Tsuji, Shoji] Univ Tokyo, Dept Neurol, Grad Sch Med, Bunkyo Ku, Tokyo 1138655, Japan. [Fukuda, Hideki; Nomura, Yoshiko; Segawa, Masaya] Segawa Neurol Clin Children, Chiyoda Ku, Tokyo 1010062, Japan. [Hikosaka, Okihide] NEI, Sect Neuronal Networks, Sensorimotor Res Lab, Bethesda, MD 20892 USA. [Ugawa, Yoshikazu] Fukushima Med Univ, Dept Neurol, Sch Med, Fukushima 9601295, Japan. RP Terao, Y (reprint author), Univ Tokyo, Dept Neurol, Grad Sch Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM yterao-tky@umin.ac.jp NR 75 TC 37 Z9 37 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUN PY 2011 VL 49 IS 7 BP 1794 EP 1806 DI 10.1016/j.neuropsychologia.2011.03.002 PG 13 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 782LA UT WOS:000292009400017 PM 21420990 ER PT J AU Knutson, KM DeTucci, KA Grafman, J AF Knutson, Kristine M. DeTucci, Karen A. Grafman, Jordan TI Implicit attitudes in prosopagnosia SO NEUROPSYCHOLOGIA LA English DT Article DE Prosopagnosia; Implicit attitudes; Brain lesions; Traumatic brain injury; Social cognition ID MIDDLE FUSIFORM GYRUS; COVERT FACE RECOGNITION; ACQUIRED PROSOPAGNOSIA; ASSOCIATION TEST; FACIAL RECOGNITION; FAMILIAR FACES; NEURAL SYSTEM; HUMAN BRAIN; PATIENT; CORTEX AB We studied a male with acquired prosopagnosia using a battery of Implicit Association Tests (IATs) to investigate whether observing faces varying by social category would activate the patient's implicit social biases. We also asked him to categorize faces explicitly by race, gender, and political party. The patient, GB., was marginally slower to categorize black compared to white faces. He showed congruency effects in the race and celebrity IATs, but not in the gender or political IATs. These results indicate that G.B. possesses an implicit social sensitivity to certain facial stimuli despite an inability to overtly recognize familiar faces. The results demonstrate that social biases can be retrieved based on facial stimuli via pathways bypassing the fusiform gyri. Thus the IAT effect can be added to the list of covert recognition effects found in prosopagnosia. Published by Elsevier Ltd. C1 [Knutson, Kristine M.; DeTucci, Karen A.; Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA. RP Grafman, J (reprint author), Kessler Fdn Res Ctr, Traumat Brain Injury Res Lab, 1199 Pleasant Valley Way, W Orange, NJ 07052 USA. EM knutsonk@ninds.nih.gov; kdetucci@yahoo.com; jgrafman@kesslerfoundation.org OI Grafman, Jordan H./0000-0001-8645-4457; Knutson, Kristine/0000-0003-4626-4514 FU National Institute of Neurological Disorders and Stroke, National Institutes of Health; John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development FX We thank G.B. for his participation, Joshua Poore for his comments on an earlier manuscript, Tianxia Wu for her statistical guidance, and the anonymous reviewers for their insightful comments. This study was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. The authors declare no conflict of interest. Some of the faces were obtained from the MacBrain Face Stimulus Set. Development of the MacBrain Face Stimulus Set was overseen by Nim Tottenham and supported by the John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development. Please contact Nim Tottenham at tott0006@tc.umn.edu for more information concerning the stimulus set. The Caltech Frontal face dataset (Faces 1999) was collected by Markus Weber at the California Institute of Technology and can be obtained at http://www.vision.caltech.edu/html-files/archive.html. NR 94 TC 1 Z9 1 U1 3 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JUN PY 2011 VL 49 IS 7 BP 1851 EP 1862 DI 10.1016/j.neuropsychologia.2011.03.009 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 782LA UT WOS:000292009400023 PM 21414330 ER PT J AU Zhang, Y Lee, ET Cowan, LD Fabsitz, RR Howard, BV AF Zhang, Y. Lee, E. T. Cowan, L. D. Fabsitz, R. R. Howard, B. V. TI Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: The Strong Heart Study SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Article DE Coffee; Diabetes mellitus; type 2; Indians; North American ID CARDIOVASCULAR-DISEASE; AMERICAN-INDIANS; IMPAIRED GLUCOSE; CHLOROGENIC ACID; DIETARY FIBER; RISK-FACTORS; CAFFEINE; MELLITUS; HUMANS; ANTIOXIDANTS AB Background and aims: It was reported that high coffee consumption was related to decreased diabetes risk. The aim of this study is to examine the association between coffee consumption and the incidence of type 2 diabetes in persons with normal glucose tolerance in a population with a high incidence and prevalence of diabetes. Methods and results: In a prospective cohort study, information about daily coffee consumption was collected at the baseline examination (1989-1992) in a population-based sample of American Indian men and women 45-74 years of age. Participants with normal glucose tolerance (N = 1141) at the baseline examination were followed for an average of 7.6 years. The incidence of diabetes was compared across the categories of daily coffee consumption. The hazard ratios of diabetes related to coffee consumption were calculated using Cox proportional hazards models, adjusted for potential confounders. Levels of coffee consumption were positively related to levels of current smoking and inversely related to body mass index, waist circumference, female gender, and hypertension. Compared to those who did not drink coffee, participants who drank 12 or more cups of coffee daily had 67% less risk of developing diabetes during the follow-up (hazard ratio: 0.33, 95% confidence interval: 0.13, 0.81). Conclusion: In this population, a high level of coffee consumption was associated with a reduced risk of deterioration of glucose metabolism over an average 7.6 years of follow-up. More work is needed to understand whether there is a plausible biological mechanism for this observation. (C) 2009 Elsevier B.V. All rights reserved. C1 [Zhang, Y.; Lee, E. T.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK 73190 USA. [Lee, E. T.; Cowan, L. D.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Dept Biostat & Epidemiol, Oklahoma City, OK 73190 USA. [Fabsitz, R. R.] NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. [Howard, B. V.] MedStar Res Inst, Washington, DC USA. RP Zhang, Y (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, POB 26901, Oklahoma City, OK 73190 USA. EM Ying-zhang4@ouhsc.edu FU National Heart, Lung, and Blood Institute, Bethesda, MD [U01-HL41642, U01-HL41652, UL01-HL41654, U01-HL65520, U01-HL65521]; Ak-Chin Tohono O'Odham (Papago)/Pima; Apache; Caddo; Cheyenne River Sioux; Comanche; Delaware; Spirit Lake Sioux; Fort Sill Apache; Gila River Pima Maricopa; Kiowa; Oglala Sioux; Salt River Pima/Maricopa; Wichita Indian communities FX This study was supported by cooperative agreement grants U01-HL41642, U01-HL41652, UL01-HL41654, U01-HL65520, and U01-HL65521 from the National Heart, Lung, and Blood Institute, Bethesda, MD. The authors acknowledge the assistance and cooperation of the Ak-Chin Tohono O'Odham (Papago)/Pima, Apache, Caddo, Cheyenne River Sioux, Comanche, Delaware, Spirit Lake Sioux, Fort Sill Apache, Gila River Pima Maricopa, Kiowa, Oglala Sioux, Salt River Pima/Maricopa and Wichita Indian communities. It would have been impossible to conduct this study without their support. The authors also want to thank the Indian Health Service hospitals and clinics at each center, the directors of the Strong Heart Study clinics, the field coordinators, and their staffs. In addition, we thank Holly A. Anderson for editing the manuscript. NR 39 TC 16 Z9 16 U1 2 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0939-4753 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD JUN PY 2011 VL 21 IS 6 BP 418 EP 423 DI 10.1016/j.numecd.2009.10.020 PG 6 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA 781ZY UT WOS:000291978100006 PM 20171062 ER PT J AU Houston, DK Ding, J Lee, JS Garcia, M Kanaya, AM Tylavsky, FA Newman, AB Visser, M Kritchevsky, SB AF Houston, D. K. Ding, J. Lee, J. S. Garcia, M. Kanaya, A. M. Tylavsky, F. A. Newman, A. B. Visser, M. Kritchevsky, S. B. CA Hlth ABC Study TI Dietary fat and cholesterol and risk of cardiovascular disease in older adults: The Health ABC Study SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Article DE Cardiovascular disease; Dietary fat; Dietary cholesterol; Eggs; Older adults; Type 2 diabetes ID CORONARY-HEART-DISEASE; EGG CONSUMPTION; MORTALITY; WOMEN; STROKE; MEN; POPULATION; PREDICTORS; ADHERENCE; COHORT AB Background and aims: Although dietary fats and cholesterol have previously been associated with risk of cardiovascular disease (CVD) in middle-aged populations, less is known among older adults. The purpose of this study was to determine the association between dietary fats, cholesterol, and eggs and CVD risk among community-dwelling adults aged 70-79 in the Health, Aging and Body Composition Study. Methods and results: Diet was assessed using an interviewer-administered 108-item food frequency questionnaire (n = 1941). CVD events were defined as a confirmed myocardial infarction, coronary death, or stroke. Relative rates of CVD over 9 years of follow-up were estimated using Cox proportional hazards models. During follow-up, there were 203 incident cases of CVD. There were no significant associations between dietary fats and CVD risk. Dietary cholesterol (HR (95% CI): 1.47 (0.93, 2.32) for the upper vs. lower tertile; P for trend, 0.10) and egg consumption (HR (95% CI): 1.68 (1.12, 2.51) for 3+/week vs. < 1/week; P for trend, 0.01) were associated with increased CVD risk. However, in sub-group analyses, dietary cholesterol and egg consumption were associated with increased CVD risk only among older adults with type 2 diabetes (HR (95% CI): 3.66 (1.09, 12.29) and 5.02 (1.63, 15.52), respectively, for the upper vs. lower tertile/group). Conclusions: Dietary cholesterol and egg consumption were associated with increased CVD risk among older, community-dwelling adults with type 2 diabetes. Further research on the biological mechanism(s) for the increased CVD risk with higher dietary cholesterol and frequent egg consumption among older adults with diabetes is warranted. (C) 2009 Elsevier B.V. All rights reserved. C1 [Houston, D. K.; Ding, J.; Kritchevsky, S. B.] Wake Forest Univ, Sch Med, Sect Gerontol & Geriatr Med, Sticht Ctr Aging,Dept Internal Med, Winston Salem, NC 27157 USA. [Lee, J. S.] Univ Georgia, Dept Foods & Nutr, Athens, GA 30601 USA. [Garcia, M.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Kanaya, A. M.] Univ Calif San Francisco, San Francisco, CA 94115 USA. [Tylavsky, F. A.] Univ Tennessee, Dept Prevent Med, Memphis, TN 38105 USA. [Newman, A. B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Visser, M.] Vrije Univ Amsterdam, Inst Hlth Sci, Amsterdam, Netherlands. RP Houston, DK (reprint author), Wake Forest Univ, Sch Med, Sect Gerontol & Geriatr Med, Sticht Ctr Aging,Dept Internal Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM dhouston@wfubmc.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIH, National Institute on Aging; National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; Wake Forest University Claude D. Pepper Older Americans Independence Center [P30-AG21332]; American Egg Board/Egg Nutrition Center FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging; National Institute on Aging contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; the Wake Forest University Claude D. Pepper Older Americans Independence Center (P30-AG21332); and the American Egg Board/Egg Nutrition Center. NR 27 TC 36 Z9 41 U1 2 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0939-4753 EI 1590-3729 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD JUN PY 2011 VL 21 IS 6 BP 430 EP 437 DI 10.1016/j.numecd.2009.11.007 PG 8 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA 781ZY UT WOS:000291978100008 PM 20338738 ER PT J AU Dettman, EJ Simko, SJ Ayanga, B Carofino, BL Margolin, JF Morse, HC Justice, MJ AF Dettman, E. J. Simko, S. J. Ayanga, B. Carofino, B. L. Margolin, J. F. Morse, H. C., III Justice, M. J. TI Prdm14 initiates lymphoblastic leukemia after expanding a population of cells resembling common lymphoid progenitors SO ONCOGENE LA English DT Article DE leukemia; Prdm14; leukemia-initiating cell; pluripotency; common lymphoid progenitor; acute lymphoblastic leukemia ID BREAST-CANCER; STEM-CELLS; RETROVIRAL INSERTIONS; MEIOTIC RECOMBINATION; BONE-MARROW; IN-VITRO; C-KIT; GENE; MICE; EXPRESSION AB Understanding the heterogeneous genetic mechanisms of tumor initiation in lymphoid leukemias (LL) will lead to improvements in prognostic classification and treatment regimens. In previous studies of mouse leukemias, we showed that retroviral insertion at the ecotropic viral insertion site 32 locus leads to increased expression of Prdm14, a pluripotency gene implicated in the self-renewal capacity of embryonic stem cells and the early stages of breast cancer. Here, we show that PRDM14 is also overexpressed in similar to 25% of human lymphoid neoplasms, with increased frequencies in T-cell acute LL and hyperdiploid precursor B-cell acute LL. To test if Prdm14 overexpression could initiate leukemia, mice were transduced with bone marrow cells transfected with a Prdm14 expression vector. LLs developed in 96% of female mice and 42% of male mice. Before the onset of leukemia, differentiation of transduced cells was biased up to 1000-fold toward cells with features of common lymphoid progenitors (CLPs), and lymphoid differentiation showed a relative block at the pro-B stage. Microarray gene expression analysis of expanded CLP-like cells before the onset of leukemia demonstrated upregulation of genes involved in pluripotency, tumor initiation, early B-lineage commitment, Wnt/Ras signaling and the epithelial-to-mesenchymal transition. Among the dysregulated genes were imprinted genes and non-coding RNAs including Dlk1 and Meg3, which are also key pluripotency mediators. Heightened expression of the estrogen-dependent oncogene, Myb, in tumors suggests a basis for the increased frequency of cancer in female mice. These data provide the first direct evidence for the association of Prdm14 with cancer initiation in an in vivo mouse model and in human lymphoid malignancies, while suggesting mechanisms for Prdm14's mode of action. Oncogene (2011) 30, 2859-2873; doi:10.1038/onc.2011.12; published online 21 February 2011 C1 [Dettman, E. J.; Ayanga, B.; Carofino, B. L.; Justice, M. J.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Simko, S. J.; Margolin, J. F.] Baylor Coll Med, Sect Hematol & Oncol, Dept Pediat, Houston, TX 77030 USA. [Morse, H. C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD USA. [Justice, M. J.] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. RP Justice, MJ (reprint author), Baylor Coll Med, Dept Mol & Human Genet, MS227,1 Baylor Plaza R804, Houston, TX 77030 USA. EM mjustice@bcm.edu RI liang, yan/H-3894-2011; OI Morse, Herbert/0000-0002-9331-3705 FU NIH [R01 CA63229, R01 CA15530]; Baylor College of Medicine; NIH National Research Service [3 T32 CA115303-04]; NIH, National Institute of Allergy and Infectious Diseases FX The work by MJJ was supported by NIH R01 CA63229, R01 CA15530 and a Baylor College of Medicine Interim funding award. SJS was supported by an NIH National Research Service Award Institutional Training Grant 3 T32 CA115303-04, 'Pediatric Oncology Research Training Program.' HCM was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. We thank John Belmont and Molly Bray at the Laboratory for Translational Genomics at BCM for microarray data production; Jill Crowe for excellent technical assistance; and Frank Probst for the critical reading of the paper. NR 69 TC 22 Z9 22 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUN PY 2011 VL 30 IS 25 BP 2859 EP 2873 DI 10.1038/onc.2011.12 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 781ZV UT WOS:000291977800006 PM 21339739 ER PT J AU Rame, JE Barouch, LA Sack, MN Lynn, EG Abu-Asab, M Tsokos, M Kern, SJ Barb, JJ Munson, PJ Halushka, MK Miller, KL Fox-Talbot, K Zhang, JH Hare, JM Solomon, MA Danner, RL AF Rame, J. Eduardo Barouch, Lili A. Sack, Michael N. Lynn, Edward G. Abu-Asab, Mones Tsokos, Maria Kern, Steven J. Barb, Jennifer J. Munson, Peter J. Halushka, Marc K. Miller, Karen L. Fox-Talbot, Karen Zhang, Jianhua Hare, Joshua M. Solomon, Michael A. Danner, Robert L. TI Caloric restriction in leptin deficiency does not correct myocardial steatosis: failure to normalize PPAR alpha/PGC1 alpha and thermogenic glycerolipid/fatty acid cycling SO PHYSIOLOGICAL GENOMICS LA English DT Article DE leptin; cardiac metabolism; lipotoxicity; glycerolipid/free fatty acid metabolism; peroxisome proliferator-activated receptor; peroxisome proliferator-activated receptor gamma coactivator ID PPAR-ALPHA; CARDIAC-HYPERTROPHY; INSULIN-RESISTANCE; DIABETES-MELLITUS; MYOCYTE APOPTOSIS; TRANSGENIC MICE; OB/OB MICE; OXIDATION; OBESITY; CARDIOMYOPATHY AB Rame JE, Barouch LA, Sack MN, Lynn EG, Abu-Asab M, Tsokos M, Kern SJ, Barb JJ, Munson PJ, Halushka MK, Miller KL, Fox-Talbot K, Zhang J, Hare JM, Solomon MA, Danner RL. Caloric restriction in leptin deficiency does not correct myocardial steatosis: failure to normalize PPAR alpha/PGC1 alpha and thermogenic glycerolipid/fatty acid cycling. Physiol Genomics 43: 726-738, 2011. First published March 22, 2011; doi:10.1152/physiolgenomics.00088.2010.-Objective: Evidence supports an antilipotoxic role for leptin in preventing inappropriate peripheral tissue lipid deposition. Obese, leptin-deficient mice develop left ventricular (LV) hypertrophy and myocardial steatosis with increased apoptosis and decreased longevity. Here we investigated the cardiac effects of caloric restriction versus leptin repletion in obese leptin-deficient (ob/ob) mice. Methods: Echocardiography was performed on 7 mo old C57BL/6 wild-type mice (WT) and ob/ob mice fed ad libitum, leptin-repleted (LR-ob/ob), or calorie-restricted (CR-ob/ob) for 4 wk. Ventricular tissue was examined by electron microscopy (EM), triglyceride (TAG) content, oil red O staining, mitochondrial coupling assay, and microarray expression profiling. Results: LR and CR-ob/ob mice showed decreased body and heart weight, and LV wall thickness compared with ad libitum ob/ob mice. LV fractional shortening was decreased in ad libitum ob/ob mice, but restored to WT in LR and CR groups. However, myocardial lipid content by EM and TAG analysis revealed persistent cardiac steatosis in the CR-ob/ob group. Although CR restored mitochondrial coupling to WT levels, PPAR alpha was suppressed and genes associated with oxidative stress and cell death were upregulated in CR-ob/ob animals. In contrast, LR eliminated cardiac steatosis, normalized mitochondrial coupling, and restored PGC1 alpha and PPAR alpha expression, while inducing core genes involved in glycerolipid/free fatty acid (GL/FFA) cycling, a thermogenic pathway that can reduce intracellular lipids. Conclusions: Thus, CR in the absence of leptin fails to normalize cardiac steatosis. GL/FFA cycling may be, at least in part, leptin-dependent and a key pathway that protects the heart from lipid accumulation. C1 [Rame, J. Eduardo] Univ Penn, Heart & Vasc Ctr, E Perelman Ctr Adv Med 2, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Miller, Karen L.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD USA. [Sack, Michael N.; Lynn, Edward G.; Solomon, Michael A.] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA. [Abu-Asab, Mones; Tsokos, Maria] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Kern, Steven J.; Zhang, Jianhua; Solomon, Michael A.; Danner, Robert L.] Ctr Clin, Dept Crit Care Med, Funct Genom & Prote Facil, Bethesda, MD USA. [Barb, Jennifer J.; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. [Halushka, Marc K.; Fox-Talbot, Karen] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Hare, Joshua M.] Univ Miami, Sch Med, Dept Med, Interdisciplinary Stem Cell Inst,Div Cardiovasc, Miami, FL USA. RP Rame, JE (reprint author), Univ Penn, Heart & Vasc Ctr, E Perelman Ctr Adv Med 2, Div Cardiovasc Med, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM eduardo.rame@uphs.upenn.edu OI Abu-Asab, Mones/0000-0002-4047-1232; Lynn, Edward/0000-0002-8011-5558 FU National Heart, Lung, and Blood Institute (NHLBI) [R01-HL-077785, K08-HL-076220]; American Heart Association [0730375N]; NHLBI Division of Intramural Research; National Institutes of Health Clinical Center FX This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) Cardiovascular Medicine Fellowship (J. E. Rame), the American Heart Association National Scientist Development Grant 0730375N (J. E. Rame), NHLBI Division of Intramural Research (M. N. Sack), National Institutes of Health Clinical Center (R. L. Danner), and NHLBI Grants R01-HL-077785 and K08-HL-076220 (L. A. Barouch). NR 41 TC 10 Z9 10 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUN PY 2011 VL 43 IS 12 BP 726 EP 738 DI 10.1152/physiolgenomics.00088.2010 PG 13 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 784DX UT WOS:000292136200002 PM 21427359 ER PT J AU Field, D Amaral-Zettler, L Cochrane, G Cole, JR Dawyndt, P Garrity, GM Gilbert, J Glockner, FO Hirschman, L Karsch-Mizrachi, I Klenk, HP Knight, R Kottmann, R Kyrpides, N Meyer, F Gil, IS Sansone, SA Schriml, LM Sterk, P Tatusova, T Ussery, DW White, O Wooley, J AF Field, Dawn Amaral-Zettler, Linda Cochrane, Guy Cole, James R. Dawyndt, Peter Garrity, George M. Gilbert, Jack Gloeckner, Frank Oliver Hirschman, Lynette Karsch-Mizrachi, Ilene Klenk, Hans-Peter Knight, Rob Kottmann, Renzo Kyrpides, Nikos Meyer, Folker San Gil, Inigo Sansone, Susanna-Assunta Schriml, Lynn M. Sterk, Peter Tatusova, Tatiana Ussery, David W. White, Owen Wooley, John TI The Genomic Standards Consortium SO PLOS BIOLOGY LA English DT Editorial Material ID MINIMUM INFORMATION; MICROBIOME PROJECT; OMICS DATA; RESOURCE; SEQUENCE; ANNOTATION; COLLECTION AB A vast and rich body of information has grown up as a result of the world's enthusiasm for 'omics technologies. Finding ways to describe and make available this information that maximise its usefulness has become a major effort across the 'omics world. At the heart of this effort is the Genomic Standards Consortium (GSC), an open-membership organization that drives community-based standardization activities, Here we provide a short history of the GSC, provide an overview of its range of current activities, and make a call for the scientific community to join forces to improve the quality and quantity of contextual information about our public collections of genomes, metagenomes, and marker gene sequences. C1 [Field, Dawn] Ctr Ecol & Hydrol, Wallingford, Oxon, England. [Amaral-Zettler, Linda] Marine Biol Lab, Josephine Bay Paul Ctr Comparat Mol Biol & Evolut, Woods Hole, MA 02543 USA. [Cochrane, Guy] Wellcome Trust Genome Campus, EBI, European Mol Biol Lab Outstn, Cambridge, England. [Cole, James R.] Michigan State Univ, Ctr Microbial Ecol, E Lansing, MI 48824 USA. [Dawyndt, Peter] Univ Ghent, Dept Appl Math & Comp Sci, B-9000 Ghent, Belgium. [Garrity, George M.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. [Gilbert, Jack; Meyer, Folker] Argonne Natl Lab, Argonne, IL 60439 USA. [Gilbert, Jack] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. [Gloeckner, Frank Oliver; Kottmann, Renzo] Max Planck Inst Marine Microbiol, Microbial Genom Grp, Bremen, Germany. [Gloeckner, Frank Oliver; Kottmann, Renzo] Univ Bremen, Bremen, Germany. [Hirschman, Lynette] Mitre Corp, Ctr Informat Technol, Bedford, MA 01730 USA. [Karsch-Mizrachi, Ilene; Tatusova, Tatiana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Klenk, Hans-Peter] DSMZ German Collect Microorganisms & Cell Culture, Braunschweig, Germany. [Knight, Rob] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Kyrpides, Nikos] US DOE, Joint Genome Inst, Walnut Creek, CA USA. [Meyer, Folker] Univ Chicago, Computat Inst, Chicago, IL 60637 USA. [San Gil, Inigo] Univ New Mexico, Dept Biol, LTER Network Off, Albuquerque, NM 87131 USA. [Sansone, Susanna-Assunta] Univ Oxford, Oxford E Res Ctr, Oxford, England. [Schriml, Lynn M.; White, Owen] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Sterk, Peter] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Cambridge, England. [Ussery, David W.] Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Wooley, John] Univ Calif San Diego, La Jolla, CA 92093 USA. RP Field, D (reprint author), Ctr Ecol & Hydrol, Maclean Bldg, Wallingford, Oxon, England. EM dfield@ceh.ac.uk RI Dawyndt, Peter/A-1566-2013; Garrity, George/F-7551-2013; Knight, Rob/D-1299-2010; Kyrpides, Nikos/A-6305-2014; OI Dawyndt, Peter/0000-0002-1623-9070; Garrity, George/0000-0002-4465-7034; Kyrpides, Nikos/0000-0002-6131-0462; Cochrane, Guy/0000-0001-7954-7057; Sterk, Peter/0000-0003-1668-7778; Meyer, Folker/0000-0003-1112-2284; Schriml, Lynn/0000-0001-8910-9851; Ussery, David/0000-0003-3632-5512 FU NERC [NE/3521773/1, NE/E007325/1]; National Science Foundation [RCN4GSC, DBI-0840989]; NERC; NIEeS; NSF [RCN4GSC]; Gordon and Betty Moore Foundation; DOE FX NERC International Opportunities Fund Award NE/3521773/1 and NE/E007325/1 (http://www.nerc.ac.uk/funding/) and National Science Foundation grant RCN4GSC, DBI-0840989 (http://www.nsf.gov/funding/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The GSC acknowledges all participants in past GSC meetings for their thoughtful contributions. The GSC also acknowledges a range of funding sources for its past meetings, including NERC, NIEeS, NSF, the Gordon and Betty Moore Foundation and DOE. In particular, funding from NERC helped launch the GSC and allow essential infrastructure to be built. Funding from the NSF in the form of the Research Co-ordination Network (RCN4GSC) is supporting exchange visits of early career scientists and working group activities. NR 26 TC 96 Z9 96 U1 2 U2 23 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 JUN PY 2011 VL 9 IS 6 AR e1001088 DI 10.1371/journal.pbio.1001088 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 784XF UT WOS:000292191200014 PM 21713030 ER PT J AU Pan, YP Nussinov, R AF Pan, Yongping Nussinov, Ruth TI The Role of Response Elements Organization in Transcription Factor Selectivity: The IFN-beta Enhanceosome Example SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID NF-KAPPA-B; EMPIRICAL FORCE-FIELD; MOLECULAR-DYNAMICS; DNA-BINDING; CRYSTAL-STRUCTURE; GENE-EXPRESSION; IN-VITRO; HELICOIDAL ANALYSIS; SIGNALING PATHWAYS; NUCLEIC-ACIDS AB What is the mechanism through which transcription factors (TFs) assemble specifically along the enhancer DNA? The IFN-beta enhanceosome provides a good model system: it is small; its components' crystal structures are available; and there are biochemical and cellular data. In the IFN-beta enhanceosome, there are few protein-protein interactions even though consecutive DNA response elements (REs) overlap. Our molecular dynamics (MD) simulations on different motif combinations from the enhanceosome illustrate that cooperativity is achieved via unique organization of the REs: specific binding of one TF can enhance the binding of another TF to a neighboring RE and restrict others, through overlap of REs; the order of the REs can determine which complexes will form; and the alternation of consensus and non-consensus REs can regulate binding specificity by optimizing the interactions among partners. Our observations offer an explanation of how specificity and cooperativity can be attained despite the limited interactions between neighboring TFs on the enhancer DNA. To date, when addressing selective TF binding, attention has largely focused on RE sequences. Yet, the order of the REs on the DNA and the length of the spacers between them can be a key factor in specific combinatorial assembly of the TFs on the enhancer and thus in function. Our results emphasize cooperativity via RE binding sites organization. C1 [Pan, Yongping; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Pan, YP (reprint author), NCI, Basic Sci Program, SAIC Frederick, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. EM ruthnu@helix.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. This research was supported (in part) by 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 71 TC 6 Z9 6 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JUN PY 2011 VL 7 IS 6 AR e1002077 DI 10.1371/journal.pcbi.1002077 PG 14 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 787MW UT WOS:000292381900023 PM 21698143 ER PT J AU Volz, EM Miller, JC Galvani, A Meyers, LA AF Volz, Erik M. Miller, Joel C. Galvani, Alison Meyers, Lauren Ancel TI Effects of Heterogeneous and Clustered Contact Patterns on Infectious Disease Dynamics SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID RECOVERED EPIDEMICS; RANDOM NETWORKS; SIR DYNAMICS; MODELS; TRANSMISSION; POPULATIONS; SPREAD; GRAPHS AB The spread of infectious diseases fundamentally depends on the pattern of contacts between individuals. Although studies of contact networks have shown that heterogeneity in the number of contacts and the duration of contacts can have far-reaching epidemiological consequences, models often assume that contacts are chosen at random and thereby ignore the sociological, temporal and/or spatial clustering of contacts. Here we investigate the simultaneous effects of heterogeneous and clustered contact patterns on epidemic dynamics. To model population structure, we generalize the configuration model which has a tunable degree distribution (number of contacts per node) and level of clustering (number of three cliques). To model epidemic dynamics for this class of random graph, we derive a tractable, low-dimensional system of ordinary differential equations that accounts for the effects of network structure on the course of the epidemic. We find that the interaction between clustering and the degree distribution is complex. Clustering always slows an epidemic, but simultaneously increasing clustering and the variance of the degree distribution can increase final epidemic size. We also show that bond percolation-based approximations can be highly biased if one incorrectly assumes that infectious periods are homogeneous, and the magnitude of this bias increases with the amount of clustering in the network. We apply this approach to model the high clustering of contacts within households, using contact parameters estimated from survey data of social interactions, and we identify conditions under which network models that do not account for household structure will be biased. C1 [Volz, Erik M.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Miller, Joel C.] Harvard Univ, Dept Epidemiol, Cambridge, MA 02138 USA. [Miller, Joel C.] NIH, Fogarty Int Ctr, Washington, DC USA. [Galvani, Alison] Yale Univ, Dept Epidemiol, New Haven, CT USA. [Meyers, Lauren Ancel] Santa Fe Inst, Santa Fe, NM 87501 USA. [Meyers, Lauren Ancel] Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA. RP Volz, EM (reprint author), Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. EM erikvolz@umich.edu RI Miller, Joel/C-4229-2015; OI Miller, Joel/0000-0003-4426-0405; Volz, Erik/0000-0001-6268-8937 FU NIH [U01 GM087719] FX The authors acknowledge financial support from NIH U01 GM087719. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 56 Z9 57 U1 2 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JUN PY 2011 VL 7 IS 6 AR e1002042 DI 10.1371/journal.pcbi.1002042 PG 13 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 787MW UT WOS:000292381900004 PM 21673864 ER PT J AU Atun, R Branson, B Burns, D Calleja, JMG Busch, M Constestable, P Dallabetta, G Domingo, G Goosby, AE Garrett, P Ghys, P Gilbreath, M Hallett, T Hirnschall, G Holmes, C Kaldor, J Kim, A Laeyendecker, O Mermin, J McWalter, T Mink, R Murphy, G Murtagh, M Owen, SM Padian, N Parekh, B Piot, P Quinn, T Ridzon, R Rodriguez, B Rousseau, C Schito, M Sexton, C Sharma, U Welte, A Wong, A AF Atun, Rifat Branson, Bernard Burns, David Garcia Calleja, Jesus Maria Busch, Mike Constestable, Paul Dallabetta, Gina Domingo, Gonzalo Goosby, Amb Eric Garrett, Patricia Ghys, Peter Gilbreath, Michael Hallett, Tim Hirnschall, Gottfried Holmes, Charles Kaldor, John Kim, Andrea Laeyendecker, Oliver Mermin, Jonathan McWalter, Tom Mink, Ronald Murphy, Gary Murtagh, Maurine Owen, Sherry M. (Michele) Padian, Nancy Parekh, Bharat Piot, Peter Quinn, Tom Ridzon, Renee Rodriguez, Bill Rousseau, Christine Schito, Marco Sexton, Connie Sharma, Usha Welte, Alex Wong, Amy CA Incidence Assay Critical Path Work TI More and Better Information to Tackle HIV Epidemics: Towards Improved HIV Incidence Assays SO PLOS MEDICINE LA English DT Editorial Material ID CAPTURE ENZYME-IMMUNOASSAY; RECENT INFECTION; AVIDITY; AFRICA; ACCURACY; UGANDA; TESTS; GP41 C1 [Hallett, Tim; Piot, Peter] Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. [Branson, Bernard; Kim, Andrea; Mermin, Jonathan; Owen, Sherry M. (Michele); Parekh, Bharat; Sexton, Connie] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Burns, David; Gilbreath, Michael; Schito, Marco; Sharma, Usha] Natl Inst Hlth, Bethesda, MD USA. [Garcia Calleja, Jesus Maria; Hirnschall, Gottfried] WHO, New York, NY USA. [Kaldor, John] Univ New S Wales, Sydney, NSW 2052, Australia. [Laeyendecker, Oliver; Quinn, Tom] Johns Hopkins Univ, Baltimore, MD 21218 USA. [McWalter, Tom] Univ Witwatersrand, ZA-2050 Wits, South Africa. RP Hallett, T (reprint author), Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England. EM timothy.hallett@imperial.ac.uk RI Laeyendecker, Oliver/B-9331-2009; Mermin, Jonathan/J-9847-2012; Kaldor, John /D-4545-2011 NR 37 TC 0 Z9 0 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JUN PY 2011 VL 8 IS 6 AR e1001045 DI 10.1371/journal.pmed.1001045 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 784EC UT WOS:000292136800009 ER PT J AU Alemu, G Ayele, FT Daniel, T Ahrens, C Davey, G AF Alemu, Getahun Ayele, Fasil Tekola Daniel, Takele Ahrens, Christel Davey, Gail TI Burden of Podoconiosis in Poor Rural Communities in Gulliso woreda, West Ethiopia SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID NON-FILARIAL ELEPHANTIASIS; ENDEMIC ELEPHANTIASIS; LOWER LEGS; SOUTHERN ETHIOPIA; BANCROFTIAN FILARIASIS; DISTRICT; CAMEROON; AFRICA; AREA; PREVALENCE AB Background: Podoconiosis is an environmental lymphoedema affecting people living and working barefoot on irritant red clay soil. Podoconiosis is relatively well described in southern Ethiopia, but remains neglected in other parts of the Ethiopian highlands. This study aimed to assess the burden of podoconiosis in rural communities in western Ethiopia. Methodology/Principal Findings: A cross-sectional study was conducted in Gulliso woreda (district), west Ethiopia. A household survey in the 26 rural kebeles (villages) of this district was conducted to identify podoconiosis patients and to measure disease prevalence. A more detailed study was done in six randomly selected kebeles to describe clinical features of the disease, patients' experiences of foot hygiene, and shoe wearing practice. 1,935 cases of podoconiosis were registered, giving a prevalence of 2.8%. The prevalence was higher in those aged 15-64 years (5.2%) and in females than males (prevalence ratio 2.6:1). 90.3% of patients were in the 15-64 year age group. In the detailed study, 335 cases were interviewed and their feet assessed. The majority of patients were farmers, uneducated, and poor. Two-third of patients developed the disease before the age of thirty. Almost all patients (97.0%) had experienced adenolymphangitis (ALA - red, hot legs, swollen and painful groin) at least once during the previous year. Patients experienced an average of 5.5 ALA episodes annually, each of average 4.4 days, thus 24 working days were lost annually. The incidence of ALA in podoconiosis patients was higher than that reported for filariasis in other countries. Shoe wearing was limited mainly due to financial problems. Conclusions: We have documented high podoconiosis prevalence, frequent adenolymphangitis and high disease-related morbidity in west Ethiopia. Interventions must be developed to prevent, treat and control podoconiosis, one of the core neglected tropical diseases in Ethiopia. C1 [Alemu, Getahun] SOS Childrens Villages Int, Addis Ababa, Ethiopia. [Ayele, Fasil Tekola] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Daniel, Takele] Addis Ababa Hlth Bur, Addis Ababa, Ethiopia. [Ahrens, Christel] Int Inst Child Hlth, London, England. [Davey, Gail] Brighton & Sussex Med Sch, Brighton, E Sussex, England. RP Alemu, G (reprint author), SOS Childrens Villages Int, Addis Ababa, Ethiopia. EM ayeleft@mail.nih.gov OI Davey, Gail/0000-0003-2796-7468; Tekola-Ayele, Fasil/0000-0003-4194-9370 FU Wellcome Trust [079791] FX This study was supported by the Wellcome Trust (grant #079791). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 27 Z9 27 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JUN PY 2011 VL 5 IS 6 AR e1184 DI 10.1371/journal.pntd.0001184 PG 6 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 784EZ UT WOS:000292139600024 PM 21666795 ER PT J AU Carlton, JM Sina, BJ Adams, JH AF Carlton, Jane M. Sina, Barbara J. Adams, John H. TI Why Is Plasmodium vivax a Neglected Tropical Disease? SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID MALARIA; INFECTIONS; COLOMBIA C1 [Carlton, Jane M.] NYU, Sch Med, Dept Med Parasitol, New York, NY 10012 USA. [Sina, Barbara J.] NIH, Div Int Training & Res, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Adams, John H.] Univ S Florida, Coll Publ Hlth, Dept Global Hlth, Tampa, FL USA. RP Carlton, JM (reprint author), NYU, Sch Med, Dept Med Parasitol, New York, NY 10012 USA. EM sinab@mail.nih.gov RI Adams, John/G-1800-2015 OI Adams, John/0000-0003-3707-7979 FU NIAID NIH HHS [R01 AI064478, R01 AI064478-06] NR 20 TC 50 Z9 50 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JUN PY 2011 VL 5 IS 6 AR e1160 DI 10.1371/journal.pntd.0001160 PG 4 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 784EZ UT WOS:000292139600014 PM 21738804 ER PT J AU Dowd, KA Jost, CA Durbin, AP Whitehead, SS Pierson, TC AF Dowd, Kimberly A. Jost, Christiane A. Durbin, Anna P. Whitehead, Stephen S. Pierson, Theodore C. TI A Dynamic Landscape for Antibody Binding Modulates Antibody-Mediated Neutralization of West Nile Virus SO PLOS PATHOGENS LA English DT Article ID BORNE ENCEPHALITIS-VIRUS; DENGUE VIRUS; MONOCLONAL-ANTIBODIES; ENVELOPE PROTEIN; DEPENDENT ENHANCEMENT; FLAVIVIRUS INFECTION; STRUCTURAL BASIS; IMMUNE-RESPONSE; E-GLYCOPROTEIN; PRM PROTEIN AB Neutralizing antibodies are a significant component of the host's protective response against flavivirus infection. Neutralization of flaviviruses occurs when individual virions are engaged by antibodies with a stoichiometry that exceeds a required threshold. From this "multiple-hit" perspective, the neutralizing activity of antibodies is governed by the affinity with which it binds its epitope and the number of times this determinant is displayed on the surface of the virion. In this study, we investigated time-dependent changes in the fate of West Nile virus (WNV) decorated with antibody in solution. Experiments with the well-characterized neutralizing monoclonal antibody (MAb) E16 revealed a significant increase in neutralization activity over time that could not be explained by the kinetics of antibody binding, virion aggregation, or the action of complement. Additional kinetic experiments using the fusion-loop specific MAb E53, which has limited neutralizing activity because it recognizes a relatively inaccessible epitope on mature virions, identified a role of virus "breathing" in regulating neutralization activity. Remarkably, MAb E53 neutralized mature WNV in a time- and temperature-dependent manner. This phenomenon was confirmed in studies with a large panel of MAbs specific for epitopes in each domain of the WNV envelope protein, with sera from recipients of a live attenuated WNV vaccine, and in experiments with dengue virus. Given enough time, significant inhibition of infection was observed even for antibodies with very limited, or no neutralizing activity in standard neutralization assays. Together, our data suggests that the structural dynamics of flaviviruses impacts antibody-mediated neutralization via exposure of otherwise inaccessible epitopes, allowing for antibodies to dock on the virion with a stoichiometry sufficient for neutralization. C1 [Dowd, Kimberly A.; Jost, Christiane A.; Pierson, Theodore C.] NIH, Viral Dis Lab, Viral Pathogenesis Sect, Bethesda, MD 20892 USA. [Durbin, Anna P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD USA. [Whitehead, Stephen S.] NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Dowd, KA (reprint author), NIH, Viral Dis Lab, Viral Pathogenesis Sect, Bldg 10, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov FU National Institutes of Allergy and Infectious Diseases (NIAID) FX This work was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases (NIAID) and a gift from the Pediatric Dengue Vaccine Initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 69 TC 73 Z9 73 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2011 VL 7 IS 6 AR e1002111 DI 10.1371/journal.ppat.1002111 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 787MC UT WOS:000292379600043 PM 21738473 ER PT J AU Le Nouen, C Hillyer, P Winter, CC McCarty, T Rabin, RL Collins, PL Buchholz, UJ AF Le Nouen, Cyril Hillyer, Philippa Winter, Christine C. McCarty, Thomas Rabin, Ronald L. Collins, Peter L. Buchholz, Ursula J. TI Low CCR7-Mediated Migration of Human Monocyte Derived Dendritic Cells in Response to Human Respiratory Syncytial Virus and Human Metapneumovirus SO PLOS PATHOGENS LA English DT Article ID CHEMOKINE-MEDIATED MIGRATION; UNITED-STATES; IN-VITRO; PARAINFLUENZA VIRUS; RECEPTOR SWITCH; GENE-EXPRESSION; INFLUENZA-VIRUS; CILIATED CELLS; MUCOSAL SITES; LYMPH-NODES AB Human respiratory syncytial virus ( HRSV) and, to a lesser extent, human metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV) largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells ( DC) is critical in initiating the adaptive immune response. Antigen uptake by DC induces maturational changes that include decreased expression of the chemokine receptors CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and increased expression of CCR7 that mediates the migration of antigen-bearing DC to lymphatic tissue. We stimulated human monocyte-derived DC (MDDC) with virus and found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7 expression. Consistent with the differences in CCR7 mRNA and protein expression, MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we showed that the subpopulation of MDDC that was robustly infected with HRSV was particularly inefficient in chemokine receptor modulation. HMPV- or HRSV-stimulated MDDC responded to secondary stimulation with bacterial lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than irreversibly inhibit MDDC migration. This also suggests that the low concentration of proinflammatory cytokines released from HRSV- and HMPV-stimulated MDDC is partly responsible for the low CCR7-mediated migration. We propose that inefficient migration of HRSV- and HMPV- stimulated DC to lymphatic tissue contributes to reduced adaptive responses to these viruses. C1 [Le Nouen, Cyril; Winter, Christine C.; McCarty, Thomas; Collins, Peter L.; Buchholz, Ursula J.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Hillyer, Philippa; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Le Nouen, C (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nih.gov FU NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 16 Z9 16 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2011 VL 7 IS 6 AR e1002105 DI 10.1371/journal.ppat.1002105 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 787MC UT WOS:000292379600039 PM 21731495 ER PT J AU Martinelli, E Tharinger, H Frank, I Arthos, J Piatak, M Lifson, JD Blanchard, J Gettie, A Robbiani, M AF Martinelli, Elena Tharinger, Hugo Frank, Ines Arthos, James Piatak, Michael, Jr. Lifson, Jeffrey D. Blanchard, James Gettie, Agegnehu Robbiani, Melissa TI HSV-2 Infection of Dendritic Cells Amplifies a Highly Susceptible HIV-1 Cell Target SO PLOS PATHOGENS LA English DT Article ID HERPES-SIMPLEX-VIRUS; RETINOIC ACID RECEPTORS; T-CELLS; IN-VIVO; INTEGRIN ALPHA(4)BETA(7); CHLAMYDIA-TRACHOMATIS; RHESUS MACAQUES; LYMPH-NODE; VITAMIN-A; MUCOSAL AB Herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection and, although several reports describe the interaction between these two viruses, the exact mechanism for this increased susceptibility remains unclear. Dendritic cells (DCs) at the site of entry of HSV-2 and HIV-1 contribute to viral spread in the mucosa. Specialized DCs present in the gut-associated lymphoid tissues produce retinoic acid (RA), an important immunomodulator, able to influence HIV-1 replication and a key mediator of integrin alpha(4)beta(7) on lymphocytes. alpha(4)beta(7) can be engaged by HIV-1 on the cell-surface and CD4(+) T cells expressing high levels of this integrin (alpha(4)beta(high)(7)) are particularly susceptible to HIV-1 infection. Herein we provide in-vivo data in macaques showing an increased percentage of alpha(4)beta(7) high CD4(+) T cells in rectal mucosa, iliac lymph nodes and blood within 6 days of rectal exposure to live (n = 11), but not UV-treated (n = 8), HSV-2. We found that CD11c(+) DCs are a major target of HSV-2 infection in in-vitro exposed PBMCs. We determined that immature monocyte-derived DCs (moDCs) express aldehyde dehydrogenase ALDH1A1, an enzyme essential for RA production, which increases upon HSV-2 infection. Moreover, HSV-2-infected moDCs significantly increase alpha(4)beta(7) expression on CD4(+) T lymphocytes and HIV-1 infection in DC-T cell mixtures in a RA-dependent manner. Thus, we propose that HSV-2 modulates its microenviroment, influencing DC function, increasing RA production capability and amplifying a alpha(4)beta(7) (high)CD4(+) T cells. These factors may play a role in increasing the susceptibility to HIV-1. C1 [Martinelli, Elena; Tharinger, Hugo; Frank, Ines; Robbiani, Melissa] Populat Council, Ctr Biomed Res, New York, NY 10021 USA. [Arthos, James] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] SAIC Frederick Inc, NCI, AIDS & Canc Virus Program, Frederick, MD USA. [Blanchard, James] Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Covington, LA USA. [Gettie, Agegnehu] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA. RP Martinelli, E (reprint author), Populat Council, Ctr Biomed Res, 1230 York Ave, New York, NY 10021 USA. EM emartinelli@popcouncil.org; mrobbiani@popcouncil.org FU NIH [R37 AI040877, RR00164]; National Cancer Institute, NIH [HHSN261200800001E] FX This work was supported by the NIH grant R37 AI040877, the NIH base grant RR00164, and in part with Federal funds from the National Cancer Institute, NIH, under contract HHSN261200800001E. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 32 Z9 32 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2011 VL 7 IS 6 AR e1002109 DI 10.1371/journal.ppat.1002109 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 787MC UT WOS:000292379600042 PM 21738472 ER PT J AU Nelson, MI Lemey, P Tan, Y Vincent, A Lam, TTY Detmer, S Viboud, C Suchard, MA Rambaut, A Holmes, EC Gramer, M AF Nelson, Martha I. Lemey, Philippe Tan, Yi Vincent, Amy Lam, Tommy Tsan-Yuk Detmer, Susan Viboud, Cecile Suchard, Marc A. Rambaut, Andrew Holmes, Edward C. Gramer, Marie TI Spatial Dynamics of Human-Origin H1 Influenza A Virus in North American Swine SO PLOS PATHOGENS LA English DT Article ID UNITED-STATES; GENETIC-CHARACTERIZATION; PIGS; REASSORTMENT; PHYLOGENY; EMERGENCE; EVOLUTION; ACCURATE; MODELS; CANADA AB The emergence and rapid global spread of the swine-origin H1N1/09 pandemic influenza A virus in humans underscores the importance of swine populations as reservoirs for genetically diverse influenza viruses with the potential to infect humans. However, despite their significance for animal and human health, relatively little is known about the phylogeography of swine influenza viruses in the United States. This study utilizes an expansive data set of hemagglutinin (HA1) sequences (n = 1516) from swine influenza viruses collected in North America during the period 2003-2010. With these data we investigate the spatial dissemination of a novel influenza virus of the H1 subtype that was introduced into the North American swine population via two separate human-to-swine transmission events around 2003. Bayesian phylogeographic analysis reveals that the spatial dissemination of this influenza virus in the US swine population follows long-distance swine movements from the Southern US to the Midwest, a corn-rich commercial center that imports millions of swine annually. Hence, multiple genetically diverse influenza viruses are introduced and co-circulate in the Midwest, providing the opportunity for genomic reassortment. Overall, the Midwest serves primarily as an ecological sink for swine influenza in the US, with sources of virus genetic diversity instead located in the Southeast (mainly North Carolina) and South-central (mainly Oklahoma) regions. Understanding the importance of long-distance pig transportation in the evolution and spatial dissemination of the influenza virus in swine may inform future strategies for the surveillance and control of influenza, and perhaps other swine pathogens. C1 [Nelson, Martha I.; Tan, Yi; Viboud, Cecile; Rambaut, Andrew; Holmes, Edward C.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Lemey, Philippe] Katholieke Univ Leuven, Dept Microbiol & Immunol, Louvain, Belgium. [Vincent, Amy] USDA ARS, Virus & Prion Dis Livestock Res Unit, Natl Anim Dis Ctr, Ames, IA USA. [Lam, Tommy Tsan-Yuk; Holmes, Edward C.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Detmer, Susan; Gramer, Marie] Univ Minnesota, Vet Diagnost Lab, St Paul, MN 55108 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Genet, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Rambaut, Andrew] Univ Edinburgh, Ashworth Labs, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland. RP Nelson, MI (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM nelsonma@mail.nih.gov RI Lam, Tommy Tsan-Yuk/D-4837-2012; Chiang, Vincent, Ming-Hsien/D-4312-2016; OI Rambaut, Andrew/0000-0003-4337-3707; Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863; Holmes, Edward/0000-0001-9596-3552 FU European Research Council under the European Community [260864]; NIH [R01 GM080533, R01 GM086887]; NSF [DMS 0856099]; National Evolutionary Synthesis Center (NESCent), NSF [EF-0423641] FX The research leading to these results has received funding in part from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no. 260864; NIH grant R01 GM080533; NSF grant DMS 0856099; NIH grant R01 GM086887; and the National Evolutionary Synthesis Center (NESCent), NSF EF-0423641. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 52 Z9 52 U1 0 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2011 VL 7 IS 6 AR e1002077 DI 10.1371/journal.ppat.1002077 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 787MC UT WOS:000292379600015 PM 21695237 ER PT J AU Raghwani, J Rambaut, A Holmes, EC Hang, VT Hien, TT Farrar, J Wills, B Lennon, NJ Birren, BW Henn, MR Simmons, CP AF Raghwani, Jayna Rambaut, Andrew Holmes, Edward C. Vu Ty Hang Tran Tinh Hien Farrar, Jeremy Wills, Bridget Lennon, Niall J. Birren, Bruce W. Henn, Matthew R. Simmons, Cameron P. TI Endemic Dengue Associated with the Co-Circulation of Multiple Viral Lineages and Localized Density-Dependent Transmission SO PLOS PATHOGENS LA English DT Article ID AEDES-AEGYPTI; PUERTO-RICO; MOLECULAR EVOLUTION; HEMORRHAGIC-FEVER; VIRUS TYPE-2; DISPERSAL; EMERGENCE; SELECTION; EPIDEMIC; THAILAND AB Dengue is one of the most important infectious diseases of humans and has spread throughout much of the tropical and subtropical world. Despite this widespread dispersal, the determinants of dengue transmission in endemic populations are not well understood, although essential for virus control. To address this issue we performed a phylogeographic analysis of 751 complete genome sequences of dengue 1 virus (DENV-1) sampled from both rural (Dong Thap) and urban (Ho Chi Minh City) populations in southern Viet Nam during the period 2003-2008. We show that DENV-1 in Viet Nam exhibits strong spatial clustering, with likely importation from Cambodia on multiple occasions. Notably, multiple lineages of DENV-1 co-circulated in Ho Chi Minh City. That these lineages emerged at approximately the same time and dispersed over similar spatial regions suggests that they are of broadly equivalent fitness. We also observed an important relationship between the density of the human host population and the dispersion rate of dengue, such that DENV-1 tends to move from urban to rural populations, and that densely populated regions within Ho Chi Minh City act as major transmission foci. Despite these fluid dynamics, the dispersion rates of DENV-1 are relatively low, particularly in Ho Chi Minh City where the virus moves less than an average of 20 km/year. These low rates suggest a major role for mosquito-mediated dispersal, such that DENV-1 does not need to move great distances to infect a new host when there are abundant susceptibles, and imply that control measures should be directed toward the most densely populated urban environments. C1 [Raghwani, Jayna; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland. [Rambaut, Andrew; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Vu Ty Hang; Farrar, Jeremy; Wills, Bridget; Simmons, Cameron P.] Hosp Trop Dis, Oxford Univ Clin Res Unit, Ho Chi Minh City, Vietnam. [Farrar, Jeremy; Wills, Bridget] Univ Oxford, Nuffield Dept Med, Ctr Trop Med, Oxford, England. [Lennon, Niall J.; Birren, Bruce W.; Henn, Matthew R.] MIT & Harvard, Broad Inst, Cambridge, MA USA. RP Raghwani, J (reprint author), Univ Edinburgh, Inst Evolutionary Biol, Ashworth Labs, Edinburgh, Midlothian, Scotland. EM csimmons@oucru.org OI Simmons, Cameron P./0000-0002-9039-7392; Raghwani, Jayna/0000-0001-8538-4995; Rambaut, Andrew/0000-0003-4337-3707; Farrar, Jeremy/0000-0002-2700-623X; Holmes, Edward/0000-0001-9596-3552 FU BBSRC [R67185C]; Wellcome Trust; ERC; NIH [R01 GM080533]; National Institute of Allergy and Infectious Disease, National Institutes of Health, Department of Health and Human Services [HHSN266200400001C, HHSN272200900006C] FX JR is supported by a BBSRC DTG Studentship R67185C. AR is supported by the Wellcome Trust, the BBSRC and the ERC. ECH is in part supported by NIH grant R01 GM080533. CPS is supported by the Wellcome Trust. This project was funded in part with United States federal funds from the National Institute of Allergy and Infectious Disease, National Institutes of Health, Department of Health and Human Services, under Contract Nos. HHSN266200400001C (BWB), & HHSN272200900006C (BWB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 46 Z9 47 U1 1 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JUN PY 2011 VL 7 IS 6 AR e1002064 DI 10.1371/journal.ppat.1002064 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 787MC UT WOS:000292379600005 PM 21655108 ER PT J AU Wynn, TA Anderson-Lewis, C Johnson, R Hardy, C Hardin, G Walker, S Marron, J Fouad, M Partridge, E Scarinci, I AF Wynn, Theresa Ann Anderson-Lewis, Charkarra Johnson, Rhoda Hardy, Claudia Hardin, Gail Walker, Shundra Marron, John Fouad, Mona Partridge, Edward Scarinci, Isabel TI Developing a Community Action Plan to Eliminate Cancer Disparities: Lessons Learned SO PROGRESS IN COMMUNITY HEALTH PARTNERSHIPS-RESEARCH EDUCATION AND ACTION LA English DT Article AB Background: African Americans bear an unequal burden of breast, cervical, and colorectal cancer. The Deep South Network for Cancer Control (DSN) is a community-academic partnership operating in Alabama and Mississippi that was funded by the National Cancer Institute (NCI) to address cancer disparities using community-based participatory research approaches. Objective: In addition to reporting on the plans of this work in progress, we describe the participatory process that local residents and the DSN used to identify needs and priorities, and elaborate on lessons learned from applying a participatory approach to the development of a community action plan. Methods: We conducted 24 community discussion groups involving health care professionals, government officials, faith-based leaders, and other stakeholders to identify cancer health disparity needs, community resources/assets, and county priorities to eliminate cancer health disparities. To develop a community action plan, four working groups explored the themes that emerged from the discussion groups, taking into consideration evidence-based strategies and promising community practices. Results: The DSN formulated a community action plan focusing on (1) increasing physical activity by implementing a campaign for individual-level focused activity; (2) increasing the consumption of fruits and vegetables by implementing NCI's Body and Soul Program in local churches; (3) increasing cancer screening by raising awareness through individual; system, and provider agents of change; and (4) training community partners to become effective advocates. Conclusions: A community-academic partnership must involve trust, respect, and an appreciation of partners' strengths and differences. The DSN applied these guiding principles and learned pivotal lessons. C1 [Wynn, Theresa Ann; Fouad, Mona; Scarinci, Isabel] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35205 USA. [Anderson-Lewis, Charkarra; Walker, Shundra] Univ So Mississippi, Dept Community Hlth Sci, Hattiesburg, MS 39406 USA. [Johnson, Rhoda] Univ Alabama, Dept Womens Studies, Tuscaloosa, AL 35487 USA. [Hardy, Claudia; Marron, John; Partridge, Edward] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35205 USA. [Hardin, Gail] NCI, Canc Informat Midsouth Reg Vanderbilt Ingram Canc, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL 35205 USA. FU NCI NIH HHS [U01 CA114619, CA U01CA114619] NR 29 TC 9 Z9 9 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1557-0541 EI 1557-055X J9 PROG COMM HLTH PARTN JI Prog. Community Health Partnersh. PD SUM PY 2011 VL 5 IS 2 SI SI BP 161 EP 168 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V33MM UT WOS:000209022900009 PM 21623018 ER PT J AU Casagrande, SS Franco, M Gittelsohn, J Zonderman, AB Evans, MK Kuczmarski, MF Gary-Webb, TL AF Casagrande, Sarah Stark Franco, Manuel Gittelsohn, Joel Zonderman, Alan B. Evans, Michele K. Kuczmarski, Marie Fanelli Gary-Webb, Tiffany L. TI Healthy food availability and the association with BMI in Baltimore, Maryland SO PUBLIC HEALTH NUTRITION LA English DT Article DE Healthy food availability; BMI; Socio-economic status ID NEIGHBORHOOD CHARACTERISTICS; ATHEROSCLEROSIS RISK; VEGETABLE INTAKE; UNITED-STATES; OBESITY; ENVIRONMENT; COMMUNITIES; STORES; PREVALENCE; OVERWEIGHT AB Objective: To study the association between the availability of healthy foods and BMI by neighbourhood race and socio-economic status (SES). Design: Trained staff collected demographic information, height, weight and 24 h dietary recalls between 2004 and 2008. Healthy food availability was determined in thirty-four census tracts of varying racial and SES composition using the Nutrition Environment Measures Survey-Stores in 2007. Multilevel linear regression was used to estimate associations between healthy food availability and BMI. Setting: Baltimore City, Maryland, USA. Subjects: Adults aged 30-64 years (n 2616) who participated in the Healthy Aging in Neighborhoods of Diversity across the Life Span study. Results: Among individuals living in predominantly white neighbourhoods, high availability of healthy foods was associated with significantly higher BMI compared with individuals living in neighbourhoods with low availability of healthy food after adjustment for demographic variables (beta = 3.22, P = 0.001). Associations were attenuated but remained significant after controlling for dietary quality (beta = 2.81, P = 0.012). Conclusions: Contrary to expectations, there was a positive association between the availability of healthy food and higher BMI among individuals living in predominantly white neighbourhoods. This result could be due to individuals in neighbourhoods with low healthy food availability travelling outside their neighbourhood to obtain healthy food. C1 [Casagrande, Sarah Stark; Franco, Manuel; Gittelsohn, Joel; Gary-Webb, Tiffany L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Franco, Manuel] Ctr Nacl Invest Cardiovasc, Madrid, Spain. [Kuczmarski, Marie Fanelli] Univ Delaware, Coll Hlth Sci, Newark, DE USA. [Zonderman, Alan B.; Evans, Michele K.] NIA, Baltimore, MD 21224 USA. RP Casagrande, SS (reprint author), Social & Sci Syst, 8757 Georgia Ave, Silver Spring, MD 20910 USA. EM scasagrande@s-3.com OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institutes of Health, National Institute on Aging; National Heart, Lung, and Blood Institute [K01 - HL084700] FX The current research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Data on healthy food availability were supported by the Center for a Livable Future at the Johns Hopkins Bloomberg School of Public Health. T.L.G.-W. was funded by a grant from the National Heart, Lung, and Blood Institute (K01 - HL084700). The authors have no conflicts of interest to disclose. S. S. C. conceived the study design, performed data analyses and led the writing. T.L.G.-W. contributed to the study origination, supervised the study and assisted with the writing. J.G., A.B.Z. and M. K. E. contributed to the study origination and supervised the study. M. F. contributed the healthy food availability data. M. F. K. assisted with the dietary intake data. All authors helped to conceptualize ideas, interpret findings and review drafts of the manuscript. NR 33 TC 19 Z9 19 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 EI 1475-2727 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD JUN PY 2011 VL 14 IS 6 BP 1001 EP 1007 DI 10.1017/S1368980010003812 PG 7 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 763CF UT WOS:000290530400010 PM 21272422 ER PT J AU Cole, VT Weinberger, DR Dickinson, D AF Cole, Veronica T. Weinberger, Daniel R. Dickinson, Dwight TI Intra-individual variability across neuropsychological tasks in schizophrenia: A comparison of patients, their siblings, and healthy controls SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Intra-individual variability; Schizophrenia genetic susceptibility ID WECHSLER-BELLEVUE SCATTER; WORKING-MEMORY; PERFORMANCE; RISK; DOPAMINE; DEMENTIA AB Recently, higher degrees of intra-individual variability (IIV) across neuropsychological tasks have been linked to risk for developing schizophrenia. Extending these findings to examine not only disease risk but genetic susceptibility to schizophrenia, we examined IIV across five factor-based cognitive scores in a sample of schizophrenia patients, their unaffected siblings, and healthy volunteers. IIV was significantly different among probands, siblings, and controls, with groups showing decreasing variability in that order. In addition, modest associations between IIV, age, and functioning ability were found. In light of these results, IIV indices might represent useful tools in understanding cognition in schizophrenia. Published by Elsevier B.V. C1 [Cole, Veronica T.; Weinberger, Daniel R.; Dickinson, Dwight] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Dickinson, D (reprint author), NIMH, Clin Brain Disorders Branch, 10 Ctr Dr 7SE-5350, Bethesda, MD 20892 USA. EM Dwight.Dickinson@mail.nih.gov FU National Institute of Mental Health FX Funding for this study was provided by the Intramural Research Program of the National Institute of Mental Health; the NIMH IRP had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 23 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUN PY 2011 VL 129 IS 1 BP 91 EP 93 DI 10.1016/j.schres.2011.03.007 PG 3 WC Psychiatry SC Psychiatry GA 781BN UT WOS:000291905700014 PM 21470829 ER PT J AU Liu, WL Zhang, K Locatis, C Ackerman, M AF Liu, Wei-Li Zhang, Kai Locatis, Craig Ackerman, Michael TI Internet-Based Videoconferencing Coder/Decoders and Tools for Telemedicine SO TELEMEDICINE AND E-HEALTH LA English DT Article DE technology; telecommunications; telemedicine; distance learning ID COMMUNICATION AB Alternative videoconferencing technologies for providing telemedicine via the Internet are described. Background information about how digital video applications have been instantiated using Internet protocols is presented. Specific methods for encoding and decoding video are discussed and video applications that have been tested at the National Library of Medicine are reviewed. This article suggests that no one technology is best and that the appropriateness of a method depends on specific applications. Some technologies, however, have lower, more flexible bandwidth requirements and are more standardized, making them more practical. Still, emerging, yet-to-be-standardized applications offer new capabilities warranting further investigation. C1 [Liu, Wei-Li; Zhang, Kai; Locatis, Craig; Ackerman, Michael] Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. RP Liu, WL (reprint author), Natl Lib Med, Off High Performance Comp & Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM wliu@mail.nih.gov NR 25 TC 6 Z9 6 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 EI 1556-3669 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JUN PY 2011 VL 17 IS 5 BP 358 EP 362 DI 10.1089/tmj.2010.0193 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 784ZX UT WOS:000292198300008 PM 21563926 ER PT J AU Ma, DY Xu, XQ An, S Liu, H Yang, XN Andersen, JF Wang, YP Tokumasu, F Ribeiro, JMC Francischetti, IMB Lai, R AF Ma, Dongying Xu, Xueqing An, Su Liu, Huan Yang, Xuening Andersen, John F. Wang, Yipeng Tokumasu, Fuyuki Ribeiro, Jose M. C. Francischetti, Ivo M. B. Lai, Ren TI A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets alpha(IIb)beta(3) or alpha(V)beta(3) and inhibits platelet aggregation and angiogenesis SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Haematophagy; blood-sucking; disintegrin; thrombosis; sialogenins ID SNAKE-VENOM DISINTEGRINS; GLYCOPROTEIN-IIB-IIIA; SPECIFICALLY BINDS; THROMBUS FORMATION; VIPER VENOMS; ACTIVATION; INTEGRINS; PROTEINS; RECOGNITION; ANTAGONISTS AB A novel family of RGD-containing molecules (Tablysin-15) has been molecularly characterised from the salivary gland of the haematophagous horsefly Tabanus yao. Tablysin-15 does not share primary sequence homology to any disintegrin discovered so far, and displays an RGD motif in the N-terminus of the molecule. It is also distinct from disintegrins from Viperidae since its mature form is not released from a metalloproteinase precursor. Tablysin-15 exhibits high affinity binding for platelet alpha(IIb)beta(3) and endothelial cell alpha(V)beta(3) integrins, but not for alpha(5)beta(1) or alpha(2)beta(1). Accordingly, it blocks endothelial cell adhesion to vitronectin (IC50 similar to 1 nM) and marginally to fibronectin (IC50 similar to 1 mu M), but not to collagen. It also inhibits fibroblast growth factor (FGF)-induced endothelial cell proliferation, and attenuates tube formation in vitro. In platelets, Tablysin-15 inhibits aggregation induced by collagen, ADP and convulxin, and prevents static platelet adhesion to immobilised fibrinogen. In addition, solid-phase assays and flow cytometry demonstrates that a(IIb)beta(3) binds to Tablysin-15. Moreover, immobilised Tablysin-15 supports platelet adhesion by a mechanism which was blocked by anti-integrin a(IIb)beta(3) monoclonal antibody (e.g. abciximab) or by EDTA. Furthermore, Tablysin-15 dose-dependently attenuates thrombus formation to collagen under flow. Consistent with these findings, Tablysin-15 displays antithrombotic properties in vivo suggesting that it is a useful tool to block a(IIb)beta(3), or as a prototype to develop antithrombotics. The RGD motif in the unique sequence of Tablysin-15 represents a novel template for studying the structure-function relationship of the disintegrin family of inhibitors. C1 [Ma, Dongying; An, Su; Liu, Huan; Yang, Xuening; Wang, Yipeng; Lai, Ren] Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China. [Xu, Xueqing; Andersen, John F.; Ribeiro, Jose M. C.; Francischetti, Ivo M. B.] NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Tokumasu, Fuyuki] NIAID, Malaria Genet Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [An, Su] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China. RP Lai, R (reprint author), Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China. EM ifrancischetti@niaid.nih.gov; rlai@mail.kiz.ac.cn RI ma, dongying/D-8623-2012; OI Tokumasu, Fuyuki/0000-0003-2790-1071 FU Chinese National Natural Science Foundation [30830021, 30800185]; Chinese Ministry of Science and Technology [2010CB529800]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The authors thank NIAID intramural editor Brenda Rae Marshall for assistance. This work was supported by the Chinese National Natural Science Foundation (30830021 and 30800185), the Chinese Ministry of Science and Technology (2010CB529800) and the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Because I.M.B.F., J.M.C.R., J.A. and F.T. are government employees and this is a government work, the work is in the public domain in the United States. Notwithstanding any other agreements, the NIH reserves the right to provide the work to PubMedCentral for display and use by the public, and PubMedCentral may tag or modify the work consistent with its customary practices. You can establish rights outside of the U.S. subject to a government use license. NR 50 TC 23 Z9 27 U1 0 U2 13 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 2011 VL 105 IS 6 BP 1032 EP 1045 DI 10.1160/TH11-01-0029 PG 14 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 781VK UT WOS:000291964900011 PM 21475772 ER PT J AU Heim, KF Fleisher, TA Stroncek, DF Holland, SM Gallin, JI Malech, HL Leitman, SF AF Heim, K. F. Fleisher, T. A. Stroncek, D. F. Holland, S. M. Gallin, J. I. Malech, H. L. Leitman, S. F. TI The relationship between alloimmunization and posttransfusion granulocyte survival: experience in a chronic granulomatous disease cohort SO TRANSFUSION LA English DT Article ID COLONY-STIMULATING FACTOR; RESPIRATORY BURST ACTIVITY; G-CSF; INDIUM-111-LABELED GRANULOCYTES; TRANSFUSION THERAPY; GENE-THERAPY; NEUTROPHIL; DEXAMETHASONE; COMPONENTS; TRIAL AB BACKGROUND: The efficacy of granulocyte transfusions in patients with HLA alloimmunization is uncertain. A flow cytometric assay using dihydrorhodamine 123 (DHR), a marker for cellular NADPH oxidase activity, was used to monitor the differential survival of transfused oxidase-positive granulocytes in alloimmunized patients with chronic granulomatous disease (CGD). STUDY DESIGN AND METHODS: Ten patients with CGD and serious infections were treated with daily granulocyte transfusions derived from steroid and granulocyte-colony-stimulating factor-stimulated donors. The proportion of neutrophils with intact oxidase activity was quantitated by DHR fluorescence on samples drawn before and 1 hour after transfusion. The incidence of acute transfusion reactions was correlated with the results of DHR fluorescence and biweekly HLA serologic screening assays. RESULTS: Eight of 10 patients experienced acute adverse reactions in association with granulocyte transfusions. Four had only chills and/or fever, and four experienced respiratory compromise; all eight exhibited HLA alloimmunization. Mean (+/- SD) oxidase-positive cell recovery was 19.7 +/- 17.4% (n = 15 transfusions) versus 0.95 +/- 1.59% (n = 16) in the absence and presence of HLA allosensitization, respectively (p < 0.01). Greater than 1% in vivo recovery of DHR-enhancing donor granulocytes was strongly correlated with lack of HLA alloimmunization. CONCLUSION: The ability to detect DHR-positive donor granulocytes by flow cytometry is strongly correlated with absence of HLA alloimmunization and lack of acute reactions to granulocyte transfusions in patients with CGD. If HLA antibodies are present and the survival of donor granulocytes is low by DHR analysis, transfusions should be discontinued, avoiding a therapy associated with high risk and unclear benefit. C1 [Leitman, S. F.] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD USA. RP Leitman, SF (reprint author), NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C-711, Bethesda, MD 20892 USA. EM sleitman@cc.nih.gov OI Malech, Harry/0000-0001-5874-5775 FU Intramural NIH HHS [ZIA CL002124-01] NR 30 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2011 VL 51 IS 6 BP 1154 EP 1162 DI 10.1111/j.1537-2995.2010.02993.x PG 9 WC Hematology SC Hematology GA 780PN UT WOS:000291870500007 PM 21175646 ER PT J AU Troyer, JL Brown, MA AF Troyer, Jennifer L. Brown, Meredith A. TI Feline models of viral pathogenesis: Opportunity knocks SO VETERINARY JOURNAL LA English DT Editorial Material ID IMMUNODEFICIENCY VIRUS-INFECTION; LEUKEMIA-VIRUS; LENTIVIRUS INFECTION; CAT; FELIDAE; DISEASE; FIV; TRANSMISSION; GLYCOPROTEIN; SEQUENCE C1 [Troyer, Jennifer L.] NCI Frederick, Lab Genom Div, SAIC Frederick Inc, Frederick, MD 21702 USA. [Brown, Meredith A.] Univ Coll Dublin, Vet Sci Ctr, Belfield Dublin 4, Ireland. RP Troyer, JL (reprint author), NCI Frederick, Lab Genom Div, SAIC Frederick Inc, Frederick, MD 21702 USA. EM troyerj@mail.nih.gov RI Troyer, Jennifer/B-8415-2012 FU Intramural NIH HHS [Z01 BC005385-24, Z99 CA999999] NR 32 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 1090-0233 J9 VET J JI Vet. J. PD JUN PY 2011 VL 188 IS 3 BP 252 EP 253 DI 10.1016/j.tvjl.2010.07.013 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 781UR UT WOS:000291962500003 PM 20716490 ER PT J AU Jones, KS Lambert, S Bouttier, M Benit, L Ruscetti, FW Hermine, O Pique, C AF Jones, Kathryn S. Lambert, Sophie Bouttier, Manuella Benit, Laurence Ruscetti, Frank W. Hermine, Olivier Pique, Claudine TI Molecular Aspects of HTLV-1 Entry: Functional Domains of the HTLV-1 Surface Subunit (SU) and Their Relationships to the Entry Receptors SO VIRUSES-BASEL LA English DT Review DE retrovirus; viral entry; Env; proteoglycans; neuropilin; GLUT ID CELL LEUKEMIA-VIRUS; HEPARAN-SULFATE PROTEOGLYCANS; COMPLETE NUCLEOTIDE-SEQUENCE; HUMAN MONOCLONAL-ANTIBODIES; GLUCOSE-TRANSPORTER GLUT-1; CD4(+) T-CELLS; BINDING DOMAIN; TYPE-1 HTLV-1; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION AB The initial step in retroviral infection involves specific interactions between viral envelope proteins (Env) and specific receptors on the surface of target cells. For many years, little was known about the entry receptors for HTLV-1. During this time, however, functional domains of the HTLV-1 Env were identified by analyzing the effects of neutralizing antibodies and specific mutations in Env on HTLV-1 infectivity. More recent studies have revealed that HTLV-1 infectivity involves interactions with three different molecules: heparan sulfate proteoglycans (HSPG), the VEGF-165 receptor Neuropilin 1 (NRP-1) and glucose transporter type 1 (GLUT1). Here, we revisit previously published data on the functional domains of Env in regard to the recent knowledge acquired about this multi-receptor complex. We also discuss the similarities and differences between HTLV-1 and other deltaretroviruses in regards to receptor usage. C1 [Lambert, Sophie; Bouttier, Manuella; Benit, Laurence; Pique, Claudine] Inst Cochin, INSERM, U1016, F-75014 Paris, France. [Jones, Kathryn S.] NCI Frederick, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Lambert, Sophie; Bouttier, Manuella; Benit, Laurence; Pique, Claudine] CNRS, UMR8104, F-75014 Paris, France. [Lambert, Sophie; Bouttier, Manuella; Benit, Laurence; Pique, Claudine] Univ Paris 05, F-75006 Paris, France. [Ruscetti, Frank W.] NCI Frederick, Canc & Inflammat Program, Frederick, MD 21702 USA. [Hermine, Olivier] Hop Necker Enfants Malad, Serv Hematol Adulte, F-75743 Paris 15, France. RP Pique, C (reprint author), Inst Cochin, INSERM, U1016, 22 Rue Mechain, F-75014 Paris, France. EM joneska@mail.nih.gov; s.lambert@inserm.fr; manuella.bouttier@igmm.cnrs.fr; laurence.benit@inserm.fr; ruscettf@mail.nih.gov; ohermine@gmail.com; claudine.pique@inserm.fr FU Cent pour sang la Vie; Institut National du cancer (INCA); Association pour la Recherche sur le cancer (ARC); Ligue Nationale contre le Cancer; Fondation pour la Recherche Medicale; Fondation de France; National Cancer Institute, National Institutes of Health [HHSN26120080001E]; NIH, National Cancer Institute, Center for Cancer Research FX The authors would like to thank Cent pour sang la Vie, Institut National du cancer (INCA), Association pour la Recherche sur le cancer (ARC), Ligue Nationale contre le Cancer, Fondation pour la Recherche Medicale and the Fondation de France for the financial supports of their works. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 67 TC 23 Z9 23 U1 0 U2 0 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD JUN PY 2011 VL 3 IS 6 BP 794 EP 810 DI 10.3390/v3060794 PG 17 WC Virology SC Virology GA 782RL UT WOS:000292027700008 PM 21994754 ER PT J AU Edwards, D Fenizia, C Gold, H de Castro-Amarante, MF Buchmann, C Pise-Masison, CA Franchini, G AF Edwards, Dustin Fenizia, Claudio Gold, Heather de Castro-Amarante, Maria Fernanda Buchmann, Cody Pise-Masison, Cynthia A. Franchini, Genoveffa TI Orf-I and Orf-II-Encoded Proteins in HTLV-1 Infection and Persistence SO VIRUSES-BASEL LA English DT Review DE human T-cell leukemia/lymphoma virus type-1; HTLV-1; ORF-I; ORF-II; p8; p12; p13; p30 ID T-CELL-LEUKEMIA; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; OPEN READING FRAMES; VACUOLAR H+-ATPASE; TYPE-1 P12(I); MESSENGER-RNAS; VIRAL INFECTIVITY; HUMAN MACROPHAGES; E5 ONCOPROTEIN AB The 3' end of the human T-cell leukemia/lymphoma virus type-1 (HTLV-1) genome contains four overlapping open reading frames (ORF) that encode regulatory proteins. Here, we review current knowledge of HTLV-1 orf-I and orf-II protein products. Singly spliced mRNA from orf-I encodes p12, which can be proteolytically cleaved to generate p8, while differential splicing of mRNA from orf-II results in production of p13 and p30. These proteins have been demonstrated to modulate transcription, apoptosis, host cell activation and proliferation, virus infectivity and transmission, and host immune responses. Though these proteins are not essential for virus replication in vitro, p8, p12, p13, and p30 have an important role in the establishment and maintenance of HTLV-1 infection in vivo. C1 [Edwards, Dustin; Fenizia, Claudio; Gold, Heather; de Castro-Amarante, Maria Fernanda; Buchmann, Cody; Pise-Masison, Cynthia A.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM edwardsd2@mail.nih.gov; feniziac@mail.nih.gov; goldhl@mail.nih.gov; amarantem@mail.nih.gov; buchmannc@mail.nih.gov; masisonc@mail.nih.gov; franchinig@mail.nih.gov FU National Institute of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institute of Health, National Cancer Institute, Center for Cancer Research. NR 118 TC 15 Z9 15 U1 0 U2 1 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD JUN PY 2011 VL 3 IS 6 BP 861 EP 885 DI 10.3390/v3060861 PG 25 WC Virology SC Virology GA 782RL UT WOS:000292027700012 PM 21994758 ER PT J AU Liu, MH Eiden, MV AF Liu, Meihong Eiden, Maribeth V. TI Role of Human Endogenous Retroviral Long Terminal Repeats (LTRs) in Maintaining the Integrity of the Human Germ Line SO VIRUSES-BASEL LA English DT Article DE genomic stability; retroelement; primate evolution ID EXPRESSION; P63; ENHANCER; OOCYTES; COMPLEX; GATA-2; CELLS; P53 AB Retroviruses integrate a reverse transcribed double stranded DNA copy of their viral genome into the chromosomal DNA of cells they infect. Occasionally, exogenous retroviruses infect germ cells and when this happens a profound shift in the virus host dynamic occurs. Retroviruses maintained as hereditable viral genetic material are referred to as endogenous retroviruses (ERVs). After millions of years of co-evolution with their hosts many human ERVs retain some degree of function and a few have even become symbionts. Thousands of copies of endogenous retrovirus long terminal repeats (LTRs) exist in the human genome. There are approximately 3000 to 4000 copies of the ERV-9 LTRs in the human genome and like other solo LTRs, ERV-9 LTRs can exhibit distinct promoter/enhancer activity in different cell lineages. It has been recently reported that a novel transcript of p63, a primordial member of the p53 family, is under the transcriptional control of an ERV-9 LTR [1]. The expression of different p63 transcript isoforms has been previously shown to have an important role in replenishing cutaneous epithelial stem cells and maintaining the fidelity of the female germ line [2]. In this recent report, a novel p63 transcript, designated GTAp63, is described as specifically expressed in healthy human testes and germ cell precursors of human testes but not in testicular cancer cells. The ability of ERV-9 regulatory regions to contribute to the maintenance of male germ line stability is yet another example of how ERVs have evolved to serve an important function in the physiology of their human hosts. C1 [Liu, Meihong; Eiden, Maribeth V.] NIH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Eiden, MV (reprint author), NIH, Lab Cellular & Mol Regulat, 49 Convent Dr,MSC 4483, Bethesda, MD 20892 USA. EM lmeihong@mail.nih.gov; eidenm@mail.nih.gov FU National Institute of Mental Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health. NR 16 TC 4 Z9 4 U1 1 U2 7 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD JUN PY 2011 VL 3 IS 6 BP 901 EP 905 DI 10.3390/v3060901 PG 5 WC Virology SC Virology GA 782RL UT WOS:000292027700014 PM 21994760 ER PT J AU Minor, RK Lopez, M Younts, CM Jones, B Pearson, KJ Anson, RM Dieguez, C de Cabo, R AF Minor, Robin K. Lopez, Miguel Younts, Caitlin M. Jones, Bruce Pearson, Kevin J. Anson, Robert Michael Dieguez, Carlos de Cabo, Rafael TI The arcuate nucleus and neuropeptide Y contribute to the antitumorigenic effect of calorie restriction SO AGING CELL LA English DT Article DE calorie restriction; hypothalamus; monosodium glutamate; neuroendocrine; neuropeptide Y; tumorigenesis ID MONOSODIUM GLUTAMATE; ADIPONECTIN RECEPTORS; ENERGY HOMEOSTASIS; ADIPOSE-TISSUE; INSULIN ACTION; LIFE-SPAN; LEPTIN; HYPOTHALAMUS; GROWTH; MICE AB P>Calorie restriction (CR) is known to have profound effects on tumor incidence. A typical consequence of CR is hunger, and we hypothesized that the neuroendocrine response to CR might in part mediate CR's antitumor effects. We tested CR under appetite suppression using two models: neuropeptide Y (NPY) knockout mice and monosodium glutamate-injected mice. While CR was protective in control mice challenged with a two-stage skin carcinogenesis model, papilloma development was neither delayed nor reduced by CR in the monosodium glutamate-treated and NPY knockout mice. Adiponectin levels were also not increased by CR in the appetite-suppressed mice. We propose that some of CR's beneficial effects cannot be separated from those imposed on appetite, and that NPY neurons in the arcuate nucleus of the hypothalamus are involved in the translation of reduced intake to downstream physiological and functional benefits. C1 [Minor, Robin K.; Younts, Caitlin M.; Jones, Bruce; Pearson, Kevin J.; Anson, Robert Michael; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Lopez, Miguel; Dieguez, Carlos] Univ Santiago de Compostela, Inst Invest Sanitaria, Dept Physiol, Sch Med, Santiago De Compostela 15782, A Coruna, Spain. [Lopez, Miguel; Dieguez, Carlos] CIBER Fisiopatol Obesidad & Nutr CIBERobn, Barcelona, Spain. [Pearson, Kevin J.] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY 40536 USA. [Anson, Robert Michael] CCBC Sch Math & Sci, Baltimore, MD 21222 USA. RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, NIH, 251 Bayview Blvd,Suite 100,Room 9C218, Baltimore, MD 21224 USA. EM decabora@mail.nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU National Institute on Aging (NIH); Fondo Investigationes Sanitarias [PS09/01880]; Ministerio de Educacion y Ciencia [BFU2008, RyC-2007-00211]; European Union [Health-F2-2008-223713]; Xunta de Galicia [10PXIB208164PR] FX This work was supported by the Intramural Research Program of the National Institute on Aging (NIH), Fondo Investigationes Sanitarias (ML: PS09/01880), Ministerio de Educacion y Ciencia (CD: BFU2008; ML: RyC-2007-00211), the European Union (CD and ML: Health-F2-2008-223713: Reprobesity), and Xunta de Galicia (ML: 10PXIB208164PR). CIBER de Fisiopatologia de la Obesidad y Nutricion is an initiative of ISCIII. We also acknowledge the excellent technical assistance of Dawn Nines, Dawn Phillips-Boyer and Justine Lucas. NR 48 TC 11 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD JUN PY 2011 VL 10 IS 3 BP 483 EP 492 DI 10.1111/j.1474-9726.2011.00693.x PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 763CR UT WOS:000290531900012 PM 21385308 ER PT J AU Koehly, LM Ashida, S Goergen, AF Skapinsky, KF Hadley, DW Wilkinson, AV AF Koehly, Laura M. Ashida, Sato Goergen, Andrea F. Skapinsky, Kaley F. Hadley, Donald W. Wilkinson, Anna V. TI Willingness of Mexican-American Adults to Share Family Health History with Healthcare Providers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID GENETICS; KNOWLEDGE; SCIENCE; DISEASE AB Background: Collecting family health history (FHH) information to share with healthcare providers is an important aspect of health-risk assessment. Purpose: To examine associations between the content of FHH-informed risk feedback and willingness to share the information with a healthcare provider. Methods: Data were collected between June 2008 and July 2009 from 475 Mexican-origin adults residing in 161 households. Participants completed surveys 3 months after receiving FHH-informed risk feedback. Households were randomly assigned to feedback conditions in which household members received one or more of the following: an FHH pedigree, personalized risk assessments (PRAs), and tailored behavioral recommendations. Logistic regression models were fitted using generalized estimating equations, with exchangeable covariances, to account for the clustering of responses within and the random assignment of feedback condition to household. Analyses were completed in May 2010. Results: Participants who received personalized risk assessments were more willing to share their feedback with a provider than those who received a pedigree only (OR=2.25, p=0.02). The receipt of tailored behavioral recommendations did not significantly increase willingness to share feedback with a provider (OR=0.79, p=0.48). Conclusions: The provision of PRAs in FHH assessments appears to motivate participants to consider sharing their FHH with a healthcare provider. (Am J Prev Med 2011;40(6):633-636) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Koehly, Laura M.; Ashida, Sato; Goergen, Andrea F.; Skapinsky, Kaley F.; Hadley, Donald W.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Wilkinson, Anna V.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. RP Koehly, LM (reprint author), 31 Ctr Dr,Bldg 31,Room B1B37D, Bethesda, MD 20892 USA. EM koehlyl@mail.nih.gov FU National Human Genome Research Institute at the NIH [Z01HG200335]; MACS; National Cancer Institute [CA126988] FX This study was supported by the Intramural Research Program of the National Human Genome Research Institute at the NIH (Z01HG200335 to LMK). We thank Dr. ML Bondy and the Mexican American Cohort Study (MACS) staff for their ongoing work with participant recruitment and follow-up. The MACS is funded pursuant to the Comprehensive Tobacco Settlement of 1998 and appropriated by the 76th legislature to the University of Texas MD Anderson Cancer Center, by the Caroline W. Law Fund for Cancer Prevention, and the Dan Duncan Family Institute. AVW is funded by the National Cancer Institute (CA126988). In addition, we thank the Risk Assessment for Mexican Americans research team for their hard work collecting the data for this project and Greg Feero, Alan Guttmacher, Colleen M. McBride, and Richard L Street Jr. for comments on an earlier draft of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the DHHS or the U. S. Government. NR 30 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2011 VL 40 IS 6 BP 633 EP 636 DI 10.1016/j.amepre.2011.02.013 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 762IS UT WOS:000290470400011 PM 21565656 ER PT J AU Hipp, JD Lucas, DR Emmert-Buck, MR Compton, CC Balis, UJ AF Hipp, Jason D. Lucas, David R. Emmert-Buck, Michael R. Compton, Carolyn C. Balis, Ulysses J. TI Digital Slide Repositories for Publications Lessons Learned From the Microarray Community SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; PROTEOMICS DATA; STEM-CELLS; INFORMATION; TRANSFORMATION; PROFILES; CANCER C1 [Hipp, Jason D.; Lucas, David R.; Balis, Ulysses J.] Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI 48109 USA. [Emmert-Buck, Michael R.] NCI, Pathol Lab, Adv Technol Ctr, Gaithersburg, MD USA. [Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. RP Hipp, JD (reprint author), Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI 48109 USA. EM jason.hipp@gmail.com NR 32 TC 5 Z9 5 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 2011 VL 35 IS 6 BP 783 EP 786 DI 10.1097/PAS.0b013e31821946b6 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA 763NW UT WOS:000290567400001 PM 21552111 ER PT J AU Kluczynski, MA Lamonte, MJ Mares, JA Wactawski-Wende, J Smith, AW Engelman, CD Andrews, CA Snetselaar, LG Sarto, GE Millen, AE AF Kluczynski, Melissa A. Lamonte, Michael J. Mares, Julie A. Wactawski-Wende, Jean Smith, Ashley Wilder Engelman, Corinne D. Andrews, Christopher A. Snetselaar, Linda G. Sarto, Gloria E. Millen, Amy E. TI Duration of Physical Activity and Serum 25-hydroxyvitamin D Status of Postmenopausal Women SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Epidemiology; 25-Hydroxyvitamin D; Physical Activity; Serum; Sunlight Exposure; Vitamin D; Women ID VITAMIN-D STATUS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; MINERAL METABOLISM; HYPOVITAMINOSIS-D; AFRICAN-AMERICAN; D INSUFFICIENCY; CLINICAL-TRIAL; US POPULATION; D INADEQUACY AB PURPOSE: To investigate whether the association between physical activity and serum 25-hydroxyvitamin D (25(OH)D) concentrations is independent of sun exposure, body size, and other potential explanatory variables. METHODS: By using data from a sample of 1343 postmenopausal women from the Women's Health Initiative, we used linear regression to examine the associations of duration (minutes/week) of recreational activity and of yard work with 25(OH)D concentrations (nmol/L). RESULTS: In age-adjusted analyses, positive associations were observed between 25(OH)D concentrations and both duration of recreational physical activity (beta = 0.71, SE [0.09], p < .001) and yard work (beta = 0.36, SE [0.10], p = .004). After further adjustment for vitamin D intake, self-reported sunlight exposure, waist circumference, and season of blood draw, 25 (OH)D was significantly associated with recreational activity (beta = 0.21, SE [0.091, p = .014) but not with yard work (beta = 0.18, SE [0.09], p = .061). Interactions were observed between season and both recreational activity (P-interaction = .082) and yard work (P-interaction = .038) such that these activity-25(OH)D associations were greater during summer/fall compared with winter/spring. Self-reported sunlight exposure and measures of body size did not modify the associations. CONCLUSIONS: The observed age-adjusted activity-25(OH)D associations were attenuated after adjusting for explanatory variables and were modified by season of blood draw. Adopting a lifestyle that incorporates outdoor physical activity during summer/fall, consuming recommended amounts of vitamin D, and maintaining a healthy weight may improve or maintain vitamin D status in postmenopausal women. Ann Epidemiol 201121:440-449. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kluczynski, Melissa A.; Lamonte, Michael J.; Wactawski-Wende, Jean; Smith, Ashley Wilder] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14214 USA. [Mares, Julie A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Smith, Ashley Wilder] NCI, Outcomes Res Branch, Appl Res Program, Bethesda, MD 20892 USA. [Engelman, Corinne D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Andrews, Christopher A.] SUNY Buffalo, Dept Biostat, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA. [Snetselaar, Linda G.] Univ Iowa, Dept Community & Behav Hlth, Coll Publ Hlth, Iowa City, IA USA. [Snetselaar, Linda G.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA. [Sarto, Gloria E.] Univ Wisconsin, Dept Obstet & Gynecol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Millen, AE (reprint author), SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, 270 Farber Hall, Buffalo, NY 14214 USA. EM aemillen@buffalo.edu FU National Institutes of Health [EY13018, EY016886]; Research to Prevent Blindness; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221] FX This research was supported by grants EY13018 and EY016886 from the National Institutes of Health and by Research to Prevent Blindness. It was part of the Carotenoids and Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative (WHI). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. NR 52 TC 14 Z9 14 U1 0 U2 4 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 JUN PY 2011 VL 21 IS 6 BP 440 EP 449 DI 10.1016/j.annepidem.2010.11.011 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 764CT UT WOS:000290606700007 PM 21414803 ER PT J AU Yang, HP Black, A Falk, RT Brinton, LA Potischman, N Wentzensen, N Faupel-Badger, JM Sherman, ME AF Yang, Hannah P. Black, Amanda Falk, Roni T. Brinton, Louise A. Potischman, Nancy Wentzensen, Nicolas Faupel-Badger, Jessica M. Sherman, Mark E. TI Association of Serum Sex Steroid Hormone Hemodilution and Body Mass Index Among Healthy Postmenopausal Women SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Sex Steroid Hormones; Obesity; Hemodilution ID ENDOMETRIAL CANCER-RISK; PLASMA-VOLUME; OBESITY; MEN; PROSTATE; SIZE; FAT AB PURPOSE: Hemodilution refers to reduced concentrations of analytes in the blood secondary to increased fluid volume. Given that obesity is associated with expanded vascular volume, hemodilution may result in a lower ratio of blood concentrations of analytes among heavier subjects. Assessing the relationship of hormone concentration to total mass varies by body mass index (BMI) is etiologically important because obesity is related to hormone metabolism and cancer risk. METHODS: We evaluated data for 194 postmenopausal controls in an endometrial cancer case-control study. Height, weight, and serum hormone concentrations were measured previously. We estimated serum hormone mass from concentration based on estimates of calculated plasma volume. We assessed the effect of BM I on relationships of sex steroid hormone concentration and mass using multivariate linear regression. RESULTS: Higher BMI was associated with increased estrone, estrone sulfate, estradiol, and albumin-bound estradiol concentrations and masses (p-trend <= 0.001). With increasing BMI, androstenedione concentration did not change significantly (p-trend = 0.548), but its mass increased (p-trend = 0.024). CONCLUSIONS: Relationships of sex steroid hormone concentration and mass were generally similar, except for androstenedione in which the relationship was only significant for mass. Future studies to assess both sex steroid hormone concentration and mass may have value in etiological research. Ann Epidemiol 2011;21:466-471. Published by Elsevier Inc. C1 [Yang, Hannah P.; Falk, Roni T.; Brinton, Louise A.; Wentzensen, Nicolas; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Black, Amanda] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Potischman, Nancy] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Faupel-Badger, Jessica M.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. RP Yang, HP (reprint author), NCI, 6120 Execut Blvd,EPS-5102, Rockville, MD 20852 USA. EM yanghan@mail.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU Intramural NIH HHS [Z99 CA999999] NR 23 TC 3 Z9 3 U1 0 U2 3 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 JUN PY 2011 VL 21 IS 6 BP 466 EP 471 DI 10.1016/j.annepidem.2011.01.003 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 764CT UT WOS:000290606700010 PM 21435901 ER PT J AU Kedei, N Telek, A Czap, A Lubart, ES Czifra, G Yang, DZ Chen, JQ Morrison, T Goldsmith, PK Lim, LS Mannan, P Garfield, SH Kraft, MB Li, W Keck, GE Blumberg, PM AF Kedei, Noemi Telek, Andrea Czap, Alexandra Lubart, Emanuel S. Czifra, Gabriella Yang, Dazhi Chen, Jinqiu Morrison, Tyler Goldsmith, Paul K. Lim, Langston Mannan, Poonam Garfield, Susan H. Kraft, Matthew B. Li, Wei Keck, Gary E. Blumberg, Peter M. TI The synthetic bryostatin analog Merle 23 dissects distinct mechanisms of bryostatin activity in the LNCaP human prostate cancer cell line SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Protein kinase C; Phorbol ester; Cell signaling; Bryostatin analog ID PROTEIN-KINASE-C; ESTER-INDUCED APOPTOSIS; CONFORMATIONALLY CONSTRAINED ANALOGS; PHORBOL ESTER; DOWN-REGULATION; MEMBRANE TRANSLOCATION; TUMOR PROMOTION; MOUSE SKIN; PKC-ALPHA; DELTA AB Bryostatin 1 has attracted considerable attention both as a cancer chemotherapeutic agent and for its unique activity. Although it functions, like phorbol esters, as a potent protein kinase C (PKC) activator, it paradoxically antagonizes many phorbol ester responses in cells. Because of its complex structure, little is known of its structure-function relations. Merle 23 is a synthetic derivative, differing from bryostatin 1 at only four positions. However, in U-937 human leukemia cells. Merle 23 behaves like a phorbol ester and not like bryostatin 1. Here, we characterize the behavior of Merle 23 in the human prostate cancer cell line LNCaP. In this system, bryostatin 1 and phorbol ester have contrasting activities, with the phorbol ester but not bryostatin 1 blocking cell proliferation or tumor necrosis factor alpha secretion, among other responses. We show that Merle 23 displays a highly complex pattern of activity in this system. Depending on the specific biological response or mechanistic change, it was bryostatin-like, phorbol ester-like, intermediate in its behavior, or more effective than either. The pattern of response, moreover, varied depending on the conditions. We conclude that the newly emerging bryostatin derivatives such as Merle 23 provide powerful tools to dissect subsets of bryostatin mechanism and response. Published by Elsevier Inc. C1 [Kedei, Noemi; Telek, Andrea; Czap, Alexandra; Lubart, Emanuel S.; Czifra, Gabriella; Yang, Dazhi; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Chen, Jinqiu; Morrison, Tyler; Goldsmith, Paul K.] NCI, Antibody & Prot Purificat Unit, Ctr Canc Res, Bethesda, MD 20892 USA. [Lim, Langston; Mannan, Poonam; Garfield, Susan H.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Kraft, Matthew B.; Li, Wei; Keck, Gary E.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA. RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Room 4048,Bldg 37,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM kedein@mail.nih.gov; teleka@mail.nih.gov; Alexandra.czap@gmail.com; lubartes@mail.nih.gov; czifrag@gmail.com; yangda@mail.nih.gov; chenj13@mail.nih.gov; morrisont@gmail.com; paulg@mail.nih.gov; limla@mail.nih.gov; mannamp@mail.nih.gov; garfiels@mail.nih.gov; mkraft@chem.utah.edu; weili@chem.utah.edu; keck@chem.utah.edu; blumberp@dc37a.nci.nih.gov FU National Institutes of Health, Center for Cancer Research, National Cancer Institute; [GM28961] FX This research was supported in part by the Intramural Research Program, National Institutes of Health, Center for Cancer Research, National Cancer Institute and by Grant GM28961 to GEK. NR 55 TC 23 Z9 23 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 1 PY 2011 VL 81 IS 11 BP 1296 EP 1308 DI 10.1016/j.bcp.2011.03.018 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 763ZM UT WOS:000290598200004 PM 21458422 ER PT J AU Takeda, Y Nakaseko, C Tanaka, H Takeuchi, M Yui, M Saraya, A Miyagi, S Wang, CS Tanaka, S Ohwada, C Sakaida, E Yamaguchi, N Yokote, K Hennighausen, L Iwama, A AF Takeda, Yusuke Nakaseko, Chiaki Tanaka, Hiroaki Takeuchi, Masahiro Yui, Makiko Saraya, Atsunori Miyagi, Satoru Wang, Changshan Tanaka, Satomi Ohwada, Chikako Sakaida, Emiko Yamaguchi, Naoto Yokote, Koutaro Hennighausen, Lothar Iwama, Atsushi TI Direct activation of STAT5 by ETV6-LYN fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE ETV6-LYN; STAT5; myeloproliferative neoplasm; myelofibrosis ID LYN TYROSINE KINASE; POLYCYTHEMIA-VERA; EXPRESSION CLONING; MYELOID-LEUKEMIA; SELF-RENEWAL; BONE-MARROW; CELLS; DISEASE; GENE; DIFFERENTIATION AB P>Myeloproliferative neoplasms (MPN), a group of haematopoietic stem cell (HSC) disorders, are often accompanied by myelofibrosis. We previously identified the fusion of the ETV6 gene to the LYN gene (ETV6-LYN) in idiopathic myelofibrosis with ins(12;8)(p13;q11q21). The introduction of ETV6-LYN into HSCs resulted in fatal MPN with massive myelofibrosis in mice, implicating the rearranged LYN kinase in the pathogenesis of MPN with myelofibrosis. However, the signalling molecules directly downstream from and activated by ETV6-LYN remain unknown. In this study, we demonstrated that the direct activation of STAT5 by ETV6-LYN is crucial for the development of MPN. ETV6-LYN was constitutively active as a kinase through autophosphorylation. ETV6-LYN, but not its kinase-dead mutant, supported cytokine-free proliferation of haematopoietic cells. STAT5 was activated in a JAK2-independent manner in ETV6-LYN-expressing cells. ETV6-LYN interacted with STAT5 and directly activated STAT5 both in vitro and in vivo. Of note, ETV6-LYN did not support the formation of colonies by Stat5-deficient HSCs under cytokine-free conditions and the capacity of ETV6-LYN to induce MPN with myelofibrosis was profoundly attenuated in a Stat5-null background. These findings define STAT5 as a direct target of ETV6-LYN and unveil the LYN-STAT5 axis as a novel pathway to augment proliferative signals in MPN and leukaemia. C1 [Nakaseko, Chiaki] Chiba Univ, Grad Sch Med, Div Haematol, Dept Clin Cell Biol,Chuo Ku, Chiba 2608670, Japan. [Takeda, Yusuke; Yui, Makiko; Saraya, Atsunori; Miyagi, Satoru; Wang, Changshan; Tanaka, Satomi; Iwama, Atsushi] Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chiba 2608670, Japan. [Yamaguchi, Naoto] Chiba Univ, Grad Sch Pharmaceut Sci, Dept Mol Cell Biol, Chiba 2608670, Japan. [Hennighausen, Lothar] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. [Saraya, Atsunori; Miyagi, Satoru; Wang, Changshan; Iwama, Atsushi] CREST, Chiyoda Ku, Tokyo, Japan. RP Nakaseko, C (reprint author), Chiba Univ, Grad Sch Med, Div Haematol, Dept Clin Cell Biol,Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM chiaki-nakaseko@faculty.chiba-u.jp; aiwama@faculty.chiba-u.jp FU (Global Centre for Education and Research in Immune System Regulation and Treatment), MEXT, Japan; Japan Science and Technology Corporation (JST); Takeda Science Foundation; National Institutes of Health (NIDDK); [20591110] FX We thank Dr T. Kitamura and W. Pear for providing the pMXs-puro vector and MigR1 vector, respectively. This work was supported in part by Grants-in-Aid for scientific research (#20591110) and the Global COE Program (Global Centre for Education and Research in Immune System Regulation and Treatment), MEXT, Japan, a Grant-in-aid for Core Research for Evolutional Science and Technology (CREST) from the Japan Science and Technology Corporation (JST), and a grant from the Takeda Science Foundation. LH was supported by the international program of the National Institutes of Health (NIDDK). NR 38 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2011 VL 153 IS 5 BP 589 EP 598 DI 10.1111/j.1365-2141.2011.08663.x PG 10 WC Hematology SC Hematology GA 762CO UT WOS:000290450100005 PM 21492125 ER PT J AU Cheng, J Ma, XC Gonzalez, FJ AF Cheng, Jie Ma, Xiaochao Gonzalez, Frank J. TI Pregnane X receptor- and CYP3A4-humanized mouse models and their applications SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE PXR; CYP3A4; mouse model ID NF-KAPPA-B; CONSTITUTIVE ANDROSTANE RECEPTOR; INFLAMMATORY-BOWEL-DISEASE; HUMAN CYP3A4 GENE; CYTOCHROME-P450 3A4; XENOBIOTIC RECEPTOR; NUCLEAR RECEPTORS; TRANSGENIC MICE; DRUG-INTERACTIONS; BILE-ACIDS AB Pregnane X receptor (PXR) is a pivotal nuclear receptor modulating xenobiotic metabolism primarily through its regulation of CYP3A4, the most important enzyme involved in drug metabolism in humans. Due to the marked species differences in ligand recognition by PXR, PXR-humanized (hPXR) mice, and mice expressing human PXR and CYP3A4 (Tg3A4/hPXR) were established. hPXR and Tg3A4/hPXR mice are valuable models for investigating the role of PXR in xenobiotic metabolism and toxicity, in lipid, bile acid and steroid hormone homeostasis, and in the control of inflammation. C1 [Cheng, Jie; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ma, Xiaochao] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov FU National Cancer Institute FX This work was supported by the National Cancer Institute Intramural Research Program. NR 51 TC 16 Z9 21 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUN PY 2011 VL 163 IS 3 BP 461 EP 468 DI 10.1111/j.1476-5381.2010.01129.x PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 762QN UT WOS:000290494600002 PM 21091656 ER PT J AU Tsihlis, ND Oustwani, CS Vavra, AK Jiang, Q Keefer, LK Kibbe, MR AF Tsihlis, Nick D. Oustwani, Chris S. Vavra, Ashley K. Jiang, Qun Keefer, Larry K. Kibbe, Melina R. TI Nitric Oxide Inhibits Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia by Increasing the Ubiquitination and Degradation of UbcH10 SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article; Proceedings Paper CT 2nd Annual Ubiquitin Drug Discovery and Diagnostics Conference CY AUG 23-25, 2010 CL Philadelphia, PA DE Neointimal hyperplasia; Nitric oxide; Proteasome; UbcH10; Ubiquitin ID INTIMAL HYPERPLASIA; PROTEASOME PATHWAY; CONJUGATING ENZYME; SYSTEM; ATHEROSCLEROSIS; PROTEIN; CARCINOMAS; ACTIVATION; EXPRESSION; PREVENTION AB Nitric oxide (NO) limits formation of neointimal hyperplasia in animal models of arterial injury in large part by inhibiting vascular smooth muscle cell (VSMC) proliferation through cell cycle arrest. The ubiquitin-conjugating enzyme UbcH10 is responsible for ubiquitinating cell cycle proteins for proper exit from mitosis. We hypothesize that NO prevents VSMC proliferation, and hence neointimal hyperplasia, by decreasing levels of UbcH10. Western blotting and immunofluorescent staining showed that NO reduced UbcH10 levels in a concentration-dependent manner in VSMC harvested from the abdominal aortas of Sprague-Dawley rats. Treatment with NO or siRNA to UbcH10 decreased both UbcH10 levels and VSMC proliferation (P < 0.001), while increasing UbcH10 levels by plasmid transfection or angiotensin II stimulation increased VSMC proliferation to 150% (P = 0.008) and 212% (P = 0.002) of control, respectively. Immunofluorescent staining of balloon-injured rat carotid arteries showed a similar to 4-fold increase in UbcH10 levels, which was profoundly decreased following treatment with NO. Western blotting of carotid artery lysates showed no UbcH10 in uninjured vessels, a substantial increase in the injury alone group, and a significant decrease in the injury + NO group (similar to 3-fold reduction versus injury alone). Importantly, in vitro and in vivo, a marked increase in polyubiquitinated UbcH10 was observed in the NO-treated VSMC and carotid arteries, respectively, indicating that NO may be decreasing unmodified UbcH10 levels by increasing its ubiquitination. Central to our hypothesis, we report that NO decreases UbcH10 levels in VSMC in vitro and following arterial injury in vivo in association with increasing polyubiquitinated-UbcH10 levels. These changes in UbcH10 levels correlate with VSMC proliferation and neointimal hyperplasia, making UbcH10 a promising therapeutic target for inhibiting this proliferative disease. C1 [Tsihlis, Nick D.; Oustwani, Chris S.; Vavra, Ashley K.; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Kibbe, MR (reprint author), Northwestern Univ, Div Vasc Surg, 676 N St Clair,650, Chicago, IL 60611 USA. EM mkibbe@nmh.org RI Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Tsihlis, Nick/0000-0002-0410-0143 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-2008-00001]; NHLBI NIH HHS [1K08HL0842-03] NR 29 TC 25 Z9 27 U1 0 U2 7 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PD JUN PY 2011 VL 60 IS 1-2 BP 89 EP 97 DI 10.1007/s12013-011-9179-3 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 763PV UT WOS:000290573100010 PM 21448667 ER PT J AU Keay, S Kaczmarek, P Zhang, CO Koch, K Szekely, Z Barchi, JJ Michejda, C AF Keay, Susan Kaczmarek, Piotr Zhang, Chen-Ou Koch, Kristopher Szekely, Zoltan Barchi, Joseph J., Jr. Michejda, Christopher TI Normalization of Proliferation and Tight Junction Formation in Bladder Epithelial Cells from Patients with Interstitial Cystitis/Painful Bladder Syndrome by d-Proline and d-Pipecolic Acid Derivatives of Antiproliferative Factor SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE antiproliferative factor; bladder; epithelium; interstitial cystitis; tight junctions ID EPIDERMAL-GROWTH-FACTOR; EXPRESSION; MARKERS; PERMEABILITY; PEPTIDE; URINE; GENE; DIFFERENTIATION; PATHOGENESIS; DYSFUNCTION AB Interstitial cystitis/painful bladder syndrome is a chronic bladder disorder with epithelial thinning or ulceration, pain, urinary frequency and urgency, for which there is no reliably effective therapy. We previously reported that interstitial cystitis/painful bladder syndrome bladder epithelial cells make a glycopeptide antiproliferative factor or 'APF' (Neu5Ac alpha 2-3Gal beta 1-3GalNAc alpha-O-TVPAAVVVA) that induces abnormalities in normal cells similar to those in interstitial cystitis/painful bladder syndrome cells in vitro, including decreased proliferation, decreased tight junction formation, and increased paracellular permeability. We screened inactive APF derivatives for their ability to block antiproliferative activity of asialylated-APF ('as-APF') in normal bladder cells and determined the ability of as-APF-blocking derivatives to normalize tight junction protein expression, paracellular permeability, and/or proliferation of interstitial cystitis/painful bladder syndrome cells. Only two of these derivatives [Gal beta 1-3GalNAc alpha-O-TV-(d-pipecolic acid)-AAVVVA and Gal beta 1-3GalNAc alpha-O-TV-(d-proline)-AAVVVA] blocked as-APF antiproliferative activity in normal cells (p < 0.001 for both). Both of these antagonists also 1) significantly increased mRNA expression of ZO-1, occludin, and claudins 1, 4, 8, and 12 in interstitial cystitis/painful bladder syndrome cells by qRT-PCR; 2) normalized interstitial cystitis/painful bladder syndrome epithelial cell tight junction protein expression and tight junction formation by confocal immunofluorescence microscopy; and 3) decreased paracellular permeability of 14C-mannitol and 3H-inulin between confluent interstitial cystitis/painful bladder syndrome epithelial cells on Transwell plates, suggesting that these potent APF antagonists may be useful for the development as interstitial cystitis/painful bladder syndrome therapies. C1 [Keay, Susan; Koch, Kristopher] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Keay, Susan] Vet Adm Maryland Hlth Care Syst, Baltimore, MD USA. [Kaczmarek, Piotr; Szekely, Zoltan; Michejda, Christopher] NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Kaczmarek, Piotr; Barchi, Joseph J., Jr.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Zhang, Chen-Ou] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP Keay, S (reprint author), Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. EM skeay@medicine.umaryland.edu RI Barchi Jr., Joseph/N-3784-2014 FU National Institutes of Health [NIDDK R01 DK52596]; Veterans Affairs; NCI, National Institutes of Health FX This work was supported by grants from the National Institutes of Health Grant NIDDK R01 DK52596 and the Merit Review Funding from Veterans Affairs (to SK) and by the Intramural Research Program of the NCI, National Institutes of Health (JB and CM). NR 39 TC 13 Z9 13 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD JUN PY 2011 VL 77 IS 6 BP 421 EP 430 DI 10.1111/j.1747-0285.2011.01108.x PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 763VL UT WOS:000290587700003 PM 21352500 ER PT J AU Chi, A Wildfire, J McLoughlin, R Wood, RA Bloomberg, GR Kattan, M Gergen, P Gold, DR Witter, F Chen, T Holick, M Visness, C Gern, J O'Connor, GT AF Chi, A. Wildfire, J. McLoughlin, R. Wood, R. A. Bloomberg, G. R. Kattan, M. Gergen, P. Gold, D. R. Witter, F. Chen, T. Holick, M. Visness, C. Gern, J. O'Connor, G. T. TI Umbilical cord plasma 25-hydroxyvitamin D concentration and immune function at birth: the Urban Environment and Childhood Asthma study SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE asthma; umbilical cord plasma; vitamin D ID VITAMIN-D DEFICIENCY; REGULATORY T-CELLS; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; 1,25-DIHYDROXYVITAMIN D-3; PREGNANCY; ALLERGY; TRANSPLANTATION; CYTOKINES; RESPONSES; INNATE AB P>Background Recent studies have reported conflicting data on the association between maternal intake of vitamin D during pregnancy and asthma. Objective To assess the influence of prenatal vitamin D status on immune function at birth. Methods In an inner-city birth cohort of 568 newborns, 520 of whom had at least one atopic parent, we measured the umbilical cord (UC) plasma concentration of 25-hydroxyvitamin D (25(OH)D) and the cytokine responses of UC blood mononuclear cells (UCMCs) to stimuli including phytohaemagglutinin (PHA), lipopolysaccharide (LPS), and peptidoglycan. In a subset, the UCMC expression of regulatory T cell markers and the suppressive activity of CD4+CD25+UCMCs were measured. Results The 25th, 50th, and 75th percentiles of UC plasma 25(OH)D level were 15.0, 20.2, and 25.6 ng/mL, respectively. Most cytokine responses of UCMC were not correlated with UC 25(OH)D concentration; however, IFN-gamma release after LPS stimulation was weakly positively correlated with UC 25(OH)D concentration (r=0.11, P=0.01). PHA responses were not significantly correlated with 25(OH)D concentration. The UC plasma 25(OH)D concentration was inversely related to the number of CD25+ (r=-0.20, P=0.06), CD25Bright (r=-0.21, P=0.05), and CD25+FoxP3 (r=-0.29, P=0.06) cells as a proportion of CD4+ T cells in UC blood (r=-0.26, P=0.04) but not to the suppressive activity of CD4+CD25+cells (r=0.17, P=0.22). Conclusion and Clinical Relevance UC 25(OH)D concentration was not correlated with most UCMC cytokine responses to multiple stimuli. There was a suggestion of a weakly positive correlation with IFN-gamma release after LPS stimulation. The proportions of CD25+, CD25Bright, and CD25+FoxP3 cells to total CD4+ T cells were inversely correlated with UC 25(OH)D concentration. Our findings suggest that higher vitamin D levels at birth may be associated with a lower number of T-regulatory cells. Vitamin D status in utero may influence immune regulation in early life. C1 [Chi, A.] Tufts Univ, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02111 USA. [Wildfire, J.; Visness, C.] Rho Inc, Chapel Hill, NC USA. [McLoughlin, R.; Gold, D. R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Wood, R. A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Bloomberg, G. R.] Washington Univ, Sch Med, Dept Pediat, Div Allergy Immunol & Pulm, St Louis, MO 63110 USA. [Kattan, M.] Columbia Univ, Sch Med, Div Pediat Pulmonol, New York, NY USA. [Gergen, P.] NIAID, NIH, Bethesda, MD 20892 USA. [Witter, F.] Johns Hopkins Univ, Sch Med, Div Maternal Fetal Med, Baltimore, MD USA. [Chen, T.; Holick, M.] Boston Univ, Sch Med, Dept Endocrinol, Boston, MA 02118 USA. [Gern, J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat & Med, Madison, WI USA. [O'Connor, G. T.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. RP Chi, A (reprint author), Tufts Univ, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02111 USA. EM achi@tuftsmedicalcenter.org RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Chen, Tai/0000-0002-5704-5694; Holick, Michael/0000-0001-6023-9062; O'Connor, George/0000-0002-6476-3926; McLoughlin, Rachel/0000-0003-4553-018X FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [NO1-AI-25496, NO1-AI-25482]; 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 Contracts number NO1-AI-25496 and NO1-AI-25482, and from the National Center for Research Resources, National Institutes of Health, under grants RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, and 5UL1RR024992-02. NR 36 TC 40 Z9 40 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD JUN PY 2011 VL 41 IS 6 BP 842 EP 850 DI 10.1111/j.1365-2222.2011.03712.x PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 762OR UT WOS:000290489800012 PM 21481021 ER PT J AU Rahman, F Pechnik, S Gross, D Sewell, L Goldstein, DS AF Rahman, Faisal Pechnik, Sandra Gross, Daniel Sewell, LaToya Goldstein, David S. TI Low frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Power spectral analysis; Heart rate variability; Sympathetic; Parasympathetic; Autonomic ID SPECTRAL-ANALYSIS; PARKINSONS-DISEASE; NOREPINEPHRINE SPILLOVER; ORTHOSTATIC HYPOTENSION; AUTONOMIC FAILURE; PANIC DISORDER; DENERVATION; HUMANS; INDEX AB Background Power spectral analysis of heart rate variability is used to assess cardiac autonomic function. The relationship of low frequency (LF) power to cardiac sympathetic tone has been unclear. We reported previously that LF power may reflect baroreflex modulation. In this study we attempted to replicate our findings in additional subject cohorts, taking into account possible influences of respiration and using different methods to measure baroreflex-cardiovagal gain (BCG). Objective We assessed relationships of LF power, including respiration-adjusted LF power (LFa), with cardiac sympathetic innervation and baroreflex function in subjects with or without neuroimaging evidence of cardiac sympathetic denervation. Methods Values for LF power at baseline supine, seated, and during the Valsalva maneuver were compared between subject groups with low or normal myocardial concentrations of 6-[(18)F]fluorodopamine-derived radioactivity. BCG was calculated from the slope of cardiac interbeat interval vs. systolic pressure during Phase II of the Valsalva maneuver or after i.v. nitroglycerine injection (the Oxford technique). Results LF and LFa were unrelated to myocardial 6-[(18)F]fluorodopamine-derived radioactivity. During sitting rest and the Valsalva maneuver logs of LF and LFa correlated positively with the log of Phase II BCG (r = 0.61, p = 0.0005; r = 0.47, p = 0.009; r = 0.69, p < 0.0001; r = 0.60, p = 0.0006). Groups with Low BCG (<= 3 ms/mmHg) had low LF and LFa regardless of cardiac innervation. The log of LF power during supine rest correlated with the log of Oxford BCG (r = 0.74, p < 0.0001). Conclusion LF power, with or without respiratory adjustment, reflects baroreflex modulation and not cardiac sympathetic tone. C1 [Rahman, Faisal; Pechnik, Sandra; Gross, Daniel; Sewell, LaToya; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC 1620,Bldg 10,Room 5N220, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov OI Rahman, Faisal/0000-0002-7946-0311 FU NIH, National Institute of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. Ms. Tereza Jenkins coordinated patient travel. Division of Intramural Research, NINDS, NIH. The authors have no conflicts of interest to disclose. NR 23 TC 60 Z9 64 U1 1 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD JUN PY 2011 VL 21 IS 3 BP 133 EP 141 DI 10.1007/s10286-010-0098-y PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 763PL UT WOS:000290572100001 PM 21279414 ER PT J AU Stanley, CJ Creighton, RA Gross, MT Garrett, WE Yu, B AF Stanley, Christopher J. Creighton, R. Alexander Gross, Michael T. Garrett, William E. Yu, Bing TI Effects of a Knee Extension Constraint Brace on Lower Extremity Movements after ACL Reconstruction SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ANTERIOR CRUCIATE LIGAMENT; STOP-JUMP TASK; GENDER-DIFFERENCES; MOTION PATTERNS; RISK-FACTORS; INJURY; STRAIN; REHABILITATION; KINEMATICS; FORCES AB Patients have high reinjury rates after ACL reconstruction. Small knee flexion angles and large peak posterior ground reaction forces in landing tasks increase ACL loading. We determined the effects of a knee extension constraint brace on knee flexion angle, peak posterior ground reaction force, and movement speed in functional activities of patients after ACL reconstruction. Six male and six female patients 3.5 to 6.5 months after ACL reconstruction participated in the study. Three-dimensional videographic and force plate data were collected while patients performed level walking, jogging, and stair descent wearing a knee extension constraint brace, wearing a nonconstraint brace, and not wearing a knee brace. Knee flexion angle at initial foot contact with the ground, peak posterior ground reaction force, and movement speed were compared across brace conditions and between genders. Wearing the knee extension constraint brace increased the knee flexion angle at initial foot contact for each activity when compared with the other two brace conditions. Wearing the knee extension constraint brace also decreased peak posterior ground reaction force during walking but not during jogging and stair descent. Although the knee extension constraint brace did not consistently reduce the peak posterior ground reaction force in all functional activities, it consistently increased knee flexion angle and should reduce ACL loading as suggested by previous studies. These results suggest the knee extension constraint brace has potential as a rehabilitation tool to alter lower extremity movement patterns of patients after ACL reconstruction to address high reinjury rates. Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. C1 [Gross, Michael T.; Yu, Bing] Univ N Carolina, Div Phys Therapy, Ctr Human Movement Sci, Chapel Hill, NC 27599 USA. [Stanley, Christopher J.] NIH, Bethesda, MD 20892 USA. [Creighton, R. Alexander; Yu, Bing] Univ N Carolina, Dept Orthopaed Surg, Chapel Hill, NC 27599 USA. [Garrett, William E.] Duke Univ, Med Ctr, Div Orthopaed Surg, Durham, NC 27710 USA. RP Yu, B (reprint author), Univ N Carolina, Div Phys Therapy, Ctr Human Movement Sci, CB 7135,Bondurant Hall, Chapel Hill, NC 27599 USA. EM byu@med.unc.edu FU DJO LLC (Vista, CA) FX One of the authors (BY) has received funding from DJO LLC (Vista, CA). All other authors certify that they have no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. NR 43 TC 10 Z9 10 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUN PY 2011 VL 469 IS 6 BP 1774 EP 1780 DI 10.1007/s11999-010-1633-9 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 763PE UT WOS:000290571400035 PM 21046300 ER PT J AU Eberlein, M Garrity, ER Orens, JB AF Eberlein, Michael Garrity, Edward R. Orens, Jonathan B. TI Lung Allocation in the United States SO CLINICS IN CHEST MEDICINE LA English DT Article DE Lung transplantation; Lung allocation; Lung allocation score ID TRANSPLANTATION; SCORE; SURVIVAL; IMPACT AB Lung allocation in the United States has changed significantly with the introduction of the Lung Allocation Score (LAS) system in May 2005. Since then, organ allocation is no longer based on waiting time but on a measure of transplant benefit (the difference between survival with vs without a transplant). The LAS system has met its primary goal of reducing time and mortality on the waiting list. Better understanding of pretransplant factors that influence long-term posttransplant outcomes of the individual patient will be instrumental in improving the LAS system in the future. C1 [Eberlein, Michael; Orens, Jonathan B.] Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. [Eberlein, Michael] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Garrity, Edward R.] Univ Chicago, Med Ctr, Div Pulm & Crit Care Med, Chicago, IL 60637 USA. RP Eberlein, M (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Div Pulm & Crit Care Med, 1830 E Monument St,5th floor, Baltimore, MD 21205 USA. EM meberle3@jhmi.edu NR 16 TC 23 Z9 23 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD JUN PY 2011 VL 32 IS 2 BP 213 EP + DI 10.1016/j.ccm.2011.02.004 PG 11 WC Respiratory System SC Respiratory System GA 764OX UT WOS:000290642500003 PM 21511084 ER PT J AU Gururajan, A Kamalakannan, S Sari-Sarraf, H Shahriar, M Long, R Antani, S AF Gururajan, Arunkumar Kamalakannan, Sridharan Sari-Sarraf, Hamed Shahriar, Muneem Long, Rodney Antani, Sameer TI On the creation of a segmentation library for digitized cervical and lumbar spine radiographs SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE Shape segmentation; Radiographic spine images; Segmentation library; Cervical spine segmentation; Lumbar spine segmentation AB In this paper, we address the issue of computer-assisted indexing in one specific case, i.e., for the 17,000 digitized images of the spine acquired during the National Health and Nutrition Examination Survey (NHANES). The crucial step in this process is to accurately segment the cervical and lumbar spine in the radiographic images. To that end, we have implemented a unique segmentation system that consists of a suite of spine-customized automatic and semi-automatic statistical shape segmentation algorithms. Using the aforementioned system, we have developed experiments to optimally generate a library of spine segmentations, which currently include 2000 cervical and 2000 lumbar spines. This work is expected to contribute toward the creation of a biomedical Content-Based Image Retrieval system that will allow retrieval of vertebral shapes by using query by image example or query by shape example. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Gururajan, Arunkumar; Kamalakannan, Sridharan; Sari-Sarraf, Hamed; Shahriar, Muneem] Texas Tech Univ, Dept Elect & Comp Engn, Lubbock, TX 79409 USA. [Long, Rodney; Antani, Sameer] Natl Lib Med, Commun Engn Lab, Bethesda, MD 20894 USA. RP Gururajan, A (reprint author), VuCOMP Inc, 1231 W Campbell Rd, Richardson, TX 75080 USA. EM arunkumar.gururajan@ttu.edu RI Shahriar, Selim/B-7270-2009; OI Antani, Sameer/0000-0002-0040-1387; Kamalakannan, Sridharan/0000-0003-4106-9728 FU National Institutes of Health (NIH); National Library of Medicine (NLM); Lister Hill National Center for Biomedical Communications (LHNCBC) FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Library of Medicine (NLM), and Lister Hill National Center for Biomedical Communications (LHNCBC). NR 15 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-6111 EI 1879-0771 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD JUN PY 2011 VL 35 IS 4 BP 251 EP 265 DI 10.1016/j.compmedimag.2010.11.006 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 762IF UT WOS:000290467900001 PM 21377835 ER PT J AU Roche, B Drake, JM Rohani, P AF Roche, Benjamin Drake, John M. Rohani, Pejman TI The curse of the Pharaoh revisited: evolutionary bi-stability in environmentally transmitted pathogens SO ECOLOGY LETTERS LA English DT Letter DE Adaptative dynamics; curse of the pharaoh; environmental transmission; evolutionary bi-stability ID AVIAN INFLUENZA-VIRUSES; VIRULENCE EVOLUTION; LIFE-HISTORY; WILD BIRDS; TRADE-OFF; TRANSMISSION; CHOLERA; DYNAMICS; STRAIN; SUPERINFECTION AB P>It is increasingly evident that for a number of high-profile pathogens, transmission involves both direct and environmental pathways. Much of the distinguished evolutionary theory has, however, focused on each of transmission component separately. Herein, we use the framework of adaptive dynamics to study the evolutionary consequences of mixed transmission. We find that environmental transmission can select for increased virulence when direct transmission is low. Increasing the efficiency of direct transmission gives rise to an evolutionary bi-stability, with coexistence of different levels of virulence. We conclude that the overlooked contribution of environmental transmission may explain the curious appearance of high virulence in pathogens that are typically only moderately pathogenic, as observed for avian influenza viruses and cholera. C1 [Roche, Benjamin; Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [Roche, Benjamin] UMI IRD UPMC 209 UMMISCO, F-93143 Bondy, France. [Drake, John M.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA. [Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. [Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Roche, B (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. EM benjamin.roche@ird.fr RI Drake, John/D-6622-2012; OI Roche, Benjamin/0000-0001-7975-4232; Drake, John/0000-0003-4646-1235 FU CLC NIH HHS [5U19CL000401] NR 48 TC 21 Z9 21 U1 0 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1461-023X J9 ECOL LETT JI Ecol. Lett. PD JUN PY 2011 VL 14 IS 6 BP 569 EP 575 DI 10.1111/j.1461-0248.2011.01619.x PG 7 WC Ecology SC Environmental Sciences & Ecology GA 763UE UT WOS:000290584400005 PM 21496194 ER PT J AU Koscso, B Csoka, B Pacher, P Hasko, G AF Koscso, Balazs Csoka, Balazs Pacher, Pal Hasko, Gyoergy TI Investigational A(3) adenosine receptor targeting agents SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE A(3) adenosine receptor; asthma; cancer; IB-MECA; rheumatoid arthritis ID NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; RHEUMATOID-ARTHRITIS PATIENTS; TRIGGERED RESPIRATORY BURST; ADJUVANT-INDUCED ARTHRITIS; ENDOTHELIAL GROWTH-FACTOR; COLON-CARCINOMA GROWTH; ISCHEMIC BRAIN-INJURY; CL-IB-MECA; MAST-CELLS AB Introduction: Adenosine is an endogenous nucleoside that accumulates in the extracellular space in response to metabolic stress and cell damage. Extracellular adenosine is a signaling molecule that signals by activating four GPCRs: the A(1), A(2A), A(2B) and A(3) receptors. Since the discovery of A(3) adenosine receptors, accumulating evidence has identified these receptors as potential targets for therapeutic intervention. Areas covered : A(3) adenosine receptors are expressed on the surface of most immune cell types, including neutrophils, macrophages, dendritic cells, lymphocytes and mast cells. A(3) adenosine receptor activation on immune cells governs a broad array of immune cell functions, which include cytokine production, degranulation, chemotaxis, cytotoxicity, apoptosis and proliferation. In accordance with their multitudinous immunoregulatory actions, targeting A(3) adenosine receptors has been shown to impact the course of a wide spectrum of immune-related diseases, such as asthma, rheumatoid arthritis, cancer, ischemia and inflammatory disorders. Expert opinion : Given the existence of both preclinical and early clinical data supporting the utility of A(3) adenosine receptor ligands in treating immune-related diseases, further development of A(3) adenosine receptor ligands is anticipated. C1 [Koscso, Balazs; Csoka, Balazs; Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, Bethesda, MD 20892 USA. [Hasko, Gyoergy] Univ Debrecen, Med & Hlth Sci Ctr, Dept Med Chem, H-4032 Debrecen, Hungary. RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA. EM haskoge@umdnj.edu RI Pacher, Pal/B-6378-2008; OI Pacher, Pal/0000-0001-7036-8108; Csoka, Balazs/0000-0002-7562-1130 FU National Institutes of Health [R01GM66189]; USAMRMC [09065004]; Hungarian Scientific Research Fund (OTKA) [CK 78275]; NIH/NIAAA FX The authors declare no conflict of interests. This work was supported by National Institutes of Health Grant R01GM66189, USAMRMC grant 09065004, Hungarian Scientific Research Fund (OTKA) grant CK 78275, and Intramural Research Program of NIH/NIAAA. NR 121 TC 11 Z9 11 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUN PY 2011 VL 20 IS 6 BP 757 EP 768 DI 10.1517/13543784.2011.573785 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 762OA UT WOS:000290488100005 PM 21457061 ER PT J AU Bhattacharjee, S Deterding, LJ Chatterjee, S Jiang, JJ Ehrenshaft, M Lardinois, O Ramirez, DC Tomer, KB Mason, RP AF Bhattacharjee, Suchandra Deterding, Leesa J. Chatterjee, Saurabh Jiang, JinJie Ehrenshaft, Marilyn Lardinois, Olivier Ramirez, Dario C. Tomer, Kenneth B. Mason, Ronald P. TI Site-specific radical formation in DNA induced by Cu(II)H2O2 oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Spin trapping; DNA radicals; Copper; Nucleosides; Cells; ESR; IST; LC-MS/MS; Detect; Identify; Free radicals ID TANDEM MASS-SPECTROMETRY; HYDROGEN-PEROXIDE; CHARGE-TRANSPORT; COMET ASSAY; ELECTRON-TRANSFER; OXIDATIVE DAMAGE; CELLULAR-DNA; NUCLEAR-DNA; BASE DAMAGE; 8-HYDROXYDEOXYGUANOSINE AB Oxidative stress-related damage to the DNA macromolecule produces a multitude of lesions that are implicated in mutagenesis, carcinogenesis, reproductive cell death, and aging. Many of these lesions have been studied and characterized by various techniques. Of the techniques that are available, the comet assay, HPLC-EC, GC-MS, HPLC-MS, and especially HPLC-MS/MS remain the most widely used and have provided invaluable information on these lesions. However, accurate measurement of DNA damage has been a matter of debate. In particular, there have been reports of artifactual oxidation leading to erroneously high damage estimates. Further, most of these techniques measure the end product of a sequence of events and thus provide only limited information on the initial radical mechanism. We report here a qualitative measurement of DNA damage induced by a Cu(II)-H2O2 oxidizing system using immuno-spin trapping (IST) with electron paramagnetic resonance (EPR), MS, and MS/MS. The radical generated is trapped by DMPO immediately upon formation. The DMPO adduct formed is initially EPR active but subsequently is oxidized to the stable nitrone, which can then be detected by IST and further characterized by MS and MS/MS. Published by Elsevier Inc. C1 [Bhattacharjee, Suchandra; Chatterjee, Saurabh; Jiang, JinJie; Ehrenshaft, Marilyn; Lardinois, Olivier; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Deterding, Leesa J.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Ramirez, Dario C.] Oklahoma Med Res Fdn, Free Rad Biol & Aging Res Program, Oklahoma City, OK 73104 USA. RP Bhattacharjee, S (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM bhattac1@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013; RAMIREZ, DARIO/K-3312-2013 OI RAMIREZ, DARIO/0000-0001-6725-3326 FU National Institutes of Health; National Institute of Environmental Health Sciences FX We gratefully acknowledge Jean Corbett for her unconditional help during all stages of the project. We thank Dr. Ann Motten and Mary Mason for their invaluable help in preparing the manuscript. We are very thankful to Dr. Mike P. Waalkes and Dr. Birandra Sinha for reviewing the manuscript. We thank Chrissy Pratter for the technical help. This work was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences. NR 56 TC 15 Z9 17 U1 1 U2 26 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 JUN 1 PY 2011 VL 50 IS 11 BP 1536 EP 1545 DI 10.1016/j.freeradbiomed.2011.02.034 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 764BP UT WOS:000290603700009 PM 21382477 ER PT J AU Espey, MG Chen, P Chalmers, B Drisko, J Sun, AY Levine, M Chen, Q AF Espey, Michael Graham Chen, Ping Chalmers, Brian Drisko, Jeanne Sun, Andrew Y. Levine, Mark Chen, Qi TI Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Pancreatic cancer; Drug synergy; Ascorbate; Vitamin C; Gemcitabine; Free radicals ID DOSE VITAMIN-C; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; DNA-DAMAGE; MESENCHYMAL TRANSITION; INDUCED CYTOTOXICITY; CONTROLLED-TRIAL; DRUG-RESISTANCE; CELLS; ACID AB Conventional treatment approaches have had little impact on the course of pancreatic cancer, which has the highest fatality rate among cancers. Gemcitabine, the primary therapeutic agent for pancreatic carcinoma, produces minimal survival benefit as a single agent. Therefore, numerous efforts have focused on gemcitabine combination treatments. Using a ratio design, this study established that combining pharmacologically achievable concentrations of ascorbate with gemcitabine resulted in a synergistic cytotoxic response in eight pancreatic tumor cell lines. Sensitization was evident regardless of inherent gemcitabine resistance and epithelial-mesenchymal phenotype. Our analysis suggested that the promiscuous oxidative actions of H(2)O(2) derived from pharmacologic ascorbate can culminate in synergism independent of the cancer cell's underlying phenotype and resistance to gemcitabine monotherapy. Gemcitabine-ascorbate combinations administered to mice bearing pancreatic tumor xenografts consistently enhanced inhibition of growth compared to gemcitabine alone, produced 50% growth inhibition in a tumor type not responsive to gemcitabine, and demonstrated a gemcitabine dose-sparing effect. These data support the testing of pharmacologic ascorbate in adjunctive treatments for cancers prone to high failure rates with conventional therapeutic regimens, such as pancreatic cancer. (C) 2011 Elsevier Inc. All rights reserved. C1 [Chen, Ping; Chalmers, Brian; Drisko, Jeanne; Chen, Qi] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Program Integrat Med, Kansas City, KS 66160 USA. [Chen, Ping] Xi An Jiao Tong Univ, Sch Med, Dept Genet & Mol Biol, Xian 710061, Peoples R China. [Espey, Michael Graham; Sun, Andrew Y.; Levine, Mark] NIDDKD, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Chen, Q (reprint author), Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Program Integrat Med, Kansas City, KS 66160 USA. EM qchen@kumc.edu RI Chen, Qi/D-8278-2015 OI Chen, Qi/0000-0002-7173-8411 FU American Cancer Society [QK84541F]; NIDDK, NIH; Hilton Family Foundation FX This research was supported by an American Cancer Society Institutional Research Pilot Grant (QK84541F) and in part by the Intramural Research Program of the NIDDK, NIH, and The Hilton Family Foundation. NR 60 TC 47 Z9 47 U1 1 U2 11 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 JUN 1 PY 2011 VL 50 IS 11 BP 1610 EP 1619 DI 10.1016/j.freeradbiomed.2011.03.007 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 764BP UT WOS:000290603700017 PM 21402145 ER PT J AU Boyd, O Weng, P Sun, XP Alberico, T Laslo, M Obenland, DM Kern, B Zou, S AF Boyd, Olga Weng, Peter Sun, Xiaoping Alberico, Thomas Laslo, Mara Obenland, David M. Kern, Bradley Zou, Sige TI Nectarine promotes longevity in Drosophila melanogaster SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Aging; Nectarine; Peach; Life span; Oxidative stress; Reproductive aging; JNK signaling pathway; Nutraceutical; 4-Hydroxynonenal-protein adduct; Free radicals ID LIFE-SPAN EXTENSION; DIETARY-RESTRICTION; PHENOLIC-COMPOUNDS; CAENORHABDITIS-ELEGANS; ANASTREPHA-LUDENS; DNA-DAMAGE; FRUIT-FLY; RESVERATROL; PEACH; POLYPHENOLS AB Fruits containing high antioxidant capacities and other bioactivities are ideal for promoting longevity and health span. However, few fruits are known to improve the survival and health span in animals, let alone the underlying mechanisms. Here we investigate the effects of nectarine, a globally consumed fruit, on life span and health span in Drosophila melanogaster. Wild-type flies were fed standard, dietary restriction (DR), or high-fat diet supplemented with 0-4% nectarine extract. We measured life span, food intake, locomotor activity, fecundity, gene expression changes, and oxidative damage indicated by the level of 4-hydroxynonenal-protein adduct in these flies. We also measured life span, locomotor activity, and oxidative damage in sod1 mutant flies on the standard diet supplemented with 0-4% nectarine. Supplementation with 4% nectarine extended life span, increased fecundity, and decreased expression of some metabolic genes, including a key gluconeogenesis gene, PEPCK, and oxidative stress-response genes, including peroxiredoxins, in female wild-type flies fed the standard, DR, or high-fat diet. Nectarine reduced oxidative damage in wildtype females fed the high-fat diet. Moreover, nectarine improved the survival of and reduced oxidative damage in female sod1 mutant flies. Together, these findings suggest that nectarine promotes longevity and health span partly by modulating glucose metabolism and reducing oxidative damage. Published by Elsevier Inc. C1 [Boyd, Olga; Weng, Peter; Sun, Xiaoping; Alberico, Thomas; Laslo, Mara; Kern, Bradley; Zou, Sige] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Obenland, David M.] ARS, USDA, Parlier, CA 93648 USA. RP Zou, S (reprint author), NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. EM zous@mail.nih.gov FU National Institute on Aging, NIH FX We thank Paul Neipp for preparing the nectarine extract, Dr. Vilhelm Bohr for encouraging us to initiate this study, and Dr. Nan-ping Weng and Edward Spangler for valuable comments and suggestions on the manuscript. This study was supported by the Intramural Research Program of the National Institute on Aging, NIH, to S.Z. NR 66 TC 27 Z9 29 U1 1 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 JUN 1 PY 2011 VL 50 IS 11 BP 1669 EP 1678 DI 10.1016/j.freeradbiomed.2011.03.011 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 764BP UT WOS:000290603700023 PM 21406223 ER PT J AU Wahl, M Huebers, A Lauterbach-Soon, B Hattingen, E Jung, P Cohen, LG Ziemann, U AF Wahl, Mathias Huebers, Annemarie Lauterbach-Soon, Birgit Hattingen, Elke Jung, Patrick Cohen, Leonardo G. Ziemann, Ulf TI Motor Callosal Disconnection in Early Relapsing-Remitting Multiple Sclerosis SO HUMAN BRAIN MAPPING LA English DT Article DE motor corpus callosum; diffusion tensor imaging; interhemispheric inhibition; effective connectivity; bifocal transcranial magnetic stimulation; multiple sclerosis ID APPEARING WHITE-MATTER; ANISOTROPIC WATER DIFFUSION; ADAPTIVE FUNCTIONAL-CHANGES; SINGLE CLINICAL ATTACK; HUMAN CORPUS-CALLOSUM; INTERHEMISPHERIC INHIBITION; MAGNETIC-RESONANCE; HUMAN BRAIN; NERVOUS-SYSTEM; FOLLOW-UP AB In relapsing-remitting multiple sclerosis (RRMS) the corpus callosum (CC) is often and early affected by macroscopic lesions when investigated by conventional MRI. We sought to determine to which extent microstructural and effective disconnection of the CC are already present in RRMS patients at the earliest stages of the disease prior to evidence of macroscopic CC lesion. We compared 16 very early RRMS patients (median expanded disability status scale (EDSS), 1.5; range, 0-2.0) to an age-matched group of healthy controls and focused analysis to the motor CC, i.e. that part of the CC relaying interhemispheric motor information. A combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure was applied to identify the callosal motor fibers (CMFs) connecting the hand areas of the primary motor cortices of the two hemispheres. Fractional anisotropy (FA) within the motor CC (FA-CC) assessed the CMF microstructural integrity. Bifocal paired transcranial magnetic stimulation (TMS) tested short-interval interhemispheric inhibition (S-IHI), an established measure of CMF effective connectivity. FA-CC and S-IHI were significantly reduced in early RRMS compared to healthy controls. Furthermore, a significant linear correlation between microstructure (FA-CC) and function (S-IHI) in the controls was broken down in the patients. These abnormalities were obtained in the absence of macroscopic CMF lesion in conventional MRI, and whilst motor hand/arm function in the nine-hole-peg test and corticospinal conduction time were normal. Findings suggest that reductions in FA and S-IHI may serve as surrogate markers of motor callosal disconnection at the earliest stages of RRMS prior to development of macroscopic lesion. Hum Brain Mapp 32:846-855, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Wahl, Mathias; Huebers, Annemarie; Lauterbach-Soon, Birgit; Jung, Patrick; Ziemann, Ulf] Goethe Univ Frankfurt, Dept Neurol, D-60528 Frankfurt, Germany. [Hattingen, Elke] Goethe Univ Frankfurt, Inst Neuroradiol, D-60528 Frankfurt, Germany. [Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. RP Ziemann, U (reprint author), Goethe Univ Frankfurt, Dept Neurol, Schleusenweg 2-16, D-60528 Frankfurt, Germany. EM u.ziemann@em.uni-frankfurt.de RI Hattingen, Elke/D-7880-2015 FU TEVA Pharma GmbH; Heinrich und Erna Schaufler Stiftung FX Contract grant sponsors: TEVA Pharma GmbH; Heinrich und Erna Schaufler Stiftung. NR 56 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUN PY 2011 VL 32 IS 6 BP 846 EP 855 DI 10.1002/hbm.21071 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 762AX UT WOS:000290445800002 PM 21495114 ER PT J AU Parikh, H Wang, ZM Pettigrew, KA Jia, JP Daugherty, S Yeager, M Jacobs, KB Hutchinson, A Burdett, L Cullen, M Qi, LQ Boland, J Collins, I Albert, TJ Vatten, LJ Hveem, K Njolstad, I Cancel-Tassin, G Cussenot, O Valeri, A Virtamo, J Thun, MJ Feigelson, HS Diver, WR Chatterjee, N Thomas, G Albanes, D Chanock, SJ Hunter, DJ Hoover, R Hayes, RB Berndt, SI Sampson, J Amundadottir, L AF Parikh, Hemang Wang, Zhaoming Pettigrew, Kerry A. Jia, Jinping Daugherty, Sarah Yeager, Meredith Jacobs, Kevin B. Hutchinson, Amy Burdett, Laura Cullen, Michael Qi, Liqun Boland, Joseph Collins, Irene Albert, Thomas J. Vatten, Lars J. Hveem, Kristian Njolstad, Inger Cancel-Tassin, Geraldine Cussenot, Olivier Valeri, Antoine Virtamo, Jarmo Thun, Michael J. Feigelson, Heather Spencer Diver, W. Ryan Chatterjee, Nilanjan Thomas, Gilles Albanes, Demetrius Chanock, Stephen J. Hunter, David J. Hoover, Robert Hayes, Richard B. Berndt, Sonja I. Sampson, Joshua Amundadottir, Laufey TI Fine mapping the KLK3 locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; MULTIPLE; RISK; MORTALITY; VARIANTS; PROFILE; COHORT; 8Q24 AB Measurements of serum prostate-specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (KLK3) have been shown to be associated with both serum PSA levels and prostate cancer. Based on a resequencing analysis of a 56 kb region on chromosome 19q13.33, centered on the KLK3 gene, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five case-control studies. We did not observe a strong association with the KLK3 variant, reported in previous studies to confer risk for prostate cancer (rs2735839; P = 0.20) but did observe three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) associated with prostate cancer [P = 3.41 x 10(-4), per-allele trend odds ratio (OR) = 0.77, 95% CI = 0.67-0.89]. The signal was apparent only for nonaggressive prostate cancer cases with Gleason score < 7 and disease stage < III (P = 4.72 x 10(-5), per-allele trend OR = 0.68, 95% CI = 0.57-0.82) and not for advanced cases with Gleason score > 8 or stage a parts per thousand yenIII (P = 0.31, per-allele trend OR = 1.12, 95% CI = 0.90-1.40). One of the three highly correlated SNPs, rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact. Baseline PSA levels were 43.7% higher in control subjects with no minor alleles (1.61 ng/ml, 95% CI = 1.49-1.72) than in those with one or more minor alleles at any one of the three SNPs (1.12 ng/ml, 95% CI = 0.96-1.28) (P = 9.70 x 10(-5)). Together our results suggest that germline KLK3 variants could influence the diagnosis of nonaggressive prostate cancer by influencing the likelihood of biopsy. C1 [Amundadottir, Laufey] NIH, Lab Translat Genom, Div Canc Epidemiol & Genet, Gaithersburg, MD 20877 USA. [Parikh, Hemang; Pettigrew, Kerry A.; Jia, Jinping; Collins, Irene; Amundadottir, Laufey] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA. [Wang, Zhaoming; Yeager, Meredith; Jacobs, Kevin B.; Hutchinson, Amy; Burdett, Laura; Cullen, Michael; Qi, Liqun; Boland, Joseph] SAIC Frederick Inc, Core Genotyping Facil, NCI Frederick, Frederick, MD 21702 USA. [Pettigrew, Kerry A.] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland. [Albert, Thomas J.] Roche NimbleGen, Madison, WI 53711 USA. [Vatten, Lars J.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, N-7489 Trondheim, Norway. [Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, N-9037 Tromso, Norway. [Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine] Hop Tenon, AP HP, Ctr Rech Pathol Prostat CeRePP, F-75020 Paris, France. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00300, Finland. [Thun, Michael J.; Feigelson, Heather Spencer; Diver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Thomas, Gilles] Ctr Leon Berard, INSERM, U590, F-69373 Lyon 08, France. [Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, Dept Environm Med, New York, NY 10016 USA. RP Amundadottir, L (reprint author), NIH, Lab Translat Genom, Div Canc Epidemiol & Genet, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM amundadottirl@mail.nih.gov RI Pettigrew, Kerry/B-2485-2013; Albanes, Demetrius/B-9749-2015; Amundadottir, Laufey/L-7656-2016; OI Pettigrew, Kerry/0000-0002-6027-0462; Amundadottir, Laufey/0000-0003-1859-8971; Hayes, Richard/0000-0002-0918-661X; Cancel-Tassin, Geraldine/0000-0002-9583-6382 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH); Ireland-Northern Ireland-National Cancer Institute Cancer Consortium; Royal Society FX This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH). K. A. P was supported through an "Ireland-Northern Ireland-National Cancer Institute Cancer Consortium, Joint Research Project in Cancer" fellowship and a Royal Society international travel grant. The authors thank Drs. Christine Berg and Philip Prorok, Division of Cancer Prevention, NCI, the screening center investigators and staff of the PLCO Cancer Screening Trial, Mr. Thomas Riley and staff at Information Management Services, Inc., and Ms. Barbara O'Brien and staff at Westat, Inc. for their contributions to the PLCO Cancer Screening Trial. Finally, we acknowledge and thank the study participants for donating their time and making this study possible. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. NR 33 TC 21 Z9 21 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 2011 VL 129 IS 6 BP 675 EP 685 DI 10.1007/s00439-011-0953-5 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 763FO UT WOS:000290540900009 PM 21318478 ER PT J AU Kote-Jarai, Z Al Olama, AA Leongamornlert, D Tymrakiewicz, M Saunders, E Guy, M Giles, GG Severi, G Southey, M Hopper, JL Sit, KC Harris, JM Batra, J Spurdle, AB Clements, JA Hamdy, F Neal, D Donovan, J Muir, K Pharoah, PDP Chanock, SJ Brown, N Benlloch, S Castro, E Mahmud, N O'Brien, L Hall, A Sawyer, E Wilkinson, R Easton, DF Eeles, RA AF Kote-Jarai, Z. Al Olama, A. Amin Leongamornlert, D. Tymrakiewicz, M. Saunders, E. Guy, M. Giles, G. G. Severi, G. Southey, M. Hopper, J. L. Sit, K. C. Harris, J. M. Batra, J. Spurdle, A. B. Clements, J. A. Hamdy, F. Neal, D. Donovan, J. Muir, K. Pharoah, P. D. P. Chanock, S. J. Brown, N. Benlloch, S. Castro, E. Mahmud, N. O'Brien, L. Hall, A. Sawyer, E. Wilkinson, R. Easton, D. F. Eeles, R. A. TI Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript SO HUMAN GENETICS LA English DT Article ID MOLECULAR-DYNAMICS; ANTIGEN; KALLIKREINS; SIMULATION; FAMILY; RISK; LOCI AB Genome-wide association studies (GWAS) have identified more than 30 prostate cancer (PrCa) susceptibility loci. One of these (rs2735839) is located close to a plausible candidate susceptibility gene, KLK3, which encodes prostate-specific antigen (PSA). PSA is widely used as a biomarker for PrCa detection and disease monitoring. To refine the association between PrCa and variants in this region, we used genotyping data from a two-stage GWAS using samples from the UK and Australia, and the Cancer Genetic Markers of Susceptibility (CGEMS) study. Genotypes were imputed for 197 and 312 single nucleotide polymorphisms (SNPs) from HapMap2 and the 1000 Genome Project, respectively. The most significant association with PrCa was with a previously unidentified SNP, rs17632542 (combined P = 3.9 x 10(-22)). This association was confirmed by direct genotyping in three stages of the UK/Australian GWAS, involving 10,405 cases and 10,681 controls (combined P = 1.9 x 10(-34)). rs17632542 is also shown to be associated with PSA levels and it is a non-synonymous coding SNP (Ile179Thr) in KLK3. Using molecular dynamic simulation, we showed evidence that this variant has the potential to introduce alterations in the protein or affect RNA splicing. We propose that rs17632542 may directly influence PrCa risk. C1 [Kote-Jarai, Z.; Leongamornlert, D.; Tymrakiewicz, M.; Saunders, E.; Guy, M.; Brown, N.; Castro, E.; Mahmud, N.; O'Brien, L.; Hall, A.; Sawyer, E.; Wilkinson, R.; Eeles, R. A.] Inst Canc Res, Sutton SM2 5NG, Surrey, England. [Al Olama, A. Amin; Benlloch, S.; Easton, D. F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Epidemiol, Strangeways Lab, Cambridge CB1 8RN, England. [Giles, G. G.; Severi, G.; Southey, M.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia. [Giles, G. G.; Severi, G.; Southey, M.; Hopper, J. L.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia. [Sit, K. C.; Harris, J. M.; Batra, J.; Clements, J. A.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Kelvin Grove, Qld 4059, Australia. [Spurdle, A. B.] Queensland Inst Med Res, Genet & Populat Hlth Div, Herston, Qld 4006, Australia. [Hamdy, F.] Univ Oxford, Nuffield Dept Surg, Oxford OX3 9DU, England. [Neal, D.] Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Cambridge CB2 2QQ, England. [Neal, D.] Univ Cambridge, Addenbrookes Hosp, Dept Surg, Cambridge CB2 2QQ, England. [Donovan, J.] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Muir, K.] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Al Olama, A. Amin; Pharoah, P. D. P.; Benlloch, S.; Easton, D. F.] Univ Cambridge, Dept Oncol, Strangeways Lab, Cambridge CB1 8RN, England. [Chanock, S. J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Eeles, R. A.] Royal Marsden NHS Fdn Trust, Surrey SM2 5PT, England. RP Kote-Jarai, Z (reprint author), Inst Canc Res, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England. EM zsofia.kote-jarai@icr.ac.uk RI Batra, Jyotsna/B-4130-2011; Castro, Elena/K-9043-2014; Spurdle, Amanda/A-4978-2011; OI Saunders, Ed/0000-0003-4343-3570; Eeles, Rosalind/0000-0002-3698-6241; Spurdle, Amanda/0000-0003-1337-7897; Neal, David/0000-0002-6033-5086; Leongamornlert, Daniel/0000-0002-3486-3168; Giles, Graham/0000-0003-4946-9099; Clements, Judith/0000-0001-6026-1964 FU Cancer Research UK [10119, 10118, 10124, 11021, A10119, A10124]; Medical Research Council [G0900871] NR 19 TC 45 Z9 45 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 2011 VL 129 IS 6 BP 687 EP 694 DI 10.1007/s00439-011-0981-1 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 763FO UT WOS:000290540900010 PM 21465221 ER PT J AU Fox, ER Young, JH Li, YL Dreisbach, AW Keating, BJ Musani, SK Liu, K Morrison, AC Ganesh, S Kutlar, A Ramachandran, VS Polak, JF Fabsitz, RR Dries, DL Farlow, DN Redline, S Adeyemo, A Hirschorn, JN Sun, YV Wyatt, SB Penman, AD Palmas, W Rotter, JI Townsend, RR Doumatey, AP Tayo, BO Mosley, TH Lyon, HN Kang, SJ Rotimi, CN Cooper, RS Franceschini, N Curb, JD Martin, LW Eaton, CB Kardia, SLR Taylor, HA Caulfield, MJ Ehret, GB Johnson, T Chakravarti, A Zhu, XF Levy, D AF Fox, Ervin R. Young, J. Hunter Li, Yali Dreisbach, Albert W. Keating, Brendan J. Musani, Solomon K. Liu, Kiang Morrison, Alanna C. Ganesh, Santhi Kutlar, Abdullah Ramachandran, Vasan S. Polak, Josef F. Fabsitz, Richard R. Dries, Daniel L. Farlow, Deborah N. Redline, Susan Adeyemo, Adebowale Hirschorn, Joel N. Sun, Yan V. Wyatt, Sharon B. Penman, Alan D. Palmas, Walter Rotter, Jerome I. Townsend, Raymond R. Doumatey, Ayo P. Tayo, Bamidele O. Mosley, Thomas H., Jr. Lyon, Helen N. Kang, Sun J. Rotimi, Charles N. Cooper, Richard S. Franceschini, Nora Curb, J. David Martin, Lisa W. Eaton, Charles B. Kardia, Sharon L. R. Taylor, Herman A. Caulfield, Mark J. Ehret, Georg B. Johnson, Toby Chakravarti, Aravinda Zhu, Xiaofeng Levy, Daniel CA Int Consortium Blood Pressure Geno TI Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HYPERTENSION PREVALENCE; RECEPTOR; DISEASE; FAMILY; LOCI; VASCULATURE; AWARENESS; TRAITS; DESIGN AB The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P = 3.6 x 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P = 4.7 x 10(-8)). The top IBC association for SBP was rs2012318 (P = 6.4 x 10(-6)) near SLC25A42 and for DBP was rs2523586 (P = 1.3 x 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n 5 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P = 0.009; TBX3-TBX5, P = 0.03; and CSK-ULK3, P = 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. C1 [Fox, Ervin R.; Dreisbach, Albert W.; Musani, Solomon K.; Penman, Alan D.; Mosley, Thomas H., Jr.; Taylor, Herman A.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Wyatt, Sharon B.] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA. [Young, J. Hunter] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Young, J. Hunter] Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD USA. [Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA. [Li, Yali; Kang, Sun J.; Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Redline, Susan] Case Western Reserve Univ, Div Clin Epidemiol, Cleveland, OH 44106 USA. [Keating, Brendan J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Dries, Daniel L.; Townsend, Raymond R.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Morrison, Alanna C.] Univ Texas Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Ganesh, Santhi] Univ Michigan Hlth Syst, Div Cardiovasc Med, Ann Arbor, MI USA. [Kutlar, Abdullah] Med Coll Georgia, Augusta, GA USA. [Ramachandran, Vasan S.] Boston Univ, Sch Med, Dept Med, Framingham, MA USA. [Polak, Josef F.] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA USA. [Fabsitz, Richard R.] NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD USA. [Farlow, Deborah N.] MIT & Harvard, Broad Inst, Cambridge, MA USA. [Adeyemo, Adebowale; Doumatey, Ayo P.; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD USA. [Hirschorn, Joel N.; Lyon, Helen N.] Childrens Hosp Boston, Dept Genet, Boston, MA USA. [Sun, Yan V.; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Tayo, Bamidele O.; Cooper, Richard S.] Loyola Univ, Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA. [Franceschini, Nora] Univ N Carolina, UNC Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Curb, J. David] Pacific Hlth Res Inst, Honolulu, HI USA. [Martin, Lisa W.] George Washington Univ, Div Cardiol, Washington, DC USA. [Eaton, Charles B.] Brown Univ, Div Biol & Med, Providence, RI 02912 USA. [Caulfield, Mark J.; Johnson, Toby] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Genome Ctr, London, England. [Ehret, Georg B.] Univ Hosp Geneva, Dept Cardiol, Geneva, Switzerland. RP Fox, ER (reprint author), Univ Mississippi, Med Ctr, Dept Med, 2500 N State St, Jackson, MS 39216 USA. EM efox@umc.edu RI Smith, Albert Vernon/K-5150-2015; Mattace- Raso, Francesco/L-2541-2015; Polasek, Ozren/B-6002-2011; Meitinger, Thomas/O-1318-2015; Prokopenko, Inga/H-3241-2014; Lyytikainen, Leo-Pekka/C-8544-2016; Shi, Gang/D-3301-2016; Matullo, Giuseppe/K-6383-2016; Bochud, Murielle/A-3981-2010; Johnson, Andrew/G-6520-2013; Sun, Yan/A-7461-2008; Grobbee, Diederick/C-7651-2014; Palmer, Lyle/K-3196-2014; Onland-Moret, N. Charlotte/G-9185-2011; Gudnason, Vilmundur/K-6885-2015; Singleton, Andrew/C-3010-2009; Arora, Pankaj/F-3437-2011; EHRET, Georg/A-9532-2009; Lucas, Gavin/D-4346-2012; Rudan, Igor/I-1467-2012; Laan, Maris/A-4100-2011; Kuznetsova, Tatiana/I-6882-2013; Colaus, PsyColaus/K-6607-2013 OI Kivimaki, Mika/0000-0002-4699-5627; Johnson, Toby/0000-0002-5998-3270; Ikram, Mohammad Arfan/0000-0003-0372-8585; Smith, Albert Vernon/0000-0003-1942-5845; Martin, Lisa Warsinger/0000-0003-4352-0914; Ramachandran, Vasan/0000-0001-7357-5970; Humphries, Stephen E/0000-0002-8221-6547; Adeyemo, Adebowale/0000-0002-3105-3231; Watkins, Hugh/0000-0002-5287-9016; Marmot, Michael/0000-0002-2431-6419; Lawlor, Debbie A/0000-0002-6793-2262; Bergmann, Sven/0000-0002-6785-9034; Wain, Louise/0000-0003-4951-1867; Polasek, Ozren/0000-0002-5765-1862; Prokopenko, Inga/0000-0003-1624-7457; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Bochud, Murielle/0000-0002-5727-0218; Seshadri, Sudha/0000-0001-6135-2622; Org, Elin/0000-0003-1451-9375; Grobbee, Diederick/0000-0003-4472-4468; Palmer, Lyle/0000-0002-1628-3055; Gudnason, Vilmundur/0000-0001-5696-0084; Arora, Pankaj/0000-0003-2420-3550; EHRET, Georg/0000-0002-5730-0675; Rudan, Igor/0000-0001-6993-6884; Laan, Maris/0000-0002-8519-243X; Kuznetsova, Tatiana/0000-0003-3564-7405; FU National Heart, Lung, and Blood Institute; National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-32102, 32105, 32106, 32108, 32109, 32111-32113, 32115, 32118, 32119, 32122, 42107-42126, 42129-42132, 44221]; National Institutes of Health, National Heart, Lung, Blood Institute [HL087660, HL100245, HL074166]; National Institute on Minority Health and Health Disparities [MD002249]; Barts and The London Cardiovascular Biomedical Research Unit; National Heart, Lung, Blood Institute [HL086694, HL086718]; National Human Genome Research Institute [HG003054]; NIGMS/MBRS/SCORE; NHGRI/NIH [Z01HG200362]; NIH/NHLBI; University of Mississippi Medical Center FX The CARe authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. The following nine parent studies have contributed parent study data, ancillary study data and DNA samples through the Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community. Atherosclerotic Risk in Communities (ARIC): University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55017), University of North Carolina, Forsyth County (N01-HC-55018); Cardiovascular Health Study (CHS): University of Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of Pittsburgh (N01-HC-85082), University of California, Davis (N01-HC-85083), University of California, Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), University of Washington (N01 HC-55222, U01 HL080295); Cleveland Family Study (CFS): Case Western Reserve University (RO1 HL46380-01-16); Cooperative Study of Sickle Cell Disease (CSSCD): University of Illinois (N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB-72994), University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children's Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston, Inc.; (N01-HB-73003), Children's Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St Luke's Hospital-New York (N01-HB-73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB-97058), St Jude's Children's Research Hospital (N01-HB-97066), Research Foundation, State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart Study (FHS): Boston University (N01-HC-25195); Jackson Heart Study (JHS): Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington (N01-HC-95159), Regents of the University of California (01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Johns Hopkins University (N01-HC-95168), Harbor-UCLA Research and Education Institute (N01-HC-95169); Sleep Heart Health Study (SHHS): Johns Hopkins University (U01 HL064360), Case Western University (U01 HL063463), University of California, Davis (U01 HL053916), University of Arizona (U01 HL053938), University of Minnesota (relocating in 2006 to University Arizona) (U01 HL053934), University of Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar Research Institute (U01 HL063429), Johns Hopkins University (U01 HL053937). The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-32102, 32105, 32106, 32108, 32109, 32111-32113, 32115, 32118, 32119, 32122, 42107-42126, 42129-42132, and 44221. Genetic Epidemiology Network of Arteriopathy (GENOA) study is supported by the National Institutes of Health, grant numbers HL087660 and HL100245 from National Heart, Lung, Blood Institute, and MD002249 from National Institute on Minority Health and Health Disparities. M.J.C. and T.J.'s contribution was facilitated by National Institute for Health Research support of the Barts and The London Cardiovascular Biomedical Research Unit. A. C. and a portion of the genotyping supported by HL086694 from National Heart, Lung, Blood Institute. Maywood African-American study are supported by the National Institutes of Health, grant number HL074166 from the National Heart, Lung, Blood Institute. Y.L. and X.Z. are supported by HL086718 from National Heart, Lung, Blood Institute and HG003054 from the National Human Genome Research Institute. The Howard University Family Study (HUFS) was supported by NIGMS/MBRS/SCORE grants to C.N.R. and A. A.; with additional support from the Coriell Institute for Biomedical Sciences and the Intramural Research Program in the Center for Research in Genomics and Global Health, NHGRI/IH (Z01HG200362). The ICBP-GWAS consortium was supported by many funding bodies including NIH/NHLBI, European and private funding agencies. Many of the participating studies and authors in ICBP-GWAS are members of the CHARGE and Global BPgen consortia. Details are provided in ref. 11. Funding to pay the Open Access publication charges for this article was provided by Herman Taylor, University of Mississippi Medical Center. NR 32 TC 78 Z9 84 U1 2 U2 17 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 JUN 1 PY 2011 VL 20 IS 11 BP 2273 EP 2284 DI 10.1093/hmg/ddr092 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 763WG UT WOS:000290589800017 PM 21378095 ER PT J AU Zhu, XF Young, JH Fox, E Keating, BJ Franceschini, N Kang, SJ Tayo, B Adeyemo, A Sun, YV Li, YL Morrison, A Newton-Cheh, C Liu, K Ganesh, SK Kutlar, A Vasan, RS Dreisbach, A Wyatt, S Polak, J Palmas, W Musani, S Taylor, H Fabsitz, R Townsend, RR Dries, D Glessner, J Chiang, CWK Mosley, T Kardia, S Curb, D Hirschhorn, JN Rotimi, C Reiner, A Eaton, C Rotter, JI Cooper, RS Redline, S Chakravarti, A Levy, D AF Zhu, Xiaofeng Young, J. H. Fox, Ervin Keating, Brendan J. Franceschini, Nora Kang, Sunjung Tayo, Bamidele Adeyemo, Adebowale Sun, Yun V. Li, Yali Morrison, Alanna Newton-Cheh, Christopher Liu, Kiang Ganesh, Santhi K. Kutlar, Abdullah Vasan, Ramachandran S. Dreisbach, Albert Wyatt, Sharon Polak, Joseph Palmas, Walter Musani, Solomon Taylor, Herman Fabsitz, Richard Townsend, Raymond R. Dries, Daniel Glessner, Joseph Chiang, Charleston W. K. Mosley, Thomas Kardia, Sharon Curb, David Hirschhorn, Joel N. Rotimi, Charles Reiner, Alexander Eaton, Charles Rotter, Jerome I. Cooper, Richard S. Redline, Susan Chakravarti, Aravinda Levy, Daniel TI Combined admixture mapping and association analysis identifies a novel blood pressure genetic locus on 5p13: contributions from the CARe consortium SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; NATRIURETIC PEPTIDE SYSTEM; MULTILOCUS GENOTYPE DATA; POPULATION-STRUCTURE; QUANTITATIVE TRAITS; ADMIXED POPULATIONS; AFRICAN-AMERICANS; DISEASE GENES; LINKAGE; HYPERTENSION AB Admixture mapping based on recently admixed populations is a powerful method to detect disease variants with substantial allele frequency differences in ancestral populations. We performed admixture mapping analysis for systolic blood pressure (SBP) and diastolic blood pressure (DBP), followed by trait-marker association analysis, in 6303 unrelated African-American participants of the Candidate Gene Association Resource (CARe) consortium. We identified five genomic regions (P < 0.001) harboring genetic variants contributing to inter-individual BP variation. In follow-up association analyses, correcting for all tests performed in this study, three loci were significantly associated with SBP and one significantly associated with DBP (P < 10 25). Further analyses suggested that six independent single-nucleotide polymorphisms (SNPs) contributed to the phenotypic variation observed in the admixture mapping analysis. These six SNPs were examined for replication in multiple, large, independent studies of African-Americans [Women's Health Initiative (WHI), Maywood, Genetic Epidemiology Network of Arteriopathy (GENOA) and Howard University Family Study (HUFS)] as well as one native African sample (Nigerian study), with a total replication sample size of 11 882. Meta-analysis of the replication set identified a novel variant (rs7726475) on chromosome 5 between the SUB1 and NPR3 genes, as being associated with SBP and DBP (P < 0.0015 for both); in meta-analyses combining the CARe samples with the replication data, we observed P-values of 4.45 x 10(-7) for SBP and 7.52 x 10(-7) for DBP for rs7726475 that were significant after accounting for all the tests performed. Our study highlights that admixture mapping analysis can help identify genetic variants missed by genome-wide association studies because of drastically reduced number of tests in the whole genome. C1 [Zhu, Xiaofeng; Kang, Sunjung; Li, Yali] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Young, J. H.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Fox, Ervin; Dreisbach, Albert; Musani, Solomon; Taylor, Herman; Mosley, Thomas] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Wyatt, Sharon] Univ Mississippi, Med Ctr, Sch Nursing, Jackson, MS 39216 USA. [Keating, Brendan J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Townsend, Raymond R.; Dries, Daniel] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, UNC Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Tayo, Bamidele; Cooper, Richard S.] Loyola Univ, Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA. [Adeyemo, Adebowale; Rotimi, Charles] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Sun, Yun V.; Kardia, Sharon] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Morrison, Alanna] Univ Texas Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA. [Newton-Cheh, Christopher] Harvard Univ, Harvard & MIT, Broad Inst, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Redline, Susan] Harvard Univ, Dept Med, Boston, MA 02115 USA. [Chiang, Charleston W. K.; Hirschhorn, Joel N.] Harvard Univ, Childrens Hosp Boston, Dept Genet, Boston, MA 02115 USA. [Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Ganesh, Santhi K.] Univ Michigan Hlth Syst, Div Cardiovasc Med, Ann Arbor, MI USA. [Kutlar, Abdullah] Med Coll Georgia, Augusta, GA 30912 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Framingham, MA USA. [Polak, Joseph] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA USA. [Palmas, Walter] Columbia Univ, Dept Med, New York, NY USA. [Fabsitz, Richard] NHLBI, Div Epidemiol & Clin Applicat, Framingham, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Glessner, Joseph] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA. [Curb, David] Pacific Hlth Res Inst, Honolulu, HI USA. [Reiner, Alexander] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Eaton, Charles] Brown Univ, Div Biol & Med, Providence, RI 02912 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. RP Zhu, XF (reprint author), Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, 2103 Cornell Rd, Cleveland, OH 44106 USA. EM xiaofeng.zhu@case.edu; aravinda@jhmi.edu RI Sun, Yan/A-7461-2008; OI Chiang, Charleston/0000-0002-0668-7865; Ramachandran, Vasan/0000-0001-7357-5970; Adeyemo, Adebowale/0000-0002-3105-3231 FU National Heart, Lung, and Blood Institute [HL086718]; National Institutes of Health, National Heart, Lung, and Blood Institute [HL074166, HL53353, HL087660, HL100245]; National Human Genome Research Institute [HG003054]; National Heart, Lung, and Blood Institute, National Institutes of Health; U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-32102, 32105, 32106, 32108-32109, 32111-32113, 32115, 32118, 32119, 32122, 42107-42126, 42129-42132, 44221] FX CARe. The authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute. The following nine parent studies have contributed parent study data, ancillary study data, and DNA samples through the Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community: Atherosclerotic Risk in Communities (ARIC): University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55017), University of North Carolina, Forsyth County (N01-HC-55018); Cardiovascular Health Study (CHS): University of Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of Pittsburgh (N01-HC-85082), University of California, Davis (N01-HC-85083), University of California, Irvine (N01-H-C-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), University of Washington (N01 HC-55222, U01 HL080295); Cleveland Family Study (CFS): Case Western Reserve University (RO1 HL46380-01-16); Cooperative Study of Sickle Cell Disease (CSSCD): University of Illinois (N01-HB-72982, N01-HB-9-7062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB-72994), University of Tennessee (N01-H-B-72995, N01-HB-97070), Yale University (N01-H-B-72996, N01-HB-97072), Children's Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston, Inc. (N01-HB-73003), Children's Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St. Luke's Hospital-New York (N01-HB-73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB-97058), St.; Jude's Children's Research Hospital (N01-HB-97066), Research Foundation, State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart Study (FHS): Boston University (N01-HC-25195); Jackson Heart Study (JHS): Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington (N01-HC-95159), Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162), University of Minnesota (N01-HC-95163), Northwestern Univesity (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Johns Hopkins University (N01-HC-95168), Harbor-UCLA Research and Education Institute (N01-HC-95169); Sleep Heart Health Study (SHHS): Johns Hopkins University (U01 HL064360), Case Western University (U01 HL063463), University of California, Davis (U01 HL053916), University of Arizona (U01 HL053938), University of Minnesota (relocating in 2006 to University Arizona) (U01 HL053934), University of Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar Research Institute (U01 HL063429), Johns Hopkins University (U01 HL053937).; Maywood African-American and Nigeria studies are supported by the National Institutes of Health, grant numbers HL074166 and HL53353 from the National Heart, Lung, and Blood Institute. Y. L. and X. Z. are supported by HL086718 from the National Heart, Lung, and Blood Institute and HG003054 from the National Human Genome Research Institute.; Genetic Epidemiology Network of Arteriopathy (GENOA) study is supported by the National Institutes of Health, grant numbers HL087660 and HL100245 from the National Heart, Lung, and Blood Institute.; The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-32102, 32105, 32106, 32108-32109, 32111-32113, 32115, 32118, 32119, 32122, 42107-42126, 42129-42132, and 44221. NR 41 TC 39 Z9 41 U1 0 U2 0 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 JUN 1 PY 2011 VL 20 IS 11 BP 2285 EP 2295 DI 10.1093/hmg/ddr113 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 763WG UT WOS:000290589800018 PM 21422096 ER PT J AU Waters, EA Klein, WMP Moser, RP Yu, MD Waldron, WR McNeel, TS Freedman, AN AF Waters, Erika A. Klein, William M. P. Moser, Richard P. Yu, Mandi Waldron, William R. McNeel, Timothy S. Freedman, Andrew N. TI Correlates of unrealistic risk beliefs in a nationally representative sample SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Unrealistic optimism; Unrealistic pessimism; Breast cancer; Health behavior ID BREAST-CANCER RISK; PERCEIVED RISK; RANDOMIZED TRIAL; PERSONAL RISK; OPTIMISM; PERCEPTIONS; WOMEN; PESSIMISM; BEHAVIOR; DISEASE AB Unrealistically optimistic or pessimistic risk perceptions may be associated with maladaptive health behaviors. This study characterized factors associated with unrealistic optimism (UO) and unrealistic pessimism (UP) about breast cancer. Data from the 2005 National Health Interview Survey were analyzed (N = 14,426 women). After accounting for objective risk status, many (43.8%) women displayed UO, 12.3% displayed UP, 34.5% had accurate risk perceptions (their perceived risk matched their calculated risk), and 9.5% indicated "don't know/no response." Multivariate multinomial logistic regression indicated that UO was associated with higher education and never smoking. UP was associated with lower education, lower income, being non-Hispanic Black, having a parts per thousand yen3 comorbidities, current smoking, and being overweight. UO was more likely to emerge in younger and older than in middle-aged individuals. UO and UP are associated with different demographic, health, and behavioral characteristics. Population segments that are already vulnerable to negative health outcomes displayed more UP than less vulnerable populations. C1 [Waters, Erika A.] Washington Univ, Sch Med, Dept Surg Prevent & Control, St Louis, MO 63110 USA. [Klein, William M. P.; Moser, Richard P.; Yu, Mandi; Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Waldron, William R.; McNeel, Timothy S.] Informat Management Serv Inc, Silver Spring, MD USA. RP Waters, EA (reprint author), Washington Univ, Sch Med, Dept Surg Prevent & Control, Campus Box 8100,660 S Euclid, St Louis, MO 63110 USA. EM waterse@wudosis.wustl.edu OI Waters, Erika/0000-0001-7402-0133 FU Intramural NIH HHS [Z99 CA999999] NR 52 TC 17 Z9 18 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD JUN PY 2011 VL 34 IS 3 BP 225 EP 235 DI 10.1007/s10865-010-9303-7 PG 11 WC Psychology, Clinical SC Psychology GA 759WB UT WOS:000290278100008 PM 21110077 ER PT J AU Ikenaga, T Urban, JM Gebhart, N Hatta, K Kawakami, K Ono, F AF Ikenaga, Takanori Urban, Jason M. Gebhart, Nichole Hatta, Kohei Kawakami, Koichi Ono, Fumihito TI Formation of the Spinal Network in Zebrafish Determined by Domain-Specific Pax Genes SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE spinal cord; transcription factor; differentiation; gene trap; cell fate; paired box gene ID LARVAL ZEBRAFISH; FLUORESCENT PROTEIN; MOTONEURON SUBTYPE; MIDBRAIN-HINDBRAIN; INTERNEURONS; EXPRESSION; NEURONS; CIRCUITS; CELLS; CORD AB In the formation of the spinal network, various transcription factors interact to develop specific cell types. By using a gene trap technique, we established a stable line of zebrafish in which the red fluorescent protein (RFP) was inserted into the pax8 gene. RFP insertion marked putative pax8-lineage cells with fluorescence and inhibited pax8 expression in homozygous embryos. Pax8 homozygous embryos displayed defects in the otic vesicle, as previously reported in studies with morpholinos. The pax8 homozygous embryos survived to adulthood, in contrast to mammalian counterparts that die prematurely. RFP is expressed in the dorsal spinal cord. Examination of the axon morphology revealed that RFP(+) neurons include commissural bifurcating longitudinal (CoBL) interneurons, but other inhibitory neurons such as commissural local (CoLo) interneurons and circumferential ascending (CiA) interneurons do not express RFP. We examined the effect of inhibiting pax2a/pax8 expression on interneuron development. In pax8 homozygous fish, the RFP(+) cells underwent differentiation similar to that of pax8 heterozygous fish, and the swimming behavior remained intact. In contrast, the RFP(+) cells of pax2a/pax8 double mutants displayed altered cell fates. CoBLs were not observed. Instead, RFP(+) cells exhibited axons descending ipsilaterally, a morphology resembling that of V2a/V2b interneurons. J. Comp. Neurol. 519: 1562-1579, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Ikenaga, Takanori; Urban, Jason M.; Ono, Fumihito] NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Gebhart, Nichole] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA. [Hatta, Kohei] Univ Hyogo, Grad Sch Life Sci, Kobe, Hyogo 6781297, Japan. [Kawakami, Koichi] Natl Inst Genet, Div Mol & Dev Biol, Mishima, Shizuoka 4118540, Japan. [Kawakami, Koichi] Grad Univ Adv Studies SOKENDAI, Dept Genet, Mishima, Shizuoka 4118540, Japan. RP Ono, F (reprint author), NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. EM onof@mail.nih.gov OI Ikenaga, Takanori/0000-0002-7321-9703 FU National Institute of Neurological Disorders and Stroke [1R01NS050388-01A1]; Muscular Dystrophy Association [MDA3818]; National Institute on Alcohol Abuse and Alcoholism FX Grant sponsor: National Institute of Neurological Disorders and Stroke; Grant number: 1R01NS050388-01A1 (to F.O.); Grant sponsor: Muscular Dystrophy Association; Grant number: MDA3818 (to F.O.); Grant sponsor: National Institute on Alcohol Abuse and Alcoholism. NR 46 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 1 PY 2011 VL 519 IS 8 BP 1562 EP 1579 DI 10.1002/cne.22585 PG 18 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 763AO UT WOS:000290525500009 PM 21452218 ER PT J AU Briest, W Cooper, TK Tae, HJ Krawczyk, M McDonnell, NB Talan, MI AF Briest, Wilfried Cooper, Timothy K. Tae, Hyun-Jin Krawczyk, Melissa McDonnell, Nazli B. Talan, Mark I. TI Doxycycline Ameliorates the Susceptibility to Aortic Lesions in a Mouse Model for the Vascular Type of Ehlers-Danlos Syndrome SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SYNDROME TYPE-IV; ANTIINFLAMMATORY DOSE DOXYCYCLINE; MARFAN-SYNDROME; MATRIX METALLOPROTEINASES; CLINICAL-TRIAL; III COLLAGEN; ANEURYSMS; INHIBITION; THERAPY; MULTICENTER AB The vascular form of Ehlers-Danlos syndrome (vEDS), a rare disease with grave complications resulting from rupture of major arteries, is caused by mutations of collagen type III [alpha 1 chain of collagen type III (COL3A1)]. The only, recently proven, preventive strategy consists of the reduction of arterial wall stress by beta-adrenergic blockers. The heterozygous (HT) Col3a1 knockout mouse has reduced expression of collagen III and recapitulates features of a mild presentation of the disease. The objective of this study was to determine whether changing the balance between synthesis and degradation of collagen by chronic treatment with doxycycline, a nonspecific matrix metalloproteinase (MMP) inhibitor, could prevent the development of vascular pathology in HT mice. After 3 months of treatment with doxycycline or placebo, 9-month-old HT or wild-type (WT) mice were subjected to surgical stressing of the aorta. A 3-fold increase in stress-induced aortic lesions found in untreated HT mice 1 week after intervention (cumulative score 4.5 +/- 0.87 versus 1.3 +/- 0.34 in WT, p < 0.001) was fully prevented in the doxycycline-treated group (1.1 +/- 0.56, p < 0.001). Untreated HT mice showed increased MMP-9 activity in the carotid artery and decreased collagen content in the aorta; however, in doxycycline-treated animals there was normalization to the levels observed in WT mice. Doxycycline treatment inhibits the activity of tissue MMP and attenuates the decrease in the collagen content in aortas of mice haploinsufficient for collagen III, as well as prevents the development of stress-induced vessel pathology. The results suggest that doxycycline merits clinical testing as a treatment for vEDS. C1 [Briest, Wilfried; Tae, Hyun-Jin; Krawczyk, Melissa; Talan, Mark I.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [McDonnell, Nazli B.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA. [Cooper, Timothy K.] Penn State Univ, Milton S Hershey Med Ctr, Dept Comparat Med, Hershey, PA 17033 USA. RP Briest, W (reprint author), Ferdinand Lassalle Str 16, D-04109 Leipzig, Germany. EM wilfried.briest@arcor.de OI Briest, Wilfried/0000-0003-4556-4849 FU National Institutes of Health National Institute on Aging; Gerhard Schuler, Department of Cardiology, Heart Center, Leipzig, Germany FX This work was supported by the Intramural Research Program of the National Institutes of Health National Institute on Aging. W.B. was partially supported by the research grants of Gerhard Schuler, Department of Cardiology, Heart Center, Leipzig, Germany. NR 39 TC 7 Z9 7 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2011 VL 337 IS 3 BP 621 EP 627 DI 10.1124/jpet.110.177782 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 764GO UT WOS:000290618000006 PM 21363928 ER PT J AU Xie, G Sun, Y Nie, T Mackenzie, GG Huang, LQ Kopelovich, L Komninou, D Rigas, B AF Xie, Gang Sun, Yu Nie, Ting Mackenzie, Gerardo G. Huang, Liqun Kopelovich, Levy Komninou, Despina Rigas, Basil TI Phospho-Ibuprofen (MDC-917) Is a Novel Agent against Colon Cancer: Efficacy, Metabolism, and Pharmacokinetics in Mouse Models SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HUMAN LIVER-MICROSOMES; STEREOSELECTIVE METABOLISM; IN-VITRO; PREVENTION; ASPIRIN; ESTER; RAT; CARBOXYLESTERASE; GLUCURONIDATION AB We have developed a novel chemical modification of conventional nonsteroidal anti-inflammatory drugs to reduce their toxicity and enhance their efficacy. Phospho-ibuprofen [(PI) 2-(4-isobutyl-phenyl)-propionic acid-4-(diethoxy-phosphoryloxy)-butyl ester (MDC-917)], a novel derivative of ibuprofen, strongly inhibited the growth of human colon cancer cells in vitro and SW480 human colon cancer xenografts in nude mice. PI was metabolized minimally by cultured cells, but extensively by liver microsomes and mice, undergoing regioselective oxidation to produce 1-OH-PI and carboxyl-PI, which can be hydrolyzed to 1-OH-ibuprofen and carboxyl-ibuprofen, respectively. PI also can be hydrolyzed to release ibuprofen, which can generate 2-OH-ibuprofen, carboxyl-ibuprofen, and ibuprofen glucuronide. After a single oral administration (400 mg/kg) of PI, ibuprofen and ibuprofen glucuronide are the main plasma metabolites of PI; they have, respectively, C(max) of 530 and 215 mu M, T(max) of 1 and 2 h, elimination t(1/2) of 7.7 and 5.3 h, and area under the concentration-time curve (0-24 h) of 1816 and 832 mu M x h. Intact PI was detected in several tissues but not in plasma; at a higher PI dose (1200 mg/kg), PI plasma levels were 12.4 mu M. PI generated the same metabolites in mouse plasma as conventional ibuprofen, but with much lower levels, perhaps accounting for the enhanced safety of PI. The antitumor effect of PI was significantly associated with plasma ibuprofen levels (p = 0.016) but not with xenograft ibuprofen levels (p = 0.08), suggesting a complex anticancer effect. These results provide a pharmacological basis to explain, at least in part, the anticancer efficacy and safety of this promising compound and indicate that PI merits further evaluation as an anticancer agent. C1 [Rigas, Basil] SUNY Stony Brook, Canc Prevent Div, HSC, Dept Med, Stony Brook, NY 11794 USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Komninou, Despina] Medicon Pharmaceut Inc, Stony Brook, NY USA. RP Rigas, B (reprint author), SUNY Stony Brook, Canc Prevent Div, HSC, Dept Med, T17-080, Stony Brook, NY 11794 USA. EM basil.rigas@stonybrook.edu RI Nie, Ting/A-9837-2010 FU National Institutes of Health National Cancer Institute [STTR-CA156920A, R01-CA153662, 1N01-CN43302WA22] FX This work was supported by the National Institutes of Health National Cancer Institute [Grants STTR-CA156920A, R01-CA153662 and Contract 1N01-CN43302WA22]. NR 31 TC 27 Z9 27 U1 0 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2011 VL 337 IS 3 BP 876 EP 886 DI 10.1124/jpet.111.180224 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 764GO UT WOS:000290618000034 PM 21422165 ER PT J AU Kim, HY Bierbaum, VM AF Kim, Hee-Yong Bierbaum, Veronica M. TI Focus in Honor of Marvin L. Vestal, Recipient of the 2010 Award for a Distinguished Contribution in Mass Spectrometry SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Editorial Material C1 [Kim, Hee-Yong] NIAAA, NIH, Bethesda, MD USA. [Bierbaum, Veronica M.] Univ Colorado, Boulder, CO 80309 USA. RP Kim, HY (reprint author), NIAAA, NIH, Bethesda, MD USA. EM hykim@nih.gov; Veronica.Bierbaum@Colorado.EDU NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JUN PY 2011 VL 22 IS 6 BP 949 EP 952 DI 10.1007/s13361-011-0132-x PG 4 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 762DD UT WOS:000290451600001 PM 21953035 ER PT J AU Olson, MT Epstein, JA Sackett, DL Yergey, AL AF Olson, Matthew T. Epstein, Jonathan A. Sackett, Dan L. Yergey, Alfred L. TI Production of Reliable MALDI Spectra with Quality Threshold Clustering of Replicates SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article DE MALDI; Peptide fragmentation; Tubulin; Consensus spectrum; QT clustering; Pearson's correlation coefficient ID ASSISTED-LASER-DESORPTION/IONIZATION; FLIGHT-MASS-SPECTROMETRY; INTACT PROTEIN-ANALYSIS; ACID MATRIX; IONIZATION; DESORPTION; TIME; PEPTIDE; IDENTIFICATION; TUBULIN AB We present the first application of the quality threshold (QT) clustering algorithm to mass spectrometry (MS) data. The unique abilities of QT clustering to yield precision nodes that are commensurate with the mass measurement precision of the instrument are exploited to generate a consensus spectrum out of multiple replicate spectra. The spectral dot product and confidence intervals are used as a tool for evaluating the similarity and reproducibility between the consensus and replicates. The method is equally applicable to high and low resolution measurements. This paper demonstrates applications to linear spectra from a matrix assisted laser desorption ionization (MALDI) time of flight (TOF) instrument as well as peptide fragmentation data obtained from a TOF/TOF after unimolecular decomposition. The advantages of clustering to mitigate the inherent precision the shortcomings of MALDI data are discussed. C1 [Epstein, Jonathan A.; Sackett, Dan L.; Yergey, Alfred L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, IRP, Bethesda, MD USA. [Olson, Matthew T.] Johns Hopkins Med Inst, Dept Pathol, Bethesda, MD USA. RP Yergey, AL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, IRP, Bethesda, MD USA. EM aly@helix.nih.gov NR 41 TC 3 Z9 3 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JUN PY 2011 VL 22 IS 6 BP 969 EP 975 DI 10.1007/s13361-011-0097-9 PG 7 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 762DD UT WOS:000290451600004 PM 21953038 ER PT J AU Hankin, JA Farias, SE Barkley, R Heidenreich, K Frey, LC Hamazaki, K Kim, HY Murphy, RC AF Hankin, Joseph A. Farias, Santiago E. Barkley, Robert M. Heidenreich, Kim Frey, Lauren C. Hamazaki, Kei Kim, Hee-Yong Murphy, Robert C. TI MALDI Mass Spectrometric Imaging of Lipids in Rat Brain Injury Models SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article DE MALDI; IMS; Imaging mass spectrometry; Sublimation; Brain; Phosphatidylcholine; Ceramide; Traumatic brain injury; Ischemia reperfusion; Brain injury; Alkali metal adduct images; CA1; Hippocampus damage ID GERBIL HIPPOCAMPUS; FOREBRAIN ISCHEMIA; MATRIX; PHOSPHOLIPIDS; TISSUE; DAMAGE; IMS AB Matrix-assisted laser desorption ionization/ionization imaging mass spectrometry (MALDI IMS) with a time-of-flight analyzer was used to characterize the distribution of lipid molecular species in the brain of rats in two injury models. Ischemia/reperfusion injury of the rat brain after bilateral occlusion of the carotid artery altered appearance of the phospholipids present in the hippocampal region, specifically the CA1 region. These brain regions also had a large increase in the ion abundance at m/z 548.5 and collisional activation supported identification of this ion as arising from ceramide (d18:1/18:0), a lipid known to be associated with cellular apoptosis. Traumatic brain injury model in the rat was examined by MALDI IMS and the area of damage also showed an increase in ceramide (d18:1/18:0) and a remarkable loss of signal for the potassium adduct of the most abundant phosphocholine molecular species 16:0/18:1 (PC) with a corresponding increase in the sodium adduct ion. This change in PC alkali attachment ion was suggested to be a result of edema and influx of extracellular fluid likely through a loss of Na/K-ATPase caused by the injury. These studies reveal the value of MALDI IMS to examine tissues for changes in lipid biochemistry and will provide data needed to eventually understand the biochemical mechanisms relevant to tissue injury. C1 [Hankin, Joseph A.; Farias, Santiago E.; Barkley, Robert M.; Heidenreich, Kim; Murphy, Robert C.] Univ Colorado Denver, Dept Pharmacol, Aurora, CO USA. [Hamazaki, Kei; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD USA. [Frey, Lauren C.] Univ Colorado Denver, Dept Neurol, Aurora, CO USA. RP Murphy, RC (reprint author), Univ Colorado Denver, Dept Pharmacol, Aurora, CO USA. EM Robert.Murphy@ucdenver.edu FU General Medical Sciences Institute of the National Institutes of Health [GM069338]; Colorado TBI Trust; NIAAA, NIH FX The authors acknowledge that this work was supported, in part, by a grant from the LipidMAPS Large Scale Collaborative grant from General Medical Sciences Institute (GM069338) of the National Institutes of Health and Colorado TBI Trust Fund. A part of this research (Kei H. and H.Y.K.) was supported by the intramural program of NIAAA, NIH. The authors thank Erin Genova (UC Denver Pathology Department) for assistance in preparation of FPI tissue sections. NR 32 TC 48 Z9 48 U1 5 U2 40 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JUN PY 2011 VL 22 IS 6 BP 1014 EP 1021 DI 10.1007/s13361-011-0122-z PG 8 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 762DD UT WOS:000290451600008 PM 21953042 ER PT J AU Xiao, TJ Wallace, J Felsenfeld, G AF Xiao, Tiaojiang Wallace, Julie Felsenfeld, Gary TI Specific Sites in the C Terminus of CTCF Interact with the SA2 Subunit of the Cohesin Complex and Are Required for Cohesin-Dependent Insulation Activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; BETA-GLOBIN INSULATOR; CCCTC-BINDING FACTOR; TRANSCRIPTION FACTOR; GENE-EXPRESSION; CONTROL REGION; METHYLATION; CHROMATIN; MECHANISMS; PROMOTER AB Recent studies have shown that the protein CTCF, which plays an important role in insulation and in large-scale organization of chromatin within the eukaryotic nucleus, depends for both activities on recruitment of the cohesin complex. We show here that the interaction of CTCF with the cohesin complex involves direct contacts between the cohesin subunit SA2 and specific regions of the C-terminal tail of CTCF. All other cohesin components are recruited through their interaction with SA2. Expression in vivo of CTCF mutants lacking the C-terminal domain, or with mutations at sites within it required for SA2 binding, disrupts the normal expression profile of the imprinted genes IGF2-H19 and also results in a loss of insulation activity. Taken together, our results demonstrate that specific sites on the C terminus of CTCF are essential for cohesin binding and insulator function. The only direct interaction between CTCF and cohesin involves contact with SA2, which is external to the cohesin ring. This suggests that in recruiting cohesin to CTCF, SA2 could bind first and the ring could assemble subsequently. C1 [Xiao, Tiaojiang; Wallace, Julie; Felsenfeld, Gary] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM gary.felsenfeld@nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases, NIH FX This work was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. NR 46 TC 75 Z9 79 U1 1 U2 3 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 JUN PY 2011 VL 31 IS 11 BP 2174 EP 2183 DI 10.1128/MCB.05093-11 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 762KI UT WOS:000290475100001 PM 21444719 ER PT J AU Chun, KS Langenbach, R AF Chun, Kyung-Soo Langenbach, Robert TI The Prostaglandin E-2 Receptor, EP2, Regulates Survivin Expression Via an EGFR/STAT3 Pathway in UVB-Exposed Mouse Skin SO MOLECULAR CARCINOGENESIS LA English DT Article DE COX-2; PGE(2); EP4; EP1; butaprost; apoptosis ID GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; COLON-CANCER CELLS; PROSTANOID RECEPTORS; BREAST-CANCER; CYCLOOXYGENASE-2 OVEREXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNALING PATHWAY; INDUCED APOPTOSIS; TUMOR-DEVELOPMENT AB We previously reported that cycloogenase (COX)-2-generated prostaglandin E-2 (PGE(2)) had anti-apoptotic effects in UVB-exposed mouse skin that involved EP2-mediated signaling (Chun et al., Cancer Res. 2007; 67: 2015). Because survivin is a regulator of cell survival, the possible involvement of COX-2 and EP2 in survivin expression following UVB exposure of mouse skin was investigated. In wild type mice, UVB exposure time-dependently increased the levels of survivin and phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), a transcription factor that regulates survivin expression; and COX-2- or EP2-deficiency significantly reduced their induction. Topical application of the COX-2 inhibitor, celecoxib, also reduced UVB-induced survivin levels. To further investigate the roles of PGE(2) and EP2 in the regulation of survivin, indomethacin was used to inhibit UVB-induced endogenous PG production. UVB-induced survivin levels were reduced by indomethacin, and PGE(2) and the EP2 agonist, butaprost, partially restored survivin levels. The epidermal growth factor receptor (EGFR) is a downstream effector of EP2 and EGFR inhibition (AG1478) significantly reduced UVB activation of STAT3 and survivin levels. UVB-induced epidermal apoptosis in COX-2-/- mice was reduced by butaprost and EGFR inhibition blocked butaprost's protective effects. Furthermore, butaprost in the absence of UVB exposure time-dependently increased p-EGFR, p-STAT3, and survivin levels in naive mouse skin, whereas the EP4 agonist, PGE(1) alcohol, did not significantly increase p-STAT3 or survivin levels. These data suggest that COX-2-generated PGE(2) regulates survivin expression in mouse skin, in part, via an EP2-mediated EGFR/STAT3 pathway. Therefore, targeting the EP2/survivin pathway may provide a strategy for the chemoprevention/chemotherapy of skin cancer. (C) 2011 Wiley-Liss, Inc. C1 [Chun, Kyung-Soo; Langenbach, Robert] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. RP Langenbach, R (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, MD C4-09,POB 12233, Res Triangle Pk, NC 27709 USA. FU NIEHS/NIH FX This research was supported by the Intramural Research Program of the NIEHS/NIH. We are thankful to Dr. Richard Breyer for supplying EP2-/- mice. We thank Chris A. Lee for animal husbandry and mice genotyping. We also thank Dr. Thomas Eling, Dr. Darryl Zeldin, Huei-Chen Lao, and Carol Trempus for their critical review of manuscript. NR 63 TC 11 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUN PY 2011 VL 50 IS 6 BP 439 EP 448 DI 10.1002/mc.20728 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 762QS UT WOS:000290495100005 PM 21268125 ER PT J AU Makarova, KS Haft, DH Barrangou, R Brouns, SJJ Charpentier, E Horvath, P Moineau, S Mojica, FJM Wolf, YI Yakunin, AF van der Oost, J Koonin, EV AF Makarova, Kira S. Haft, Daniel H. Barrangou, Rodolphe Brouns, Stan J. J. Charpentier, Emmanuelle Horvath, Philippe Moineau, Sylvain Mojica, Francisco J. M. Wolf, Yuri I. Yakunin, Alexander F. van der Oost, John Koonin, Eugene V. TI Evolution and classification of the CRISPR-Cas systems SO NATURE REVIEWS MICROBIOLOGY LA English DT Article ID PROVIDES ACQUIRED-RESISTANCE; DNA-REPAIR SYSTEM; IMMUNE-SYSTEM; SMALL RNA; REPEATS; PROKARYOTES; BACTERIA; DEFENSE; ARCHAEA; PROTEIN AB The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR-Cas systems and Cas proteins. Three major types of CRISPR-Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR-Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a 'polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR-cas loci. C1 [Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Haft, Daniel H.] J Craig Venter Inst, Rockville, MD 20850 USA. [Barrangou, Rodolphe] Danisco USA Inc, Madison, WI 53716 USA. [Brouns, Stan J. J.; van der Oost, John] Wageningen Univ, Microbiol Lab, NL-6703 HB Wageningen, Netherlands. [Charpentier, Emmanuelle] Umea Univ, Lab Mol Infect Med Sweden, Umea Ctr Microbial Res, Dept Mol Biol, S-90187 Umea, Sweden. [Horvath, Philippe] Danisco France SAS, F-86220 Dange St Romain, France. [Moineau, Sylvain] Univ Laval, Dept Biochim Microbiol & Bioinformat, Fac Sci & Genie, Quebec City, PQ G1V 0A6, Canada. [Mojica, Francisco J. M.] Univ Alicante, Dept Fisiol Genet & Microbiol, E-03080 Alicante, Spain. [Yakunin, Alexander F.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Moineau, Sylvain/N-3578-2013; Yakunin, Alexander/J-1519-2014; Mojica, Francisco/K-2414-2014; Barrangou, Rodolphe/I-2878-2014; HORVATH, Philippe/K-5266-2015; OI Mojica, Francisco/0000-0002-6660-4996; Barrangou, Rodolphe/0000-0002-0648-3504; HORVATH, Philippe/0000-0003-2015-8123; Yakunin, Alexander/0000-0003-0813-6490 FU US Department of Health and Human Services (National Library of Medicine); US National Institutes of Health [1 R01 HG004881]; Umea University, Sweden; Swedish Research Council; National Sciences and Engineering Research Council of Canada; University of Alicante, Spain; Government of Canada through Genome Canada; Ontario Genomics Institute [2009-OGI-ABC-1405]; Netherlands Organization for Scientific Research (NWO) FX The authors thank M. Terns for critical reading of the manuscript and useful discussions. K.S.M., Y.I.W. and E.V.K. are supported by the intramural funds of the US Department of Health and Human Services (National Library of Medicine); D.H.H. is supported by a US National Institutes of Health grant (1 R01 HG004881); E.C. acknowledges funding from Umea University, Sweden, and the Swedish Research Council. S.M. acknowledges funding from the National Sciences and Engineering Research Council of Canada (the Discovery programme); F.J.M.M. acknowledges support from the University of Alicante, Spain, (Vicerrectorado de Investigacion, and Desarrollo e Innovacion) for the use of its research technical services; A.F.Y. is supported by the Government of Canada through Genome Canada and the Ontario Genomics Institute (grant 2009-OGI-ABC-1405). S.J.B. and J.O. are supported by Veni and TOP grants from the Netherlands Organization for Scientific Research (NWO). NR 50 TC 721 Z9 788 U1 79 U2 522 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD JUN PY 2011 VL 9 IS 6 BP 467 EP 477 DI 10.1038/nrmicro2577 PG 11 WC Microbiology SC Microbiology GA 764FI UT WOS:000290614100019 PM 21552286 ER PT J AU Gold, LS Stewart, PA Milliken, K Purdue, M Severson, R Seixas, N Blair, A Hartge, P Davis, S De Roos, AJ AF Gold, Laura S. Stewart, Patricia A. Milliken, Kevin Purdue, Mark Severson, Richard Seixas, Noah Blair, Aaron Hartge, Patricia Davis, Scott De Roos, Anneclaire J. TI The relationship between multiple myeloma and occupational exposure to six chlorinated solvents SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID EXTENDED FOLLOW-UP; CANCER INCIDENCE; ORGANIC-SOLVENTS; WORKERS; TRICHLOROETHYLENE; MORTALITY; RISK; COHORT; CHEMICALS; LYMPHOMA AB Objectives Few studies have examined whether exposure to chlorinated solvents is associated with multiple myeloma. We evaluated associations between multiple myeloma and occupational exposure to six chlorinated solvents: 1,1,1-trichloroethane, trichloroethylene (TCE), methylene chloride (DCM), perchloroethylene, carbon tetrachloride and chloroform. Methods In-person interviews obtained occupational histories and information on jobs with likely solvent exposure. We assigned exposure metrics of probability, frequency, intensity and confidence using job-exposure matrices modified by job-specific questionnaire information. We used logistic regression to estimate ORs and 95% CIs for associations between multiple myeloma and ever exposure to each, and any, chlorinated solvent and analysed whether associations varied by duration and cumulative exposure. We also considered all occupations that were given the lowest confidence scores as unexposed and repeated all analyses. Results Risk of multiple myeloma was elevated for subjects ever exposed to 1,1,1-trichloroethane (OR (95% CI): 1.8 (1.1 to 2.9)). Ever exposure to TCE or DCM also entailed elevated, but not statistically significant, risks of multiple myeloma; these became statistically significant when occupations with low confidence scores were considered unexposed (TCE: 1.7 (1.0 to 2.7); DCM: 2.0 (1.2 to 3.2)). Increasing cumulative exposure to perchloroethylene was also associated with increasing multiple myeloma risk. We observed non-significantly increased multiple myeloma risks with exposure to chloroform; however, few subjects were exposed. Conclusions Evidence from this relatively large case-control study suggests that exposures to certain chlorinated solvents may be associated with increased incidence of multiple myeloma; however, the study is limited by relatively low participation (52%) among controls. C1 [Gold, Laura S.; Milliken, Kevin; Davis, Scott; De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Gold, Laura S.; Milliken, Kevin; Davis, Scott; De Roos, Anneclaire J.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA USA. [Purdue, Mark; Blair, Aaron; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Severson, Richard] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Karmanos Canc Inst, Detroit, MI USA. [Seixas, Noah] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. RP Gold, LS (reprint author), 1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA. EM goldl@u.washington.edu FU National Occupational Research Agenda (NORA) FX This research was funded in part by a grant from the National Occupational Research Agenda (NORA). NR 55 TC 14 Z9 14 U1 2 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUN PY 2011 VL 68 IS 6 BP 391 EP 399 DI 10.1136/oem.2009.054809 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 762XX UT WOS:000290516600004 PM 20833760 ER PT J AU Rossi, S Testa, F Li, A Di Iorio, V Zhang, J Gesualdo, C Della Corte, M Chan, CC Hejtmancik, JF Simonelli, F AF Rossi, Settimio Testa, Francesco Li, Anren Di Iorio, Valentina Zhang, Jun Gesualdo, Carlo Della Corte, Michele Chan, Chi-Chao Hejtmancik, J. Fielding Simonelli, Francesca TI An Atypical Form of Bietti Crystalline Dystrophy SO OPHTHALMIC GENETICS LA English DT Article ID CORNEO-RETINAL DYSTROPHY; RETINOPATHY; MUTATIONS; CYP4V2 AB Methods: The patient underwent a thorough medical anamnesis, genetic counseling, peripheral blood draw for CYP4V2 gene analysis and electron microscopy, and a complete ophthalmological assessment including optical coherence tomography, indocyanine green angiography, microperimetry, full-field electroretinogram and multifocal electroretinogram. Results: The most striking features of the retina were deposits of yellowish-white glistening crystals and focal lobular areas of choriocapillary atrophy at the posterior pole and midperiphery. The full-field electroretinogram was normal and the multifocal electroretinogram showed extinguished central recordings. Mutation analysis revealed a homozygous c. 332T > C p.I111T mutation in exon 3 of the CYP4V2 gene. Typical cytoplasmic inclusions containing crystalline-like structure and large degenerative lysosomes were seen on electron microscopy of peripheral leukocytes. Conclusion: Here we describe a patient with Bietti crystalline dystrophy with a CYP4V2 gene mutation and typical leukocyte inclusions who showed the classical retinal lesions but had a normal electroretinogram. This suggests the existence of less severe forms of BCD related to relatively mild CYP4V2 mutations. C1 [Rossi, Settimio; Testa, Francesco; Di Iorio, Valentina; Gesualdo, Carlo; Della Corte, Michele; Simonelli, Francesca] Univ Naples 2, Dept Ophthalmol, Naples, Italy. [Li, Anren; Hejtmancik, J. Fielding] Natl Eye Inst, Ophthalm Genet & Visual Funct Branch, Rockville, MD USA. [Zhang, Jun; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Simonelli, F (reprint author), Via Pansini 5, Naples, Italy. EM franctes@tin.it RI Testa, Francesco/J-3185-2012; Rossi, Settimio/J-4922-2012; Zhang, Jun/K-2424-2012; OI DELLA CORTE, MICHELE/0000-0003-1320-1883; Simonelli, Francesca/0000-0001-8520-6769; Testa, Francesco/0000-0002-1482-1577; Di iorio, Valentina/0000-0002-8179-5970 FU Intramural NIH HHS [ZIA EY000222-25] NR 12 TC 8 Z9 8 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1381-6810 J9 OPHTHALMIC GENET JI Ophthalmic Genet. PD JUN PY 2011 VL 32 IS 2 BP 118 EP 121 DI 10.3109/13816810.2011.559653 PG 4 WC Genetics & Heredity; Ophthalmology SC Genetics & Heredity; Ophthalmology GA 762OE UT WOS:000290488500009 PM 21385027 ER PT J AU Cohen-Gihon, I Sharan, R Nussinov, R AF Cohen-Gihon, Inbar Sharan, Roded Nussinov, Ruth TI Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement SO PHYSICAL BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; PROTEINS; YEAST; DUPLICABILITY; COMPLEXITY; DATABASE; GENOME; RECOMBINATION; ARCHITECTURES; ANNOTATION AB During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently. C1 [Cohen-Gihon, Inbar; Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. [Sharan, Roded] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] NCI Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Nussinov, R (reprint author), Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. EM ruthnu@helix.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research; Tel-Aviv University; Israel Science Foundation [385/06] FX We thank Nir Yosef for providing us with the protein-protein interaction network data. We thank Itai Yanai for helpful advice. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. ICG is a fellow of the Edmond J Safra Bioinformatics Program and of the Ela Kodesz Research and Scholarship Fund at Tel-Aviv University. RS was supported by a research grant from the Israel Science Foundation (no. 385/06). NR 49 TC 8 Z9 8 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3975 J9 PHYS BIOL JI Phys. Biol. PD JUN PY 2011 VL 8 IS 3 AR 035009 DI 10.1088/1478-3975/8/3/035009 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 763MB UT WOS:000290560100010 PM 21572172 ER PT J AU Hashimoto, K Nishi, H Bryant, S Panchenko, AR AF Hashimoto, Kosuke Nishi, Hafumi Bryant, Stephen Panchenko, Anna R. TI Caught in self-interaction: evolutionary and functional mechanisms of protein homooligomerization SO PHYSICAL BIOLOGY LA English DT Article ID HUMAN THYMIDYLATE SYNTHASE; KINASE TYPE M2; QUATERNARY STRUCTURE; LEUCINE-ZIPPER; DOMAIN INTERACTIONS; CRYSTALLINE STATE; OLIGOMERIC STATE; BINDING; INTERFACES; DIMER AB Many soluble and membrane proteins form homooligomeric complexes in a cell which are responsible for the diversity and specificity of many pathways, may mediate and regulate gene expression, activity of enzymes, ion channels, receptors, and cell adhesion processes. The evolutionary and physical mechanisms of oligomerization are very diverse and its general principles have not yet been formulated. Homooligomeric states may be conserved within certain protein subfamilies and might be important in providing specificity to certain substrates while minimizing interactions with other unwanted partners. Moreover, recent studies have led to a greater awareness that transitions between different oligomeric states may regulate protein activity and provide the switch between different pathways. In this paper we summarize the biological importance of homooligomeric assemblies, physico-chemical properties of their interfaces, experimental and computational methods for their identification and prediction. We particularly focus on homooligomer evolution and describe the mechanisms to develop new specificities through the formation of different homooligomeric complexes. Finally, we discuss the possible role of oligomeric transitions in the regulation of protein activity and compile a set of experimental examples with such regulatory mechanisms. C1 [Hashimoto, Kosuke; Nishi, Hafumi; Bryant, Stephen; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Panchenko, AR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM panch@ncbi.nlm.nih.gov OI Nishi, Hafumi/0000-0002-0846-0330 FU National Institutes of Health/DHHS; Japan Society for the Promotion of Science FX We thank Tom Madej for careful reading of the manuscript. This work was supported by National Institutes of Health/DHHS (Intramural Research program of the National Library of Medicine). KH was supported by a JSPS Research Fellowship from the Japan Society for the Promotion of Science. NR 89 TC 31 Z9 31 U1 1 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3975 J9 PHYS BIOL JI Phys. Biol. PD JUN PY 2011 VL 8 IS 3 AR 035007 DI 10.1088/1478-3975/8/3/035007 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 763MB UT WOS:000290560100008 PM 21572178 ER PT J AU Kim, YA Przytycki, JH Wuchty, S Przytycka, TM AF Kim, Yoo-Ah Przytycki, Jozef H. Wuchty, Stefan Przytycka, Teresa M. TI Modeling information flow in biological networks SO PHYSICAL BIOLOGY LA English DT Article ID PROTEIN INTERACTION NETWORK; GENES; MAP; IDENTIFICATION; INTERACTOME; LANDSCAPE; REVEALS; YEAST AB Large-scale molecular interaction networks are being increasingly used to provide a system level view of cellular processes. Modeling communications between nodes in such huge networks as information flows is useful for dissecting dynamical dependences between individual network components. In the information flow model, individual nodes are assumed to communicate with each other by propagating the signals through intermediate nodes in the network. In this paper, we first provide an overview of the state of the art of research in the network analysis based on information flow models. In the second part, we describe our computational method underlying our recent work on discovering dysregulated pathways in glioma. Motivated by applications to inferring information flow from genotype to phenotype in a very large human interaction network, we generalized previous approaches to compute information flows for a large number of instances and also provided a formal proof for the method. C1 [Kim, Yoo-Ah; Wuchty, Stefan; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, NLM, Bethesda, MD 20894 USA. [Przytycki, Jozef H.] George Washington Univ, Dept Math, Washington, DC 20052 USA. RP Kim, YA (reprint author), NIH, Natl Ctr Biotechnol Informat, NLM, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM kimy3@ncbi.nlm.nih.gov; przytyck@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine; Polish Scientific grant [N N201387034]; GWU; CCAS/UFF award FX YAK, SW and TMP are supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. JHP was partially supported by the Polish Scientific grant no N N201387034, the GWU REF grant and the CCAS/UFF award. NR 26 TC 10 Z9 11 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 EI 1478-3975 J9 PHYS BIOL JI Phys. Biol. PD JUN PY 2011 VL 8 IS 3 AR 035012 DI 10.1088/1478-3975/8/3/035012 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 763MB UT WOS:000290560100013 PM 21572171 ER PT J AU Levens, D Benham, CJ AF Levens, David Benham, Craig J. TI DNA stress and strain, in silico, in vitro and in vivo SO PHYSICAL BIOLOGY LA English DT Article ID COVALENT HISTONE MODIFICATIONS; C-MYC EXPRESSION; G-QUADRUPLEX DNA; NUCLEOSOME ORGANIZATION; TORSIONAL STRESS; SUPERCOILED DNA; GENE-EXPRESSION; B-DNA; CHROMATIN FIBER; UPSTREAM DNA AB A vast literature has explored the genetic interactions among the cellular components regulating gene expression in many organisms. Early on, in the absence of any biochemical definition, regulatory modules were conceived using the strict formalism of genetics to designate the modifiers of phenotype as either cis- or trans-acting depending on whether the relevant genes were embedded in the same or separate DNA molecules. This formalism distilled gene regulation down to its essence in much the same way that consideration of an ideal gas reveals essential thermodynamic and kinetic principles. Yet just as the anomalous behavior of materials may thwart an engineer who ignores their non-ideal properties, schemes to control and manipulate the genetic and epigenetic programs of cells may falter without a fuller and more quantitative elucidation of the physical and chemical characteristics of DNA and chromatin in vivo. C1 [Levens, David] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Benham, Craig J.] Univ Calif Davis, UC Davis Genome Ctr, Davis, CA 95616 USA. RP Levens, D (reprint author), NCI, Pathol Lab, 10 Ctr Dr,Bldg 10,Room 2N106, Bethesda, MD 20892 USA. EM levens@helix.nih.gov; cjbenham@ucdavis.edu RI Benham, Craig/G-1512-2013; Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU National Science Foundation [DBI 08-50214]; US National Institues of Health, National Cancer Institue, Center for Cancer Research FX This work was supported in part by grant DBI 08-50214 to CJB from the National Science Foundation. DL is supported by the Intramural Research Program of the US National Institues of Health, National Cancer Institue, Center for Cancer Research. NR 79 TC 9 Z9 9 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3975 J9 PHYS BIOL JI Phys. Biol. PD JUN PY 2011 VL 8 IS 3 AR 035011 DI 10.1088/1478-3975/8/3/035011 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 763MB UT WOS:000290560100012 PM 21572180 ER PT J AU Nussinov, R Panchenko, AR Przytycka, T AF Nussinov, Ruth Panchenko, Anna R. Przytycka, Teresa TI Physics approaches to protein interactions and gene regulation PREFACE SO PHYSICAL BIOLOGY LA English DT Editorial Material C1 [Nussinov, Ruth] NCI Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Panchenko, Anna R.; Przytycka, Teresa] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA. RP Nussinov, R (reprint author), NCI Frederick, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. FU Intramural NIH HHS NR 0 TC 6 Z9 6 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3975 J9 PHYS BIOL JI Phys. Biol. PD JUN PY 2011 VL 8 IS 3 AR 030301 DI 10.1088/1478-3975/8/3/030301 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 763MB UT WOS:000290560100001 PM 21572176 ER PT J AU Kifer, I Nussinov, R Wolfson, HJ AF Kifer, Ilona Nussinov, Ruth Wolfson, Haim J. TI Protein structure prediction using a docking-based hierarchical folding scheme SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE protein folding; structure prediction; fragment based; hierarchical folding; docking; template ranking ID SECONDARY STRUCTURE; STRUCTURE ALIGNMENT; CASP8; DICTIONARY; REFINEMENT; FRAGMENTS AB The pathways by which proteins fold into their specific native structure are still an unsolved mystery. Currently, many methods for protein structure prediction are available, and most of them tackle the problem by relying on the vast amounts of data collected from known protein structures. These methods are often not concerned with the route the protein follows to reach its final fold. This work is based on the premise that proteins fold in a hierarchical manner. We present FOBIA, an automated method for predicting a protein structure. FOBIA consists of two main stages: the first finds matches between parts of the target sequence and independently folding structural units using profile-profile comparison. The second assembles these units into a 3D structure by searching and ranking their possible orientations toward each other using a docking-based approach. We have previously reported an application of an initial version of this strategy to homology based targets. Since then we have considerably enhanced our method's abilities to allow it to address the more difficult template-based target category. This allows us to now apply FOBIA to the template-based targets of CASP8 and to show that it is both very efficient and promising. Our method can provide an alternative for template-based structure prediction, and in particular, the docking-based ranking technique presented here can be incorporated into any profile-profile comparison based method. Proteins 2011; 79:1759-1773. (C) 2011 Wiley-Liss, Inc. C1 [Kifer, Ilona; Wolfson, Haim J.] Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Kifer, I (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. EM ilonak@post.tau.ac.il; wolfson@post.tau.ac.il FU Israel Science Foundation [1403/09]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Institute FX Grant sponsor: Israel Science Foundation; Grant number: 1403/09; Grant sponsor: National Cancer Institute, National Institutes of Health; Grant number: HHSN261200800001E; Grant sponsor: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Institute. NR 30 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-3585 J9 PROTEINS JI Proteins PD JUN PY 2011 VL 79 IS 6 BP 1759 EP 1773 DI 10.1002/prot.22999 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 762NF UT WOS:000290485500007 PM 21445943 ER PT J AU Revilla-Lopez, G Rodriguez-Ropero, F Curco, D Torras, J Calaza, MI Zanuy, D Jimenez, AI Cativiela, C Nussinov, R Aleman, C AF Revilla-Lopez, Guillem Rodriguez-Ropero, Francisco Curco, David Torras, Juan Isabel Calaza, M. Zanuy, David Jimenez, Ana I. Cativiela, Carlos Nussinov, Ruth Aleman, Carlos TI Integrating the intrinsic conformational preferences of noncoded alpha-amino acids modified at the peptide bond into the Noncoded Amino acids Database SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE N-substituted amino acids; thio-amino acids; diamines; diacids; retropeptides; protein engineering; amino acids survey ID PARTIALLY MODIFIED RETRO; LINEAR OLIGOPEPTIDES; RIBONUCLEASE-S; N-METHYLATION; GENETIC-CODE; PROTEIN; ALANINE; RESIDUES; DIPEPTIDES; CHEMISTRY AB Recently, we reported a database (Noncoded Amino acids Database; http://recerca.upc.edu/imem/index.htm) that was built to compile information about the intrinsic conformational preferences of nonproteinogenic residues determined by quantum mechanical calculations, as well as bibliographic information about their synthesis, physical and spectroscopic characterization, the experimentally established conformational propensities, and applications (Revilla-Lopez et al., J Phys Chem B 2010;114:7413-7422). The database initially contained the information available for alpha-tetrasubstituted a-amino acids. In this work, we extend NCAD to three families of compounds, which can be used to engineer peptides and proteins incorporating modifications at the -NHCO- peptide bond. Such families are: N-substituted alpha-amino acids, thio-alpha-amino acids, and diamines and diacids used to build retropeptides. The conformational preferences of these compounds have been analyzed and described based on the information captured in the database. In addition, we provide an example of the utility of the database and of the compounds it compiles in protein and peptide engineering. Specifically, the symmetry of a sequence engineered to stabilize the 3(10)-helix with respect to the alpha-helix has been broken without perturbing significantly the secondary structure through targeted replacements using the information contained in the database. Proteins 2011; 79:1841-1852. (C) 2011 Wiley-Liss, Inc. C1 [Revilla-Lopez, Guillem; Rodriguez-Ropero, Francisco; Zanuy, David; Aleman, Carlos] Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain. [Curco, David] Univ Barcelona, Fac Quim, Dept Engn Quim, E-08028 Barcelona, Spain. [Torras, Juan] Univ Politecn Cataluna, EEI, Dept Engn Quim, Igualada 08700, Spain. [Isabel Calaza, M.; Jimenez, Ana I.; Cativiela, Carlos] Univ Zaragoza, Dept Quim Organ, Inst Ciencia Mat Aragon, CSIC, E-50009 Zaragoza, Spain. [Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. [Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-8028 Barcelona, Spain. RP Aleman, C (reprint author), Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, Diagonal 647, E-08028 Barcelona, Spain. EM carlos.aleman@upc.edu RI Rodriguez-Ropero, Francisco/F-2458-2011; Revilla-Lopez, Guillem/G-8552-2011; Zanuy, David/G-3930-2014; Torras, Juan/F-5622-2015 OI Rodriguez-Ropero, Francisco/0000-0001-7435-8986; Zanuy, David/0000-0001-7704-2178; Torras, Juan/0000-0001-8737-7609 FU Ministerio de Ciencia e Innovacion - FEDER [CTQ2007-62245, CTQ2008-00423-E/BQU, CTQ2010-17436]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Generalitat de Catalunya [2009 SGR 925]; Gobierno de Aragon [E40]; NIH, National Cancer Institute, Center for Cancer Research FX Grant sponsor: Ministerio de Ciencia e Innovacion - FEDER; Grant numbers: CTQ2007-62245, CTQ2008-00423-E/BQU, CTQ2010-17436; Grant sponsor: National Cancer Institute, National Institutes of Health; Grant numbers: HHSN261200800001E; Grant sponsors: Generalitat de Catalunya (research group 2009 SGR 925; XRQTC), Gobierno de Aragon (research group E40), Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research NR 71 TC 5 Z9 5 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-3585 J9 PROTEINS JI Proteins PD JUN PY 2011 VL 79 IS 6 BP 1841 EP 1852 DI 10.1002/prot.23009 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 762NF UT WOS:000290485500014 PM 21491493 ER PT J AU Detels, R Green, AM Klausner, JD Katzenstein, D Gaydos, C Handsfield, HH Pequegnat, W Mayer, K Hartwell, TD Quinn, TC AF Detels, Roger Green, Annette M. Klausner, Jeffrey D. Katzenstein, David Gaydos, Charlotte Handsfield, H. Hunter Pequegnat, Willo Mayer, Kenneth Hartwell, Tyler D. Quinn, Thomas C. TI The Incidence and Correlates of Symptomatic and Asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae Infections in Selected Populations in Five Countries SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED INFECTIONS; ACID AMPLIFICATION TESTS; SYNDROMIC MANAGEMENT; NATURAL COURSE; MEN; PREVALENCE; PREVENTION; CHINA; WOMEN; THAILAND AB Background: Asymptomatic Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea) infections pose diagnostic and control problems in developing countries. Methods: Participants in China, India, Peru, Russia, and Zimbabwe were screened for C. trachomatis and N. gonorrhoeae infections and symptoms. Results: A total of 18,014 participants were evaluated at baseline, 15,054 at 12 months, and 14,243 at 24 months. The incidence of chlamydia in men was 2.0 per 100 person years both from baseline to 12 months and from 12 to 24 months, and in women, 4.6 from baseline to 12 months and 3.6 from 12 to 24 months; a range of 31.2% to 100% reported no symptoms across the 5 countries. The incidence of gonorrhea in men was 0.3 per 100 person years both from baseline to 12 months and from 12 to 24 months, and in women, 1.4 from baseline to 12 months and 1.1 from 12 to 24 months; a range of 66.7% to 100% reported no symptoms. Being female, aged 18 to 24 years, and having more than 1 partner were associated with both the infections. In addition, being divorced, separated, or widowed was associated with gonorrhea. Being male, having 6+ years of education, and reporting only 1 partner were associated with having no symptoms among those infected with chlamydia. No variables correlated with asymptomatic gonorrhea among those infected. Conclusion: A high prevalence and incidence of asymptomatic sexually transmitted infections was identified among men and women in a wide variety of settings. More effective programs are needed to identify and treat chlamydia and gonorrhea infections, especially among women, young adults, those with multiple partners, those repeatedly infected, and particularly those at risk without symptoms. The risk of transmission from persons with no symptoms requires further study. C1 [Detels, Roger] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. [Green, Annette M.; Hartwell, Tyler D.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Katzenstein, David] Stanford Univ, Ctr AIDS Res, Stanford, CA 94305 USA. [Klausner, Jeffrey D.] UCSF, Dept Med, San Francisco, CA USA. [Gaydos, Charlotte; Quinn, Thomas C.] Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA. [Handsfield, H. Hunter] Univ Washington, Ctr AIDS & STDs, Seattle, WA 98195 USA. [Pequegnat, Willo] NIMH, NIH, Bethesda, MD 20892 USA. [Mayer, Kenneth] Brown Univ, Providence, RI 02912 USA. [Quinn, Thomas C.] NIAID, NIH, Baltimore, MD USA. RP Detels, R (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, 71-269 CHS,Box 951772, Los Angeles, CA 90095 USA. EM detels@ucla.edu FU NIH/NIMH [U10 MH61513]; 5-country Cooperative Agreement conducted in China, India, Peru, Russia, and Zimbabwe FX Supported by NIH/NIMH grant U10 MH61513, a 5-country Cooperative Agreement conducted in China, India, Peru, Russia, and Zimbabwe. Each site selected a different venue and population with which to implement the prevention program entitled "The Community Public Opinion Leader (C-POL) Intervention." NR 30 TC 37 Z9 39 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JUN PY 2011 VL 38 IS 6 BP 503 EP 509 DI 10.1097/OLQ.0b013e318206c288 PG 7 WC Infectious Diseases SC Infectious Diseases GA 763MH UT WOS:000290561200008 PM 22256336 ER PT J AU Lyke, KE Fernandez-Vina, MA Cao, K Hollenbach, J Coulibaly, D Kone, AK Guindo, A Burdett, LA Hartzman, RJ Wahl, AR Hildebrand, WH Doumbo, OK Plowe, CV Sztein, MB AF Lyke, K. E. Fernandez-Vina, M. A. Cao, K. Hollenbach, J. Coulibaly, D. Kone, A. K. Guindo, A. Burdett, L. A. Hartzman, R. J. Wahl, A. R. Hildebrand, W. H. Doumbo, O. K. Plowe, C. V. Sztein, M. B. TI Association of HLA alleles with Plasmodium falciparum severity in Malian children SO TISSUE ANTIGENS LA English DT Article DE children; human leukocyte antigen class I; human leukocyte antigen class II; malaria; Mali; Plasmodium falciparum ID CD8(+) T-CELLS; SEVERE MALARIA; CEREBRAL MALARIA; HEALTHY CONTROLS; RESISTANCE; POPULATION; PEPTIDE; INTERLEUKIN-10; PROTECTION; HLA-DRB1 AB Pre-erythrocytic immunity to Plasmodium falciparum malaria is likely to be mediated by T-cell recognition of malaria epitopes presented on infected host cells via class I and II major histocompatibility complex (MHC) antigens. To test for associations of human leukocyte antigen (HLA) alleles with disease severity, we performed high-resolution typing of HLA class I and II loci and compared the distributions of alleles of HLA-A, -B, -C and -DRB1 loci in 359 Malian children of Dogon ethnicity with uncomplicated or severe malaria. We observed that alleles A*30:01 and A*33:01 had higher frequency in the group of patients with cerebral disease compared to patients with uncomplicated disease [A*30:01: gf = 0.2031 vs gf = 0.1064, odds ratio (OR) = 3.17, P = 0.004, confidence interval (CI) (1.94-5.19)] and [A*33:01: gf = 0.0781 vs gf = 0.0266, 4.21, P = 0.005, CI (1.89-9.84)], respectively. The A*30:01 and A*33:01 alleles share some sequence motifs and A*30:01 appears to have a unique peptide binding repertoire compared to other A*30 group alleles. Computer algorithms predicted malaria peptides with strong binding affinity for HLA-A*30:01 and HLA-A*33:01 but not to closely related alleles. In conclusion, we identified A*30:01 and A*33:01 as potential susceptibility factors for cerebral malaria, providing further evidence that polymorphism of MHC genes results in altered malaria susceptibility. C1 [Lyke, K. E.; Plowe, C. V.; Sztein, M. B.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Dept Med, Baltimore, MD 21201 USA. [Fernandez-Vina, M. A.] Univ Texas MD Anderson Canc Ctr, Lab Med, Houston, TX 77030 USA. [Cao, K.] Cedars Sinai Hlth Syst, HLA Lab, Comprehens Transplant Ctr, Los Angeles, CA USA. [Cao, K.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. [Hollenbach, J.] Childrens Hosp Oakland, Res Inst, Ctr Genet, Oakland, CA 94609 USA. [Coulibaly, D.; Kone, A. K.; Guindo, A.; Doumbo, O. K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali. [Burdett, L. A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Burdett, L. A.] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Hartzman, R. J.] Georgetown Univ, CW Bill Young DoD Marrow Donor Program, Naval Med Res Inst, Kensington, MD USA. [Wahl, A. R.; Hildebrand, W. H.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. [Plowe, C. V.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Howard Hughes Med Inst, Baltimore, MD 21201 USA. RP Sztein, MB (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, Dept Med, 685 W Baltimore St HSF 1,Rm 480, Baltimore, MD 21201 USA. EM msztein@medicine.umaryland.edu RI Cao, Kai/I-4448-2013 FU NIH from the National Institute of Allergy and Infectious Diseases [N01-AI85346]; Doris Duke Clinical Scientist Development Award; Doris Duke Charitable Foundation; Howard Hughes Medical Institute FX The conduct of the trial was supported by an NIH contract N01-AI85346 from the National Institute of Allergy and Infectious Diseases. KEL is supported by a Doris Duke Clinical Scientist Development Award and CVP is supported by both a Doris Duke Distinguished Clinical Scientist Award from the Doris Duke Charitable Foundation and the Howard Hughes Medical Institute. Program staff from the National Institute of Allergy and Infectious Diseases contributed to study design discussions but played no role in the collection, analysis or interpretation of data, writing the paper or the decision to submit it for publication. In addition, we would like to thank Drs. Mark Travassos, Shannon Takala and Andrea Barry for their thoughtful contributions toward malaria protein sequences and strain variance. NR 48 TC 8 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUN PY 2011 VL 77 IS 6 BP 562 EP 571 DI 10.1111/j.1399-0039.2011.01661.x PG 10 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 759FR UT WOS:000290226600006 PM 21447146 ER PT J AU Hoofnagle, JH Sarkar, S AF Hoofnagle, J. H. Sarkar, S. TI Fatigue and serum carnitine levels in chronic liver disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Letter ID CHRONIC HEPATITIS-C; QUALITY-OF-LIFE; INFECTION; RIBAVIRIN; ALPHA-2A; THERAPY; HEALTH C1 [Hoofnagle, J. H.; Sarkar, S.] NIDDKD, Liver Dis Branch, Intramural Div, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Branch, Intramural Div, NIH, Bethesda, MD 20892 USA. EM HoofnagleJ@nih.gov OI Sarkar, Souvik/0000-0002-9358-4257 NR 7 TC 0 Z9 0 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD JUN 1 PY 2011 VL 33 IS 11 BP 1252 EP 1253 DI 10.1111/j.1365-2036.2011.04642.x PG 2 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 758OL UT WOS:000290174300009 PM 21535052 ER PT J AU Jessup, JM Gunderson, LL Greene, FL Washington, MK Compton, CC Sobin, LH Minsky, B Goldberg, RM Hamilton, SR AF Jessup, J. Milburn Gunderson, Leonard L. Greene, Frederick L. Washington, Mary Kay Compton, Carolyn C. Sobin, Leslie H. Minsky, Bruce Goldberg, Richard M. Hamilton, Stanley R. TI 2010 Staging System for Colon and Rectal Carcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; MICROSATELLITE INSTABILITY; CIRCUMFERENTIAL MARGIN; ADJUVANT THERAPY; CANCER; RECURRENCE; SURVIVAL; CATEGORIZATION; FLUOROURACIL; CHEMOTHERAPY C1 [Jessup, J. Milburn] NCI, Canc Diag Program, Rockville, MD USA. [Gunderson, Leonard L.] Mayo Clin, Ctr Canc, Dept Radiat Therapy, Rochester, MN USA. [Greene, Frederick L.] Carolinas Med Ctr, Dept Surg, Charlotte, NC 28203 USA. [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, Rockville, MD USA. [Sobin, Leslie H.] Int Union Canc, Geneva, Switzerland. [Minsky, Bruce] Univ Chicago, Dept Radiat Oncol, Med Ctr, Chicago, IL 60637 USA. [Goldberg, Richard M.] Univ N Carolina, Div Hematol & Oncol, Chapel Hill, NC USA. [Hamilton, Stanley R.] UTMD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX USA. RP Jessup, JM (reprint author), NCI, Canc Diag Program, Rockville, MD USA. EM jessupj@mail.nih.gov RI Goldberg , Richard/M-1311-2013 NR 27 TC 8 Z9 8 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2011 VL 18 IS 6 BP 1513 EP 1517 DI 10.1245/s10434-010-1360-1 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 759TL UT WOS:000290271300001 ER PT J AU Jonsson, H Helgadottir, GP Aspelund, T Eiriksdottir, G Sigurdsson, S Siggeirsdottir, K Ingvarsson, T Harris, TB Launer, L Gudnason, V AF Jonsson, Helgi Helgadottir, Gudrun P. Aspelund, Thor Eiriksdottir, Gudny Sigurdsson, Sigurdur Siggeirsdottir, Kristin Ingvarsson, Thorvaldur Harris, Tamara B. Launer, Lenore Gudnason, Vilmundur TI The presence of total knee or hip replacements due to osteoarthritis enhances the positive association between hand osteoarthritis and atherosclerosis in women: the AGES-Reykjavik study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID KLOTHO GENE; DISEASE; PROTEASES AB Objective This study examines the relationship between total knee replacements (TKR), total hip replacements (THR) or replacements of either joint (total joint replacement; TJR) due to osteoarthritis and atherosclerosis in a large population-based study. Methods The participants were 2195 men and 2975 women, mean age 76 +/- 6 years. The osteoarthritis data were analysed in relation to measures of atherosclerosis, including carotid artery intima media thickness and plaque severity (ultrasound), coronary and aortic calcifications (CT), cerebral white matter lesions (MRI) and a history of previous cardiac and cerebral events. Results The prevalence of TKR was 223 (4.3%) and THR 316 (6.1%). The presence of TJR in women was associated with a non-significant trend towards increased carotid plaque severity, coronary calcifications and periventricular white matter hyperintensities (PVH) but not with a history of cardiac or cerebral events. No associations were seen in men. When TJR were grouped according to the presence or absence of hand osteoarthritis (HOA) there was a highly significant association in the order -TJR/-HOA < + TJR/-HOA < -TJR/+HOA < +TJR/+HOA, for carotid plaque severity, coronary calcifications and PVH. Conclusion The presence of TJR did not show a significant independent association with atherosclerosis but enhanced the strength of the positive association between HOA and subclinical atherosclerosis in women. C1 [Jonsson, Helgi] Univ Iceland, Landspitalinn Univ Hosp, IS-108 Reykjavik, Iceland. [Helgadottir, Gudrun P.; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, IS-108 Reykjavik, Iceland. [Aspelund, Thor; Eiriksdottir, Gudny; Sigurdsson, Sigurdur; Siggeirsdottir, Kristin; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Ingvarsson, Thorvaldur] Akureyri Cent Hosp, Akureyri, Iceland. [Harris, Tamara B.; Launer, Lenore] NIA, Bethesda, MD 20892 USA. RP Jonsson, H (reprint author), Univ Iceland, Landspitalinn Univ Hosp, IS-108 Reykjavik, Iceland. EM helgi@hi.is RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 FU NIH [N01-AG-12100]; NIA; Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament); Icelandic Osteoarthritis Fund; University of Iceland FX The Age, Gene/Environment Susceptibility Reykjavik Study (AGES-Reykjavik) has been funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament), the Icelandic Osteoarthritis Fund and the University of Iceland Research Fund. NR 20 TC 9 Z9 9 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2011 VL 70 IS 6 BP 1087 EP 1090 DI 10.1136/ard.2010.144980 PG 4 WC Rheumatology SC Rheumatology GA 758GF UT WOS:000290149900034 PM 21367759 ER PT J AU Lee, SJ Koo, H Lee, DE Min, S Lee, S Chen, XY Choi, Y Leary, JF Park, K Jeong, SY Kwon, IC Kim, K Choi, K AF Lee, So Jin Koo, Heebeom Lee, Dong-Eun Min, Solki Lee, Seulki Chen, Xiaoyuan Choi, Yongseok Leary, James F. Park, Kinam Jeong, Seo Young Kwon, Ick Chan Kim, Kwangmeyung Choi, Kuiwon TI Tumor-homing photosensitizer-conjugated glycol chitosan nanoparticles for synchronous photodynamic imaging and therapy based on cellular on/off system SO BIOMATERIALS LA English DT Article DE Photosensitizer; Nanoparticle; Photodynamic therapy; Drug delivery; Glycol chitosan; Cellular on-off system ID POLYMERIC MICELLES; AQUEOUS-SOLUTION; RELEASE; DELIVERY; CANCER; AGENTS; CELLS AB Herein, we developed the photosensitizer, protoporphyrin IX (PpIX), conjugated glycol chitosan (GC) nanoparticles (PpIX-GC-NPs) as tumor-homing drug carriers with cellular on/off system for photodynamic imaging and therapy, simultaneously. In order to prepare PpIX-GC-NPs, hydrophobic PpIXs were chemically conjugated to GC polymer and the amphiphilic PpIX-GC conjugates formed a stable nanoparticle structure in aqueous condition, wherein conjugated PpIX molecules formed hydrophobic inner-cores and they were covered by the hydrophilic GC polymer shell. Based on the nanoparticle structure. PpIX-GC-NPs showed the self-quenching effect that is 'off' state with no fluorescence signal and phototoxicity with light exposure. It is due to the compact crystallized PpIX molecules in the nanoparticles as confirmed by dynamic light scattering and X-ray diffraction methods. However, after cellular uptake, compact nanoparticle structure gradually decreased to generate strong fluorescence signal and singlet oxygen generation when irradiated. Importantly, PpIX-GC-NPs-treated mice presented prolonged blood circulation, enhanced tumor targeting ability, and improved in vivo therapeutic efficiency in tumor-bearing mice, compared to that of free PpIX-treated mice. These results proved that this tumor-homing cellular 'on/off nanoparticle system of PpIX-GC-NPs has a great potential for synchronous photodynamic imaging and therapy in cancer treatment. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Lee, So Jin; Koo, Heebeom; Lee, Dong-Eun; Min, Solki; Kwon, Ick Chan; Kim, Kwangmeyung; Choi, Kuiwon] Korea Inst Sci & Technol, Biomed Res Ctr, Seoul 136791, South Korea. [Lee, So Jin; Choi, Yongseok] Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South Korea. [Min, Solki; Jeong, Seo Young] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea. [Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Leary, James F.; Park, Kinam] Purdue Univ, Dept Biomed Engn, W Lafayette, IN 47907 USA. [Leary, James F.; Park, Kinam] Purdue Univ, Dept Pharmaceut, W Lafayette, IN 47907 USA. RP Kim, K (reprint author), Korea Inst Sci & Technol, Biomed Res Ctr, 39-1 Hawolgok Dong, Seoul 136791, South Korea. EM kim@kist.re.kr; choi@kist.re.kr RI Choi, Yongseok/F-8375-2012; Leary, James/H-8554-2014 OI Choi, Yongseok/0000-0002-3622-3439; Leary, James/0000-0002-0250-4427 FU MEST [2009-0081876]; KIST FX This work was financially supported by the Real-Time Molecular Imaging Project, GRL Program of MEST, Fusion Technology Project (2009-0081876) of MEST, and by grant to the Intramural Research Program of KIST. NR 27 TC 81 Z9 83 U1 9 U2 75 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JUN PY 2011 VL 32 IS 16 BP 4021 EP 4029 DI 10.1016/j.biomaterials.2011.02.009 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 758WA UT WOS:000290196700015 PM 21376388 ER PT J AU Caron, P Simonds, WF Maiza, JC Rubin, M Cantor, T Rousseau, L Bilezikian, JP Souberbielle, JC D'Amour, P AF Caron, Philippe Simonds, William F. Maiza, Jean-Christophe Rubin, Mishaela Cantor, Tom Rousseau, Louise Bilezikian, John P. Souberbielle, Jean-Claude D'Amour, Pierre TI Nontruncated amino-terminal parathyroid hormone overproduction in two patients with parathyroid carcinoma: a possible link to HRPT2 gene inactivation SO CLINICAL ENDOCRINOLOGY LA English DT Article ID FAMILIAL ISOLATED HYPERPARATHYROIDISM; SECONDARY HYPERPARATHYROIDISM; PTH DISTINCT; FORM; RATIO; HPTH(1-84); MUTATION; 3RD AB P>Objective Some patients with parathyroid carcinoma present with an over-production of nontruncated amino-terminal (NT-N) parathyroid hormone (PTH), a post-transcriptionally modified form of PTH(1-84). This is usually picked up on an elevated whole (W) PTH (third-generation)/total (T) (second-generation) PTH assay ratio (N > 0 center dot 8). Patients and design Two parathyroid cancer patients with several episodes of hypercalcaemia and multiple surgeries are described. In both patients, W-PTH, T-PTH and circulating PTH molecular forms separated by high-pressure liquid chromatography (HPLC) were measured with the same assays. qPCR was used to study HRPT2 gene mutation. Results The first patient had total calcium of 3 center dot 8 and 3 center dot 22 mmol/l before the fourth and fifth surgeries, and third/second-generation PTH ratios of 2 center dot 95 and 3 center dot 6, respectively. After the fourth surgery, the ratio remained normal for 1 year and increased progressively to 3 center dot 6 over 15 months. This preceded hypercalcaemia by 6 months. The ratio became normal after the fifth surgery. HPLC analysis disclosed an over-expression of NT-N PTH to 82 center dot 2% (N < 10%) relative to hPTH(1-84) before the fifth surgery. A deletion of all the tested exons of the HRPT2 gene was identified. In the second patient, W-PTH/T-PTH ratio was 0 center dot 89 when serum calcium was 3 center dot 3 mmol/l. NT-N PTH was also over-expressed at 51 center dot 9%. An inactivating mutation of the HRPT2 gene was also identified. Conclusions This may suggest that a progressive rise in third/second-generation ratio may have possible clinical utility to monitor parathyroid cancer recurrence. A possible association between NT-N PTH overproduction and HRPT2 gene inactivation is also suggested. C1 [Rousseau, Louise; D'Amour, Pierre] Hop St Luc, Ctr Hosp Univ Montreal CRCHUM, Ctr Rech, Montreal, PQ H2X 1P1, Canada. [Caron, Philippe; Maiza, Jean-Christophe] Ctr Hosp Univ Larrey, Dept Endocrinol & Metab Dis, Toulouse, France. [Simonds, William F.] NIH, Metab Dis Branch, Bethesda, MD 20892 USA. [Rubin, Mishaela; Bilezikian, John P.] Columbia Univ, Dept Med, New York, NY USA. [Cantor, Tom] Scantibodies Lab Inc, Santee, CA USA. [Souberbielle, Jean-Claude] Hop Necker Enfants Malad, Physiol Lab, Paris, France. RP D'Amour, P (reprint author), Hop St Luc, CHUM, Ctr Rech, 264,Boul Rene Levesque Est, Montreal, PQ H2X 1P1, Canada. EM rechcalcium.chum@ssss.gouv.qc.ca FU NIH; National Institute of Diabetes and Digestive and Kidney Diseases; Scantibodies Laboratory Inc., Santee, CA, USA FX This work was supported by grants from NIH to John Bilezikian and Mishaela Rubin, from the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases to William F. Simonds, and by a grant from Scantibodies Laboratory Inc., Santee, CA, USA to Pierre D'Amour. Tom Cantor is President of Scantibodies Laboratory Inc. The authors wish to thank Manon Livernois for typing this manuscript and Ovid Da Silva for editing it. NR 14 TC 11 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUN PY 2011 VL 74 IS 6 BP 694 EP 698 DI 10.1111/j.1365-2265.2011.04021.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760IS UT WOS:000290318600006 PM 21521290 ER PT J AU Carmona-Rivera, C Hess, RA O'Brien, K Golas, G Tsilou, E White, JG Gahl, WA Huizing, M AF Carmona-Rivera, C. Hess, R. A. O'Brien, K. Golas, G. Tsilou, E. White, J. G. Gahl, W. A. Huizing, M. TI Novel mutations in the HPS1 gene among Puerto Rican patients SO CLINICAL GENETICS LA English DT Article DE albinism; bleeding diathesis; BLOC-3; platelet dense body; pulmonary fibrosis ID HERMANSKY-PUDLAK-SYNDROME; LOCUS HETEROGENEITY; PULMONARY-FIBROSIS; SYNDROME TYPE-1; BIOGENESIS; ORGANELLES; COMPLEX; PROTEIN; FORM; TRAFFICKING AB Hermansky-Pudlak syndrome (HPS) is a disorder of oculocutaneous albinism (OCA) and platelet storage pool deficiency. Eight different disease-causing genes have been identified, whose gene products are thought to be involved in the biogenesis of lysosome-related organelles. HPS type 1 (HPS-1) is the most common HPS subtype in Puerto Rico, with a frequency of 1:1800 in the northwest of the island due to a founder mutation, i.e. a 16-bp duplication in exon 15 of the HPS1 gene (c.1472_1487dup16; p.H497QfsX90). We identified three Puerto Rican HPS-1 patients who carried compound heterozygous HPS1 mutations. One patient was heterozygous for c.937G > A, causing a missense mutation (p.G313S) at the 3' splice junction of exon 10. This mutation resulted in activation of a cryptic intronic splice site causing an aberrantly spliced HPS1 mRNA that included 144-bp of intronic sequence, producing 11 novel amino acids followed by a stop codon. The other two patients were heterozygous for the previously reported c.972delC in HPS1, resulting in a frameshift and a premature stop codon (p.M325WfsX6). These findings indicate that, among Puerto Ricans, other HPS1 mutations apart from the 16-bp duplication should be considered in the analysis of this population. C1 [Carmona-Rivera, C.; Hess, R. A.; Gahl, W. A.; Huizing, M.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [O'Brien, K.; Golas, G.; Gahl, W. A.] NIH, Off Rare Dis, Intramural Program, Off Director, Bethesda, MD 20892 USA. [Tsilou, E.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [White, J. G.] Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. RP Carmona-Rivera, C (reprint author), NIH, Natl Human Genome Res, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C-103, Bethesda, MD 20892 USA. EM carmonac@mail.nih.gov FU National Human Genome Research Institute; National Eye Institute, National Institutes of Health, Bethesda, Maryland FX We thank the patients for participating in the NIH protocol. This work was supported by the Intramural Research program of the National Human Genome Research Institute and the National Eye Institute, National Institutes of Health, Bethesda, Maryland. NR 28 TC 3 Z9 3 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUN PY 2011 VL 79 IS 6 BP 561 EP 567 DI 10.1111/j.1399-0004.2010.01491.x PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 759TJ UT WOS:000290271100011 PM 20662851 ER PT J AU Rousset, X Shamburek, R Vaisman, B Amar, M Remaley, AT AF Rousset, Xavier Shamburek, Robert Vaisman, Boris Amar, Marcelo Remaley, Alan T. TI Lecithin Cholesterol Acyltransferase: An Anti- or Pro-atherogenic Factor? SO CURRENT ATHEROSCLEROSIS REPORTS LA English DT Article DE Lecithin cholesterol acyltransferase; High-density lipoprotein; Fish-eye disease; Cholesterol; Reverse cholesterol transport; Atherosclerosis; Enzyme replacement therapy; Biomarker ID HIGH-DENSITY-LIPOPROTEIN; TRANSPORT IN-VIVO; TRANSGENIC MICE; LCAT GENE; INCREASED ATHEROSCLEROSIS; HDL CONCENTRATIONS; PLASMA LECITHIN; DEFICIENT MICE; A-I; OVEREXPRESSION AB Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme that esterifies cholesterol and raises high-density lipoprotein cholesterol, but its role in atherosclerosis is not clearly established. Studies of various animal models have yielded conflicting results, but studies done in rabbits and non-human primates, which more closely simulate human lipoprotein metabolism, indicate that LCAT is likely atheroprotective. Although suggestive, there are also no biomarker studies that mechanistically link LCAT with cardiovascular disease. Imaging studies of patients with LCAT deficiency have also not yielded a clear answer to the role of LCAT in atherosclerosis. Recombinant LCAT, however, is currently being developed as a therapeutic product for enzyme replacement therapy of patients with genetic disorders of LCAT for the prevention and/or treatment of renal disease, but it may also have value for the treatment of acute coronary syndrome. C1 [Rousset, Xavier; Shamburek, Robert; Vaisman, Boris; Amar, Marcelo; Remaley, Alan T.] NHLBI, Inst Hlth, Cardiopulm Branch, Lipoprot Metab Sect, Bethesda, MD 20814 USA. RP Rousset, X (reprint author), NHLBI, Inst Hlth, Cardiopulm Branch, Lipoprot Metab Sect, 10 Ctr Dr Bldg,10-8N224, Bethesda, MD 20814 USA. EM roussetx@nhlbi.nih.gov RI Rousset, Xavier/B-3352-2008; Rousset, Xavier/H-5490-2015 OI Rousset, Xavier/0000-0002-5830-6577; Rousset, Xavier/0000-0002-5830-6577 FU National Institutes of Health FX All authors were supported by intramural NHLBI funds from the National Institutes of Health. NR 51 TC 37 Z9 41 U1 0 U2 5 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1523-3804 J9 CURR ATHEROSCLER REP JI Curr. Atherosclerol. Rep. PD JUN PY 2011 VL 13 IS 3 BP 249 EP 256 DI 10.1007/s11883-011-0171-6 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 758MB UT WOS:000290167800008 PM 21331766 ER PT J AU Sabia, M Hirsh, RA Torjman, MC Wainer, IW Cooper, N Domsky, R Goldberg, ME AF Sabia, Michael Hirsh, Robert A. Torjman, Marc C. Wainer, Irving W. Cooper, Niti Domsky, Richard Goldberg, Michael E. TI Advances in Translational Neuropathic Research: Example of Enantioselective Pharmacokinetic-Pharmacodynamic Modeling of Ketamine-induced Pain Relief in Complex Regional Pain Syndrome SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Complex regional pain syndrome; Hydroxylated metabolites; Dehydronorketamine; NMDA receptor; (R,S) Ketamine; (R,S) Norketamine; Enantioselective; Pharmacokinetics; Pharmacodynamics; Cytochromes; Neuropathic pain ID REFLEX SYMPATHETIC DYSTROPHY; RECEPTOR ANTAGONIST KETAMINE; SURGICAL-PATIENTS; INFUSION THERAPY; NERVE INJURY; DOUBLE-BLIND; RAT MODEL; VOLUNTEERS; SYMPTOMS; S(+)-KETAMINE AB Historically, complex regional pain syndrome (CRPS) was poorly defined, which meant that scientists and clinicians faced much uncertainty in the study, diagnosis, and treatment of the syndrome. The problem could be attributed to a nonspecific diagnostic criteria, unknown pathophysiologic causes, and limited treatment options. The two forms of CRPS still are painful, debilitating disorders whose sufferers carry heavy emotional burdens. Current research has shown that CRPS I and CRPS II are distinctive processes, and the presence or absence of a partial nerve lesion distinguishes them apart. Ketamine has been the focus of various studies involving the treatment of CRPS; however, currently, there is incomplete data from evidence-based studies. The question as to why ketamine is effective in controlling the symptoms of a subset of patients with CRPS and not others remains to be answered. A possible explanation to this phenomenon is pharmacogenetic differences that may exist in different patient populations. This review summarizes important translational work recently published on the treatment of CRPS using ketamine. C1 [Sabia, Michael; Hirsh, Robert A.; Torjman, Marc C.; Cooper, Niti; Domsky, Richard; Goldberg, Michael E.] Cooper Univ Hosp, Dept Anesthesiol, Camden, NJ 08103 USA. [Sabia, Michael; Hirsh, Robert A.; Torjman, Marc C.; Cooper, Niti; Domsky, Richard; Goldberg, Michael E.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. [Wainer, Irving W.] Natl Inst Hlth, Baltimore, MD 21224 USA. RP Sabia, M (reprint author), Cooper Univ Hosp, Dept Anesthesiol, 1 Cooper Plaza, Camden, NJ 08103 USA. EM Sabia-Michael@cooperhealth.edu FU National Institutes of Health, National Institute on Aging FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 45 TC 7 Z9 7 U1 1 U2 12 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1531-3433 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD JUN PY 2011 VL 15 IS 3 BP 207 EP 214 DI 10.1007/s11916-011-0185-3 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 758NB UT WOS:000290170400009 PM 21360034 ER PT J AU Holloway, GP Chou, CJ Lally, J Stellingwerff, T Maher, AC Gavrilova, O Haluzik, M Alkhateeb, H Reitman, ML Bonen, A AF Holloway, G. P. Chou, C. J. Lally, J. Stellingwerff, T. Maher, A. C. Gavrilova, O. Haluzik, M. Alkhateeb, H. Reitman, M. L. Bonen, A. TI Increasing skeletal muscle fatty acid transport protein 1 (FATP1) targets fatty acids to oxidation and does not predispose mice to diet-induced insulin resistance SO DIABETOLOGIA LA English DT Article DE Lipid membrane transport; Lipid metabolism; Lipid oxidation; Lipid trafficking; Skeletal muscle ID PALMITATE OXIDATION; LIPID-METABOLISM; IN-VIVO; INCREASED RATES; KNOCKOUT MICE; OVEREXPRESSION; FAT/CD36; MITOCHONDRIA; OBESITY; CELLS AB We examined in skeletal muscle (1) whether fatty acid transport protein (FATP) 1 channels long-chain fatty acid (LCFA) to specific metabolic fates in rats; and (2) whether FATP1-mediated increases in LCFA uptake exacerbate the development of diet-induced insulin resistance in mice. We also examined whether FATP1 is altered in insulin-resistant obese Zucker rats. LCFA uptake, oxidation and triacylglycerol esterification rates were measured in control and Fatp1-transfected soleus muscles to determine FATP1-mediated lipid handling. The effects of FATP1 on insulin sensitivity and triacylglycerol accumulation were determined in high-fat diet-fed wild-type mice and in muscle-specific Fatp1 (also known as Slc27a1) overexpressing transgenic mice driven by the muscle creatine kinase (Mck [also known as Ckm]) promoter. We also examined the relationship between FATP1 and both fatty acid transport and metabolism in insulin-resistant obese Zucker rats. Transient Fatp1 overexpression in soleus muscle increased (p < 0.05) palmitate transport (24%) and oxidation (35%), without altering triacylglycerol esterification or the intrinsic rate of palmitate oxidation in isolated mitochondria. In Mck/Fatp1 animals, Fatp1 mRNA and 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid uptake in skeletal muscle were upregulated (75%). However, insulin sensitivity and intramuscular triacylglycerol content did not differ between wild-type and Mck/Fatp1 mice following a 16 week high-fat diet. In insulin-resistant obese Zucker rats, LCFA transport and triacylglycerol accumulation were increased (85% and 24%, respectively), but this was not attributable to Fatp1 expression, as neither total cellular nor sarcolemmal FATP1 content were altered. Overexpression of Fatp1 in skeletal muscle increased the rate of LCFA transport and channelled these lipids to oxidation, not to intramuscular lipid accumulation. Therefore, skeletal muscle FATP1 overabundance does not predispose animals to diet-induced insulin resistance. C1 [Holloway, G. P.; Lally, J.; Maher, A. C.; Bonen, A.] Univ Guelph, Dept Human Hlth & Nutr Sci, Guelph, ON N1G 2W1, Canada. [Chou, C. J.; Gavrilova, O.; Haluzik, M.; Reitman, M. L.] NIDDK, Diabet Branch, NIH, Bethesda, MD USA. [Stellingwerff, T.] Nestle Res Ctr, Dept Nutr & Hlth, CH-1000 Lausanne, Switzerland. [Alkhateeb, H.] Hashemite Univ, Dept Lab Med Sci, Zarqa, Jordan. RP Holloway, GP (reprint author), Univ Guelph, Dept Human Hlth & Nutr Sci, 50 Stone Rd,ANNU Bldg,70, Guelph, ON N1G 2W1, Canada. EM ghollowa@uoguelph.ca RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 FU Canadian Institutes of Health Research; Natural Sciences and Engineering Research Council of Canada; National Institute of Diabetes, Digestive and Kidney Diseases FX This work was funded by the Canadian Institutes of Health Research (to A. Bonen) and the Natural Sciences and Engineering Research Council of Canada (to A. Bonen and G. P. Holloway). Mck/Fatp1 transgenic mouse studies were funded by the intramural programme of the National Institute of Diabetes, Digestive and Kidney Diseases (to M. L. Reitman, C. J. Chous, O. Gavrilova and M. Haluzik). A. Bonen is the Canada Research Chair in Metabolism and Health. NR 46 TC 16 Z9 17 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 2011 VL 54 IS 6 BP 1457 EP 1467 DI 10.1007/s00125-011-2114-8 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760ML UT WOS:000290328300024 PM 21442160 ER PT J AU El-Remessy, AB Rajesh, M Mukhopadhyay, P Horvath, B Patel, V Al-Gayyar, MMH Pillai, BA Pacher, P AF El-Remessy, A. B. Rajesh, M. Mukhopadhyay, P. Horvath, B. Patel, V. Al-Gayyar, M. M. H. Pillai, B. A. Pacher, P. TI Cannabinoid 1 receptor activation contributes to vascular inflammation and cell death in a mouse model of diabetic retinopathy and a human retinal cell line SO DIABETOLOGIA LA English DT Article DE Apoptosis; Cannabinoid; CB1; ICAM-1; NF kappa B; Rimonabant; SR141716; VCAM-1 ID ENDOTHELIAL GROWTH-FACTOR; GLYCATION END-PRODUCTS; FACTOR-KAPPA-B; OXIDATIVE STRESS; ENDOCANNABINOID SYSTEM; PROTEIN-KINASE; CB1 RECEPTORS; ZUCKER RATS; PEROXYNITRITE; CANNABIDIOL AB Recent studies have demonstrated that cannabinoid-1 (CB1) receptor blockade ameliorated inflammation, endothelial and/or cardiac dysfunction, and cell death in models of nephropathy, atherosclerosis and cardiomyopathy. However the role of CB1 receptor signalling in diabetic retinopathy remains unexplored. Using genetic deletion or pharmacological inhibition of the CB1 receptor with SR141716 (rimonabant) in a rodent model of diabetic retinopathy or in human primary retinal endothelial cells (HREC) exposed to high glucose, we explored the role of CB1 receptors in the pathogenesis of diabetic retinopathy. Diabetes was induced using streptozotocin in C57BL/6J Cb (1) (also known as Cnr1)(+/+) and Cb (1) (-/-) mice aged 8 to 12 weeks. Samples from mice retina or HREC were used to determine: (1) apoptosis; (2) activity of nuclear factor kappa B, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), poly (ADP-ribose) polymerase and caspase-3; (3) content of 3-nitrotyrosine and reactive oxygen species; and (4) activation of p38/Jun N-terminal kinase/mitogen-activated protein kinase (MAPK). Deletion of CB1 receptor or treatment of diabetic mice with CB1 receptor antagonist SR141716 prevented retinal cell death. Treatment of diabetic mice or HREC cells exposed to high glucose with SR141716 attenuated the oxidative and nitrative stress, and reduced levels of nuclear factor kappa B, ICAM-1 and VCAM-1. In addition, SR141716 attenuated the diabetes- or high glucose-induced pro-apoptotic activation of MAPK and retinal vascular cell death. Activation of CB1 receptors may play an important role in the pathogenesis of diabetic retinopathy by facilitating MAPK activation, oxidative stress and inflammatory signalling. Conversely, CB1 receptor inhibition may be beneficial in the treatment of this devastating complication of diabetes. C1 [Rajesh, M.; Mukhopadhyay, P.; Horvath, B.; Patel, V.; Pacher, P.] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [El-Remessy, A. B.; Al-Gayyar, M. M. H.; Pillai, B. A.] Univ Georgia, Program Clin & Expt Therapeut, Coll Pharm, Augusta, GA USA. [El-Remessy, A. B.; Al-Gayyar, M. M. H.; Pillai, B. A.] Charlie Norwood VA Med Ctr, Augusta, GA USA. [Horvath, B.] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, H-1085 Budapest, Hungary. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Horvath, Bela/A-7368-2009; Pacher, Pal/B-6378-2008; MUKHOPADHYAY, PARTHA/G-3890-2010; Al-Gayyar, Mohammed/E-8250-2014 OI Pacher, Pal/0000-0001-7036-8108; MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Al-Gayyar, Mohammed/0000-0003-4777-3919 FU JDRF [2-2008-149]; Vision Discovery Institute; NKTH-OTKA-EU [MB08-A-80238] FX This work was supported by intramural research grants to NIH-NIAAA to P. Pacher and grants from JDRF (2-2008-149) and Vision Discovery Institute to A. B. El-Remessy. B. Horvath was supported by an NKTH-OTKA-EU fellowship (MB08-A-80238). The authors are indebted to G. Kunos (Scientific Director of NIH-NIAAA) for providing key resources for the completion of this study. NR 50 TC 25 Z9 28 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUN PY 2011 VL 54 IS 6 BP 1567 EP 1578 DI 10.1007/s00125-011-2061-4 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 760ML UT WOS:000290328300035 PM 21373835 ER PT J AU Oliveira, JHM Goncalves, RLS Oliveira, GA Oliveira, PL Oliveira, MF Barillas-Mury, C AF Oliveira, Jose Henrique M. Goncalves, Renata L. S. Oliveira, Giselle A. Oliveira, Pedro L. Oliveira, Marcus F. Barillas-Mury, Carolina TI Energy metabolism affects susceptibility of Anopheles gambiae mosquitoes to Plasmodium infection SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Mosquito; Anopheles gambiae; Metabolism; Mitochondria; Plasmodium infection; Refractoriness; Electron leak; Reactive oxygen species ID IMMUNITY; MITOCHONDRIA; DETERMINANT; NITRATION; OXIDASE; BERGHEI; CELLS AB Previous studies showed that Anopheles gambiae L3-5 females, which are refractory (R) to Plasmodium infection, express higher levels of genes involved in redox-metabolism and mitochondrial respiration than susceptible (S) G3 females. Our studies revealed that R females have reduced longevity, faster utilization of lipid reserves, impaired mitochondrial state-3 respiration, increased rate of mitochondrial electron leak and higher expression levels of several glycolytic enzyme genes. Furthermore, when state-3 respiration was reduced in S females by silencing expression of the adenine nucleotide translocator (ANT), hydrogen peroxide generation was higher and the mRNA levels of lactate dehydrogenase increased in the midgut, while the prevalence and intensity of Plasmodium berghei infection were significantly reduced. We conclude that there are broad metabolic differences between R and S An. gambiae mosquitoes that influence their susceptibility to Plasmodium infection. Published by Elsevier Ltd. C1 [Oliveira, Jose Henrique M.; Goncalves, Renata L. S.; Oliveira, Giselle A.; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Oliveira, Jose Henrique M.; Oliveira, Pedro L.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Lab Bioquim Artropodes Hematofagos, Rio De Janeiro, Brazil. [Goncalves, Renata L. S.; Oliveira, Marcus F.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Lab Bioquim Redox, Rio De Janeiro, Brazil. [Goncalves, Renata L. S.; Oliveira, Marcus F.] Univ Fed Rio de Janeiro, Inst Nacl Ciencia & Tecnol Biol Estrutural & Bioi, Lab Inflamacao & Metab, Rio De Janeiro, Brazil. RP Barillas-Mury, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. EM cbarillas@niaid.nih.gov RI Oliveira, Marcus/G-3158-2011; Entomologiamolecular, Inct/J-8214-2013; Inbeb, Inct/K-2317-2013; OI Oliveira, Marcus/0000-0002-9890-8425; Oliveira, Giselle/0000-0002-5898-7843; Oliveira, Pedro/0000-0003-0307-354X FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Brazilian Government through CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior); CAPES; CNPq-Brazil (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) FX We thank Andre Laughinghouse and Kevin Lee for insectary support and Lindsey Garver and Alvaro Molina-Cruz for their comments and insight. 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. R.L.S.G. was funded by a fellowship from the Brazilian Government through CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior); J.H.M.O. was funded by CAPES and CNPq-Brazil (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico). M.F.O. and P.L.O. are research scholars from CNPq. NR 23 TC 15 Z9 15 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JUN PY 2011 VL 41 IS 6 BP 349 EP 355 DI 10.1016/j.ibmb.2011.02.001 PG 7 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 760WO UT WOS:000290355300001 PM 21320598 ER PT J AU Omata, N Chiu, CT Moya, PR Leng, Y Wang, ZF Hunsberger, JG Leeds, P Chuang, DM AF Omata, Naoto Chiu, Chi-Tso Moya, Pablo R. Leng, Yan Wang, Zhifei Hunsberger, Joshua G. Leeds, Peter Chuang, De-Maw TI Lentivirally mediated GSK-3 beta silencing in the hippocampal dentate gyrus induces antidepressant-like effects in stressed mice SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Antidepressant-like effects; forced swim test; GSK-3 shRNA; hippocampal dentate gyrus; lentivirus ID SYNTHASE KINASE-3 ISOFORMS; NEUROTROPHIC FACTOR; BIPOLAR DISORDER; LITHIUM; GLYCOGEN-SYNTHASE-KINASE-3-BETA; SENSITIVITY; INHIBITOR; NEUROGENESIS; BEHAVIOR; PROTEIN AB Inhibition of glycogen synthase kinase-3 (GSK-3) by pharmacological tools can produce antidepressantlike effects in rodents. However, the GSK-3 isoform(s) and brain region(s) involved in regulating these behavioural effects remain elusive. We studied the effects of bilateral intra-hippocampal injections of lentivirus-expressing short-hairpin (sh) RNA targeting GSK-3 beta on behavioural performance in mice subjected to chronic stress. Pre-injection of lentivirus-expressing GSK-3 beta shRNA into the hippocampal dentate gyrus significantly decreased immobility time in both forced swim and tail suspension tests, while the locomotor activity of these mice was unchanged. These results suggest that lentiviral GSK-3 beta shRNA injection induces antidepressant-like effects in chronically stressed mice. Under these conditions, the expression levels of GSK-3 beta were persistently and markedly reduced in the hippocampus following GSK-3 beta shRNA injection. To our knowledge, this is the first demonstration that a single injection of lentivirus-expressing GSK-3 beta shRNA in the hippocampal dentate gyrus of chronically stressed mice has antidepressant-like effects elicited by gene silencing. C1 [Omata, Naoto; Chiu, Chi-Tso; Leng, Yan; Wang, Zhifei; Hunsberger, Joshua G.; Leeds, Peter; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Omata, Naoto] Univ Fukui, Fac Med Sci, Dept Neuropsychiat, Fukui 910, Japan. [Moya, Pablo R.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Rm 3D-38,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov RI Wang, Zhifei/I-2787-2013 FU National Institute of Mental Health, National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. The editorial assistance of Ms. Ioline Henter is greatly appreciated. NR 27 TC 28 Z9 30 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2011 VL 14 IS 5 BP 711 EP 717 DI 10.1017/S1461145710000726 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 757SW UT WOS:000290109000013 PM 20604988 ER PT J AU Boris, RS Benhammou, J Merino, M Pinto, PA Linehan, WM Bratslavsky, G AF Boris, Ronald S. Benhammou, Jihane Merino, Maria Pinto, Peter A. Linehan, W. Marston Bratslavsky, Gennady TI The Impact of Germline BHD Mutation on Histological Concordance and Clinical Treatment of Patients With Bilateral Renal Masses and Known Unilateral Oncocytoma SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma; adenoma, oxyphilic; neoplastic syndromes, hereditary; germ-line mutation ID HOGG-DUBE-SYNDROME; GENETIC-BASIS; SPONTANEOUS PNEUMOTHORAX; KIDNEY NEOPLASIA; FOLLOW-UP; TUMORS; CANCER; MANAGEMENT; FAMILIES; FEATURES AB Purpose: Managing oncocytoma in the setting of bilateral renal masses is a challenging scenario. Nevertheless, to our knowledge the pathological concordance of an oncocytic neoplasm in 1 kidney with tumors in the contralateral kidney is not known. We evaluated the influence of germline Birt-Hogg-Dube mutation on concordance rates to assist in managing these cases. Materials and Methods: We reviewed the records of patients at the National Institutes of Health between 1983 and 2009 who had bilateral renal masses, known pathology bilaterally and oncocytoma or an oncocytic neoplasm in at least 1 kidney. Oncocytoma or an oncocytic neoplasm in 2 renal units was considered concordant. Demographic, pathological and clinical data were collected. Results: The population consisted of 40 patients, including 23 with and 17 without a diagnosis of Birt-Hogg-Dube syndrome. Patients with the syndrome were younger (p < 0.01) but there were no other differences between the 2 groups. However, patients with the syndrome had statistically lower histological concordance between bilateral masses than patients without the diagnosis (Fisher's exact test p < 0.01). Also, the 8 patients without Birt-Hogg-Dube syndrome who had multifocal renal masses showed 100% oncocytoma concordance between renal units. Conclusions: Of patients with bilateral renal masses those with Birt-Hogg-Dube syndrome have significantly lower histological concordance than those without the syndrome. Patients with Birt-Hogg-Dube syndrome should be monitored and treated differently than those without detected genetic mutations, especially patients with multifocal oncocytomas. Genetic testing for Birt-Hogg-Dube should be considered in the treatment algorithm of patients with bilateral renal masses and known oncocytoma. C1 [Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, CRC, Bethesda, MD 20892 USA. RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, NIH, CRC, 10 Ctr Dr,MSC 1107,Bldg 10,Room 2W-5942, Bethesda, MD 20892 USA. EM bratslag@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 27 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2011 VL 185 IS 6 BP 2050 EP 2055 DI 10.1016/j.juro.2011.02.051 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 761HW UT WOS:000290389600011 PM 21496834 ER PT J AU Holmes, EC AF Holmes, Edward C. TI What Does Virus Evolution Tell Us about Virus Origins? SO JOURNAL OF VIROLOGY LA English DT Review ID 1.2-MEGABASE GENOME SEQUENCE; LARGE DNA VIRUSES; CRYSTAL-STRUCTURE; RNA-POLYMERASES; LINEAGE; MUTATION; CELLS; RATES; GENE; LIFE AB Despite recent advances in our understanding of diverse aspects of virus evolution, particularly on the epidemiological scale, revealing the ultimate origins of viruses has proven to be a more intractable problem. Herein, I review some current ideas on the evolutionary origins of viruses and assess how well these theories accord with what we know about the evolution of contemporary viruses. I note the growing evidence for the theory that viruses arose before the last universal cellular ancestor (LUCA). This ancient origin theory is supported by the presence of capsid architectures that are conserved among diverse RNA and DNA viruses and by the strongly inverse relationship between genome size and mutation rate across all replication systems, such that pre-LUCA genomes were probably both small and highly error prone and hence RNA virus-like. I also highlight the advances that are needed to come to a better understanding of virus origins, most notably the ability to accurately infer deep evolutionary history from the phylogenetic analysis of conserved protein structures. C1 [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, Mueller Lab, University Pk, PA 16802 USA. EM ech15@psu.edu OI Holmes, Edward/0000-0001-9596-3552 NR 52 TC 38 Z9 38 U1 4 U2 31 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 JUN PY 2011 VL 85 IS 11 BP 5247 EP 5251 DI 10.1128/JVI.02203-10 PG 5 WC Virology SC Virology GA 760CE UT WOS:000290298700002 PM 21450811 ER PT J AU Murcia, PR Wood, JLN Holmes, EC AF Murcia, Pablo R. Wood, James L. N. Holmes, Edward C. TI Genome-Scale Evolution and Phylodynamics of Equine H3N8 Influenza A Virus SO JOURNAL OF VIROLOGY LA English DT Article ID UNITED-KINGDOM; HEMAGGLUTININ; GENES; DYNAMICS; DETERMINANTS; LINEAGES; OUTBREAK; ORIGIN; HORSES; TRANSMISSION AB Equine influenza viruses (EIVs) of the H3N8 and H7N7 subtypes are the causative agents of an important disease of horses. While EIV H7N7 apparently is extinct, H3N8 viruses have circulated for more than 50 years. Like human influenza viruses, EIV H3N8 caused a transcontinental pandemic followed by further outbreaks and epidemics, even in populations with high vaccination coverage. Recently, EIV H3N8 jumped the species barrier to infect dogs. Despite its importance as an agent of infectious disease, the mechanisms that underpin the evolutionary and epidemiological dynamics of EIV are poorly understood, particularly at a genomic scale. To determine the evolutionary history and phylodynamics of EIV H3N8, we conducted an extensive analysis of 82 complete viral genomes sampled during a 45-year span. We show that both intra- and intersubtype reassortment have played a major role in the evolution of EIV, and we suggest that intrasubtype reassortment resulted in enhanced virulence while heterosubtypic reassortment contributed to the extinction of EIV H7N7. We also show that EIV evolves at a slower rate than other influenza viruses, even though it seems to be subject to similar immune selection pressures. However, a relatively high rate of amino acid replacement is observed in the polymerase acidic (PA) segment, with some evidence for adaptive evolution. Most notably, an analysis of viral population dynamics provided evidence for a major population bottleneck of EIV H3N8 during the 1980s, which we suggest resulted from changes in herd immunity due to an increase in vaccination coverage. C1 [Murcia, Pablo R.; Wood, James L. N.] Univ Cambridge, Dept Vet Med, Cambridge Infect Dis Consortium, Cambridge CB3 0ES, England. [Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Murcia, PR (reprint author), Univ Cambridge, Dept Vet Med, Cambridge Infect Dis Consortium, Madingley Rd,CB3 0ES, Cambridge CB3 0ES, England. EM prm42@cam.ac.uk RI Wood, James/A-1626-2008; OI Wood, James/0000-0002-0258-3188; Holmes, Edward/0000-0001-9596-3552 FU Wellcome Trust; Alborada Trust; Science and Technology Directorate, Department of Homeland Security; National Institutes of Health [R01 GM080533] FX P.R.M. is supported by a Wellcome Trust Veterinary Postdoctoral Fellowship. J.L.N.W. is supported by the Alborada Trust and the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security. E.C.H. is supported in part by grant R01 GM080533 from the National Institutes of Health. NR 65 TC 35 Z9 35 U1 0 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 JUN PY 2011 VL 85 IS 11 BP 5312 EP 5322 DI 10.1128/JVI.02619-10 PG 11 WC Virology SC Virology GA 760CE UT WOS:000290298700008 PM 21430049 ER PT J AU Cordoba, L Huang, YW Opriessnig, T Harral, KK Beach, NM Finkielstein, CV Emerson, SU Meng, XJ AF Cordoba, Laura Huang, Yao-Wei Opriessnig, Tanja Harral, Kylie K. Beach, Nathan M. Finkielstein, Carla V. Emerson, Suzanne U. Meng, Xiang-Jin TI Three Amino Acid Mutations (F51L, T59A, and S390L) in the Capsid Protein of the Hepatitis E Virus Collectively Contribute to Virus Attenuation SO JOURNAL OF VIROLOGY LA English DT Article ID CROSS-SPECIES INFECTION; BURSAL DISEASE VIRUS; ORF3 PROTEIN; IN-VIVO; MONOCLONAL-ANTIBODIES; RECEPTOR-BINDING; HELICASE DOMAIN; VIRAL-RNA; SWINE HEV; CELLS AB Hepatitis E virus (HEV) is an important but extremely understudied human pathogen, and the mechanisms of HEV replication and pathogenesis are largely unknown. We previously identified an attenuated genotype 3 HEV mutant (pSHEV-1) containing three unique amino acid mutations (F51L, T59A, and S390L) in the capsid protein. To determine the role of each of these mutations, we constructed three HEV single mutants (rF51L, rT59A, and rS390L) which were all found to be replication competent in Huh7 liver cells. To determine the pathogenicities of the mutants, we utilized the specific-pathogen-free (SPF) pig model for HEV and a unique inoculation procedure that bypasses the need for propagating infectious HEV in vitro. A total of 60 pigs were intrahepatically inoculated, via an ultrasound-guided technique, with in vitro-transcribed full-length capped RNA transcripts from the infectious clones of each single mutant, the pSHEV-1 triple mutant, wild-type pSHEV-3, or phosphate-buffered saline (PBS) buffer (n = 10). The results showed that the F51L mutation partially contributed to virus attenuation, whereas the T59A and S390L mutations resulted in more drastic attenuation of HEV in pigs, as evidenced by a significantly lower incidence of viremia, a delayed appearance and shorter duration of fecal virus shedding and viremia, and lower viral loads in liver, bile, and intestinal content collected at three different necropsy times. The results indicate that the three mutations in the capsid protein collectively contribute to HEV attenuation. This study has important implications for developing a modified live-attenuated vaccine against HEV. C1 [Cordoba, Laura; Huang, Yao-Wei; Harral, Kylie K.; Beach, Nathan M.; Meng, Xiang-Jin] Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, Ctr Mol Med & Infect Dis, Blacksburg, VA 24061 USA. [Opriessnig, Tanja] Iowa State Univ, Dept Vet Diagnost & Prod Anim Med, Ames, IA USA. [Finkielstein, Carla V.] Virginia Polytech Inst & State Univ, Dept Biol Sci, Integrated Cellular Responses Lab, Blacksburg, VA 24061 USA. [Emerson, Suzanne U.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Meng, XJ (reprint author), Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, Ctr Mol Med & Infect Dis, CRC Integrated Life Sci Bldg,1981 Kraft Dr, Blacksburg, VA 24061 USA. EM xjmeng@vt.edu RI Huang, Yaowei/B-1468-2009; Beach, Nathan/A-5461-2011; Meng, X.J./B-8769-2009; Opriessnig, Tanja/F-2984-2012; OI Huang, Yaowei/0000-0001-9755-8411; Meng, X.J./0000-0002-2739-1334; Opriessnig, Tanja/0000-0001-9642-0904; finkielstein, carla/0000-0002-8417-4643 FU National Institutes of Health [R01AI050611, R01AI074667] FX This study was supported by grants from the National Institutes of Health (R01AI050611 and R01AI074667). NR 69 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2011 VL 85 IS 11 BP 5338 EP 5349 DI 10.1128/JVI.02278-10 PG 12 WC Virology SC Virology GA 760CE UT WOS:000290298700011 PM 21450834 ER PT J AU Subbiah, M Khattar, SK Collins, PL Samal, SK AF Subbiah, Madhuri Khattar, Sunil K. Collins, Peter L. Samal, Siba K. TI Mutations in the Fusion Protein Cleavage Site of Avian Paramyxovirus Serotype 2 Increase Cleavability and Syncytium Formation but Do Not Increase Viral Virulence in Chickens SO JOURNAL OF VIROLOGY LA English DT Article ID NEWCASTLE-DISEASE-VIRUS; HEMAGGLUTININ-NEURAMINIDASE PROTEIN; COMPLETE GENOME SEQUENCE; CLONED CDNA; FOREIGN GENE; EXPRESSION; STRAIN; PATHOGENICITY; GENERATION; ISOLATIONS AB Avian paramyxovirus serotype 2 (APMV-2) is one of the nine serotypes of APMV, which infect a wide variety of avian species around the world. In this study, we constructed a reverse genetics system for recovery of infectious recombinant APMV-2 strain Yucaipa (APMV-2/Yuc) from cloned cDNA. The rescued recombinant virus (rAPMV-2) resembled the biological virus in growth properties in vitro and in pathogenicity in vivo. The reverse genetics system was used to analyze the role of the cleavage site of the fusion (F) protein in viral replication and pathogenesis. The cleavage site of APMV-2/Yuc (KPASR down arrow F) contains only a single basic residue (position - 1) that matches the preferred furin cleavage site [RX(K/R)R down arrow]. (Underlining indicates the basic amino acids at the F protein cleavage site, and the arrow indicates the site of cleavage.) Contrary to what would be expected for this cleavage sequence, APMV-2 does not require, and is not augmented by, exogenous protease supplementation for growth in cell culture. However, it does not form syncytia, and the virus is avirulent in chickens. A total of 12 APMV-2 mutants with F protein cleavage site sequences derived from APMV serotypes 1 to 9 were generated. These sites contain from 1 to 5 basic residues. Whereas a number of these cleavage sites are associated with protease dependence and lack of syncytium formation in their respective native viruses, when transferred into the APMV-2 backbone, all of them conferred protease independence, syncytium formation, and increased replication in cell culture. Examination of selected mutants during a pulse-chase experiment demonstrated an increase in F protein cleavage compared to that for wild-type APMV-2. Despite the gains in cleavability, replication, and syncytium formation, analysis of viral pathogenicity in 9-day-old embryonated chicken eggs, 1-day-old chicks, and 2-week-old chickens showed that the F protein cleavage site mutants did not exhibit increased pathogenicity and remained avirulent. These results imply that structural features in addition to the cleavage site play a major role in the cleavability of the F protein and the activity of the cleaved protein. Furthermore, cleavage of the F protein is not a determinant of APMV-2 pathogenicity in chickens. C1 [Subbiah, Madhuri; Khattar, Sunil K.; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. [Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. EM ssamal@umd.edu FU NIAID [N01A060009]; NIAID NIH FX This research was supported by NIAID contract no. N01A060009 (85% support) and the NIAID NIH Intramural Research Program (15% support). NR 36 TC 11 Z9 11 U1 0 U2 0 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 JUN PY 2011 VL 85 IS 11 BP 5394 EP 5405 DI 10.1128/JVI.02696-10 PG 12 WC Virology SC Virology GA 760CE UT WOS:000290298700016 PM 21450835 ER PT J AU Mehedi, M Falzarano, D Seebach, J Hu, XJ Carpenter, MS Schnittler, HJ Feldmann, H AF Mehedi, Masfique Falzarano, Darryl Seebach, Jochen Hu, Xiaojie Carpenter, Michael S. Schnittler, Hans-Joachim Feldmann, Heinz TI A New Ebola Virus Nonstructural Glycoprotein Expressed through RNA Editing SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-DELTA-VIRUS; P/C MESSENGER-RNA; NIPAH-VIRUS; BARRIER FUNCTION; W-PROTEINS; DC-SIGNR; SECRETED GLYCOPROTEIN; VIRION GLYCOPROTEINS; PHOSPHOPROTEIN GENE; ZAIRE-EBOLAVIRUS AB Ebola virus (EBOV), an enveloped, single-stranded, negative-sense RNA virus, causes severe hemorrhagic fever in humans and nonhuman primates. The EBOV glycoprotein (GP) gene encodes the nonstructural soluble glycoprotein (sGP) but also produces the transmembrane glycoprotein (GP(1,2)) through transcriptional editing. A third GP gene product, a small soluble glycoprotein (ssGP), has long been postulated to be produced also as a result of transcriptional editing. To identify and characterize the expression of this new EBOV protein, we first analyzed the relative ratio of GP gene-derived transcripts produced during infection in vitro (in Vero E6 cells or Huh7 cells) and in vivo (in mice). The average percentages of transcripts encoding sGP, GP(1,2), and ssGP were approximately 70, 25, and 5%, respectively, indicating that ssGP transcripts are indeed produced via transcriptional editing. N-terminal sequence similarity with sGP, the absence of distinguishing antibodies, and the abundance of sGP made it difficult to identify ssGP through conventional methodology. Optimized 2-dimensional (2D) gel electrophoresis analyses finally verified the expression and secretion of ssGP in tissue culture during EBOV infection. Biochemical analysis of recombinant ssGP characterized this protein as a disulfide-linked homodimer that was exclusively N glycosylated. In conclusion, we have identified and characterized a new EBOV nonstructural glycoprotein, which is expressed as a result of transcriptional editing of the GP gene. While ssGP appears to share similar structural properties with sGP, it does not appear to have the same anti-inflammatory function on endothelial cells as sGP. C1 [Feldmann, Heinz] NIAID, Rocky Mt Labs, Virol Lab, Div Intramural Res,NIH, Hamilton, MT 59840 USA. [Mehedi, Masfique; Falzarano, Darryl; Carpenter, Michael S.; Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. [Mehedi, Masfique; Falzarano, Darryl; Feldmann, Heinz] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. [Seebach, Jochen; Schnittler, Hans-Joachim] Univ Munster, Dept Anat & Vasc Biol, Munster, Germany. RP Feldmann, H (reprint author), NIAID, Rocky Mt Labs, Virol Lab, Div Intramural Res,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM feldmannh@niaid.nih.gov RI Mehedi, masfique/J-6618-2014 OI Mehedi, masfique/0000-0003-1728-3126 FU National Microbiology Laboratory (NML) of the Public Health Agency of Canada (PHAC); NIAID, NIH FX This study was supported by the National Microbiology Laboratory (NML) of the Public Health Agency of Canada (PHAC) and the Intramural Research Program of NIAID, NIH. NR 60 TC 57 Z9 62 U1 3 U2 14 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 JUN PY 2011 VL 85 IS 11 BP 5406 EP 5414 DI 10.1128/JVI.02190-10 PG 9 WC Virology SC Virology GA 760CE UT WOS:000290298700017 PM 21411529 ER PT J AU Asmal, M Sun, Y Lane, S Yeh, W Schmidt, SD Mascola, JR Letvin, NL AF Asmal, Mohammed Sun, Yue Lane, Sophie Yeh, Wendy Schmidt, Stephen D. Mascola, John R. Letvin, Norman L. TI Antibody-Dependent Cell-Mediated Viral Inhibition Emerges after Simian Immunodeficiency Virus SIVmac251 Infection of Rhesus Monkeys Coincident with gp140-Binding Antibodies and Is Effective against Neutralization-Resistant Viruses SO JOURNAL OF VIROLOGY LA English DT Article ID SUBTYPE-C INFECTION; HIV-1 INFECTION; MONOCLONAL-ANTIBODIES; RESPONSES; TYPE-1; CYTOTOXICITY; VACCINE; EPITOPE; GP120; ENVELOPE AB Antibody-dependent cell-mediated viral inhibition (ADCVI) is an attractive target for vaccination because it takes advantage of both the anamnestic properties of an adaptive immune response and the rapid early response characteristics of an innate immune response. Effective utilization of ADCVI in vaccine strategies will depend on an understanding of the natural history of ADCVI during acute and chronic human immunodeficiency virus type 1 (HIV-1) infection. We used the simian immunodeficiency virus (SIV)-infected rhesus monkey as a model to study the kinetics of ADCVI in early infection, the durability of ADCVI through the course of infection, and the effectiveness of ADCVI against viruses with envelope mutations that are known to confer escape from antibody neutralization. We demonstrate the development of ADCVI, capable of inhibiting viral replication 100-fold, within 3 weeks of infection, preceding the development of a comparable-titer neutralizing antibody response by weeks to months. The emergence of ADCVI was temporally associated with the emergence of gp140-binding antibodies, and in most animals, ADCVI persisted through the course of infection. Highly evolved viral envelopes from viruses isolated at late time points following infection that were resistant to plasma neutralization remained susceptible to ADCVI, suggesting that the epitope determinants of neutralization escape are not shared by antibodies that mediate ADCVI. These findings suggest that despite the ability of SIV to mutate and adapt to multiple immunologic pressures during the course of infection, SIV envelope may not escape the binding of autologous antibodies that mediate ADCVI. C1 [Asmal, Mohammed; Sun, Yue; Lane, Sophie; Yeh, Wendy; Letvin, Norman L.] Harvard Univ, Div Viral Pathogenesis, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Schmidt, Stephen D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Asmal, M (reprint author), Harvard Univ, Div Viral Pathogenesis, Sch Med, Beth Israel Deaconess Med Ctr, E CLS 1030,330 Brookline Ave, Boston, MA 02215 USA. EM masmal@bidmc.harvard.edu RI Schmidt, Stephen/B-5398-2012 FU NIH [AI060354-06, AI-067854]; Center for HIV/AIDS Vaccine Immunology; Harvard University Center for AIDS Research FX This research was supported by grants from the NIH AI060354-06 and AI-067854 and the Center for HIV/AIDS Vaccine Immunology and Harvard University Center for AIDS Research. NR 49 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2011 VL 85 IS 11 BP 5465 EP 5475 DI 10.1128/JVI.00313-11 PG 11 WC Virology SC Virology GA 760CE UT WOS:000290298700023 PM 21450829 ER PT J AU Singer, R Derby, N Rodriguez, A Kizima, L Kenney, J Aravantinou, M Chudolij, A Gettie, A Blanchard, J Lifson, JD Piatak, M Fernandez-Romero, JA Zydowsky, TM Robbiani, M AF Singer, R. Derby, N. Rodriguez, A. Kizima, L. Kenney, J. Aravantinou, M. Chudolij, A. Gettie, A. Blanchard, J. Lifson, J. D. Piatak, M., Jr. Fernandez-Romero, J. A. Zydowsky, T. M. Robbiani, M. TI The Nonnucleoside Reverse Transcriptase Inhibitor MIV-150 in Carrageenan Gel Prevents Rectal Transmission of Simian/Human Immunodeficiency Virus Infection in Macaques SO JOURNAL OF VIROLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; CARRAGUARD VAGINAL GEL; T-CELL RESPONSES; RHESUS MACAQUES; VIRAL LOAD; HIV-1 INFECTION; DENDRITIC CELLS; HIGH-RISK; WOMEN; SIV AB Development of a microbicide that prevents rectal transmission of human immunodeficiency virus (HIV) is a vital component in reducing HIV spread. We recently demonstrated that a formulation of the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan reduced vaginal infection of macaques with simian immunodeficiency virus SIVmac239 with HIV-1(HxB2) reverse transcriptase (SHIV-RT). Herein, we performed the first testing of MIV-150-carrageenan against rectal infection. Rhesus macaques were treated rectally with MIV-150-carrageenan or methyl cellulose (MC) placebo gel up to 4 h prior to rectal challenge with 10(3) or 10(4) 50% tissue culture infective doses (TCID(50)) of SHIV-RT. Infection was assessed by measuring plasma virus RNA as well as T and B cell responses. MIV-150-carrageenan protected all animals challenged with 10(3) TCID(50) when gel was applied either 30 min or 4 h prior to challenge, while 100% of the MC-treated animals became infected (n = 4 each; P < 0.03). Partial protection (2 of 4 animals) by MIV-150-carrageenan was observed for rectal challenge with 10-fold more virus applied 4 h after the gel. Sequencing of the RT gene from plasma virus RNA isolated at peak viremia confirmed that both of these animals (like infected MC controls) were infected with wild-type virus. Infection correlated with the development of SIV-specific T and B cell responses. MIV-150 was detected in the rectal fluids and tissues 4 h after gel application but was not detected in the blood at any time (0.5 to 24 h). These data are promising for the development of NNRTI-containing gels to prevent rectal HIV transmission. C1 [Robbiani, M.] Populat Council, Ctr Biomed Res, HIV & AIDS Program, New York, NY 10065 USA. [Gettie, A.] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA. [Blanchard, J.] Tulane Univ, TNPRC, Covington, LA USA. [Lifson, J. D.; Piatak, M., Jr.] NCI, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA. RP Robbiani, M (reprint author), Populat Council, Ctr Biomed Res, HIV & AIDS Program, 1230 York Ave, New York, NY 10065 USA. EM mrobbiani@popcouncil.org FU Swedish Ministry for Foreign Affairs; Swedish International Development Cooperation Agency; United States Agency for International Development (USAID); National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported by the Swedish Ministry for Foreign Affairs and the Swedish International Development Cooperation Agency, with additional support provided by the United States Agency for International Development (USAID) Cooperative Agreement. This research is made possible by the generous support of the American people through the USAID and was supported in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. M.R. is a 2002 Elizabeth Glaser Scientist. NR 53 TC 33 Z9 34 U1 1 U2 5 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 JUN PY 2011 VL 85 IS 11 BP 5504 EP 5512 DI 10.1128/JVI.02422-10 PG 9 WC Virology SC Virology GA 760CE UT WOS:000290298700027 PM 21411526 ER PT J AU Liu, WJ Rourke, MF Holmes, EC Aaskov, JG AF Liu, Wen J. Rourke, Michelle F. Holmes, Edward C. Aaskov, John G. TI Persistence of Multiple Genetic Lineages within Intrahost Populations of Ross River Virus SO JOURNAL OF VIROLOGY LA English DT Article ID WEST-NILE-VIRUS; ALPHAVIRUSES; INFECTION; DIVERSITY; POLYMERASE; MOSQUITOS; EVOLUTION AB We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances. C1 [Aaskov, John G.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. [Liu, Wen J.; Rourke, Michelle F.; Aaskov, John G.] Australian Army Malaria Inst, Brisbane, Qld, Australia. [Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Aaskov, JG (reprint author), Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia. EM j.aaskov@qut.edu.au OI Holmes, Edward/0000-0001-9596-3552 FU National Health and Medical Research Council of Australia; Cook Estate; National Institutes of Health [R01GM80533-04] FX This study was supported by grants from the National Health and Medical Research Council of Australia and the Cook Estate. E.C.H. was funded, in part, by grant R01GM80533-04 from the National Institutes of Health. NR 26 TC 3 Z9 3 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2011 VL 85 IS 11 BP 5674 EP 5678 DI 10.1128/JVI.02622-10 PG 5 WC Virology SC Virology GA 760CE UT WOS:000290298700044 PM 21430052 ER PT J AU Seto, D Chodosh, J Brister, JR Jones, MS AF Seto, Donald Chodosh, James Brister, J. Rodney Jones, Morris S. CA Adenovirus Res Community TI Using the Whole-Genome Sequence To Characterize and Name Human Adenoviruses SO JOURNAL OF VIROLOGY LA English DT Letter C1 [Seto, Donald] George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA. [Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab, Boston, MA 02114 USA. [Brister, J. Rodney] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Jones, Morris S.] Calif Dept Publ Hlth, Viral & Rickettsial Dis Lab, Richmond, CA 94804 USA. RP Seto, D (reprint author), George Mason Univ, Sch Syst Biol, 10900 Univ Blvd,MSN 5B3, Manassas, VA 20110 USA. EM dseto@gmu.edu RI Zhang, Qiwei/D-9110-2012; Leppard, Keith/A-1853-2009; Lukashev, Alexander/G-2777-2013; Kremer, Eric /D-3734-2013; San Martin, Carmen/A-4074-2010; van Raaij, Mark/B-3678-2009; Greber, Urs/G-9458-2015; OI Smith, Jason/0000-0001-6727-5269; Zhang, Qiwei/0000-0002-2770-111X; Leppard, Keith/0000-0003-2155-7919; Kremer, EJ/0000-0001-6114-7530; Lukashev, Alexander/0000-0001-7365-0352; San Martin, Carmen/0000-0001-9799-175X; van Raaij, Mark/0000-0002-4781-1375; Greber, Urs/0000-0003-2278-120X; Heim, Albert/0000-0002-9447-1561 FU Intramural NIH HHS; NEI NIH HHS [R01 EY013124, EY013124, P30 EY014104, P30EY014104] NR 0 TC 48 Z9 55 U1 1 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 JUN PY 2011 VL 85 IS 11 BP 5701 EP 5702 DI 10.1128/JVI.00354-11 PG 2 WC Virology SC Virology GA 760CE UT WOS:000290298700049 PM 21450823 ER PT J AU Sun, XL Niu, G Chan, N Shen, BZ Chen, XY AF Sun, Xilin Niu, Gang Chan, Nicholas Shen, Baozhong Chen, Xiaoyuan TI Tumor Hypoxia Imaging SO MOLECULAR IMAGING AND BIOLOGY LA English DT Review DE Hypoxia; Molecular imaging; Positron emission tomography (PET); Single-photon emission computed tomography (SPECT); Optical imaging; Magnetic resonance imaging (MRI) ID POSITRON-EMISSION-TOMOGRAPHY; SQUAMOUS-CELL CARCINOMAS; INDUCIBLE FACTOR 1-ALPHA; CARBONIC-ANHYDRASE-IX; SOFT-TISSUE SARCOMAS; MAGNETIC-RESONANCE-SPECTROSCOPY; NECK-CANCER PATIENTS; IN-VIVO EVALUATION; OXYGENATION STATUS; RADIATION-THERAPY AB There is a need to measure tumor hypoxia in assessing the aggressiveness of tumor and predicting the outcome of therapy. A number of invasive and noninvasive techniques have been exploited to measure tumor hypoxia, including polarographic needle electrodes, immunohistochemical staining, radionuclide imaging (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]), magnetic resonance imaging (MRI), optical imaging (bioluminescence and fluorescence), and so on. This review article summarizes and discusses the pros and cons of each currently available method for measuring tissue oxygenation. Special emphasis was placed on noninvasive imaging hypoxia with emerging new agents and new imaging technologies to detect the molecular events that are relevant to tumor hypoxia. C1 [Sun, Xilin; Niu, Gang; Chan, Nicholas; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Sun, Xilin; Shen, Baozhong] Harbin Med Coll, Affiliated Hosp 4, Dept Med Imaging & Nucl Med, Harbin 150001, Peoples R China. [Niu, Gang] Ctr Clin, Imaging Sci Training Program, Bethesda, MD 20892 USA. RP Niu, G (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); Radiology and Imaging Sciences Department, NIH Clinical Center FX This research was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). G.N., who currently has an Imaging Sciences Training Fellowship, is jointly supported by the Radiology and Imaging Sciences Department, NIH Clinical Center, and the Intramural Research Program, NIBIB, NIH. NR 142 TC 32 Z9 32 U1 3 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JUN PY 2011 VL 13 IS 3 BP 399 EP 410 DI 10.1007/s11307-010-0420-z PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 759VT UT WOS:000290277300001 PM 20838906 ER PT J AU Moussouttas, M Lai, EW Dombrowski, K Huynh, TT Khoury, J Carmona, G DeCaro, M Pacak, K AF Moussouttas, Michael Lai, Edwin W. Dombrowski, Keith Huynh, Thanh T. Khoury, John Carmona, Gilberto DeCaro, Matthew Pacak, Karel TI CSF Catecholamine Profile in Subarachnoid Hemorrhage Patients with Neurogenic Cardiomyopathy SO NEUROCRITICAL CARE LA English DT Article DE Subarachnoid hemorrhage; Sympathetic nervous system; Neurogenic cardiomyopathy; Cerebrospinal fluid; Catecholamines ID SYMPATHETIC NERVOUS ACTIVITY; CEREBROSPINAL-FLUID; NEUROCARDIOGENIC INJURY; NOREPINEPHRINE CONCENTRATIONS; AFFECTIVE-ILLNESS; EMOTIONAL-STRESS; ANIMAL-MODEL; PLASMA; DYSFUNCTION; METABOLISM AB Background Patients experiencing apoplectic intracranial processes may develop neurogenic cardiomyopathy (NC). The purpose of this research is to determine whether cerebrospinal fluid (CSF) catecholamine levels are elevated in subarachnoid hemorrhage (SAH) patients with NC when compared to those without NC. Methods Observational study of consecutive grades 3-5 SAH patients requiring ventriculostomy. All patients underwent CSF sampling for catecholamine levels, and transthoracic echocardiography (TTE) to assess for NC, within 48 h of SAH onset. Univariate analyses were performed to identify clinical and laboratory variables associated with NC. Clinical variables associated with NC in the univaritate analysis were entered into logistic regression models along with the candidate catecholamine variables to identify predictors of NC. Results The study group contained 100 patients-mean age of study subjects was 58 years, 73% were female, and 15% developed NC. NC patients were more likely to have a worse clinical grade than patients without NC (80 vs. 34%, P = 0.001). NC patients possessed greater DOPA levels (5.83 vs. 4.60 nmol/l, P = 0.044), and a trend toward greater noradrenergic activity as determined by NE/DHPG ratio (0.3799 vs. 0.2519, P = 0.073). Multivariate analysis identified worse clinical grade (OR 7.09, P = 0.005) and possibly NE levels (OR 1.005, P = 0.057) as independent predictors of NC. Bivariate analysis reinforced the findings for NE (OR 1.006, P = 0.022), and also identified DOPA levels (OR 1.001, P = 0.034) and NE/DHPG (OR 22.18, P = 0.019) as predictors of NC. Conclusions SAH patients with NC tend to have greater CSF catecholamine levels than those without NC. However, the development of NC may also be related to factors not evaluated by our study. C1 [Moussouttas, Michael] Thomas Jefferson Med Ctr, Cerebrovasc & Neurocrit Care Div, Philadelphia, PA 19107 USA. [Lai, Edwin W.; Huynh, Thanh T.; Carmona, Gilberto; Pacak, Karel] NIH, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, Bethesda, MD 20892 USA. [Dombrowski, Keith; Khoury, John] Thomas Jefferson Med Ctr, Dept Neurol, Philadelphia, PA 19107 USA. [DeCaro, Matthew] Thomas Jefferson Med Ctr, Dept Med, Philadelphia, PA 19107 USA. RP Moussouttas, M (reprint author), Thomas Jefferson Med Ctr, Cerebrovasc & Neurocrit Care Div, 900 Walnut St,Suite 200, Philadelphia, PA 19107 USA. EM arista1@pol.net FU NIH/NICHD FX The authors express gratitude to the nurses of the neurological intensive care unit from the Jefferson Hospital of Neurosciences at Thomas Jefferson University Medical Center for their assistance in this project. This research study was supported in part by the Intramural Research Program of the NIH/NICHD. NR 33 TC 8 Z9 8 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD JUN PY 2011 VL 14 IS 3 BP 401 EP 406 DI 10.1007/s12028-011-9527-6 PG 6 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 759FT UT WOS:000290226800012 PM 21409493 ER PT J AU von Leupoldt, A Vovk, A Bradley, MM Lang, PJ Davenport, PW AF von Leupoldt, Andreas Vovk, Andrea Bradley, Margaret M. Lang, Peter J. Davenport, Paul W. TI Habituation in neural processing and subjective perception of respiratory sensations SO PSYCHOPHYSIOLOGY LA English DT Article DE Asthma; Dyspnea; EEG; Habituation; Respiratory perception; Respiratory-related evoked potential ID INSPIRATORY RESISTIVE LOADS; LIFE-THREATENING ASTHMA; NEAR-FATAL ASTHMA; EVOKED-POTENTIALS; SYMPTOM PERCEPTION; AIRWAY OCCLUSION; DYSPNEA; HUMANS; HYPERCAPNIA; CHILDREN AB Reduced perception of respiratory sensations is associated with negative treatment outcome in asthma. We examined whether habituation in the neural processing of repeatedly experienced respiratory sensations may underlie subjective reports of reduced respiratory perception. Respiratory-related evoked potentials (RREP) elicited by inspiratory occlusions and reports of respiratory perception were compared between early and late experimental periods in healthy subjects. Reports of respiratory perception were reduced during late, compared to early, experimental periods. This was paralleled by reduced magnitudes in RREP components N1, P2, and P3 in late, compared to early, experimental periods. Habituation in the neural processing of respiratory sensations is a potential mechanism that underlies subjective reports of reduced respiratory perception and might represent a risk factor for reduced perception of respiratory sensations in asthma. C1 [von Leupoldt, Andreas] Univ Hamburg, Dept Psychol, D-20146 Hamburg, Germany. [von Leupoldt, Andreas; Vovk, Andrea; Davenport, Paul W.] Univ Florida, Dept Physiol Sci, Gainesville, FL 32610 USA. [von Leupoldt, Andreas] Univ Med Ctr Hamburg Eppendorf, Dept Syst Neurosci, Hamburg, Germany. [von Leupoldt, Andreas; Bradley, Margaret M.; Lang, Peter J.] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL USA. RP von Leupoldt, A (reprint author), Univ Hamburg, Dept Psychol, Von Melle Pk 5, D-20146 Hamburg, Germany. EM andreas.vonleupoldt@uni-hamburg.de FU German Research Society (Deutsche Forschungsgemeinschaft, DFG) [DFG LE 1843/9-1]; National Institute of Mental Health [P50 MH 72850] FX This study was supported in part by a stipend (Heisenberg-Stipendium, DFG LE 1843/9-1) from the German Research Society (Deutsche Forschungsgemeinschaft, DFG) to Andreas von Leupoldt and by a grant from the National Institute of Mental Health (P50 MH 72850) to Peter J. Lang. The authors thank Andreas Keil for his valuable support of the present study. NR 30 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JUN PY 2011 VL 48 IS 6 BP 808 EP 812 DI 10.1111/j.1469-8986.2010.01141.x PG 5 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 758OY UT WOS:000290175700009 PM 21039587 ER PT J AU Brinton, LA AF Brinton, Louise A. TI Breast cancer risk among patients with Klinefelter syndrome SO ACTA PAEDIATRICA LA English DT Article DE Genetics; Gynaecomastia; Hormones; Klinefelter syndrome; Male breast cancer; Risk ID CARCINOMA; MEN; MORTALITY; COHORT; HYPOGONADISM; ASSOCIATION; MALES AB Aim: To evaluate male breast cancer (MBC) risk among patients with Klinefelter syndrome (KS) and relate this to possible biological explanations. Methods: A literature review was conducted to identify case series and epidemiologic studies that have evaluated MBC risk among patients with KS. Results: Case reports without expected values have often led to false impressions of risk. Problems include that a diagnosis of cancer can prompt a karyotypic evaluation and that many cases of KS are unrecognized, resulting in incomplete denominators. Few carefully conducted epidemiologic studies have been undertaken given that both KS and MBC are rare events. The largest study found 19.2- and 57.8-fold increases in incidence and mortality, respectively, with particularly high risks among 47,XXY mosaics. These risks were still approximately 70% lower than among females, contradicting case reports that patients with KS have breast cancer rates similar to females. Altered hormone levels (especially the ratio of oestrogens to androgens), administration of exogenous androgens, gynaecomastia and genetic factors have been offered as possible explanations for the high risks. Conclusions: Additional well-designed epidemiologic studies are needed to clarify which patients with KS are at a high risk of developing MBC and to distinguish between possible predisposing factors, including altered endogenous hormones. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Brinton, LA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5018, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU Intramural NIH HHS [ZIA CP010158-13] NR 29 TC 15 Z9 15 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD JUN PY 2011 VL 100 IS 6 BP 814 EP 818 DI 10.1111/j.1651-2227.2010.02131.x PG 5 WC Pediatrics SC Pediatrics GA 755QE UT WOS:000289949900004 PM 21241366 ER PT J AU Gao, YD Majumdar, D Jovanovic, B Shaifer, C Lin, PC Zijlstra, A Webb, DJ Li, DY AF Gao, Yandong Majumdar, Devi Jovanovic, Bojana Shaifer, Candice Lin, P. Charles Zijlstra, Andries Webb, Donna J. Li, Deyu TI A versatile valve-enabled microfluidic cell co-culture platform and demonstration of its applications to neurobiology and cancer biology SO BIOMEDICAL MICRODEVICES LA English DT Article DE Cell culture; Cell-cell interaction; Synapse formation; Cell migration ID ENDOTHELIAL GROWTH-FACTOR; SYNAPSE FORMATION; SOFT LITHOGRAPHY; HYPOXIA; CULTURE; SYSTEM; ANGIOGENESIS; POLY(DIMETHYLSILOXANE); MODELS; HEPATOCYTES AB A versatile microfluidic platform allowing co-culture of multiple cell populations in close proximity with separate control of their microenvironments would be extremely valuable for many biological applications. Here, we report a simple and compact microfluidic platform that has these desirable features and allows for real-time, live-cell imaging of cell-cell interactions. Using a pneumatically/hydraulically controlled poly(dimethylsiloxane) (PDMS) valve barrier, distinct cell types can be cultured in side-by-side microfluidic chambers with their optimum culture media and treated separately without affecting the other cell population. The platform is capable of both two-dimensional and three-dimensional cell co-culture and through variations of the valve barrier design, the platform allows for cell-cell interactions through either direct cell contact or soluble factors alone. The platform has been used to perform dynamic imaging of synapse formation in hippocampal neurons by separate transfection of two groups of neurons with fluorescent pre- and post-synaptic protein markers. In addition, cross-migration of 4T1 tumor cells and endothelial cells has been studied under normoxic and hypoxic conditions, which revealed different migration patterns, suggesting the importance of the microenvironments in cell-cell interactions and biological activities. C1 [Gao, Yandong; Li, Deyu] Vanderbilt Univ, Dept Mech Engn, Nashville, TN 37235 USA. [Majumdar, Devi; Webb, Donna J.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA. [Majumdar, Devi; Webb, Donna J.] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37235 USA. [Jovanovic, Bojana; Webb, Donna J.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37235 USA. [Shaifer, Candice] Meharry Med Coll, Dept Biochem & Canc Biol, Nashville, TN 37208 USA. [Lin, P. Charles] NCI, Ctr Canc Res, Frederick, MD 21702 USA. [Zijlstra, Andries] Vanderbilt Univ, Dept Pathol, Nashville, TN 37235 USA. RP Li, DY (reprint author), Vanderbilt Univ, Dept Mech Engn, Nashville, TN 37235 USA. EM deyu.li@vanderbilt.edu RI Li, Deyu/D-2938-2012; zijlstra, andries/G-4564-2013 OI Li, Deyu/0000-0001-8364-0924; zijlstra, andries/0000-0001-8460-8803 FU NIH [MH071674, GM092914]; National Center for Research Resources at NIH [S10RR025524]; NSF [CBET0643583]; DoD [W81XWH-07-1-0507] FX We thank Anne Marie Craig, Mark Dewhirst, and Freda Miller for kindly providing us with reagents and Dmitry Markov for helpful discussions. We also thank Lan Hu for technical assistance in preparing neuronal cultures. This work was supported by grants MH071674 and GM092914 from NIH and S10RR025524 from the National Center for Research Resources at NIH to D.J.W. and grant CBET0643583 from NSF and W81XWH-07-1-0507 from DoD to D.L. NR 58 TC 56 Z9 57 U1 2 U2 45 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD JUN PY 2011 VL 13 IS 3 BP 539 EP 548 DI 10.1007/s10544-011-9523-9 PG 10 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 757PG UT WOS:000290099600013 PM 21424383 ER PT J AU Robinson, OJ Letkiewicz, AM Overstreet, C Ernst, M Grillon, C AF Robinson, Oliver J. Letkiewicz, Allison M. Overstreet, Cassie Ernst, Monique Grillon, Christian TI The effect of induced anxiety on cognition: threat of shock enhances aversive processing in healthy individuals SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article DE Anxiety; Threat of shock; Affective bias; Conflict adaptation; Resilience; BIS/BAS ID ACUTE TRYPTOPHAN DEPLETION; ERROR-RELATED NEGATIVITY; BEHAVIORAL-INHIBITION; WORKING-MEMORY; NEUROCOGNITIVE MECHANISMS; PUNISHMENT PREDICTION; POTENTIATED STARTLE; RESOLVE CONFLICT; NEURAL RESPONSES; TRAIT ANXIETY AB Individuals with anxiety disorders demonstrate altered cognitive performance including (1) cognitive biases towards negative stimuli (affective biases) and (2) increased cognitive rigidity (e.g., impaired conflict adaptation) on affective Stroop tasks. Threat of electric shock is frequently used to induce anxiety in healthy individuals, but the extent to which this manipulation mimics the cognitive impairment seen in anxiety disorders is unclear. In this study, 31 healthy individuals completed an affective Stroop task under safe and threat-of-shock conditions. We showed that threat (1) enhanced aversive processing and abolished a positive affective bias but (2) had no effect on conflict adaptation. Threat of shock thus partially models the effects of anxiety disorders on affective Stroop tasks. We suggest that the affective state of anxiety-which is common to both threat and anxiety disorders-modulates the neural inhibition of subcortical aversive processing, whilst pathologies unique to anxiety disorders modulate conflict adaptation. C1 [Robinson, Oliver J.; Letkiewicz, Allison M.; Overstreet, Cassie; Ernst, Monique; Grillon, Christian] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Robinson, OJ (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM oliver.j.robinson@gmail.com RI Robinson, Oliver/B-3646-2011 OI Robinson, Oliver/0000-0002-3100-1132 FU National Institute of Mental Health FX This research was supported by the Intramural Research Program of the National Institute of Mental Health. We also acknowledge the anonymous reviewers, whose useful suggestions improved this article. NR 67 TC 41 Z9 42 U1 5 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD JUN PY 2011 VL 11 IS 2 BP 217 EP 227 DI 10.3758/s13415-011-0030-5 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 756QB UT WOS:000290028300008 PM 21484411 ER PT J AU Johnson, T Nath, A AF Johnson, Tory Nath, Avindra TI Immune reconstitution inflammatory syndrome and the central nervous system SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE encephalitis; HIV-associated neurocognitive disorders; HIV dementia; immune restoration; multiple sclerosis ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; CD4(+) T-CELLS; CLINICAL-MANIFESTATIONS; CRYPTOCOCCUS-NEOFORMANS; TAT PROTEIN; DISEASE; AIDS; RESTORATION AB Purpose of review Central nervous system-immune reconstitution inflammatory syndrome (CNS-IRIS) is a recently recognized, devastating, T-cell-mediated encephalitis that occurs in the setting of treatment of HIV infection or autoimmune diseases, the management of which remains challenging. We review the pathophysiology, the clinical subtypes and present guidelines for prevention, diagnosis and treatment of this entity. Recent findings Nearly all patients with multiple sclerosis who develop progressive multifocal leukoencephalopathy (PML) following treatment with natalizumab develop IRIS which carries a high morbidity and mortality rate. Chronic lymphocyte activation is commonly present in the CNS of HIV-infected patients despite adequate treatment with antiretroviral therapy (ART), suggesting that a chronic from of CNS-IRIS may contribute to the neurocognitive impairment in this population. Summary The risk for CNS-IRIS can be decreased by starting ART early in the course of the illness or by reducing antigenic burden with antimicrobial treatment for opportunistic infections prior to starting ART. Of all the forms of CNS-IRIS, the management of IRIS associated with PML due to JC virus infection remains the most challenging, as no antimicrobial drug against this virus is available and the treatment of IRIS requires the use of corticosteroids, which impair the immune cells needed to control the infection. C1 [Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. [Johnson, Tory; Nath, Avindra] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RP Nath, A (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA. EM natha@mail.nih.gov FU NIH [R01NS039253, R01NS056884, R01NS055628, R01DA024593] FX This study was supported by the NIH grants, R01NS039253, R01NS039253, R01NS056884, R01NS055628 and R01DA024593. NR 60 TC 39 Z9 40 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD JUN PY 2011 VL 24 IS 3 BP 284 EP 290 DI 10.1097/WCO.0b013e328346be57 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 756UB UT WOS:000290039100015 PM 21499099 ER PT J AU Likhtarov, I Kovgan, L Chepurny, M Ivanova, O Boyko, Z Ratia, G Masiuk, S Gerasymenko, V Drozdovitch, V Berkovski, V Hatch, M Brenner, A Luckyanov, N Voilleque, P Bouville, A AF Likhtarov, I. Kovgan, L. Chepurny, M. Ivanova, O. Boyko, Z. Ratia, G. Masiuk, S. Gerasymenko, V. Drozdovitch, V. Berkovski, V. Hatch, M. Brenner, A. Luckyanov, N. Voilleque, P. Bouville, A. TI ESTIMATION OF THE THYROID DOSES FOR UKRAINIAN CHILDREN EXPOSED IN UTERO AFTER THE CHERNOBYL ACCIDENT SO HEALTH PHYSICS LA English DT Article DE dose assessment; Chernobyl; children; thyroid ID I-131 AB This paper describes methods for estimating thyroid doses to Ukrainian children who were subjects of an epidemiological study of prenatal exposure and presents the calculated doses. Participants were 2,582 mother-child pairs in which the mother had been pregnant at the time of the Chernobyl accident on 26 April 1986 or in the 2-3 mo following when I-131 in fallout was still present. Among these, 1,494 were categorized as "exposed;" a comparison group of 1,088 was considered " relatively unexposed." Individual in utero thyroid dose estimates were found to range from less than 1 mGy to 3,200 mGy, with an arithmetic mean of 72 mGy. Thyroid doses varied primarily according to stage of pregnancy at the time of exposure and level of radioactive contamination at the location of residence. There was a marked difference between the dose distributions of the exposed and comparison groups, although nine children in the latter group had calculated doses in the range 100-200 mGy. For those children who were born after the accident and prior to the end of June 1986, postnatal thyroid doses were also estimated. About 7.7% (200) of the subjects received thyroid doses after birth that were at least 10% of their cumulative doses. Health Phys. 100(6): 583-593; 2011 C1 [Drozdovitch, V.; Hatch, M.; Brenner, A.; Luckyanov, N.; Bouville, A.] NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Likhtarov, I.; Kovgan, L.; Chepurny, M.; Ivanova, O.; Boyko, Z.; Ratia, G.; Masiuk, S.; Gerasymenko, V.] Sci Res Ctr Radiat Med, Div Dosimetry & Radiat Hyg, Kiev, Ukraine. [Berkovski, V.] IAEA, A-1400 Vienna, Austria. [Voilleque, P.] MJP Risk Assessment Inc, Denver, CO 80220 USA. RP Bouville, A (reprint author), NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Execut Plaza S,EPS 7094, Bethesda, MD 20892 USA. EM bouvilla@mail.nih.gov FU U.S. National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX The research was supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. NR 15 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUN PY 2011 VL 100 IS 6 BP 583 EP 593 DI 10.1097/HP.0b013e3181ff391a PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 755XZ UT WOS:000289975700003 PM 22004928 ER PT J AU Rogan, SC Roth, BL AF Rogan, Sarah C. Roth, Bryan L. TI Remote Control of Neuronal Signaling SO PHARMACOLOGICAL REVIEWS LA English DT Review ID PROTEIN-COUPLED RECEPTORS; MUSCARINIC ACETYLCHOLINE-RECEPTORS; BETA-ADRENERGIC-RECEPTOR; DESIGNED G(I)-COUPLED RECEPTOR; IONOTROPIC GLUTAMATE-RECEPTOR; ACTIVATION BINDING-SITES; SYNTHETIC LIGANDS RASSL; GATED SODIUM-CHANNEL; CLOZAPINE-N-OXIDE; IN-VIVO CONTROL AB A significant challenge for neuroscientists is to determine how both electrical and chemical signals affect the activity of cells and circuits and how the nervous system subsequently translates that activity into behavior. Remote, bidirectional manipulation of those signals with high spatiotemporal precision is an ideal approach to addressing that challenge. Neuroscientists have recently developed a diverse set of tools that permit such experimental manipulation with varying degrees of spatial, temporal, and directional control. These tools use light, peptides, and small molecules to primarily activate ion channels and G protein-coupled receptors (GPCRs) that in turn activate or inhibit neuronal firing. By monitoring the electrophysiological, biochemical, and behavioral effects of such activation/inhibition, researchers can better understand the links between brain activity and behavior. Here, we review the tools that are avail-able for this type of experimentation. We describe the development of the tools and highlight exciting in vivo data. We focus primarily on designer GPCRs (receptors activated solely by synthetic ligands, designer receptors exclusively activated by designer drugs) and microbial opsins (e. g., channelrhodopsin-2, halorhodopsin, Volvox carteri channelrhodopsin) but also describe other novel techniques that use orthogonal receptors, caged ligands, allosteric modulators, and other approaches. These tools differ in the direction of their effect (activation/inhibition, hyperpolarization/depolarization), their onset and offset kinetics (milliseconds/minutes/hours), the degree of spatial resolution they afford, and their invasiveness. Although none of these tools is perfect, each has advantages and disadvantages, which we describe, and they are all still works in progress. We conclude with suggestions for improving upon the existing tools. C1 [Rogan, Sarah C.; Roth, Bryan L.] Univ N Carolina, Sch Pharm, Dept Pharmacol, Chapel Hill, NC 27514 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Dept Psychiat, Chapel Hill, NC 27514 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Program Neurosci, Chapel Hill, NC 27514 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Neurodev Disorders Res Ctr, Chapel Hill, NC 27514 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Dept Med Chem & Nat Prod, Chapel Hill, NC 27514 USA. [Roth, Bryan L.] Natl Inst Mental Hlth Psychoact, Drug Screening Program, Chapel Hill, NC USA. RP Roth, BL (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, 120 Mason Farm Rd, Chapel Hill, NC 27514 USA. EM bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 FU National Institutes of Health National Institute of Mental Health [MH087074, U19-MH082441, MH061887]; National Institute of Mental Health; National Institute of General Medical Sciences [GM008719]; National Alliance for Research on Schizophrenia and Depression; Triangle Community Foundation; Michael Hooker Chair FX This work was supported by the National Institutes of Health National Institute of Mental Health [Grants MH087074 (to S. C. R.), U19-MH082441, MH061887], the National Institute of Mental Health Psychoactive Drug Screening Program (to B. L. R.)], the National Institute of General Medical Sciences [Grant GM008719 (to S. C. R.)], a Distinguished Investigator Award from the National Alliance for Research on Schizophrenia and Depression (to B. L. R.), a Gertrude B. Elion Mentored Medical Student Research Award from the Triangle Community Foundation (to S. C. R.), and the Michael Hooker Chair. NR 172 TC 136 Z9 136 U1 3 U2 40 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD JUN PY 2011 VL 63 IS 2 BP 291 EP 315 DI 10.1124/pr.110.003020 PG 25 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 754VI UT WOS:000289885400002 PM 21415127 ER PT J AU Cunningham, CW Rothman, RB Prisinzano, TE AF Cunningham, Christopher W. Rothman, Richard B. Prisinzano, Thomas E. TI Neuropharmacology of the Naturally Occurring kappa-Opioid Hallucinogen Salvinorin A SO PHARMACOLOGICAL REVIEWS LA English DT Review ID SAGE SALVIA-DIVINORUM; GLYCOPROTEIN SUBSTRATE ACTIVITY; PLANT-DERIVED HALLUCINOGEN; GAS CHROMATOGRAPHY/MASS SPECTROMETRY; INTRACRANIAL SELF-STIMULATION; ACTIVE INGREDIENT SALVINORIN; THIN-LAYER-CHROMATOGRAPHY; PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; FORCED SWIM TEST AB Salvia divinorum is a perennial sage native to Oaxaca, Mexico, that has been used traditionally in divination rituals and as a treatment for the "semimagical" disease panzon de borrego. Because of the intense "out-of-body" experiences reported after inhalation of the pyrolized smoke, S. divinorum has been gaining popularity as a recreational hallucinogen, and the United States and several other countries have regulated its use. Early studies isolated the neoclerodane diterpene salvinorin A as the principal psychoactive constituent responsible for these hallucinogenic effects. Since the finding that salvinorin A exerts its potent psy-chotropic actions through the activation of KOP receptors, there has been much interest in elucidating the underlying mechanisms behind its effects. These effects are particularly remarkable, because 1) salvinorin A is the first reported non-nitrogenous opioid receptor agonist, and 2) its effects are not mediated by the 5-HT(2A) receptor, the classic target of hallucinogens such as lysergic acid diethylamide and mescaline. Rigorous investigation into the structural features of salvinorin A responsible for opioid receptor affinity and selectivity has produced numerous receptor probes, affinity labels, and tools for evaluating the biological processes responsible for its observed psychological effects. Salvinorin A has therapeutic potential as a treatment for pain, mood and personality disorders, substance abuse, and gastrointestinal disturbances, and suggests that nonalkaloids are potential scaffolds for drug development for aminergic G-protein coupled receptors. C1 [Cunningham, Christopher W.; Prisinzano, Thomas E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. [Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. RP Prisinzano, TE (reprint author), 1251 Wescoe Hall Dr,4070 Malott Hall, Lawrence, KS 66045 USA. EM prisinza@ku.edu FU National Institute on Drug Abuse [DA-018151] FX This work was supported by a grant from the National Institute on Drug Abuse [Grant DA-018151] (to T. E. P.) and, in part, by the Intramural Research Program of the National Institute on Drug Abuse (to R.B.R.). NR 226 TC 47 Z9 47 U1 2 U2 27 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD JUN PY 2011 VL 63 IS 2 BP 316 EP 347 DI 10.1124/pr.110.003244 PG 32 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 754VI UT WOS:000289885400003 PM 21444610 ER PT J AU Gremel, CM Young, EA Cunningham, CL AF Gremel, Christina M. Young, Emily A. Cunningham, Christopher L. TI Blockade of opioid receptors in anterior cingulate cortex disrupts ethanol-seeking behavior in mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Ethanol; Cue-induced drug seeking; Incentive motivation; Opioid receptors; Anterior cingulate cortex; Conditioned place preference ID CONDITIONED PLACE PREFERENCE; MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS CORE; AMYGDALA DOPAMINE; RATS; REINSTATEMENT; EXPRESSION; ACTIVATION; ALCOHOLICS; NALTREXONE AB The anterior cingulate cortex (ACC) and opioid receptors have been suggested to play a role in attributing incentive motivational properties to drug-related cues. We examined whether blockade of ACC opioid receptors would reduce cue-induced ethanol-seeking behavior in mice. We show that intra-ACC opioid receptor blockade disrupted expression of an ethanol-induced conditioned place preference, suggesting that endogenous opioid modulation in the ACC may be critical for maintaining the cue's conditioned rewarding effects. (C) 2011 Elsevier B.V. All rights reserved. C1 [Gremel, Christina M.; Young, Emily A.; Cunningham, Christopher L.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland Alcohol Res Ctr, Portland, OR 97239 USA. RP Gremel, CM (reprint author), NIAAA, Sect Invivo Neural Funct, Lab Integrat Neurosci, NIH, 5625 Fishers Ln,TS 20, Bethesda, MD 20892 USA. EM gremelc@mail.nih.gov FU NIH-NIAAA [AA016041, AA007468, AA007702] FX This research was supported by NIH-NIAAA grants AA016041, AA007468, and AA007702. Experiments within this manuscript comply with the current laws of the United States of America. NR 43 TC 6 Z9 6 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JUN 1 PY 2011 VL 219 IS 2 BP 358 EP 362 DI 10.1016/j.bbr.2010.12.033 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 752PD UT WOS:000289703700024 PM 21219940 ER PT J AU Anastasio, NC Stoffel, EC Fox, RG Bubar, MJ Rice, KC Moeller, FG Cunningham, KA AF Anastasio, Noelle C. Stoffel, Erin C. Fox, Robert G. Bubar, Marcy J. Rice, Kenner C. Moeller, Frederick G. Cunningham, Kathryn A. TI Serotonin (5-hydroxytryptamine) 5-HT2A receptor: association with inherent and cocaine-evoked behavioral disinhibition in rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE behavioral disinhibition; cocaine; differential reinforcement of low rate task; 5-HT2A receptor; impulsivity; one-choice serial reaction time task; rat ID REACTION-TIME-TASK; DISCRIMINATIVE STIMULUS PROPERTIES; SCHEDULE-CONTROLLED BEHAVIOR; INDUCED LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX; IMPULSIVE CHOICE; SEEKING BEHAVIOR; DOPAMINERGIC MECHANISMS; EXTRACELLULAR DOPAMINE AB Alterations in the balance of functional activity within the serotonin [5-hydroxytryptamine (5-HT)] system are hypothesized to underlie impulse control. Cocaine-dependent subjects consistently show greater impulsivity relative to nondrug using control subjects. Preclinical studies suggest that the 5-HT2A receptor (5-HT2AR) contributes to the regulation of impulsive behavior and also mediates some of the behavioral effects of cocaine. We hypothesized that the selective 5-HT2AR antagonist M100907 would reduce inherent levels of impulsivity and attenuate impulsive responding induced by cocaine in two animal models of impulsivity, the differential reinforcement of low rate (DRL) task and the one-choice serial reaction time (1-CSRT) task. M100907 reduced rates of responding in the DRL task and premature responding in the 1-CSRT task. Conversely, cocaine disrupted rates of responding in the DRL task and increased premature responding in the 1-CSRT task. M100907 attenuated cocaine-induced increases in specific markers of behavioral disinhibition in the DRL and 1-CSRT tasks. These results suggest that the 5-HT2AR regulates inherent impulsivity, and that blockade of the 5-HT2AR alleviates specific aspects of elevated levels of impulsivity induced by cocaine exposure. These data point to the 5-HT2AR as an important regulatory substrate in impulse control. Behavioural Pharmacology 22: 248-261 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Anastasio, Noelle C.; Stoffel, Erin C.; Fox, Robert G.; Bubar, Marcy J.; Moeller, Frederick G.; Cunningham, Kathryn A.] Univ Texas Galveston, Med Branch, Ctr Addict Res, Galveston, TX 77555 USA. [Anastasio, Noelle C.; Stoffel, Erin C.; Fox, Robert G.; Bubar, Marcy J.; Cunningham, Kathryn A.] Univ Texas Galveston, Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA. [Moeller, Frederick G.] Univ Texas Houston, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Houston, TX 77225 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Drug Design & Synth Sect, Intramural Res Program,NIH, Bethesda, MD 20892 USA. RP Cunningham, KA (reprint author), Univ Texas Galveston, Med Branch, Ctr Addict Res, 301 Univ Blvd Route 0617, Galveston, TX 77555 USA. EM kcunning@utmb.edu RI Cunningham, Kathryn/O-2718-2013 FU National Institute on Drug Abuse [DA006511, DA000260, DA020087, DA07287, DA00403]; Peter F. McManus Charitable Trust; Jeane B. Kempner Postdoctoral Scholar Award; Ruth L. Kirchstein National Research Service Award [DA0121438]; National Institute on Alcohol Abuse and Alcoholism FX The study was supported by the National Institute on Drug Abuse grants DA006511 (K.A.C.), DA000260 (K.A.C.), DA020087 (K.A.C.), DA07287 (K.A.C.), DA00403 (F.G.M.), the Peter F. McManus Charitable Trust (K.A.C.), the Jeane B. Kempner Postdoctoral Scholar Award (N.C.A.), and the Ruth L. Kirchstein National Research Service Award DA0121438 (E.C.S.). A part of this study was also supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism (K.C.R.). NR 89 TC 18 Z9 19 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD JUN PY 2011 VL 22 IS 3 BP 248 EP 261 DI 10.1097/FBP.0b013e328345f90d PG 14 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 753KE UT WOS:000289770900007 PM 21499079 ER PT J AU Mathews, LA Cabarcas, SM Farrar, WL AF Mathews, Lesley A. Cabarcas, Stephanie M. Farrar, William L. TI DNA repair: the culprit for tumor-initiating cell survival? SO CANCER AND METASTASIS REVIEWS LA English DT Review DE Tumor-initiating cells; DNA repair; Metastasis ID CANCER STEM-CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; PROSTATE-CANCER; PANCREATIC-CANCER; BREAST-CANCER; DAMAGE RESPONSE; IN-VITRO; DIFFERENTIATED CELLS; EXPRESSION ANALYSIS; MISMATCH REPAIR AB The existence of "tumor-initiating cells" (TICs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has led to an abundance of evidence supporting their existence. TICs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately leading to metastasis and patient demise. This review summarizes DNA repair mechanism(s) and their role in the maintenance and regulation of stem cells. There is evidence supporting the hypothesis that TICs, similar to embryonic stem (ES) cells and hematopoietic stem cells (HSCs), display an increase in their ability to survive genotoxic stress and injury. Mechanistically, the ability of ES cells, HSCs and TICs to survive under stressful conditions can be attributed to an increase in the efficiency at which these cells undergo DNA repair. Furthermore, the data presented in this review summarize the results found by our lab and others demonstrating that TICs have an increase in their genomic stability, which can allow for TIC survival under conditions such as anticancer treatments, while the bulk population of tumor cells dies. We believe that these data will greatly impact the development and design of future therapies being engineered to target and eradicate this highly aggressive cancer cell population. C1 [Mathews, Lesley A.; Cabarcas, Stephanie M.; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. RP Farrar, WL (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, 1050 Boyles St,Bldg 560,Room 21-81, Frederick, MD 21702 USA. EM farrarw@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract 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 US Government. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 86 TC 18 Z9 18 U1 4 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 2011 VL 30 IS 2 BP 185 EP 197 DI 10.1007/s10555-011-9277-0 PG 13 WC Oncology SC Oncology GA 750SM UT WOS:000289568300004 PM 21340664 ER PT J AU Hubbard, J Erlichman, C Toft, DO Qin, R Stensgard, BA Felten, S Ten Eyck, C Batzel, G Ivy, SP Haluska, P AF Hubbard, Joleen Erlichman, Charles Toft, David O. Qin, Rui Stensgard, Bridget A. Felten, Sara Ten Eyck, Cynthia Batzel, Gretchen Ivy, S. Percy Haluska, Paul TI Phase I study of 17-allylamino-17 demethoxygeldanamycin, gemcitabine and/or cisplatin in patients with refractory solid tumors SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE 17-allyaminogeldanamycin; Phase I; Heat shock protein 90; Cisplatin; Gemcitabine; Heat shock protein 70; ILK ID HEAT-SHOCK RESPONSE; ADVANCED CANCER; DOSE-ESCALATION; DNA-DAMAGE; HSP90; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; GELDANAMYCIN; TRIAL; CHECKPOINT; STRESS AB Purpose: To determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLT) of 17-AAG, gemcitabine and/or cisplatin. Levels of the proteins Hsp90, Hsp70 and ILK were measured in peripheral blood mononuclear cell (PMBC) lysates to assess the effects of 17-AAG. Experimental design: Phase I dose-escalating trial using a "3 + 3" design performed in patients with advanced solid tumors. Once the MTD of gemcitabine + 17-AAG + cisplatin was determined, dose escalation of 17-AAG with constant doses of gemcitabine and cisplatin was attempted. After significant hematologic toxicity occurred, the protocol was amended to evaluate three cohorts: gemcitabine and 17-AAG; 17-AAG and cisplatin; and gemcitabine, 17-AAG and cisplatin with modified dosing. Results: The 39 patients enrolled were evaluable for toxicity and response. The MTD for cohort A was 154 mg/m(2) of 17-AAG, 750 mg/m(2) of gemcitabine, and 40 mg/m(2) of cisplatin. In cohort A, DLTs were observed at the higher dose level and included neutropenia, hyperbilirubinemia, dehydration, GGT elevation, hyponatremia, nausea, vomiting, and thrombocytopenia. The MTD for cohort C was 154 mg/m(2) of 17-AAG and 750 mg/m(2) of gemcitabine, with one DLT observed (alkaline phosphatase elevation) observed. In cohort C, DLTs of thrombocytopenia, fever and dyspnea were seen at the higher dose level. The remaining cohorts were closed to accrual due to toxicity. Six patients experienced partial responses. Mean Hsp90 levels were decreased and levels of Hsp70 were increased compared to baseline. Conclusions: 17-AAG in combination with gemcitabine and cisplatin demonstrated antitumor activity, but significant hematologic toxicities were encountered. 17-AAG combined with gemcitabine is tolerable and has demonstrated evidence of activity at the MTD. The recommended phase II dose is defined as 154 mg/m(2) of 17-AAG and 750 mg/m(2) of gemcitabine, and is currently being investigated in phase II studies in ovarian and pancreatic cancers. There is no recommended phase II dose for the cisplatin-containing combinations. C1 [Hubbard, Joleen; Erlichman, Charles; Ten Eyck, Cynthia; Batzel, Gretchen; Haluska, Paul] Mayo Clin, Coll Med, Div Med Oncol, Rochester, MN 55905 USA. [Qin, Rui; Felten, Sara] Mayo Clin, Coll Med, Div Biostat, Rochester, MN 55905 USA. [Toft, David O.; Stensgard, Bridget A.] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. [Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Haluska, P (reprint author), Mayo Clin, Coll Med, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM haluska.paul@mayo.edu RI Qin, Rui/H-5638-2012 FU [CA66912]; [CA15083]; [CA090628] FX Grant support CA66912 (C.E.), CA15083, CA090628 (P.H.). NR 31 TC 22 Z9 23 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD JUN PY 2011 VL 29 IS 3 BP 473 EP 480 DI 10.1007/s10637-009-9381-y PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 750DZ UT WOS:000289526400008 PM 20082116 ER PT J AU Benhammou, JN Vocke, CD Santani, A Schmidt, LS Baba, M Seyama, K Wu, XL Korolevich, S Nathanson, KL Stolle, CA Linehan, WM AF Benhammou, Jihane N. Vocke, Cathy D. Santani, Avni Schmidt, Laura S. Baba, Masaya Seyama, Kuniaki Wu, Xiaolin Korolevich, Susana Nathanson, Katherine L. Stolle, Catherine A. Linehan, W. Marston TI Identification of Intragenic Deletions and Duplication in the FLCN Gene in Birt-Hogg-Dube Syndrome SO GENES CHROMOSOMES & CANCER LA English DT Article ID GERMLINE DELETIONS; TANDEM DUPLICATION; KIDNEY NEOPLASIA; RECOMBINATION; MUTATIONS; CANCER; PHENOTYPE; PROTEIN; REARRANGEMENTS; ACROCHORDONS AB Birt-Hogg-Dube syndrome (BHDS), caused by germline mutations in the folliculin (FLCN) gene, predisposes individuals to develop fibrofolliculomas, pulmonary cysts, spontaneous pneumothoraces, and kidney cancer. The FLCN mutation detection rate by bidirectional DNA sequencing in the National Cancer Institute BHDS cohort was 88%. To determine if germline FLCN intragenic deletions/duplications were responsible for BHDS in families lacking FLCN sequence alterations, 23 individuals from 15 unrelated families with clinically confirmed BHDS but no sequence variations were analyzed by real-time quantitative PCR (RQ-PCR) using primers for all 14 exons. Multiplex ligation-dependent probe amplification (MLPA) assay and array-based comparative genomic hybridization (aCGH) were utilized to confirm and fine map the rearrangements. Long-range PCR followed by DNA sequencing was used to define the breakpoints. We identified six unique intragenic deletions in nine patients from six different BHDS families including four involving exon 1, one that spanned exons 2-5, and one that encompassed exons 7-14 of FLCN. Four of the six deletion breakpoints were mapped, revealing deletions ranging from 5688 to 9189 bp. In addition, one 1341 bp duplication, which included exons 10 and 11, was identified and mapped. This report confirms that large intragenic FLCN deletions can cause BHDS and documents the first large intragenic FLCN duplication in a BHDS patient. Additionally, we identified a deletion "hot spot" in the 5'-noncoding-exon 1 region that contains the putative FLCN promoter based on a luciferase reporter assay. RQ-PCR, MLPA and aCGH may be used for clinical molecular diagnosis of BHDS in patients who are FLCN mutation-negative by DNA sequencing. C1 [Benhammou, Jihane N.; Vocke, Cathy D.; Schmidt, Laura S.; Baba, Masaya; Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Santani, Avni; Stolle, Catherine A.] Childrens Hosp Philadelphia, Mol Genet Lab, Dept Pathol & Lab Med, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Schmidt, Laura S.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Seyama, Kuniaki] Juntendo Univ, Sch Med, Dept Resp Med, Tokyo 113, Japan. [Wu, Xiaolin; Korolevich, Susana] NCI, Lab Mol Technol, Frederick, MD 21702 USA. [Nathanson, Katherine L.] Univ Penn, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Nathanson, Katherine L.] Univ Penn, Dept Med, Div Med Genet, Philadelphia, PA 19104 USA. RP Schmidt, LS (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10-CRC-1-3961,10 Ctr Dr MSC1107, Bethesda, MD 20892 USA. EM schmidtl@mail.nih.gov RI Baba, Masaya/L-7490-2013; OI Baba, Masaya/0000-0002-5308-6683; Nathanson, Katherine/0000-0002-6740-0901 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN 261200800001E] FX Supported by: Intramural Research Program of National Institutes of Health, National Cancer Institute, Center for Cancer Research; funded in part with federal funds from National Cancer Institute, National Institutes of Health; Contract number HHSN 261200800001E. NR 36 TC 20 Z9 20 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-2257 EI 1098-2264 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUN PY 2011 VL 50 IS 6 BP 466 EP 477 DI 10.1002/gcc.20872 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 748FQ UT WOS:000289375800009 PM 21412933 ER PT J AU Gadalla, SM Rajan, A Pfeiffer, R Kristinsson, SY Bjorkholm, M Landgren, O Giaccone, G AF Gadalla, Shahinaz M. Rajan, Arun Pfeiffer, Ruth Kristinsson, Sigurdur Y. Bjorkholm, Magnus Landgren, Ola Giaccone, Giuseppe TI A population-based assessment of mortality and morbidity patterns among patients with thymoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE thymoma; autoimmunity; second cancer ID ORGANIZATION HISTOLOGIC CLASSIFICATION; MYASTHENIA-GRAVIS; MALIGNANT THYMOMA; UNITED-STATES; THYMECTOMY; TUMORS; RISK AB Thymomas are rare tumors of the mediastinum; a limited number of small studies have evaluated the outcomes in these patients. We identified 668 patients with thymoma from the Swedish Cancer Registry, and 2,719 population-based matched controls. We obtained information on autoimmunity from the nationwide inpatient/outpatient hospital discharge Registry. We constructed Kaplan-Meier curves for survival analysis, conditional regression and Cox proportional hazards models to evaluate the association between thymoma and autoimmune diseases, and standardized incidence ratios (SIRs) to evaluate the risk for second cancers following thymoma. Compared with controls, patients with benign or malignant thymoma had a poorer (p < 0.001) 5-year (79%, 53% vs. 91%), 10-year (65%, 39% vs. 78%) and 20-year (43%, 18% vs. 55%) overall survival. For thymoma patients, younger age at diagnosis and being diagnosed in recent years were associated with a better survival. Compared with controls, thymoma patients were more likely to have an autoimmune disease at some point during their lives (32.7% vs. 2.4%, respectively, p < 0.001), most frequently myasthenia gravis (24.5%), systemic lupus erythematosus (2.4%) and red cell aplasia (1.2%). Thymoma patients had twofold excess risk for second cancers compared with the general population, most notably: non-melanoma skin cancer (SIR = 10.6, 95% confidence intervals (CI) = 6.0-17.3), non-Hodgkin lymphoma (SIR = 6.8, 95% CI = 3.00-13.0), and cervical (SIR = 6.9, 95% CI = 1.4-20.1), endocrine (SIR = 4.7, 95% CI = 1.3-12.0), and prostate cancer (SIR = 3.0, 95% CI = 1.7-4.8). Despite the improved survival for thymoma patients over time, they have worse survival than controls. Thymoma patients are in need for follow-up to detect and manage autoimmune diseases and cancer. C1 [Rajan, Arun; Landgren, Ola; Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Gadalla, Shahinaz M.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Gadalla, Shahinaz M.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Pfeiffer, Ruth] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp Solna, Div Hematol, Dept Med, Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Inst, Stockholm, Sweden. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, 10 Ctr Dr,Bldg 10,Room12N226, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; Kristinsson, Sigurdur /M-2910-2015; Giaccone, Giuseppe/E-8297-2017 OI Kristinsson, Sigurdur /0000-0002-4964-7476; Giaccone, Giuseppe/0000-0002-5023-7562 FU Swedish Cancer Society; Stockholm County Council; Karolinska Institutet Foundations, Sweden; National Cancer Institute, USA FX Grant sponsors: Swedish Cancer Society, Stockholm County Council, The Karolinska Institutet Foundations, Sweden, The Intramural Research Program of the National Cancer Institute, USA NR 25 TC 14 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 2011 VL 128 IS 11 BP 2688 EP 2694 DI 10.1002/ijc.25583 PG 7 WC Oncology SC Oncology GA 748EE UT WOS:000289372000019 PM 20669226 ER PT J AU Xu, ZL Bensen, JT Smith, GJ Mohler, JL Taylor, JA AF Xu, Zongli Bensen, Jeannette T. Smith, Gary J. Mohler, James L. Taylor, Jack A. TI GWAS SNP Replication Among African American and European American Men in the North Carolina-Louisiana Prostate Cancer Project (PCaP) SO PROSTATE LA English DT Article DE SNP; prostate cancer; African American; genome-wide association; admixture ID GENOME-WIDE ASSOCIATION; RISK-ASSOCIATED LOCI; 5 GENETIC-VARIANTS; SUSCEPTIBILITY; 8Q24; POPULATIONS; REGIONS; 11Q13; 17Q12 AB BACKGROUND. Genome-wide association studies (GWAS) have identified numerous common SNPs associated with prostate cancer (CaP) risk in men of European descent. This study evaluates GWAS SNPs associated with CaP in African Americans (AAs) and European Americans (EA). METHODS. Eight hundred SNPs were genotyped, including 32 from European-based GWAS and 35 flanking SNPs, in 417 AA and 455 EA cases from the NC-LA Prostate Cancer Project (PCaP) and compared to 925 AA and 1,687 EA controls from Illumina's iControlDB. The 32 GWAS SNPs were evaluated for their predictive power to discriminate between cases and controls using ROC curves. RESULTS. Of the 32 GWAS SNPs, 13 were significant at P < 0.05 in EA and 4 in AA (rs6983267, rs7017300, rs1859962, rs6501455). Three of 35 flanking SNPs, all from chromosome 8q, reached study-wide significance (P < 3.5 x 10(-5)); 2 in AA (rs10505476 rs6985504) and 1 in EA (rs16901970). Among the remaining 656 SNPs, 2 were associated with CaP (P < 3.5 x 10(-5)): rs1472606 (OR: 1.43 in EA) and rs9351265 (OR: 1.48 in AA) both in intergenic regions. For the 32 GWASSNPs, ROC plots yielded AUC estimates too low for clinical use (EA AUC = 0.60 and AA AUC = 0.56). CONCLUSIONS. This study confirms a large proportion of CaP associated regions implicated by European-based GWAS and provides evidence that some regions may be important in AA CaP risk. Despite the identification of a large panel of GWAS replicated SNPs for CaP, this panel is not appropriate for clinical screening. Prostate 71: 881-891, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Xu, Zongli; Taylor, Jack A.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Bensen, Jeannette T.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Bensen, Jeannette T.; Mohler, James L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Smith, Gary J.; Mohler, James L.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA. [Mohler, James L.] SUNY Buffalo, Dept Urol, Sch Med & Biotechnol, Buffalo, NY 14260 USA. [Mohler, James L.] Univ N Carolina, Div Urol, Dept Surg, Chapel Hill, NC USA. [Taylor, Jack A.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Taylor, JA (reprint author), NIEHS, Epidemiol Branch, MD A3-05,111 Tw Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM taylor@niehs.nih.gov OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398 FU Department of Defense [DAMD 17-03-2-0052]; NIH, National Institute of Environmental Health Sciences; NIH National Center on Minority Health and Health Disparities FX The authors thank the North Carolina Central Cancer Registry and the PCaP staff, advisory committees and participants for their important contributions. The Prostate Cancer Project (PCaP) is carried out as a collaborative study supported by the Department of Defense contract DAMD 17-03-2-0052. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences and the NIH National Center on Minority Health and Health Disparities. NR 34 TC 19 Z9 19 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD JUN 1 PY 2011 VL 71 IS 8 BP 881 EP 891 DI 10.1002/pros.21304 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 750BB UT WOS:000289517500009 PM 21456070 ER PT J AU Bruno, RD Smith, GH AF Bruno, Robert D. Smith, Gilbert H. TI Functional Characterization of Stem Cell Activity in the Mouse Mammary Gland SO STEM CELL REVIEWS AND REPORTS LA English DT Article DE Stem cells; Mammary gland; Niche; Label-retaining cells; Asymmetric DNA segregation; Parity identified mammary epithelial cells; Lobule progenitor; Ductal progenitor ID LABEL-RETAINING CELLS; TEMPLATE DNA STRANDS; EPITHELIAL-CELLS; IN-VIVO; TGF-BETA-1 EXPRESSION; SELECTIVE SEGREGATION; DIFFERENTIATION; RECEPTOR; CANCER; MICROENVIRONMENT AB Any portion of the mouse mammary gland is capable of recapitulating a clonally derived complete and functional mammary tree upon transplantation into an epithelial divested mammary fat-pad of a recipient host. As such, it is an ideal model tissue for the study somatic stem cell function. This review will outline what is known regarding the function of stem/progenitor cells in the mouse mammary gland, including how progenitor populations can be functionally defined, the evidence for and potential role of selective DNA strand segregation, and the role of the niche in maintaining and controlling stem cell function. C1 [Bruno, Robert D.; Smith, Gilbert H.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, 37 Convent Dr, Bethesda, MD 20892 USA. EM smithg@mail.nih.gov OI Bruno, Robert/0000-0003-3329-9478 FU Intramural NIH HHS [Z99 CA999999] NR 48 TC 12 Z9 13 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1550-8943 J9 STEM CELL REV REP JI Stem Cell Rev. Rep. PD JUN PY 2011 VL 7 IS 2 BP 238 EP 247 DI 10.1007/s12015-010-9191-9 PG 10 WC Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 747CJ UT WOS:000289297600003 PM 20853073 ER PT J AU Arnaldez, F Yeung, C Grohar, P Helman, L AF Arnaldez, Fernanda Yeung, Choh Grohar, Patrick Helman, Lee TI TRAVEL STIPEND AWARD WINNER IN VIVO AND IN VITRO ALVEOLAR RHABDOMYOSARCOMA CELL GROWTH IS AFFECTED BY TNK2 EXPRESSION SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Arnaldez, Fernanda; Yeung, Choh; Grohar, Patrick; Helman, Lee] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 902 EP 902 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100020 ER PT J AU Giri, N Alter, B Lee, R Faro, A Huddleston, C White, F Savage, S AF Giri, Neelam Alter, Blanche Lee, Rees Faro, Albert Huddleston, Charles White, Frances Savage, Sharon TI LUNG TRANSPLANTATION FOR PULMONARY FIBROSIS IN DYSKERATOSIS CONGENITA: CASE REPORT AND LITERATURE REVIEW SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Giri, Neelam; Alter, Blanche; Lee, Rees; Faro, Albert; Huddleston, Charles; White, Frances; Savage, Sharon] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 905 EP 905 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100032 ER PT J AU Perkins, K Davis, J Price, S Uzel, G Su, H Aldridge, P Dominado, M Tretler, J Pittaluga, S Jaffe, E Olivier, K Rao, VK AF Perkins, Katie Davis, Joie Price, Susan Uzel, Gulbu Su, Helen Aldridge, Patricia Dominado, Margaret Tretler, Jean Pittaluga, Stefania Jaffe, Elaine Olivier, Kenneth Rao, V. Koneti TI EXTRA-NODAL MANIFESTATIONS OF ALPS AND RELATED DISORDERS: INFILTRATIVE PULMONARY LESIONS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Perkins, Katie; Davis, Joie; Price, Susan; Uzel, Gulbu; Su, Helen; Aldridge, Patricia; Dominado, Margaret; Tretler, Jean; Pittaluga, Stefania; Jaffe, Elaine; Olivier, Kenneth; Rao, V. Koneti] NIH, Bethesda, MD 20892 USA. RI Su, Helen/H-9541-2015 OI Su, Helen/0000-0002-5582-9110 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 906 EP 906 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100037 ER PT J AU Rao, VK Hornung, R Price, S Davis, J OLiviera, JB AF Rao, V. Koneti Hornung, Ronald Price, Susan Davis, Joie OLiviera, Joao B. TI ELEVATED B CELL-ACTIVATING FACTOR OF THE TUMOR NECROSIS FACTOR FAMILY (BAFF) NOTED IN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME DUE TO FAS DEFECT (ALPS-FAS) SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Rao, V. Koneti; Hornung, Ronald; Price, Susan; Davis, Joie; OLiviera, Joao B.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 908 EP 908 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100044 ER PT J AU Wayne, A Bhojwani, D Richards, K Stetler-Stevenson, M Silverman, L Jeha, S Pui, CH McDevitt, J FitzGerald, D Kreitman, R Lechleider, R Pastan, I AF Wayne, Alan Bhojwani, Deepa Richards, Kelly Stetler-Stevenson, Maryalice Silverman, Lewis Jeha, Sima Pui, Ching-Hon McDevitt, Jennifer FitzGerald, David Kreitman, Robert Lechleider, Robert Pastan, Ira TI A PHASE I STUDY OF MOXETUMOMAB PASUDOTOX, AN ANTI-CD22 IMMUNOTOXIN, IN PATIENTS WITH PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA (ALL): UPDATED RESULTS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Wayne, Alan; Bhojwani, Deepa; Richards, Kelly; Stetler-Stevenson, Maryalice; Silverman, Lewis; Jeha, Sima; Pui, Ching-Hon; McDevitt, Jennifer; FitzGerald, David; Kreitman, Robert; Lechleider, Robert; Pastan, Ira] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 919 EP 919 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100081 ER PT J AU Salzer, W Asselin, B Supko, J Devidas, M Kaiser, N Plourde, P Winick, N Reaman, G Raetz, E Carroll, W Hunger, S AF Salzer, Wanda Asselin, Barbara Supko, Jeffrey Devidas, Meenakshi Kaiser, Nicole Plourde, Paul Winick, Naomi Reaman, Gregory Raetz, Elizabeth Carroll, William Hunger, Stephen TI ADMINISTRATION OF ERWINIA ASPARAGINASE FOLLOWING ALLERGY TO PEG-ASPARAGINASE IN CHILDREN AND YOUNG ADULTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA ACHIEVES THERAPEUTIC NADIR SERUM ASPARAGINASE ACTIVITY: A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP (COG) SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Salzer, Wanda; Asselin, Barbara; Supko, Jeffrey; Devidas, Meenakshi; Kaiser, Nicole; Plourde, Paul; Winick, Naomi; Reaman, Gregory; Raetz, Elizabeth; Carroll, William; Hunger, Stephen] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 922 EP 922 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100091 ER PT J AU Dave, H Baskar, S Wayne, A Khan, J Rader, C AF Dave, Hema Baskar, Sivasubramanian Wayne, Alan Khan, Javed Rader, Christoph TI ROR1 AS A NOVEL TARGET FOR PRE-B ACUTE LYMPHOBLASTIC LEUKEMIA AND NEUROBLASTOMA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Dave, Hema; Baskar, Sivasubramanian; Wayne, Alan; Khan, Javed; Rader, Christoph] NCI, NIH, Johns Hopkins Hosp, Bethesda, MD 20892 USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 923 EP 923 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100095 ER PT J AU Peredo-Pinto, H Alter, B Giri, N Elghetany, T Maric, I Savage, S Arthur, D AF Peredo-Pinto, Helkha Alter, Blanche Giri, Neelam Elghetany, Tarek Maric, Irina Savage, Sharon Arthur, Diane TI SIGNIFICANCE OF BONE MARROW KARYOTYPES AND MORPHOLOGY IN PATIENTS WITH INHERITED BONE MARROW FAILURE SYNDROMES SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Peredo-Pinto, Helkha; Alter, Blanche; Giri, Neelam; Elghetany, Tarek; Maric, Irina; Savage, Sharon; Arthur, Diane] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 926 EP 926 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100105 ER PT J AU Levine, D Wendler, D Cohen, K AF Levine, Deena Wendler, Dave Cohen, Kenneth TI MEDICAL PATERNALISM VS. RESPONSIBLE THERAPEUTICS: AN ETHICAL ANALYSIS OF THE TREATMENT OF BRAIN TUMORS IN YOUNG CHILDREN SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Levine, Deena; Wendler, Dave; Cohen, Kenneth] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 945 EP 945 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100172 ER PT J AU Kato, G Sable, C Ensing, G Dham, N Minniti, C Remaley, A Campbell, A Arteta, M Rana, S Darbari, D Nouraie, SM Onyekwere, O Gladwin, M Castro, O Gordeuk, V AF Kato, Gregory Sable, Craig Ensing, Greg Dham, Niti Minniti, Caterina Remaley, Alan Campbell, Andrew Arteta, Manuel Rana, Sohail Darbari, Deepika Nouraie, Seyed-Mehdi Onyekwere, Onyinye Gladwin, Mark Castro, Oswaldo Gordeuk, Victor TI PLASMA LEVEL OF NT-PROBNP IN CHILDREN WITH SICKLE CELL DISEASE IS ASSOCIATED WITH DEGREE OF ANEMIA AND LEFT VENTRICULAR MEASURES: THE PUSH STUDY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Kato, Gregory; Sable, Craig; Ensing, Greg; Dham, Niti; Minniti, Caterina; Remaley, Alan; Campbell, Andrew; Arteta, Manuel; Rana, Sohail; Darbari, Deepika; Nouraie, Seyed-Mehdi; Onyekwere, Onyinye; Gladwin, Mark; Castro, Oswaldo; Gordeuk, Victor] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 947 EP 947 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100181 ER PT J AU Kratz, C Giri, N Suuriniemi, M Edelman, D Meltzer, P Alter, B AF Kratz, Christian Giri, Neelam Suuriniemi, Miia Edelman, Daniel Meltzer, Paul Alter, Blanche TI CLINICAL AND MOLECULAR CHARACTERIZATION OF PATIENTS WITH DIAMOND-BLACKFAN ANEMIA CAUSED BY RPL35A GENE DELETIONS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Kratz, Christian; Giri, Neelam; Suuriniemi, Miia; Edelman, Daniel; Meltzer, Paul; Alter, Blanche] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 949 EP 949 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100188 ER PT J AU Darbari, D Onyekwere, O Campbell, A Luchtman-Jones, L Dham, N Sable, C Rana, S Ensing, G Nouraie, SM Gordeuk, V Minniti, C Castro, O Kato, G AF Darbari, Deepika Onyekwere, Onyinye Campbell, Andrew Luchtman-Jones, Lori Dham, Niti Sable, Craig Rana, Sohail Ensing, Greg Nouraie, Seyed-Mehdi Gordeuk, Victor Minniti, Caterina Castro, Oswaldo Kato, Gregory TI MARKERS OF SEVERE VASO-OCCLUSIVE PAINFUL EPISODES IN CHILDREN AND ADOLESCENTS WITH SICKLE CELL ANEMIA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 NIH, Multictr Study, Childrens Natl Med Ctr, Washington, DC USA. Howard Univ, Washington, DC 20059 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 950 EP 950 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100192 ER PT J AU Alter, B Rosenberg, P Day, T Menzel, S Giri, N Savage, S Thein, SL AF Alter, Blanche Rosenberg, Philip Day, Thomas Menzel, Stephan Giri, Neelam Savage, Sharon Thein, Swee Lay TI GENETIC REGULATION OF FETAL HEMOGLOBIN IN PATIENTS WITH INHERITED BONE MARROW FAILURE SYNDROMES SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Alter, Blanche; Rosenberg, Philip; Day, Thomas; Menzel, Stephan; Giri, Neelam; Savage, Sharon; Thein, Swee Lay] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 951 EP 952 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100196 ER PT J AU Wentzensen, I Giri, N Shamburek, R Alter, B Savage, S AF Wentzensen, Ingrid Giri, Neelam Shamburek, Robert Alter, Blanche Savage, Sharon TI RESPONSE TO ANDROGEN THERAPY AND SIDE EFFECTS IN PATIENTS WITH DYSKERATOSIS CONGENITA SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Wentzensen, Ingrid; Giri, Neelam; Shamburek, Robert; Alter, Blanche; Savage, Sharon] NCI, DCEG, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN PY 2011 VL 56 IS 6 SI SI BP 955 EP 955 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 736AY UT WOS:000288463100210 ER PT J AU Troendle, JF Westfall, PH AF Troendle, James F. Westfall, Peter H. TI Permutational multiple testing adjustments with multivariate multiple group data SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE Adverse events; Closed testing; Exchangeability; Familywise error rate; Power AB We consider the multiple comparison problem where multiple outcomes are each compared among several different collections of groups in a multiple group setting. In this case there are several different types of hypotheses, with each specifying equality of the distributions of a single outcome over a different collection of groups. Each type of hypothesis requires a different permutational approach. We show that under a certain multivariate condition it is possible to use closure over all hypotheses, although intersection hypotheses are tested using Boole's inequality in conjunction with permutation distributions in some cases. Shortcut tests are then found so that the resulting testing procedure is easily performed. The error rate and power of the new method is compared to existing competitors through simulation of correlated data. An example is analyzed, consisting of multiple adverse events in a clinical trial. Published by Elsevier B.V. C1 [Troendle, James F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Bethesda, MD USA. [Westfall, Peter H.] Texas Tech Univ, Lubbock, TX 79409 USA. RP Troendle, JF (reprint author), NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH,DHHS, Bld RKL2,Room 9195, Bethesda, MD 20892 USA. EM jt3t@nih.gov FU NIH, NICHD FX This research was supported in part by the Intramural Research Program of the NIH, NICHD. NR 10 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUN PY 2011 VL 141 IS 6 BP 2021 EP 2029 DI 10.1016/j.jspi.2010.12.012 PG 9 WC Statistics & Probability SC Mathematics GA 734BT UT WOS:000288308900002 PM 21516184 ER PT J AU Malone, JH Oliver, B AF Malone, John H. Oliver, Brian TI Microarrays, deep sequencing and the true measure of the transcriptome SO BMC BIOLOGY LA English DT Review ID GENE-EXPRESSION MEASUREMENTS; RNA-SEQ EXPERIMENTS; DROSOPHILA-MELANOGASTER; HUMAN GENOME; PREDICTION; PLATFORMS; QUALITY; REPRODUCIBILITY; NORMALIZATION; ARRAYS AB Microarrays first made the analysis of the transcriptome possible, and have produced much important information. Today, however, researchers are increasingly turning to direct high-throughput sequencing - RNA-Seq - which has considerable advantages for examining transcriptome fine structure - for example in the detection of allele-specific expression and splice junctions. In this article, we discuss the relative merits of the two techniques, the inherent biases in each, and whether all of the vast body of array work needs to be revisited using the newer technology. We conclude that microarrays remain useful and accurate tools for measuring expression levels, and RNA-Seq complements and extends microarray measurements. C1 [Malone, John H.; Oliver, Brian] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Malone, JH (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM malonej@niddk.nih.gov FU NIH, NIDDK FX We thank members of the Oliver lab for useful comments and discussion. This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 51 TC 222 Z9 227 U1 10 U2 94 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD MAY 31 PY 2011 VL 9 AR 34 DI 10.1186/1741-7007-9-34 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 772EI UT WOS:000291215700001 PM 21627854 ER PT J AU Zivcec, M Safronetz, D Haddock, E Feldmann, H Ebihara, H AF Zivcec, Marko Safronetz, David Haddock, Elaine Feldmann, Heinz Ebihara, Hideki TI Validation of assays to monitor immune responses in the Syrian golden hamster (Mesocricetus auratus) SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Syrian Golden hamster; qRT-PCR; Host immune response; Reference genes ID VESICULAR STOMATITIS-VIRUS; VALLEY FEVER VIRUS; ENCEPHALITIS-VIRUS; EQUINE ENCEPHALITIS; VISCERAL LEISHMANIASIS; RNA EXPRESSION; ANIMAL-MODEL; INFECTION; DISEASE; IMMUNIZATION AB The Syrian golden hamster (Mesocricetus auratus) is a valuable but under-utilized animal model for studies of human viral pathogens such as bunyaviruses, arenaviruses, flaviviruses, henipaviruses, and SARS-coronavinis. A lack of suitable reagents and specific assays for monitoring host responses has limited the use of this animal model to clinical observations, pathology and humoral immune responses. The objective of this study was to establish and validate assays to monitor host immune responses in the hamster including important pro-inflammatory, anti-inflammatory and innate immune responses, as well as markers of apoptosis, cell proliferation, cell junction integrity and coagulation. Commercially available mouse and rat ELISA and luminex panels were screened for potential cross-reactivity, but were found to be of limited value for studying host responses in hamsters. Subsequently, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays for the detection of 51 immune-related and four internal reference genes were developed. To validate the immune-related assays, hamsters were infected with vesicular stomatitis virus (VSV), Indiana species, or treated with lipopolysaccharide (LPS) and host immune responses were monitored in selected organs. Ribosomal protein L18 was identified as the most stable internal reference gene. In conclusion, these new assays will greatly improve the use of the hamster as an important small animal model in infectious disease research. Published by Elsevier B.V. C1 [Zivcec, Marko; Safronetz, David; Haddock, Elaine; Feldmann, Heinz; Ebihara, Hideki] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. [Zivcec, Marko; Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB, Canada. RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM feldmannh@niaid.nih.gov; ebiharah@niaid.nih.gov OI Zivcec, Marko/0000-0003-4337-8487 FU Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health FX The authors would like to thank Allen Grolla, Public Health Agency of Canada, Winnipeg, Canada, for help with the initial primer design and PCR; Katharine N. Bossart, Boston University, Boston, USA, for her fruitful discussion concerning realtime PCR; Gary Hettrick, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Disease (NIAID), NIH, Hamilton, USA, for his help with visual graphics; and Joseph Prescott, DIR, NIAID, NIH, for his helpful suggestions regarding the manuscript. This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health. NR 39 TC 36 Z9 36 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAY 31 PY 2011 VL 368 IS 1-2 BP 24 EP 35 DI 10.1016/j.jim.2011.02.004 PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 771BH UT WOS:000291131700002 PM 21334343 ER PT J AU Briggs, J Paoloni, M Chen, QR Wen, XY Khan, J Khanna, C AF Briggs, Joseph Paoloni, Melissa Chen, Qing-Rong Wen, Xinyu Khan, Javed Khanna, Chand TI A Compendium of Canine Normal Tissue Gene Expression SO PLOS ONE LA English DT Article ID MICROARRAY; PROFILES; MOUSE; MODEL; DOG; TRANSCRIPTOMES; ANNOTATION; BLAST2GO; HEALTHY AB Background: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. Methodology/Principal Findings: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. Conclusions/Significance: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large. C1 [Briggs, Joseph; Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Paoloni, Melissa; Khanna, Chand] NCI, Comparat Oncol Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chen, Qing-Rong; Wen, Xinyu; Khan, Javed] NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Briggs, J (reprint author), NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 39 TC 7 Z9 8 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 31 PY 2011 VL 6 IS 5 AR e17107 DI 10.1371/journal.pone.0017107 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770OP UT WOS:000291097600001 PM 21655323 ER PT J AU Dmitrieva, NI Burg, MB AF Dmitrieva, Natalia I. Burg, Maurice B. TI Increased Insensible Water Loss Contributes to Aging Related Dehydration SO PLOS ONE LA English DT Article ID ASSESSING HYDRATION STATUS; CELLULAR SENESCENCE; HIGH NACL; VASOPRESSIN; AGE; DELETION; BARRIER; KIDNEY AB Dehydration with aging is attributed to decreased urine concentrating ability and thirst. We further investigated by comparing urine concentration and water balance in 3, 18 and 27 month old mice, consuming equal amounts of water. During water restriction, 3 month old mice concentrate their urine sufficiently to maintain water balance (stable weight). 18 month old mice concentrate their urine as well, but still lose weight (negative water balance). 27 month old mice do not concentrate their urine as well and lose even more weight than the 18 month old mice, indicating a larger negative water balance. Negative water balance in older mice is accompanied by increased vasopressin excretion, providing further evidence of dehydration. All 3 groups maintain water balance while consuming only the water in gel food containing 56% water. However, both older groups excrete a smaller volume of urine of higher osmolality, indicating greater extra urinary water loss. Since their feces also contain less water, the excess water lost by the older mice apparently is through other routes, presumably insensible loss through the respiratory tract and skin. The greater insensible water loss occurs at an earlier age (18 months) than decreased urine concentrating ability (27 months). We propose that insensible water loss through skin and respiration increases with age, making a major contribution to aging related dehydration. C1 [Dmitrieva, Natalia I.; Burg, Maurice B.] NHLBI, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD 20892 USA. RP Dmitrieva, NI (reprint author), NHLBI, Lab Kidney & Electrolyte Metab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dmitrien@nhlbi.nih.gov RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 FU National Heart, Lung and Blood Institute FX This work was supported by the Intramural Program of the National Heart, Lung and Blood Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 8 Z9 8 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 31 PY 2011 VL 6 IS 5 AR e20691 DI 10.1371/journal.pone.0020691 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770OP UT WOS:000291097600123 PM 21655199 ER PT J AU Schafer, JM Peters, DE Morley, T Liu, SH Molinolo, AA Leppla, SH Bugge, TH AF Schafer, Jeffrey M. Peters, Diane E. Morley, Thomas Liu, Shihui Molinolo, Alfredo A. Leppla, Stephen H. Bugge, Thomas H. TI Efficient Targeting of Head and Neck Squamous Cell Carcinoma by Systemic Administration of a Dual uPA and MMP-Activated Engineered Anthrax Toxin SO PLOS ONE LA English DT Article ID CAPILLARY MORPHOGENESIS PROTEIN-2; THERAPY PRODUCES REGRESSIONS; INHIBITORS STEFIN-A; ATHYMIC NUDE-MICE; MATRIX-METALLOPROTEINASE; LETHAL FACTOR; PLASMINOGEN-ACTIVATOR; PROTECTIVE ANTIGEN; CATHEPSIN-B; IN-VIVO AB Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Although considerable progress has been made in elucidating the etiology of the disease, the prognosis for individuals diagnosed with HNSCC remains poor, underscoring the need for development of additional treatment modalities. HNSCC is characterized by the upregulation of a large number of proteolytic enzymes, including urokinase plasminogen activator (uPA) and an assortment of matrix metalloproteinases (MMPs) that may be expressed by tumor cells, by tumor-supporting stromal cells or by both. Here we explored the use of an intercomplementing anthrax toxin that requires combined cell surface uPA and MMP activities for cellular intoxication and specifically targets the ERK/MAPK pathway for the treatment of HNSCC. We found that this toxin displayed strong systemic anti-tumor activity towards a variety of xenografted human HNSCC cell lines by inducing apoptotic and necrotic tumor cell death, and by impairing tumor cell proliferation and angiogenesis. Interestingly, the human HNSCC cell lines were insensitive to the intercomplementing toxin when cultured ex vivo, suggesting that either the toxin targets the tumor-supporting stromal cell compartment or that the tumor cell requirement for ERK/MAPK signaling differs in vivo and ex vivo. This intercomplementing toxin warrants further investigation as an anti-HNSCC agent. C1 [Schafer, Jeffrey M.; Peters, Diane E.; Molinolo, Alfredo A.; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Peters, Diane E.] Tufts Univ, Sch Med, Program Pharmacol & Expt Therapeut, Boston, MA 02111 USA. [Morley, Thomas; Liu, Shihui; Leppla, Stephen H.] NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. RP Schafer, JM (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov FU NIAID; NIDCR FX This research was supported by NIAID and NIDCR Intramural Research Programs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 79 TC 13 Z9 13 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 31 PY 2011 VL 6 IS 5 AR e20532 DI 10.1371/journal.pone.0020532 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770OP UT WOS:000291097600089 PM 21655226 ER PT J AU Aronow, WS Fleg, JL Pepine, CJ Artinian, NT Bakris, G Brown, AS Ferdinand, KC Forciea, MA Frishman, WH Jaigobin, C Kostis, JB Mancia, G Oparil, S Ortiz, E Reisin, E Rich, MW Schocken, DD Weber, MA Wesley, DJ Harrington, RA Bates, ER Bhatt, DL Bridges, CR Eisenberg, MJ Ferrari, VA Fisher, JD Gardner, TJ Gentile, F Gilson, MF Hlatky, MA Jacobs, AK Kaul, S Moliterno, DJ Mukherjee, D Rosenson, RS Stein, JH Weitz, HH Wesley, DJ AF Aronow, Wilbert S. Fleg, Jerome L. Pepine, Carl J. Artinian, Nancy T. Bakris, George Brown, Alan S. Ferdinand, Keith C. Forciea, Mary Ann Frishman, William H. Jaigobin, Cheryl Kostis, John B. Mancia, Giuseppi Oparil, Suzanne Ortiz, Eduardo Reisin, Efrain Rich, Michael W. Schocken, Douglas D. Weber, Michael A. Wesley, Deborah J. Harrington, Robert A. Bates, Eric R. Bhatt, Deepak L. Bridges, Charles R. Eisenberg, Mark J. Ferrari, Victor A. Fisher, John D. Gardner, Timothy J. Gentile, Federico Gilson, Michael F. Hlatky, Mark A. Jacobs, Alice K. Kaul, Sanjay Moliterno, David J. Mukherjee, Debabrata Rosenson, Robert S. Stein, James H. Weitz, Howard H. Wesley, Deborah J. TI ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents SO CIRCULATION LA English DT Article DE AHA Scientific Statements; antihypertensive agents; elderly; risk assessment; hypertension comorbidities; hypertension pathophysiology; hypertension therapy ID ISOLATED SYSTOLIC HYPERTENSION; RENAL-ARTERY STENOSIS; AMBULATORY BLOOD-PRESSURE; LEFT-VENTRICULAR HYPERTROPHY; RANDOMIZED CONTROLLED-TRIAL; CONVERTING-ENZYME-INHIBITORS; CONGESTIVE-HEART-FAILURE; VERAPAMIL SR-TRANDOLAPRIL; RENIN-ANGIOTENSIN SYSTEM; NONSTEROIDAL ANTIINFLAMMATORY DRUGS C1 [Fleg, Jerome L.; Ortiz, Eduardo] NHLBI, Bethesda, MD 20892 USA. NR 740 TC 143 Z9 152 U1 4 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 31 PY 2011 VL 123 IS 21 BP 2434 EP 2506 DI 10.1161/CIR.0b013e31821daaf6 PG 73 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 770QQ UT WOS:000291104000018 PM 21518977 ER PT J AU Noseworthy, PA Tikkanen, JT Porthan, K Oikarinen, L Pietila, A Harald, K Peloso, GM Merchant, FM Jula, A Vaananen, H Hwang, SJ O'Donnell, CJ Salomaa, V Newton-Cheh, C Huikuri, HV AF Noseworthy, Peter A. Tikkanen, Jani T. Porthan, Kimmo Oikarinen, Lasse Pietila, Arto Harald, Kennet Peloso, Gina M. Merchant, Faisal M. Jula, Antti Vaananen, Heikki Hwang, Shih-Jen O'Donnell, Christopher J. Salomaa, Veikko Newton-Cheh, Christopher Huikuri, Heikki V. TI The Early Repolarization Pattern in the General Population Clinical Correlates and Heritability SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE early repolarization; ECG; heritability ID SUDDEN CARDIAC DEATH; J-WAVE SYNDROMES; QT INTERVAL; CHANNEL; DISEASE; VARIANT; HEART AB Objectives This study sought to describe the clinical correlates and heritability of the early repolarization pattern (ERP) in 2 large, population-based cohorts. Background There is growing recognition that ERP is associated with adverse outcomes. Methods Participants of the Framingham Heart Study (FHS) (N = 3,995) and the Health 2000 Survey (H2K) (N = 5,489) were included. ERP was defined as a J-point elevation >= 0.1 mV in >= 2 leads in either the inferior (II, III, aVF) or lateral (I, aVL, V(4-6)) territory or both. We tested the association between clinical characteristics and ERP, and estimated sibling recurrence risk. Results ERP was present in 243 of 3,955 (6.1%) of FHS and 180 of 5,489 (3.3%) of H2K subjects. Male sex, younger age, lower systolic blood pressure, higher Sokolow-Lyon index, and lower Cornell voltage were independently associated with the presence of ERP. In the FHS sample, siblings of individuals with ERP had an ERP prevalence of 11.6% (recurrence risk ratio of 1.89). Siblings of individuals with ERP had an increased unadjusted odds of ERP (odds ratio: 2.22, 95% confidence interval: 1.01 to 4.85, p = 0.047). Conclusions ERP has strong association with clinical factors and has evidence for a heritable basis in the general population. Further assessment of the genetic determinants of ERP is warranted. (J Am Coll Cardiol 2011;57:2284-9) (C) 2011 by the American College of Cardiology Foundation C1 [Tikkanen, Jani T.; Huikuri, Heikki V.] Univ Oulu, Dept Internal Med, Inst Clin Med, FIN-90014 Oulu, Finland. [Noseworthy, Peter A.; Merchant, Faisal M.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Noseworthy, Peter A.; Merchant, Faisal M.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Noseworthy, Peter A.; Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Porthan, Kimmo; Oikarinen, Lasse; Vaananen, Heikki] Univ Helsinki, Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland. [Vaananen, Heikki] Aalto Univ, Dept Biomed Engn & Computat Sci, Helsinki, Finland. [Pietila, Arto; Harald, Kennet; Jula, Antti; Salomaa, Veikko] Natl Inst Hlth & Welf, Turku, Finland. [Pietila, Arto; Harald, Kennet; Jula, Antti; Salomaa, Veikko] Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland. [Peloso, Gina M.; Hwang, Shih-Jen; O'Donnell, Christopher J.; Newton-Cheh, Christopher] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Peloso, Gina M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hwang, Shih-Jen; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. RP Huikuri, HV (reprint author), Univ Oulu, Dept Internal Med, Inst Clin Med, POB 5000, FIN-90014 Oulu, Finland. EM veikkosalomaa@thl.fi; cnewtoncheh@chgr.mgh.harvard.edu; heikki.huikuri@oulu.fi RI Library, Woodruff Health/A-6096-2012; Vaananen, Heikki/F-7013-2012 OI Vaananen, Heikki/0000-0001-8649-1047 FU Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology; Burroughs Wellcome Fund; National Institutes of Health/National Heart, Lung, and Blood Institute [HL080025, HL098283]; Doris Duke Charitable Foundation; Academy of Finland [129494]; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Sigrid Juselius Foundation; National Heart, Lung, and Blood Institute of the National Institutes of Health; Boston University School of Medicine [N01-HC-25195] FX From the *Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; the dagger Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; the double dagger Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland; the Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; the parallel to Department of Biomedical Engineering and Computational Science, Aalto University, Helsinki, Finland; National Institute for Health and Welfare, Turku and Helsinki, Finland; #National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts; the **Departmen of Biostatistics, Boston University School of Public Health, Boston, Massachusetts; and the dagger dagger Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, Maryland. This work was supported by the Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology, and a Burroughs Wellcome Fund travel grant (to Dr. Noseworthy); the National Institutes of Health/National Heart, Lung, and Blood Institute (HL080025; HL098283), the Doris Duke Charitable Foundation, and the Burroughs Wellcome Fund (to Dr. Newton- Cheh); the Academy of Finland, grant number 129494 (to Dr. Salomaa); the Finnish Foundation for Cardiovascular Research (to Drs. Porthan, Tikkanen, Oikarinen, and Huikuri); the Finnish Cultural Foundation (to Dr. Tikkanen); and the Sigrid Juselius Foundation (to Dr. Huikuri). The Framingham Heart Study was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine (Contract No. N01-HC-25195). Dr. Newton-Cheh is on a Merck scientific advisory board. All other authors have reported that they have no relationships to disclose. Drs. Noseworthy, Tikkanen, and Porthan contributed equally to this work. Drs. Salomaa, Newton- Cheh, and Huikuri are joint senior authors of this work. NR 15 TC 84 Z9 87 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 31 PY 2011 VL 57 IS 22 BP 2284 EP 2289 DI 10.1016/j.jacc.2011.04.003 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 769IP UT WOS:000291006400011 PM 21600720 ER PT J AU Louis, JM Aniana, A Weber, IT Sayer, JM AF Louis, John M. Aniana, Annie Weber, Irene T. Sayer, Jane M. TI Inhibition of autoprocessing of natural variants and multidrug resistant mutant precursors of HIV-1 protease by clinical inhibitors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calorimetry; drug resistance; precursor processing; inhibitor binding; aspartic protease ID DRUG-RESISTANCE; GROUP-N; DARUNAVIR; BINDING; PHARMACOKINETICS; MECHANISM; RELEVANCE; KINETICS AB Self-cleavage at the N terminus of HIV-1 protease from the Gag-Pol precursor (autoprocessing) is crucial for stabilizing the protease dimer required for onset of mature-like catalytic activity, viral maturation, and propagation. Among nine clinical protease inhibitors (PIs), darunavir and saquinavir were the most effective in inhibiting wild-type HIV-1 group M precursor autoprocessing, with an IC(50) value of 1-2 mu M, 3-5 orders of magnitude higher than their binding affinities to the corresponding mature protease. Accordingly, both group M and N precursor-PI complexes exhibit T(m)s 17-21 degrees C lower than those of the corresponding mature protease-PI complexes suggestive of markedly reduced stabilities of the precursor dimer-PI ensembles. Autoprocessing of group N (natural variant) and three group M precursors bearing 11-20 mutations associated with multidrug resistance was either weakly responsive or fully unresponsive to inhibitors at concentrations up to a practical limit of approximately 150 mu M PI. This observation parallels decreases of up to 8 x 10(3)-fold (e. g., 5 pM to 40 nM) in the binding affinity of darunavir and saquinavir to mature multidrug resistant proteases relative to wild type, suggesting that inhibition of some of these mutant precursors will occur only in the high mu M to mM range in extreme PI-resistance, which is an effect arising from coordinated multiple mutations. An extremely darunavir-resistant mutant precursor is more responsive to inhibition by saquinavir. These findings raise the questions whether clinical failure of PI therapy is related to lack of inhibition of autoprocessing and whether specific inhibitors can be designed with low-nM affinity to target autoprocessing. C1 [Louis, John M.; Aniana, Annie; Sayer, Jane M.] NIDDKD, Chem Phys Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA. RP Louis, JM (reprint author), NIDDKD, Chem Phys Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM johnl@intra.niddk.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health (NIH); Office of the Director, NIH; NIH [GM062920] FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), and the Intramural AIDS-Targeted Program of the Office of the Director, NIH, and Grant GM062920 from the NIH. We are grateful to Ad Bax for reading and conveying critical comments. PIs used in this study were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH, and DMP323 from DuPont Pharmaceuticals. NR 25 TC 31 Z9 31 U1 0 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2011 VL 108 IS 22 BP 9072 EP 9077 DI 10.1073/pnas.1102278108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770RM UT WOS:000291106200037 PM 21576495 ER PT J AU Wei, Z Angerer, RC Angerer, LM AF Wei, Zheng Angerer, Robert C. Angerer, Lynne M. TI Direct development of neurons within foregut endoderm of sea urchin embryos SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell fate specification; embryonic development; neurogenesis; enteric nerve ID ENTERIC NERVOUS-SYSTEM; STEM-CELLS; REGULATORY NETWORK; SPECIFICATION; NEUROGENESIS; EXPRESSION; GENE; SOX2; PLURIPOTENCY; PATTERNS AB Although it is well established that neural cells are ectodermal derivatives in bilaterian animals, here we report the surprising discovery that some of the pharyngeal neurons of sea urchin embryos develop de novo from the endoderm. The appearance of these neurons is independent of mouth formation, in which the stomodeal ectoderm joins the foregut. The neurons do not derive from migration of ectoderm cells to the foregut, as shown by lineage tracing with the photoactivatable protein KikGR. Their specification and development depend on expression of Nkx3-2, which in turn depends on Six3, both of which are expressed in the foregut lineage. SoxB1, which is closely related to the vertebrate Sox factors that support a neural precursor state, is also expressed in the foregut throughout gastrulation, suggesting that this region of the fully formed archenteron retains an unexpected pluripotency. Together, these results lead to the unexpected conclusion that, within a cell lineage already specified to be endoderm by a well-established gene regulatory network [Peter IS, Davidson EH (2010) Dev Biol 340: 188-199], there also operates a Six3/Nkx3-2-dependent pathway required for the de novo specification of some of the neurons in the pharynx. As a result, neuroendoderm precursors form in the foregut aided by retention of a SoxB1-dependent pluripotent state. C1 [Wei, Zheng; Angerer, Robert C.; Angerer, Lynne M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Angerer, LM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. EM langerer@mail.nih.gov FU National Institute of Dental and Craniofacial Research FX We thank Dr. Sarah Knox for assistance with confocal microscopy and Dr. Robert Burke for the SynB antibody. This work was supported by the Intramural Research Program, National Institute of Dental and Craniofacial Research. NR 34 TC 17 Z9 17 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2011 VL 108 IS 22 BP 9143 EP 9147 DI 10.1073/pnas.1018513108 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770RM UT WOS:000291106200049 PM 21576476 ER PT J AU St John, AL Rathore, APS Yap, H Ng, ML Metcalfe, DD Vasudevan, SG Abraham, SN AF St John, Ashley L. Rathore, Abhay P. S. Yap, Han Ng, Mah-Lee Metcalfe, Dean D. Vasudevan, Subhash G. Abraham, Soman N. TI Immune surveillance by mast cells during dengue infection promotes natural killer (NK) and NKT-cell recruitment and viral clearance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS-SPECIFIC CD8(+); DOUBLE-STRANDED-RNA; T-CELLS; RIG-I; DENDRITIC CELLS; TNF-ALPHA; ACTIVATION; RELEASE; TRAFFICKING; HISTAMINE AB A wealth of evidence supports the essential contributions of mast cells (MCs) to immune defense against bacteria and parasites; however, the role of MCs in viral infections has not been defined. We now report that rodent, monkey, and human MCs are able to detect dengue virus (DENV), a lymphotropic, enveloped, single-stranded, positive-sense RNA virus that results in MC activation and degranulation. We observe that the response of MCs to DENV also involves the activation of antiviral intracellular host response pathways, melanoma differentiation-associated gene 5 (MDA5) and retinoic acid inducible gene 1 (RIG-I), and the de novo transcription of cytokines, including TNF-alpha and IFN-alpha, and chemokines, such as CCL5, CXCL12, and CX3CL1. This multifaceted response of MCs to DENV is consequential to the containment of DENV in vivo because, after s.c. infection, MC-deficient mice show increased viral burden within draining lymph nodes, which are known to be targeted organs during DENV spread, compared with MC-sufficient mice. This containment of DENV is linked to the MC-driven recruitment of natural killer and natural killer T cells into the infected skin. These findings support expanding the defined role of immunosurveillance by MCs to include viral pathogens. C1 [St John, Ashley L.; Rathore, Abhay P. S.; Vasudevan, Subhash G.; Abraham, Soman N.] Duke Natl Univ Singapore, Program Emerging Infect Dis, Singapore 169857, Singapore. [Abraham, Soman N.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [St John, Ashley L.; Abraham, Soman N.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Abraham, Soman N.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Yap, Han; Ng, Mah-Lee] Natl Univ Singapore, Dept Microbiol, Singapore 117597, Singapore. [Metcalfe, Dean D.] NIH, Bethesda, MD 20892 USA. RP St John, AL (reprint author), Duke Natl Univ Singapore, Program Emerging Infect Dis, Singapore 169857, Singapore. EM ashley.st.john@duke-nus.edu.sg FU Duke-NUS GMS; US National Institutes of Health [R01DK077159, R01AI50021, R37DK5081]; National Institutes of Health, National Institute of Allergy and Infectious Diseases FX We thank D. Sergio, E. E. Ooi, P. Paradkar, C. Chan, and W. X. G. Ang. This work was supported by start-up funds from Duke-NUS GMS; US National Institutes of Health Grants R01DK077159, R01AI50021, and R37DK5081; and the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 43 TC 70 Z9 71 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2011 VL 108 IS 22 BP 9190 EP 9195 DI 10.1073/pnas.1105079108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770RM UT WOS:000291106200057 PM 21576486 ER PT J AU Boltz, VF Zheng, Y Lockman, S Hong, FY Halvas, EK McIntyre, J Currier, JS Chibowa, MC Kanyama, C Nair, A Owino-Ong'or, W Hughes, M Coffin, JM Mellors, JW AF Boltz, Valerie F. Zheng, Yu Lockman, Shahin Hong, Feiyu Halvas, Elias K. McIntyre, James Currier, Judith S. Chibowa, Margret C. Kanyama, Cecelia Nair, Apsara Owino-Ong'or, Willis Hughes, Michael Coffin, John M. Mellors, John W. TI Role of low-frequency HIV-1 variants in failure of nevirapine-containing antiviral therapy in women previously exposed to single-dose nevirapine SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mother-to-child transmission; nonnucleoside reverse transcriptase inhibitors ID TO-CHILD TRANSMISSION; IMMUNODEFICIENCY-VIRUS TYPE-1; RANDOMIZED-TRIAL; RESISTANT HIV-1; ANTIRETROVIRAL THERAPY; INTRAPARTUM; PREVENTION; ZIDOVUDINE; PERSISTENCE; MUTATIONS AB In the OCTANE/A5208 study of initial antiretroviral therapy (ART) in women exposed to single-dose nevirapine (sdNVP) >= 6 mo earlier, the primary endpoint (virological failure or death) was significantly more frequent in the NVP-containing treatment arm than in the lopinavir/ritonavir-containing treatment arm. Detection of NVP resistance in plasma virus at study entry by standard population genotype was strongly associated with the primary endpoint in the NVP arm, but two-thirds of endpoints occurred in women without NVP resistance. We hypothesized that low-frequency NVP-resistant mutants, missed by population genotype, explained excess failure in the NVP treatment arm. Plasma samples from 232 participants were analyzed by allele-specific PCR at study entry to quantify NVP-resistant mutants down to 0.1% for 103N and 190A and to 0.3% for 181C. Of 201 women without NVP resistance by population genotype, 70 (35%) had NVP-resistant mutants detected by allele-specific PCR. Among these 70 women, primary endpoints occurred in 12 (32%) of 38 women in the NVP arm vs. 3 (9%) of 32 in the lopinavir/ritonavir-containing arm (hazard ratio = 3.84). The occurrence of a primary endpoint in the NVP arm was significantly associated with the presence of K103N or Y181C NVP-resistant mutations at frequencies >1%. The risk for a study endpoint associated with NVP-resistant mutant levels did not decrease with time. Therefore, among women with prior exposure to sdNVP, low-frequency NVP-resistant mutants were associated with increased risk for failure of NVP-containing ART. The implications for choosing initial ART for sdNVP-exposed women are discussed. C1 [Boltz, Valerie F.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Zheng, Yu; Hughes, Michael] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lockman, Shahin] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Hong, Feiyu; Halvas, Elias K.; Mellors, John W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA 15260 USA. [McIntyre, James] Anova Hlth Inst, Johannesburg, South Africa. [Currier, Judith S.] Univ Calif Los Angeles, Care Ctr, Los Angeles, CA 90035 USA. [Chibowa, Margret C.] Univ Teaching Hosp, Dept Med, Lusaka, Zambia. [Kanyama, Cecelia] Univ N Carolina Project Kamuzu Cent Hosp, Lilongwe, Malawi. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Nair, Apsara] Frontier Sci & Technol Res Fdn Inc, Amherst, NY 14226 USA. [Owino-Ong'or, Willis] Moi Univ, Sch Med, Dept Med, Eldoret, Kenya. RP Coffin, JM (reprint author), Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. EM john.coffin@tufts.edu; jwm1@pitt.edu FU Kenya Medical Research Institute/Walter Reed Project Clinical Research Center, Kericho, Kenya [12501]; National Institute of Allergy and Infectious Diseases [U01AI068636]; National Institute of Mental Health and National Institute of Dental and Craniofacial Research; Division of AIDS, National Institute of Allergy and Infectious Diseases [1U01 AI069494-01]; AIDS Clinical Trials Group Central Group [204VC009, 1 U01AI068636-01]; AIDS Clinical Trials Group Statistical and Data Management Center [1 U01-AI068634]; National Cancer Institute [25XS119]; F. M. Kirby Foundation; [U01AI69463-03]; [IAAY1AI8374]; [5 U01AI069518]; [AI69453]; [AACTG 50.5208.07]; [5U01AI069455-03]; [3U01AI32775-13S5]; [5U01AI069456-03]; [AI-069501]; [AI69426] FX We thank the women who participated in the study and the following members of the A5208 AIDS Clinical Trials Group Study Team: Beth Zwickl, Cissy Kityo Mutuluuza, Christine Kaseba, Charles C. Maponga, Heather Watts, Daniel Kuritzkes, Thomas B. Campbell, Lynn Kidd-Freeman, Monica Carten, Jane Hitti, Mary Marovich, Peter N. Mugyenyi, Sandra Rwambuya, Ian M. Sanne, Beverly Putnam, Cheryl Marcus, Carolyn Wester, Robin DiFrancesco, Margaret Bedison, Sandra Lehrman, Francesca Aweeka, Betty Dong, Peter Ndhleni Ziba, Michael S. Saag, William C. Holmes, Scott M. Hammer, and Robert T. Schooley. This study would not have been possible without the 10 study sites in Africa and key personnel who implemented the study-Elizabeth Dangaiso: University of Zimbabwe-Parirenyatwa, Harare, Zimbabwe clinical research site (site 30313), clinical trials unit Grant U01AI069436; Dr. Mohammed S. Rassool and Josephine Tsotsotetsi: University of Witwatersrand HIV Research Group, Johannesburg, South Africa (site 11101), clinical trials unit Grant U01AI69463-03; Kenya Medical Research Institute/Walter Reed Project Clinical Research Center, Kericho, Kenya (site 12501), clinical trials unit Grant IAAY1AI8374; Charity Potani and Regina Mwausegha: University of North Carolina Project, Kamuzu Central Hospital, Lilongwe, Malawi (site 12001), clinical trials unit Grant 5 U01AI069518; Dr. Fatima Laher and Reinet Hen-Boisen: Soweto, South Africa AIDS Clinical Trials Group clinical trials unit (site 12301), clinical trials unit Grant AI69453; Kipruto Kirwa and Agnes Nzioka: Moi University, Eldoret, Kenya clinical research site (site 12601) Contract No. AACTG 50.5208.07, US Military HIV Research Program; Drs. Margaret Chibowa and Jeffrey Stringer: Centre for Infectious Disease Research, Kalingalinga, Lusaka, Zambia (site 12801), clinical trials unit Grants 5U01AI069455-03 and 3U01AI32775-13S5; Kagiso Sebina, Kinuthia Mburu, and Tebogo Kakhu (Gaborone Unit), Banno Moorad (Molepolole Unit): Botswana (site 12701), clinical trials unit Grant 5U01AI069456-03; Cissy Kityo and SandraRwambuya: Joint Clinical Research Center, Kampala, Uganda (site 12401), clinical trials unit Grant AI-069501; and Drs. Farida Amod, Umesh Lalloo, and Sandy Pillay: University of Natal, Durban, South Africa (site 11201), clinical trials unit Grant AI69426. We also thank Frank Maldarelli and Mary Kearney for helpful discussions and comments. This study was supported by Award No. U01AI068636 from the National Institute of Allergy and Infectious Diseases as well as by the National Institute of Mental Health and National Institute of Dental and Craniofacial Research. This study was also supported by the Division of AIDS, National Institute of Allergy and Infectious Diseases (University of Pittsburgh clinical trials unit Grant 1U01 AI069494-01), by Virology Support Laboratory Subcontract 204VC009 of the AIDS Clinical Trials Group Central Group (Grant 1 U01AI068636-01) and AIDS Clinical Trials Group Statistical and Data Management Center (Grant 1 U01-AI068634), and by the National Cancer Institute (Science Applications International Corporation Contract 25XS119). J. M. C was the recipient of a Research Professorship from the American Cancer Society, with support from the F. M. Kirby Foundation. NR 21 TC 29 Z9 29 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2011 VL 108 IS 22 BP 9202 EP 9207 DI 10.1073/pnas.1105688108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770RM UT WOS:000291106200059 PM 21576473 ER PT J AU Takayama, Y Clore, GM AF Takayama, Yuki Clore, G. Marius TI Intra- and intermolecular translocation of the bi-domain transcription factor Oct1 characterized by liquid crystal and paramagnetic NMR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE multidomain protein-DNA recognition; direct transfer; one-dimensional diffusion; nuclear magnetic resonance spectroscopy ID RESIDUAL DIPOLAR COUPLINGS; DNA COGNATE SITES; RELAXATION ENHANCEMENT; POU DOMAIN; BIOLOGICAL MACROMOLECULES; BINDING; PROTEIN; COMPLEXES; VISUALIZATION; SPECTROSCOPY AB The intra- and intermolecular translocation processes whereby the bi-domain transcription factor Oct1 searches for its specific DNA target site have been investigated by residual dipolar coupling (RDC) and paramagnetic relaxation enhancement (PRE) measurements. The RDC data show that the orientation of the POU(S) and POU(HD) domains of Oct1 relative to the long axis of the DNA is the same for specific and nonspecific complexes with DNA. In the context of the specific Oct1-DNA complex, sparsely-populated, spectroscopically "invisible" states reveal their footprints on the PRE profiles observed for the specific complex. Analysis of the PRE data indicates that the POU(HD) domain searches the DNA primarily by rotation-coupled sliding (intramolecular translocation), while the POU(S) domain functions as an antenna to promote inter-segment transfer via intermolecular translocation. The latter involves the formation of a bridged intermediate in which the POU(HD) domain is located on the first DNA molecule and the POU(S) domain on the second. The formation of the bridge intermediate promotes the completion of intermolecular translocation of Oct1 via a first order process involving dissociation and association of the POU(HD) domain from one DNA molecule to another. Thus cross-talk between the POU(S) and POU(HD) domains, each fulfilling different and complementary components of the search process ensures efficient sampling of DNA, thereby facilitating the location of specific Oct1 target sites. C1 [Takayama, Yuki; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM mariusc@mail.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Office of the Director of the NIH FX We thank Dr. M. Doucleff for initial help at the start of this work, and Drs. Garrett, Baber and Ying for technical support. This work was supported by the intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and by the AIDS Targeted Antiviral Program of the Office of the Director of the NIH (G.M.C.). NR 42 TC 22 Z9 22 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 31 PY 2011 VL 108 IS 22 BP E169 EP E176 DI 10.1073/pnas.1100050108 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 770RM UT WOS:000291106200007 PM 21555551 ER PT J AU Baron, GS Hughson, AG Raymond, GJ Offerdahl, DK Barton, KA Raymond, LD Dorward, DW Caughey, B AF Baron, Gerald S. Hughson, Andrew G. Raymond, Gregory J. Offerdahl, Danielle K. Barton, Kelly A. Raymond, Lynne D. Dorward, David W. Caughey, Byron TI Effect of Glycans and the Glycophosphatidylinositol Anchor on Strain Dependent Conformations of Scrapie Prion Protein: Improved Purifications and Infrared Spectra SO BIOCHEMISTRY LA English DT Article ID TRANSMISSIBLE MINK ENCEPHALOPATHY; FT-IR SPECTROSCOPY; SPONGIFORM-ENCEPHALOPATHY; SECONDARY STRUCTURE; MOLECULAR-BASIS; LIPID RAFTS; ELECTRON CRYSTALLOGRAPHY; RIBONUCLEASE-A; GLYCOSYLATION; CONVERSION AB Mammalian prion diseases involve conversion of normal prion protein, PrP(C), to a pathological aggregated state (PrP(res)). The three-dimensional structure of PrPres is not known, but infrared (IR) spectroscopy has indicated high, strain-dependent beta-sheet content. PrP(res) molecules usually contain a glycophosphatidylinositol (GPI) anchor and large Asn-linked glycans, which can also vary with strain. Using IR spectroscopy, we tested the conformational effects of these post-translational modifications by comparing wild-type PrP(res) with GPI- and glycan-deficient PrP(res) produced in GPI-anchorless PrP transgenic mice. These analyses required the development of substantially improved purification protocols. Spectra of both types of PrP(res) revealed conformational differences between the 22L, ME7, and Chandler (RML) murine scrapie strains, most notably in bands attributed to beta-sheets. These PrP(res) spectra were also distinct from those of the hamster 263K scrapie strain. Spectra of wild-type and anchorless 22L PrP(res) were nearly indistinguishable. With ME7 PrP(res), modest differences between the wild-type and anchorless spectra were detected, notably an similar to 2 cm(-1) shift in an apparent beta-sheet band. Collectively, the data provide evidence that the glycans and anchor do not grossly affect the strain-specific secondary structures of PrP(res), at least relative to the differences observed between strains, but can subtly affect turns and certain beta-sheet components. Recently reported H D exchange analyses of anchorless PrPres preparations strongly suggested the presence of strain-dependent, solvent-inaccessible beta-core structures throughout most of the C-terminal half of PrP(res) molecules, with no remaining a-helix. Our IR data provide evidence that similar core structures also comprise wild-type PrP(res). C1 [Baron, Gerald S.; Hughson, Andrew G.; Raymond, Gregory J.; Offerdahl, Danielle K.; Barton, Kelly A.; Raymond, Lynne D.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. [Dorward, David W.] NIAID, Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Baron, GS (reprint author), NIAID, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. EM gbaron@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 60 TC 45 Z9 45 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 31 PY 2011 VL 50 IS 21 BP 4479 EP 4490 DI 10.1021/bi20039307 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 767EF UT WOS:000290837400010 PM 21539311 ER PT J AU Hayashi, R Tanoue, K Durell, SR Chatterjee, DK Jenkins, LMM Appella, DH Appella, E AF Hayashi, Ryo Tanoue, Kan Durell, Stewart R. Chatterjee, Deb K. Jenkins, Lisa M. Miller Appella, Daniel H. Appella, Ettore TI Optimization of a Cyclic Peptide Inhibitor of Ser/Thr Phosphatase PPM1D (Wip1) SO BIOCHEMISTRY LA English DT Article ID CELL-PENETRATING PEPTIDES; PROTEIN-TYROSINE PHOSPHATASES; PTC AMINO-ACIDS; SERINE/THREONINE PHOSPHATASES; STRUCTURAL-ANALYSIS; TUMOR-SUPPRESSOR; BREAST-CANCER; HPLC ANALYSIS; CHK2 KINASE; 3RD METAL AB PPM1D (PP2C delta or Wip1) was identified as a wild-type p53-induced Ser/Thr phosphatase that accumulates after DNA damage and classified into the PP2C family. It dephosphorylates and inactivates several proteins critical for cellular stress responses, including p38 MAPK, p53, and ATM. Furthermore, PPM1D is amplified and/or overexpressed in a number of human cancers. Thus, inhibition of its activity could constitute an important new strategy for therapeutic intervention to halt the progression of several different cancers. Previously, we reported die development of a cyclic thioether peptide with low micromolar inhibitory activity toward PPM1D. Here, we describe important improvements in the inhibitory activity of this class of cyclic peptides and also present a binding model based upon the results. We found that specific interaction of an aromatic ring at the X1 position and negative charge at the X5 and X6 positions significantly increased the inhibitory activity of the cyclic peptide, with the optimized molecule having a K(i) of 110 nM. To the best of our knowledge, this represents the highest inhibitory activity reported for an inhibitor of PPM1D. We further developed an inhibitor selective for PPM1D over PPM1A with a K(i) of 2.9 mu M. Optimization of the cyclic peptide and mutagenesis experiments suggest that a highly basic loop unique to PPM1D is related to substrate specificity. We propose a new model for the catalytic site of PPM1D and inhibition by the cyclic peptides that will be useful both for the subsequent design of PPM1D inhibitors and for identification of new substrates. C1 [Hayashi, Ryo; Tanoue, Kan; Durell, Stewart R.; Jenkins, Lisa M. Miller; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Chatterjee, Deb K.] NCI, Prot Express Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Appella, E (reprint author), 37 Convent Dr,Room 2140, Bethesda, MD 20892 USA. EM appellae@pop.nci.nih.gov FU National Cancer Institute; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN 261 2008 00001E] FX This research was supported by the Intramural Research Program of the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health and federal funds from the National Cancer Institute, National Institutes of Health, under HHSN 261 2008 00001E. NR 55 TC 23 Z9 23 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 31 PY 2011 VL 50 IS 21 BP 4537 EP 4549 DI 10.1021/bi101949t PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 767EF UT WOS:000290837400015 PM 21528848 ER PT J AU Louis, JM Zhang, Y Sayer, JM Wang, YF Harrison, RW Weber, IT AF Louis, John M. Zhang, Ying Sayer, Jane M. Wang, Yuan-Fang Harrison, Robert W. Weber, Irene T. TI The L76V Drug Resistance Mutation Decreases the Dimer Stability and Rate of Autoprocessing of HIV-1 Protease by Reducing Internal Hydrophobic Contacts SO BIOCHEMISTRY LA English DT Article ID RESOLUTION CRYSTAL-STRUCTURES; VIRUS TYPE-1 PROTEASE; HUMAN-IMMUNODEFICIENCY; THERMODYNAMIC BASIS; INHIBITOR; MUTANTS; SITE; SUSCEPTIBILITY; BINDING; PREVALENCE AB The mature HIV-1 protease (PR) bearing the L76V drug resistance mutation (PRL76V) is significantly less stable, with a >7-fold higher dimer dissociation constant (K-d) of 71 +/- 24 nM and twice the sensitivity to urea denaturation (UC50 = 0.85 M) relative to those of PR. Differential scanning calorimetry showed decreases in T-m of 12 degrees C for PRL76V in the absence of inhibitors and 5-7 degrees C in the presence of inhibitors darunavir (DRV), saquinavir (SQV), and lopinavir (LPV), relative to that of PR Isothermal titration calorimetry gave a ligand dissociation constant of 0.8 nM for DRV, similar to 160-fold higher than that of PR, consistent with DRV resistance. Crystal structures of PRL76V in complexes with DRV and SQV were determined at resolutions of 1.45-1.46 angstrom. Compared to the corresponding PR complexes, the mutated Val76 lacks hydrophobic interactions with Asp30, Lys45, Ile47, and Thr74 and exhibits closer interactions with Val32 and Val56. The bound DRV lacks one hydrogen bond with the main chain of Asp30 in PRL76V relative to PR, possibly accounting for the resistance to DRV. SQV shows slightly improved polar interactions with PRL76V compared to those with PR. Although the L76V mutation significantly slows the N-terminal autoprocessing of the precursor TFR-PRL76V to give rise to the mature PRL76V, the coselected M46I mutation counteracts the effect by enhancing this rate but renders the TFR-PRM461/L76V precursor less responsive to inhibition by 6 mu M LPV while preserving inhibition by SQV and DRV. The correlation of lowered stability, higher K-d, and impaired autoprocessing with reduced internal hydrophobic contacts suggests a novel molecular mechanism for drug resistance. C1 [Louis, John M.; Sayer, Jane M.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Zhang, Ying; Weber, Irene T.] Georgia State Univ, Dept Chem, Mol Basis Dis Program, Atlanta, GA 30303 USA. [Wang, Yuan-Fang; Harrison, Robert W.; Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA. [Harrison, Robert W.] Georgia State Univ, Dept Comp Sci, Mol Basis Dis Program, Atlanta, GA 30303 USA. RP Weber, IT (reprint author), Georgia State Univ, Dept Biol, POB 4010, Atlanta, GA 30302 USA. EM johnl@intra.niddk.nih.gov; iweber@gsu.edu FU National Institutes of Health (NIH) [GM062920]; National Institute of Diabetes and Digestive and Kidney Diseases; Office of the Director, NIH; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX This research was supported, in whole or in part, by National Institutes of Health (NIH) Grant GM062920, the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, and Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH.; We thank Annie Aniana for technical assistance and the staff at SER-CAT beamline at the Advanced Photon Source for assistance during X-ray data collection. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38. DRV, LPV, and SQV were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, NIH. NR 42 TC 6 Z9 6 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 31 PY 2011 VL 50 IS 21 BP 4786 EP 4795 DI 10.1021/bi200033z PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 767EF UT WOS:000290837400038 PM 21446746 ER PT J AU Zhang, Z Addo, OY Himes, JH Hediger, ML Albert, PS Gollenberg, AL Lee, PA Louis, GMB AF Zhang, Z. Addo, O. Y. Himes, J. H. Hediger, M. L. Albert, P. S. Gollenberg, A. L. Lee, P. A. Louis, G. M. Buck TI A two-part model for reference curve estimation subject to a limit of detection SO STATISTICS IN MEDICINE LA English DT Article DE centile curve; identifiability; LMS; missing data; quantile regression; z-score ID AGE-RELATED CENTILES; REFERENCE INTERVALS; REFERENCE RANGES; REGRESSION QUANTILES; LIKELIHOOD; PARAMETERS AB Reference curves are commonly used to identify individuals with extreme values of clinically relevant variables or stages of progression which depend naturally on age or maturation. Estimation of reference curves can be complicated by a technical limit of detection (LOD) that censors the measurement from the left, as is the case in our study of reproductive hormone levels in boys around the time of the onset of puberty. We discuss issues with common approaches to the LOD problem in the context of our pubertal hormone study, and propose a two-part model that addresses these issues. One part of the proposed model specifies the probability of a measurement exceeding the LOD as a function of age. The other part of the model specifies the conditional distribution of a measurement given that it exceeds the LOD, again as a function of age. Information from the two parts can be combined to estimate the identifiable portion (i.e. above the LOD) of a reference curve and to calculate the relative standing of a given measurement above the LOD. Unlike some common approaches to LOD problems, the two-part model is free of untestable assumptions involving unobservable quantities, flexible for modeling the observable data, and easy to implement with existing software. The method is illustrated with hormone data from the Third National Health and Nutrition Examination Survey. Published in 2011 by John Wiley & Sons, Ltd. C1 [Zhang, Z.; Hediger, M. L.; Albert, P. S.; Gollenberg, A. L.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Addo, O. Y.; Himes, J. H.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Lee, P. A.] Penn State Coll Med, Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA USA. RP Zhang, Z (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. EM zhiwei.zhang@nih.gov OI Addo, O.Yaw/0000-0003-1269-759X; Buck Louis, Germaine/0000-0002-1774-4490 FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development 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. The authors thank the associate editor and two anonymous reviewers for their insightful comments that have greatly improved the paper. NR 33 TC 1 Z9 1 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD MAY 30 PY 2011 VL 30 IS 12 BP 1455 EP 1465 DI 10.1002/sim.4189 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 762IQ UT WOS:000290470200011 PM 21264894 ER PT J AU Mirabello, L Yu, K Berndt, SI Burdett, L Wang, ZM Chowdhury, S Teshome, K Uzoka, A Hutchinson, A Grotmol, T Douglass, C Hayes, RB Hoover, RN Savage, SA AF Mirabello, Lisa Yu, Kai Berndt, Sonja I. Burdett, Laurie Wang, Zhaoming Chowdhury, Salma Teshome, Kedest Uzoka, Arinze Hutchinson, Amy Grotmol, Tom Douglass, Chester Hayes, Richard B. Hoover, Robert N. Savage, Sharon A. CA Natl Osteosarcoma Etiology Study G TI A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma SO BMC CANCER LA English DT Article ID BONE CANCER; PAGETS-DISEASE; RISK-FACTORS; GROWTH; CHILDREN; POLYMORPHISMS; RECEPTOR; ANEMIA; TUMORS; EPIDEMIOLOGY AB Background: Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways. Methods: We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI). Results: Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene FANCM (ORs 1.9-2.0, P = 0.003-0.004) and 2 SNPs downstream of the growth hormone gene GH1 (OR 1.6, P = 0.002; OR 0.5, P = 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: MDM2, MPG, FGF2, FGFR3, GNRH2, and IGF1. Conclusions: Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings. C1 [Mirabello, Lisa; Yu, Kai; Berndt, Sonja I.; Hoover, Robert N.; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Burdett, Laurie; Wang, Zhaoming; Chowdhury, Salma; Teshome, Kedest; Uzoka, Arinze; Hutchinson, Amy] SAIC Frederick Inc, Core Genotyping Facil, NCI, Gaithersburg, MD USA. [Grotmol, Tom] Canc Registry Norway, NO-0304 Oslo, Norway. [Douglass, Chester] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Hayes, Richard B.] NYU, Dept Environm Med, Div Epidemiol, New York, NY 10016 USA. RP Mirabello, L (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. EM mirabellol@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU National Institutes of Health; National Cancer Institute; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We are grateful to the BDISO and PLCO participants for their valuable contributions. The National Osteosarcoma Etiology Study Group is represented by Michael A. Simon (University of Chicago), Marc C. Gebhardt (Massachusetts General Hospital), Mark T. Scarborough (Shands Medical Center, University of Florida), Steven Gitelis (Rush Presbyterian and St. Lukes Medical Center), Jeffrey J. Eckardt (University of California at Los Angeles School of Medicine), James R. Neff (Nebraska Health System), Michael J. Joyce (Cleveland Clinic Foundation), Martin Malawer (Washington Cancer Institute), Michael McGuire, (Creighton University), and H. Clarke Anderson (University of Kansas Medical Center). This work was supported in part by the intramural research program of the National Institutes of Health and the National Cancer Institute. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, 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 48 TC 28 Z9 32 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAY 29 PY 2011 VL 11 AR 209 DI 10.1186/1471-2407-11-209 PG 8 WC Oncology SC Oncology GA 790RM UT WOS:000292606900001 PM 21619704 ER PT J AU Szabo, G Zakhari, S AF Szabo, Gyongyi Zakhari, Samir TI Mechanisms of alcohol-mediated hepatotoxicity in human-immunodeficiency-virus-infected patients SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Hepatitis C virus; Hepatitis B virus; Liver; Intestine; Inflammation ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-POSITIVE PATIENTS; LIVER-DISEASE; HEPATITIS-C; MICROBIAL TRANSLOCATION; IMMUNE ACTIVATION; MACROPHAGE ACTIVATION; DENDRITIC CELLS; RISK-FACTORS; INJURY AB Clinical observations have demonstrated that excessive chronic alcohol use negatively affects human immunodeficiency virus (HIV) infection and contributes to the liver manifestations of the disease, even in HIV mono-infection. HIV/hepatitis C virus (HCV) co-infection is associated with increased progression of HVC liver disease compared to HCV infection alone, and both of these are negatively affected by alcohol use. Recent data suggest that alcohol use and HIV infection have common targets that contribute to progression of liver disease. Both HIV infection and chronic alcohol use are associated with increased gut permeability and elevated plasma levels of lipopolysaccharide; a central activator of inflammatory responses. Both alcoholic liver disease and HIV infection result in non-specific activation of innate immunity, proinflammatory cytokine cascade upregulation, as well as impaired antigen presenting cell and dendritic cell functions. Finally, alcohol, HIV and antiretroviral therapy affect hepatocyte functions, which contributes to liver damage. The common targets of alcohol and HIV infection in liver disease are discussed in this mini-review. (C) 2011 Baishideng. All rights reserved. C1 [Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, LRB 208, Worcester, MA 01605 USA. [Zakhari, Samir] NIAAA, NIH, Bethesda, MD 20892 USA. RP Szabo, G (reprint author), Univ Massachusetts, Sch Med, Dept Med, LRB 208, 364 Plantat St, Worcester, MA 01605 USA. EM gyongyi.szabo@umassmed.edu FU NIAAA NIH HHS [R37 AA014372] NR 81 TC 12 Z9 14 U1 0 U2 1 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAY 28 PY 2011 VL 17 IS 20 BP 2500 EP 2506 DI 10.3748/wjg.v17.i20.2500 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 773RC UT WOS:000291325400006 PM 21633654 ER PT J AU Schulte, RR Linkous, AG Hallahan, DE Yazlovitskaya, EM AF Schulte, Rachael R. Linkous, Amanda G. Hallahan, Dennis E. Yazlovitskaya, Eugenia M. TI Cytosolic phospholipase A2 as a molecular target for the radiosensitization of ovarian cancer SO CANCER LETTERS LA English DT Article DE Cytosolic phospholipase A2; Ovarian cancer; Radiation therapy; Lysophosphatidylcholine; Lysophosphatidic acid ID SIGNAL-REGULATED KINASE; LYSOPHOSPHATIDIC ACID RECEPTORS; LYSOPHOSPHOLIPASE-D; ELEVATED LEVELS; LPA PRODUCTION; CELL-LINES; CARCINOMA; CISPLATIN; EXPRESSION; A(2) AB In ovarian cancer, the molecular targeted chemotherapeutics could increase the efficiency of low-dose radiotherapy while decreasing injury to adjusted organs. In irradiated A2780 human ovarian carcinoma cells, cytosolic phospholipase A2 (cPLA(2)) inhibitor AACOCF(3) prevented activation of pro-survival Akt signaling and enhanced cell death. The potential molecular mechanisms of this effect could involve signaling through lysophosphatidic acid receptors. In the heterotopic A2780 tumor model using nude mice, cPLA(2) inhibition significantly delayed tumor growth compared to treatment with radiation or vehicle alone. These results identify cPLA(2) as a molecular target to enhance the therapeutic ratio of radiation in ovarian cancer. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Schulte, Rachael R.] Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, Nashville, TN 37232 USA. [Linkous, Amanda G.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Hallahan, Dennis E.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA. [Hallahan, Dennis E.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. [Hallahan, Dennis E.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Yazlovitskaya, Eugenia M.] Vanderbilt Univ, Med Ctr, Dept Med Nephrol, Nashville, TN 37232 USA. [Yazlovitskaya, Eugenia M.] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. RP Yazlovitskaya, EM (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Div Nephrol, Nashville, TN 37232 USA. EM eugenia.yazlovitskaya@vanderbilt.edu FU National Institutes of Health (Washington, DC) [R01-140220, R01-CA112385, R01-CA88076]; Elsa U. Pardee foundation (Midland, MI) FX We would like to thank Ms. Allie Fu for help with animal studies. This work was supported by the Elizabeth H. and James S. McDonnell Distinguished Professorship and grants from the National Institutes of Health grants to D.E.H. (Washington, DC; R01-140220; R01-CA112385 and R01-CA88076) and to E.M.Y. from Elsa U. Pardee foundation (Midland, MI). NR 50 TC 2 Z9 2 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD MAY 28 PY 2011 VL 304 IS 2 BP 137 EP 143 DI 10.1016/j.canlet.2011.02.015 PG 7 WC Oncology SC Oncology GA 751EX UT WOS:000289601400008 PM 21397389 ER PT J AU Chae, JJ Cho, YH Lee, GS Cheng, J Liu, PP Feigenbaum, L Katz, SI Kastner, DL AF Chae, Jae Jin Cho, Young-Hun Lee, Geun-Shik Cheng, Jun Liu, P. Paul Feigenbaum, Lionel Katz, Stephen I. Kastner, Daniel L. TI Gain-of-Function Pyrin Mutations Induce NLRP3 Protein-Independent Interleukin-1 beta Activation and Severe Autoinflammation in Mice SO IMMUNITY LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; NF-KAPPA-B; MEFV; CASPASE-1; ANAKINRA; DISEASE; GENE; TRANSPLANTATION; INFLAMMASOME; EXPRESSION AB Missense mutations in the C-terminal B30.2 domain of pyrin cause familial Mediterranean fever (FMF), the most common Mendelian autoinflammatory disease. However, it remains controversial as to whether FMF is due to the loss of an inhibitor of inflammation or to the activity of a proinflammatory molecule. We generated both pyrin-deficient mice and "knockin" mice harboring mutant human B30.2 domains. Homozygous knockin, but not pyrin-deficient, mice exhibited spontaneous bone marrow-dependent inflammation similar to but more severe than human FMF. Caspase-1 was constitutively activated in knockin macrophages and active IL-1 beta was secreted when stimulated with lipopolysaccharide alone, which is also observed in FMF patients. The inflammatory phenotype of knockin mice was completely ablated by crossing with IL-1 receptor-deficient or adaptor molecule ASC-deficient mice, but not NLRP3-deficient mice. Thus, our data provide evidence for an ASC-dependent NLRP3-independent inflammasome in which gain-of-function pyrin mutations cause autoinflammatory disease. C1 [Chae, Jae Jin; Lee, Geun-Shik; Kastner, Daniel L.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Cho, Young-Hun; Katz, Stephen I.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cheng, Jun; Liu, P. Paul] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] NCI, Lab Anim Sci Program, Sci Applicat Int Corp Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Chae, JJ (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM chaej@mail.nih.gov; kastnerd@mail.nih.gov RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NIAMS, NCI; NHGRI, NIH FX This work was supported by the Intramural Research Program of NIAMS, NCI, and NHGRI, NIH. NR 30 TC 154 Z9 156 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY 27 PY 2011 VL 34 IS 5 BP 755 EP 768 DI 10.1016/j.immuni.2011.02.020 PG 14 WC Immunology SC Immunology GA 775JV UT WOS:000291456500014 PM 21600797 ER PT J AU Egen, JG Rothfuchs, AG Feng, CG Horwitz, MA Sher, A Germain, RN AF Egen, Jackson G. Rothfuchs, Antonio Gigliotti Feng, Carl G. Horwitz, Marcus A. Sher, Alan Germain, Ronald N. TI Intravital Imaging Reveals Limited Antigen Presentation and T Cell Effector Function in Mycobacterial Granulomas SO IMMUNITY LA English DT Article ID DENDRITIC CELLS; LYMPH-NODES; IMMUNE-RESPONSE; IN-VIVO; TUBERCULOSIS; MICE; CD4; ACTIVATION; INFECTION; DYNAMICS AB Cell-mediated adaptive immunity is critical for host defense, but little is known about T cell behavior during delivery of effector function. Here we investigate relationships among antigen presentation, T cell motility, and local production of effector cytokines by CD4(+) T cells within hepatic granulomas triggered by Bacille Calmette-Guerin or Mycobacterium tuberculosis. At steady-state, only small fractions of mycobacteria-specific T cells showed antigen-induced migration arrest within granulomas, resulting in low-level, polarized secretion of cytokines. However, exogenous antigen elicited rapid arrest and robust cytokine production by the vast majority of effector T cells. These findings suggest that limited antigen presentation and/or recognition within granulomas evoke a muted T cell response drawing on only a fraction of the host's potential effector capacity. Our results provide new insights into the regulation of host-protective functions, especially how antigen availability influences T cell dynamics and, in turn, effector T cell function during chronic infection. C1 [Egen, Jackson G.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Rothfuchs, Antonio Gigliotti; Feng, Carl G.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Germain, Ronald N.] NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, Bethesda, MD 20892 USA. [Horwitz, Marcus A.] Univ Calif Los Angeles, Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA 90095 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rgermain@nih.gov RI Rothfuchs, Antonio/F-5981-2013; OI Rothfuchs, Antonio/0000-0001-6001-7240; Egen, Jackson/0000-0003-2053-0837 FU NIAID, NIH FX We would like to thank W. Kastenmuller, M. Gerner, N. Vrisekoop, and M. Clatworthy for helpful discussions and/or critical reading of the manuscript, O. Schwartz and L. Koo (Research Technology Branch/NIAID) for technical assistance with intravital microscopy under BSL3 conditions, and A. Rinker, I. Ifrim, and S. White for technical support. We are extremely grateful to J. Ernst for providing valuable reagents used in this study, as well as for insightful discussions, sharing of unpublished data, and helpful comments on the manuscript. This work was supported by the Intramural Research Program of the NIAID, NIH. NR 41 TC 108 Z9 108 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY 27 PY 2011 VL 34 IS 5 BP 807 EP 819 DI 10.1016/j.immuni.2011.03.022 PG 13 WC Immunology SC Immunology GA 775JV UT WOS:000291456500018 PM 21596592 ER PT J AU Nguitragool, W Bokhari, AAB Pillai, AD Rayavara, K Sharma, P Turpin, B Aravind, L Desai, SA AF Nguitragool, Wang Bokhari, Abdullah A. B. Pillai, Ajay D. Rayavara, Kempaiah Sharma, Paresh Turpin, Brad Aravind, L. Desai, Sanjay A. TI Malaria Parasite clag3 Genes Determine Channel-Mediated Nutrient Uptake by Infected Red Blood Cells SO CELL LA English DT Article ID SURFACE ANION CHANNEL; PLASMODIUM-FALCIPARUM MALARIA; HOST ERYTHROCYTE; MULTIGENE FAMILY; RHOPTRY PROTEIN; EXPRESSION; MEMBRANE; INVASION; CYTOADHERENCE; PERMEABILITY AB Development of malaria parasites within vertebrate erythrocytes requires nutrient uptake at the host cell membrane. The plasmodial surface anion channel (PSAC) mediates this transport and is an antimalarial target, but its molecular basis is unknown. We report a parasite gene family responsible for PSAC activity. We used high-throughput screening for nutrient uptake inhibitors to identify a compound highly specific for channels from the Dd2 line of the human pathogen P. falciparum. Inheritance of this compound's affinity in a Dd2xHB3 genetic cross maps to a single parasite locus on chromosome 3. DNA transfection and in vitro selections indicate that PSAC-inhibitor interactions are encoded by two clag3 genes previously assumed to function in cytoadherence. These genes are conserved in plasmodia, exhibit expression switching, and encode an integral protein on the host membrane, as predicted by functional studies. This protein increases host cell permeability to diverse solutes. C1 [Nguitragool, Wang; Bokhari, Abdullah A. B.; Pillai, Ajay D.; Rayavara, Kempaiah; Sharma, Paresh; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Turpin, Brad] Natl Instruments Inc, Austin, TX 78730 USA. [Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov FU Medicines for Malaria Venture (MMV); National Institutes of Health, National Institute of Allergy and Infectious Diseases, and the National Library of Medicine FX We thank John Adams, Alan Cowman, and Thomas Wellems for providing reagents; Mehreen Baakza, Kent Barbian, Yasmin El-Sayed, Juraj Kabat, Glenn Nardone, Son Nguyen, Norton Peet, Steve Porcella, Jose Riberio, Lattha Souvannaseng, Kurt Wollenberg, and Albert Youn for technical help; and the NIAID Scientific Director's office for providing required temporary laboratory space. We thank Edwin McCleskey and Thomas Wellems for critical reading of the manuscript. S. D. is a named inventor on a provisional patent application describing the PSAC antimalarial target identified in this article. B. T. is an employee and shareholder of National Instruments, Inc., which markets data analysis software used in this study. This research was supported by the Medicines for Malaria Venture (MMV) and the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and the National Library of Medicine. NR 55 TC 92 Z9 93 U1 2 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 27 PY 2011 VL 145 IS 5 BP 665 EP 677 DI 10.1016/j.cell.2011.05.002 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 769MR UT WOS:000291018600008 PM 21620134 ER PT J AU Bangash, MA Park, JM Melnikova, T Wang, DH Jeon, SK Lee, D Syeda, S Kim, J Kouser, M Schwartz, J Cui, YY Zhao, X Speed, HE Kee, SE Tu, JC Hu, JH Petralia, RS Linden, DJ Powell, CM Savonenko, A Xiao, B Worley, PF AF Bangash, M. Ali Park, Joo Min Melnikova, Tatiana Wang, Dehua Jeon, Soo Kyeong Lee, Deidre Syeda, Sbaa Kim, Juno Kouser, Mehreen Schwartz, Joshua Cui, Yiyuan Zhao, Xia Speed, Haley E. Kee, Sara E. Tu, Jian Cheng Hu, Jia-Hua Petralia, Ronald S. Linden, David J. Powell, Craig M. Savonenko, Alena Xiao, Bo Worley, Paul F. TI Enhanced Polyubiquitination of Shank3 and NMDA Receptor in a Mouse Model of Autism (Retracted article. See vol. 152, pg. 367, 2013) SO CELL LA English DT Article; Retracted Publication ID SCAFFOLDING PROTEIN SHANK3; X MENTAL-RETARDATION; SPECTRUM DISORDERS; SCHIZOPHRENIA; MUTATIONS; HOMER; GENE; MICE; RECOGNITION; EXPRESSION AB We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/Delta C) mice], Shank3 Delta C protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This "gain-of-function" phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/Delta C) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/Delta C) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder. C1 [Bangash, M. Ali; Park, Joo Min; Jeon, Soo Kyeong; Kim, Juno; Schwartz, Joshua; Tu, Jian Cheng; Hu, Jia-Hua; Linden, David J.; Xiao, Bo; Worley, Paul F.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. [Melnikova, Tatiana; Lee, Deidre; Syeda, Sbaa; Savonenko, Alena] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Melnikova, Tatiana; Lee, Deidre; Syeda, Sbaa; Savonenko, Alena] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. [Kouser, Mehreen; Speed, Haley E.; Kee, Sara E.; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Kouser, Mehreen; Speed, Haley E.; Kee, Sara E.; Powell, Craig M.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Wang, Dehua; Cui, Yiyuan; Zhao, Xia; Xiao, Bo] Sichuan Univ, State Key Lab Biotherapy, W China Hosp, Chengdu 610065, Peoples R China. [Petralia, Ronald S.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Worley, PF (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. EM pworley@jhmi.edu FU National Institute of Neurological Disorders and Stroke [5R01NS070301-02]; National Institute of Mental Health [5P50MH084020-03]; National 973 Basic Research Program of China [20009CB941400, R21HD065290, R01MH081164]; Autism Speaks; Autism Science Foundation; Hartwell Foundation; NIDCD FX M.A.B., A. S., B. X., and P. F. W. designed the study. M. A. B. executed and analyzed all the biochemistry, immunocytochemistry, and DiI experiments. B. X., M. A. B., D. W., Y.C., and X.Z. created the Shank3 mouse. J.M.P., S.K.J., and J.K. did the electrophysiology experiments and analysis supervised by P. F. W. and D.J.L. R. S. P. did the electron microscopy. T. M., D. L., S. S., M. K., H. E. S., and S. E. K. did the behavior experiments and analysis supervised by A. S. and C. M. P. J.C.T. and J.-H.H. provided reagents. M. A. B., A. S., and P. F. W. wrote the manuscript and P. F. W. supervised the overall project. We thank Maria Papapavlou for administrative assistance; Holly Wellington, Ann Lawler, Johnisha Witherspoon, and Charles Hawkins for assistance in generating the Shank3(+/Delta C) mice; Uejin Kim, Jasmin Harpe, Matt Jo, Pennson Wang, Dakim Gaines, Olivia Tong, Julia Wynne, and Eugenia Cho for help with behavioral testing and data handling; Ya-Xian Wang for help with the electron microscopy preparation. This work was supported by National Institute of Neurological Disorders and Stroke grant 5R01NS070301-02 (P. F. W.), National Institute of Mental Health Core grant 5P50MH084020-03 (P. F. W.), National 973 Basic Research Program of China 20009CB941400 (B. X.), R21HD065290 (C. M. P.), R01MH081164 (C. M. P.), Autism Speaks (C. M. P. and M. K.), The Autism Science Foundation (C. M. P. and H. S.), The Hartwell Foundation (C. M. P.), NIDCD Intramural Program (R. S. P.), and Weatherstone predoctoral fellowship from Autism Speaks (M.A.B.). NR 25 TC 77 Z9 81 U1 0 U2 30 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 27 PY 2011 VL 145 IS 5 BP 758 EP 772 DI 10.1016/j.cell.2011.03.052 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 769MR UT WOS:000291018600015 PM 21565394 ER PT J AU Aguda, BD Marsh, CB Thacker, M Crouser, ED AF Aguda, Baltazar D. Marsh, Clay B. Thacker, Michael Crouser, Elliott D. TI An In Silico Modeling Approach to Understanding the Dynamics of Sarcoidosis SO PLOS ONE LA English DT Article ID REGULATORY T-CELLS; DISEASE; DIFFERENTIATION; INFLIXIMAB; BEHAVIOR; THERAPY; CANCER; TRIAL; MICE; CD8 AB Background: Sarcoidosis is a polygenic disease with diverse phenotypic presentations characterized by an abnormal antigen-mediated Th1 type immune response. At present, progress towards understanding sarcoidosis disease mechanisms and the development of novel treatments is limited by constraints attendant to conducting human research in a rare disease in the absence of relevant animal models. We sought to develop a computational model to enhance our understanding of the pathological mechanisms of and predict potential treatments of sarcoidosis. Methodology/Results: Based upon the literature, we developed a computational model of known interactions between essential immune cells (antigen-presenting macrophages, effector and regulatory T cells) and cytokine mediators (IL-2, TNF alpha, IFN gamma) of granulomatous inflammation during sarcoidosis. The dynamics of these interactions are described by a set of ordinary differential equations. The model predicts bistable switching behavior which is consistent with normal (self-limited) and "sarcoidosis-like'' (sustained) activation of the inflammatory components of the system following a single antigen challenge. By perturbing the influence of model components using inhibitors of the cytokine mediators, distinct clinically relevant disease phenotypes were represented. Finally, the model was shown to be useful for pre-clinical testing of therapies based upon molecular targets and dose-effect relationships. Conclusions/Significance: Our work illustrates a dynamic computer simulation of granulomatous inflammation scenarios that is useful for the investigation of disease mechanisms and for pre-clinical therapeutic testing. In lieu of relevant in vitro or animal surrogates, our model may provide for the screening of potential therapies for specific sarcoidosis disease phenotypes in advance of expensive clinical trials. C1 [Aguda, Baltazar D.] NCI, Ctr Canc Res, Neurooncol Branch, Bethesda, MD 20892 USA. [Marsh, Clay B.; Crouser, Elliott D.] Ohio State Univ, Med Ctr, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA. [Thacker, Michael] Ohio State Univ, Med Ctr, Dept Elect & Comp Engn, Columbus, OH 43210 USA. RP Aguda, BD (reprint author), NCI, Ctr Canc Res, Neurooncol Branch, Bethesda, MD 20892 USA. EM Elliott.Crouser@osumc.edu RI Crouser, Elliott/E-2933-2011 FU American Thoracic Society/Foundation for Sarcoidosis Research (EDC) FX Funding was provided by the American Thoracic Society/Foundation for Sarcoidosis Research (EDC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 3 Z9 3 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 27 PY 2011 VL 6 IS 5 AR e19544 DI 10.1371/journal.pone.0019544 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 769XV UT WOS:000291052500007 PM 21637752 ER PT J AU Chen, ZG Schiffman, M Herrero, R DeSalle, R Anastos, K Segondy, M Sahasrabuddhe, VV Gravitt, PE Hsing, AW Burk, RD AF Chen, Zigui Schiffman, Mark Herrero, Rolando DeSalle, Rob Anastos, Kathryn Segondy, Michel Sahasrabuddhe, Vikrant V. Gravitt, Patti E. Hsing, Ann W. Burk, Robert D. TI Evolution and Taxonomic Classification of Human Papillomavirus 16 (HPV16)-Related Variant Genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67 SO PLOS ONE LA English DT Article ID SQUAMOUS INTRAEPITHELIAL LESIONS; MULTIPLE SEQUENCE ALIGNMENT; GRADE CERVICAL LESIONS; HIGH-RISK; EPIDERMODYSPLASIA-VERRUCIFORMIS; GENETIC-HETEROGENEITY; PHYLOGENETIC ANALYSIS; GENITAL-TRACT; WOMEN; INFECTION AB Background: Human papillomavirus 16 (HPV16) species group (alpha-9) of the Alphapapillomavirus genus contains HPV16, HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. These HPVs account for 75% of invasive cervical cancers worldwide. Viral variants of these HPVs differ in evolutionary history and pathogenicity. Moreover, a comprehensive nomenclature system for HPV variants is lacking, limiting comparisons between studies. Methods: DNA from cervical samples previously characterized for HPV type were obtained from multiple geographic regions to screen for novel variants. The complete 8 kb genomes of 120 variants representing the major and minor lineages of the HPV16-related alpha-9 HPV types were sequenced to capture maximum viral heterogeneity. Viral evolution was characterized by constructing phylogenic trees based on complete genomes using multiple algorithms. Maximal and viral region specific divergence was calculated by global and pairwise alignments. Variant lineages were classified and named using an alphanumeric system; the prototype genome was assigned to the A lineage for all types. Results: The range of genome-genome sequence heterogeneity varied from 0.6% for HPV35 to 2.2% for HPV52 and included 1.4% for HPV31, 1.1% for HPV33, 1.7% for HPV58 and 1.1% for HPV67. Nucleotide differences of approximately 1.0% - 10.0% and 0.5%-1.0% of the complete genomes were used to define variant lineages and sublineages, respectively. Each gene/region differs in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1)/noncoding region 2 (NCR2) > upstream regulatory region (URR) > E6/E7 > E2/L2 > E1/L1. Conclusions: These data define maximum viral genomic heterogeneity of HPV16-related alpha-9 HPV variants. The proposed nomenclature system facilitates the comparison of variants across epidemiological studies. Sequence diversity and phylogenies of this clinically important group of HPVs provides the basis for further studies of discrete viral evolution, epidemiology, pathogenesis and preventative/therapeutic interventions. C1 [Chen, Zigui; Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY USA. [Schiffman, Mark; Sahasrabuddhe, Vikrant V.; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Herrero, Rolando] Fdn INCIENSA, Proyect Epidemiol Guanacaste, San Jose, Costa Rica. [DeSalle, Rob] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Med, New York, NY USA. [Segondy, Michel] Montpellier Univ Hosp, Dept Biol & Pathol, Montpellier, France. [Sahasrabuddhe, Vikrant V.] Vanderbilt Univ, Inst Global Hlth, Nashville, TN USA. [Gravitt, Patti E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, New York, NY USA. [Chen, Zigui; Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, New York, NY USA. RP Chen, ZG (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY USA. EM robert.burk@einstein.yu.edu RI Chen, Zigui/E-8490-2017 FU National Cancer Institute [CA78527, AI-51519]; Einstein Cancer Research Center, NCI [P30CA013330]; American Museum of Natural History FX This work was supported in part by the National Cancer Institute (CA78527), the Einstein-Montefiore Center for AIDS funded by the National Institutes of Health (AI-51519), and the Einstein Cancer Research Center (P30CA013330) from the NCI. RD thanks the Louis and Dorothy Cullman Program in Molecular Systematics at the American Museum of Natural History for support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 66 Z9 69 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 27 PY 2011 VL 6 IS 5 AR e20183 DI 10.1371/journal.pone.0020183 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 769XV UT WOS:000291052500039 PM 21673791 ER PT J AU Lee, BC Lobanov, AV Marino, SM Kaya, A Seravalli, J Hatfield, DL Gladyshev, VN AF Lee, Byung Cheon Lobanov, Alexey V. Marino, Stefano M. Kaya, Alaattin Seravalli, Javier Hatfield, Dolph L. Gladyshev, Vadim N. TI A 4-Selenocysteine, 2-Selenocysteine Insertion Sequence (SECIS) Element Methionine Sulfoxide Reductase from Metridium senile Reveals a Non-catalytic Function of Selenocysteines SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FORMATE DEHYDROGENASE; ESCHERICHIA-COLI; SELENOPROTEIN SYNTHESIS; GLYCINE REDUCTASE; IDENTIFICATION; SELENIUM; GENE; EXPRESSION; PROTEINS; FAMILY AB Selenocysteine (Sec) residues occur in thiol oxidoreductase families, and functionally characterized selenoenzymes typically have a single Sec residue used directly for redox catalysis. However, how new Sec residues evolve and whether non-catalytic Sec residues exist in proteins is not known. Here, we computationally identified several genes with multiple Sec insertion sequence (SECIS) elements, one of which was a methionine-R-sulfoxide reductase (MsrB) homolog from Metridium senile that has four in-frame UGA codons and two nearly identical SECIS elements. One of the UGA codons corresponded to the conserved catalytic Sec or Cys in MsrBs, whereas the three other UGA codons evolved recently and had no homologs with Sec or Cys in these positions. Metabolic (75)Se labeling showed that all four in-frame UGA codons supported Sec insertion and that both SECIS elements were functional and collaborated in Sec insertion at each UGA codon. Interestingly, recombinant M. senile MsrB bound iron, and further analyses suggested the possibility of binding an iron-sulfur cluster by the protein. These data show that Sec residues may appear transiently in genes containing SECIS elements and be adapted for non-catalytic functions. C1 [Lee, Byung Cheon; Lobanov, Alexey V.; Marino, Stefano M.; Kaya, Alaattin; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA. [Kaya, Alaattin; Seravalli, Javier] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Kaya, Alaattin; Seravalli, Javier] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA. [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, New Res Bldg,Rm 435,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vgladyshev@rics.bwh.harvard.edu RI Gladyshev, Vadim/A-9894-2013; OI Kaya, Alaattin/0000-0002-6132-5197 FU National Institutes of Health [AG021518, GM061603]; Center for Cancer Research, NCI, National Institutes of Health FX This work was supported, in whole or in part, by National Institutes of Health Grants AG021518 and GM061603 (to V. N. G.) and by the Intramural Research Program at the Center for Cancer Research, NCI, National Institutes of Health (to D. L. H.). NR 40 TC 12 Z9 12 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 27 PY 2011 VL 286 IS 21 BP 18747 EP 18755 DI 10.1074/jbc.M111.229807 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766ME UT WOS:000290785700047 PM 21393246 ER PT J AU Park, H Adsit, FG Boyington, JC AF Park, HaJeung Adsit, Floyd G. Boyington, Jeffrey C. TI The 1.5 angstrom crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding (vol 285, pg 40762, 2010) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Correction C1 [Adsit, Floyd G.] NIEHS, Qual Assurance Lab, Vet Med Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Boyington, JC (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 27 PY 2011 VL 286 IS 21 BP 19178 EP 19178 DI 10.1074/jbc.A110.169276 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 766ME UT WOS:000290785700087 ER PT J AU Mackem, S Lewandoski, M AF Mackem, Susan Lewandoski, Mark TI Limb Cells Don't Tell Time SO SCIENCE LA English DT Editorial Material ID VERTEBRATE LIMB; REGENERATION; AXIS; WNT C1 [Mackem, Susan; Lewandoski, Mark] NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Mackem, S (reprint author), NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM mackems@mail.nih.gov; lewandom@mail.nih.gov NR 11 TC 1 Z9 1 U1 1 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 27 PY 2011 VL 332 IS 6033 BP 1038 EP 1039 DI 10.1126/science.1207554 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 769FN UT WOS:000290996700028 PM 21617061 ER PT J AU Sinha, R Daniel, CR Devasenapathy, N Shetty, H Yurgalevitch, S Ferrucci, LM George, PS Morrissey, KG Ramakrishnan, L Graubard, BI Kapur, K Reddy, KS McAdams, MJ Rastogi, T Chatterjee, N Gupta, PC Wacholder, S Prabhakaran, D Mathew, AA AF Sinha, Rashmi Daniel, Carrie R. Devasenapathy, Niveditha Shetty, Hemali Yurgalevitch, Susan Ferrucci, Leah M. George, Preethi S. Morrissey, Kerry Grace Ramakrishnan, Lakshmy Graubard, Barry I. Kapur, Kavita Reddy, K. Srinath McAdams, Mary J. Rastogi, Tanuja Chatterjee, Nilanjan Gupta, Prakash C. Wacholder, Sholom Prabhakaran, Dorairaj Mathew, Aleyamma A. TI Multi-center feasibility study evaluating recruitment, variability in risk factors and biomarkers for a diet and cancer cohort in India SO BMC PUBLIC HEALTH LA English DT Article ID SPICE-DERIVED PHYTOCHEMICALS; ISCHEMIC-HEART-DISEASE; INSULIN-RESISTANCE; STOMACH-CANCER; ASIAN INDIANS; UNITED-STATES; PREVENTION; NUTRITION; HEALTH; POPULATION AB Background: India's population exhibits diverse dietary habits and chronic disease patterns. Nutritional epidemiologic studies in India are primarily of cross-sectional or case-control design and subject to biases, including differential recall of past diet. The aim of this feasibility study was to evaluate whether a diet-focused cohort study of cancer could be established in India, providing insight into potentially unique diet and lifestyle exposures. Methods: Field staff contacted 7,064 households within three regions of India (New Delhi, Mumbai, and Trivandrum) and found 4,671 eligible adults aged 35-69 years. Participants completed interviewer-administered questionnaires (demographic, diet history, physical activity, medical/reproductive history, tobacco/alcohol use, and occupational history), and staff collected biological samples (blood, urine, and toenail clippings), anthropometric measurements (weight, standing and sitting height; waist, hip, and thigh circumference; triceps, sub-scapula and supra-patella skin fold), and blood pressure measurements. Results: Eighty-eight percent of eligible subjects completed all questionnaires and 67% provided biological samples. Unique protein sources by region were fish in Trivandrum, dairy in New Delhi, and pulses (legumes) in Mumbai. Consumption of meat, alcohol, fast food, and soft drinks was scarce in all three regions. A large percentage of the participants were centrally obese and had elevated blood glucose levels. New Delhi participants were also the least physically active and had elevated lipids levels, suggesting a high prevalence of metabolic syndrome. Conclusions: A high percentage of participants complied with study procedures including biological sample collection. Epidemiologic expertise and sufficient infrastructure exists at these three sites in India to successfully carry out a modest sized population-based study; however, we identified some potential problems in conducting a cohort study, such as limited number of facilities to handle biological samples. C1 [Sinha, Rashmi; Daniel, Carrie R.; Ferrucci, Leah M.; Graubard, Barry I.; Chatterjee, Nilanjan; Wacholder, Sholom] NCI, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Devasenapathy, Niveditha; Reddy, K. Srinath; Prabhakaran, Dorairaj] Ctr Chron Dis Control, New Delhi, India. [Shetty, Hemali; Gupta, Prakash C.] Sekhsaria Inst Publ Hlth, Navi Mumbai, India. [Yurgalevitch, Susan; Morrissey, Kerry Grace] Westat Corp, Rockville, MD USA. [George, Preethi S.; Mathew, Aleyamma A.] Reg Canc Ctr, Trivandrum 695011, Kerala, India. [Ramakrishnan, Lakshmy] All India Inst Med Sci, New Delhi, India. [Kapur, Kavita] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [McAdams, Mary J.] Informat Management Serv Inc, Silver Spring, MD USA. [Rastogi, Tanuja] UN World Food Program, Rome, Italy. RP Sinha, R (reprint author), NCI, NIH, Dept Hlth & Human Serv, Rockville, MD USA. EM sinhar@mail.nih.gov RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Prabhakaran, Dorairaj/0000-0002-3172-834X FU NIH, National Cancer Institute FX We are indebted to the participants in the IHS for their patience and outstanding cooperation even during the busy times of their day. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. The authors would like to thank all the field, laboratory, data-entry, and office staff at the three centers for their dedicated work to make this study possible. Our special thanks go to Sriram Hariharan of Atribs for developing the NINA-DISH software and Puneet Chadda for taking charge of the New Delhi dietary component, and Mangesh Pednekar and Binukumar for their continued support. The network support provided by the team at the Capital Technology Information Services, Inc., Raj Shah, Anil Srivastava, Chirag Shah, Sachin Parikh, and Keyur Shah, was invaluable for the success of the IHS. We would also like to expresses our gratitude to Eric Berger of the Information Management Systems, Inc., and Judy Walsh, Sujata Dixit-Joshi and Viji Narayana of Westat for data management. NR 68 TC 3 Z9 3 U1 3 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD MAY 27 PY 2011 VL 11 AR 405 DI 10.1186/1471-2458-11-405 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 785XJ UT WOS:000292265900002 PM 21619649 ER PT J AU Jiao, S Li, Z AF Jiao, Song Li, Zheng TI Nonapoptotic Function of BAD and BAX in Long-Term Depression of Synaptic Transmission SO NEURON LA English DT Article ID AMPA RECEPTOR TRAFFICKING; NON-APOPTOTIC ROLE; BCL-X-L; HIPPOCAMPAL LTD; DEFICIENT MICE; MITOCHONDRIA; PLASTICITY; DEATH; ACTIVATION; SYNAPSES AB It has recently been found that caspases not only function in apoptosis, but are also crucial for nonapoptotic processes such as NMDA receptor-dependent long-term depression (LTD) of synaptic transmission. It remains unknown, however, how caspases are activated and how neurons escape death in LTD. Here we show that caspase-3 is activated by the BAD-BAX cascade for LTD induction. This cascade is required specifically for NMDA receptor-dependent LTD but not for mGluR-LTD, and its activation is sufficient to induce synaptic depression. In contrast to apoptosis, however, BAD is activated only moderately and transiently and BAX is not translocated to mitochondria, resulting in only modest caspase-3 activation. We further demonstrate that the intensity and duration of caspase-3 activation determine whether it leads to cell death or LTD, thus fine-tuning of caspase-3 activation is critical in distinguishing between these two pathways. C1 [Jiao, Song; Li, Zheng] NIMH, Unit Synapse Dev & Plast, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. RP Li, Z (reprint author), NIMH, Unit Synapse Dev & Plast, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. EM lizheng2@mail.nih.gov RI Li, Zheng/I-8016-2014; Jiao, Song/L-2803-2015 OI Li, Zheng/0000-0002-2978-2531; Jiao, Song/0000-0003-0496-6454 FU NIMH Division FX We thank Dr. Nika N Danial (Harvard University) for providing the BAD knockout mice, Dr. Richard Youle (NINDS/NIH) for providing the BAD BH3 Delta construct and for critical reading of the manuscript, Dr. Kazutoshi Nakazawa (NIMH/NIH) for providing the CA3-specific Cre mice, Dr. Tsan Xiao for providing the GB1 vector (NIAID/NIH), Dr. Heinz Arnheiter (NINDS/NIH) for provocative discussions and critical reading of the manuscript. This work is supported by NIMH Division of Intramural Research Programs. NR 46 TC 69 Z9 72 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 26 PY 2011 VL 70 IS 4 BP 758 EP 772 DI 10.1016/j.neuron.2011.04.004 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 792NR UT WOS:000292754300016 PM 21609830 ER PT J AU Zou, JZ Sweeney, CL Chou, BK Choi, U Pan, J Wang, HM Dowey, SN Cheng, LZ Malech, HL AF Zou, Jizhong Sweeney, Colin L. Chou, Bin-Kuan Choi, Uimook Pan, Jason Wang, Hongmei Dowey, Sarah N. Cheng, Linzhao Malech, Harry L. TI Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease-mediated safe harbor targeting SO BLOOD LA English DT Article ID PLURIPOTENT STEM-CELLS; GENE-THERAPY; ADENOASSOCIATED VIRUS; INTEGRATION; ACTIVATION; EXPRESSION; SCID-X1; PATIENT; DERIVATION; VECTOR AB We have developed induced pluripotent stem cells (iPSCs) from a patient with X-linked chronic granulomatous disease (X-CGD), a defect of neutrophil microbicidal reactive oxygen species (ROS) generation resulting from gp91(phox) deficiency. We demonstrated that mature neutrophils differentiated from X-CGD iPSCs lack ROS production, reproducing the pathognomonic CGD cellular phenotype. Targeted gene transfer into iPSCs, with subsequent selection and full characterization to ensure no off-target changes, holds promise for correction of monogenic diseases without the insertional mutagenesis caused by multisite integration of viral or plasmid vectors. Zinc finger nuclease-mediated gene targeting of a single-copy gp91(phox) therapeutic minigene into one allele of the "safe harbor" AAVS1 locus in X-CGD iPSCs without off-target inserts resulted in sustained expression of gp91(phox) and substantially restored neutrophil ROS production. Our findings demonstrate how precise gene targeting may be applied to correction of X-CGD using zinc finger nuclease and patient iPSCs. (Blood. 2011; 117(21): 5561-5572) C1 [Zou, Jizhong; Chou, Bin-Kuan; Dowey, Sarah N.; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Dept Med,Div Hematol, Baltimore, MD 21205 USA. [Zou, Jizhong; Chou, Bin-Kuan; Dowey, Sarah N.; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA. [Sweeney, Colin L.; Choi, Uimook; Pan, Jason; Wang, Hongmei; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Chou, Bin-Kuan; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Grad Program Cellular & Mol Med, Baltimore, MD 21205 USA. RP Cheng, LZ (reprint author), Johns Hopkins Univ, Sch Med, Inst Cell Engn, Dept Med,Div Hematol, 733 N Broadway,BRB780, Baltimore, MD 21205 USA. EM lcheng2@jhmi.edu; hmalech@nih.gov RI Zou, Jizhong/B-4902-2011; OI Malech, Harry/0000-0001-5874-5775 FU NIH [RO1 HL073781]; Maryland Stem Cell Research Fund [2010-MSCRFE-0044-00]; NIAID [Z01-AI-000644, Z01-AI-000988]; Chronic Granulomatous Disorder Research Trust (United Kingdom) [J4G/09/10] FX Research conducted at JHU was supported by NIH grant RO1 HL073781 and Maryland Stem Cell Research Fund Exploratory Grant 2010-MSCRFE-0044-00. Research conducted at NIH was supported by NIAID intramural program projects Z01-AI-000644 and Z01-AI-000988. This work was supported by Grant Award J4G/09/10 from the Chronic Granulomatous Disorder Research Trust (United Kingdom) to L. C., H. L. M., and J.Z. NR 37 TC 135 Z9 141 U1 2 U2 11 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 MAY 26 PY 2011 VL 117 IS 21 BP 5561 EP 5572 DI 10.1182/blood-2010-12-328161 PG 12 WC Hematology SC Hematology GA 769KD UT WOS:000291010500006 PM 21411759 ER PT J AU Korde, N Kristinsson, SY Landgren, O AF Korde, Neha Kristinsson, Sigurdur Y. Landgren, Ola TI Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies SO BLOOD LA English DT Review ID INDEPENDENT RISK-FACTOR; LIGHT-CHAIN RATIO; WORKING GROUP; EARLY-DIAGNOSIS; RAS MUTATIONS; LONG-TERM; FOLLOW-UP; PROGRESSION; DISEASE; PATHOGENESIS AB Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed. (Blood. 2011; 117(21): 5573-5581) C1 [Korde, Neha] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Landgren, Ola] NCI, Med Oncol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. [Kristinsson, Sigurdur Y.] Karolinska Univ Hosp & Inst, Hematol Ctr, Stockholm, Sweden. RP Korde, N (reprint author), NHLBI, Hematol Branch, NIH, 9000 Rockville Pike,Bldg 10,Rm 7C422A, Bethesda, MD 20892 USA. EM korden@nhlbi.nih.gov; landgreo@mail.nih.gov RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU National Cancer Institute of the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health. NR 66 TC 79 Z9 82 U1 1 U2 11 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 MAY 26 PY 2011 VL 117 IS 21 BP 5573 EP 5581 DI 10.1182/blood-2011-01-270140 PG 9 WC Hematology SC Hematology GA 769KD UT WOS:000291010500007 PM 21441462 ER PT J AU Desmond, R Dunfee, A Racke, F Dunbar, CE Larochelle, A AF Desmond, Ronan Dunfee, Ashley Racke, Frederick Dunbar, Cynthia E. Larochelle, Andre TI CD9 up-regulation on CD34(+) cells with ingenol 3,20-dibenzoate does not improve homing in NSG mice SO BLOOD LA English DT Letter C1 [Desmond, Ronan; Dunfee, Ashley; Dunbar, Cynthia E.; Larochelle, Andre] NHLBI, Mol Hematopoiesis Sect, Hematol Branch, Bethesda, MD 20892 USA. [Racke, Frederick] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, Bldg 10-4E-5132,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov NR 3 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 26 PY 2011 VL 117 IS 21 BP 5774 EP 5776 DI 10.1182/blood-2011-01-332031 PG 5 WC Hematology SC Hematology GA 769KD UT WOS:000291010500031 PM 21617010 ER PT J AU Klaus, A Yu, S Plenz, D AF Klaus, Andreas Yu, Shan Plenz, Dietmar TI Statistical Analyses Support Power Law Distributions Found in Neuronal Avalanches SO PLOS ONE LA English DT Article ID FLIGHT SEARCH PATTERNS; GIBRATS LAW; WANDERING ALBATROSSES; CORTICAL NETWORKS; CRITICALITY; CITIES; LEVY; LIKELIHOOD; CORTEX; RANGE AB The size distribution of neuronal avalanches in cortical networks has been reported to follow a power law distribution with exponent close to -1.5, which is a reflection of long-range spatial correlations in spontaneous neuronal activity. However, identifying power law scaling in empirical data can be difficult and sometimes controversial. In the present study, we tested the power law hypothesis for neuronal avalanches by using more stringent statistical analyses. In particular, we performed the following steps: (i) analysis of finite-size scaling to identify scale-free dynamics in neuronal avalanches, (ii) model parameter estimation to determine the specific exponent of the power law, and (iii) comparison of the power law to alternative model distributions. Consistent with critical state dynamics, avalanche size distributions exhibited robust scaling behavior in which the maximum avalanche size was limited only by the spatial extent of sampling ("finite size" effect). This scale-free dynamics suggests the power law as a model for the distribution of avalanche sizes. Using both the Kolmogorov-Smirnov statistic and a maximum likelihood approach, we found the slope to be close to -1.5, which is in line with previous reports. Finally, the power law model for neuronal avalanches was compared to the exponential and to various heavy-tail distributions based on the Kolmogorov-Smirnov distance and by using a log-likelihood ratio test. Both the power law distribution without and with exponential cut-off provided significantly better fits to the cluster size distributions in neuronal avalanches than the exponential, the lognormal and the gamma distribution. In summary, our findings strongly support the power law scaling in neuronal avalanches, providing further evidence for critical state dynamics in superficial layers of cortex. C1 [Klaus, Andreas; Yu, Shan; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. [Klaus, Andreas] Karolinska Inst, Nobel Inst Neurophysiol, Dept Neurosci, S-10401 Stockholm, Sweden. [Klaus, Andreas] Stockholm Brain Inst, Stockholm, Sweden. RP Klaus, A (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA. EM Andreas.Klaus@frontiersin.org RI Klaus, Andreas/B-3392-2009; OI Klaus, Andreas/0000-0002-4133-351X FU NIMH FX This work was supported by the NIMH Division of Intramural Research Programs. AK was in addition supported by the NIH-Karolinska Institute joint PhD program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 71 Z9 71 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 26 PY 2011 VL 6 IS 5 AR e19779 DI 10.1371/journal.pone.0019779 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 769XS UT WOS:000291052200015 PM 21720544 ER PT J AU Xue, W Cojocaru, RI Dudley, VJ Brooks, M Swaroop, A Sarthy, VP AF Xue, Wei Cojocaru, Radu I. Dudley, V. Joseph Brooks, Matthew Swaroop, Anand Sarthy, Vijay P. TI Ciliary Neurotrophic Factor Induces Genes Associated with Inflammation and Gliosis in the Retina: A Gene Profiling Study of Flow-Sorted, Muller Cells SO PLOS ONE LA English DT Article ID INTRACELLULAR SIGNALING PATHWAYS; FACTOR PREVENTS DEGENERATION; LEUKEMIA INHIBITORY FACTOR; FIBROBLAST GROWTH-FACTOR; AAV-MEDIATED DELIVERY; GANGLION-CELLS; RAT RETINA; PHOTORECEPTOR DEGENERATION; PIGMENT EPITHELIUM; NERVOUS-SYSTEM AB Background: Ciliary neurotrophic factor (CNTF), a member of the interleukin-6 cytokine family, has been implicated in the development, differentiation and survival of retinal neurons. The mechanisms of CNTF action as well as its cellular targets in the retina are poorly understood. It has been postulated that some of the biological effects of CNTF are mediated through its action via retinal glial cells; however, molecular changes in retinal glia induced by CNTF have not been elucidated. We have, therefore, examined gene expression dynamics of purified Muller (glial) cells exposed to CNTF in vivo. Methodology/Principal Findings: Muller cells were flow-sorted from mgfap-egfp transgenic mice one or three days after intravitreal injection of CNTF. Microarray analysis using RNA from purified Muller cells showed differential expression of almost 1,000 transcripts with two-to seventeen-fold change in response to CNTF. A comparison of transcriptional profiles from Muller cells at one or three days after CNTF treatment showed an increase in the number of transcribed genes as well as a change in the expression pattern. Ingenuity Pathway Analysis showed that the differentially regulated genes belong to distinct functional types such as cytokines, growth factors, G-protein coupled receptors, transporters and ion channels. Interestingly, many genes induced by CNTF were also highly expressed in reactive Muller cells from mice with inherited or experimentally induced retinal degeneration. Further analysis of gene profiles revealed 20-30% overlap in the transcription pattern among Muller cells, astrocytes and the RPE. Conclusions/Significance: Our studies provide novel molecular insights into biological functions of Muller glial cells in mediating cytokine response. We suggest that CNTF remodels the gene expression profile of Muller cells leading to induction of networks associated with transcription, cell cycle regulation and inflammatory response. CNTF also appears to function as an inducer of gliosis in the retina. C1 [Xue, Wei; Dudley, V. Joseph; Sarthy, Vijay P.] Northwestern Univ, Dept Ophthalmol, Feinberg Med Sch, Chicago, IL 60611 USA. [Cojocaru, Radu I.; Brooks, Matthew; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. RP Xue, W (reprint author), Northwestern Univ, Dept Ophthalmol, Feinberg Med Sch, Chicago, IL 60611 USA. EM vjsarthy@northwestern.edu OI Swaroop, Anand/0000-0002-1975-1141 FU NIH [EY019325]; National Eye Institute FX This work was supported by NIH grant EY019325 (VS), unrestricted funds from Research to Prevent Blindness and intramural program of the National Eye Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 89 TC 26 Z9 27 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 26 PY 2011 VL 6 IS 5 AR e20326 DI 10.1371/journal.pone.0020326 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 769XS UT WOS:000291052200052 PM 21637858 ER PT J AU Banala, AK Levy, BA Khatri, SS Furman, CA Roof, RA Mishra, Y Griffin, SA Sibley, DR Luedtke, RR Newman, AH AF Banala, Ashwini K. Levy, Benjamin A. Khatri, Sameer S. Furman, Cheryse A. Roof, Rebecca A. Mishra, Yogesh Griffin, Suzy A. Sibley, David R. Luedtke, Robert R. Newman, Amy Hauck TI N-(3-Fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl)piperazine-1-yl)butyl)arylcarboxamides as Selective Dopamine D3 Receptor Ligands: Critical Role of the Carboxamide Linker for D3 Receptor Selectivity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; FUNCTIONALIZED LINKING CHAINS; BINDING-SITE CREVICE; D2 RECEPTOR; THERAPEUTIC AGENTS; CRYSTAL-STRUCTURE; HIGH-AFFINITY; D-3; ANTAGONISTS; ANALOGS AB N-(3-Fluoro-4-(4-(2,3-dichloro- or 2-methoxyphenyl)piperazine-1-yl)butyl)arylcarboxamides were prepared and evaluated for binding and function at dopamine D3 receptors (D3Rs) and dopamine D2 receptors (D2Rs). In this series, we discovered some of the most D3R selective compounds reported to date (e.g., 8d and 8j, > 1000-fold D3R-selective over D2R). In addition, chimeric receptor studies further identified the second extracellular (E2) loop as an important contributor to D3R binding selectivity. Further, compounds lacking the carbonyl group in the amide linker were synthesized, and while these amine-linked analogues bound with similar affinities to the amides at D2R, this modification dramatically reduced binding affinities at D3R by > 100-fold (e.g., D3R K-i for 15b = 393 vs for 8j = 2.6 nM), resulting in compounds with significantly reduced D3R selectivity. This study supports a pivotal role for the D3R E2 loop and the carbonyl group in the 4-phenylpiperazine class of compounds and further reveals a point of separation between structure-activity relationships at D3R and D2R. C1 [Banala, Ashwini K.; Levy, Benjamin A.; Khatri, Sameer S.; Newman, Amy Hauck] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Khatri, Sameer S.; Mishra, Yogesh; Griffin, Suzy A.; Luedtke, Robert R.] Univ N Texas, Dept Pharmacol & Neurosci, Hlth Sci Ctr, Ft Worth, TX 76107 USA. [Furman, Cheryse A.; Roof, Rebecca A.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Rockville, MD 20852 USA. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov FU NIDA; NINDS; NIH [DA13584-03S1, DA13584-01]; NIDA with SRI [N01DA-1-8816] FX This work was supported by the NIDA (A.H.N.) and NINDS (D.R.S.) Intramural Research Programs, NIH Grants DA13584-03S1 and DA13584-01 (R.R.L.), and NIDA Addiction Treatment Discovery Program contract with SRI (Grant N01DA-1-8816). A.K.B. was supported by an NIH Postdoctoral Visiting Fellowship. B.A.L. was supported by an NIH Summer Student Fellowship, and S.S.K. was supported by an NIH Postbacca-laureate Intramural Research Training Award (IRTA) Fellowship. The authors thank Drs. Robert H. Mach and Zhude Tu in Department of Radiology at Washington University School of Medicine in St. Louis, MO, for generously providing us with the precursor that was used for the radioiodination of 125I-IABN, and Dr. Aaron Janowski and Robert Johnson, Oregon Health and Science University, for obtaining the mitogenesis data for sulpiride. The authors also thank Drs. Jonathan Javitch and Lei Shi for helpful discussions during the preparation of this manuscript. NR 32 TC 40 Z9 40 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 26 PY 2011 VL 54 IS 10 BP 3581 EP 3594 DI 10.1021/jm200288r PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 764SB UT WOS:000290651800010 PM 21495689 ER PT J AU Hansen, SG Ford, JC Lewis, MS Ventura, AB Hughes, CM Coyne-Johnson, L Whizin, N Oswald, K Shoemaker, R Swanson, T Legasse, AW Chiuchiolo, MJ Parks, CL Axthelm, MK Nelson, JA Jarvis, MA Piatak, M Lifson, JD Picker, LJ AF Hansen, Scott G. Ford, Julia C. Lewis, Matthew S. Ventura, Abigail B. Hughes, Colette M. Coyne-Johnson, Lia Whizin, Nathan Oswald, Kelli Shoemaker, Rebecca Swanson, Tonya Legasse, Alfred W. Chiuchiolo, Maria J. Parks, Christopher L. Axthelm, Michael K. Nelson, Jay A. Jarvis, Michael A. Piatak, Michael, Jr. Lifson, Jeffrey D. Picker, Louis J. TI Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine SO NATURE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY VIRUS SIVMAC239; PRIMARY HIV-1 INFECTION; IMMUNE-RESPONSES; RHESUS-MONKEYS; MACAQUE MODEL; REPLICATION; CHALLENGE; PROTECTION; AIDS AB The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms(1-3). However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control(4). Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors(5) establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (>= 1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8(+) T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated TEM responses might significantly contribute to an efficacious HIV/AIDS vaccine. C1 [Hansen, Scott G.; Ford, Julia C.; Lewis, Matthew S.; Ventura, Abigail B.; Hughes, Colette M.; Coyne-Johnson, Lia; Whizin, Nathan; Swanson, Tonya; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Jarvis, Michael A.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol & Immunol, Beaverton, OR 97006 USA. [Hansen, Scott G.; Ford, Julia C.; Lewis, Matthew S.; Ventura, Abigail B.; Hughes, Colette M.; Coyne-Johnson, Lia; Whizin, Nathan; Swanson, Tonya; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Jarvis, Michael A.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Pathol, Beaverton, OR 97006 USA. [Hansen, Scott G.; Ford, Julia C.; Lewis, Matthew S.; Ventura, Abigail B.; Hughes, Colette M.; Coyne-Johnson, Lia; Whizin, Nathan; Swanson, Tonya; Legasse, Alfred W.; Axthelm, Michael K.; Nelson, Jay A.; Jarvis, Michael A.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. [Oswald, Kelli; Shoemaker, Rebecca; Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Chiuchiolo, Maria J.; Parks, Christopher L.] Int AIDS Vaccine Initiat, Vaccine Design & Dev Lab, Brooklyn, NY 11220 USA. RP Picker, LJ (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol & Immunol, Beaverton, OR 97006 USA. EM pickerl@ohsu.edu FU National Institute of Allergy and Infectious Diseases [RO1 AI060392, HHSN272200900037C]; International AIDS Vaccine Initiative (IAVI); United States Agency for International Development (USAID); Bill & Melinda Gates Foundation; National Center for Research Resources [P51 RR00163, R24 RR016001]; National Cancer Institute [HHSN261200800001E] FX This work was supported by the National Institute of Allergy and Infectious Diseases (RO1 AI060392; contract #HHSN272200900037C); the International AIDS Vaccine Initiative (IAVI) and its donors, particularly the United States Agency for International Development (USAID); the Bill & Melinda Gates Foundation-supported Collaboration for AIDS Vaccine Discovery; the National Center for Research Resources (P51 RR00163; R24 RR016001); and the National Cancer Institute (contract HHSN261200800001E). We thank A. Sylwester, D. Seiss, R. Lum, H. Park and A. Okoye for specialized technical assistance; P. Barry, G. Pavlakis, G. Franchini, C. Miller, N. Wilson, and K. Reimann and Nonhuman Primate Reagent Resource for provision of crucial constructs or reagents; D. Watkins for MHC typing; D. Montefiori for neutralizing antibody assays; N. Letvin and L. Shen for TRIM5a typing; S. Mongoue-Tchokote and M. Mori for statistical assistance; A. Townsend and T. Schroyer for figure preparation; and K. Fruh, D. Watkins, B. Beresford, A. McDermott, R. King and W. Koff for discussion and advice. NR 36 TC 459 Z9 466 U1 6 U2 61 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 26 PY 2011 VL 473 IS 7348 BP 523 EP U270 DI 10.1038/nature10003 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768QM UT WOS:000290951300043 PM 21562493 ER PT J AU DiMaio, F Terwilliger, TC Read, RJ Wlodawer, A Oberdorfer, G Wagner, U Valkov, E Alon, A Fass, D Axelrod, HL Das, D Vorobiev, SM Iwai, H Pokkuluri, PR Baker, D AF DiMaio, Frank Terwilliger, Thomas C. Read, Randy J. Wlodawer, Alexander Oberdorfer, Gustav Wagner, Ulrike Valkov, Eugene Alon, Assaf Fass, Deborah Axelrod, Herbert L. Das, Debanu Vorobiev, Sergey M. Iwai, Hideo Pokkuluri, P. Raj Baker, David TI Improved molecular replacement by density- and energy-guided protein structure optimization SO NATURE LA English DT Article ID LOW-RESOLUTION; CRYSTALLOGRAPHIC REFINEMENT; SOFTWARE; PREDICTION; ACCURACY; ROSETTA AB Molecular replacement(1-4) procedures, which search for placements of a starting model within the crystallographic unit cell that best account for the measured diffraction amplitudes, followed by automatic chain tracing methods(5-8), have allowed the rapid solution of large numbers of protein crystal structures. Despite extensive work(9-14), molecular replacement or the subsequent rebuilding usually fail with more divergent starting models based on remote homologues with less than 30% sequence identity. Here we show that this limitation can be substantially reduced by combining algorithms for protein structure modelling with those developed for crystallographic structure determination. An approach integrating Rosetta structure modelling with Autobuild chain tracing yielded high-resolution structures for 8 of 13 X-ray diffraction data sets that could not be solved in the laboratories of expert crystallographers and that remained unsolved after application of an extensive array of alternative approaches. We estimate that the new method should allow rapid structure determination without experimental phase information for over half the cases where current methods fail, given diffraction data sets of better than 3.2 angstrom resolution, four or fewer copies in the asymmetric unit, and the availability of structures of homologous proteins with >20% sequence identity. C1 [Terwilliger, Thomas C.] Los Alamos Natl Lab, Los Alamos, NM 87545 USA. [DiMaio, Frank; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [DiMaio, Frank; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Read, Randy J.] Univ Cambridge, Dept Haematol, Cambridge Inst Med Res, Cambridge CB2 0XY, England. [Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. [Oberdorfer, Gustav; Wagner, Ulrike] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria. [Valkov, Eugene] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England. [Alon, Assaf; Fass, Deborah] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. [Axelrod, Herbert L.; Das, Debanu] SLAC Natl Accelerator Lab, Joint Ctr Struct Genom, Menlo Pk, CA 94025 USA. [Axelrod, Herbert L.; Das, Debanu] SLAC Natl Accelerator Lab, SSRL, Menlo Pk, CA 94025 USA. [Vorobiev, Sergey M.] Columbia Univ, NE Struct Genom Consortium, New York, NY 10027 USA. [Iwai, Hideo] Univ Helsinki, Inst Biotechnol, FI-00014 Helsinki, Finland. [Pokkuluri, P. Raj] Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Terwilliger, TC (reprint author), Los Alamos Natl Lab, POB 1663, Los Alamos, NM 87545 USA. EM terwilliger@lanl.gov; dabaker@u.washington.edu RI Iwai, Hideo/A-6416-2009; Valkov, Eugene/C-1554-2010; Read, Randy/L-1418-2013; Terwilliger, Thomas/K-4109-2012; Baker, David/K-8941-2012 OI Iwai, Hideo/0000-0001-7376-5264; Read, Randy/0000-0001-8273-0047; Terwilliger, Thomas/0000-0001-6384-0320; Baker, David/0000-0001-7896-6217 FU NIH [5R01GM092802, P41RR002250]; Wellcome Trust; HHMI; Israel Science Foundation; DK Molecular Enzymology [W901]; Austrian Science Fund [P19858]; NIH, National Cancer Institute, Center for Cancer Research; academy of Finland [1131413]; Protein Structure Initiative of National Institute of General Medical Sciences [U54 GM074958]; US Department of Energy's Office of Science, Biological and Environmental Research [DE-AC02-06CH11357]; NIH, National Institutes of General Medical Sciences, Protein Structure Initiative [U54 GM094586, GM074898] FX R.J.R., T.C.T. and D.B. thank the NIH (5R01GM092802), the Wellcome Trust (R.J.R.), and HHMI (D.B.) for funding this research. F.D. acknowledges the NIH (P41RR002250) and HHMI. D.F. and A.A. acknowledge support from the Israel Science Foundation. G.O. thanks DK Molecular Enzymology (FWF-project W901) and the Austrian Science Fund (FWF-project P19858). The work of A.W. was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. H.I. acknowledges support from the academy of Finland (1131413). S.M.V. was supported by a grant from the Protein Structure Initiative of National Institute of General Medical Sciences (U54 GM074958). The work of P.R.P. at Argonne National Laboratory was supported by the US Department of Energy's Office of Science, Biological and Environmental Research GTL programme under contract DE-AC02-06CH11357. We thank all members of the JCSG for their general contributions to the protein production and structural work. The JCSG is supported by the NIH, National Institutes of General Medical Sciences, Protein Structure Initiative (U54 GM094586 and GM074898). NR 29 TC 123 Z9 124 U1 2 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAY 26 PY 2011 VL 473 IS 7348 BP 540 EP U149 DI 10.1038/nature09964 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 768QM UT WOS:000290951300047 PM 21532589 ER PT J AU Miller, FG Joffe, S AF Miller, Franklin G. Joffe, Steven TI Equipoise and the Dilemma of Randomized Clinical Trials REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Miller, Franklin G.] NIH, Bethesda, MD 20892 USA. [Joffe, Steven] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Miller, FG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 26 PY 2011 VL 364 IS 21 BP 2077 EP 2077 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 768QR UT WOS:000290952000037 ER PT J AU Ali, S Riazuddin, SA Shahzadi, A Nasir, IA Khan, SN Husnain, T Akram, J Sieving, PA Hejtmancik, JF Riazuddin, S AF Ali, Shahbaz Riazuddin, S. Amer Shahzadi, Amber Nasir, Idrees A. Khan, Shaheen N. Husnain, Tayyab Akram, Javed Sieving, Paul A. Hejtmancik, J. Fielding Riazuddin, Sheikh TI Mutations in the beta-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa SO MOLECULAR VISION LA English DT Article ID INHIBITORY GAMMA-SUBUNIT; CGMP PHOSPHODIESTERASE; GENE; PDE6 AB Purpose: This study was designed to identify pathogenic mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families. Methods: Two consanguineous families affected with autosomal recessive RP were identified from the Punjab Province of Pakistan. All affected individuals underwent a thorough ophthalmologic examination. Blood samples were collected, and genomic DNAs were extracted. Exclusion analysis was completed, and two-point LOD scores were calculated. Bidirectional sequencing of the beta subunit of phosphodiesterase 6 (PDE6 beta) was completed. Results: During exclusion analyses both families localized to chromosome 4p, harboring PDE6 beta, a gene previously associated with autosomal recessive RP. Sequencing of PDE6 beta identified missense mutations: c.1655G>A (p.R552Q) and c.1160C>T (p.P387L) in families PKRP161 and PKRP183, respectively. Bioinformatic analyses suggested that both mutations are deleterious for the native three-dimensional structure of the PDE6 beta protein. Conclusions: These results strongly suggest that mutations in PDE6 beta are responsible for the disease phenotype in the consanguineous Pakistani families. C1 [Ali, Shahbaz; Riazuddin, S. Amer; Shahzadi, Amber; Nasir, Idrees A.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan. [Sieving, Paul A.; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan. EM riaz@aimrc.org RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015 FU Higher Education Commission; Ministry of Science and Technology Islamabad, Pakistan FX The authors are grateful to the family members for their participation in this study. This study was supported, in part by Higher Education Commission and Ministry of Science and Technology Islamabad, Pakistan. NR 16 TC 8 Z9 8 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD MAY 25 PY 2011 VL 17 IS 154 BP 1373 EP 1380 PG 8 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 772PW UT WOS:000291247700001 PM 21655355 ER PT J AU Hara, Y Park, CS Janssen, WGM Punsoni, M Rapp, PR Morrison, JH AF Hara, Yuko Park, C. Sehwan Janssen, William G. M. Punsoni, Michael Rapp, Peter R. Morrison, John H. TI Synaptic Characteristics of Dentate Gyrus Axonal Boutons and Their Relationships with Aging, Menopause, and Memory in Female Rhesus Monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; SEGMENTED POSTSYNAPTIC DENSITIES; RAT CEREBRAL-CORTEX; AGE-RELATED-CHANGES; RECOGNITION MEMORY; AXOSPINOUS SYNAPSES; STRUCTURAL PLASTICITY; ALZHEIMERS-DISEASE; IN-VIVO; PERFORATED SYNAPSES AB Age-related memory impairment occurs in many mammalian species, including humans. Moreover, women undergoing the menopausal transition often complain of problems with memory. We recently reported that rhesus monkeys display age-and menopause-related recognition memory impairment on a hippocampus-reliant test [delayed nonmatching-to-sample (DNMS)]. In the same monkeys, perforated synapse densities in the dentate gyrus outer molecular layer (OML) correlated with DNMS recognition accuracy, while total axospinous synapse density was similar across age and menses groups. The current study examined whether synaptic characteristics of OML axonal boutons are coupled with age-or menopause-related memory deficits. Using serial section electron microscopy, we measured the frequencies of single-synapse boutons (SSBs), multiple-synapse boutons (MSBs), and boutons with no apparent synaptic contacts [nonsynaptic boutons (NSBs)] in the OML. Aged females had double the percentage of NSBs compared with young females, and this measure correlated positively and inversely with DNMS acquisition (number of trials to criterion) and delay performance (average accuracy), respectively. Aged compared with young females also had a lower frequency of MSBs and a lower number of synaptic contacts per MSB, and the latter variable inversely correlated with DNMS acquisition. Although proportions of NSBs, SSBs, and MSBs were similar across menses groups, compared with premenopausal monkeys, peri/postmenopausal monkeys had fewer MSBs contacting one or more segmented perforated synapses, and the abundance of this bouton subtype positively correlated with DNMS performance. These results suggest that age-and menopause-related shifts in OML synaptic subtypes may be coupled with deficits in task acquisition and recognition memory. C1 [Morrison, John H.] Mt Sinai Sch Med, Dept Neurosci, Computat Neurobiol & Imaging Ctr, New York, NY 10029 USA. [Hara, Yuko; Park, C. Sehwan; Janssen, William G. M.; Punsoni, Michael; Morrison, John H.] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY 10029 USA. [Hara, Yuko; Park, C. Sehwan; Janssen, William G. M.; Punsoni, Michael; Morrison, John H.] Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, New York, NY 10029 USA. [Morrison, John H.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Rapp, Peter R.] Natl Inst Aging, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Morrison, JH (reprint author), Mt Sinai Sch Med, Dept Neurosci, Computat Neurobiol & Imaging Ctr, Box 1065,1 Gustave L Levy Pl, New York, NY 10029 USA. EM john.morrison@mssm.edu RI Hara, Yuko/B-9172-2012; Morrison, John/F-9229-2012 OI Hara, Yuko/0000-0001-5828-442X; FU National Institute on Aging [R37 AG06647, R01 AG010606] FX This work was supported by National Institute on Aging Grants R37 AG06647 and R01 AG010606 to J.H.M., and in part by the Intramural Research Program of the National Institute on Aging. This study was conducted while Y.H. was an Ellison Medical Foundation/AFAR Postdoctoral Fellow. We thank Mary Roberts, Sania Fong, Deborah Kent, Katie Hartley, Sona Santos, Heather McKay, Anne Canfield, Susan Fink, Ginelle Andrews, Shannon Wadsworth, and Rishi Puri for expert technical assistance, and Dr. Donald Canfield for assistance in veterinary work. NR 60 TC 34 Z9 34 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 25 PY 2011 VL 31 IS 21 BP 7737 EP 7744 DI 10.1523/JNEUROSCI.0822-11.2011 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 768RX UT WOS:000290956400015 PM 21613486 ER PT J AU Wieser, MJ Keil, A AF Wieser, Matthias J. Keil, Andreas TI Temporal Trade-Off Effects in Sustained Attention: Dynamics in Visual Cortex Predict the Target Detection Performance during Distraction SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SELECTIVE ATTENTION; SPATIAL ATTENTION; TIME-COURSE; HUMAN BRAIN; BLINK; MECHANISMS; POTENTIALS; CAPACITY; AREAS; TASK AB Models of visual selective attention have suggested that the representation of specific features characterizing a target object is enhanced in the visual cortex, at the cost of competing task-irrelevant information. In psychophysical studies, however, such attentional enhancement has been shown to result in reduced perceptual sensitivity when maintained over periods of several seconds. Two experiments examined the relationship between target detection behavior and electrocortical facilitation in human visual cortex during sustained attention under competition, in near real time. Steady-state visual evoked potentials (ssVEPs) were used in a change detection paradigm, in which a stream of flickering grating stimuli containing target events was fully overlapping with distractor faces (experiment 1) or competing complex scenes (experiment 2), covering the same part of the visual field. Beamformer source localization was used to test plausibility of lower-tier visual cortex involvement in modulation of the ssVEP signal. Results of both experiments suggest that early overallocation of visual cortical resources to the attended stimulus stream is associated with rapid reduction of electrocortical facilitation and poor change detection across the entire trial. By contrast, temporally balanced dynamics in visual cortex predicted accurate change detection. Together, the present results support models of sustained selective attention that emphasize competition for resources in lower-tier visual cortex. These models can be extended by a temporal dimension, on which attentive behavior is characterized by frugal resource sharing across the viewing time. C1 [Wieser, Matthias J.] Univ Wurzburg, Dept Psychol, D-97070 Wurzburg, Germany. [Wieser, Matthias J.; Keil, Andreas] Univ Florida, NIMH Ctr Study Emot & Attent, Gainesville, FL 32610 USA. RP Wieser, MJ (reprint author), Univ Wurzburg, Dept Psychol, Marcusstr 9-11, D-97070 Wurzburg, Germany. EM wieser@psychologie.uni-wuerzburg.de RI Wieser, Matthias/E-7614-2010; Keil, Andreas/F-9427-2011 OI Keil, Andreas/0000-0002-4064-1924 FU NIMH [R01 MH084932-02] FX This research was supported by NIMH (Grant R01 MH084932-02 to A.K.). We thank Kayla Gurak, Forest Gruss, and Michael Gray for help in data acquisition. NR 30 TC 20 Z9 21 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 25 PY 2011 VL 31 IS 21 BP 7784 EP 7790 DI 10.1523/JNEUROSCI.5632-10.2011 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 768RX UT WOS:000290956400020 PM 21613491 ER PT J AU Murase, S Owens, DF Mckay, RD AF Murase, Sachiko Owens, David F. Mckay, Ronald D. TI In the Newborn Hippocampus, Neurotrophin-Dependent Survival Requires Spontaneous Activity and Integrin Signaling SO JOURNAL OF NEUROSCIENCE LA English DT Article ID OCCURRING CELL-DEATH; NERVE GROWTH-FACTOR; IN-VITRO; NEURONAL DEATH; BRAIN; RAT; EXPRESSION; RECEPTORS; KINASE; AKT AB The nervous system develops through a program that first produces neurons in excess and then eliminates as many as half in a specific period of early postnatal life. Neurotrophins are widely thought to regulate neuronal survival, but this role has not been clearly defined in the CNS. Here we show that neurotrophins promote survival of young neurons by promoting spontaneous activity. Survival of hippocampal neurons in neonatal rat requires spontaneous activity that depends on the excitatory action of GABA. Neurotrophins facilitate recruitment of cultured neurons into active networks, and it is this activity, combined with integrin receptor signaling, that controls neuronal survival. In vivo, neurotrophins require integrin signaling to control neuron number. These data are the first to link the early excitatory action of GABA to the developmental death period and to assign an essential role for activity in neurotrophin-mediated survival that establishes appropriate networks. C1 [Mckay, Ronald D.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA. [Murase, Sachiko; Owens, David F.; Mckay, Ronald D.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mckay, RD (reprint author), Lieber Inst Brain Dev, 855 N Wolfe St, Baltimore, MD 21205 USA. EM ronaldmckay@mac.com FU National Institutes of Health, National Institute of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. We thank Drs. Antonella Antignani and Richard Youle for providing LFn-Bcl-XL and PA, Drs. Joby Joseph and Mark Stopfer for advice on statistics and electrophysiological recording, and Drs. Arek Szklarczyk, Steve W. Poser, and Peter H. Maughan for the culture preparation. We also thank Drs. Moses Chao, Michael Sendtner, and Mu-Ming Poo for helpful advice on the manuscript. NR 50 TC 13 Z9 14 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 25 PY 2011 VL 31 IS 21 BP 7791 EP 7800 DI 10.1523/JNEUROSCI.0202-11.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 768RX UT WOS:000290956400021 PM 21613492 ER PT J AU Volkow, ND Tomasi, D Vaska, P AF Volkow, Nora D. Tomasi, Dardo Vaska, Paul TI Cell Phone Activation and Brain Glucose Metabolism Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. [Tomasi, Dardo] NIAAA, Bethesda, MD USA. [Vaska, Paul] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. RP Volkow, ND (reprint author), NIDA, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov RI Tomasi, Dardo/J-2127-2015 NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 25 PY 2011 VL 305 IS 20 BP 2067 EP 2068 DI 10.1001/jama.2011.672 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 768AC UT WOS:000290901700014 ER PT J AU Karami, S Boffetta, P Stewart, PS Brennan, P Zaridze, D Matveev, V Janout, V Kollarova, H Bencko, V Navratilova, M Szeszenia-Dabrowska, N Mates, D Gromiec, J Slamova, A Chow, WH Rothman, N Moore, LE AF Karami, S. Boffetta, P. Stewart, P. S. Brennan, P. Zaridze, D. Matveev, V. Janout, V. Kollarova, H. Bencko, V. Navratilova, M. Szeszenia-Dabrowska, N. Mates, D. Gromiec, J. Slamova, A. Chow, W-H Rothman, N. Moore, L. E. TI Occupational exposure to dusts and risk of renal cell carcinoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE renal cell carcinoma; occupational dust exposure; fibreglass; mineral wool; brick dust ID LUNG-CANCER RISK; CHROMOSOMAL-ABERRATIONS; KIDNEY CANCER; PRODUCTION PLANT; SILICA EXPOSURE; FIBER WORKERS; UNITED-STATES; FOLLOW-UP; MORTALITY; ASBESTOS AB BACKGROUND: Occupational exposures to dusts have generally been examined in relation to cancers of the respiratory system and have rarely been examined in relation to other cancers, such as renal cell carcinoma (RCC). Although previous epidemiological studies, though few, have shown certain dusts, such as asbestos, to increase renal cancer risk, the potential for other occupational dust exposures to cause kidney damage and/or cancer may exist. We investigated whether asbestos, as well as 20 other occupational dust exposures, were associated with RCC risk in a large European, multi-center, hospital-based renal case-control study. METHODS: General occupational histories and job-specific questionnaires were reviewed by occupational hygienists for subject-specific information. Odds ratios (ORs) and 95% confidence intervals (95% CIs) between RCC risk and exposures were calculated using unconditional logistic regression. RESULTS: Among participants ever exposed to dusts, significant associations were observed for glass fibres (OR: 2.1; 95% CI: 1.1-3.9), mineral wool fibres (OR: 2.5; 95% CI: 1.2-5.1), and brick dust (OR: 1.5; 95% CI: 1.0-2.4). Significant trends were also observed with exposure duration and cumulative exposure. No association between RCC risk and asbestos exposure was observed. CONCLUSION: Results suggest that increased RCC risk may be associated with occupational exposure to specific types of dusts. Additional studies are needed to replicate and extend findings. British Journal of Cancer (2011) 104, 1797-1803. doi:10.1038/bjc.2011.148 www.bjcancer.com Published online 3 May 2011 (C) 2011 Cancer Research UK C1 [Karami, S.; Stewart, P. S.; Chow, W-H; Rothman, N.; Moore, L. E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS,Occupat & Environm Epidemiol Branch, Rockville, MD 20852 USA. [Boffetta, P.; Brennan, P.] Int Agcy Res Canc, F-69008 Lyon, France. [Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA. [Boffetta, P.] Int Prevent Res Inst, F-69006 Lyon, France. [Stewart, P. S.] Stewart Exposure Assessments LLC, Arlington, VA USA. [Zaridze, D.; Matveev, V.] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow 115478, Russia. [Janout, V.; Kollarova, H.] Palacky Univ, Dept Prevent Med, Fac Med, Olomouc 77515, Czech Republic. [Bencko, V.; Slamova, A.] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague 12800, Czech Republic. [Navratilova, M.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic. [Szeszenia-Dabrowska, N.] Nofer Inst Occupat Med, Dept Epidemiol, PL-90950 Lodz, Poland. [Mates, D.] Inst Publ Hlth, Bucharest 76256, Romania. [Gromiec, J.] Nofer Inst Occupat Med, Dept Chem Hazards, PL-91348 Lodz, Poland. RP Karami, S (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS,Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8121, Rockville, MD 20852 USA. EM karamis@mail.nih.gov RI Zaridze, David/K-5605-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI mates, dana/0000-0002-6219-9807 NR 47 TC 7 Z9 7 U1 3 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY 24 PY 2011 VL 104 IS 11 BP 1797 EP 1803 DI 10.1038/bjc.2011.148 PG 7 WC Oncology SC Oncology GA 768RA UT WOS:000290953200021 PM 21540858 ER PT J AU Stasch, JP Pacher, P Evgenov, OV AF Stasch, Johannes-Peter Pacher, Pal Evgenov, Oleg V. TI Soluble Guanylate Cyclase as an Emerging Therapeutic Target in Cardiopulmonary Disease SO CIRCULATION LA English DT Article DE cardiovascular diseases; hypertension, pulmonary; nitric oxide; riociguat; soluble guanylate cyclase ID PULMONARY ARTERIAL-HYPERTENSION; SYSTEMIC VASODILATOR RESPONSES; NO-INDEPENDENT STIMULATORS; MUSCLE-CELL-PROLIFERATION; NITRIC-OXIDE RECEPTOR; HEART-FAILURE; BAY 41-2272; CYCLIC-GMP; SGC STIMULATOR; YC-1-INDUCED ACTIVATION C1 [Evgenov, Oleg V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Stasch, Johannes-Peter] Univ Halle Wittenberg, Inst Pharm, Halle, Germany. [Stasch, Johannes-Peter] Bayer HealthCare, Cardiol Res, Wuppertal, Germany. [Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Evgenov, OV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Gray Bigelow 444, Boston, MA 02114 USA. EM oevgenov@partners.org RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU National Institutes of Health FX This work was supported in part by departmental funds and the National Institutes of Health Intramural Research Program. NR 140 TC 159 Z9 165 U1 0 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAY 24 PY 2011 VL 123 IS 20 BP 2263 EP 2273 DI 10.1161/CIRCULATIONAHA.110.981738 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 767JI UT WOS:000290852200021 PM 21606405 ER PT J AU Cho, TJ Zangmeister, RA MacCuspie, RI Patri, AK Hackley, VA AF Cho, Tae Joon Zangmeister, Rebecca A. MacCuspie, Robert I. Patri, Anil K. Hackley, Vincent A. TI Newkome-Type Dendron-Stabilized Gold Nanoparticles: Synthesis, Reactivity, and Stability SO CHEMISTRY OF MATERIALS LA English DT Article DE gold nanoparticle; dendrimer; dendron; conjugate; characterization; stability ID SURFACE-PLASMON RESONANCE; ANISOTROPIC METAL NANOPARTICLES; AU NANOPARTICLES; COLLOIDAL GOLD; POLY(AMIDOAMINE) DENDRIMER; FUNCTIONALIZED DENDRONS; CONTROLLED NUCLEATION; OPTICAL-PROPERTIES; CORED DENDRIMERS; MICELLES SERIES AB We report the synthesis and evaluation of four Newkome-type dendrons, G1-COOH, G2-COOH, SH-G1-COOH, and TA-G1-COOH, and their respective gold dendron conjugates, where GX represents the generation number. Gl- and G2-COOH are two-directional symmetric dendrons that have cystamine cores containing a disulfide group. SH-G1-COOH was prepared by treatment of G1-COOH with dithioerythritol to yield a free thiol group to replace the disulfide linkage. TA-G1-COOH has a thioctic acid moiety, which is a five-membered ring containing a disulfide group that cleaves to produce two anchoring thiols to bond with the gold surface. All dendrons have peripheral carboxylate groups to afford hydrophilicity and functionality. Gold nanoparticle conjugates were prepared by reaction of each dendron solution with a suspension of gold colloid (nominally 10 nm diameter) and purified by stirred cell ultrafiltration. Chemical structures were confirmed by H-1 and C-13 nuclear magnetic resonance spectroscopy and matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Particle size and surface plasmon resonance of the conjugates were characterized by dynamic light scattering (DLS) and UV-vis spectroscopy, respectively. X-ray photoelectron spectroscopy (XPS) was utilized to confirm covalent bonding between the thiols on the dendron and the gold surface. XPS also revealed changes in the S/Au intensity ratio as a function of the dendron chemical structure, suggesting steric effects play a role in the reaction and/or conformation of dendrons on the gold surface. The colloidal and chemical stability of the conjugates as a function of temperature, pH, and suspending medium, and with respect to chemical resistance toward KCN, was investigated using DLS and UV-vis absorption. C1 [Cho, Tae Joon; Zangmeister, Rebecca A.; MacCuspie, Robert I.; Hackley, Vincent A.] Natl Inst Stand & Technol, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Patri, Anil K.] NCI, SAIC Frederick Inc, Adv Technol Program, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA. RP Hackley, VA (reprint author), Natl Inst Stand & Technol, Mat Measurement Lab, Gaithersburg, MD 20899 USA. EM vince.hackley@nist.gov RI Sanders, Susan/G-1957-2011; Nanotechnology Characterization Lab, NCL/K-8454-2012; Zangmeister, Rebecca/D-6641-2017; OI Zangmeister, Rebecca/0000-0002-0540-6240; MacCuspie, Robert/0000-0002-6618-6499; Hackley, Vincent/0000-0003-4166-2724 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The authors thank Dr. John T. Simpson and Mr. Sonny Man of the Protein Chemistry Laboratory and the Nanotechnology Characterization Laboratory, respectively, for help in performing MALDI-TOF mass spectrometer measurements used in this study. Their laboratories operate under the Advanced Technology Program, SAIC-Frederick, Inc., for the National Cancer Institute at Frederick. This project has been funded in part by the National Cancer Institute, National Institutes of Health, under Contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services. NR 97 TC 37 Z9 37 U1 0 U2 52 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0897-4756 EI 1520-5002 J9 CHEM MATER JI Chem. Mat. PD MAY 24 PY 2011 VL 23 IS 10 BP 2665 EP 2676 DI 10.1021/cm200591h PG 12 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 763YD UT WOS:000290594700023 PM 21686078 ER PT J AU McDonald, C Abhyankar, S AF McDonald, Clement Abhyankar, Swapna TI Clinical Decision Support and Rich Clinical Repositories A Symbiotic Relationship SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material C1 [McDonald, Clement; Abhyankar, Swapna] NIH, Lister Hill Ctr Biomed Commun, Natl Lib Med, Bethesda, MD USA. RP McDonald, C (reprint author), Lister Hill Ctr, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM clement.mcdonald@nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 6 TC 5 Z9 5 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 23 PY 2011 VL 171 IS 10 BP 903 EP 905 DI 10.1001/archinternmed.2010.518 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 767RT UT WOS:000290874400006 PM 21263079 ER PT J AU Betz, JM AF Betz, Joseph M. TI Monacolin Levels in Red Yeast Rice: Methodological Questions SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID IODINE CONTENT; PRENATAL VITAMINS C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Betz, JM (reprint author), NIH, Off Dietary Supplements, 6100 Executive Blvd,Ste 3B01, Bethesda, MD 20892 USA. EM betzj@od.nih.gov NR 5 TC 0 Z9 0 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 23 PY 2011 VL 171 IS 10 BP 950 EP 951 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 767RT UT WOS:000290874400022 PM 21606105 ER PT J AU Kasukurti, A Potcoava, M Desai, SA Eggleton, C Marr, DWM AF Kasukurti, A. Potcoava, M. Desai, S. A. Eggleton, C. Marr, D. W. M. TI Single-cell isolation using a DVD optical pickup SO OPTICS EXPRESS LA English DT Article ID UP HEAD; MICROFLUIDIC SYSTEMS; ACCELEROMETER; MANIPULATION; PARTICLE AB A low-cost single-cell isolation system incorporating a digital versatile disc burner (DVD RW) optical pickup has been developed. We show that these readily available modules have the required laser power and focusing optics to provide a steady Gaussian beam capable of optically trapping micron-sized colloids and red blood cells. Utility of the pickup is demonstrated through the non-destructive isolation of such particles in a laminar-flow based microfluidic device that captures and translates single microscale objects across streamlines into designated channel exits. In this, the integrated objective lens focusing coils are used to steer the optical trap across the channel, resulting in the isolation of colloids and red blood cells using a very inexpensive off-the-shelf optical component. (C) 2011 Optical Society of America C1 [Kasukurti, A.; Potcoava, M.; Marr, D. W. M.] Colorado Sch Mines, Dept Chem Engn, Golden, CO 80401 USA. [Desai, S. A.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Eggleton, C.] Univ Maryland Baltimore Cty, Dept Mech Engn, Baltimore, MD 21250 USA. RP Kasukurti, A (reprint author), Colorado Sch Mines, Dept Chem Engn, Golden, CO 80401 USA. EM dmarr@mines.edu FU National Institutes of Health [1R01 AI079347-01] FX We acknowledge support from the National Institutes of Health under grant 1R01 AI079347-01 and thank Kevin Roth and Tobias Sawetzki for useful discussions. NR 33 TC 12 Z9 12 U1 0 U2 13 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD MAY 23 PY 2011 VL 19 IS 11 BP 10377 EP 10386 DI 10.1364/OE.19.010377 PG 10 WC Optics SC Optics GA 767JN UT WOS:000290852800034 PM 21643294 ER PT J AU Fernandez-Medina, RD Struchiner, CJ Ribeiro, JMC AF Fernandez-Medina, Rita D. Struchiner, Claudio J. Ribeiro, Jose M. C. TI Novel transposable elements from Anopheles gambiae SO BMC GENOMICS LA English DT Article ID AFRICAN MALARIA MOSQUITO; INVERTED-REPEAT ELEMENTS; MULTIPLE SEQUENCE ALIGNMENT; LTR RETROTRANSPOSONS; PHYLOGENETIC ANALYSIS; NUCLEOTIDE-SEQUENCES; REPETITIVE ELEMENTS; EUKARYOTIC GENOMES; TY3/GYPSY GROUP; P-ELEMENTS AB Background: Transposable elements (TEs) are DNA sequences, present in the genome of most eukaryotic organisms that hold the key characteristic of being able to mobilize and increase their copy number within chromosomes. These elements are important for eukaryotic genome structure and evolution and lately have been considered as potential drivers for introducing transgenes into pathogen-transmitting insects as a means to control vector-borne diseases. The aim of this work was to catalog the diversity and abundance of TEs within the Anopheles gambiae genome using the PILER tool and to consolidate a database in the form of a hyperlinked spreadsheet containing detailed and readily available information about the TEs present in the genome of An. gambiae. Results: Here we present the spreadsheet named AnoTExcel that constitutes a database with detailed information on most of the repetitive elements present in the genome of the mosquito. Despite previous work on this topic, our approach permitted the identification and characterization both of previously described and novel TEs that are further described in detailed. Conclusions: Identification and characterization of TEs in a given genome is important as a way to understand the diversity and evolution of the whole set of TEs present in a given species. This work contributes to a better understanding of the landscape of TEs present in the mosquito genome. It also presents a novel platform for the identification, analysis, and characterization of TEs on sequenced genomes. C1 [Fernandez-Medina, Rita D.; Struchiner, Claudio J.] Escola Nacl Saude Publ Sergio Arouca, Fdn Oswaldo Cruz, BR-21040360 Rio De Janeiro, Brazil. [Struchiner, Claudio J.] Univ Estado Rio de Janeiro, Inst Social Med, BR-20550011 Rio De Janeiro, Brazil. [Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Fernandez-Medina, RD (reprint author), Escola Nacl Saude Publ Sergio Arouca, Fdn Oswaldo Cruz, Av Brasil 4365, BR-21040360 Rio De Janeiro, Brazil. EM dfernandezmedina@gmail.com RI Struchiner, Claudio/M-9360-2013; OI Ribeiro, Jose/0000-0002-9107-0818 FU FAPERJ (Fundacao de Amparo a Pesquisa do Estado de Rio de Janeiro); CNPQ (Conselho Nacional de Pesquisa); 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. We thank NIAID intramural editor Brenda Rae Marshall for assistance. RDFM and CJS were funded by FAPERJ (Fundacao de Amparo a Pesquisa do Estado de Rio de Janeiro) and CNPQ (Conselho Nacional de Pesquisa). NR 72 TC 10 Z9 10 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAY 23 PY 2011 VL 12 AR 260 DI 10.1186/1471-2164-12-260 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 781NX UT WOS:000291941200001 PM 21605407 ER PT J AU Purohit, V Rapaka, RS Schnur, P Shurtleff, D AF Purohit, Vishnudutt Rapaka, Rao S. Schnur, Paul Shurtleff, David TI Potential impact of drugs of abuse on mother-to-child transmission (MTCT) of HIV in the era of highly active antiretroviral therapy (HAART) SO LIFE SCIENCES LA English DT Editorial Material DE HIV; HAART; MTCT; Drugs of abuse ID IMMUNODEFICIENCY-VIRUS TYPE-1; CRACK-COCAINE USE; BLOOD MONONUCLEAR PHAGOCYTES; FRENCH PERINATAL COHORT; NORMAL HUMAN ASTROCYTES; LOW-BIRTH-WEIGHT; CIGARETTE-SMOKING; VERTICAL TRANSMISSION; DENDRITIC CELLS; MESSENGER-RNA AB This report is a summary of a symposium entitled "Mother-to-Child Transmission (MTCT) of HIV and Drugs of Abuse in Highly Active Antiretroviral Therapy (HAART) Era," organized by The National Institute on Drug Abuse, National Institutes of Health in Rockville, Maryland, October 13, 2009. In the pre-HAART era, the prevalence of MTCT of HIV was about 25% and exposure of pregnant mothers to drugs of abuse (illicit drugs and tobacco smoking) was a significant factor in MTCT. However, with the introduction of HAART, the rate of MTCT of HIV has decreased to less that 2%. In the Unites States, it is estimated that currently about 5.1% of pregnant women use illicit drugs and 16.4% smoke tobacco. The residual prevalence of MTCT in the HAART era is still of concern and may be related to this continued prevalence of substance use among pregnant mothers. In this report, we review and present evidence that supports the hypothesis that drugs of abuse do have the potential to increase MTCT of HIV in the presence of HAART. Exposure to drugs of abuse during pregnancy may increase MTCT of HIV through a variety of mechanisms including possible damage to the placenta, induction of preterm birth, and increasing maternal plasma viral load through a variety of putative mechanisms such as: a) promoting HIV mutation and replication through non-adherence to HAART; b) impairing the efficacy of HAART through drug drug interaction; and c) promoting HIV replication in monocyte/macrophages. Drugs of abuse may promote HIV replication by increasing the expression of CCR5 receptors, decreasing the expression of CCR5 receptor ligands, increasing the expression of CXCR4 receptors, increasing the expression of DC-SIGN, and possibly inducing epigenetic changes. Published by Elsevier Inc. C1 [Purohit, Vishnudutt; Rapaka, Rao S.; Schnur, Paul; Shurtleff, David] NIDA, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. RP Purohit, V (reprint author), NIDA, Div Basic Neurosci & Behav Res, NIH, 6001 Execut Blvd,Room 4282,MSC 9555, Bethesda, MD 20892 USA. EM vpurohit@nida.nih.gov NR 121 TC 4 Z9 4 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAY 23 PY 2011 VL 88 IS 21-22 SI SI BP 909 EP 916 DI 10.1016/j.lfs.2011.03.022 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 771GB UT WOS:000291144100001 PM 21477599 ER PT J AU Straub, CP Lau, WH Preston, FM Headlam, MJ Gorman, JJ Collins, PL Spann, KM AF Straub, Claire P. Lau, Wei-Har Preston, Faith M. Headlam, Madeleine J. Gorman, Jeffery J. Collins, Peter L. Spann, Kirsten M. TI Mutation of the elongin C binding domain of human respiratory syncytial virus non-structural protein 1 (NS1) results in degradation of NS1 and attenuation of the virus SO VIROLOGY JOURNAL LA English DT Article DE RSV; NS1; attenuation ID INTERFERON REGULATORY FACTOR-3; NF-KAPPA-B; VACCINE CANDIDATES; IN-VITRO; CELLS; EXPRESSION; GROWTH; GENES; RSV; TRANSCRIPTION AB Background: Human respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in the paediatic population, immunocompromised individuals and the elderly worldwide. However, despite global efforts over the past several decades there are no commercially available vaccines. RSV encodes 2 non-structural proteins, NS1 and NS2, that are type I interferon antagonists. RSV restricts type I interferon signaling and the expression of antiviral genes by degrading STAT2. It has been proposed that NS1 binds to elongin C to form a ubiquitin ligase (E3) complex that targets STAT2 for ubiquitination and proteosomal degradation. Results: Here, we have engineered a live recombinant RSV in which the 3 consensus amino acids of the NS1 elongin C binding domain have been replaced with alanine (NS1F-ELCmut). Mutation of this region of NS1 resulted in attenuation of RSV replication in A549 cells to levels similar to that observed when the NS1 gene is completely deleted (Delta NS1). This mutation also resulted in moderate attenuation in Vero cells. Attenuation was correlated to intracellular degradation of the mutated NS1 protein. Time course analysis showed that mutant NS1 protein accumulated in cytoplasmic bodies that contained the lysosomal marker LAMP1. However lack of cleavage of LC3 suggested that autophagy was not involved. Induction of IFN-beta mRNA expression also was observed in association with the degradation of NS1 protein and attenuation of viral growth. Conclusions: These results indicate that the elongin C binding region of NS1 is crucial for survival of the protein and that disruption of this region results in the degradation of NS1 and restriction of RSV replication. C1 [Straub, Claire P.; Lau, Wei-Har; Preston, Faith M.; Spann, Kirsten M.] Univ Queensland, Clin Med Virol Ctr, Brisbane, Qld 4072, Australia. [Headlam, Madeleine J.; Gorman, Jeffery J.; Spann, Kirsten M.] Queensland Inst Med Res, Prot Discovery Ctr, Herston, Qld 4029, Australia. [Collins, Peter L.] NIAID, Resp Virus Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Spann, KM (reprint author), Univ Queensland, Clin Med Virol Ctr, Brisbane, Qld 4072, Australia. EM K.Spann@uq.edu.au RI Spann, Kirsten/B-4524-2013; OI Spann, Kirsten/0000-0003-0567-8382; Headlam, Madeleine/0000-0001-6812-2459 FU Australian National Health and Medical Research Council [511020]; Brisbane Royal Children's Hospital Foundation [9120-012]; QIMR (MTH); NIAID FX This work was funded by the Australian National Health and Medical Research Council, grant number 511020, the Brisbane Royal Children's Hospital Foundation grant number 9120-012 and QIMR (MTH). PLC was supported by the NIAID Intramural Program. NR 38 TC 5 Z9 5 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD MAY 22 PY 2011 VL 8 AR 252 DI 10.1186/1743-422X-8-252 PG 12 WC Virology SC Virology GA 782HV UT WOS:000292000000001 PM 21600055 ER PT J AU Goldenberg, RL McClure, EM Bhutta, ZA Belizan, JM Reddy, UM Rubens, CE Mabeya, H Flenady, V Darmstadt, GL AF Goldenberg, Robert L. McClure, Elizabeth M. Bhutta, Zulfiqar A. Belizan, Jose M. Reddy, Uma M. Rubens, Craig E. Mabeya, Hillary Flenady, Vicki Darmstadt, Gary L. CA Lancet's Stillbirths Series Steeri TI Stillbirths 6 Stillbirths: the vision for 2020 SO LANCET LA English DT Article ID TRADITIONAL BIRTH ATTENDANTS; EMERGENCY OBSTETRIC CARE; NEONATAL DEATHS; DEVELOPING-COUNTRIES; MATERNAL MORTALITY; PREVENTION; STRATEGIES; RISK AB Stillbirth is a common adverse pregnancy outcome, with nearly 3 million third-trimester stillbirths occurring worldwide each year. 98% occur in low-income and middle-income countries, and more than 1 million stillbirths occur in the intrapartum period, despite many being preventable. Nevertheless, stillbirth is practically unrecognised as a public health issue and few data are reported. In this final paper in the Stillbirths Series, we call for inclusion of stillbirth as a recognised outcome in all relevant international health reports and initiatives. We ask every country to develop and implement a plan to improve maternal and neonatal health that includes a reduction in stillbirths, and to count stillbirths in their vital statistics and other health outcome surveillance systems. We also ask for increased investment in stillbirth-related research, and especially research aimed at identifying and addressing barriers to the aversion of stillbirths within the maternal and neonatal health systems of low-income and middle-income countries. Finally, we ask all those interested in reducing stillbirths to join with advocates for the improvement of other pregnancy-related outcomes, for mothers and their offspring, so that a united front for improved pregnancy and neonatal care for all will become a reality. C1 [Goldenberg, Robert L.] Drexel Univ, Coll Med, Dept Obstet & Gynecol, Philadelphia, PA 19102 USA. [McClure, Elizabeth M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Bhutta, Zulfiqar A.] Aga Khan Univ, Div Women & Child Hlth, Karachi, Pakistan. [Belizan, Jose M.] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Rubens, Craig E.] Global Alliance Prevent Prematur & Stillbirth, Seattle, WA USA. [Mabeya, Hillary] Moi Univ, Eldoret, Kenya. [Flenady, Vicki] Mater Med Res Inst, Brisbane, Qld, Australia. [Flenady, Vicki] Int Stillbirth Alliance, Baltimore, MD USA. [Flenady, Vicki] Univ Queensland, Brisbane, Qld, Australia. [Darmstadt, Gary L.] Bill & Melinda Gates Fdn, Global Hlth Program, Family Hlth Div, Seattle, WA USA. RP Goldenberg, RL (reprint author), Drexel Univ, Coll Med, Dept Obstet & Gynecol, 245 N 15th St,17th Floor,Room 17113, Philadelphia, PA 19102 USA. EM rgoldenb@drexelmed.edu RI Froen, J. Frederik/C-3271-2009; Flenady, Vicki/O-9609-2014 FU Bill & Melinda Gates Foundation; Global Alliance to Prevent Prematurity and Stillbirth; International Stillbirth Alliance; Partnership for Maternal, Newborn and Child Health; National Institute of Child Health and Human Development Global Network; Research Triangle Institute, Research Triangle Park, NC, USA FX We thank Joy E Lawn, Robert Pattinson, and J Frederik Froen for their extensive contributions to this article, and the Bill & Melinda Gates Foundation, the Global Alliance to Prevent Prematurity and Stillbirth, the International Stillbirth Alliance, and the Partnership for Maternal, Newborn and Child Health for their financial support to The Lancet's Stillbirths Series. CER has received funding from the Bill & Melinda Gates Foundation, and support for RLG and EMM was provided by the National Institute of Child Health and Human Development Global Network, and the Maternal and Neonatal Directed Assessment of Technology project of the Research Triangle Institute, Research Triangle Park, NC, USA. NR 43 TC 61 Z9 61 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 21 PY 2011 VL 377 IS 9779 BP 1798 EP 1805 DI 10.1016/S0140-6736(10)62235-0 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 771AS UT WOS:000291130200038 PM 21496912 ER PT J AU Huff, J AF Huff, James TI Primary Prevention of Cancer SO SCIENCE LA English DT Letter ID ENVIRONMENTAL CANCER; RISKS C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM huff1@niehs.nih.gov NR 11 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 20 PY 2011 VL 332 IS 6032 BP 916 EP 917 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 766FO UT WOS:000290766600022 PM 21596974 ER PT J AU Lee, HW Choi, WJ Jacobson, KA Jeong, LS AF Lee, Hyuk Woo Choi, Won Jun Jacobson, Kenneth A. Jeong, Lak Shin TI Synthesis and Binding Affinity of Homologated Adenosine Analogues as A(3) Adenosine Receptor Ligands SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY LA English DT Article DE Co-2(CO)(8)-catalyzed siloxymethylation; A(3) adenosine receptor; Homologation ID PHARMACOLOGY; ANTAGONISTS; DERIVATIVES; SUBTYPES; AGONISTS; CELLS AB Homologated analogues 3a and 3b of potent and selective A(3) adenosine receptor ligands, IB-MECA and dimethyl-IB-MECA were synthesized from commercially available 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose (4) via Co-2(CO)(8)-catalyzed siloxymethylation as a key step. Unfortunately, homologated analogues 3a and 3b did not show significant binding affinities at three subtypes of adenosine receptors, indicating that free rotation, resulting from homologation, induced unfavorable interactions in the binding site of the receptor maybe due to the presence of many conformations. C1 [Lee, Hyuk Woo; Choi, Won Jun; Jeong, Lak Shin] Ewha Womans Univ, Dept Bioinspired Sci, Coll Pharm, Seoul 120750, South Korea. [Lee, Hyuk Woo; Choi, Won Jun; Jeong, Lak Shin] Ewha Womans Univ, Med Chem Lab, Coll Pharm, Seoul 120750, South Korea. [Choi, Won Jun] Dongguk Univ, Coll Pharm, Kyonggi Do 410774, South Korea. [Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jeong, LS (reprint author), Ewha Womans Univ, Dept Bioinspired Sci, Coll Pharm, Seoul 120750, South Korea. EM lakjeong@ewha.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Ewha Womans University FX This work was supported by RP-Grant (2010-2011) of Ewha Womans University. NR 13 TC 2 Z9 2 U1 0 U2 7 PU KOREAN CHEMICAL SOC PI SEOUL PA 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 0253-2964 J9 B KOREAN CHEM SOC JI Bull. Korean Chem. Soc. PD MAY 20 PY 2011 VL 32 IS 5 BP 1620 EP 1624 DI 10.5012/bkcs.2011.32.5.1620 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 771OQ UT WOS:000291171000034 PM 26120223 ER PT J AU Zhang, Y Lu, L Li, HQ Liu, W Tang, ZR Fang, H Chen, JY Ma, Y Zhao, Y Chen, RY Zhang, FJ AF Zhang Yao Lu Lin Li Hui-qin Liu Wei Tang Zhi-rong Fang Hua Chen, Jennifer Y. Ma Ye Zhao Yan Chen, Ray Y. Zhang Fu-jie TI Engaging HIV-infected patients in antiretroviral therapy services: CD4 cell count testing after HIV diagnosis from 2005 to 2009 in Yunnan and Guangxi, China SO CHINESE MEDICAL JOURNAL LA English DT Article DE human immunodeficiency virus; CD4 cell count testing; care linkage; risk factors ID TREATMENT PROGRAM; SOUTH-AFRICA; CARE; MORTALITY; LINKAGE; SITES; MEN; SEX AB Background The initiation and expansion of China's national free antiretroviral therapy program has led to significant improvement of survival among its participants. Success of further scaling up treatment coverage rests upon intensifying HIV screening and efficient linkage of care. Timely CD4 cell count testing after HIV diagnosis is necessary to determine whether a patient meets criteria for antiretroviral treatment, and represents a crucial link to engage HIV-infected patients in appropriate care, which has not been evaluated in China. Methods We evaluated all patients >= 6 years who tested HIV positive from 2005 to 2009 in Yunnan and Guangxi. Multivariate Logistic regression models were applied to identify factors associated with lack of CD4 cell count testing within 6 months after HIV diagnosis. Results A total of 83 556 patients were included. Over the study period, 30 635 (37%) of subjects received a CD4 cell count within 6 months of receiving the HIV diagnosis. The rate of CD4 cell count testing within 6 months of HIV diagnosis increased significantly from 7% in 2005 to 62% in 2009. Besides the earlier years of HIV diagnosis, negative predictors for CD4 cell count testing in multivariate analyses included older age, not married or unclear marriage status, incarceration, diagnosis at sexual transmitted disease clinics, mode of HIV transmission classified as men who have sex with men, intravenous drug users or transmission route unclear, while minority ethnicity, receipt of high school or higher education, diagnosis at voluntary counseling and testing clinics, and having HIV positive parents were protective. Conclusions Significant progress has been made in increasing CD4 testing among newly diagnosed HIV positive patients in Yunnan and Guangxi from 2005-2009. However, a sizable proportion of HIV positive patients still lack CD4 testing within 6 months of diagnosis. Improving CD4 testing, particularly among patients with identified risk factors, is essential to link patients with ART services and optimize treatment coverage. Chin Med J 2011;124(10):1488-1492 C1 [Zhang Yao; Fang Hua; Ma Ye; Zhao Yan; Zhang Fu-jie] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Div Treatment & Care, Beijing 100050, Peoples R China. [Lu Lin] Yunnan Ctr Dis Control & Prevent, Kunming 650022, Yunnan, Peoples R China. [Li Hui-qin] Yunnan AIDS Care Ctr, Kunming 650118, Yunnan, Peoples R China. [Liu Wei] Guangxi Ctr Dis Control & Prevent, Div HIV & Sexually Transmitted Dis, Nanning 530012, Guangxi, Peoples R China. [Tang Zhi-rong] Prov Ctr Dis Control & Prevent, Outpatient Clin, Nanning 530000, Guangxi, Peoples R China. [Chen, Jennifer Y.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Ray Y.] US Natl Inst Hlth, NIAID, Off Global Res, Beijing 100600, Peoples R China. [Zhang Fu-jie] Capital Med Univ, Beijing Ditan Hosp, Beijing 100015, Peoples R China. RP Zhang, FJ (reprint author), Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Div Treatment & Care, 27 Nanwei Rd, Beijing 100050, Peoples R China. EM treatment@chinaaids.cn OI Chen, Ray/0000-0001-6344-1442 FU Chinese National Basic Research Program (973) [2006CB504201] FX This study was supported by the grant from the Chinese National Basic Research Program (973, No. 2006CB504201). NR 22 TC 11 Z9 11 U1 1 U2 7 PU CHINESE MEDICAL ASSOC PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD MAY 20 PY 2011 VL 124 IS 10 BP 1488 EP 1492 DI 10.3760/cma.j.issn.0366-6999.2011.10.009 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 771QP UT WOS:000291176100009 PM 21740803 ER PT J AU Marconi, VC Grandits, G Okulicz, JF Wortmann, G Ganesan, A Crum-Cianflone, N Polis, M Landrum, M Dolan, MJ Ahuja, SK Agan, B Kulkarni, H AF Marconi, Vincent C. Grandits, Greg Okulicz, Jason F. Wortmann, Glenn Ganesan, Anuradha Crum-Cianflone, Nancy Polis, Michael Landrum, Michael Dolan, Matthew J. Ahuja, Sunil K. Agan, Brian Kulkarni, Hemant CA Infect Dis Clinical Res Program TI Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS SO PLOS ONE LA English DT Article ID PROTEASE INHIBITOR THERAPY; VIRUS TYPE-1 RNA; TERM-FOLLOW-UP; CELL COUNT; HIV-1-INFECTED PATIENTS; DISEASE PROGRESSION; DRUG-RESISTANCE; INTERMITTENT VIREMIA; PROGNOSTIC MARKERS; CLINICAL-OUTCOMES AB Background: The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown. Methods and Findings: Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U. S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56-3.62, p < 0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p < 0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/mu L; p = 0.001) even after adjusting for potential confounders. Conclusions: In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution. C1 [Marconi, Vincent C.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA 30322 USA. [Marconi, Vincent C.; Grandits, Greg; Okulicz, Jason F.; Wortmann, Glenn; Ganesan, Anuradha; Crum-Cianflone, Nancy; Polis, Michael; Landrum, Michael; Agan, Brian] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Grandits, Greg] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Okulicz, Jason F.; Landrum, Michael] Brooke Army Med Ctr, San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. [Wortmann, Glenn] Walter Reed Army Med Ctr, Infect Dis Serv, Washington, DC 20307 USA. [Ganesan, Anuradha] Natl Naval Med Ctr, Infect Dis Clin, Bethesda, MD USA. [Crum-Cianflone, Nancy] USN, Infect Dis Clin, San Diego Med Ctr, San Diego, CA 92152 USA. [Polis, Michael] NIAID, NIH, Bethesda, MD 20892 USA. [Dolan, Matthew J.] Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA. [Ahuja, Sunil K.; Kulkarni, Hemant] S Texas Vet Hlth Care Syst, Vet Adm Res Ctr AIDS & HIV 1 Infect, San Antonio, TX USA. [Ahuja, Sunil K.; Kulkarni, Hemant] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. RP Marconi, VC (reprint author), Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA 30322 USA. EM vcmarco@emory.edu; kulkarnih@uthscsa.edu RI Marconi, Vincent/N-3210-2014; OI Marconi, Vincent/0000-0001-8409-4689; Polis, Michael/0000-0002-9151-2268; Agan, Brian/0000-0002-5114-1669 FU Infectious Disease Clinical Research Program [IDCRP-000-03]; Department of Defense through the Uniformed Services University of the Health Sciences; National Institute of Allergy and Infectious Diseases, National Institutes of Health [Y1-AI-5072]; Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System; NIH [R37046326]; VA; Elizabeth Glaser Scientist Award; Burroughs Wellcome Clinical Scientist Award; Doris Duke Distinguished Clinical Scientist Award FX Support for this work (IDCRP-000-03) was provided by the Infectious Disease Clinical Research Program, a Department of Defense program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under Inter-Agency Agreement Y1-AI-5072. This work was also supported by the Veterans Administration Center on AIDS and HIV infection of the South Texas Veterans Health Care System, and a MERIT (R37046326) award from the NIH to SKA. SKA is also supported by a VA MERIT award and is a recipient of the Elizabeth Glaser Scientist Award, the Burroughs Wellcome Clinical Scientist Award in Translational Research, and the Doris Duke Distinguished Clinical Scientist Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 25 Z9 25 U1 2 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 20 PY 2011 VL 6 IS 5 AR e17956 DI 10.1371/journal.pone.0017956 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 766OI UT WOS:000290793400001 PM 21625477 ER PT J AU Heise, RL Stober, V Cheluvaraju, C Hollingsworth, JW Garantziotis, S AF Heise, Rebecca L. Stober, Vandy Cheluvaraju, Chaitra Hollingsworth, John W. Garantziotis, Stavros TI Mechanical Stretch Induces Epithelial-Mesenchymal Transition in Alveolar Epithelia via Hyaluronan Activation of Innate Immunity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; PULMONARY-FIBROSIS; TARGETED DISRUPTION; IN-VIVO; CELLS; MATRIX; CD44; DIFFERENTIATION; VENTILATION AB Epithelial injury is a central event in the pathogenesis of many inflammatory and fibrotic lung diseases like acute respiratory distress syndrome, pulmonary fibrosis, and iatrogenic lung injury. Mechanical stress is an often underappreciated contributor to lung epithelial injury. Following injury, differentiated epithelia can assume a myofibroblast phenotype in a process termed epithelial to mesenchymal transition (EMT), which contributes to aberrant wound healing and fibrosis. We demonstrate that cyclic mechanical stretch induces EMT in alveolar type II epithelial cells, associated with increased expression of low molecular mass hyaluronan (sHA). We show that sHA is sufficient for induction of EMT in statically cultured alveolar type II epithelial cells and necessary for EMT during cell stretch. Furthermore, stretch-induced EMT requires the innate immune adaptor molecule MyD88. We examined the Wnt/beta-catenin pathway, which is known to mediate EMT. The Wnt target gene Wnt-inducible signaling protein 1 (wisp-1) is significantly up-regulated in stretched cells in hyaluronan- and MyD88-dependent fashion, and blockade of WISP-1 prevents EMT in stretched cells. In conclusion, we show for the first time that innate immunity transduces mechanical stress responses through the matrix component hyaluronan, and activation of the Wnt/beta-catenin pathway. C1 [Heise, Rebecca L.; Stober, Vandy; Cheluvaraju, Chaitra; Garantziotis, Stavros] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Hollingsworth, John W.] Duke Univ, Dept Med, Med Ctr, Durham, NC 27710 USA. RP Garantziotis, S (reprint author), NIEHS, Lab Resp Biol, NIH, POB 12233,MD CU01, Res Triangle Pk, NC 27709 USA. EM garantziotis@niehs.nih.gov RI Heise, Rebecca/N-7797-2016; Garantziotis, Stavros/A-6903-2009 OI Heise, Rebecca/0000-0002-6602-6700; Garantziotis, Stavros/0000-0003-4007-375X FU National Institutes of Health [ES016126]; Division of Intramural Research, NIEHS/National Institutes of Health FX This work was supported, in whole or in part, by National Institutes of Health Grant ES016126 (to J. W. H.). This work was also supported by intramural funds from the Division of Intramural Research, NIEHS/National Institutes of Health (to S. G.). NR 54 TC 46 Z9 50 U1 2 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 2011 VL 286 IS 20 BP 17435 EP 17444 DI 10.1074/jbc.M110.137273 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763UM UT WOS:000290585200005 PM 21398522 ER PT J AU Boutz, DR Collins, PJ Suresh, U Lu, MZ Ramirez, CM Fernandez-Hernando, C Huang, YF Abreu, RD Le, SY Shapiro, BA Liu, AM Luk, JM Aldred, SF Trinklein, ND Marcotte, EM Penalva, LOF AF Boutz, Daniel R. Collins, Patrick J. Suresh, Uthra Lu, Mingzhu Ramirez, Cristina M. Fernandez-Hernando, Carlos Huang, Yufei Abreu, Raquel de Sousa Le, Shu-Yun Shapiro, Bruce A. Liu, Angela M. Luk, John M. Aldred, Shelley Force Trinklein, Nathan D. Marcotte, Edward M. Penalva, Luiz O. F. TI Two-tiered Approach Identifies a Network of Cancer and Liver Disease-related Genes Regulated by miR-122 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE PHOSPHATASES; HUMAN BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; TUMOR-SUPPRESSOR; MESSENGER-RNAS; IN-VIVO; STIMULATED PHOSPHORYLATION; THERAPEUTIC TARGETS; INSULIN SENSITIVITY; MICRORNA TARGETS AB MicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporter-based screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function. C1 [Boutz, Daniel R.; Marcotte, Edward M.] Univ Texas Austin, Ctr Syst & Synthet Biol, Inst Cellular & Mol Biol, Austin, TX 78712 USA. [Collins, Patrick J.; Aldred, Shelley Force; Trinklein, Nathan D.] SwitchGear Genom, Menlo Pk, CA 94025 USA. [Suresh, Uthra; Huang, Yufei; Abreu, Raquel de Sousa; Penalva, Luiz O. F.] Univ Texas Hlth Sci Ctr San Antonio, Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Lu, Mingzhu; Huang, Yufei] Univ Texas San Antonio, Dept Elect & Comp Engn, San Antonio, TX 78249 USA. [Ramirez, Cristina M.; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Med, Leon H Charney Div Cardiol, New York, NY 10016 USA. [Le, Shu-Yun; Shapiro, Bruce A.; Penalva, Luiz O. F.] NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21702 USA. [Liu, Angela M.; Luk, John M.] Univ Hong Kong, Queen Mary Hosp, Dept Surg, Hong Kong, Hong Kong, Peoples R China. [Liu, Angela M.; Luk, John M.] Natl Univ Singapore, Dept Pharmacol, Singapore 117597, Singapore. [Luk, John M.] Natl Univ Singapore, Dept Surg, Singapore 117597, Singapore. [Luk, John M.] Natl Univ Singapore, Canc Sci Inst, Singapore 117597, Singapore. [Marcotte, Edward M.] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA. [Penalva, Luiz O. F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Boutz, DR (reprint author), Univ Texas Austin, Ctr Syst & Synthet Biol, Inst Cellular & Mol Biol, 2500 Speedway,MBB 3-210, Austin, TX 78712 USA. EM dboutz@mail.utexas.edu; penalva@uthscsa.edu RI Luk, John/A-4085-2008; Boutz, Daniel/M-4872-2013; OI Luk, John/0000-0002-6323-7940; Boutz, Daniel/0000-0001-7462-4105; Ramirez, Cristina M/0000-0003-2589-0786 FU National Institutes of Health [GM076536, GM067779, GM088624]; Welch Foundation [F-1515]; Packard Foundation; NCI Center for Cancer Research; Children's Cancer Research Institute; University of Texas Health Science Center at San Antonio; SwitchGear Genomics FX This work was supported, in whole or in part, by National Institutes of Health Grants GM076536, GM067779, and GM088624, and Grant F-1515 from the Welch Foundation and by the Packard Foundation. (to E. M. M.) and the NCI Center for Cancer Research Intramural Research Program (to the B. A. S. laboratory). This work was also supported by the Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio (to the L. O. F. P. laboratory), and by SwitchGear Genomics. N. D. T., S. F. A., and P. J. C. are employees of and hold stock in SwitchGear Genomics. SwitchGear Genomics sells 3'UTR reporter vectors commercially. SwitchGear Genomics is the owner by assignment of patents or patent applications related to the 3'UTR reporter platform. NR 87 TC 32 Z9 36 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 2011 VL 286 IS 20 BP 18066 EP 18078 DI 10.1074/jbc.M110.196451 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763UM UT WOS:000290585200068 PM 21402708 ER PT J AU Tiso, M Tejero, J Basu, S Azarov, I Wang, XD Simplaceanu, V Frizzell, S Jayaraman, T Geary, L Shapiro, C Ho, C Shiva, S Kim-Shapiro, DB Gladwin, MT AF Tiso, Mauro Tejero, Jesus Basu, Swati Azarov, Ivan Wang, Xunde Simplaceanu, Virgil Frizzell, Sheila Jayaraman, Thottala Geary, Lisa Shapiro, Calli Ho, Chien Shiva, Sruti Kim-Shapiro, Daniel B. Gladwin, Mark T. TI Human Neuroglobin Functions as a Redox-regulated Nitrite Reductase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGAND-BINDING; MYOCARDIAL-ISCHEMIA; OXYGEN-AFFINITY; GLOBIN FAMILY; CYTOCHROME-C; BLOOD-CELLS; HEME; OXIDE; HEMOGLOBIN; CYTOGLOBIN AB Neuroglobin is a highly conserved hemoprotein of uncertain physiological function that evolved from a common ancestor to hemoglobin and myoglobin. It possesses a six-coordinate heme geometry with proximal and distal histidines directly bound to the heme iron, although coordination of the sixth ligand is reversible. We show that deoxygenated human neuroglobin reacts with nitrite to form nitric oxide (NO). This reaction is regulated by redox-sensitive surface thiols, cysteine 55 and 46, which regulate the fraction of the five-coordinated heme, nitrite binding, and NO formation. Replacement of the distal histidine by leucine or glutamine leads to a stable five-coordinated geometry; these neuroglobin mutants reduce nitrite to NO similar to 2000 times faster than the wild type, whereas mutation of either Cys-55 or Cys-46 to alanine stabilizes the six-coordinate structure and slows the reaction. Using lentivirus expression systems, we show that the nitrite reductase activity of neuroglobin inhibits cellular respiration via NO binding to cytochrome c oxidase and confirm that the six-to-five-coordinate status of neuroglobin regulates intracellular hypoxic NO-signaling pathways. These studies suggest that neuroglobin may function as a physiological oxidative stress sensor and a post-translationally redox-regulated nitrite reductase that generates NO under six-to-five-coordinate heme pocket control. We hypothesize that the six-coordinate heme globin superfamily may subserve a function as primordial hypoxic and redox-regulated NO-signaling proteins. C1 [Tiso, Mauro; Tejero, Jesus; Frizzell, Sheila; Jayaraman, Thottala; Geary, Lisa; Shapiro, Calli; Shiva, Sruti; Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA. [Basu, Swati; Azarov, Ivan; Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. [Simplaceanu, Virgil; Ho, Chien] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. [Wang, Xunde] NHLBI, NIH, Bethesda, MD 20892 USA. [Shiva, Sruti] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA. RP Gladwin, MT (reprint author), Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA. EM gladwinmt@upmc.edu RI Ho, Chien/O-6112-2016; OI Ho, Chien/0000-0002-4094-9232; Tejero, Jesus/0000-0003-3245-9978; Azarov, Ivan/0000-0002-9886-3298 FU National Institutes of Health [HL058091, GM084614, HL098032]; Institute for Transfusion Medicine, Hemophilia Center of Western Pennsylvania; American Heart Association [109SDG2150066] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL058091 (to D. B. K.-S.), GM084614 (to C. H.), and HL098032 (to M. T. G.). This work was also supported by Institute for Transfusion Medicine, Hemophilia Center of Western Pennsylvania (to M. T. G. and S. S.), and American Heart Association Grant 109SDG2150066 (to S. S.). M. Tiso, M. T. Gladwin, and D. B. Kim-Shapiro are listed as co-inventors on a patent application entitled "Neuroglobin as a Six-to-Five-coordinate Regulated Nitrite Reductase." NR 56 TC 116 Z9 118 U1 3 U2 31 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 2011 VL 286 IS 20 BP 18277 EP 18289 DI 10.1074/jbc.M110.159541 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763UM UT WOS:000290585200088 PM 21296891 ER PT J AU Giaccone, G Rajan, A Berman, A Kelly, RJ Szabo, E Lopez-Chavez, A Trepel, J Lee, MJ Cao, L Espinoza-Delgado, I Spittler, J Loehrer, PJ AF Giaccone, Giuseppe Rajan, Arun Berman, Arlene Kelly, Ronan J. Szabo, Eva Lopez-Chavez, Ariel Trepel, Jane Lee, Min-Jung Cao, Liang Espinoza-Delgado, Igor Spittler, John Loehrer, Patrick J., Sr. TI Phase II Study of Belinostat in Patients With Recurrent or Refractory Advanced Thymic Epithelial Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; REGULATORY T-CELLS; ADVANCED THYMOMA; SOLID TUMORS; CARCINOMA; TRICHOSTATIN; SYSTEM; TRIAL AB Purpose Thymic epithelial tumors are rare malignancies, and there is no standard treatment for patients with advanced disease in whom chemotherapy has failed. Antitumor activity of histone deacetylase (HDAC) inhibitors in this disease has been documented, including one patient with thymoma treated with the pan-HDAC inhibitor belinostat. Patients and Methods Patients with advanced thymic epithelial malignancies in whom at least one line of platinum-containing chemotherapy had failed were eligible for this study. Other eligibility criteria included adequate organ function and good performance status. Belinostat was administered intravenously at 1 g/m(2) on days 1 to 5 of a 21-day cycle until disease progression or development of intolerance. The primary objective was response rate in patients with thymoma. Results Of the 41 patients enrolled, 25 had thymoma, and 16 had thymic carcinoma; patients had a median of two previous systemic regimens (range, one to 10 regimens). Treatment was well tolerated, with nausea, vomiting, and fatigue being the most frequent adverse effects. Two patients achieved partial response (both had thymoma; response rate, 8%; 95% CI, 2.2% to 25%), 25 had stable disease, and 13 had progressive disease; there were no responses among patients with thymic carcinoma. Median times to progression and survival were 5.8 and 19.1 months, respectively. Survival of patients with thymoma was significantly longer than that of patients with thymic carcinoma (median not reached v 12.4 months; P = .001). Protein acetylation, regulatory T-cell numbers, and circulating angiogenic factors did not predict outcome. Conclusion Belinostat has modest antitumor activity in this group of heavily pretreated thymic malignancies. However, the duration of response and disease stabilization is intriguing, and additional testing of belinostat in this disease is warranted. C1 [Giaccone, Giuseppe] NCI, NIH, Med Oncol Branch, Bethesda, MD 20892 USA. Indiana Univ, Indianapolis, IN 46204 USA. RP Giaccone, G (reprint author), NCI, NIH, Med Oncol Branch, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 25 TC 60 Z9 65 U1 0 U2 2 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 MAY 20 PY 2011 VL 29 IS 15 BP 2052 EP 2059 DI 10.1200/JCO.2010.32.4467 PG 8 WC Oncology SC Oncology GA 765OC UT WOS:000290716900035 PM 21502553 ER PT J AU Keedy, VL Temin, S Somerfield, MR Beasley, MB Johnson, DH McShane, LM Milton, DT Strawn, JR Wakelee, HA Giaccone, G AF Keedy, Vicki Leigh Temin, Sarah Somerfield, Mark R. Beasley, Mary Beth Johnson, David H. McShane, Lisa M. Milton, Daniel T. Strawn, John R. Wakelee, Heather A. Giaccone, Giuseppe TI American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients With Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PLUS GEMCITABINE GEM; ACQUIRED-RESISTANCE; PHASE-III; ACTIVATING MUTATIONS; GENE-MUTATIONS; PATIENTS PTS; CTONG 0802; OPEN-LABEL; ERLOTINIB; GEFITINIB AB Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This PCO addresses the clinical utility of using epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small-cell lung cancer (NSCLC) to predict the benefit of taking a first-line EGFR tyrosine kinase inhibitor (TKI). Clinical Context Patients with EGFR-mutated NSCLC have a significantly higher rate of partial responses to the EGFR TKIs gefitinib and erlotinib. In the United States, approximately 15% of patients with adenocarcinoma of the lung harbor activating EGFR mutations. EGFR mutation testing is widespread at academic medical centers and in some locales in community practice. As of yet, there is no evidence of an overall survival (OS) benefit from selecting treatment based on performing this testing. Recent Data One large phase III trial (the Iressa Pan-Asia Study [IPASS] trial), three smaller phase III randomized controlled trials using progression-free survival as the primary end point, and one small phase III trial with OS as the primary end point, all involving first-line EGFR TKIs and chemotherapy doublets, form the basis of this PCO. Provisional Clinical Opinion On the basis of the results of five phase III randomized controlled trials, patients with NSCLC who are being considered for first-line therapy with an EGFR TKI (patients who have not previously received chemotherapy or an EGFR TKI) should have their tumor tested for EGFR mutations to determine whether an EGFR TKI or chemotherapy is the appropriate first-line therapy. NOTE. ASCO's provisional clinical opinions (PCOs) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and settings for further research. Because of the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical practice and cannot be assumed to apply to the use of these interventions in the context of clinical trials. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO's PCOs, or for any errors or omissions. C1 [Keedy, Vicki Leigh] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NCI, Bethesda, MD 20892 USA. Hematol Oncol Indiana, Indianapolis, IN USA. Stanford Univ, Stanford, CA 94305 USA. RP Keedy, VL (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU Genentech; AstraZeneca FX Employment or Leadership Position: None Consultant or Advisory Role: Heather A. Wakelee, Genentech (U) Stock Ownership: None Honoraria: None Research Funding: Daniel T. Milton, Genentech; Heather A. Wakelee, AstraZeneca, Genentech Expert Testimony: None Other Remuneration: None NR 21 TC 267 Z9 277 U1 4 U2 20 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 MAY 20 PY 2011 VL 29 IS 15 BP 2121 EP 2127 DI 10.1200/JCO.2010.31.8923 PG 7 WC Oncology SC Oncology GA 765OC UT WOS:000290716900044 PM 21482992 ER PT J AU Rhind, N Chen, ZH Yassour, M Thompson, DA Haas, BJ Habib, N Wapinski, I Roy, S Lin, MF Heiman, DI Young, SK Furuya, K Guo, YB Pidoux, A Chen, HM Robbertse, B Goldberg, JM Aoki, K Bayne, EH Berlin, AM Desjardins, CA Dobbs, E Dukaj, L Fan, L FitzGerald, MG French, C Gujja, S Hansen, K Keifenheim, D Levin, JZ Mosher, RA Muller, CA Pfiffner, J Priest, M Russ, C Smialowska, A Swoboda, P Sykes, SM Vaughn, M Vengrova, S Yoder, R Zeng, QD Allshire, R Baulcombe, D Birren, BW Brown, W Ekwall, K Kellis, M Leatherwood, J Levin, H Margalit, H Martienssen, R Nieduszynski, CA Spatafora, JW Friedman, N Dalgaard, JZ Baumann, P Niki, H Regev, A Nusbaum, C AF Rhind, Nicholas Chen, Zehua Yassour, Moran Thompson, Dawn A. Haas, Brian J. Habib, Naomi Wapinski, Ilan Roy, Sushmita Lin, Michael F. Heiman, David I. Young, Sarah K. Furuya, Kanji Guo, Yabin Pidoux, Alison Chen, Huei Mei Robbertse, Barbara Goldberg, Jonathan M. Aoki, Keita Bayne, Elizabeth H. Berlin, Aaron M. Desjardins, Christopher A. Dobbs, Edward Dukaj, Livio Fan, Lin FitzGerald, Michael G. French, Courtney Gujja, Sharvari Hansen, Klavs Keifenheim, Dan Levin, Joshua Z. Mosher, Rebecca A. Mueller, Carolin A. Pfiffner, Jenna Priest, Margaret Russ, Carsten Smialowska, Agata Swoboda, Peter Sykes, Sean M. Vaughn, Matthew Vengrova, Sonya Yoder, Ryan Zeng, Qiandong Allshire, Robin Baulcombe, David Birren, Bruce W. Brown, William Ekwall, Karl Kellis, Manolis Leatherwood, Janet Levin, Henry Margalit, Hanah Martienssen, Rob Nieduszynski, Conrad A. Spatafora, Joseph W. Friedman, Nir Dalgaard, Jacob Z. Baumann, Peter Niki, Hironori Regev, Aviv Nusbaum, Chad TI Comparative Functional Genomics of the Fission Yeasts SO SCIENCE LA English DT Article ID SCHIZOSACCHAROMYCES-POMBE; REPLICATION ORIGINS; GENES; HETEROCHROMATIN; CENTROMERE; RNAI; TRANSCRIPTOME; EXPRESSION; INTEGRITY; PROTEINS AB The fission yeast clade-comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus-occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade. C1 [Rhind, Nicholas; Dukaj, Livio; Keifenheim, Dan] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Chen, Zehua; Haas, Brian J.; Heiman, David I.; Young, Sarah K.; Goldberg, Jonathan M.; Berlin, Aaron M.; Desjardins, Christopher A.; Fan, Lin; FitzGerald, Michael G.; Gujja, Sharvari; Levin, Joshua Z.; Pfiffner, Jenna; Priest, Margaret; Russ, Carsten; Sykes, Sean M.; Zeng, Qiandong; Birren, Bruce W.; Nusbaum, Chad] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02141 USA. [Yassour, Moran; Thompson, Dawn A.; Wapinski, Ilan; Roy, Sushmita; Kellis, Manolis; Regev, Aviv] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA 02142 USA. [Yassour, Moran; Regev, Aviv] MIT, Dept Biol, Cambridge, MA 02139 USA. [Yassour, Moran; Habib, Naomi; Friedman, Nir] Hebrew Univ Jerusalem, Sch Engn & Comp Sci, IL-91904 Jerusalem, Israel. [Habib, Naomi; French, Courtney; Margalit, Hanah] Hebrew Univ Jerusalem, Fac Med, Dept Microbiol & Mol Genet, IL-91120 Jerusalem, Israel. [Wapinski, Ilan] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Roy, Sushmita; Lin, Michael F.; Kellis, Manolis] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Furuya, Kanji; Aoki, Keita; Niki, Hironori] Res Org Informat & Syst, Genet Strains Res Ctr, Natl Inst Genet, Microbial Genet Lab, Mishima, Shizuoka 4118540, Japan. [Guo, Yabin; Levin, Henry] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Pidoux, Alison; Bayne, Elizabeth H.; Dobbs, Edward; Allshire, Robin] Univ Edinburgh, Sch Biol Sci, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland. [Chen, Huei Mei; Leatherwood, Janet] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. [Robbertse, Barbara; Yoder, Ryan; Spatafora, Joseph W.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Hansen, Klavs; Vaughn, Matthew; Martienssen, Rob] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Mosher, Rebecca A.; Baulcombe, David] Univ Cambridge, Dept Plant Sci, Cambridge CB2 3EA, England. [Mueller, Carolin A.; Brown, William; Nieduszynski, Conrad A.] Univ Nottingham, Queens Med Ctr, Ctr Genet & Genom, Nottingham NG7 2UH, England. [Smialowska, Agata; Swoboda, Peter; Ekwall, Karl] Karolinska Inst, Dept Biosci & Nutr, Ctr Biosci, S-14138 Huddinge, Sweden. [Smialowska, Agata; Ekwall, Karl] Sodertorns Hgsk, Dept Life Sci, S-14189 Huddinge, Sweden. [Vengrova, Sonya; Dalgaard, Jacob Z.] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Friedman, Nir] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, IL-91904 Jerusalem, Israel. [Baumann, Peter] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Baumann, Peter] Univ Kansas, Sch Med, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA. [Baumann, Peter; Regev, Aviv] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Rhind, N (reprint author), Univ Massachusetts, Sch Med, 364 Plantat St, Worcester, MA 01605 USA. EM nick.rhind@umassmed.edu; aregev@broad.mit.edu; chad@broadinstitute.org RI Nieduszynski, Conrad/B-2170-2010; Mosher, Rebecca/F-4800-2010; Chen, Zehua/E-6356-2011; chen, zehua/H-1260-2011; Friedman, Nir/H-9692-2012; Bayne, Elizabeth/G-5411-2010; Margalit, Hanah/H-1651-2013; OI , Guo/0000-0001-8316-8527; Swoboda, Peter/0000-0001-6416-8572; Rhind, Nicholas/0000-0003-1758-7736; Baulcombe, David/0000-0003-0780-6878; Nieduszynski, Conrad/0000-0003-2001-076X; Dalgaard, Jacob/0000-0001-9545-7254; Mosher, Rebecca/0000-0003-2195-0825; Friedman, Nir/0000-0002-9678-3550; Bayne, Elizabeth/0000-0001-8775-999X; Vaughn, Matthew/0000-0002-1384-4283; Keifenheim, Daniel/0000-0002-4235-8903; Baumann, Peter/0000-0003-4892-1485 FU National Human Genome Research Institute (NHGRI), NIH; NHGRI; Clore Fellowship; NSF; NIH; Danish Research Council; Biotechnology and Biological Science Research Council; Stowers Institute; HHMI; National Institute of Child Health and Human Development, NIH; Sloan Foundation; Human Frontier Science Program; Career Award at the Scientific Interface from the Burroughs Wellcome Fund FX Assemblies and annotations are available at GenBank (S. octosporus, ABHY04000000; S. cryophilus, ACQJ02000000; S. japonicus, AATM02000000), the Broad Institute's Schizosaccharomyces Web site (www.broadinstitute.org/annotation/genome/schizosaccharomyces_group), which provides search and visualization tools and pomBase (www.pombase.org). The RNA-Seq and single-nucleotide polymorphism (SNP) data are at the National Center for Biological Information (NCBI), NIH, Sequence Read Archive (see table S42). The S. japonicus siRNA data sets are at NCBI GEO as GSE26902 and GSE27837. This work was supported by the National Human Genome Research Institute (NHGRI), NIH. C.N. and M.F.L. were supported by NHGRI; M.Y. was supported by a Clore Fellowship; I.W. is the Howard Hughes Medical Institute (HHMI) fellow of the Damon Runyon Cancer Research Foundation; S.R. was supported by NSF; R.M. was supported by NIH; K.H. was supported by Danish Research Council; C.A.N and C.A.M were supported by the Biotechnology and Biological Science Research Council; P.B. was supported by the Stowers Institute and HHMI; Y.G. and H.L. were supported by the National Institute of Child Health and Human Development, NIH; M.K. was supported by the NIH, an NSF CAREER award, and the Sloan Foundation; A.R. was supported by the Human Frontier Science Program, a Career Award at the Scientific Interface from the Burroughs Wellcome Fund, the Sloan Foundation, an NIH Director's PIONEER award and HHMI. We thank the Broad Institute Sequencing Platform; A. Fujiyama and A. Toyoda for generating DNA sequence; M. Lara and N. Stange-Thomann for developing molecular biology protocols; J. Robinson, M. Garber, and P. Muller for technical advice and support; A. Klar for providing S. pombe var. kambucha (SPK1820); L. Gaffney for assistance with the figures; K. Mar and J. Mwangi for administrative support; and C. Cuomo for comments on the manuscript. NR 43 TC 202 Z9 657 U1 7 U2 79 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 20 PY 2011 VL 332 IS 6032 BP 930 EP 936 DI 10.1126/science.1203357 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 766FO UT WOS:000290766600034 PM 21511999 ER PT J AU Abou-Alfa, GK Gansukh, B Chou, JF Shia, J Capanu, M Kalin, M Chen, HX Zojwalla, NJ Katz, S Reidy, DL Kelsen, DP Saltz, L AF Abou-Alfa, G. K. Gansukh, B. Chou, J. F. Shia, J. Capanu, M. Kalin, M. Chen, H. X. Zojwalla, N. J. Katz, S. Reidy, D. L. Kelsen, D. P. Saltz, L. TI Phase II study of cixutumumab (IMC-A12, NSC742460; C) in hepatocellular carcinoma (HCC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. CTEP Natl Canc Inst, Bethesda, MD USA. ImClone Syst, Branchburg, NJ USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 4043 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300454 PM 28020518 ER PT J AU Adelberg, D Apolo, AB Madan, RA Gulley, JL Pierpoint, A Kohler, DR Trepel, JB Steinberg, SM Price, D Leigh, BR Theuer, CP Figg, WD Dahut, WL AF Adelberg, D. Apolo, A. B. Madan, R. A. Gulley, J. L. Pierpoint, A. Kohler, D. R. Trepel, J. B. Steinberg, S. M. Price, D. Leigh, B. R. Theuer, C. P. Figg, W. D. Dahut, W. L. TI A phase I study of TRC105 (anti-CD105 monoclonal antibody) in metastatic castration-resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NIH, Mol Pharmacol Sect, Bethesda, MD 20892 USA. Tracon Pharmaceut Inc, San Diego, CA USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e15070 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303774 PM 28020420 ER PT J AU Ahmed, SR Cosgrove, D Ball, D Donehower, RC Nelkin, B Petito, E Downs, M Chen, HX Doyle, A Scardina, A Carducci, MA Azad, NS AF Ahmed, S. R. Cosgrove, D. Ball, D. Donehower, R. C. Nelkin, B. Petito, E. Downs, M. Chen, H. X. Doyle, A. Scardina, A. Carducci, M. A. Azad, N. S. TI A phase I, single-institution open-label, dose-escalation trial with an expansion cohort evaluating the safety and tolerability of AZD6244 and IMC-A12 in subjects with advanced solid malignancies. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NCI, CTEP, Bethesda, MD 20892 USA. NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS156 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304581 PM 28022975 ER PT J AU Alberts, SR Thibodeau, SN Sargent, DJ Mahoney, MR Sinicrope, F Shields, AF Chan, E Goldberg, RM Gill, S Kahlenberg, MS Quesenberry, JT Smyrk, TC Grothey, A Nair, G AF Alberts, S. R. Thibodeau, S. N. Sargent, D. J. Mahoney, M. R. Sinicrope, F. Shields, A. F. Chan, E. Goldberg, R. M. Gill, S. Kahlenberg, M. S. Quesenberry, J. T. Smyrk, T. C. Grothey, A. Nair, G. TI Influence of KRAS and BRAF mutational status and rash on disease-free survival (DFS) in patients with resected stage III colon cancer receiving cetuximab (Cmab): Results from NCCTG N0147 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Mayo Clin, Coll Med, Rochester, MN USA. Wayne State Univ, Natl Surg Adjuvant Breast & Bowel Project, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Vanderbilt Univ Sch Med, Nashville, TN USA. Univ N Carolina, Chapel Hill, NC USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. St Lukes Reg Med Ctr, Sioux City, IA USA. Lehigh Valley Hosp, Allentown, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3607 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300381 PM 28020864 ER PT J AU Allegra, CJ Yothers, GA O'Connell, MJ Sharif, S Petrelli, NJ Colangelo, LH Wolmark, N AF Allegra, C. J. Yothers, G. A. O'Connell, M. J. Sharif, S. Petrelli, N. J. Colangelo, L. H. Wolmark, N. TI Overall survival (OS) and updated disease-free survival (DFS) results of the NSABP C-08 trial assessing bevacizumab (B) in stage II and III colon cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NSABP, Newark, DE USA. Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3508 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300282 ER PT J AU Amir, E Cecchini, RS Ganz, PA Costantino, JP Beddows, S Hood, N Goodwin, PJ AF Amir, E. Cecchini, R. S. Ganz, P. A. Costantino, J. P. Beddows, S. Hood, N. Goodwin, P. J. TI 25-hydroxy vitamin D (VitD) and associated variables as predictors of breast cancer (BC) risk and tamoxifen benefit in NSABP-P1 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Princess Margaret Hosp, Div Med Oncol & Hematol, Toronto, ON M4X 1K9, Canada. Univ Toronto, Toronto, ON, Canada. Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 1528 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301143 PM 28024079 ER PT J AU Amiri-Kordestani, L Jawed, I Wilkerson, J Stein, WD Fojo, AT Swain, SM Bates, SE AF Amiri-Kordestani, L. Jawed, I. Wilkerson, J. Stein, W. D. Fojo, A. T. Swain, S. M. Bates, S. E. TI Early assessment of efficacy of ixabepilone (IXA) by analysis of the rate of tumor growth and decay using data from phase II and phase III clinical trials in metastatic breast cancer (MBC) patients (Pts). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, CCR, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Jerusalem, Israel. Washington Hosp Ctr, Washington Canc Inst, NSABP, Washington, DC 20010 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2527 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301342 PM 28022342 ER PT J AU Amoako, MO Merchant, MS Bernstein, DB Baird, K Mackall, C AF Amoako, M. O. Merchant, M. S. Bernstein, D. B. Baird, K. Mackall, C. TI Pilot immunotherapy trial in high-risk pediatric sarcomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Amoako, M. O.; Merchant, M. S.; Bernstein, D. B.; Baird, K.; Mackall, C.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 9541 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302564 PM 28019769 ER PT J AU Andreopoulou, E Chen, AP Zujewski, J Kim, M Hershman, DL Kalinsky, K Cigler, T Vahdat, LT Raptis, G Ramaswamy, B Novik, Y Muggia, F Sparano, JA AF Andreopoulou, E. Chen, A. P. Zujewski, J. Kim, M. Hershman, D. L. Kalinsky, K. Cigler, T. Vahdat, L. T. Raptis, G. Ramaswamy, B. Novik, Y. Muggia, F. Sparano, J. A. TI Randomized, double-blind, placebo-controlled phase II trial of low-dose metronomic cyclophosphamide alone or in combination with veliparib (ABT-888) in chemotherapy-resistant ER and/or PR-positive, HER2/neu-negative metastatic breast cancer: New York Cancer Consortium trial P8853. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. NCI, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Columbia Univ, Med Ctr, New York, NY USA. Weill Cornell Med Coll, New York, NY USA. Mt Sinai Sch Med, Dept Med Oncol, New York, NY USA. Ohio State Univ, Columbus, OH 43210 USA. NYU, Sch Med, New York, NY USA. NYU, Langone Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS114 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304539 PM 28022838 ER PT J AU Apolo, AB Tepede, A Reece, KM Price, DK Dahut, WL Figg, WD AF Apolo, A. B. Tepede, A. Reece, K. M. Price, D. K. Dahut, W. L. Figg, W. D. TI Impact of lenalidomide on the antiproliferative effect of gemcitabine/carboplatin (GC) and gemcitabine/cisplatin (GP) against urothelial carcinoma (UC) cells in vitro. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e15164 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304065 PM 28020891 ER PT J AU Argiris, A Kotsakis, AP Kim, S Worden, FP Savvides, P Gibson, MK Blumenschein, GR Chen, HX Grandis, JR Kies, MS AF Argiris, A. Kotsakis, A. P. Kim, S. Worden, F. P. Savvides, P. Gibson, M. K. Blumenschein, G. R. Chen, H. X. Grandis, J. R. Kies, M. S. TI Phase II trial of cetuximab (C) and bevacizumab (B) in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN): Final results. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. Cleveland Med Ctr, Univ Hosp, CASE Comprehens Canc Ctr, Cleveland, OH USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, CTEP, Bethesda, MD 20892 USA. RI Kotsakis, Athanasios/Q-4600-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5564 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301705 PM 28022138 ER PT J AU Balar, AV Milowsky, MI Apolo, AB Ostrovnaya, I Iasonos, A Trout, A Regazzi, AM Garcia-Grossman, IR Gallagher, DJ Bajorin, DF AF Balar, A. V. Milowsky, M. I. Apolo, A. B. Ostrovnaya, I. Iasonos, A. Trout, A. Regazzi, A. M. Garcia-Grossman, I. R. Gallagher, D. J. Bajorin, D. F. TI Phase II trial of gemcitabine, carboplatin, and bevacizumab (Bev) in patients (pts) with advanced/metastatic urothelial carcinoma (UC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 4566 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300607 PM 28023353 ER PT J AU Ball, ER Saloustros, ES Xekouki, P Horvath, A Assie, G Yehuda, S Stratakis, CA AF Ball, E. R. Saloustros, E. S. Xekouki, P. Horvath, A. Assie, G. Yehuda, S. Stratakis, C. A. TI Candidate gene analysis of gastrointestinal stromal tumors and paragangliomas in patients with carneys triad SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. INSERM, Inst Cochin, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e12018 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303205 PM 28021497 ER PT J AU Baruchel, S Wu, B Mokhtari, RB Bender, JLG DuBois, SG Widemann, BC Park, JR Stempak, D Ahern, CH Weigel, B AF Baruchel, S. Wu, B. Mokhtari, R. B. Bender, J. L. Glade DuBois, S. G. Widemann, B. C. Park, J. R. Stempak, D. Ahern, C. H. Weigel, B. TI Surrogate biomarkers of antiangiogenesis in Children's Oncology Group (COG) phase I trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Columbia Univ, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Seattle Childrens Hosp, Seattle, WA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 9502 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302526 PM 28019822 ER PT J AU Bauer, TM Bekaii-Saab, TS Li, X Villalona-Calero, MA Philip, PA Shields, AF Zalupski, MM Hammad, N El-Rayes, BF AF Bauer, T. M. Bekaii-Saab, T. S. Li, X. Villalona-Calero, M. A. Philip, P. A. Shields, A. F. Zalupski, M. M. Hammad, N. El-Rayes, B. F. TI CA19-9 for the prediction of efficacy of chemotherapy in patients with advanced pancreas cancer: A pooled analysis of six prospective trials. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Natl Surg Adjuvant Breast & Bowel Project, Detroit, MI USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Queens Univ, Canc Ctr Southeastern Ontario, Kingston, ON, Canada. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. RI Bekaii-Saab, Tanios/E-2733-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 4071 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300481 PM 28020465 ER PT J AU Bear, HD Tang, G Rastogi, P Geyer, CE Robidoux, A Atkins, JN Baez, L Brufsky, A Mehta, RS Fehrenbacher, L Pajon, ER Senecal, FM Gaur, R Margolese, RG Adams, PT Gross, HM Swain, SM Mamounas, EP Costantino, JP Wolmark, N AF Bear, H. D. Tang, G. Rastogi, P. Geyer, C. E. Robidoux, A. Atkins, J. N. Baez, L. Brufsky, A. Mehta, R. S. Fehrenbacher, L. Pajon, E. R. Senecal, F. M. Gaur, R. Margolese, R. G. Adams, P. T. Gross, H. M. Swain, S. M. Mamounas, E. P. Costantino, J. P. Wolmark, N. TI The effect on pCR of bevacizumab and/or antimetabolites added to standard neoadjuvant chemotherapy: NSABP protocol B-40. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Virginia Commonwealth Univ, Masey Canc Ctr, Richmond, VA USA. NSABBP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Magee Womens Canc Program, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. CHUM Hotel Dieu, Montreal, PQ, Canada. SCCC CCOP, Winston Salem, NC USA. San Juan MBCCOP, San Juan, PR USA. Univ Calif Irvine, Irvine Sch Med, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA. Kaiser Permanente No Calif, Vallejo, CA USA. Colorado Canc Res Program, Denver, CO USA. Northwest Med Specialties, Tacoma, WA USA. Kansas City CCOP, Kansas City, KS USA. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. Genesys Reg Med Ctr, Flint, MI USA. Dayton CCOP, Dayton, OH USA. Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. Natl Surg Adjuvant Breast & Bowel Project, Canton, OH USA. Aultman Hlth Fdn, Canton, OH USA. Univ Pittsburgh, Grad Sch Publ Hlth, Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA LBA1005 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300144 ER PT J AU Beckjord, EB Rechis, R Shulman, LN Hesse, B AF Beckjord, E. B. Rechis, R. Shulman, L. N. Hesse, B. TI Perspectives on electronic health information exchange among people affected by cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. LIVESTRONG, Austin, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 6123 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302001 PM 28022502 ER PT J AU Bender, JLG Lee, A Adamson, PC Ingle, AM Ahern, CH Wu, B Baruchel, S Harris, PJ Ames, MM Weigel, B Blaney, S AF Bender, J. L. Glade Lee, A. Adamson, P. C. Ingle, A. M. Ahern, C. H. Wu, B. Baruchel, S. Harris, P. J. Ames, M. M. Weigel, B. Blaney, S. CA Children's Oncology Grp TI Phase I study of pazopanib in children with relapsed or refractory solid tumors (ADVL0815): A Children's Oncology Group Phase I Consortium Trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Oncol Grp, Arcadia, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. NCI, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. Univ Minnesota, Minneapolis, MN USA. Texas Childrens Canc Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 9501 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302525 ER PT J AU Berkowitz, JL Fernandez, A Dichmann, R Kennedy, KA DiCarlo, BA AF Berkowitz, J. L. Fernandez, A. Dichmann, R. Kennedy, K. A. DiCarlo, B. A. TI Clinical trials networks, accrual strategies, and enrollment of historically underrepresented populations in medical oncology trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Cent Coast Med Oncol, Santa Maria, CA USA. Cent Coast Med Oncology Corp, Santa Maria, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e16549 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304262 PM 28022055 ER PT J AU Blagoev, KB Wilkerson, J Stein, WD Motzer, RJ Bates, SE Fojo, AT AF Blagoev, K. B. Wilkerson, J. Stein, W. D. Motzer, R. J. Bates, S. E. Fojo, A. T. TI Effect of sunitinib (SU) administration on post-treatment survival in patients with metastatic renal cell carcinoma (mRCC) treated on the upfront randomized phase III trial of sunitinib or interferon alfa (IFN). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Natl Sci Fdn, Arlington, VA 22230 USA. NCI, Med Oncol Branch, CCR, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Jerusalem, Israel. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 4634 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300674 PM 28023954 ER PT J AU Buys, SS Partridge, E Black, A Johnson, C Lamerato, L Isaacs, C Reding, D Greenlee, R Kessel, B Fouad, M Chia, D Ragard, L Rathmell, J Hartge, P Pinsky, P Izmirlian, G Xu, J Prorok, P Berg, CD AF Buys, S. S. Partridge, E. Black, A. Johnson, C. Lamerato, L. Isaacs, C. Reding, D. Greenlee, R. Kessel, B. Fouad, M. Chia, D. Ragard, L. Rathmell, J. Hartge, P. Pinsky, P. Izmirlian, G. Xu, J. Prorok, P. Berg, C. D. TI Effect of screening on ovarian cancer mortality in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer randomized screening trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Alabama Birmingham, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. Henry Ford Hlth Syst, Detroit, MI USA. Henry Ford Hosp, Detroit, MI 48202 USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. Marshfield Clin Res Fdn, Marshfield, WI USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. Pacific Hlth Res Educ Inst, Honolulu, HI USA. Minor Hlth & Hlth Dispar Res Ctr, Birmingham, AL USA. Dept Pathol & Lab Med, Los Angeles, CA USA. Westat Corp, Rockville, MD USA. Informat Management Serv Inc, Bethesda, MD USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RI Berg , Christine/K-1047-2014 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5001 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301537 PM 28023771 ER PT J AU Chapman, JW O'Callaghan, C Hu, N Ding, K Yothers, GA Catalano, PJ Shi, Q Gray, RG O'Connell, MJ Sargent, DJ AF Chapman, J. W. O'Callaghan, C. Hu, N. Ding, K. Yothers, G. A. Catalano, P. J. Shi, Q. Gray, R. G. O'Connell, M. J. Sargent, D. J. CA ACCENT Collaborative Grp TI Comparison of innovative estimation of efficacy to standard using the ACCENT database SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Queens Univ, NCIC Clin Trials Grp, Kingston, ON, Canada. NCIC Clin Trials Grp, Kingston, ON, Canada. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Oxford, Oxford, England. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3616 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300390 PM 28020847 ER PT J AU Chaturvedi, A Engels, E Pfeiffer, R Hernandez, BY Xiao, W Kim, E Jiang, B Goodman, M Sibug-Saber, M Cozen, W Liu, L Lynch, C Wentzensen, N Jordan, R Altekruse, S Anderson, WF Rosenberg, P Gillison, ML AF Chaturvedi, A. Engels, E. Pfeiffer, R. Hernandez, B. Y. Xiao, W. Kim, E. Jiang, B. Goodman, M. Sibug-Saber, M. Cozen, W. Liu, L. Lynch, C. Wentzensen, N. Jordan, R. Altekruse, S. Anderson, W. F. Rosenberg, P. Gillison, M. L. TI Human papillomavirus (HPV) and rising oropharyngeal cancer incidence and survival in the United States. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Canc Res Ctr Hawaii, Honolulu, HI USA. Ohio State Univ, Columbus, OH 43210 USA. Univ So Calif, Los Angeles, CA USA. Univ Iowa, Iowa City, IA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NCI, Dept Hlth & Human Serv, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5529 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301673 PM 28021397 ER PT J AU De Groot, JF Cloughesy, T Lieberman, FS Chang, SM Omuro, AMP Drappatz, J Batchelor, T DeAngelis, LM Gilbert, MR Yung, WKA Fisher, JD Ye, X Lamborn, K Chen, AP Grossman, SA Prados, M Wen, PY AF De Groot, J. F. Cloughesy, T. Lieberman, F. S. Chang, S. M. Omuro, A. M. P. Drappatz, J. Batchelor, T. DeAngelis, L. M. Gilbert, M. R. Yung, W. K. A. Fisher, J. D. Ye, X. Lamborn, K. Chen, A. P. Grossman, S. A. Prados, M. Wen, P. Y. TI Phase I study of aflibercept (VEGF Trap) and temozolomide in newly diagnosed, high-grade glioma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Med Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2043 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301259 PM 28023799 ER PT J AU Deeken, JF Rudek, MA Aboulafia, DM Sullivan, RJ Gerecitano, JF Cianfrocca, ME Henry, DH Ratner, L Dezube, BJ Mosby, K Tibbals, M Little, RF Ivy, SP Moore, PC Mitsuyasu, RT AF Deeken, J. F. Rudek, M. A. Aboulafia, D. M. Sullivan, R. J. Gerecitano, J. F. Cianfrocca, M. E. Henry, D. H. Ratner, L. Dezube, B. J. Mosby, K. Tibbals, M. Little, R. F. Ivy, S. P. Moore, P. C. Mitsuyasu, R. T. TI AIDS malignancy consortium (AMC) study 061: A phase I/PK study of sunitinib (S) with highly active antiretroviral therapy (HAART) in HIV plus patients with solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Northwestern Univ, Chicago, IL 60611 USA. Penn Hosp, Philadelphia, PA 19107 USA. Washington Univ, St Louis, MO USA. EMMES Corp, Rockville, MD USA. NCI, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Calif Los Angeles, Care Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2591 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301406 PM 28022235 ER PT J AU Dilts, DM Cheng, SK Wiltrout, RH Dahut, WL Bronez, M Helman, LJ AF Dilts, D. M. Cheng, S. K. Wiltrout, R. H. Dahut, W. L. Bronez, M. Helman, L. J. TI Strategic alignment of clinical trials at the National Cancer Institute Center for Cancer Research: Development of the clinical mission and baseline portfolio metrics SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NCI, Frederick, MD 21701 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e16619 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304324 PM 28022808 ER PT J AU DiPiazza, K Souhan, E Finnigan, S Denicoff, A Friedman, S Montello, M Mooney, MM Schettino, P Zwiebel, JA Doroshow, JH Abrams, JS AF DiPiazza, K. Souhan, E. Finnigan, S. Denicoff, A. Friedman, S. Montello, M. Mooney, M. M. Schettino, P. Zwiebel, J. A. Doroshow, J. H. Abrams, J. S. TI The Cancer Therapy Evaluation Program's (CTEP) implementation of the Operational Efficiency Working Group (OEWG) recommendations. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 EMMES Corp, Rockville, MD USA. NCI, Rockville, MD USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 6113 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301788 PM 28022518 ER PT J AU Dookeran, KA Ferrer, K Sekosan, M Holloway, N McCaskill-Stevens, WJ Gehlert, SJ AF Dookeran, K. A. Ferrer, K. Sekosan, M. Holloway, N. McCaskill-Stevens, W. J. Gehlert, S. J. TI The influence of sociodemographic factors on breast cancer tumor biology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Canc Fdn Minor & Underserved Populat, Chicago, IL USA. Stroger Hosp, Dept Pathol, Chicago, IL USA. John H Stroger Hosp Cook Cty, Chicago, IL USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. Washington Univ, Brown Sch, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 1552 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301167 ER PT J AU Duchnowska, R Jassem, J Szutowicz, E Biernat, W Jankowski, T Och, W Staszkiewicz, R Chudzik, M Rogowski, W Flores, N Woditschka, S Li, L Goswami, C Thorat, MA Gokmen-Polar, Y Sledge, GW Steeg, PS Palmieri, D Badve, SS AF Duchnowska, R. Jassem, J. Szutowicz, E. Biernat, W. Jankowski, T. Och, W. Staszkiewicz, R. Chudzik, M. Rogowski, W. Flores, N. Woditschka, S. Li, L. Goswami, C. Thorat, M. A. Gokmen-Polar, Y. Sledge, G. W. Steeg, P. S. Palmieri, D. Badve, S. S. TI RAD51 and brain metastases (BM) in patients (pts) with HER2+breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mil Inst Med, Warsaw, Poland. Med Univ Gdansk, Gdansk, Poland. Med Univ, Gdansk, Poland. Reg Canc Ctr, Lublin, Poland. Reg Hosp, Olsztyn, Poland. Reg Oncol Ctr, Olsztyn, Poland. Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland. Inst Oncol, Warsaw, Poland. NCI, Womens Canc Sect, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Indiana Univ Sch Med, Indianapolis, IN 46202 USA. Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. CRUK Ctr Epidemiol, Wolfson Inst Prevent Med, London, England. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 634 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300002 PM 28020595 ER PT J AU Fisch, M Lee, J Weiss, M Wagner, LI Chang, VT Cella, D Manola, J Minasian, LM McCaskill-Stevens, WJ Mendoza, TR Cleeland, CS AF Fisch, M. Lee, J. Weiss, M. Wagner, L. I. Chang, V. T. Cella, D. Manola, J. Minasian, L. M. McCaskill-Stevens, W. J. Mendoza, T. R. Cleeland, C. S. TI Prospective and observational study of pain and analgesic prescribing in medical oncology outpatients with breast, colorectal, lung, or prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Marshfield Clin Minocqua Ctr, Minocqua, WI USA. Northwestern Univ, Chicago, IL 60611 USA. VA New Jersey Hlth Care Syst, E Orange, NJ USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NCI, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 6008 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301742 PM 28022009 ER PT J AU Forsythe, LP Arora, N Weaver, KE Potosky, AL Alfano, CM Aziz, N Hamilton, AS Rowland, JH AF Forsythe, L. P. Arora, N. Weaver, K. E. Potosky, A. L. Alfano, C. M. Aziz, N. Hamilton, A. S. Rowland, J. H. TI Patterns of post-treatment care among non-Hodgkin lymphoma (NHL) survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Wake Forest Univ Hlth Sci, Dept Social Sci & Hlth Policy, Div Publ Hlth Sci, Winston Salem, NC USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. NINR, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA USA. NCI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e19512 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302661 PM 28020876 ER PT J AU Gadgeel, SM Ruckdeschel, JC Wozniak, AJ Chen, W Hackstock, D Galasso, C Burger, A Ivy, SP LoRusso, P Edelman, MJ AF Gadgeel, S. M. Ruckdeschel, J. C. Wozniak, A. J. Chen, W. Hackstock, D. Galasso, C. Burger, A. Ivy, S. P. LoRusso, P. Edelman, M. J. TI Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Karmanos Canc Inst, Detroit, MI USA. Nevada Canc Inst, Las Vegas, NV USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. NCI, Bethesda, MD 20892 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 7564 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302290 PM 28023152 ER PT J AU Gandara, DR Van Dyke, TA Ohler, ZW Li, T Lara, P Mack, PC Calhoun, RF Gandour-Edwards, R Danenberg, KD White, RD Goodwin, N AF Gandara, D. R. Van Dyke, T. A. Ohler, Z. Weaver Li, T. Lara, P. Mack, P. C. Calhoun, R. F. Gandour-Edwards, R. Danenberg, K. D. White, R. de Vere Goodwin, N. TI Integrated research platform (iGXT) for enhancing drug development and personalizing cancer therapy: Pilot study results. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Calif Davis, Sacramento, CA 95817 USA. NCI, Ctr Adv Preclin Res, Frederick, MD 21701 USA. Response Genet Inc, Los Angeles, CA USA. Jackson Lab, Sacramento, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3053 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301482 PM 28022591 ER PT J AU Garrido-Laguna, I Kurzrock, R Wheler, JJ Falchook, GS Piha-Paul, SA Fu, S Naing, A Hinojosa, C Mistry, R Scamardo, A Culotta, KS Ekmekcioglu, S Wen, S Camacho, LH Ivy, SP Hong, DS AF Garrido-Laguna, I. Kurzrock, R. Wheler, J. J. Falchook, G. S. Piha-Paul, S. A. Fu, S. Naing, A. Hinojosa, C. Mistry, R. Scamardo, A. Culotta, K. S. Ekmekcioglu, S. Wen, S. Camacho, L. H. Ivy, S. P. Hong, D. S. TI Dual inhibition of VEGF pathway: Phase I trial of bevacizumab and cediranib in advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Program 1, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Houston, TX 77030 USA. Oncol Consultants, Houston, TX USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3065 PG 2 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301494 PM 28022565 ER PT J AU Goetz, MP Reid, JM Qi, Y Chen, A McGovern, RM Kuffel, MJ Scanlon, PD Erlichman, C Ames, MM AF Goetz, M. P. Reid, J. M. Qi, Y. Chen, A. McGovern, R. M. Kuffel, M. J. Scanlon, P. D. Erlichman, C. Ames, M. M. TI A phase I study of once-weekly aminoflavone prodrug (AFP464) in solid tumor patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mayo Clin, Coll Med, Rochester, MN USA. Mayo Clin, Rochester, MN USA. NCI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2546 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301361 PM 28022321 ER PT J AU Gramza, AW Wells, SA Balasubramaniam, S Fojo, AT AF Gramza, A. W. Wells, S. A. Balasubramaniam, S. Fojo, A. T. TI Phase I/II trial of vandetanib and bortezomib in adults with locally advanced or metastatic medullary thyroid cancer: Phase I results. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Gramza, A. W.; Wells, S. A.; Balasubramaniam, S.; Fojo, A. T.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5565 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301706 PM 28022147 ER PT J AU Grant, C Dunleavy, K Tweito, M Steinberg, SM Pittaluga, S Jaffe, ES Wiestner, A Wilson, WH AF Grant, C. Dunleavy, K. Tweito, M. Steinberg, S. M. Pittaluga, S. Jaffe, E. S. Wiestner, A. Wilson, W. H. TI Bortezomib plus DA-EPOCH-rituximab followed by bortezomib maintenance versus observation in previously untreated mantle cell lymphoma (MCL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 8022 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302343 PM 28022964 ER PT J AU Grubbs, SS Go, RS Berger, MZ Gonzalez, M Thompson, MA Enos, R St Germain, DC Denicoff, A Servididio, C Bearden, JD Zaren, H Wilkinson, K Krasna, M McCaskill-Stevens, W Bell, M Freeman, RK Miesfeldt, S Ravikumar, TS Nair, SG Bashey, A AF Grubbs, S. S. Go, R. S. Berger, M. Z. Gonzalez, M. Thompson, M. A. Enos, R. St Germain, D. C. Denicoff, A. Servididio, C. Bearden, J. D. Zaren, H. Wilkinson, K. Krasna, M. McCaskill-Stevens, W. Bell, M. Freeman, R. K. Miesfeldt, S. Ravikumar, T. S. Nair, S. G. Bashey, A. TI Early success in narrowing age, gender, and racial disparities in clinical trial accrual: Targeted screening efforts through the National Cancer Institute Community Cancer Centers Program (NCCCP). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Christiana Care, Helen Graham Canc Ctr, Newark, DE USA. Gundersen Lutheran Canc Ctr, La Crosse, WI USA. Mary Bird Perkins Canc Ctr, Baton Rouge, LA USA. St Joseph Hosp, Orange, CA USA. ProHlth Reg Canc Ctr, Waukesha, WI USA. EMMES Corp, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. NCI, Rockville, MD USA. Hartford Hosp, Hartford, CT 06115 USA. Gibbs Canc Ctr, Spartanburg, SC USA. St Josephs Candler Hlth Syst Inc, Savannah, GA USA. Billings Clin, Billings, MT USA. St Joseph Med Ctr, Towson, MD USA. Community Oncol & Prevent Trials Res Grp, Rockville, MD USA. Sanford USD Med Ctr, Sioux Falls, SD USA. St Vincent Hlth & Hosp Syst, Indianapolis, IN USA. Maine Med Ctr, Inst Canc, Scarborough, ME USA. Geisinger Wyoming Valley Med Ctr, Danville, PA USA. Lehigh Valley Hosp, Allentown, PA USA. BMT Grp Georgia, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 6110 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301003 PM 28022513 ER PT J AU Hassan, R Sharon, E Schuler, B Mallory, Y Zhang, J Ling, A Pastan, I AF Hassan, R. Sharon, E. Schuler, B. Mallory, Y. Zhang, J. Ling, A. Pastan, I. TI Antitumor activity of SS1P with pemetrexed and cisplatin for front-line treatment of pleural mesothelioma and utility of serum mesothelin as a marker of tumor response. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 4 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 7026 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302165 PM 28020067 ER PT J AU Hays, JL Kim, G Mariani, J Murphy, RF Angelos, M McCollum, A Lu, J Widemann, BC Lee, J Kohn, EC AF Hays, J. L. Kim, G. Mariani, J. Murphy, R. F. Angelos, M. McCollum, A. Lu, J. Widemann, B. C. Lee, J. Kohn, E. C. TI Sequence specific effects on DNA and cell damage with the PARP inhibitor olaparib (AZD2281) and carboplatin. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Mol Signaling Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5025 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301558 PM 28023735 ER PT J AU Heery, CR Pinto, PA Schlom, J Tsang, KY Madan, RA Poole, D Vergati, M Rodriguez, BW Merino, M Gulley, JL AF Heery, C. R. Pinto, P. A. Schlom, J. Tsang, K. Y. Madan, R. A. Poole, D. Vergati, M. Rodriguez, B. Walter Merino, M. Gulley, J. L. TI Intraprostatic PSA-TRICOM vaccine administration in patients with locally recurrent prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD USA. NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Lab Tumor Immunol & Biol, Bethesda, MD USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2530 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301345 PM 28022325 ER PT J AU Hipp, SJ Steffen-Smith, EA Herscovitch, P Patronas, NJ Solomon, JM Bent, R Steinberg, SM Warren, KE AF Hipp, S. J. Steffen-Smith, E. A. Herscovitch, P. Patronas, N. J. Solomon, J. M. Bent, R. Steinberg, S. M. Warren, K. E. TI A comparative study of pediatric CNS tumor activity as assessed by [18F]-FDG PET imaging and proton magnetic resonance spectroscopic imaging. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. Med Numer Inc, Germantown, MD USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2101 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301315 PM 28020003 ER PT J AU Huang, X Ning, YM Mulquin, M Madan, RA Gulley, JL Kluetz, PG Adelberg, D Arlen, PM Parnes, HL Adesunloye, B Steinberg, SM Wright, JJ Trepel, JB Chen, C Bassim, C Apolo, AB Figg, WD Dahut, WL AF Huang, X. Ning, Y. M. Mulquin, M. Madan, R. A. Gulley, J. L. Kluetz, P. G. Adelberg, D. Arlen, P. M. Parnes, H. L. Adesunloye, B. Steinberg, S. M. Wright, J. J. Trepel, J. B. Chen, C. Bassim, C. Apolo, A. B. Figg, W. D. Dahut, W. L. TI Phase II trial of bevacizumab (A), lenalidomide (R), docetaxel (D), and prednisone (P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, US FDA, Silver Spring, MD USA. Neogenix Oncol Inc, Rockville, MD USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Rockville, MD USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA. Natl Inst Dent & Craniolfacial Res, NIH, Bethesda, MD USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 4574 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300615 PM 28023318 ER PT J AU Jasinski, S Wang, E Dressler, S Lichtenfels, R Recktenwald, C Marincola, F Seliger, B AF Jasinski, S. Wang, E. Dressler, S. Lichtenfels, R. Recktenwald, C. Marincola, F. Seliger, B. TI Altered expression proteins involved in cytoskeletal formation and metabolic pathways in renal cell carcinoma linked to microRNA expression. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Halle Wittenberg, Inst Med Immunol, D-06108 Halle, Germany. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e15125 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304029 PM 28021195 ER PT J AU Jatana, K Balasubramanian, P Lang, JC Teknos, TN Schuller, DE Chalmers, JJ AF Jatana, K. Balasubramanian, P. Lang, J. C. Teknos, T. N. Schuller, D. E. Chalmers, J. J. TI Correlation of circulating tumor cells in SCCNH patients to cancer reoccurrence using a negative enrichment technology. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. NCI, Columbus, OH USA. Ohio State Univ, Med Ctr, James Canc Hosp, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5511 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301656 PM 28021419 ER PT J AU Jawed, I Amiri-Kordestani, L Velarde, M Adams, K Balasubramaniam, S Reynolds, J Pacak, K Fojo, AT AF Jawed, I. Amiri-Kordestani, L. Velarde, M. Adams, K. Balasubramaniam, S. Reynolds, J. Pacak, K. Fojo, A. T. TI High efficacy and continued tumor shrinkage with cyclophosphamide, vincristine, and dacarbazine (CVD) in patients (Pts) with malignant pheochromocytoma/paraganglioma harboring succinate dehydrogenase subunit B (SDHB) mutations. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2526 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301341 PM 28022341 ER PT J AU Jolles, PR Kostakoglu, L Bear, HD Idowu, MO Kurdziel, KA Shankar, L Mankoff, DA Duan, F L'Heureux, D AF Jolles, P. R. Kostakoglu, L. Bear, H. D. Idowu, M. O. Kurdziel, K. A. Shankar, L. Mankoff, D. A. Duan, F. L'Heureux, D. TI ACRIN 6688 phase II study of fluorine-18 3 '-deoxy-3 ' fluorothymidine (FLT) in invasive breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Virginia Commonwealth Univ, Richmond, VA USA. Mt Sinai Sch Med, New York, NY USA. Virginia Commonwealth Univ, Masey Canc Ctr, Richmond, VA USA. NCI, Mol Imaging Program, Bethesda, MD 20892 USA. NCI, Canc Imaging Program, Rockville, MD USA. Univ Washington, Seattle, WA 98195 USA. Brown Univ, Providence, RI 02912 USA. Amer Coll Radiol, Philadelphia, PA USA. RI Duan, Fenghai/J-3709-2014 OI Duan, Fenghai/0000-0002-5084-0070 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS125 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304550 PM 28022932 ER PT J AU Julian, TB Costantino, JP Vicini, FA White, JR Winter, KA Arthur, DW Kuske, RR Rabinovitch, R Parda, DS Mamounas, EP Curran, WJ Wolmark, N AF Julian, T. B. Costantino, J. P. Vicini, F. A. White, J. R. Winter, K. A. Arthur, D. W. Kuske, R. R. Rabinovitch, R. Parda, D. S. Mamounas, E. P. Curran, W. J. Wolmark, N. TI Early toxicity results with 3D conformal external beam therapy (CEBT) from the NSABP B-39/RTOG 0413 accelerated partial breast irradiation (APBI) trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Radiat Therapy Oncol Grp, Milwaukee, WI USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RTOG Stat Ctr, Philadelphia, PA USA. Virginia Commonwealth Univ, Richmond, VA USA. Arizona Breast Canc Specialists, Scottsdale, AZ USA. Univ Colorado, Aurora, CO USA. Aultman Hlth Fdn, Canton, OH USA. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 1011 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300150 ER PT J AU Katki, HA Kinney, WK Fetterman, B Lorey, T Poitras, NE Cheung, L Demuth, F Schiffman, M Wacholder, S Castle, PE AF Katki, H. A. Kinney, W. K. Fetterman, B. Lorey, T. Poitras, N. E. Cheung, L. Demuth, F. Schiffman, M. Wacholder, S. Castle, P. E. TI Cervical cancer risk for 330,000 women undergoing concurrent HPV testing and cervical cytology in routine clinical practice. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA. Kaiser Permanente No Calif, Oakland, CA USA. Kaiser Permanente No Calif, Sacramento, CA USA. Kaiser Permanente No Calif, Berkeley, CA USA. Informat Management Serv Inc, Silver Spring, MD USA. Amer Soc Clin Pathologists, Washington, DC USA. RI Katki, Hormuzd/B-4003-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 1508 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301123 PM 28023624 ER PT J AU Kelly, RJ Rajan, A Chun, G Lopez-Chavez, A Giaccone, G AF Kelly, R. J. Rajan, A. Chun, G. Lopez-Chavez, A. Giaccone, G. TI A phase I study of paclitaxel, carboplatin, and YM155 (survivin suppressor) in subjects with solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Kelly, R. J.; Rajan, A.; Chun, G.; Lopez-Chavez, A.; Giaccone, G.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3090 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301519 ER PT J AU Kim, HK Kim, CH Kim, J Choi, IJ Munroe, DJ Green, JE AF Kim, H. K. Kim, C. H. Kim, J. Choi, I. J. Munroe, D. J. Green, J. E. TI An evaluation of microRNA signature and response of patients with gastric cancer to cisplatin and fluorouracil SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Natl Canc Ctr, Goyang, South Korea. NCI, SAIC, Frederick, MD 21701 USA. NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 4062 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300472 PM 28020478 ER PT J AU Kohn, EC Lee, J Annunziata, CM Minasian, LM Zujewski, J Prindiville, SA Kotz, HL Squires, J Houston, ND Chen, HX Wright, JJ AF Kohn, E. C. Lee, J. Annunziata, C. M. Minasian, L. M. Zujewski, J. Prindiville, S. A. Kotz, H. L. Squires, J. Houston, N. D. Chen, H. X. Wright, J. J. TI A phase II study of intermittent sorafenib with bevacizumab in bevacizumab-naive epithelial ovarian cancer (EOC) patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Mol Signaling Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Coordinating Ctr Clin Trials, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, CTEP, Bethesda, MD 20892 USA. NCI, Rockville, MD USA. RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5019 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301552 ER PT J AU Kris, MG Johnson, BE Kwiatkowski, DJ Iafrate, AJ Wistuba, II Aronson, SL Engelman, JA Shyr, Y Khuri, FR Rudin, CM Garon, EB Pao, W Schiller, JH Haura, EB Shirai, K Giaccone, G Berry, LD Kugler, K Minna, JD Bunn, PA AF Kris, M. G. Johnson, B. E. Kwiatkowski, D. J. Iafrate, A. J. Wistuba, I. I. Aronson, S. L. Engelman, J. A. Shyr, Y. Khuri, F. R. Rudin, C. M. Garon, E. B. Pao, W. Schiller, J. H. Haura, E. B. Shirai, K. Giaccone, G. Berry, L. D. Kugler, K. Minna, J. D. Bunn, P. A. TI Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: The NCI's Lung Cancer Mutation Consortium (LCMC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Partners Hlth Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NCI, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN 37235 USA. Univ Colorado, Canc Ctr Denver, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA CRA7506 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302766 ER PT J AU Kris, MG Johnson, BE Kwiatkowski, DJ Iafrate, AJ Wistuba, II Aronson, SL Engelman, JA Shyr, Y Khuri, FR Rudin, CM Garon, EB Pao, W Schiller, JH Haura, EB Shirai, K Giaccone, G Berry, LD Kugler, K Minna, JD Bunn, PA AF Kris, M. G. Johnson, B. E. Kwiatkowski, D. J. Iafrate, A. J. Wistuba, I. I. Aronson, S. L. Engelman, J. A. Shyr, Y. Khuri, F. R. Rudin, C. M. Garon, E. B. Pao, W. Schiller, J. H. Haura, E. B. Shirai, K. Giaccone, G. Berry, L. D. Kugler, K. Minna, J. D. Bunn, P. A. TI Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: The NCI's Lung Cancer Mutation Consortium (LCMC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Partners Hlth Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NCI, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN 37235 USA. Univ Colorado, Canc Ctr Denver, Aurora, CO USA. Univ Colorado Denver, Ctr Canc, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA CRA7506 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302603 ER PT J AU Kummar, S Strassberger, A Monks, A Ivy, SP Turkbey, IB Choyke, PL Steinberg, SM Simon, R Doroshow, JH Helman, LJ AF Kummar, S. Strassberger, A. Monks, A. Ivy, S. P. Turkbey, I. B. Choyke, P. L. Steinberg, S. M. Simon, R. Doroshow, J. H. Helman, L. J. CA Natl Canc Inst TI An evaluation of cediranib as a new agent for alveolar soft part sarcoma (ASPS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Dev Therapeut Clin, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 10001 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301019 ER PT J AU Land, SR Christian, N Wickerham, DL Costantino, JP Ganz, PA AF Land, S. R. Christian, N. Wickerham, D. L. Costantino, J. P. Ganz, P. A. TI Cigarette smoking, fitness, and alcohol use as predictors of cancer outcomes among women in the National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial (BCPT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Calif Los Angeles, Los Angeles Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles Sch Publ Hlth, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 1505 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301120 PM 28023621 ER PT J AU Lee, J Squires, J Hays, JL Kotz, HL Nielsen, D Houston, ND Kohn, EC AF Lee, J. Squires, J. Hays, J. L. Kotz, H. L. Nielsen, D. Houston, N. D. Kohn, E. C. TI A pharmacokinetics/pharmacodynamics study of sequence specificity of the PARP inhibitor olaparib with carboplatin in refractory/recurrent women's cancers: NCT01237067. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Mol Signaling Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS158 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304583 PM 28022973 ER PT J AU Lee, J Annunziata, CM Minasian, LM Zujewski, J Prindiville, SA Kotz, HL Squires, J Houston, ND Ji, JJ Yu, M Doroshow, JH Kohn, EC AF Lee, J. Annunziata, C. M. Minasian, L. M. Zujewski, J. Prindiville, S. A. Kotz, H. L. Squires, J. Houston, N. D. Ji, J. J. Yu, M. Doroshow, J. H. Kohn, E. C. TI Phase I study of the PARP inhibitor olaparib (O) in combination with carboplatin (C) in BRCA1/2 mutation carriers with breast (Br) or ovarian (Ov) cancer (Ca). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Mol Signaling Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Coordinating Ctr Clin Trials, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. SAIC Frederick, Bethesda, MD USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, 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 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2520 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301335 PM 28022335 ER PT J AU Lee, J Petrini, I Hwang, J Giovannetti, E Voortman, J Wang, Y Steinberg, SM Funel, N Meltzer, PS Wang, Y Giaccone, G AF Lee, J. Petrini, I. Hwang, J. Giovannetti, E. Voortman, J. Wang, Y. Steinberg, S. M. Funel, N. Meltzer, P. S. Wang, Y. Giaccone, G. TI Array-based comparative genomic hybridization analysis to identify prognostic markers for resected pancreatic cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, Gyeonggi Do, South Korea. Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. NCI, Genet Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. Azienda Osped Univ Pisana, UO Chirurg Gen & Trapianti NellUrem & Nel Diabet, Pisa, Italy. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 4097 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300507 PM 28020443 ER PT J AU Liu, J Fleming, GF Tolaney, SM Birrer, MJ Penson, RT Berlin, ST Whalen, C Tyburski, K Matijevich, K Kasparian, E Roche, M Lee, H Winer, EP Ivy, SP Matulonis, U AF Liu, J. Fleming, G. F. Tolaney, S. M. Birrer, M. J. Penson, R. T. Berlin, S. T. Whalen, C. Tyburski, K. Matijevich, K. Kasparian, E. Roche, M. Lee, H. Winer, E. P. Ivy, S. P. Matulonis, U. TI A phase I trial of the PARP inhibitor olaparib (AZD2281) in combination with the antiangiogenic cediranib (AZD2171) in recurrent ovarian or triple-negative breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5028 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301561 PM 28023743 ER PT J AU LoRusso, P Ji, JJ Li, J Heilbrun, K Shapiro, G Sausville, EA Boerner, SA Smith, DW Pilat, MJ Zhang, J Chen, AP Nechiporchik, N Parchment, RE AF LoRusso, P. Ji, J. J. Li, J. Heilbrun, K. Shapiro, G. Sausville, E. A. Boerner, S. A. Smith, D. W. Pilat, M. J. Zhang, J. Chen, A. P. Nechiporchik, N. Parchment, R. E. TI Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888; V) in combination with irinotecan (CPT-11; Ir) in patients (pts) with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Karmanos Canc Inst, Detroit, MI USA. SAIC Frederick, Bethesda, MD USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3000 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301430 PM 28022181 ER PT J AU Lund, JL Sturmer, T Sandler, RS Sanoff, HK Harlan, LC Warren, JL AF Lund, J. L. Sturmer, T. Sandler, R. S. Sanoff, H. K. Harlan, L. C. Warren, J. L. TI Validation of specific chemotherapy drugs in Medicare data. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. Univ Virginia, Charlottesville, VA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 6012 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301744 PM 28021986 ER PT J AU Lustberg, MB Balasubramanian, P Miller, B Villa, AG Carothers, S Michael, B Mrozek, E Ramaswamy, B Layman, RM Wesolowski, R Shapiro, CL Chalmers, JJ AF Lustberg, M. B. Balasubramanian, P. Miller, B. Villa, A. Garcia Carothers, S. Michael, B. Mrozek, E. Ramaswamy, B. Layman, R. M. Wesolowski, R. Shapiro, C. L. Chalmers, J. J. TI EpCAM-negative cancer-associated circulating cells (CACS) in blood samples of women with triple-negative breast cancer (TNBC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. NCI, Columbus, OH USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. RI Layman, Rachel/E-3475-2011; Miller, Brandon/B-7645-2013 OI Miller, Brandon/0000-0003-1523-9092 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e11559 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303161 PM 28021702 ER PT J AU Madan, RA Bilusic, M Hodge, JW Tsang, KY Arlen, PM Heery, CR Rauckhorst, M McMahon, S Intrivici, C Ferrara, TA Cohn, A Apelian, D Franzusoff, A Guo, Z Schlom, J Gulley, JL AF Madan, R. A. Bilusic, M. Hodge, J. W. Tsang, K. Y. Arlen, P. M. Heery, C. R. Rauckhorst, M. McMahon, S. Intrivici, C. Ferrara, T. A. Cohn, A. Apelian, D. Franzusoff, A. Guo, Z. Schlom, J. Gulley, J. L. TI A phase I trial of a yeast-based therapeutic cancer vaccine targeting CEA. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. GlobeImmune Inc, Louisville, CO USA. Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD USA. RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016 OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2604 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301419 PM 28022440 ER PT J AU Mahoney, MR Sloan, JA Hubbard, JM Liu, H Shields, AF Chan, E Goldberg, RM Gill, S Kahlenberg, MS Nair, SG Sargent, DJ Alberts, SR AF Mahoney, M. R. Sloan, J. A. Hubbard, J. M. Liu, H. Shields, A. F. Chan, E. Goldberg, R. M. Gill, S. Kahlenberg, M. S. Nair, S. G. Sargent, D. J. Alberts, S. R. TI Quality of life (QOL) for patients treated with FOLFOX with or without cetuximab (Cmab) following complete resection of colorectal cancer (CRC): Results from North Central Cancer Treatment Group (NCCTG) phase III trial N0147. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Mayo Clin, Div Med Oncol, Rochester, MN USA. Wayne State Univ, Natl Surg Adjuvant Breast & Bowel Project, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ N Carolina, Chapel Hill, NC USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Lehigh Valley Hosp, Allentown, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3541 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300315 ER PT J AU Maitland, ML Karrison, T Bakris, GL Fox, K Janisch, LA Karovic, S Levine, MR House, L Wright, JJ Cohen, EE Fleming, GF Seiwert, TY Villaflor, VM Stadler, WM Ratain, MJ AF Maitland, M. L. Karrison, T. Bakris, G. L. Fox, K. Janisch, L. A. Karovic, S. Levine, M. R. House, L. Wright, J. J. Cohen, E. E. Fleming, G. F. Seiwert, T. Y. Villaflor, V. M. Stadler, W. M. Ratain, M. J. TI Pharmacodynamic (PD) assessment of blood pressure (BP) in a randomized dose-ranging trial of sorafenib (S). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Chicago, Chicago, IL 60637 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3016 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301445 PM 28022163 ER PT J AU Malempati, S Hembrough, TA Thyparambil, S Cao, L Darfler, M Krizman, D Hawkins, DS Skapek, S Helman, LJ Burrows, J AF Malempati, S. Hembrough, T. A. Thyparambil, S. Cao, L. Darfler, M. Krizman, D. Hawkins, D. S. Skapek, S. Helman, L. J. Burrows, J. TI Quantitative analysis of IGF-1R expression in FFPE human rhabdomyosarcoma tumor tissue by mass spectrometry. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Express Pathol Inc, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. Univ Washington, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA. Univ Chicago, Chicago, IL 60637 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 10069 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301085 PM 28021207 ER PT J AU Mankoff, DA Linden, HM Link, J Kurland, BF Schubert, EK Peterson, L Gadi, VK Specht, JM Shankar, L Eary, JF AF Mankoff, D. A. Linden, H. M. Link, J. Kurland, B. F. Schubert, E. K. Peterson, L. Gadi, V. K. Specht, J. M. Shankar, L. Eary, J. F. TI NCI-sponsored phase II study of [(18)f]fluoroestradiol (FES) as a marker of hormone sensitivity of metastatic breast cancer: Initial results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Div Med Oncol, Seattle, WA 98195 USA. NCI, Canc Imaging Program, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e11104 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303072 PM 28023805 ER PT J AU Martin, LK Jia, G Yang, X Grecula, JC Harper, EJ Kefauver, C Wei, L Shah, ZK Bloomston, M Melvin, WS Muscarella, P Ellison, EC Knopp, MV Delgado, IE Grever, MR Bekaii-Saab, TS AF Martin, L. K. Jia, G. Yang, X. Grecula, J. C. Harper, E. J. Kefauver, C. Wei, L. Shah, Z. K. Bloomston, M. Melvin, W. S. Muscarella, P. Ellison, E. C. Knopp, M. V. Delgado, I. Espinoza Grever, M. R. Bekaii-Saab, T. S. TI A dose-escalating and pharmacodynamic study of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (triapine) and radiation in patients with locally advanced pancreas cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Ohio State Univ, Columbus, OH 43210 USA. NIH, Rockville, MD USA. RI Bloomston, Mark/E-2767-2011; Grecula, John/E-3149-2011; Jia, Guang/A-1275-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e14558 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303610 PM 28020749 ER PT J AU Massett, H Parreco, LK Padberg, RM Richmond, E Dilts, DM AF Massett, H. Parreco, L. K. Padberg, R. M. Richmond, E. Dilts, D. M. TI AccrualNet: A novel approach to addressing clinical trial accruals through a knowledge-based, community of practice platform SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. NCI, Bethesda, MD 20892 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e16621 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304326 PM 28022800 ER PT J AU Matushansky, I Coakley, KE Uldrick, TS Taub, RN AF Matushansky, I. Coakley, K. E. Uldrick, T. S. Taub, R. N. TI A phase I dose-escalation study of azacitidine in combination with temozolomide in patients with soft tissue sarcomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 10073 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301089 PM 28021245 ER PT J AU McGregor, LM Spunt, SL Ward, D Wu, J Billups, C Ivy, SP Santana, VM Fouladi, M Furman, WL AF McGregor, L. M. Spunt, S. L. Ward, D. Wu, J. Billups, C. Ivy, S. P. Santana, V. M. Fouladi, M. Furman, W. L. TI A phase I study of ifosfamide, oxaliplatin, and etoposide (IOE) in pediatric patients with refractory solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NCI, Bethesda, MD 20892 USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 9545 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302568 PM 28019772 ER PT J AU Moley, JF Adkins, D Bible, KC Traynor, AM Molina, JR Colon-Otero, G Pluard, TJ Shah, MH Suresh, R Erlichman, C Ivy, SP Suman, V Geyer, SM Fracasso, PM Cohen, MS Tang, H Fialkowski, E Traugott, A Smallridge, RC AF Moley, J. F. Adkins, D. Bible, K. C. Traynor, A. M. Molina, J. R. Colon-Otero, G. Pluard, T. J. Shah, M. H. Suresh, R. Erlichman, C. Ivy, S. P. Suman, V. Geyer, S. M. Fracasso, P. M. Cohen, M. S. Tang, H. Fialkowski, E. Traugott, A. Smallridge, R. C. CA P2C TI 17-allylaminogeldanamycin in advanced medullary and differentiated thyroid carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Washington Univ, Siteman Canc Ctr, St Louis, MO USA. Washington Univ, Sch Med, St Louis, MO USA. Mayo Clin, Rochester, MN USA. Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. Mayo Clin, Jacksonville, FL 32224 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Virginia, Charlottesville, VA USA. Univ Kansas, Med Ctr, Dept Surg, Kansas City, KS 66103 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5582 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301725 PM 28022079 ER PT J AU Morgan, R Oza, AM Qin, R Laumann, KM Mackay, H Strevel, EL Welch, S Sullivan, D Wenham, RM Chen, HX Doyle, LA Gandara, DR Erlichman, C AF Morgan, R. Oza, A. M. Qin, R. Laumann, K. M. Mackay, H. Strevel, E. L. Welch, S. Sullivan, D. Wenham, R. M. Chen, H. X. Doyle, L. A. Gandara, D. R. Erlichman, C. TI A phase II trial of temsirolimus and bevacizumab in patients with endometrial, ovarian, hepatocellular carcinoma, carcinoid, or islet cell cancer: Ovarian cancer (OC) subset-A study of the Princess Margaret, Mayo, Southeast phase II, and California Cancer (CCCP) N01 Consortia NCI#8233. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 City Hope Natl Med Ctr, Duarte, CA USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Mayo Clin, Rochester, MN USA. Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada. Credit Valley Hosp, Mississauga, ON, Canada. London Reg Canc Program, London, ON, Canada. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. CTEP Natl Canc Inst, Bethesda, MD USA. NCI, NIH, Rockville, MD USA. Univ Calif Davis, Sacramento, CA 95817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5015 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301548 ER PT J AU Naing, A LoRusso, P Fu, S Hong, DS Anderson, PM Benjamin, RS Ludwig, JA Chen, HX Doyle, LA Kurzrock, R AF Naing, A. LoRusso, P. Fu, S. Hong, D. S. Anderson, P. M. Benjamin, R. S. Ludwig, J. A. Chen, H. X. Doyle, L. A. Kurzrock, R. TI Cixutumumab combined with temsirolimus in patients with refractory Ewing's sarcoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Karmanos Canc Inst, Detroit, MI USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. NCI, NIH, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 10031 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301047 PM 28021114 ER PT J AU O'Connor, DP Brennan, DJ Laursen, H Mcgee, SF McCarthy, S Zagozdzon, R Rexhepaj, E Culhane, A Martin, FM Duffy, MJ Landberg, G Ryden, L Hewitt, SM Kuhar, MJ Bernards, R Millikan, RC Crown, J Jirstrom, K Gallagher, WM AF O'Connor, D. P. Brennan, D. J. Laursen, H. Mcgee, S. F. McCarthy, S. Zagozdzon, R. Rexhepaj, E. Culhane, A. Martin, F. M. Duffy, M. J. Landberg, G. Ryden, L. Hewitt, S. M. Kuhar, M. J. Bernards, R. Millikan, R. C. Crown, J. Jirstrom, K. Gallagher, W. M. TI The prognostic value of the cocaine and amphetamine-regulated transcript (CART) in breast cancer (BC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Coll Dublin, Dublin 2, Ireland. Harvard Univ, Brookline, MA USA. St Vincents Univ Hosp, Dept Pathol Lab Med, Dublin 4, Ireland. Mol Therapeut Canc, Dublin, Ireland. Malmo Univ Hosp, Malmo, Sweden. Lund Univ, Lund, Sweden. NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Emory Univ, Atlanta, GA 30322 USA. Netherlands Canc Inst, Amsterdam, Netherlands. Univ N Carolina, Chapel Hill, NC USA. Irish Clin Oncol Res Grp, Dublin, Ireland. Lund Univ, Malmo, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 601 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300104 PM 28021182 ER PT J AU Park, TS Lagisetty, KH Sherry, RM Yang, JC Hughes, MS Morton, K White, DE Klionsky, Y Rosenberg, SA Phan, GQ AF Park, T. S. Lagisetty, K. H. Sherry, R. M. Yang, J. C. Hughes, M. S. Morton, K. White, D. E. Klionsky, Y. Rosenberg, S. A. Phan, G. Q. TI Routine imaging to detect recurrences in high-risk melanoma patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 8576 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302434 PM 28021026 ER PT J AU Peng, CR Prager, AJ Lita, E Wernick, MH McNally, D Kaushal, A Sproull, M Compton, K Dahut, WL Figg, WD Camphausen, KA AF Peng, C. R. Prager, A. J. Lita, E. Wernick, M. H. McNally, D. Kaushal, A. Sproull, M. Compton, K. Dahut, W. L. Figg, W. D. Camphausen, K. A. TI Urinary-activated HGF as a noninvasive biomarker for the diagnosis of prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Ctr Clin, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e15144 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304047 PM 28021254 ER PT J AU Petrelli, NJ Grubbs, SS Spellman, JE English, CL Shevock, A Nunley, K AF Petrelli, N. J. Grubbs, S. S. Spellman, J. E. English, C. L. Shevock, A. Nunley, K. TI A statewide evaluation of adjuvant chemotherapy for stage III colon cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NSABP, Newark, DE USA. Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA. Christiana Care, Helen F Graham Canc Ctr, Newark, DE USA. Beebe Hosp, Tunnel Canc Ctr, Lewes, DE USA. Delaware Canc Registry, Wilmington, DE USA. Delaware Div Publ Hlth, Dover, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e14034 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880303442 PM 28022616 ER PT J AU Prager, AJ Peng, CR Lita, E McNally, D Kaushal, A Sproull, M Compton, K Dahut, WL Figg, WD Camphausen, KA AF Prager, A. J. Peng, C. R. Lita, E. McNally, D. Kaushal, A. Sproull, M. Compton, K. Dahut, W. L. Figg, W. D. Camphausen, K. A. TI Urinary osteopontin as a marker for localized and metastatic prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e15147 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304050 PM 28021269 ER PT J AU Prindiville, SA Hautala, JA Miller, BJ Shoemaker, D Curt, GA Porter, PD Doroshow, JH AF Prindiville, S. A. Hautala, J. A. Miller, B. J. Shoemaker, D. Curt, G. A. Porter, P. D. Doroshow, J. H. TI Standard terms of agreement for research trials (START): A joint National Cancer Institute (NCI) and CEO-roundtable Life Sciences Consortium (LSC) project SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Coordinating Ctr Clin Trials, Bethesda, MD 20892 USA. Sci Technol Policy Inst, Washington, DC USA. AstraZeneca, Wilmington, DE USA. Hogan Lovells US LLP, Washington, DC USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e16600 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304307 PM 28022770 ER PT J AU Rajan, A Kelly, RJ Lopez-Chavez, A Carter, CA Szabo, E Scepura, B Manu, MJ Berman, AW Giaccone, G AF Rajan, A. Kelly, R. J. Lopez-Chavez, A. Carter, C. A. Szabo, E. Scepura, B. Manu, M. J. Berman, A. W. Giaccone, G. TI Management of thymic epithelial tumors (TETs) at the National Cancer Institute (NCI) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Rajan, A.; Kelly, R. J.; Lopez-Chavez, A.; Carter, C. A.; Szabo, E.; Scepura, B.; Manu, M. J.; Berman, A. W.; Giaccone, G.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e17511 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304357 PM 28020127 ER PT J AU Ramakrishna, S Gottschalk, S Morgan, R Dotti, G Brenner, MK Orentas, R Mackall, C AF Ramakrishna, S. Gottschalk, S. Morgan, R. Dotti, G. Brenner, M. K. Orentas, R. Mackall, C. TI Can the well-credentialed neuroblastoma tumor antigen GD2 be exploited for T-cell-based immunotherapy of pediatric sarcomas? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 9531 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302554 PM 28019777 ER PT J AU Richter, S Gan, HK MacKenzie, MJ Hotte, SJ Mukherjee, SD Kollmannsberger, CK Ivy, SP Fernandes, K Halford, R Massey, C Wang, L Moore, MJ Sridhar, SS AF Richter, S. Gan, H. K. MacKenzie, M. J. Hotte, S. J. Mukherjee, S. D. Kollmannsberger, C. K. Ivy, S. P. Fernandes, K. Halford, R. Massey, C. Wang, L. Moore, M. J. Sridhar, S. S. TI Evaluation of second-line response to targeted therapy following progression on first-line cediranib, an oral pan-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), in advanced renal cell carcinoma (RCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Austin Hosp, Melbourne, Vic 3084, Australia. London Reg Canc Program, London, ON, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NCI, Bethesda, MD 20892 USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Princess Margaret Hosp, Dept Biostat, Toronto, ON M4X 1K9, Canada. Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e15153 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304056 PM 28020872 ER PT J AU Roh, MS Yothers, GA O'Connell, MJ Beart, RW Pitot, HC Shields, AF Parda, DS Sharif, S Allegra, CJ Petrelli, NJ Landry, JC Ryan, DP Arora, A Evans, TL Soori, GS Chu, L Landes, RV Mohiuddin, M Lopa, S Wolmark, N AF Roh, M. S. Yothers, G. A. O'Connell, M. J. Beart, R. W. Pitot, H. C. Shields, A. F. Parda, D. S. Sharif, S. Allegra, C. J. Petrelli, N. J. Landry, J. C. Ryan, D. P. Arora, A. Evans, T. L. Soori, G. S. Chu, L. Landes, R. V. Mohiuddin, M. Lopa, S. Wolmark, N. TI The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NSABP, Pittsburgh, PA USA. MD Anderson Canc Ctr Orlando, Pittsburgh, PA USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ So Calif, Glendale, CA USA. Mayo Clin, Rochester, MN USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Florida, Gainesville, FL USA. NSABP, Newark, DE USA. Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA. Emory Univ, ECOG, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Kaiser Permanente, Hayward, CA USA. UPMC Canc Ctr, Greensburg, PA USA. Missouri Valley Canc Consotrium, Omaha, NE USA. Florida Canc Specialists, Sarasota, FL USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. Univ Pittsburgh, Grad Sch Publ Hlth, NSABP Biostat Ctr, Pittsburgh, PA USA. NR 0 TC 44 Z9 53 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3503 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300277 PM 28020345 ER PT J AU Sarantopoulos, J Lenz, H LoRusso, P Shibata, S Kummar, S Mulkerin, D Ramanathan, RK Mita, MM O'Rourke, P Remick, SC Goel, S Gutierrez, M Ramalingam, SS Murgo, A Davies, AM Mani, S Boni, J Shapiro, M Ivy, SP Takimoto, CH AF Sarantopoulos, J. Lenz, H. LoRusso, P. Shibata, S. Kummar, S. Mulkerin, D. Ramanathan, R. K. Mita, M. M. O'Rourke, P. Remick, S. C. Goel, S. Gutierrez, M. Ramalingam, S. S. Murgo, A. Davies, A. M. Mani, S. Boni, J. Shapiro, M. Ivy, S. P. Takimoto, C. H. CA Natl Canc Inst Organ Dysfunction TI Phase I pharmacokinetic study of temsirolimus (CCI-779) in patients with advanced malignancies and normal and impaired liver function: An NCI Organ Dysfunction Working Group (ODWG) study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Karmanos Canc Inst, Detroit, MI USA. City Hope Natl Med Ctr, Duarte, CA USA. NCI, Dev Therapeut Clin, Bethesda, MD 20892 USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. Scottsdale Healthcare TGen, Virginia G Piper Canc Ctr, Scottsdale, AZ USA. Mary Babb Randolph Canc Ctr, Morgantown, WV USA. Montefiore Med Ctr, Bronx, NY 10467 USA. NCI, Bethesda, MD 20892 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Univ Calif Davis, Davis Canc Ctr, Sacramento, CA 95817 USA. Pfizer Inc, Collegeville, PA USA. Pfizer Inc, Cambridge, MA USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3072 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301501 PM 28022531 ER PT J AU Shen, K Tang, G Costantino, JP Anderson, SJ Kim, C Pogue-Geile, KL Song, N Gabrin, MJ Geyer, CE Wolmark, N AF Shen, K. Tang, G. Costantino, J. P. Anderson, S. J. Kim, C. Pogue-Geile, K. L. Song, N. Gabrin, M. J. Geyer, C. E. Wolmark, N. TI Multigene predictors developed on breast cancer cell lines to predict patient chemotherapy response: A validation study on the NSABP B-27 trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Precis Therapeut Inc, Pittsburgh, PA USA. NSABBP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 1029 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300168 PM 28020738 ER PT J AU Sherman, EJ Ho, AL Haque, S Tuttle, RM Ghossein, RA Schoder, H Baum, MS Kelly, K Chen, AP Shaha, AR Pfister, DG AF Sherman, E. J. Ho, A. L. Haque, S. Tuttle, R. M. Ghossein, R. A. Schoeder, H. Baum, M. S. Kelly, K. Chen, A. P. Shaha, A. R. Pfister, D. G. TI A phase II study of VEGF trap in patients with radioactive iodine (RAI)-refractory thyroid carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5566 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301707 PM 28022149 ER PT J AU Shklovskiy-Kordi, NE Zingerman, B Varticovski, L AF Shklovskiy-Kordi, N. E. Zingerman, B. Varticovski, L. TI Electronic health records (EHR) adapted for clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Natl Ctr Hematol, Moscow, Russia. NCI, Ctr Clin, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e16582 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304293 PM 28022095 ER PT J AU Siziopikou, KP Cobleigh, MA Anderson, SJ Julian, TB Arthur, DW Zheng, P Mamounas, EP Pajon, ER Behrens, RJ Chu, L Leasure, NC Atkins, JN Polikoff, J Seay, TE McCaskill-Stevens, WJ Rabinovitch, R Wolmark, N AF Siziopikou, K. P. Cobleigh, M. A. Anderson, S. J. Julian, T. B. Arthur, D. W. Zheng, P. Mamounas, E. P. Pajon, E. R. Behrens, R. J. Chu, L. Leasure, N. C. Atkins, J. N. Polikoff, J. Seay, T. E. McCaskill-Stevens, W. J. Rabinovitch, R. Wolmark, N. TI Preliminary results of centralized HER2 testing in DCIS of the breast: NSABP B-43. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. NSABBP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Natl Surg Adjuvant Breast & Bowel Project, Richmond, VA USA. Virginia Commonwealth Univ, Richmond, VA USA. Natl Surg Adjuvant Breast & Bowel Project, Canton, OH USA. Aultman Hlth Fdn, Canton, OH USA. Colorado Canc Res Program, Denver, CO USA. Iowa Oncol Res Assoc, Des Moines, IA USA. Florida Canc Specialists, Sarasota, FL USA. Reading Reg Canc Ctr, W Reading, PA USA. SCCC CCOP, Winston Salem, NC USA. Kaiser Permanente So Calif, San Diego, CA USA. Atlanta Reg Community Clin Oncol Program, Atlanta, GA USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. Univ Colorado, Aurora, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 588 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300091 PM 28021636 ER PT J AU Sloan, JA Mahoney, MR Sargent, DJ Hubbard, JM Liu, H Basch, EM Shields, AF Chan, E Goldberg, RM Gill, S Kahlenberg, MS Alberts, SR AF Sloan, J. A. Mahoney, M. R. Sargent, D. J. Hubbard, J. M. Liu, H. Basch, E. M. Shields, A. F. Chan, E. Goldberg, R. M. Gill, S. Kahlenberg, M. S. Alberts, S. R. TI Was it worth it (WIWI)? Patient satisfaction with clinical trial participation: Results from North Central Cancer Treatment Group (NCCTG) phase III trial N0147. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Mayo Clin, Div Med Oncol, Rochester, MN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Wayne State Univ, Natl Surg Adjuvant Breast & Bowel Project, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ N Carolina, Chapel Hill, NC USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 6122 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301011 PM 28022499 ER PT J AU Sosa, JA Elisei, R Jarzab, B Bal, CS Koussis, H Gramza, AW Ben-Yosef, R Gitlitz, BJ Haugen, B Karandikar, SM Khuri, FR Licitra, LF Remick, SC Marur, S Lu, C Ondrey, FG Lu, S Balkissoon, J AF Sosa, J. A. Elisei, R. Jarzab, B. Bal, C. S. Koussis, H. Gramza, A. W. Ben-Yosef, R. Gitlitz, B. J. Haugen, B. Karandikar, S. M. Khuri, F. R. Licitra, L. F. Remick, S. C. Marur, S. Lu, C. Ondrey, F. G. Lu, S. Balkissoon, J. TI A randomized phase II/III trial of a tumor vascular disrupting agent fosbretabulin tromethamine (CA4P) with carboplatin (C) and paclitaxel (P) in anaplastic thyroid cancer (ATC): Final survival analysis for the FACT trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT USA. Univ Pisa, Pisa, Italy. MSC Mem Canc Ctr, Gliwice, Poland. All India Inst Med Sci, New Delhi, India. Ist Oncol Veneto IRCCS, Padua, Italy. NCI, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Univ Colorado, Aurora, CO USA. Ruby Hall Clin, Pune, Maharashtra, India. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. Fdn IRCCS Ist Nazl Tumori, Milan, Italy. Mary Babb Randolph Canc Ctr, Morgantown, WV USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Minnesota, Minneapolis, MN USA. OXiGENE Inc, San Francisco, CA USA. NR 0 TC 6 Z9 7 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 5502 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301647 PM 28021454 ER PT J AU Speranza, G Rubinstein, L Ivy, SP Harris, PJ AF Speranza, G. Rubinstein, L. Ivy, S. P. Harris, P. J. TI Correlation between adverse event reports of hypothyroidism and clinical response in patients treated with vascular endothelial growth factor receptor inhibitors (VEGFR-I). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Div Canc Treatment & Diag, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2602 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301417 PM 28022438 ER PT J AU Srivastava, AK Hollingshead, MG Weiner, J Khin, S Borgel, S Risbood, P Pfister, TD Lawrence, SM Kinders, RJ Bottaro, DP Tomaszewski, JE Parchment, RE Doroshow, JH AF Srivastava, A. K. Hollingshead, M. G. Weiner, J. Khin, S. Borgel, S. Risbood, P. Pfister, T. D. Lawrence, S. M. Kinders, R. J. Bottaro, D. P. Tomaszewski, J. E. Parchment, R. E. Doroshow, J. H. TI Development and validation of biomarker assays to assess pharmacodynamic modulation of MET. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, SAIC Frederick, Frederick, MD 21701 USA. NCI, Frederick, MD 21701 USA. SAIC Frederick, Frederick, MD USA. SAIC Frederick, DTP In Vivo Preclin Support, Frederick, MD USA. NCI, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Div Canc Treatment & Diag, Bethesda, MD USA. SAIC Frederick, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3042 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301471 PM 28022620 ER PT J AU Tagawa, ST Saran, A Akhtar, NH Goel, S Mileo, G Kung, S Beltran, H Milowsky, MI Mazumdar, M Wright, JJ Nanus, DM AF Tagawa, S. T. Saran, A. Akhtar, N. H. Goel, S. Mileo, G. Kung, S. Beltran, H. Milowsky, M. I. Mazumdar, M. Wright, J. J. Nanus, D. M. CA New York Canc Consortium TI Final phase II results of NCI 6981: A phase I/II study of sorafenib (S) plus gemcitabine (GEM) and capecitabine (CAP) for advanced renal cell carcinoma (RCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Weill Cornell Med Coll, New York, NY USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA e15165 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304066 PM 28020895 ER PT J AU Tan, AR Toppmeyer, D Stein, MN Moss, RA Gounder, M Lindquist, DC Ji, JJ Chen, AP Egorin, MJ Kiesel, B Beumer, JH DiPaola, RS AF Tan, A. R. Toppmeyer, D. Stein, M. N. Moss, R. A. Gounder, M. Lindquist, D. C. Ji, J. J. Chen, A. P. Egorin, M. J. Kiesel, B. Beumer, J. H. DiPaola, R. S. TI Phase I trial of veliparib, (ABT-888), a poly(ADP-ribose) polymerase (PARP) inhibitor, in combination with doxorubicin and cyclophosphamide in breast cancer and other solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Canc Inst New Jersey, New Brunswick, NJ USA. SAIC Frederick, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3041 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301470 PM 28022614 ER PT J AU Vanderwalde, AM Ye, W Frankel, PH Asuncion, DG Pezner, RD Luu, TH Shibata, S Leong, LA Margolin, KA Morgan, R Koczywas, M Chow, WA Twardowski, P Wong, JY Doroshow, JH Forman, SJ Somlo, G AF Vanderwalde, A. M. Ye, W. Frankel, P. H. Asuncion, D. G. Pezner, R. D. Luu, T. H. Shibata, S. Leong, L. A. Margolin, K. A. Morgan, R. Koczywas, M. Chow, W. A. Twardowski, P. Wong, J. Y. Doroshow, J. H. Forman, S. J. Somlo, G. TI Long-term survival after high-dose chemotherapy followed by peripheral stem cell rescue for high-risk locally advanced/inflammatory and metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 City Hope Natl Med Ctr, Duarte, CA USA. Univ Washington, Seattle, WA 98195 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 1048 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300187 PM 28020696 ER PT J AU Vener, TI Derecho, C Galkin, S Greer, J Levis, MJ Gocke, CD Malek, S Palma, JF Raponi, M Wang, Y Wright, JJ Karp, JE AF Vener, T. I. Derecho, C. Galkin, S. Greer, J. Levis, M. J. Gocke, C. D. Malek, S. Palma, J. F. Raponi, M. Wang, Y. Wright, J. J. Karp, J. E. TI Correlation of RASGRP1:APTX expression assay with response to tipifarnib plus etoposide in elderly patients with newly diagnosed AML SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Johnson & Johnson, Ortho Clin Diagnost, Raritan, NJ USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Centocor OrthoBiotech Oncol, Radnor, PA USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 6534 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302041 PM 28020211 ER PT J AU Virgo, KS Lerro, CC Klabunde, CN Earle, C Ganz, PA AF Virgo, K. S. Lerro, C. C. Klabunde, C. N. Earle, C. Ganz, P. A. TI Barriers in providing breast and colorectal cancer survivorship care: Perceptions of US primary care physicians (PCPs) and medical oncologists (MOs) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Amer Canc Soc NHO, Atlanta, GA USA. NCI, Bethesda, MD 20892 USA. Inst Clin Evaluat Sci, Toronto, ON, Canada. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA CRA9006 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302604 ER PT J AU Viswanathan, S Wesolowski, R Layman, RM Alejandra, G Miller, B Chalmers, JJ Bejastani, S Zhao, W Pierluigu, G Cotrill, J Phelps, MA Schaaf, LJ Geyer, SM Hall, N Knopp, MV Shapiro, CL Villalona-Calero, MA Chen, A Grever, MR Ramaswamy, B AF Viswanathan, S. Wesolowski, R. Layman, R. M. Alejandra, G. Miller, B. Chalmers, J. J. Bejastani, S. Zhao, W. Pierluigu, G. Cotrill, J. Phelps, M. A. Schaaf, L. J. Geyer, S. M. Hall, N. Knopp, M. V. Shapiro, C. L. Villalona-Calero, M. A. Chen, A. Grever, M. R. Ramaswamy, B. TI A phase I dose-escalation study of ABT-888 (veliparib) in combination with carboplatin in HER2-negative metastatic breast cancer (MBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 James Canc Inst, Columbus, OH USA. Solove Res Inst, Columbus, OH USA. Ohio State Univ, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Arthur G James Canc Hosp, Columbus, OH USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. NCI, Rockville, MD USA. RI Miller, Brandon/B-7645-2013 OI Miller, Brandon/0000-0003-1523-9092 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA TPS106 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880304531 PM 28022858 ER PT J AU Wen, PY Puduvalli, VK Kuhn, JG Reid, JM Lamborn, K Cloughesy, TF Chang, SM Drappatz, J Yung, WKA Gilbert, MR Robins, HI Lieberman, FS Lassman, AB McGovern, RM Desideri, S Ye, X Ames, MM Espinoza-Delgado, IJ Grossman, SA Prados, M AF Wen, P. Y. Puduvalli, V. K. Kuhn, J. G. Reid, J. M. Lamborn, K. Cloughesy, T. F. Chang, S. M. Drappatz, J. Yung, W. K. A. Gilbert, M. R. Robins, H. I. Lieberman, F. S. Lassman, A. B. McGovern, R. M. Desideri, S. Ye, X. Ames, M. M. Espinoza-Delgado, I. J. Grossman, S. A. Prados, M. TI Phase I study of vorinostat in combination with temozolomide in patients with malignant gliomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Mayo Clin, Rochester, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RI Puduvalli, Vinay/A-2411-2016; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2032 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301248 PM 28023819 ER PT J AU Williams, EH McCaskill-Stevens, WJ Lad, TE AF Williams, E. H. McCaskill-Stevens, W. J. Lad, T. E. TI Analysis of minority-based community clinical oncology program (MBCCOP) accrual activity SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. John H Stroger Hosp Cook Cty, Minor Based Community Clin Oncol Program, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 6070 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300757 PM 28021793 ER PT J AU Winick, NJ Salzer, WL Devidas, M Nachman, JB Raetz, EA Loh, ML Heerema, NA Carroll, AJ Gastier-Foster, JM Borowitz, MJ Wood, BL Willman, CL Hunger, S Carroll, WL Larsen, EC AF Winick, N. J. Salzer, W. L. Devidas, M. Nachman, J. B. Raetz, E. A. Loh, M. L. Heerema, N. A. Carroll, A. J. Gastier-Foster, J. M. Borowitz, M. J. Wood, B. L. Willman, C. L. Hunger, S. Carroll, W. L. Larsen, E. C. TI Dexamethasone (DEX) versus prednisone (PRED) during induction for children with high-risk acute lymphoblastic leukemia (HR-ALL): A report from the Children's Oncology Group Study AALL0232. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 UTSW, Dallas, TX USA. Childrens Med Ctr, Ctr Canc & Blood Disorders, Dallas, TX 75235 USA. NIH, Silver Spring, MD USA. Childrens Oncol Grp, Gainesville, FL USA. Univ Chicago, Chicago, IL 60637 USA. NYU, Langone Med Ctr, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Arthur G James Canc Hosp, Columbus, OH USA. Solove Res Inst, Columbus, OH USA. Univ Alabama Birmingham, Birmingham, AL USA. Nationwide Childrens Hosp, Columbus, OH USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ Washington, Seattle, WA 98195 USA. Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. Univ Colorado Denver, Hlth Sci Ctr, Aurora, CO USA. Maine Childrens Canc Program, Scarborough, ME USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 9504 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302528 PM 28019831 ER PT J AU Yothers, GA Allegra, CJ O'Connell, MJ George, TJ Sharif, S Petrelli, NJ Lopa, S Wolmark, N AF Yothers, G. A. Allegra, C. J. O'Connell, M. J. George, T. J. Sharif, S. Petrelli, N. J. Lopa, S. Wolmark, N. TI The efficacy of oxaliplatin (Ox) when added to 5-fluorouracil/leucovorin (FU/L) in stage II colon cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Florida, Gainesville, FL USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NSABP, Newark, DE USA. Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Newark, DE USA. NSABP, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, NSABP Biostat Ctr, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3507 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300281 PM 28020348 ER PT J AU Wu, H D'Alessio, AC Ito, S Xia, K Wang, ZB Cui, KR Zhao, KJ Sun, YE Zhang, Y AF Wu, Hao D'Alessio, Ana C. Ito, Shinsuke Xia, Kai Wang, Zhibin Cui, Kairong Zhao, Keji Sun, Yi Eve Zhang, Yi TI Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells SO NATURE LA English DT Article ID DNA METHYLATION; HISTONE H3; DEVELOPMENTAL REGULATORS; CHROMATIN-STRUCTURE; POLYCOMB; GENOME; GENES; COMPLEX; BINDING; PROTEIN AB Epigenetic modification of the mammalian genome by DNA methylation (5-methylcytosine) has a profound impact on chromatin structure, gene expression and maintenance of cellular identity(1). The recent demonstration that members of the Ten-eleven translocation (Tet) family of proteins can convert 5-methylcytosine to 5-hydroxymethylcytosine raised the possibility that Tet proteins are capable of establishing a distinct epigenetic state(2,3). We have recently demonstrated that Tet1 is specifically expressed in murine embryonic stem (ES) cells and is required for ES cell maintenance(2). Using chromatin immunoprecipitation coupled with high-throughput DNA sequencing, here we show in mouse ES cells that Tet1 is preferentially bound to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. Despite an increase in levels of DNA methylation at many Tet1-binding sites, Tet1 depletion does not lead to downregulation of all the Tet1 targets. Interestingly, although Tet1-mediated promoter hypomethylation is required for maintaining the expression of a group of transcriptionally active genes, it is also involved in repression of Polycomb-targeted developmental regulators. Tet1 contributes to silencing of this group of genes by facilitating recruitment of PRC2 to CpG-rich gene promoters. Thus, our study not only establishes a role for Tet1 in modulating DNA methylation levels at CpG-rich promoters, but also reveals a dual function of Tet1 in promoting transcription of pluripotency factors as well as participating in the repression of Polycomb-targeted developmental regulators. C1 [D'Alessio, Ana C.; Ito, Shinsuke; Xia, Kai; Zhang, Yi] Univ N Carolina, Dept Biochem & Biophys, Howard Hughes Med Inst, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Wu, Hao; Sun, Yi Eve] Univ Calif Los Angeles, David Geffen Sch Med, IDDRC Semel Inst Neurosci & Human Behav, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Wu, Hao; Sun, Yi Eve] Univ Calif Los Angeles, David Geffen Sch Med, IDDRC Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Wang, Zhibin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Lab Human Environm Epigenomes, Baltimore, MD 21025 USA. [Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Zhang, Y (reprint author), Univ N Carolina, Dept Biochem & Biophys, Howard Hughes Med Inst, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM yi_zhang@med.unc.edu RI Wu, Hao/G-4145-2013; Xia, Kai/B-7214-2014 OI Wu, Hao/0000-0002-1256-6891; FU NIH [GM68804, R56MH082068]; Division of Intramural Research of National Heart, Lung and Blood Institute, NIH FX We thank B. Abraham and I. Chepelev for Illumina sequencing and data transfer; J. He and A. T. Nguyen for FACS sorting; O. Taranova for discussion; S. Wu for critical reading of the manuscript. This work was supported by NIH grants GM68804 (to Y.Z.), R56MH082068 (to Y.E.S.) and support from the Division of Intramural Research Program of National Heart, Lung and Blood Institute, NIH (K.Z.). S. I. is a research fellow of the Japan Society for the Promotion of Science. Y.Z. is an Investigator of the Howard Hughes Medical Institute. NR 30 TC 314 Z9 324 U1 7 U2 68 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAY 19 PY 2011 VL 473 IS 7347 BP 389 EP U578 DI 10.1038/nature09934 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765QA UT WOS:000290722400052 PM 21451524 ER PT J AU Bagnara, D Kaufman, MS Calissano, C Marsilio, S Patten, PEM Simone, R Chum, P Yan, XJ Allen, SL Kolitz, JE Baskar, S Rader, C Mellstedt, H Rabbani, H Lee, A Gregersen, PK Rai, KR Chiorazzi, N AF Bagnara, Davide Kaufman, Matthew S. Calissano, Carlo Marsilio, Sonia Patten, Piers E. M. Simone, Rita Chum, Philip Yan, Xiao-Jie Allen, Steven L. Kolitz, Jonathan E. Baskar, Sivasubramanian Rader, Christoph Mellstedt, Hakan Rabbani, Hodjattallah Lee, Annette Gregersen, Peter K. Rai, Kanti R. Chiorazzi, Nicholas TI A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; RECEPTOR TYROSINE KINASE; B-CELLS; CD38 EXPRESSION; LYMPH-NODES; MOUSE MODEL; IN-VIVO; ROR1; APOPTOSIS; BLOOD AB Chronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells proliferate in nonobese diabetes/severe combined immunodeficiency/gamma c(null) mice under the influence of activated CLL-derived T lymphocytes. By cotransferring autologous T lymphocytes, activated in vivo by alloantigens, the survival and growth of primary CFSE-labeled CLL cells in vivo is achieved and quantified. Using this approach, we have identified key roles for CD4(+) T cells in CLL expansion, a direct link between CD38 expression by leukemic B cells and their activation, and support for CLL cells preferentially proliferating in secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL cells in vivo, deciphering involvement of nonleukemic elements and nongenetic factors promoting CLL cell growth, identifying and characterizing potential leukemic stem cells, and permitting preclinical studies of novel therapeutics. Because autologous activated T lymphocytes are 2-edged swords, generating unwanted graph-versus-host and possibly autologous antitumor reactions, the model may also facilitate analyses of T-cell populations involved in immune surveillance relevant to hematopoietic transplantation and tumor cytoxicity. (Blood. 2011;117(20):5463-5472) C1 [Bagnara, Davide; Kaufman, Matthew S.; Calissano, Carlo; Marsilio, Sonia; Patten, Piers E. M.; Simone, Rita; Chum, Philip; Yan, Xiao-Jie; Allen, Steven L.; Kolitz, Jonathan E.; Lee, Annette; Gregersen, Peter K.; Rai, Kanti R.; Chiorazzi, Nicholas] N Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Kaufman, Matthew S.; Rai, Kanti R.] N Shore LIJ Hlth Syst, Long Isl Jewish Med Ctr, Dept Med, New Hyde Pk, NY USA. [Kaufman, Matthew S.; Allen, Steven L.; Kolitz, Jonathan E.; Rai, Kanti R.; Chiorazzi, Nicholas] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Allen, Steven L.; Kolitz, Jonathan E.; Gregersen, Peter K.; Chiorazzi, Nicholas] N Shore LIJ Hlth Syst, N Shore Univ Hosp, Dept Med, Manhasset, NY 11030 USA. [Baskar, Sivasubramanian; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mellstedt, Hakan; Rabbani, Hodjattallah] Karolinska Inst, Canc Ctr Karolinska, Stockholm, Sweden. [Mellstedt, Hakan; Rabbani, Hodjattallah] Karolinska Univ Hosp Solna, Stockholm, Sweden. [Lee, Annette; Gregersen, Peter K.] NYU, Sch Med, Dept Med, New York, NY USA. [Chiorazzi, Nicholas] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. RP Chiorazzi, N (reprint author), N Shore LIJ Hlth Syst, Feinstein Inst Med Res, 350 Community Dr, Manhasset, NY 11030 USA. EM NChizzi@NSHS.edu RI Bagnara, Davide/L-2691-2016; OI Bagnara, Davide/0000-0001-7889-8103; Allen, Steven/0000-0002-3482-3182 FU Karches Foundation; Prince Foundation; Marks Foundation; Jerome Levy Foundation; Leon Levy Foundation; Tebil Foundation Inc; Joseph Eletto Leukemia Research Fund; Lauri Strauss Leukemia Foundation; Leukemia and Lymphoma Research, UK FX These studies were supported in part by The Karches Foundation, The Prince Foundation, The Marks Foundation, The Jerome Levy Foundation, The Leon Levy Foundation, the Tebil Foundation Inc, and the Joseph Eletto Leukemia Research Fund. D.B. was an Ambassador Felix Schnyder Postdoctoral Research Fellow of the Lauri Strauss Leukemia Foundation. P.P. is supported by Leukemia and Lymphoma Research, UK. NR 50 TC 77 Z9 77 U1 0 U2 8 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 MAY 19 PY 2011 VL 117 IS 20 BP 5463 EP 5472 DI 10.1182/blood-2010-12-324210 PG 10 WC Hematology SC Hematology GA 766AR UT WOS:000290751300025 PM 21385850 ER PT J AU O'Brien, EP Straub, JE Brooks, BR Thirumalai, D AF O'Brien, Edward P. Straub, John E. Brooks, Bernard R. Thirumalai, D. TI Influence of Nanoparticle Size and Shape on Oligomer Formation of an Amyloidogenic Peptide SO JOURNAL OF PHYSICAL CHEMISTRY LETTERS LA English DT Article ID PHYSIOLOGICAL CONSEQUENCES; PROTEIN FIBRILLATION; HEMOGLOBIN SOLUTIONS; STABILITY; DYNAMICS; SPECTROSCOPY; NUCLEATION; KINETICS; FIBRILS; ENERGY AB Understanding the influence of macromolecular crowding and nanoparticles on the formation of in-register beta-sheets, the primary structural component of amyloid fibrils, is a first step toward describing in vivo protein aggregation and interactions between synthetic materials and proteins. Using all-atom molecular simulations in implicit solvent, we illustrate the effects of nanoparticle size, shape, and volume fraction on oligomer formation of an amyloidogenic peptide from the transthyretin protein. Surprisingly, we find that inert spherical crowding particles destabilize in-register beta-sheets formed by dimers while stabilizing beta-sheets comprised of trimers and tetramers. As the radius of the nanoparticle increases, crowding effects decrease, implying that smaller crowding particles have the largest influence on the earliest amyloid species. We explain these results using a theory based on the depletion effect. Finally, we show that spherocylindrical crowders destabilize the ordered beta-sheet dimer to a greater extent than spherical crowders, which underscores the influence of nanoparticle shape on protein aggregation. C1 [O'Brien, Edward P.; Thirumalai, D.] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. [Thirumalai, D.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [O'Brien, Edward P.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Straub, John E.] Boston Univ, Dept Chem, Boston, MA 02215 USA. RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. EM thirum@umd.edu RI O'Brien, Edward/C-3587-2015 FU NIH [R01 GM076688-080]; NSF; National Heart Lung and Blood Institute of the NIH FX This work was supported by a NIH grant (R01 GM076688-080) to J.E.S. and D.T., a NSF postdoctoral Fellowship to E.O., and the intramural program at the National Heart Lung and Blood Institute of the NIH to B.B. NR 47 TC 18 Z9 18 U1 5 U2 39 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7185 J9 J PHYS CHEM LETT JI J. Phys. Chem. Lett. PD MAY 19 PY 2011 VL 2 IS 10 BP 1171 EP 1177 DI 10.1021/jz200330k PG 7 WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Atomic, Molecular & Chemical SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 767GQ UT WOS:000290843700012 PM 21691423 ER PT J AU Pressler, H Sissung, TM Venzon, D Price, DK Figg, WD AF Pressler, Heather Sissung, Tristan M. Venzon, David Price, Douglas K. Figg, William D. TI Expression of OATP Family Members in Hormone-Related Cancers: Potential Markers of Progression SO PLOS ONE LA English DT Article ID ESTROGEN-RECEPTOR; ANDROGEN; CARCINOMA; TRANSPORTERS; PROLIFERATION; POLYMORPHISMS; TESTOSTERONE AB The organic anion transporting polypeptide (OATP) family of transporters has been implicated in prostate cancer disease progression probably by transporting hormones or drugs. In this study, we aimed to elucidate the expression, frequency, and relevance of OATPs as a biomarker in hormone-dependent cancers. We completed a study examining SLCO1B3, SLCO1B1 and SLCO2B1 mRNA expression in 381 primary, independent patient samples representing 21 cancers and normal tissues. From a separate cohort, protein expression of OATP1B3 was examined in prostate, colon, and bladder tissue. Based on expression frequency, SLCO2B1 was lower in liver cancer (P = 0.04) which also trended lower with decreasing differentiation (P = 0.004) and lower magnitude in pancreatic cancer (P = 0.05). SLCO2B1 also had a higher frequency in thyroid cancer (67%) than normal (0%) and expression increased with stage (P = 0.04). SLCO1B3 was expressed in 52% of cancerous prostate samples and increased SLCO1B3 expression trended with higher Gleason score (P = 0.03). SLCO1B3 expression was also higher in testicular cancer (P = 0.02). SLCO1B1 expression was lower in liver cancer (P = 0.04) which trended lower with liver cancer grade (P = 0.0004) and higher with colon cancer grade (P = 0.05). Protein expression of OATP1B3 was examined in normal and cancerous prostate, colon, and bladder tissue samples from an independent cohort. The results were similar to the transcription data, but showed distinct localization. OATPs correlate to differentiation in certain hormone-dependent cancers, thus may be useful as biomarkers for assessing clinical treatment and stage of disease. C1 [Pressler, Heather; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. [Sissung, Tristan M.; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Pressler, Heather] Johns Hopkins Univ, Baltimore, MD USA. RP Pressler, H (reprint author), NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU National Institutes of Health, National Cancer Institute, Bethesda, MD; National Science Foundation; Department of Defense [PC094258] FX This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD www.nih.gov. Stipend support was provided for Ms. Pressler by the National Science Foundation www.nsf.gov and Department of Defense Prostate Cancer Research Training Award #PC094258 www.grants.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study. NR 21 TC 42 Z9 44 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 19 PY 2011 VL 6 IS 5 AR e20372 DI 10.1371/journal.pone.0020372 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 766HI UT WOS:000290771200057 PM 21625523 ER PT J AU Chew, EY AF Chew, Emily Y. TI Fatty Acids and Retinopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 19 PY 2011 VL 364 IS 20 BP 1970 EP 1971 DI 10.1056/NEJMcibr1101606 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 765PJ UT WOS:000290720700016 PM 21591950 ER PT J AU Chernikova, D Motamedi, S Csuros, M Koonin, EV Rogozin, IB AF Chernikova, Diana Motamedi, Sam Csueroes, Miklos Koonin, Eugene V. Rogozin, Igor B. TI A late origin of the extant eukaryotic diversity: divergence time estimates using rare genomic changes SO BIOLOGY DIRECT LA English DT Article DE bilateria; opisthokonts; angiosperms; last eukaryotic common ancestor; molecular dating ID MONOCOT-DICOT DIVERGENCE; AMINO-ACID REPLACEMENTS; MOLECULAR CLOCK; PHOTOSYNTHETIC EUKARYOTES; PHYLOGENETIC ANALYSIS; CAMBRIAN EXPLOSION; ANIMAL EVOLUTION; METAZOAN PHYLA; TREE; SUPPORT AB Background: Accurate estimation of the divergence time of the extant eukaryotes is a fundamentally important but extremely difficult problem owing primarily to gross violations of the molecular clock at long evolutionary distances and the lack of appropriate calibration points close to the date of interest. These difficulties are intrinsic to the dating of ancient divergence events and are reflected in the large discrepancies between estimates obtained with different approaches. Estimates of the age of Last Eukaryotic Common Ancestor (LECA) vary approximately twofold, from similar to 1,100 million years ago (Mya) to similar to 2,300 Mya. Results: We applied the genome-wide analysis of rare genomic changes associated with conserved amino acids (RGC_CAs) and used several independent techniques to obtain date estimates for the divergence of the major lineages of eukaryotes with calibration intervals for insects, land plants and vertebrates. The results suggest an early divergence of monocot and dicot plants, approximately 340 Mya, raising the possibility of plant-insect coevolution. The divergence of bilaterian animal phyla is estimated at similar to 400-700 Mya, a range of dates that is consistent with cladogenesis immediately preceding the Cambrian explosion. The origin of opisthokonts (the supergroup of eukaryotes that includes metazoa and fungi) is estimated at similar to 700-1,000 Mya, and the age of LECA at similar to 1,000-1,300 Mya. We separately analyzed the red algal calibration interval which is based on single fossil. This analysis produced time estimates that were systematically older compared to the other estimates. Nevertheless, the majority of the estimates for the age of the LECA using the red algal data fell within the 1,200-1,400 Mya interval. Conclusion: The inference of a "young LECA" is compatible with the latest of previously estimated dates and has substantial biological implications. If these estimates are valid, the approximately 1 to 1.4 billion years of evolution of eukaryotes that is open to comparative-genomic study probably was preceded by hundreds of millions years of evolution that might have included extinct diversity inaccessible to comparative approaches. Reviewers: This article was reviewed by William Martin, Herve Philippe (nominated by I. King Jordan), and Romain Derelle. C1 [Chernikova, Diana; Motamedi, Sam; Koonin, Eugene V.; Rogozin, Igor B.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Csueroes, Miklos] Univ Montreal, Dept Comp Sci & Operat Res, Montreal, PQ, Canada. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU National Library of Medicine at National Institutes of Health/DHHS; National Sciences and Engineering Research Council of Canada FX We thank Linda Kah for providing her unpublished data, Bill Martin, Nick Butterfield, Linda Kah, Alexander Lobkovsky, Sergei Mekhedov, Liran Carmel, Kira Makarova and Yuri Wolf for useful discussions, and especially Bill Martin for critical reading of an early version of the manuscript. We are grateful to Leonard Poliakov and Olga Batyreva for help with the calibration procedure using vertebrate divergence times. This work was supported in part by the Intramural Research Program of the National Library of Medicine at National Institutes of Health/DHHS, and by a research grant from the National Sciences and Engineering Research Council of Canada (to MC). NR 109 TC 21 Z9 21 U1 1 U2 37 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD MAY 19 PY 2011 VL 6 AR 26 DI 10.1186/1745-6150-6-26 PG 18 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 784BC UT WOS:000292127600001 PM 21595937 ER PT J AU Davis, JL Pandalai, P Ripley, RT Langan, RC Steinberg, SM Walker, M Toomey, MA Levy, E Avital, I AF Davis, Jeremy L. Pandalai, Prakash Ripley, R. Taylor Langan, Russell C. Steinberg, Seth M. Walker, Melissa Toomey, Mary Ann Levy, Elliot Avital, Itzhak TI Regional Chemotherapy in Locally Advanced Pancreatic Cancer: RECLAP Trial SO TRIALS LA English DT Article ID ARTERIAL INFUSION CHEMOTHERAPY; VASCULAR SUPPLY DISTRIBUTION; COOPERATIVE-ONCOLOGY-GROUP; DOSE RATE INFUSION; PHASE-III TRIAL; SUPERSELECTIVE EMBOLIZATION; 30-MINUTE INFUSION; I TRIAL; GEMCITABINE; CARCINOMA AB Background: Pancreatic cancer is the fourth leading cause of cancer death in the United States. Surgery offers the only chance for cure. However, less than twenty percent of patients are considered operative candidates at the time of diagnosis. A common reason for being classified as unresectable is advanced loco-regional disease. A review of the literature indicates that almost nine hundred patients with pancreatic cancer have received regional chemotherapy in the last 15 years. Phase I studies have shown regional administration of chemotherapy to be safe. The average reported response rate was approximately 26%. The average 1-year survival was 39%, with an average median survival of 9 months. Of the patients that experienced a radiographic response to therapy, 78 (78/277, 28%) patients underwent exploratory surgery following regional chemotherapy administration; thirty-two (41%) of those patients were amenable to pancreatectomy. None of the studies performed analyses to identify factors predicting response to regional chemotherapy. Progressive surgical techniques combined with current neoadjuvant chemoradiotherapy strategies have already yielded emerging support for a multimodality approach to treatment of advanced pancreatic cancer. Intravenous gemcitabine is the current standard treatment of pancreatic cancer. However, >90% of the drug is secreted unchanged affecting toxicity but not the cancer per se. Gemcitabine is converted inside the cell into its active drug form in a rate limiting reaction. We hypothesize that neoadjuvant regional chemotherapy with continuous infusion of gemcitabine will be well tolerated and may improve resectability rates in cases of locally advanced pancreatic cancer. Design: This is a phase I study designed to evaluate the feasibility and toxicity of super-selective intra-arterial administration of gemcitabine in patients with locally advanced, unresectable pancreatic adenocarcinoma. Patients considered unresectable due to locally advanced pancreatic cancer will receive super-selective arterial infusion of gemcitabine over 24 hours via subcutaneous indwelling port. Three to six patients will be enrolled per dose cohort, with seven cohorts, plus an additional six patients at the maximum tolerated dose; accrual is expected to last 36 months. Secondary objectives will include the determination of progression free and overall survival, as well as the conversion rate from unresectable to potentially resectable pancreatic cancer. C1 [Davis, Jeremy L.; Pandalai, Prakash; Ripley, R. Taylor; Langan, Russell C.; Walker, Melissa; Toomey, Mary Ann; Avital, Itzhak] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Levy, Elliot] NCI, Intervent Radiol Dept, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Avital, I (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM avitali@mail.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research, Bethesda, MD, USA FX This study is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, Bethesda, MD, USA. NR 23 TC 9 Z9 11 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD MAY 19 PY 2011 VL 12 AR 129 DI 10.1186/1745-6215-12-129 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 780TD UT WOS:000291881100001 PM 21595953 ER PT J AU Hippen, KL Merkel, SC Schirm, DK Sieben, CM Sumstad, D Kadidlo, DM McKenna, DH Bromberg, JS Levine, BL Riley, JL June, CH Scheinberg, P Douek, DC Miller, JS Wagner, JE Blazar, BR AF Hippen, Keli L. Merkel, Sarah C. Schirm, Dawn K. Sieben, Christine M. Sumstad, Darin Kadidlo, Diane M. McKenna, David H. Bromberg, Jonathan S. Levine, Bruce L. Riley, James L. June, Carl H. Scheinberg, Phillip Douek, Daniel C. Miller, Jeffrey S. Wagner, John E. Blazar, Bruce R. TI Massive ex Vivo Expansion of Human Natural Regulatory T Cells (T-regs) with Minimal Loss of in Vivo Functional Activity SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID VERSUS-HOST-DISEASE; ANTIGEN-PRESENTING CELLS; SUPPRESSIVE FUNCTION; CD28 COSTIMULATION; FOXP3 EXPRESSION; RAPAMYCIN; IMMUNOTHERAPY; VITRO; CULTURES; BLOOD AB Graft-versus-host disease (GVHD) is a frequent and severe complication after hematopoietic cell transplantation. Natural CD4(+)CD25(+) regulatory T cells (nT(regs)) have proven highly effective in preventing GVHD and autoimmunity in murine models. Yet, clinical application of nT(regs) has been severely hampered by their low frequency and unfavorable ex vivo expansion properties. Previously, we demonstrated that umbilical cord blood (UCB) nT(regs) could be purified and expanded in vitro using good manufacturing practice (GMP) reagents; however, the initial number of nT(regs) in UCB units is limited, and average yield after expansion was only 1 x 10(9) nT(regs). Therefore, we asked whether yield could be increased by using peripheral blood (PB), which contains far larger quantities of nT(regs). PB nT(regs) were purified under GMP conditions and expanded 80-fold to yield 19 x 10(9) cells using anti-CD3 antibody-loaded, cell-based artificial antigen-presenting cells (aAPCs) that expressed the high-affinity Fc receptor and CD86. A single restimulation increased expansion to similar to 3000-fold and yield to >600 x 10(9) cells while maintaining Foxp3 expression and suppressor function. nT(reg) expansion was similar to 50 million-fold when flow sort-purified nT(regs) were restimulated four times with aAPCs. Indeed, cryopreserved donor nT(regs) restimulated four times significantly reduced GVHD lethality induced by the infusion of human T cells into immune-deficient mice. The capability to efficiently produce donor cell banks of functional nT(regs) could transform the treatment of GVHD and autoimmunity by providing an off-the-shelf, cost-effective, and proven cellular therapy. C1 [Hippen, Keli L.; Merkel, Sarah C.; Schirm, Dawn K.; Sieben, Christine M.; Wagner, John E.; Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Ctr Canc, Minneapolis, MN 55455 USA. [Sumstad, Darin; Kadidlo, Diane M.; McKenna, David H.] Univ Minnesota, Mol & Cellular Therapeut Facil, Minneapolis, MN 55455 USA. [Bromberg, Jonathan S.] Univ Maryland, Sch Med, Dept Surg, Div Transplantat, Baltimore, MD 21201 USA. [Levine, Bruce L.; Riley, James L.; June, Carl H.] Univ Penn, Abramson Family Canc Ctr, Res Inst, Ctr Canc, Philadelphia, PA 19104 USA. [Scheinberg, Phillip; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Miller, Jeffrey S.] Univ Minnesota, Ctr Canc, Div Bone Marrow Transplantat, Dept Med, Minneapolis, MN 55455 USA. RP Hippen, KL (reprint author), Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Ctr Canc, Minneapolis, MN 55455 USA. EM hippe002@umn.edu; blaza001@umn.edu RI Levine, Bruce/D-1688-2009; Scheinberg, Phillip/H-5251-2012; OI Riley, James/0000-0002-1057-576X; Scheinberg, Phillip/0000-0002-9047-4538; Miller, Jeffrey S/0000-0002-0339-4944 FU Children's Cancer Research Fund; Blood and Marrow Transplant Research Fund; Leukemia and Lymphoma Translational Research [R6029-07, R37 HL56067, P01 AI056299, P01 CA067493, N01HB037164]; Becton Dickinson; JDRF Collaborative Centers for Cell Therapy; JDRF Center on Cord Blood Therapies for Type 1 Diabetes FX This work was supported in part by research grants from the Children's Cancer Research Fund and Blood and Marrow Transplant Research Fund to K. L. H.; Leukemia and Lymphoma Translational Research (grant R6029-07), R37 HL56067, and P01 AI056299 to B. R. B., P01 CA067493 and N01HB037164 to B. R. B., J.E.W., and J.S.M.; support from Miltenyi Biotec to B. R. B. and J.E.W.; a grant from Becton Dickinson to J.E.W.; and support from the JDRF Collaborative Centers for Cell Therapy and the JDRF Center on Cord Blood Therapies for Type 1 Diabetes to J.L.R. and C.H.J. NR 38 TC 97 Z9 99 U1 1 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 18 PY 2011 VL 3 IS 83 AR 83ra41 DI 10.1126/scitranslmed.3001809 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 795MV UT WOS:000292979200004 PM 21593401 ER PT J AU Barton, KA Caughey, B AF Barton, Kelly A. Caughey, Byron TI Is PrP the road to ruin? SO EMBO JOURNAL LA English DT Editorial Material ID CELLULAR PRION PROTEIN; AMYLOID-BETA OLIGOMERS; IMPAIRMENT AB Neurodegenerative disorders are one among the most debilitating diseases of an ageing population. Understanding the mechanisms of neuronal cell death during pathogenesis of diseases such as Alzheimer's, Parkinson's, Huntington's, and prion diseases is key to addressing the options for treatment and prevention of brain deterioration. One feature of many such diseases is the accumulation of specific misfolded proteins. Often these misfolded proteins take the form of large amyloid fibrils or plaques, but recent observations implicate small soluble oligomers as the primary causes of neuronal dysfunction. How these misfolded proteins trigger cell death pathways is largely unknown, but some reports have suggested mediation by normal cellular prion protein (PrP(C)). In this issue, Resenberger et al (2011) provide evidence for membrane-anchored PrP(C)'s role in recognizing a variety of beta-sheet-rich protein conformers and transducing pro-apoptotic signals. C1 [Barton, Kelly A.; Caughey, Byron] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Barton, KA (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. EM bartonk@niaid.nih.gov NR 11 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 0261-4189 J9 EMBO J JI Embo J. PD MAY 18 PY 2011 VL 30 IS 10 BP 1882 EP 1884 DI 10.1038/emboj.2011.129 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 777SN UT WOS:000291645400004 PM 21593729 ER PT J AU Kravitz, DJ Peng, CS Baker, CI AF Kravitz, Dwight J. Peng, Cynthia S. Baker, Chris I. TI Real-World Scene Representations in High-Level Visual Cortex: It's the Spaces More Than the Places SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PARAHIPPOCAMPAL CORTEX; TOPOGRAPHICAL DISORIENTATION; OBJECT REPRESENTATIONS; TEMPORAL CORTEX; HUMAN BRAIN; AREA; RECOGNITION; INFORMATION; CONTEXT; FMRI AB Real-world scenes are incredibly complex and heterogeneous, yet we are able to identify and categorize them effortlessly. In humans, the ventral temporal parahippocampal place area (PPA) has been implicated in scene processing, but scene information is contained in many visual areas, leaving their specific contributions unclear. Although early theories of PPA emphasized its role in spatial processing, more recent reports of its function have emphasized semantic or contextual processing. Here, using functional imaging, we reconstructed the organization of scene representations across human ventral visual cortex by analyzing the distributed response to 96 diverse real-world scenes. We found that, although individual scenes could be decoded in both PPA and early visual cortex (EVC), the structure of representations in these regions was vastly different. In both regions, spatial rather than semantic factors defined the structure of representations. However, in PPA, representations were defined primarily by the spatial factor of expanse (open, closed) and in EVC primarily by distance (near, far). Furthermore, independent behavioral ratings of expanse and distance correlated strongly with representations in PPA and peripheral EVC, respectively. In neither region was content (manmade, natural) a major contributor to the overall organization. Furthermore, the response of PPA could not be used to decode the high-level semantic category of scenes even when spatial factors were held constant, nor could category be decoded across different distances. These findings demonstrate, contrary to recent reports, that the response PPA primarily reflects spatial, not categorical or contextual, aspects of real-world scenes. C1 [Kravitz, Dwight J.; Peng, Cynthia S.; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Kravitz, DJ (reprint author), NIMH, Lab Brain Cognit, NIH, 10 Ctr Dr,Room 3N228, Bethesda, MD 20892 USA. EM kravitzd@mail.nih.gov RI Kravitz, Dwight/B-8430-2012; OI Baker, Chris/0000-0001-6861-8964 FU National Institute of Mental Health FX This work was supported by the National Institute of Mental Health Intramural Research Program. Thanks to Marlene Behrmann, Assaf Harel, Alex Martin, Dale Stevens, and other members of the Laboratory of Brain and Cognition, National Institute of Mental Health for helpful comments and discussion. NR 55 TC 100 Z9 101 U1 5 U2 25 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 18 PY 2011 VL 31 IS 20 BP 7322 EP 7333 DI 10.1523/JNEUROSCI.4588-10.2011 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 765OA UT WOS:000290716600011 PM 21593316 ER PT J AU Mathur, BN Capik, NA Alvarez, VA Lovinger, DM AF Mathur, Brian N. Capik, Nicole A. Alvarez, Veronica A. Lovinger, David M. TI Serotonin Induces Long-Term Depression at Corticostriatal Synapses SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ENDOCANNABINOID RELEASE; PARKINSONS-DISEASE; 5-HT1B RECEPTORS; NERVOUS-SYSTEM; SPINY NEURONS; STRIATUM; RAT; LOCALIZATION; TRANSMISSION; INHIBITION AB The striatum has important roles in motor control and action learning and, like many brain regions, receives multiple monoaminergic inputs. We have examined serotonergic modulation of rat and mouse corticostriatal neurotransmission and find that serotonin (5-HT) activates 5-HT(1b) receptors resulting in a long-term depression (LTD) of glutamate release and striatal output that we have termed 5-HT-LTD. 5-HT-LTD is presynaptically mediated, cAMP pathway dependent, and inducible by endogenous striatal 5-HT, as revealed by application of a selective 5-HT reuptake inhibitor. 5-HT-LTD is mutually occlusive with dopamine/endocannabinoid-dependent LTD, suggesting that these two forms of LTD act on the same corticostriatal terminals. Thus, serotonergic and dopaminergic mechanisms exist that may interact to persistently sculpt corticostriatal circuits, potentially influencing action learning and striatal-based disorders. C1 [Mathur, Brian N.; Capik, Nicole A.; Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20852 USA. [Alvarez, Veronica A.] NIAAA, Sect Neuronal Struct, Lab Integrat Neurosci, NIH, Bethesda, MD 20852 USA. RP Lovinger, DM (reprint author), 5625 Fishers Lane,Room TS 13A, Rockville, MD 20852 USA. EM lovindav@willco.niaaa.nih.gov RI yu, yan/C-2322-2012; Alvarez, Veronica /E-9745-2015 OI Alvarez, Veronica /0000-0003-2611-8675 FU Intramural NIH HHS [ZIA AA000416-04, Z01 AA000407-06, ZIA AA000421-02, ZIA AA000421-03] NR 27 TC 36 Z9 36 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 18 PY 2011 VL 31 IS 20 BP 7402 EP 7411 DI 10.1523/JNEUROSCI.6250-10.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 765OA UT WOS:000290716600019 PM 21593324 ER PT J AU Moreno, E Vaz, SH Cai, NS Ferrada, C Quiroz, C Barodia, SK Kabbani, N Canela, EI McCormick, PJ Lluis, C Franco, R Ribeiro, JA Sebastiao, AM Ferre, S AF Moreno, Estefania Vaz, Sandra H. Cai, Ning-Sheng Ferrada, Carla Quiroz, Cesar Barodia, Sandeep Kumar Kabbani, Nadine Canela, Enric I. McCormick, Peter J. Lluis, Carme Franco, Rafael Ribeiro, Joaquim A. Sebastiao, Ana M. Ferre, Sergi TI Dopamine-Galanin Receptor Heteromers Modulate Cholinergic Neurotransmission in the Rat Ventral Hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article ID INHIBITS ACETYLCHOLINE-RELEASE; LONG-TERM POTENTIATION; IN-VIVO; ALZHEIMERS-DISEASE; ADENOSINE A(2A); BASAL FOREBRAIN; DRUG TARGETS; D1 RECEPTOR; PROTEIN; IMMUNOREACTIVITY AB Previous studies have shown that dopamine and galanin modulate cholinergic transmission in the hippocampus, but little is known about the mechanisms involved and their possible interactions. By using resonance energy transfer techniques in transfected mammalian cells, we demonstrated the existence of heteromers between the dopamine D(1)-like receptors (D(1) and D(5)) and galanin Gal(1), but not Gal(2) receptors. Within the D(1)-Gal(1) and D(5)-Gal(1) receptor heteromers, dopamine receptor activation potentiated and dopamine receptor blockade counteracted MAPK activation induced by stimulation of Gal(1) receptors, whereas Gal(1) receptor activation or blockade did not modify D(1)-like receptor-mediated MAPK activation. Ability of a D(1)-like receptor antagonist to block galanin-induced MAPK activation (cross-antagonism) was used as a "biochemical fingerprint" of D(1)-like-Gal(1) receptor heteromers, allowing their identification in the rat ventral hippocampus. The functional role of D(1)-like-Gal receptor heteromers was demonstrated in synaptosomes from rat ventral hippocampus, where galanin facilitated acetylcholine release, but only with costimulation of D(1)-like receptors. Electrophysiological experiments in rat ventral hippocampal slices showed that these receptor interactions modulate hippocampal synaptic transmission. Thus, a D(1)-like receptor agonist that was ineffective when administered alone turned an inhibitory effect of galanin into an excitatory effect, an interaction that required cholinergic neurotransmission. Altogether, our results strongly suggest that D(1)-like-Gal(1) receptor heteromers act as processors that integrate signals of two different neurotransmitters, dopamine and galanin, to modulate hippocampal cholinergic neurotransmission. C1 [Cai, Ning-Sheng; Quiroz, Cesar; Barodia, Sandeep Kumar; Ferre, Sergi] Natl Inst Drug Abuse, Intramural Res Program, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. [Moreno, Estefania; Ferrada, Carla; Canela, Enric I.; McCormick, Peter J.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Neurodegenerat, E-08028 Barcelona, Spain. [Moreno, Estefania; Ferrada, Carla; Canela, Enric I.; McCormick, Peter J.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Dept Biochem & Mol Biol, Fac Biol, E-08028 Barcelona, Spain. [Vaz, Sandra H.; Ribeiro, Joaquim A.; Sebastiao, Ana M.] Univ Lisbon, Inst Pharmacol & Neurosci, Fac Med, P-1649028 Lisbon, Portugal. [Vaz, Sandra H.; Ribeiro, Joaquim A.; Sebastiao, Ana M.] Univ Lisbon, Inst Mol Med, Unit Neurosci, P-1649028 Lisbon, Portugal. [Kabbani, Nadine] Krasnow Inst Adv Study, Dept Mol Neurosci, Fairfax, VA 22030 USA. [Franco, Rafael] Univ Navarra, Ctr Invest Med Aplicada, Pamplona 31008, Spain. RP Ferre, S (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Dept Hlth & Human Serv, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Canela, Enric I./M-8726-2013; McCormick, Peter/E-7387-2012; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; Vaz, Sandra/L-7393-2015; OI Canela, Enric I./0000-0003-4992-7440; McCormick, Peter/0000-0002-2225-5181; Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919; Moreno, Estefania/0000-0002-2491-5753; Vaz, Sandra/0000-0003-4258-9397; Ribeiro, Joaquim/0000-0002-9330-3507; Sebastiao, Ana M/0000-0001-9030-6115 FU Spanish Ministerio de Ciencia y Tecnologia [SAF2008-03 229-E, SAF2009-07276, SAF2010-18472]; National Institute on Drug Abuse, EU [B-30]; Fundacao para a Ciencia e Tecnologia (FCT, Portugal); FCT [SFRHBD/27989/2006] FX This work was supported by the Spanish Ministerio de Ciencia y Tecnologia (Grants SAF2008-03 229-E, SAF2009-07276 and SAF2010-18472), the intramural funds of the National Institute on Drug Abuse, EU (Cost B-30 concerted action), and Fundacao para a Ciencia e Tecnologia (FCT, Portugal). S.H.V. is in receipt of a FCT PhD fellowship (SFRHBD/27989/2006). P.J.M. is a Ramon y Cajal Investigator. We acknowledge the technical help obtained from Jasmina Jimenez (Molecular Neurobiology laboratory, Barcelona University, Barcelona). NR 51 TC 16 Z9 19 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 18 PY 2011 VL 31 IS 20 BP 7412 EP 7423 DI 10.1523/JNEUROSCI.0191-11.2011 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 765OA UT WOS:000290716600020 PM 21593325 ER PT J AU Mileykovskiy, B Morales, M AF Mileykovskiy, Boris Morales, Marisela TI Duration of Inhibition of Ventral Tegmental Area Dopamine Neurons Encodes a Level of Conditioned Fear SO JOURNAL OF NEUROSCIENCE LA English DT Article ID MEDIAL FRONTAL-CORTEX; AVERSIVE STIMULI; NUCLEUS-ACCUMBENS; BEHAVIORAL REACTIONS; LATERAL HABENULA; MONKEY MIDBRAIN; RESPONSES; ACTIVATION; SIGNALS; STRESS AB It is widely accepted that midbrain dopamine (DA) neurons encode actual and expected reward values by phasic alterations in firing rate. However, how DA neurons encode negative events in the environment is still unclear because some DA neurons appear to be depressed and others excited by aversive stimuli. Here, we show that exposing fear-conditioned rats to stimuli predicting electrical shock elicited three types of biphasic responses, each of which contained an inhibitory pause, in neurochemically identified ventral tegmental area (VTA) DA neurons. The duration of the inhibitory pause in these responses of VTA DA neurons was in direct proportion to the increase in respiratory rate reflecting the level of conditioned fear. Our results suggest that the duration of inhibition of VTA DA neurons encodes negative emotional values of signals predicting aversive events in the environment. C1 [Mileykovskiy, Boris; Morales, Marisela] Natl Inst Drug Abuse, Intramural Res Program, Neuronal Network Sect, Baltimore, MD 21224 USA. RP Mileykovskiy, B (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Neuronal Network Sect, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mileykob@nida.nih.gov; mmorales@intra.nida.nih.gov FU National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse. We thank Dr. Roy Wise for comments to this manuscript. NR 33 TC 35 Z9 35 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 18 PY 2011 VL 31 IS 20 BP 7471 EP 7476 DI 10.1523/JNEUROSCI.5731-10.2011 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 765OA UT WOS:000290716600025 PM 21593330 ER PT J AU Andrade, BB Santos, CJN Camargo, LM Souza-Neto, SM Reis, A Clarencio, J Mendonca, VRR Luz, NF Camargo, EP Barral, A Silva, AAM Barral-Netto, M AF Andrade, Bruno B. Santos, Cristiane J. N. Camargo, Luis M. Souza-Neto, Sebastiao M. Reis-Filho, Antonio Clarencio, Jorge Mendonca, Vitor R. R. Luz, Nivea F. Camargo, Erney P. Barral, Aldina Silva, Antonio A. M. Barral-Netto, Manoel TI Hepatitis B Infection Is Associated with Asymptomatic Malaria in the Brazilian Amazon SO PLOS ONE LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; NECROSIS-FACTOR-ALPHA; VIRUS-INFECTION; INTERFERON-GAMMA; WESTERN AMAZON; VIVAX MALARIA; LIVER-STAGE; INTERLEUKIN-10; IMMUNITY; RESPONSES AB Background: Areas that are endemic for malaria are also highly endemic for hepatitis B virus (HBV) infection. Nevertheless, it is unknown whether HBV infection modifies the clinical presentation of malaria. This study aimed to address this question. Methodology and Findings: An observational study of 636 individuals was performed in Rondonia, western Amazon, Brazil between 2006 and 2007. Active and passive case detections identified Plasmodium infection by field microscopy and nested Polymerase Chain Reaction (PCR). HBV infections were identified by serology and confirmed by real-time PCR. Epidemiological information and plasma cytokine profiles were studied. The data were analyzed using adjusted multinomial logistic regression. Plasmodium-infected individuals with active HBV infection were more likely to be asymptomatic (OR: 120.13, P < 0.0001), present with lower levels of parasitemia and demonstrate a decreased inflammatory cytokine profile. Nevertheless, co-infected individuals presented higher HBV viremia. Plasmodium parasitemia inversely correlated with plasma HBV DNA levels (r=-0.6; P=0.0003). Conclusion: HBV infection diminishes the intensity of malaria infection in individuals from this endemic area. This effect seems related to cytokine balance and control of inflammatory responses. These findings add important insights to the understanding of the factors affecting the clinical outcomes of malaria in endemic regions. C1 [Andrade, Bruno B.; Souza-Neto, Sebastiao M.; Reis-Filho, Antonio; Clarencio, Jorge; Mendonca, Vitor R. R.; Luz, Nivea F.; Barral, Aldina; Barral-Netto, Manoel] Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, BA, Brazil. [Andrade, Bruno B.; Souza-Neto, Sebastiao M.; Reis-Filho, Antonio; Mendonca, Vitor R. R.; Luz, Nivea F.; Barral, Aldina; Barral-Netto, Manoel] Univ Fed Bahia, Fac Med Bahia, Salvador, BA, Brazil. [Santos, Cristiane J. N.; Silva, Antonio A. M.] Univ Fed Maranhao, Dept Saude Publ, Ctr Ciencias Saude, Sao Luis, Brazil. [Camargo, Luis M.; Camargo, Erney P.] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508 Sao Paulo, Brazil. [Camargo, Luis M.] Fac Sao Lucas, Fac Med, Porto Velho, Brazil. [Barral, Aldina; Barral-Netto, Manoel] INCT, Inst Invest Imunol, Sao Paulo, Brazil. RP Andrade, BB (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM mbarral@bahia.fiocruz.br RI Barral Netto, Manoel/B-3904-2009; Camargo, Luis/B-4156-2009; Clarencio, Jorge/H-3940-2012; Andrade, Bruno/J-9111-2012; Imunologia, Inct/I-2124-2013; Inagemp, Inct/J-9451-2013; Camargo, Erney/A-6765-2009; Martins de Souza Neto, Sebastiao/D-4506-2013; Silva, Antonio/B-5410-2009; OI Farias Luz, Nivea/0000-0003-1958-7043; Barral Netto, Manoel/0000-0002-5823-7903; Andrade, Bruno/0000-0001-6833-3811; Silva, Antonio/0000-0003-4968-5138; Camargo, Erney/0000-0003-0011-5871 FU FINEP [010409605]; FNDCT-CT Amazonia FX This work was supported by FINEP (010409605)/FNDCT-CT Amazonia. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 36 TC 19 Z9 21 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 18 PY 2011 VL 6 IS 5 AR e19841 DI 10.1371/journal.pone.0019841 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765PE UT WOS:000290720200038 PM 21625634 ER PT J AU Kang, YS Kim, W Huh, YH Bae, J Kim, JS Song, WK AF Kang, Yong Seok Kim, Wook Huh, Yun Hyun Bae, Jeomil Kim, Jin Soo Song, Woo Keun TI P130Cas Attenuates Epidermal Growth Factor (EGF) Receptor Internalization by Modulating EGF-Triggered Dynamin Phosphorylation SO PLOS ONE LA English DT Article ID ADAPTER PROTEIN CAS; TYROSINE PHOSPHORYLATION; C-SRC; SIGNAL-TRANSDUCTION; ERBB RECEPTORS; ENDOCYTOSIS; CELLS; ACTIVATION; KINASE; CANCER AB Background: Endocytosis controls localization-specific signal transduction via epidermal growth factor receptor (EGFR), as well as downregulation of that receptor. Extracellular matrix (ECM)-integrin coupling induces formation of macromolecular complexes that include EGFR, integrin, Src kinase and p130Cas, resulting in EGFR activation. In addition, cell adhesion to ECM increases EGFR localization at the cell surface and reduces EGFR internalization. The molecular mechanisms involved are not yet well understood. Methodology/Principal Findings: We investigated the molecular mechanism by which p130Cas affects the endocytic regulation of EGFR. Biochemical quantification revealed that cell adhesion to fibronectin (FN) increases total EGFR levels and its phosphorylation, and that p130Cas is required for this process. Measurements of Texas Red-labeled EGF uptake and cell surface EGFR revealed that p130Cas overexpression reduces EGF-induced EGFR internalization, while p130Cas depletion enhances it. In addition, both FN-mediated cell adhesion and p130Cas overexpression reduce EGF-stimulated dynamin phosphorylation, which is necessary for EGF-induced EGFR internalization. Coimmunoprecipitation and GST pull-down assays confirmed the interaction between p130Cas and dynamin. Moreover, a SH3-domain-deleted form of p130Cas, which shows diminished binding to dynamin, inhibits dynamin phosphorylation and EGF uptake less effectively than wild-type p130Cas. Conclusions/Significance: Our results show that p130Cas plays an inhibitory role in EGFR internalization via its interaction with dynamin. Given that the EGFR internalization process determines signaling density and specificity in the EGFR pathway, these findings suggest that the interaction between p130Cas and dynamin may regulate EGFR trafficking and signaling in the same manner as other endocytic regulatory proteins related to EGFR endocytosis. C1 [Kang, Yong Seok; Huh, Yun Hyun; Bae, Jeomil; Kim, Jin Soo; Song, Woo Keun] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea. [Kang, Yong Seok; Huh, Yun Hyun; Bae, Jeomil; Kim, Jin Soo; Song, Woo Keun] Gwangju Inst Sci & Technol, Bio Imaging & Cell Dynam Res Ctr, Kwangju, South Korea. [Kim, Wook] NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. RP Kang, YS (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea. EM wksong@gist.ac.kr FU Bio Imaging Research Center at GIST; Cell Dynamic Research Center [20100001616]; Korea Foundation for Cancer Research [KFCR-2009-001]; Mid-career Researcher Program [20100000344]; Korean Government (MEST) [2010K001181] FX This work was supported by grants from the Bio Imaging Research Center at GIST, the Cell Dynamic Research Center (20100001616), the Korea Foundation for Cancer Research (KFCR-2009-001), the Mid-career Researcher Program (20100000344), and the Converging Research Center Program (2010K001181) funded by the Korean Government (MEST). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 2 Z9 3 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 18 PY 2011 VL 6 IS 5 AR e20125 DI 10.1371/journal.pone.0020125 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765PE UT WOS:000290720200065 PM 21625594 ER PT J AU Gonzalez, JR Rodriguez-Santiago, B Caceres, A Pique-Regi, R Rothman, N Chanock, SJ Armengol, L Perez-Jurado, LA AF Gonzalez, Juan R. Rodriguez-Santiago, Benjamin Caceres, Alejandro Pique-Regi, Roger Rothman, Nathaniel Chanock, Stephen J. Armengol, Lluis Perez-Jurado, Luis A. TI A fast and accurate method to detect allelic genomic imbalances underlying mosaic rearrangements using SNP array data SO BMC BIOINFORMATICS LA English DT Article ID COPY-NUMBER-VARIATION; LOW-LEVEL MOSAICISM; SOMATIC MOSAICISM; CGH DATA; POLYMORPHISM; MECHANISMS; CANCER AB Background: Mosaicism for copy number and copy neutral chromosomal rearrangements has been recently identified as a relatively common source of genetic variation in the normal population. However its prevalence is poorly defined since it has been only studied systematically in one large-scale study and by using non optimal adhoc SNP array data analysis tools, uncovering rather large alterations (> 1 Mb) and affecting a high proportion of cells. Here we propose a novel methodology, Mosaic Alteration Detection-MAD, by providing a software tool that is effective for capturing previously described alterations as wells as new variants that are smaller in size and/or affecting a low percentage of cells. Results: The developed method identified all previously known mosaic abnormalities reported in SNP array data obtained from controls, bladder cancer and HapMap individuals. In addition MAD tool was able to detect new mosaic variants not reported before that were smaller in size and with lower percentage of cells affected. The performance of the tool was analysed by studying simulated data for different scenarios. Our method showed high sensitivity and specificity for all assessed scenarios. Conclusions: The tool presented here has the ability to identify mosaic abnormalities with high sensitivity and specificity. Our results confirm the lack of sensitivity of former methods by identifying new mosaic variants not reported in previously utilised datasets. Our work suggests that the prevalence of mosaic alterations could be higher than initially thought. The use of appropriate SNP array data analysis methods would help in defining the human genome mosaic map. C1 [Gonzalez, Juan R.; Caceres, Alejandro] Ctr Res Environm Epidemiol CREAL, Barcelona 08003, Spain. [Gonzalez, Juan R.; Caceres, Alejandro] IMIM, Barcelona 08003, Spain. [Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis A.] UPF, Dept Ciencies Expt & Salut, Barcelona 08003, Spain. [Pique-Regi, Roger] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Rothman, Nathaniel; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Chanock, Stephen J.] SAIC Frederick, Core Genotyping Facil, Frederick, MD 21702 USA. [Armengol, Lluis] Quantitat Genom Med Labs Ltd qGenom, Barcelona 08003, Spain. RP Gonzalez, JR (reprint author), Ctr Res Environm Epidemiol CREAL, Doctor Aiguader 88, Barcelona 08003, Spain. EM jrgonzalez@creal.cat RI Sincan, Murat /A-3794-2010; Perez Jurado, Luis Alberto/M-7706-2015; Pique-Regi, Roger/A-4110-2009; OI Pique-Regi, Roger/0000-0002-1262-2275; Rodriguez-Santiago, Benjamin/0000-0003-1167-3852 FU Spanish Ministry of Science and Innovation [MTM2008-02457]; Fondo de Investigacion Sanitaria [PI076832]; NIH, NCI; Asociacion Espanola Contra el Cancer (AECC); Fondo Investigacion Sanitaria, Spain [FIS CD06/00019] FX We thank Dr. Francisco X. Real (CNIO, Spain), Dr. Nuria Malats (CNIO, Spain), Dr. Manolis Kogevinas (CREAL, Spain) and Dr. Debra T. Silverman (NCI, U. S. A.) for contributing data and information from the Spanish Bladder Cancer study. This work has been supported by the Spanish Ministry of Science and Innovation (MTM2008-02457 to JRG), the Fondo de Investigacion Sanitaria (grant PI076832 to LAP-J), the intramural research program of the NIH, NCI (to SJC and NR) and the Asociacion Espanola Contra el Cancer (AECC) (to FXR and LAP-J). B. Rodriguez-Santiago was supported by a postdoctoral fellowship (FIS CD06/00019) of the Fondo Investigacion Sanitaria, Spain. NR 30 TC 26 Z9 26 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAY 17 PY 2011 VL 12 AR 166 DI 10.1186/1471-2105-12-166 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 778QW UT WOS:000291720700002 PM 21586113 ER PT J AU Luna, A Karac, EI Sunshine, M Chang, L Nussinov, R Aladjem, MI Kohn, KW AF Luna, Augustin Karac, Evrim I. Sunshine, Margot Chang, Lucas Nussinov, Ruth Aladjem, Mirit I. Kohn, Kurt W. TI A formal MIM specification and tools for the common exchange of MIM diagrams: an XML-Based format, an API, and a validation method SO BMC BIOINFORMATICS LA English DT Article ID MOLECULAR INTERACTION MAP; BIOREGULATORY NETWORKS; BIOLOGICAL NETWORKS; SYSTEMS BIOLOGY; PATHWAY; CHALLENGES; RESISTANCE; RATIONALE; APOPTOSIS; NOTATION AB Background: The Molecular Interaction Map (MIM) notation offers a standard set of symbols and rules on their usage for the depiction of cellular signaling network diagrams. Such diagrams are essential for disseminating biological information in a concise manner. A lack of software tools for the notation restricts wider usage of the notation. Development of software is facilitated by a more detailed specification regarding software requirements than has previously existed for the MIM notation. Results: A formal implementation of the MIM notation was developed based on a core set of previously defined glyphs. This implementation provides a detailed specification of the properties of the elements of the MIM notation. Building upon this specification, a machine-readable format is provided as a standardized mechanism for the storage and exchange of MIM diagrams. This new format is accompanied by a Java-based application programming interface to help software developers to integrate MIM support into software projects. A validation mechanism is also provided to determine whether MIM datasets are in accordance with syntax rules provided by the new specification. Conclusions: The work presented here provides key foundational components to promote software development for the MIM notation. These components will speed up the development of interoperable tools supporting the MIM notation and will aid in the translation of data stored in MIM diagrams to other standardized formats. Several projects utilizing this implementation of the notation are outlined herein. The MIM specification is available as an additional file to this publication. Source code, libraries, documentation, and examples are available at http://discover.nci.nih.gov/mim. C1 [Luna, Augustin; Sunshine, Margot; Chang, Lucas; Aladjem, Mirit I.; Kohn, Kurt W.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Luna, Augustin; Aladjem, Mirit I.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Karac, Evrim I.] Bogazici Univ, Dept Comp Engn, TR-80815 Bebek, Turkey. [Nussinov, Ruth] NCI, Ctr Canc Res, Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kohnk@dc37a.nci.nih.gov RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We would like to acknowledge discussions with Can Ozturan, Mine Edes, and Turkan Haliloglu. Also, discussions with members of the SBGN and BioPAX communities were useful to the success of this project, especially Emek Demir, Nicolas Le Novere, and Hiroaki Kitano. Discussions with Martijn van Iersel were useful in understanding the GPML format. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, as well as with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 32 TC 9 Z9 9 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAY 17 PY 2011 VL 12 AR 167 DI 10.1186/1471-2105-12-167 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 778QW UT WOS:000291720700003 PM 21586134 ER PT J AU Arico, E Castiello, L Urbani, F Rizza, P Panelli, MC Wang, E Marincola, FM Belardelli, F AF Arico, Eleonora Castiello, Luciano Urbani, Francesca Rizza, Paola Panelli, Monica C. Wang, Ena Marincola, Francesco M. Belardelli, Filippo TI Concomitant detection of IFN alpha signature and activated monocyte/dendritic cell precursors in the peripheral blood of IFN alpha-treated subjects at early times after repeated local cytokine treatments SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID CHRONIC HEPATITIS-C; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CD8(+) T-CELLS; PBL-SCID MICE; DENDRITIC CELLS; GENE-EXPRESSION; IN-VITRO; MONOCYTE SUBSETS; IMMUNE-RESPONSE; MULTIPLE-SCLEROSIS AB Background: Interferons alpha (IFN alpha) are the cytokines most widely used in clinical medicine for the treatment of cancer and viral infections. Among the immunomodulatory activities possibly involved in their therapeutic efficacy, the importance of IFNa effects on dendritic cells (DC) differentiation and activation has been considered. Despite several studies exploiting microarray technology to characterize IFNa mechanisms of action, there is currently no consensus on the core signature of these cytokines in the peripheral blood of IFN alpha-treated individuals, as well as on the existence of blood genomic and proteomic markers of low-dose IFNa administered as a vaccine adjuvant. Methods: Gene profiling analysis with microarray was performed on PBMC isolated from melanoma patients and healthy individuals 24 hours after each repeated injection of low-dose IFNa, administered as vaccine adjuvant in two separate clinical trials. At the same time points, cytofluorimetric analysis was performed on CD14(+) monocytes, to detect the phenotypic modifications exerted by IFNa on antigen presenting cells precursors. Results: An IFNa signature was consistently observed in both clinical settings 24 hours after each repeated administration of the cytokine. The observed modulation was transient, and did not reach a steady state level refractory to further stimulations. The molecular signature observed ex vivo largely matched the one detected in CD14(+) monocytes exposed in vitro to IFNa, including the induction of CXCL10 at the transcriptional and protein level. Interestingly, IFNa ex vivo signature was paralleled by an increase in the percentage and expression of costimulatory molecules by circulating CD14(+)/CD16(+) monocytes, indicated as natural precursors of DC in response to danger signals. Conclusions: Our results provide new insights into the identification of a well defined molecular signature as biomarker of IFN alpha administered as immune adjuvants, and for the characterization of new molecular and cellular players, such as CXCL10 and CD14(+)/CD16(+) cells, mediating and possibly predicting patient response to these cytokines. C1 [Arico, Eleonora; Castiello, Luciano; Urbani, Francesca; Rizza, Paola; Belardelli, Filippo] Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Arico, Eleonora; Panelli, Monica C.; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Arico, Eleonora; Panelli, Monica C.; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA. [Panelli, Monica C.] Amgen Inc, Sci Affairs, Thousand Oaks, CA 91320 USA. RP Arico, E (reprint author), Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. EM eleonora.arico@iss.it RI Castiello, Luciano/K-8616-2016 OI Castiello, Luciano/0000-0001-7146-3158 FU special ISS-NIH; Italian Association for Research on Cancer (AIRC); Italian Ministry of Health FX This work was supported in part by grants from a special ISS-NIH project, the Italian Association for Research on Cancer (AIRC) and Italian Ministry of Health. NR 53 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAY 17 PY 2011 VL 9 AR 67 DI 10.1186/1479-5876-9-67 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 779ZR UT WOS:000291821200001 PM 21586124 ER PT J AU Jin, P Duan, R Luo, FB Zhang, GF Hong, SN Chen, EH AF Jin, Peng Duan, Rui Luo, Fengbao Zhang, Guofeng Hong, Sabrina N. Chen, Elizabeth H. TI Competition between Blown Fuse and WASP for WIP Binding Regulates the Dynamics of WASP-Dependent Actin Polymerization In Vivo SO DEVELOPMENTAL CELL LA English DT Article ID WISKOTT-ALDRICH-SYNDROME; SYNDROME PROTEIN WASP; MYOBLAST FUSION; N-WASP; INTERACTING PROTEIN; IMMUNOGLOBULIN SUPERFAMILY; CYTOSKELETAL ORGANIZATION; ARP2/3 COMPLEX; DROSOPHILA; MOTILITY AB Dynamic rearrangements of the actin cytoskeleton play a key role in numerous cellular processes. In Drosophila, fusion between a muscle founder cell and a fusion competent myoblast (FCM) is mediated by an invasive, F-actin-enriched podosome-like structure (PLS). Here, we show that the dynamics of the PLS is controlled by Blown fuse (Blow), a cytoplasmic protein required for myoblast fusion but whose molecular function has been elusive. We demonstrate that Blow is an FCM-specific protein that colocalizes with WASP, WIP/Solitary, and the actin focus within the PLS. Biochemically, Blow modulates the stability of the WASP-WIP complex by competing with WASP for WIP binding, leading to a rapid exchange of WASP, WIP and G-actin within the PLS, which, in turn, actively invades the adjacent founder cell to promote fusion pore formation. These studies identify a regulatory protein that modulates the actin cytoskeletal dynamics by controlling the stability of the WASP-WIP complex. C1 [Jin, Peng; Duan, Rui; Luo, Fengbao; Hong, Sabrina N.; Chen, Elizabeth H.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. [Zhang, Guofeng] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Chen, EH (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. EM echen@jhmi.edu FU National Institute of Health; American Heart Association; Muscular Dystrophy Association FX We thank Drs. S. Bogdan, D. Kiehart, H. Nguyen, D. Menon, R. Renkawitz-Pohl, B. Patterson, and the Bloomington Stock Center for antibodies and fly stocks; Dr. Richard Leapman at LBPH, NIH for access to the HPF/FS unit; Drs. Hao Zhang and Joseph Margolick at the Johns Hopkins Bloomberg School of Public Health for assistance with flow cytometry cell sorting. We thank Drs. S. Craig, D. Robinson, E. Grote, D. Pan, and members of the Chen lab for discussions and comments on the manuscript. This work was supported by grants from the National Institute of Health, American Heart Association and the Muscular Dystrophy Association. P.J. was a predoctoral fellow of the American Heart Association. E.H.C. was a Searle Scholar and a Packard Fellow. NR 52 TC 34 Z9 34 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY 17 PY 2011 VL 20 IS 5 BP 623 EP 638 DI 10.1016/j.devcel.2011.04.007 PG 16 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 771FC UT WOS:000291141600009 PM 21571220 ER PT J AU Lubitz, SA Magnani, JW Ellinor, PT Benjamin, EJ AF Lubitz, Steven A. Magnani, Jared W. Ellinor, Patrick T. Benjamin, Emelia J. TI Atrial Fibrillation and Death After Myocardial Infarction Risk Marker or Causal Mediator? SO CIRCULATION LA English DT Editorial Material DE Editorials; epidemiology; atrial fibrillation; myocardial infarction; risk factors ID ARTERY-BYPASS GRAFT; MORTALITY; PREVALENCE; IMPACT; HEART C1 [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@bu.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [L30 HL097675] NR 20 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAY 17 PY 2011 VL 123 IS 19 BP 2063 EP 2065 DI 10.1161/CIRCULATIONAHA.111.030171 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 764GC UT WOS:000290616600006 PM 21536997 ER PT J AU Buxton, DB Antman, M Danthi, N Dilsizian, V Fayad, ZA Garcia, MJ Jaff, MR Klimas, M Libby, P Nahrendorf, M Sinusas, AJ Wickline, SA Wu, JC Bonow, RO Weissleder, R AF Buxton, Denis B. Antman, Melissa Danthi, Narasimhan Dilsizian, Vasken Fayad, Zahi A. Garcia, Mario J. Jaff, Michael R. Klimas, Michael Libby, Peter Nahrendorf, Matthias Sinusas, Albert J. Wickline, Samuel A. Wu, Joseph C. Bonow, Robert O. Weissleder, Ralph TI Report of the National Heart, Lung, and Blood Institute Working Group on the Translation of Cardiovascular Molecular Imaging SO CIRCULATION LA English DT Article DE cardiovascular diseases; molecular imaging; diagnosis ID MYOCARDIAL-INFARCTION; IN-VIVO; ATHEROSCLEROSIS; TOMOGRAPHY; INFLAMMATION; DISEASE; CELL; NANOPARTICLE; REJECTION; THERAPY C1 [Buxton, Denis B.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Dilsizian, Vasken] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Fayad, Zahi A.] Mt Sinai Sch Med, New York, NY USA. [Garcia, Mario J.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Jaff, Michael R.; Nahrendorf, Matthias; Weissleder, Ralph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Klimas, Michael] Merck Res Labs, West Point, PA USA. [Libby, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sinusas, Albert J.] Yale Univ, New Haven, CT USA. [Wickline, Samuel A.] Washington Univ, St Louis, MO USA. [Wu, Joseph C.] Stanford Univ, Palo Alto, CA 94304 USA. [Bonow, Robert O.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Buxton, DB (reprint author), NHLBI, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Room 8216, Bethesda, MD 20892 USA. EM buxtond@nhlbi.nih.gov RI Danthi, Simhan/B-7639-2014; OI Buxton, Denis/0000-0003-3077-6435 FU NHLBI, National Institutes of Health; GE Healthcare; Roche; Novartis; GlaxoSmithKline; Bristol Myers Squibb; VBL Therapeutics; Merck; Astra Zeneca; Rigel Pharmaceuticals; Lantheus Medical Imaging; Astellas Pharma; Molecular Targeting Technologies; CDL Nuclear Technologies FX This work was supported by the NHLBI, National Institutes of Health.; Dr Bonow received an honorarium from Ohio State University for a lecture on cardiovascular molecular imaging. Dr Dilsizian reports receiving consulting fees and a research grant from, and owns stock in, GE Healthcare. Dr Fayad has received research grants from Roche, Novartis, GlaxoSmithKline, Bristol Myers Squibb, VBL Therapeutics, and Merck, and has received consulting fees from Roche. Dr Garcia owns stock in Pfizer and has advisory/consultancy relationships with MD Imaging, theheart.org, BG Medicine, and the Intersocietal Accreditation Commission. Dr Klimas is an employee of Merck. Dr Libby has received in-kind research support from Astra Zeneca and Rigel Pharmaceuticals and served on advisory boards for Interleukin Genetics, Novartis, VIA Pharmaceuticals, BIND Biosciences, and Carolus Therapeutics. Dr Sinusas has received research grants from Lantheus Medical Imaging, Astellas Pharma, GE Healthcare, and Molecular Targeting Technologies, and has received consulting fees from Lantheus Medical Imaging and CDL Nuclear Technologies. Dr Wickline serves on the advisory board and owns stock in Kereos. The remaining authors report no conflicts. NR 44 TC 27 Z9 28 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 17 PY 2011 VL 123 IS 19 BP 2157 EP 2163 DI 10.1161/CIRCULATIONAHA.110.000943 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 764GC UT WOS:000290616600017 PM 21576680 ER PT J AU Farkas, IJ Korcsmaros, T Kovacs, IA Mihalik, A Palotai, R Simko, GI Szalay, KZ Szalay-Beko, M Vellai, T Wang, SJ Csermely, P AF Farkas, Illes J. Korcsmaros, Tamas Kovacs, Istvan A. Mihalik, Agoston Palotai, Robin Simko, Gabor I. Szalay, Kristof Z. Szalay-Beko, Mate Vellai, Tibor Wang, Shijun Csermely, Peter TI Network-Based Tools for the Identification of Novel Drug Targets SO SCIENCE SIGNALING LA English DT Article ID CELLULAR NETWORKS; DESIGN; DISCOVERY; PROTEINS; DYNAMICS; DISEASES; ELEMENTS; STRESS; YEAST AB In the past few years, network-based tools have become increasingly important in the identification of novel molecular targets for drug development. Systems-based approaches to predict signal transduction-related drug targets have developed into an especially promising field. Here, we summarize our studies, which indicate that modular bridges and overlaps of protein-protein interaction and signaling networks may be of key importance in future drug design. Intermodular nodes are very efficient in mediating the transmission of perturbations between signaling modules and are important in network cooperation. The analysis of stress-induced rearrangements of the yeast interactome by the ModuLand modularization algorithm indicated that components of modular overlap are key players in cellular adaptation to stress. Signaling crosstalk was much more pronounced in humans than in Caenorhabditis elegans or Drosophila melanogaster in the SignaLink (http://www.SignaLink.org) database, a uniformly curated database of eight major signaling pathways. We also showed that signaling proteins that participate in multiple pathways included multiple established drug targets and drug target candidates. Lastly, we caution that the pervasive overlap of cellular network modules implies that wider use of multitarget drugs to partially inhibit multiple individual proteins will be necessary to modify specific cellular functions, because targeting single proteins for complete disruption usually affects multiple cellular functions with little specificity for a particular process. Tools for analyzing network topology and especially network dynamics have great potential to identify alternative sets of targets for developing multitarget drugs. C1 [Korcsmaros, Tamas; Kovacs, Istvan A.; Mihalik, Agoston; Palotai, Robin; Simko, Gabor I.; Szalay, Kristof Z.; Szalay-Beko, Mate; Csermely, Peter] Semmelweis Univ, Dept Med Chem, H-1094 Budapest, Hungary. [Farkas, Illes J.] Hungarian Acad Sci, Stat & Biol Phys Grp, H-1117 Budapest, Hungary. [Korcsmaros, Tamas; Vellai, Tibor] Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary. [Kovacs, Istvan A.] Eotvos Lorand Univ, Dept Phys, H-1117 Budapest, Hungary. [Kovacs, Istvan A.] Res Inst Solid State Phys & Opt, H-1525 Budapest, Hungary. [Simko, Gabor I.] Vanderbilt Univ, Nashville, TN 37240 USA. [Wang, Shijun] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Csermely, P (reprint author), Semmelweis Univ, Dept Med Chem, 37-47 Tuzolto St, H-1094 Budapest, Hungary. EM csermely@eok.sote.hu RI Farkas, Illes/C-1504-2008; Kovacs, Istvan/A-8447-2013; Korcsmaros, Tamas/C-3526-2015; OI Farkas, Illes/0000-0001-5341-5582; Kovacs, Istvan/0000-0002-6890-6277; Korcsmaros, Tamas/0000-0003-1717-996X; Szalay, Kristof/0000-0001-7876-3516 FU Hungarian National Science Foundation [OTKA-K69105, OTKA-K75334, OTKA-K83314]; European Union [FP6-016003, TAMOP 4.2.1./B-09/1/KMR-2010-0003]; Janos Bolyai Scholarship FX The authors would like to thank members of the LINK-group (http://www.linkgroup.hu) for helpful suggestions. Work in the authors' laboratory was supported by research grants from the Hungarian National Science Foundation (OTKA-K69105, OTKA-K75334, and OTKA-K83314), from the European Union (FP6-016003; TAMOP 4.2.1./B-09/1/KMR-2010-0003), and by a Janos Bolyai Scholarship for T. V. NR 38 TC 25 Z9 27 U1 0 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD MAY 17 PY 2011 VL 4 IS 173 AR pt3 DI 10.1126/scisignal.2001950 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 764XC UT WOS:000290666900004 PM 21586727 ER PT J AU Aronow, WS Fleg, JL Pepine, CJ Artinian, NT Bakris, G Brown, AS Ferdinand, KC Forciea, MA Frishman, WH Jaigobin, C Kostis, JB Mancia, G Oparil, S Ortiz, E Reisin, E Rich, MW Schocken, DD Weber, MA Wesley, DJ AF Aronow, Wilbert S. Fleg, Jerome L. Pepine, Carl J. Artinian, Nancy T. Bakris, George Brown, Alan S. Ferdinand, Keith C. Forciea, Mary Ann Frishman, William H. Jaigobin, Cheryl Kostis, John B. Mancia, Giuseppi Oparil, Suzanne Ortiz, Eduardo Reisin, Efrain Rich, Michael W. Schocken, Douglas D. Weber, Michael A. Wesley, Deborah J. CA ACCF Task Force Members TI ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ACCF/AHA Expert Consensus Documents; antihypertensive agents; elderly; risk assessment; hypertension comorbidities; hypertension pathophysiology; hypertension therapy ID ISOLATED SYSTOLIC HYPERTENSION; RENAL-ARTERY STENOSIS; AMBULATORY BLOOD-PRESSURE; LEFT-VENTRICULAR HYPERTROPHY; RANDOMIZED CONTROLLED-TRIAL; AMERICAN-HEART-ASSOCIATION; CONVERTING-ENZYME-INHIBITORS; VERAPAMIL SR-TRANDOLAPRIL; RENIN-ANGIOTENSIN SYSTEM; QUALITY-OF-LIFE C1 [Aronow, Wilbert S.; Pepine, Carl J.; Frishman, William H.] Amer Coll Cardiol Fdn, New York, NY USA. [Fleg, Jerome L.; Ortiz, Eduardo] NHLBI, Bethesda, MD USA. [Artinian, Nancy T.; Brown, Alan S.] Amer Heart Assoc, Dallas, TX USA. [Ferdinand, Keith C.] Assoc Black Cardiologists, Atlanta, GA USA. [Forciea, Mary Ann] Amer Coll Physicians, Philadelphia, PA USA. [Jaigobin, Cheryl] Amer Acad Neurol, St Paul, MN USA. [Mancia, Giuseppi] European Soc Hypertens, Palermo, Italy. [Reisin, Efrain] Amer Soc Nephrol, Washington, DC USA. [Rich, Michael W.] Amer Geriatr Soc, New York, NY USA. [Schocken, Douglas D.] Amer Soc Prevent Cardiol, Jacksonville, FL 32216 USA. [Weber, Michael A.] Amer Soc Hypertens, New York, NY 10016 USA. [Wesley, Deborah J.] ACCF Task Force Clin Expert Consensus Documents, New York, NY USA. RP Aronow, WS (reprint author), Amer Coll Cardiol Fdn, New York, NY USA. NR 740 TC 188 Z9 206 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 17 PY 2011 VL 57 IS 20 BP 2037 EP 2114 DI 10.1016/j.jacc.2011.01.008 PG 78 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 762JK UT WOS:000290472300015 PM 21524875 ER PT J AU Park, JE Erikson, RL Lee, KS AF Park, Jung-Eun Erikson, Raymond L. Lee, Kyung S. TI Feed-forward mechanism of converting biochemical cooperativity to mitotic processes at the kinetochore plate SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLO-LIKE KINASES; CELL-CYCLE REGULATION; BOX DOMAIN; PROTEIN-KINASE; CENP-A; PLK1; PHOSPHORYLATION; LOCALIZATION; CYTOKINESIS; COMPLEX AB The feed-forward mechanism is observed in some of the intracellular events, such as metabolic and transcriptional regulatory networks, but not in dynamic mitotic processes. Mammalian polo-like kinase 1 (Plk1) rapidly accumulates at centrosomes and kinetochores as cells enter mitosis. Plk1 function is spatially regulated through the targeting activity of the polo-box domain (PBD) that binds to a phosphoepitope generated by either cyclin dependent kinase 1 (Cdk1) (non-self-priming) or Plk1 itself (self-priming). "Non-self-priming and binding" is thought to ensure the orderly execution of cell cycle events. The physiological significance of the "self-priming and binding" is unknown. Using a pair of ELISA, here we demonstrated that mutations of the self-priming site of a kinetochore component, PBIP1/MLF1IP/KLIP1/CENP-50/CENP-U (PBIP1), to a Cdk1-dependent non-self-priming site abolished product-activated cooperativity in the formation of the Plk1-PBIP1 complex. Both PBD-dependent "two-dimensional" interaction with surface-restricted PBIP1 and subsequent phosphorylation of PBIP1 by anchored Plk1 were crucial to cooperatively generate the Plk1-PBIP1 complex. Highlighting the importance of this mechanism, failure in this process resulted in improper Plk1 recruitment to kinetochores, mitotic arrest, chromosome missegregation, and apoptosis. Thus, Plk1 PBD-dependent biochemical cooperativity is tightly coupled to mitotic events at the kinetochore plate through a product-activated, feed-forward mechanism. Given the critical role of self-priming and binding in the recruitment of Plk1 to surface-confined structures, such as centrosomes, kinetochores, and midbody, we propose that the observed feed-forward mechanism serves as a fundamental biochemical process that ensures dynamic nature of Plk1 localization to and delocalization from these subcellular locations. C1 [Park, Jung-Eun; Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Erikson, Raymond L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Erikson, RL (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM erikson@mcb.harvard.edu; kyunglee@mail.nih.gov FU National Cancer Institute FX We would like to thank Paul A. Randazzo, Shilpa R. Kurian, and Susan Garfield for critical reading of the manuscript, George M. Carman for helpful discussions, and Young H. Kang and Yoshikazu Johmura for sharing the anti-CENP-Q and anti-Hice1 p-S151 antibodies, respectively. This work was supported in part by a National Cancer Institute intramural grant (K.S.L.). NR 35 TC 12 Z9 12 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 17 PY 2011 VL 108 IS 20 BP 8200 EP 8205 DI 10.1073/pnas.1102020108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765OZ UT WOS:000290719600030 PM 21525413 ER PT J AU Genest, O Hoskins, JR Camberg, JL Doyle, SM Wickner, S AF Genest, Olivier Hoskins, Joel R. Camberg, Jodi L. Doyle, Shannon M. Wickner, Sue TI Heat shock protein 90 from Escherichia coli collaborates with the DnaK chaperone system in client protein remodeling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Hsp40; DnaJ; CbpA; CbpM; GrpE ID HSP90 MOLECULAR CHAPERONE; AMINO-TERMINAL DOMAIN; ATPASE CYCLE; IN-VIVO; CONFORMATIONAL DYNAMICS; CRYSTAL-STRUCTURE; BINDING; MACHINERY; HSP70; HTPG AB Molecular chaperones are proteins that assist the folding, unfolding, and remodeling of other proteins. In eukaryotes, heat shock protein 90 (Hsp90) proteins are essential ATP-dependent molecular chaperones that remodel and activate hundreds of client proteins with the assistance of cochaperones. In Escherichia coli, the activity of the Hsp90 homolog, HtpG, has remained elusive. To explore the mechanism of action of E. coli Hsp90, we used in vitro protein reactivation assays. We found that E. coli Hsp90 promotes reactivation of heat-inactivated luciferase in a reaction that requires the prokaryotic Hsp70 chaperone system, known as the DnaK system. An Hsp90 ATPase inhibitor, geldanamycin, inhibits luciferase reactivation demonstrating the importance of the ATP-dependent chaperone activity of E. coli Hsp90 during client protein remodeling. Reactivation also depends upon the ATP-dependent chaperone activity of the DnaK system. Our results suggest that the DnaK system acts first on the client protein, and then E. coli Hsp90 and the DnaK system collaborate synergistically to complete remodeling of the client protein. Results indicate that E. coli Hsp90 and DnaK interact in vivo and in vitro, providing additional evidence to suggest that E. coli Hsp90 and the DnaK system function together. C1 [Genest, Olivier; Hoskins, Joel R.; Camberg, Jodi L.; Doyle, Shannon M.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wickner, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM wickners@mail.nih.gov FU National Institutes of Health, NCI, Center for Cancer Research FX We thank Len Neckers (NCI) for Hsp90 inhibitors, plasmid, and discussions, Aurelia Battesti for lending her expertise with the two-hybrid system, and Marika Miot for plasmids. We are also grateful to Danielle Johnston and Marika Miot for critical reading of the manuscript and helpful discussions. This research was supported by the Intramural Research Program of the National Institutes of Health, NCI, Center for Cancer Research. NR 49 TC 30 Z9 31 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 17 PY 2011 VL 108 IS 20 BP 8206 EP 8211 DI 10.1073/pnas.1104703108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765OZ UT WOS:000290719600031 PM 21525416 ER PT J AU Kondratowicz, AS Lennemann, NJ Sinn, PL Davey, RA Hunt, CL Moller-Tank, S Meyerholz, DK Rennert, P Mullins, RF Brindley, M Sandersfeld, LM Quinn, K Weller, M McCray, PB Chiorini, J Maury, W AF Kondratowicz, Andrew S. Lennemann, Nicholas J. Sinn, Patrick L. Davey, Robert A. Hunt, Catherine L. Moller-Tank, Sven Meyerholz, David K. Rennert, Paul Mullins, Robert F. Brindley, Melinda Sandersfeld, Lindsay M. Quinn, Kathrina Weller, Melodie McCray, Paul B., Jr. Chiorini, John Maury, Wendy TI T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE viral entry; viral receptor; virion internalization ID VIRUS GLYCOPROTEIN; DC-SIGN; ENVELOPE GLYCOPROTEINS; ENDOSOMAL CATHEPSINS; FUNCTIONAL RECEPTOR; IMMUNE REGULATION; SARS CORONAVIRUS; FILOVIRUS ENTRY; RHESUS-MONKEYS; HOST-CELL AB The glycoproteins (GP) of enveloped viruses facilitate entry into the host cell by interacting with specific cellular receptors. Despite extensive study, a cellular receptor for the deadly filoviruses Ebo-lavirus and Marburgvirus has yet to be identified and characterized. Here, we show that T-cell Ig and mucin domain 1 (TIM-1) binds to the receptor binding domain of the Zaire Ebola virus (EBOV) glycoprotein, and ectopic TIM-1 expression in poorly permissive cells enhances EBOV infection by 10- to 30-fold. Conversely, reduction of cell-surface expression of TIM-1 by RNAi decreased infection of highly permissive Vero cells. TIM-1 expression within the human body is broader than previously appreciated, with expression on mucosal epithelia from the trachea, cornea, and conjunctiva-tissues believed to be important during in vivo transmission of filoviruses. Recognition that TIM-1 serves as a receptor for filoviruses on these mucosal epithelial surfaces provides a mechanistic understanding of routes of entry into the human body via inhalation of aerosol particles or hand-to-eye contact. ARD5, a monoclonal antibody against the IgV domain of TIM-1, blocked EBOV binding and infection, suggesting that antibodies or small molecules directed against this cellular receptor may provide effective filovirus antivirals. C1 [Kondratowicz, Andrew S.; Lennemann, Nicholas J.; Hunt, Catherine L.; Moller-Tank, Sven; Brindley, Melinda; Sandersfeld, Lindsay M.; Maury, Wendy] Univ Iowa, Carver Coll Med, Dept Microbiol, Iowa City, IA 52242 USA. [Sinn, Patrick L.; McCray, Paul B., Jr.] Univ Iowa, Carver Coll Med, Dept Pediat, Iowa City, IA 52242 USA. [Meyerholz, David K.] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA. [Mullins, Robert F.] Univ Iowa, Carver Coll Med, Dept Ophthalmol, Iowa City, IA 52242 USA. [Davey, Robert A.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Rennert, Paul] Biogen Idec Inc, Cambridge, MA 02142 USA. [Quinn, Kathrina; Weller, Melodie; Chiorini, John] Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Maury, W (reprint author), Univ Iowa, Carver Coll Med, Dept Microbiol, Iowa City, IA 52242 USA. EM wendy-maury@uiowa.edu FU National Institutes of Health (NIH) [AI064526, AI073330, AI082409, AI063513, AI057156, HL075363, DK54759, DK054759, CA086862]; Intramural National Institute of Allergy and Infectious Diseases Biodefense; NIH National Institute of Dental and Craniofacial Research; University of Iowa [NIH DK54759]; [T32 AI 007533-12] FX We thank Dr. Jianqiang Shao in the University of Iowa Central Microscopy Core for his expert assistance with the confocal studies, and Yen-Ming Hsu and Veronique Bailly at Biogen Idec for purification of TIM-1/Fc protein. We also thank Drs. Stanley Perlman, C. Martin Stoltzfus, Beverly Davidson, Richard Roller, and Michael Welsh for critical evaluation of this manuscript. We acknowledge support from National Institutes of Health (NIH) Grants AI064526, AI073330, and AI082409 (to W. M.); AI063513 and AI057156 (to R. A. D.); and HL075363 (to P. B. M.). Support was also received from the Intramural National Institute of Allergy and Infectious Diseases Biodefense and NIH National Institute of Dental and Craniofacial Research (J.C.), the University of Iowa in Vitro Models and Cell Culture Core Grant NIH DK54759, Cell Morphology and Pathology Core Grant NIH DK54759, and Central Microscopy Core Grants NIH DK054759 and NIH CA086862. A. S. K., N.J.L, and S.M.-T. were supported by T32 AI 007533-12. NR 51 TC 126 Z9 136 U1 1 U2 36 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 17 PY 2011 VL 108 IS 20 BP 8426 EP 8431 DI 10.1073/pnas.1019030108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 765OZ UT WOS:000290719600069 PM 21536871 ER PT J AU Lee, DC Hassan, SS Romero, R Tarca, AL Bhatti, G Gervasi, MT Caruso, JA Stemmer, PM Kim, CJ Hansen, LK Becher, N Uldbjerg, N AF Lee, Deug-Chan Hassan, Sonia S. Romero, Roberto Tarca, Adi L. Bhatti, Gaurau Gervasi, Maria Teresa Caruso, Joseph A. Stemmer, Paul M. Kim, Chong Jai Hansen, Lea Kirstine Becher, Naja Uldbjerg, Niels TI Protein profiling underscores immunological functions of uterine cervical mucus plug in human pregnancy SO JOURNAL OF PROTEOMICS LA English DT Article DE Cervical mucus plug; Pregnancy; Proteomics ID LEMLI-OPITZ-SYNDROME; AMNIOTIC-FLUID; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; PRETERM LABOR; INTRAAMNIOTIC INFECTION; PRENATAL-DIAGNOSIS; MENSTRUAL-CYCLE; VAGINAL FLUID; TERM AB The cervical mucus plug (CMP) differs from the cervical secretions of non-pregnant women, and is the ultimate sealant of the uterine cavity during pregnancy. Although several studies have analyzed biochemical properties of large glycoproteins in the CMP, comprehensive information about its protein composition is yet unavailable. We hypothesized that protein profiling of the CMP could provide key clues to its physiological functions in pregnancy. For this purpose, five CMPs obtained from women in labor at term were analyzed by LC-MS/MS. Out of 291 total proteins identified, 137 were detected in two or more samples, which included S100A8, S100A9, and complement proteins (C3, C4a, C4b, C6, and C8g). Several proteins, which have not been described in the cervical mucus of non-pregnant women or in cervicovaginal fluids, such as CD81 antigen and pregnancy zone protein, were also identified. Gene ontology analysis of identified proteins showed significant enrichment of 28 biological processes such as 'activation of plasma proteins involved in acute inflammatory response' and 'positive regulation of cholesterol esterification'. We report the proteome of CMPs from pregnant women at term for the first time, and the overall findings strongly suggest an important role for the CMP in the maintenance of pregnancy and parturition. (C) 2011 Elsevier B.V. All rights reserved. C1 [Lee, Deug-Chan; Hassan, Sonia S.; Romero, Roberto; Tarca, Adi L.; Bhatti, Gaurau; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Lee, Deug-Chan; Hassan, Sonia S.; Romero, Roberto; Tarca, Adi L.; Bhatti, Gaurau; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Hassan, Sonia S.; Romero, Roberto] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Tarca, Adi L.] Wayne State Univ, Dept Comp Sci, Detroit, MI 48201 USA. [Gervasi, Maria Teresa] Azienda Osped Univ, UO Ostetricia & Ginecol, Padua, Italy. [Caruso, Joseph A.; Stemmer, Paul M.] Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48201 USA. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Hansen, Lea Kirstine; Becher, Naja; Uldbjerg, Niels] Univ Aarhus, Dept Obstet & Gynecol, Aarhus, Denmark. RP Hassan, SS (reprint author), Wayne State Univ, Sch Med, Hutzel Womens Hosp, Dept Obstet & Gynecol, Box 4, Detroit, MI 48201 USA. EM shassan@med.wayne.edu; Uldbjerg@ki.au.dk RI Uldbjerg, Niels/O-2038-2016 OI Uldbjerg, Niels/0000-0002-6449-6426 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; DHHS; National Institute of Environmental Health Sciences [P30-ES006639] FX This work was supported in part by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, and DHHS. The Proteomics Facility Core of the Institute of Environmental Health Sciences at Wayne State University is supported by National Institute of Environmental Health Sciences grant P30-ES006639. NR 56 TC 16 Z9 19 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 J9 J PROTEOMICS JI J. Proteomics PD MAY 16 PY 2011 VL 74 IS 6 BP 817 EP 828 DI 10.1016/j.jprot.2011.02.025 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 773DS UT WOS:000291287800006 PM 21362502 ER PT J AU Kedei, N Lubart, E Lewin, NE Telek, A Lim, L Mannan, P Garfield, SH Kraft, MB Keck, GE Kolusheva, S Jelinek, R Blumberg, PM AF Kedei, Noemi Lubart, Emanuel Lewin, Nancy E. Telek, Andrea Lim, Langston Mannan, Poonam Garfield, Susan H. Kraft, Matthew B. Keck, Gary E. Kolusheva, Sofiya Jelinek, Raz Blumberg, Peter M. TI Some Phorbol Esters Might Partially Resemble Bryostatin 1 in their Actions on LNCaP Prostate Cancer Cells and U937 Leukemia Cells SO CHEMBIOCHEM LA English DT Article DE biological activity; bryostatin; lipophilicity; phorbol esters; protein kinases ID PROTEIN-KINASE-C; CONFORMATIONALLY CONSTRAINED ANALOGS; CD-1 MOUSE SKIN; NONPROMOTING 12-DEOXYPHORBOL 13-ESTERS; 12-MYRISTATE 13-ACETATE; CLINICAL DEVELOPMENT; BIOLOGICAL-ACTIVITY; INDUCED APOPTOSIS; PKC-DELTA; DIACYLGLYCEROL AB Phorbol 12-myristate 13-acetate (PMA) and bryostatin 1 are both potent protein kinase C (PKC) activators. In LNCaP human prostate cancer cells, PMA induces tumor necrosis factor alpha (TNF alpha) secretion and inhibits proliferation; bryostatin 1 does not, and indeed blocks the response to PMA. This difference has been attributed to bryostatin 1 not localizing PKC delta to the plasma membrane. Since phorbol ester lipophilicity influences PKC delta localization, we have examined in LNCaP cells a series of phorbol esters and related derivatives spanning some eight logs in lipophilicity (logP) to see if any behave like bryostatin 1. The compounds showed marked differences in their effects on proliferation and TNF alpha secretion. For example, maximal responses for TNF alpha secretion relative to PMA ranged from 97% for octyl-indolactam V to 24% for phorbol 12,13-dibenzoate. Dose-response curves ranged from monophasic for indolactam V to markedly biphasic for sapintoxin D. The divergent patterns of response, however, correlated neither to lipophilicity, to plasma membrane translocation of PKC delta, nor to the ability to interact with model membranes. In U937 human leukemia cells, a second system in which PMA and bryostatin 1 have divergent effects, viz. PMA but not bryostatin 1 inhibits proliferation and induces attachment, all the compounds acted like PMA for proliferation, but several induced a reduced level or a biphasic dose-response curve for attachment. We conclude that active phorbol esters are not all equivalent. Depending on the system, some might partially resemble bryostatin 1 in their behavior; this encourages the concept that bryostatin-like behavior may be obtained from other structural templates. C1 [Kedei, Noemi; Lubart, Emanuel; Lewin, Nancy E.; Telek, Andrea; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Lim, Langston; Mannan, Poonam; Garfield, Susan H.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Kraft, Matthew B.; Keck, Gary E.] Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA. [Kolusheva, Sofiya; Jelinek, Raz] Ben Gurion Univ Negev, Dept Chem, IL-84105 Beer Sheva, Israel. RP Blumberg, PM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bldg 37,Room 4048B,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov RI JELINEK, RAZ/F-2023-2012; OI jelinek, raz/0000-0002-0336-1384 FU National Institutes of Health, Center for Cancer Research, National Cancer Institute [Z1A BC 005270]; NIH [GM28961] FX This research was supported in part by the Intramural Program, National Institutes of Health, Center for Cancer Research, National Cancer Institute (Z1A BC 005270) and in part by NIH Grant GM28961 to G. E. K. NR 43 TC 13 Z9 13 U1 0 U2 7 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI ChemBioChem PD MAY 16 PY 2011 VL 12 IS 8 BP 1242 EP 1251 DI 10.1002/cbic.201100064 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 767ND UT WOS:000290862400016 PM 21542090 ER PT J AU Liu, XX Choi, RY Jawad, SM Arnold, JT AF Liu, Xunxian Choi, Renee Y. Jawad, Shayma M. Arnold, Julia T. TI Androgen-Induced PSA Expression Requires Not Only Activation of AR But Also Endogenous IGF-I or IGF-I/PI3K/Akt Signaling in Human Prostate Cancer Epithelial Cells SO PROSTATE LA English DT Article DE Akt; AR; beta-catenin; IGF-I; prostate cancer; PSA; R1881 ID GROWTH-FACTOR-I; BETA-CATENIN; STROMAL CELLS; NUCLEAR TRANSLOCATION; STIMULATED GROWTH; FACTOR (IGF)-I; RECEPTOR; INSULIN; TESTOSTERONE; INHIBITION AB BACKGROUND. Prostate cancer (PrCa) risk is positively associated with levels of insulin-like growth factor I (IGF-I) and prostate specific antigen (PSA), both androgen receptor (AR) signaling target genes in PrCa cells. Although activated AR is required for androgen-induction of expression of both genes, effects of the IGF-I signaling pathways on the androgen-induction of PSA have not been studied. METHODS. Human prostate stromal and epithelial cancer cells were treated alone or in coculture with steroid hormone and/or inhibitors. Gene or protein expression was analyzed by real time RT-PCR or Western blotting of lysates, nuclear extracts, or immunoprecipitated products. RESULTS. In PrCa epithelial cells, endogenous IGF-I, significantly induced by R1881, was required for R1881-induction of PSA. Increased IGF-I correlated with accumulation of cytoplasmic dephospho beta-catenin (CPDP beta-catenin), a co-activator of AR signaling. Exogenous IGF-I enhanced R1881-induced PSA and accumulation of CPDP beta-catenin in LAPC-4 cells. Functional depletion of IGF-I or IGF-I receptor diminished PSA induction. Induction of IGF-I reached a plateau while PSA consecutively increased. Inhibiting PI3K abolished R1881-induced Akt phosphorylation, CPDP and nuclear beta-catenin and nuclear association of AR/beta-catenin, consequently abrogating R1881-induced expression of IGF-I and/or PSA. CONCLUSIONS. By integrating androgen, IGF-I and beta-catenin signaling pathways, these data reveal that androgen-induced PSA expression requires activation of AR and endogenous IGF-I or IGF-I/PI3K/Akt signaling, suggesting a positive feedback cycle for increased production of PSA associated with PrCa. Prostate 71: 766-777, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Liu, Xunxian; Choi, Renee Y.; Jawad, Shayma M.; Arnold, Julia T.] NIH, Endocrine Sect, Lab Clin Invest, Div Intramural Res,Natl Ctr Complementary & Alter, Bethesda, MD 20892 USA. RP Liu, XX (reprint author), NIH NCCAM Bldg 10,Rm 2B47,MSC 1547,9000 Rockville, Bethesda, MD 20892 USA. EM xunxianl@mail.nih.gov FU National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD FX We thank Jennifer Chu for technical assistance. We are grateful for Dr. Hui Chen and Dr. Ranganath Muniyappa for reviewing the manuscript and rendering valuable suggestions. This research was supported by the Intramural Research Program of the National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892. NR 41 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 15 PY 2011 VL 71 IS 7 BP 766 EP 777 DI 10.1002/pros.21293 PG 12 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 750AV UT WOS:000289516900010 PM 21031436 ER PT J AU Ehsanian, R Van Waes, C Feller, SM AF Ehsanian, Reza Van Waes, Carter Feller, Stephan M. TI Beyond DNA binding - a review of the potential mechanisms mediating quinacrine's therapeutic activities in parasitic infections, inflammation, and cancers SO CELL COMMUNICATION AND SIGNALING LA English DT Review ID NF-KAPPA-B; SQUAMOUS-CELL CARCINOMA; PROSTAGLANDIN-E SYNTHASE; ARACHIDONIC-ACID RELEASE; IRRADIATED HUMAN FIBROBLASTS; MALIGNANT PLEURAL EFFUSIONS; MULTIDRUG-RESISTANCE; PHOSPHOLIPASE A(2); TOPOISOMERASE-II; IN-VITRO AB This is an in-depth review of the history of quinacrine as well as its pharmacokinetic properties and established record of safety as an FDA-approved drug. The potential uses of quinacrine as an anti-cancer agent are discussed with particular attention to its actions on nuclear proteins, the arachidonic acid pathway, and multi-drug resistance, as well as its actions on signaling proteins in the cytoplasm. In particular, quinacrine's role on the NF-kappa B, p53, and AKT pathways are summarized. C1 [Ehsanian, Reza; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [Ehsanian, Reza] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Ehsanian, Reza; Feller, Stephan M.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Dept Mol Oncol,Cell Signalling Grp, Oxford OX3 9DS, England. RP Ehsanian, R (reprint author), Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. EM rezae@stanford.edu FU NIH; HHMI; NIDCD [ZIA-DC-000016] FX The authors would like to thank Zhong Chen, Jay Friedman, and Liesl Nottingham for their input. This work was partially supported by the HeadsUp and CRUK charities. Reza Ehsanian was supported by an NIH-Oxford Fellowship, a Stanford Medscholars Fellowship and HHMI Scholars Fellowship. RE and CVW were supported by NIDCD intramural project ZIA-DC-000016. NR 279 TC 29 Z9 30 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-811X J9 CELL COMMUN SIGNAL JI Cell Commun. Signal. PD MAY 15 PY 2011 VL 9 AR 13 DI 10.1186/1478-811X-9-13 PG 18 WC Cell Biology SC Cell Biology GA 779QW UT WOS:000291796600001 PM 21569639 ER PT J AU Kiley, JP AF Kiley, James P. TI Opportunities in Pulmonary Research Not a Time to Step Back SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. RP Kiley, JP (reprint author), NHLBI, Div Lung Dis, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY 15 PY 2011 VL 183 IS 10 BP 1283 EP 1284 DI 10.1164/rccm.201104-0636ED PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 771UP UT WOS:000291186500001 PM 21596825 ER PT J AU Talisman, IJ Kumar, V Razzaghy, J Malhotra, SV AF Talisman, Ian Jamie Kumar, Vineet Razzaghy, Jacqueline Malhotra, Sanjay V. TI O-Glycosidation reactions promoted by in situ generated silver N-heterocyclic carbenes in ionic liquids SO CARBOHYDRATE RESEARCH LA English DT Article DE O-Glycosidation; Ionic liquids; Carbohydrates; Ag-NHC complexes; Anion metathesis ID PROTIC ACID; GLYCOSYLATION; COMPLEXES; DONORS; DRUGS AB We herein report O-glycosidation reactions promoted via silver N-heterocyclic carbene complexes formed in situ in ionic liquids. Seven different room temperature ionic liquids were screened for the glycosidation reaction of 4-nitrophenol with tetra-O-acetyl-alpha-D-galactopyranosyl bromide. Good to excellent yields were obtained using Ag-NHC complexes derived from imidazolium halide salts to promote the glycosidation reaction, whereas yields considered moderate to low were obtained without use of the silver carbene complex. Anion metathesis of the ionic liquids with inexpensive alkylammonium halides also resulted in silver N-heterocyclic carbene formation and subsequent O-glycosidation in the presence of silver carbonate. Effective utility of this methodology has been demonstrated with biologically relevant acceptors (including flavones and steroids) where O-beta-glycoside products were obtained selectively in moderate to good yields. We have also demonstrated that the Ag-NHC complex is a superior promoter to traditionally used silver carbonate for the glycosidation of polyphenolic acceptors. The ionic liquids used in the study could be recycled three times without apparent loss in activity. (C) 2011 Published by Elsevier Ltd. C1 [Talisman, Ian Jamie; Kumar, Vineet; Razzaghy, Jacqueline; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Malhotra, SV (reprint author), NCI, Lab Synthet Chem, SAIC Frederick Inc, 1050 Boyles St, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HSN261200800001E] FX The authors would like to thank the NCI Developmental Therapeutics Program. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HSN261200800001E. The authors would also like to thank Jeffrey R. Deschamps and Mark Frisch, Naval Research Laboratory, Washington, DC for X-ray crystal structure studies. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 22 TC 6 Z9 6 U1 3 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAY 15 PY 2011 VL 346 IS 7 BP 883 EP 890 DI 10.1016/j.carres.2011.03.007 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 771QS UT WOS:000291176400001 PM 21459367 ER PT J AU Xiang, Y Shen, J AF Xiang, Yun Shen, Jun TI Simultaneous detection of cerebral metabolism of different substrates by in vivo C-13 isotopomer MRS SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Cerebral energy metabolism; In vivo C-13 MRS; Carboxylic/amide spectral region; Ketone body; Lactate ID MAGNETIC-RESONANCE-SPECTROSCOPY; BRAIN ENERGY-METABOLISM; RAT-BRAIN; GLUTAMATE-GLUTAMINE; KETONE-BODIES; GLUCOSE-METABOLISM; NMR-SPECTROSCOPY; AMINO-ACIDS; 11.7 TESLA; LACTATE AB In this report a new method is introduced for simultaneous detection of the metabolism of two C-13-labeled subtracts in brain in vivo. We recognized and experimentally demonstrated that when a C-13-labeled substrate generates [1,2-(13)C(2)jacetylCoA ([1-C-13]acetylCoA) only, glutamate C5, glutamine C5 and apsartate C4 doublets (singlets) are formed exclusively, regardless of the number of turns of the tricarboxylic acid cycle. We utilized the large one-bond C-13-C-13 homonuclear J coupling between a carboxylic/amide carbon and an aliphatic carbon (similar to 50 Hz) and demonstrated that it is feasible to simultaneously detect the labeling of brain metabolites by two different substrates using different isotopomer signals of the same carbon atom. Uniformly labeled glucose was used to generate the doublets and a second substrate ([2-C-13] lactate or [1,3-C-13(2)]beta-hydroxybutyrate or [1-C-13] acetate) was used to generate the singlets. It was shown that contribution to cerebral metabolism from different substrates can be simultaneously measured in vivo. Published by Elsevier B.V. C1 [Xiang, Yun; Shen, Jun] NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Intramural Res Program, NIH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU National Institute of Mental Health, National Institutes of Health (NIMH-NIH); National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services (IRP-NIMH-NIH-DHHS) FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (NIMH-NIH). The authors have no conflict of interest to disclose, financial or otherwise.; The authors are grateful to Dr. Su Xu, Mr. Christopher Johnson, Drs. Steve Li, Van Zhang, Jan Willem van der Veen and BuSik Park for their valuable help, and loline Henter for editing the manuscript. This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services (IRP-NIMH-NIH-DHHS). NR 60 TC 8 Z9 8 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAY 15 PY 2011 VL 198 IS 1 BP 8 EP 15 DI 10.1016/j.jneumeth.2011.02.021 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 771FM UT WOS:000291142600002 PM 21419161 ER PT J AU Wang, TZ Zhao, R Wu, YQ Kong, D Zhang, L Wu, D Li, C Zhang, C Yu, ZX Jin, XM AF Wang, Tianzhen Zhao, Ran Wu, Yiqi Kong, Dan Zhang, Lei Wu, Di Li, Chao Zhang, Chong Yu, Zuxi Jin, Xiaoming TI Hepatitis B virus induces G1 phase arrest by regulating cell cycle genes in HepG2.2.15 cells SO VIROLOGY JOURNAL LA English DT Article DE HepG2.2.15 HepG2; HBV; proliferation; cell cycle ID HBV-INFECTED PATIENTS; HEPATOCELLULAR-CARCINOMA; EXPRESSION; MUTATIONS; GENOTYPES; REPLICATION; COMBINATION; INTEGRATION; LAMIVUDINE; PROTEIN AB Background: To investigate the effect of HBV on the proliferative ability of host cells and explore the potential mechanism. Methods: MTT, colony formation assay and tumourigenicity in nude mice were performed to investigate the effect of HBV on the proliferative capability of host cells. In order to explore the potential mechanism, cell cycle and apoptosis were analysed. The cell cycle genes controlling the G1/S phase transition were detected by immunohistochemistry, westernblot and RT-PCR. Results: HepG2.2.15 cells showed decreased proliferation ability compared to HepG2 cells. G1 phase arrest was the main cause but was not associated with apoptosis. p53, p21 and total retinoblastoma (Rb) were determined to be up-regulated, whereas cyclinE was down-regulated at both the protein and mRNA levels in HepG2.2.15 cells. The phosphorylated Rb in HepG2.2.15 cells was decreased. Conclusions: Our results suggested that HBV inhibited the capability of proliferation of HepG2.2.15 cells by regulating cell cycle genes expression and inducing G1 arrest. C1 [Wang, Tianzhen; Zhao, Ran; Wu, Yiqi; Zhang, Lei; Li, Chao; Zhang, Chong; Jin, Xiaoming] Harbin Med Coll, Basic Med Sci Coll, Dept Pathol, Harbin 150081, Peoples R China. [Kong, Dan] Kanazawa Univ, Canc Res Inst, Kanazawa, Ishikawa 9201192, Japan. [Wu, Di] Harbin Med Coll, Affiliated Hosp 1, Dept Obstet & Gynecol, Harbin 150001, Peoples R China. [Yu, Zuxi] NHLBI, NIH, Bethesda, MD 20892 USA. RP Jin, XM (reprint author), Harbin Med Coll, Basic Med Sci Coll, Dept Pathol, 157 Baojian Rd, Harbin 150081, Peoples R China. EM Jinxm55@yahoo.com.cn FU Graduate Innovation Foundation of Harbin Medical University [HCXB2010010] FX We are grateful to Professor Yumei Wen for providing us the cell line. This work was supported by Graduate Innovation Foundation of Harbin Medical University (HCXB2010010). NR 31 TC 15 Z9 15 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD MAY 15 PY 2011 VL 8 AR 231 DI 10.1186/1743-422X-8-231 PG 8 WC Virology SC Virology GA 770QO UT WOS:000291103800001 PM 21575146 ER PT J AU Kratz, CP Rapisuwon, S Reed, H Hasle, H Rosenberg, PS AF Kratz, Christian P. Rapisuwon, Suthee Reed, Helen Hasle, Henrik Rosenberg, Philip S. TI Cancer in Noonan, Costello, Cardiofaciocutaneous and LEOPARD Syndromes SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE RASopathies; cancer risk; mortality ID JUVENILE MYELOMONOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GERMLINE PTPN11 MUTATION; ACUTE MYELOID-LEUKEMIA; RAS GENE-MUTATIONS; EMBRYONAL RHABDOMYOSARCOMA; CLONAL DUPLICATION; UNIPARENTAL DISOMY; DISORDERS; PATHWAY AB Noonan syndrome (NS), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and LEOPARD syndrome (now also referred to as Noonan syndrome with multiple lentigines or NSML) are clinically overlapping dominant disorders that are caused by mutations in RAS signaling pathway genes. The spectrum of cancer susceptibility in this group of disorders has not been studied in detail. We identified more than 1900 cases of NS, CS, CFCS, or NSML reported in the literature between 1937 and 2010; 88 cancers were reported. The most common cancers reported in 1051 NS subjects were neuroblastoma (n = 8), acute lymphoblastic leukemia (n = 8), low grade glioma (n = 6), and rhabdomyosarcoma (n = 6). These associations are biologically plausible, given that somatic RAS pathway mutations are known to occur in these specific cancers. In addition, 40 childhood cases of myeloproliferative disease were described in individuals with NS, several of whom experienced a benign course of this hematologic condition. We confirmed the previously described association between CS and cancer in 268 reported individuals: 19 had rhabdomyosarcoma, 4 had bladder cancer, and 5 had neuroblastoma. By age 20, the cumulative incidence of cancer was approximately 4% for NS and 15% for CS; both syndromes had a cancer incidence peak in childhood. The cancers described in CFCS and NSML overlapped with those reported in NS and CS. Future epidemiologic studies will be required to confirm the described cancer spectrum and to estimate precise cancer risks. Published 2011 Wiley-Liss, Inc. C1 [Kratz, Christian P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. [Hasle, Henrik] Aarhus Univ Hosp, Dept Pediat, DK-8000 Aarhus, Denmark. [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. RP Kratz, CP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7018, Rockville, MD 20892 USA. EM kratzcp@mail.nih.gov OI Rapisuwon, Suthee/0000-0002-1389-925X; Hasle, Henrik/0000-0003-3976-9231 FU National Institutes of Health; National Cancer Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. We are grateful to Drs. Blanche P. Alter and Mark H. Greene for their insightful comments. We thank Dr. William F. Anderson for his statistical support related to SEER-derived median ages of cancer in the general population. NR 32 TC 68 Z9 70 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD MAY 15 PY 2011 VL 157C IS 2 SI SI BP 83 EP 89 DI 10.1002/ajmg.c.30300 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 765OI UT WOS:000290717500002 PM 21500339 ER PT J AU Denayer, E Descheemaeker, MJ Stewart, DR Keymolen, K Plasschaert, E Ruppert, SL Snow, J Thurm, AE Joseph, LA Fryns, JP Legius, E AF Denayer, Ellen Descheemaeker, Mie-Jef Stewart, Douglas R. Keymolen, Kathelijn Plasschaert, Ellen Ruppert, Sarah L. Snow, Joseph Thurm, Audrey E. Joseph, Lisa A. Fryns, Jean-Pierre Legius, Eric TI Observations on Intelligence and Behavior in 15 Patients With Legius Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE intelligence; behavior; Legius syndrome; SPRED1; MAPK ID NEUROFIBROMATOSIS TYPE-1; MOUSE MODEL; LEARNING-DEFICITS; SPRED1; MUTATIONS; PHENOTYPE AB Legius syndrome is a RAS-MAPK syndrome characterized by pigmentary findings similar to neurofibromatosis type 1 (NF1), but without tumor complications. Learning difficulties and behavioral problems have been reported to be associated with Legius syndrome, but have not been studied systematically. We investigated intelligence and behavior in 15 patients with Legius syndrome and 7 unaffected family members. We report a mean full-scale IQ of 101.57 in patients with Legius syndrome, which does not differ from the control group. We find a significantly lower Performance IQ in children with Legius syndrome compared to their unaffected family members. Few behavioral problems are present as assessed by the Child Behavior Checklist (CBCL) questionnaire. Our observations suggest that, akin to the milder somatic phenotype, the cognitive phenotype in Legius syndrome is less severe than that of NF1. (c) 2011 Wiley-Liss, Inc. C1 [Legius, Eric] Catholic Univ Louvain, Dept Human Genet, Ctr Human Genet, Neurofibromatosis Res Grp, B-3000 Louvain, Belgium. [Fryns, Jean-Pierre; Legius, Eric] Univ Hosp Leuven, Ctr Human Genet, Div Clin Genet, Louvain, Belgium. [Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Keymolen, Kathelijn] Univ Hosp Brussels, Brussels, Belgium. [Plasschaert, Ellen] Erasmus Univ, Grp Ype Elgersma, Rotterdam, Netherlands. [Ruppert, Sarah L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD USA. [Snow, Joseph] NIMH, Off Clin Director, Intramural Res Program, Bethesda, MD USA. [Snow, Joseph] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Thurm, Audrey E.] NIMH, PDN Branch, Intramural Res Program, Bethesda, MD USA. RP Legius, E (reprint author), Catholic Univ Louvain, Dept Human Genet, Ctr Human Genet, Neurofibromatosis Res Grp, Herestr 49, B-3000 Louvain, Belgium. EM eric.legius@uzleuven.be OI Legius, Eric/0000-0003-2410-6996 FU Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0578.06, G.O551.08]; Federal Office for Scientific, Technical and Cultural Affairs, Belgium [P6/05]; K.U. Leuven; Division of Intramural Research of the National Human Genome Research Institute; National Institute of Mental Health FX Grant sponsor: Fonds voor Wetenschappelijk Onderzoek Vlaanderen; Grant numbers: G.0578.06, G.O551.08; Grant sponsor: Interuniversity Attraction Poles (IAP); Federal Office for Scientific, Technical and Cultural Affairs, Belgium (2007-2011); Grant number: P6/05; Grant sponsor: Concerted Action Grant; K.U. Leuven; Grant sponsor: Division of Intramural Research of the National Human Genome Research Institute, National Institute of Mental Health.E.D. is predoctoral researcher of the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen; This work is supported by research grants from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (G.0578.06 and G.O551.08 to E.L.); the Interuniversity Attraction Poles (IAP) granted by the Federal Office for Scientific, Technical and Cultural Affairs, Belgium (2007-2011; P6/05) (E.L.), and by a Concerted Action Grant from the K.U. Leuven (E.L.). The work was supported in part by the Division of Intramural Research of the National Human Genome Research Institute and the National Institute of Mental 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 16 TC 7 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD MAY 15 PY 2011 VL 157C IS 2 SI SI BP 123 EP 128 DI 10.1002/ajmg.c.30297 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 765OI UT WOS:000290717500006 PM 21495177 ER PT J AU Martin, OA Redon, CE Nakamura, AJ Dickey, JS Georgakilas, AG Bonner, WM AF Martin, Olga A. Redon, Christophe E. Nakamura, Asako J. Dickey, Jennifer S. Georgakilas, Alexandros G. Bonner, William M. TI Systemic DNA Damage Related to Cancer SO CANCER RESEARCH LA English DT Review ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; IN-VIVO; MCP-1; CCL2; INFLAMMATION; INDUCTION; DISEASE; GROWTH; CELLS; LEADS AB The importance of bystander effects is becoming more appreciated, as studies show they may affect the course of cancer and other chronic diseases. The term "bystander effects" refers to changes in naive cells sharing the same milieu with cells that have been damaged. Bystander cells may be in contact with, or distant from, damaged cells. In addition, it has been shown in culture that not only physically damaged cells, but also cells that have become abnormal (i.e., cancerous or senescent) may induce bystander effects. Recently, we have shown a similar effect in animals. Mice harboring subcutaneous tumors exhibited elevated levels of DNA damage in distant organs. In contrast to cell culture, immune cells seemed to be involved in tumor-induced bystander effects in animals because CCL2-null tumor-bearing mice did not exhibit increased distant DNA damage. Here, we discuss some of the implications of these observations. Cancer Res; 71(10); 3437-41. (C) 2011 AACR. C1 [Martin, Olga A.; Redon, Christophe E.; Nakamura, Asako J.; Dickey, Jennifer S.; Bonner, William M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Dickey, Jennifer S.] US FDA, Biochem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Georgakilas, Alexandros G.] E Carolina Univ, Dept Biol, Greenville, NC USA. RP Martin, OA (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bldg 37,Room 5050,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sedelnio@mail.nih.gov FU National Cancer Institute (NCI) Center for Cancer Research, NIH; NCI; Biology Department of East Carolina University FX This work was funded by the Intramural Research Program of the National Cancer Institute (NCI) Center for Cancer Research, NIH, by an NCI Career Development Award (to C.E. Redon and O.A. Martin), and a Research/Creative Activity grant and a College Research award from the Biology Department of East Carolina University (to A.G. Georgakilas). NR 30 TC 24 Z9 25 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2011 VL 71 IS 10 BP 3437 EP 3441 DI 10.1158/0008-5472.CAN-10-4579 PG 5 WC Oncology SC Oncology GA 764EH UT WOS:000290610900001 PM 21558390 ER PT J AU Catalona, WJ Bailey-Wilson, JE Camp, NJ Chanock, SJ Cooney, KA Easton, DF Eeles, RA FitzGerald, LM Freedman, ML Gudmundsson, J Kittles, RA Margulies, EH McGuire, BB Ostrander, EA Rebbeck, TR Stanford, JL Thibodeau, SN Witte, JS Isaacs, WB AF Catalona, William J. Bailey-Wilson, Joan E. Camp, Nicola J. Chanock, Stephen J. Cooney, Kathleen A. Easton, Douglas F. Eeles, Rosalind A. FitzGerald, Liesel M. Freedman, Matthew L. Gudmundsson, Julius Kittles, Rick A. Margulies, Elliott H. McGuire, Barry B. Ostrander, Elaine A. Rebbeck, Timothy R. Stanford, Janet L. Thibodeau, Stephen N. Witte, John S. Isaacs, William B. TI National Cancer Institute Prostate Cancer Genetics Workshop SO CANCER RESEARCH LA English DT Editorial Material ID SUSCEPTIBILITY; SCAN; AGGRESSIVENESS; ASSOCIATION; RISK; LOCI AB Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness-one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics. Cancer Res; 71(10); 3442-6. (C) 2011 AACR. C1 [Catalona, William J.; McGuire, Barry B.] Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. [Kittles, Rick A.] Univ Illinois, Dept Med, Chicago, IL USA. [Camp, Nicola J.] Univ Utah, Div Genet Epidemiol, Salt Lake City, UT USA. [Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, MD USA. [Isaacs, William B.] Johns Hopkins Med Inst, Dept Urol & Oncol, Baltimore, MD 21205 USA. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Chanock, Stephen J.] NCI, Core Genotyping Facil, SAIC Frederick Inc, NIH,DHHS, Gaithersburg, MD USA. [Margulies, Elliott H.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. [Cooney, Kathleen A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Easton, Douglas F.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England. [Eeles, Rosalind A.] Inst Canc Res, Surrey, England. [Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [FitzGerald, Liesel M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freedman, Matthew L.] Broad Inst, Cambridge, MA USA. [Gudmundsson, Julius] deCODE Genet Inc, Reykjavik, Iceland. [Rebbeck, Timothy R.] Univ Penn, Abramson Canc Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Thibodeau, Stephen N.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 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 94143 USA. RP Catalona, WJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Urol, 675 N St Clair St,Suite 20-150, Chicago, IL 60611 USA. EM wcatalona@nmff.org OI Bailey-Wilson, Joan/0000-0002-9153-2920; Eeles, Rosalind/0000-0002-3698-6241; Ostrander, Elaine/0000-0001-6075-9738 FU Urological Research Foundation [P50CA90386-05S2]; Robert H. Lurie Comprehensive Cancer Center [P30 CA60553]; [SPORE P50 CA69568]; [R01 CA136621] FX This workshop was supported by resources from the National Cancer Institute. Dr. Cooney wishes to acknowledge grants: SPORE P50 CA69568 and R01 CA136621.; Dr. Catalona wishes to acknowledge that his research was supported in part by the Urological Research Foundation, Prostate SPORE grant (P50CA90386-05S2), and the Robert H. Lurie Comprehensive Cancer Center grant (P30 CA60553). NR 11 TC 6 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2011 VL 71 IS 10 BP 3442 EP 3446 DI 10.1158/0008-5472.CAN-11-0314 PG 5 WC Oncology SC Oncology GA 764EH UT WOS:000290610900002 PM 21558387 ER PT J AU Olkhanud, PB Damdinsuren, B Bodogai, M Gress, RE Sen, R Wejksza, K Malchinkhuu, E Wersto, RP Biragyn, A AF Olkhanud, Purevdorj B. Damdinsuren, Bazarragchaa Bodogai, Monica Gress, Ronald E. Sen, Ranjan Wejksza, Katarzyna Malchinkhuu, Enkhzol Wersto, Robert P. Biragyn, Arya TI Tumor-Evoked Regulatory B Cells Promote Breast Cancer Metastasis by Converting Resting CD4(+) T Cells to T-Regulatory Cells SO CANCER RESEARCH LA English DT Article ID MYELOID SUPPRESSOR-CELLS; TGF-BETA; INDUCTION; TOLERANCE; EXPANSION; RESPONSES; SUBSET; MODEL; MICE; CONTRIBUTES AB Pulmonary metastasis of breast cancer requires recruitment and expansion of T-regulatory cells (Treg) that promote escape from host protective immune cells. However, it remains unclear precisely how tumors recruit Tregs to support metastatic growth. Here we report the mechanistic involvement of a unique and previously undescribed subset of regulatory B cells. These cells, designated tumor-evoked Bregs (tBreg), phenotypically resemble activated but poorly proliferative mature B2 cells (CD19(+) CD25(High) CD69(High)) that express constitutively active Stat3 and B7-H1(High) CD81(High) CD86(High) CD62L(Low) IgM(Int). Our studies with the mouse 4T1 model of breast cancer indicate that the primary role of tBregs in lung metastases is to induce TGF-beta-dependent conversion of FoxP3(+) Tregs from resting CD4(+) T cells. In the absence of tBregs, 4T1 tumors cannot metastasize into the lungs efficiently due to poor Treg conversion. Our findings have important clinical implications, as they suggest that tBregs must be controlled to interrupt the initiation of a key cancer-induced immunosuppressive event that is critical to support cancer metastasis. Cancer Res; 71(10); 3505-15. (C) 2011 AACR. C1 [Olkhanud, Purevdorj B.; Bodogai, Monica; Wejksza, Katarzyna; Malchinkhuu, Enkhzol; Biragyn, Arya] NIA, Immunotherapeut Unit, Immunol Lab, Baltimore, MD 21224 USA. [Damdinsuren, Bazarragchaa; Sen, Ranjan] NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. [Wersto, Robert P.] NIA, Flow Cytometry Unit, Res Resources Branch, Baltimore, MD 21224 USA. [Gress, Ronald E.] Expt Transplantat & Immunol Branch, Bethesda, MD USA. RP Biragyn, A (reprint author), NIA, Immunotherapeut Unit, Immunol Lab, Rm 08C220,251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM biragyna@mail.nih.gov FU National Institute on Aging, NIH FX This research was supported by the Intramural Research Program of the National Institute on Aging, NIH. NR 36 TC 131 Z9 142 U1 2 U2 23 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 MAY 15 PY 2011 VL 71 IS 10 BP 3505 EP 3515 DI 10.1158/0008-5472.CAN-10-4316 PG 11 WC Oncology SC Oncology GA 764EH UT WOS:000290610900009 PM 21444674 ER PT J AU Gabriely, G Yi, M Narayan, RS Niers, JM Wurdinger, T Imitola, J Ligon, KL Kesari, S Esau, C Stephens, RM Tannous, BA Krichevsky, AM AF Gabriely, Galina Yi, Ming Narayan, Ravi S. Niers, Johanna M. Wurdinger, Thomas Imitola, Jaime Ligon, Keith L. Kesari, Santosh Esau, Christine Stephens, Robert M. Tannous, Bakhos A. Krichevsky, Anna M. TI Human Glioma Growth Is Controlled by MicroRNA-10b SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; CELL-DEATH; STEM-CELLS; GLIOBLASTOMA; MIGRATION; INVASION; TUMORIGENESIS; GENES; LINES AB MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly upregulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell-cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2 gamma, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas expression data set reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while proapoptotic genes anticorrelate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b-mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas. Cancer Res; 71(10); 3563-72. (C) 2011 AACR. C1 [Krichevsky, Anna M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Ligon, Keith L.] Childrens Hosp Boston, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Ligon, Keith L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yi, Ming; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick Inc, Bethesda, MD 20892 USA. [Niers, Johanna M.; Wurdinger, Thomas; Tannous, Bakhos A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Narayan, Ravi S.; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Kesari, Santosh] Univ Calif San Diego, Dept Neurosci, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. [Esau, Christine] Regulus Therapeut, San Diego, CA USA. RP Krichevsky, AM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Dept Neurol, 4 Blackfan Circle,HIM 616, Boston, MA 02115 USA. EM akrichevsky@rics.bwh.harvard.edu RI Kesari, Santosh/E-8461-2013; imitola, jaime/J-8478-2015 FU National Cancer Institute (NCI) [R01CA138734]; Paul Brazen American Brain Tumor Association; Sontag awards FX This study was supported by National Cancer Institute (NCI) R01CA138734 and Sontag awards (to A.M. Krichevsky) and Paul Brazen American Brain Tumor Association Fellowship (to G. Gabriely). NR 22 TC 137 Z9 145 U1 7 U2 20 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 MAY 15 PY 2011 VL 71 IS 10 BP 3563 EP 3572 DI 10.1158/0008-5472.CAN-10-3568 PG 10 WC Oncology SC Oncology GA 764EH UT WOS:000290610900014 PM 21471404 ER PT J AU Jiao, L Weinstein, SJ Albanes, D Taylor, PR Graubard, BI Virtamo, J Stolzenberg-Solomon, RZ AF Jiao, Li Weinstein, Stephanie J. Albanes, Demetrius Taylor, Philip R. Graubard, Barry I. Virtamo, Jarmo Stolzenberg-Solomon, Rachael Z. TI Evidence That Serum Levels of the Soluble Receptor for Advanced Glycation End Products Are Inversely Associated with Pancreatic Cancer Risk: A Prospective Study SO CANCER RESEARCH LA English DT Article ID NONDIABETIC SUBJECTS; INSULIN-RESISTANCE; RAGE LIGANDS; FORM SRAGE; DISEASE; INFLAMMATION; AGE; ENDPRODUCTS; EXPRESSION; BIOMARKERS AB Cigarette smoking, obesity, type 2 diabetes, and, to a lesser extent, meat cooked at high temperatures are associated with pancreatic cancer. Cigarette smoke and foods cooked at higher temperatures are major environmental sources of advanced glycation end products (AGE). AGEs accumulate during hyperglycemia and elicit oxidative stress and inflammation through interaction with the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) acts as an anti-inflammatory factor to neutralize AGEs and block the effects mediated by RAGE. In this study, we investigated the associations of prediagnostic measures of N(epsilon)-(carboxymethyl)-lysine (CML)-AGE and sRAGE with pancreatic cancer in a case-cohort study within a cohort of 29,133 Finnish male smokers. Serum samples and exposure information were collected at baseline (1985-1988). We measured CML-AGE, sRAGE, glucose, and insulin concentrations in fasting serum from 255 incident pancreatic cancer cases that arose through April 2005 and from 485 randomly sampled subcohort participants. Weighted Cox proportional hazard regression models were used to calculate relative risks (RR) and 95% CI, adjusted for age, years of smoking, and body mass index. CML-AGE and sRAGE were mutually adjusted. CML-AGE levels were not associated with pancreatic cancer [fifth compared with first quintile, RR (95% CI): 0.68 (0.38-1.22), P(trend) -0.27]. In contrast, sRAGE levels were inversely associated with pancreatic cancer [fifth compared with first quintile, RR (95% CI): 0.46 (0.23-0.73), P(trend) = 0.002]. Further adjustment for glucose or insulin levels did not change the observed associations. Our findings suggest that sRAGE is inversely associated with pancreatic cancer risk among Finnish male smokers. Cancer Res; 71(10); 3582-9. (C) 2011 AACR. C1 [Jiao, Li; Weinstein, Stephanie J.; Albanes, Demetrius; Taylor, Philip R.; Graubard, Barry I.; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Jiao, L (reprint author), Baylor Coll Med, Dept Med, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM jiao@bcm.edu RI Albanes, Demetrius/B-9749-2015 FU Division of Cancer Epidemiology and Genetics of the National Cancer Institute at the NIH; U.S. Public Health Service, National Cancer Institute, U.S. Department of Health and Human Services [N01-CN-45165, N01-RC-45035, N01-RC-37004, HSN261201000006C]; National Cancer Institute FX This work was supported by the intramural research program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute at the NIH. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by U.S. Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004, and HSN261201000006C from the National Cancer Institute, U.S. Department of Health and Human Services, and by funding from the Intramural Research Program of the National Cancer Institute. NR 47 TC 31 Z9 33 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 MAY 15 PY 2011 VL 71 IS 10 BP 3582 EP 3589 DI 10.1158/0008-5472.CAN-10-2573 PG 8 WC Oncology SC Oncology GA 764EH UT WOS:000290610900016 PM 21540233 ER PT J AU Hopper-Borge, EA Churchill, T Paulose, C Nicolas, E Jacobs, JD Ngo, O Kuang, YH Grinberg, A Westphal, H Chen, ZS Klein-Szanto, AJ Belinsky, MG Kruh, GD AF Hopper-Borge, Elizabeth A. Churchill, Timothy Paulose, Chelsy Nicolas, Emmanuelle Jacobs, Joely D. Ngo, Olivia Kuang, Yehong Grinberg, Alex Westphal, Heiner Chen, Zhe-Sheng Klein-Szanto, Andres J. Belinsky, Martin G. Kruh, Gary D. TI Contribution of Abcc10 (Mrp7) to In Vivo Paclitaxel Resistance as Assessed in Abcc10(-/-) Mice SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; MULTIDRUG-RESISTANCE; CHEMOTHERAPY RESPONSE; PROTEIN-7 ABCC10; P-GLYCOPROTEIN; EXPRESSION; DOCETAXEL; REVERSAL AB Recently, we reported that the ATP-binding cassette transporter 10 (ABCC10), also known as multidrug resistance protein 7 (MRP7), is able to confer resistance to a variety of anticancer agents, including taxanes. However, the in vivo functions of the pump have not been determined to any extent. In this study, we generated and analyzed Abcc10(-/-) mice to investigate the ability of Abcc10 to function as an endogenous resistance factor. Mouse embryo fibroblasts derived from Abcc10(-/-) mice were hypersensitive to docetaxel, paclitaxel, vincristine, and cytarabine (Ara-C) and exhibited increased cellular drug accumulation, relative to wild-type controls. Abcc10(-/-) null mice treated with paclitaxel exhibited increased lethality associated with neutropenia and marked bone marrow toxicity. In addition, toxicity in spleen and thymus was evident. These findings indicate that Abcc10 is dispensable for health and viability and that it is an endogenous resistance factor for taxanes, other natural product agents, and nucleoside analogues. This is the first demonstration that an ATP-binding cassette transporter other than P-glycoprotein can affect in vivo tissue sensitivity toward taxanes. Cancer Res; 71(10); 3649-57. (C) 2011 AACR. C1 [Hopper-Borge, Elizabeth A.; Churchill, Timothy; Paulose, Chelsy; Jacobs, Joely D.; Ngo, Olivia; Belinsky, Martin G.] Fox Chase Canc Ctr, Dev Therapeut Program, Philadelphia, PA 19111 USA. [Nicolas, Emmanuelle] Fox Chase Canc Ctr, Genom Facil, Philadelphia, PA 19111 USA. [Klein-Szanto, Andres J.] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. [Kruh, Gary D.] Univ Illinois, Dept Med, Chicago, IL USA. [Kruh, Gary D.] Univ Illinois, Ctr Canc, Chicago, IL USA. [Kuang, Yehong; Chen, Zhe-Sheng] St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. [Kuang, Yehong; Grinberg, Alex] Cent S Univ, Xiang Ya Hosp, Dept Dermatol, Changsha, Hunan, Peoples R China. [Westphal, Heiner] NICHHD, NIH, Bethesda, MD 20892 USA. RP Hopper-Borge, EA (reprint author), Fox Chase Canc Ctr, Dev Therapeut Program, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM EA_Hopper@fccc.edu FU NIH [K01CA120091, CA073728, 1R15CA143701, CA06927] FX This work was supported by NIH grants K01CA120091 to E.A. Hopper-Borge, CA073728 to G.D. Kruh, 1R15CA143701 to Z-S. Chen, and CA06927 to Fox Chase Cancer Center. NR 25 TC 26 Z9 27 U1 0 U2 6 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 MAY 15 PY 2011 VL 71 IS 10 BP 3649 EP 3657 DI 10.1158/0008-5472.CAN-10-3623 PG 9 WC Oncology SC Oncology GA 764EH UT WOS:000290610900022 PM 21576088 ER PT J AU Yang, XP Lu, H Yan, B Romano, RA Bian, YS Friedman, J Duggal, P Allen, C Chuang, R Ehsanian, R Si, H Sinha, S Van Waes, C Chen, Z AF Yang, Xinping Lu, Hai Yan, Bin Romano, Rose-Anne Bian, Yansong Friedman, Jay Duggal, Praveen Allen, Clint Chuang, Ryan Ehsanian, Reza Si, Han Sinha, Satrajit Van Waes, Carter Chen, Zhong TI Delta Np63 Versatilely Regulates a Broad NF-kappa B Gene Program and Promotes Squamous Epithelial Proliferation, Migration, and Inflammation SO CANCER RESEARCH LA English DT Article ID CARCINOMA-CELL LINES; NECK-CANCER; TRANSCRIPTION FACTORS; P53 FAMILY; HUMAN KERATINOCYTES; TARGET GENES; P63 TARGETS; IN-VIVO; HEAD; SURVIVAL AB Head and neck squamous cell carcinoma (HNSCC) and many other epithelial malignancies exhibit increased proliferation, invasion, and inflammation, concomitant with aberrant nuclear activation of TP53 and NF-kappa B family members Delta Np63, cRel, and RelA. However, the mechanisms of cross-talk by which these transcription factors coordinate gene expression and the malignant phenotype remain elusive. In this study, we showed that Delta Np63 regulates a cohort of genes involved in cell growth, survival, adhesion, and inflammation, which substantially overlaps with the NF-kappa B transcriptome. Delta Np63 with cRel and/or RelA are recruited to form novel binding complexes on p63 or NF-kappa B/Rel sites of multitarget gene promoters. Overexpressed Delta Np63- or TNF-alpha-induced NF-kappa B and inflammatory cytokine interleukin-8 (IL-8) reporter activation depended on RelA/cRel regulatory binding sites. Depletion of RelA or Delta Np63 by small interfering RNA (siRNA) significantly inhibited NF-kappa B-specific, or TNF-alpha-induced IL-8 reporter activation. Delta Np63 siRNA significantly inhibited proliferation, survival, and migration by HNSCC cells in vitro. Consistent with these data, an increase in nuclear Delta Np63, accompanied by increased proliferation (Ki-67) and adhesion (beta 4 integrin) markers, and induced inflammatory cell infiltration was observed throughout HNSCC specimens, when compared with the basilar pattern of protein expression and minimal inflammation seen in nonmalignant mucosa. Furthermore, overexpression of Delta Np63 alpha in squamous epithelial cells in transgenic mice leads to increased suprabasilar cRel, Ki-67, and cytokine expression, together with epidermal hyperplasia and diffuse inflammation, similar to HNSCC. Our study reveals Delta Np63 as a master transcription factor that, in coordination with NF-kappa B/Rels, orchestrates a broad gene program promoting epidermal hyperplasia, inflammation, and the malignant phenotype of HNSCC. Cancer Res; 71(10); 3688-700. (C) 2011 AACR. C1 [Yan, Bin; Sinha, Satrajit] SUNY Buffalo, Dept Biochem, Ctr Excellence Bioinformat & Life Sci, Buffalo, NY 14214 USA. [Allen, Clint] NIH & Pfizer Inc, Clin Res Training Program, Bethesda, MD USA. [Ehsanian, Reza] Howard Hughes Med Inst NIH, Res Scholars Program, Chevy Chase, MD USA. [Ehsanian, Reza] NIH, Grad Partnership Program, Bethesda, MD USA. [Ehsanian, Reza] Univ Oxford, Oxford OX1 2JD, England. [Yang, Xinping; Lu, Hai; Yan, Bin; Bian, Yansong; Friedman, Jay; Duggal, Praveen; Allen, Clint; Chuang, Ryan; Ehsanian, Reza; Si, Han; Van Waes, Carter; Chen, Zhong] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Chen, Z (reprint author), NIDCD, Head & Neck Surg Branch, NIH, 10-5D55,MSC-1419, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov; chenz@nidcd.nih.gov FU NIDCD [ZIA-DC-00016, ZIA-DC-00073, ZIA-DC-00074]; NIH [R01AR049238] FX This project is supported by NIDCD Intramural projects ZIA-DC-00016, ZIA-DC-00073, and ZIA-DC-00074 and a grant from NIH R01AR049238 (S. Sinha). NR 50 TC 56 Z9 58 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 MAY 15 PY 2011 VL 71 IS 10 BP 3688 EP 3700 DI 10.1158/0008-5472.CAN-10-3445 PG 13 WC Oncology SC Oncology GA 764EH UT WOS:000290610900026 PM 21576089 ER PT J AU Cerliani, JP Guillardoy, T Giulianelli, S Vaque, JP Gutkind, JS Vanzulli, SI Martins, R Zeitlin, E Lamb, CA Lanari, C AF Cerliani, Juan P. Guillardoy, Tomas Giulianelli, Sebastian Vaque, Jose P. Gutkind, J. Silvio Vanzulli, Silvia I. Martins, Ruben Zeitlin, Eduardo Lamb, Caroline A. Lanari, Claudia TI Interaction between FGFR-2, STAT5, and Progesterone Receptors in Breast Cancer SO CANCER RESEARCH LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; MAMMARY-TUMOR GROWTH; SIGNAL TRANSDUCER; IN-VITRO; TRANSCRIPTION FACTORS; ENDOCRINE TREATMENT; LUNG-CANCER; EXPRESSION; CELLS; ACTIVATOR AB Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/ STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment. Cancer Res; 71(10); 3720-31. (C) 2011 AACR. C1 [Cerliani, Juan P.; Guillardoy, Tomas; Giulianelli, Sebastian; Lamb, Caroline A.; Lanari, Claudia] Natl Res Council Argentina CONICET, Inst Expt Biol & Med IBYME, Buenos Aires, DF, Argentina. [Vanzulli, Silvia I.] Natl Acad Med Buenos Aires, Buenos Aires, DF, Argentina. [Martins, Ruben; Zeitlin, Eduardo] Bancario Clin, Dept Pathol, Buenos Aires, DF, Argentina. [Vaque, Jose P.; Gutkind, J. Silvio] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Lanari, C (reprint author), Consejo Nacl Invest Cient & Tecn, IBYME, Obligado 2490,C1428ADN, RA-1033 Buenos Aires, DF, Argentina. EM lanari.claudia@gmail.com RI Gutkind, J. Silvio/A-1053-2009; Vaque, Jose/H-8413-2015 OI Vaque, Jose/0000-0002-3913-2495 FU SECYT [PICT 2007/932]; CONICET; NIDCR, NIH, Bethesda, MD FX This work was supported by SECYT (PICT 2007/932); CONICET and Fundacion Sales. Drs. Gutkind and Vaque are supported by the Intramural Research Program of the NIDCR, NIH, Bethesda, MD. NR 50 TC 27 Z9 29 U1 1 U2 7 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 MAY 15 PY 2011 VL 71 IS 10 BP 3720 EP 3731 DI 10.1158/0008-5472.CAN-10-3074 PG 12 WC Oncology SC Oncology GA 764EH UT WOS:000290610900029 PM 21464042 ER PT J AU Butterfield, LH Palucka, AK Britten, CM Dhodapkar, MV Hakansson, L Janetzki, S Kawakami, Y Kleen, TO Lee, PP Maccalli, C Maecker, HT Maino, VC Maio, M Malyguine, A Masucci, G Pawelec, G Potter, DM Rivoltini, L Salazar, LG Schendel, DJ Slingluff, CL Song, WR Stroncek, DF Tahara, H Thurin, M Trinchieri, G van Der Burg, SH Whiteside, TL Wigginton, JM Marincola, F Khleif, S Fox, BA Disis, ML AF Butterfield, Lisa H. Palucka, A. Karolina Britten, Cedrik M. Dhodapkar, Madhav V. Hakansson, Leif Janetzki, Sylvia Kawakami, Yutaka Kleen, Thomas-Oliver Lee, Peter P. Maccalli, Cristina Maecker, Holden T. Maino, Vernon C. Maio, Michele Malyguine, Anatoli Masucci, Giuseppe Pawelec, Graham Potter, Douglas M. Rivoltini, Licia Salazar, Lupe G. Schendel, Dolores J. Slingluff, Craig L., Jr. Song, Wenru Stroncek, David F. Tahara, Hideaki Thurin, Magdalena Trinchieri, Giorgio van Der Burg, Sjoerd H. Whiteside, Theresa L. Wigginton, Jon M. Marincola, Francesco Khleif, Samir Fox, Bernard A. Disis, Mary L. TI Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers SO CLINICAL CANCER RESEARCH LA English DT Article ID T-CELL IMMUNITY; CYTOKINE FLOW-CYTOMETRY; CANCER VACCINE CONSORTIUM; COLONY-STIMULATING FACTOR; B ELISPOT ASSAY; PHASE-II TRIAL; DENDRITIC CELLS; CLINICAL-TRIALS; HIV VACCINE; HARMONIZATION GUIDELINES AB Purpose: To facilitate development of innovative immunotherapy approaches, especially for treatment concepts exploiting the potential benefits of personalized therapy, there is a need to develop and validate tools to identify patients who can benefit from immunotherapy. Despite substantial effort, we do not yet know which parameters of antitumor immunity to measure and which assays are optimal for those measurements. Experimental Design: The iSBTc-SITC (International Society for Biological Therapy of Cancer-Society for Immunotherapy of Cancer), FDA (Food and Drug Administration), and NCI (National Cancer Institute) partnered to address these issues for immunotherapy of cancer. Here, we review the major challenges, give examples of approaches and solutions, and present our recommendations. Results and Conclusions: Although specific immune parameters and assays are not yet validated, we recommend following standardized (accurate, precise, and reproducible) protocols and use of functional assays for the primary immunologic readouts of a trial; consideration of central laboratories for immune monitoring of large, multi-institutional trials; and standardized testing of several phenotypic and functional potential potency assays specific to any cellular product. When reporting results, the full QA (quality assessment)/QC (quality control) should be conducted and selected examples of truly representative raw data and assay performance characteristics should be included. Finally, to promote broader analysis of multiple aspects of immunity, and gather data on variability, we recommend that in addition to cells and serum, RNA and DNA samples be banked (under standardized conditions) for later testing. We also recommend that sufficient blood be drawn to allow for planned testing of the primary hypothesis being addressed in the trial, and that additional baseline and posttreatment blood is banked for testing novel hypotheses (or generating new hypotheses) that arise in the field. Clin Cancer Res; 17(10); 3064-76. (C) 2011 AACR. C1 [Butterfield, Lisa H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Butterfield, Lisa H.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. [Butterfield, Lisa H.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15213 USA. [Potter, Douglas M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. [Potter, Douglas M.] Biostat Facil, Pittsburgh, PA USA. [Whiteside, Theresa L.] Univ Pittsburgh, Inst Canc, Dept Pathol, Pittsburgh, PA 15213 USA. [Palucka, A. Karolina] Baylor Inst Immunol Res, Dallas, TX USA. [Palucka, A. Karolina] Mt Sinai Sch Med, Inst Immunol, Dept Gene & Cell Med, New York, NY USA. [Dhodapkar, Madhav V.] Yale Univ, Dept Hematol & Immunobiol, New Haven, CT USA. [Janetzki, Sylvia] ZellNet Consulting Inc, Ft Lee, NJ USA. [Wigginton, Jon M.] Bristol Myers Squibb Co, Discovery Med Clin Oncol, Princeton, NJ USA. [Kleen, Thomas-Oliver] Cellular Technol Ltd, Shaker Hts, OH USA. [Lee, Peter P.] Stanford Univ, Sch Med, Dept Med Hematol, Stanford, CA USA. [Maecker, Holden T.] Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Human Immune Monitoring Ctr, Stanford, CA USA. [Maino, Vernon C.] BD Biosci, San Jose, CA USA. [Trinchieri, Giorgio] NCI, Canc & Inflammat Program, CCR, NIH, Frederick, MD 21701 USA. [Stroncek, David F.] NCI, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Marincola, Francesco] NCI, Dept Translat Med, NIH, Bethesda, MD 20892 USA. [Khleif, Samir] NCI, Canc Vaccine Sect, NIH, Bethesda, MD 20892 USA. [Thurin, Magdalena] NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH, Rockville, MD USA. [Disis, Mary L.] Univ Washington, Tumor Vaccine Grp, Div Oncol, Ctr Translat Med Womens Hlth, Seattle, WA 98109 USA. [Slingluff, Craig L., Jr.] Univ Virginia, Dept Surg, Charlottesville, VA USA. [Song, Wenru] Pfizer Oncol, New London, CT USA. [Fox, Bernard A.] Providence Portland Med Ctr, Robert W Franz Canc Ctr, Earle A Chiles Res Inst, Lab Mol & Tumor Immunol, Portland, OR USA. [Britten, Cedrik M.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Dept Internal Med, D-6500 Mainz, Germany. [Britten, Cedrik M.] BioNTech AG, Clin Dev, Mainz, Germany. [Pawelec, Graham] Univ Tubingen, Sch Med, Dept Internal Med 2, Tubingen, Germany. [Schendel, Dolores J.] Helmholth Zentrum, Inst Mol Immunol, Munich, Germany. [Schendel, Dolores J.] Helmholth Zentrum, Immune Monitoring Grp, Munich, Germany. [Masucci, Giuseppe] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. [Masucci, Giuseppe] NCEV Nord Network Centrum Excellence Antitumour V, Stockholm, Sweden. [Hakansson, Leif] CamImGuide Therapeut AB, Hollviken, Sweden. [Kawakami, Yutaka] Keio Univ, Inst Adv Med Res, Div Cellular Signaling, Sch Med, Tokyo, Japan. [Tahara, Hideaki] Univ Tokyo, Inst Med Sci, Adv Clin Res Ctr, Dept Surg & Bioengn,Minato Ku, Tokyo, Japan. [Maccalli, Cristina] Ist Sci San Raffaele, Div Mol Oncol, Unit Immunobiotherapy Melanoma & Solid Tumors, Milan, Italy. [Rivoltini, Licia] Fdn IRCCS Ist Nazl Tumori, Unit Immunotherapy Human Tumors, Milan, Italy. [Maio, Michele] Univ Hosp Siena, Ist Toscano Tumori, Siena, Italy. [Maio, Michele] Ctr Riferimento Oncol, Canc Bioimmunotherapy Unit, I-33081 Aviano, Italy. [van Der Burg, Sjoerd H.] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. RP Butterfield, LH (reprint author), Univ Pittsburgh, Dept Med, 1-27 Hillman Canc Ctr,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM butterfieldl@upmc.edu; ndisis@u.washington.edu RI Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Masucci, Giuseppe/0000-0002-9583-2306; coral, sandra/0000-0002-1308-3082; Rivoltini, Licia/0000-0002-2409-6225; Pawelec, Graham/0000-0002-3600-0163 FU NIH [P50 CA121973, RO1 CA104524, RO1 CA119123, R21 CA123864]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Bristol-Myers Squibb Company; Center for Cancer Research, National Cancer Institute; Merck Oncology; Biogen Idec; Center for Human Immunology, Autoimmunity, and Inflammation; Pfizer; Immuneering Corporation FX The study was supported by NIH grants P50 CA121973 and RO1 CA104524 to L.H. Butterfield; NIH grants RO1 CA119123 and R21 CA123864 to B.A. Fox; and research grant ("Standardization of Immune Monitoring") to C.M. Britten and S. H. van der Burg from the Wallace Coulter Foundation, Miami, FL. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, 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. The iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers was supported by educational grants obtained by iSBTc-SITC from Bristol-Myers Squibb Company, the Center for Cancer Research, National Cancer Institute, Merck Oncology, Biogen Idec, the Center for Human Immunology, Autoimmunity, and Inflammation, and with additional support from Pfizer and Immuneering Corporation. NR 77 TC 57 Z9 60 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 MAY 15 PY 2011 VL 17 IS 10 BP 3064 EP 3076 DI 10.1158/1078-0432.CCR-10-2234 PG 13 WC Oncology SC Oncology GA 764EA UT WOS:000290610000003 PM 21558394 ER PT J AU Kang, ZG Chen, JJ Yu, YK Li, B Sun, SY Zhang, BL Cao, L AF Kang, Zhigang Chen, Jun-Jie Yu, Yunkai Li, Bo Sun, Shi-Yong Zhang, Baolin Cao, Liang TI Drozitumab, a Human Antibody to Death Receptor 5, Has Potent Antitumor Activity against Rhabdomyosarcoma with the Expression of Caspase-8 Predictive of Response SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL-LINES; CANCER-CELLS; TUMOR-CELL; APOPTOSIS; GROWTH; APO2L/TRAIL; RECRUITMENT; RESISTANT; SURVIVAL; AGONISTS AB Purpose: Rhabdomyosarcoma (RMS) is a common pediatric soft-tissue tumor. In this study, we evaluated the efficacy and selectivity of drozitumab, a death receptor DR5-targeted therapeutic antibody, in RMS preclinical models. Experimental Design: A panel of 11 RMS cell lines was used for in vitro studies. The molecular marker predictive of response to drozitumab was interrogated. Selected RMS cell lines were injected into the gastrocnemius muscle of mice for in vivo assessment of the potency and selectivity of drozitumab. Results: We report that DR5, but not DR4, persisted at high levels and on the surface of all RMS cell lines. DR5 antibody drozitumab was effective in vitro against the majority of RMS cell lines. There was a strong correlation between caspase-8 expression and the sensitivity to drozitumab, which induced the rapid assembly of the death-induced signaling complex and the cleavage of caspase-8 only in sensitive cells. More importantly, caspase-8 catalytic activity was both necessary and sufficient for mediating the sensitivity to drozitumab. Furthermore, drozitumab had potent antitumor activity against established RMS xenografts with a specificity predicted from the in vitro analysis and with tumor-free status in half of the treated mice. Conclusion: Our study provides the first preclinical evaluation of the potency and selectivity of a death receptor antibody in RMS. Drozitumab is effective, in vitro, against the majority of RMS cell lines that express caspase-8 and, in vivo, may provide long-term control of RMS. Clin Cancer Res; 17(10); 3181-92. (C) 2011 AACR. C1 [Kang, Zhigang; Yu, Yunkai; Cao, Liang] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Chen, Jun-Jie; Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Kang, Zhigang; Yu, Yunkai] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. [Li, Bo; Sun, Shi-Yong] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA USA. [Li, Bo; Sun, Shi-Yong] Winship Canc Inst, Atlanta, GA USA. RP Cao, L (reprint author), NCI, Genet Branch, Ctr Canc Res, 37 Convent Dr,MSC 4265,Bldg 37,Rm 6134, Bethesda, MD 20892 USA. EM caoli@mail.nih.gov RI Chen, Jun-Jie/E-1894-2012 FU U.S. National Cancer Institute (NCI); NCI, NIH [N01-CO-12400] FX This research was supported by the Intramural Research Program of the U.S. National Cancer Institute (NCI). This project was also funded in part with federal funds from the NCI, NIH, under contract N01-CO-12400. NR 31 TC 18 Z9 19 U1 0 U2 2 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 MAY 15 PY 2011 VL 17 IS 10 BP 3181 EP 3192 DI 10.1158/1078-0432.CCR-10-2874 PG 12 WC Oncology SC Oncology GA 764EA UT WOS:000290610000013 PM 21385927 ER PT J AU Holkova, B Perkins, EB Ramakrishnan, V Tombes, MB Shrader, E Talreja, N Wellons, MD Hogan, KT Roodman, GD Coppola, D Kang, L Dawson, J Stuart, RK Peer, C Figg, WD Kolla, S Doyle, A Wright, J Sullivan, DM Roberts, JD Grant, S AF Holkova, Beata Perkins, E. Brent Ramakrishnan, Viswanathan Tombes, Mary Beth Shrader, Ellen Talreja, Neha Wellons, Martha D. Hogan, Kevin T. Roodman, G. David Coppola, Domenico Kang, Loveleen Dawson, Jana Stuart, Robert K. Peer, Cody Figg, William D., Sr. Kolla, Sarah Doyle, Austin Wright, John Sullivan, Daniel M. Roberts, John D. Grant, Steven TI Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory B-Cell Neoplasms SO CLINICAL CANCER RESEARCH LA English DT Article ID DEPENDENT KINASE INHIBITOR; MULTIPLE-MYELOMA CELLS; TRANSCRIPTIONAL REPRESSION; INTERNATIONAL WORKSHOP; PROTEASOME INHIBITORS; RESPONSE CRITERIA; DOWN-REGULATION; STEM-CELL; CYCLIN D1; LYMPHOMA AB Purpose: A phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, and mantle cell lymphoma). Experimental Design: Patients received bortezomib by intravenous push on days 1, 4, 8, and 11. Patients also received alvocidib on days 1 and 8 by 30-minute bolus infusion followed by a 4-hour continuous infusion. Treatment was on a 21-day cycle, with indefinite continuation for patients experiencing responses or stable disease. Dose escalation employed a standard 3 + 3 design until the MTD was identified on the basis of DLTs. Pharmacokinetic studies and pharmacodynamic studies were conducted. Results: Sixteen patients were treated. The MTD was established as 1.3 mg/m(2) for bortezomib and 30 mg/m(2) for alvocidib (both the 30-minute bolus and 4-hour infusions). Common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Common nonhematologic toxicities included fatigue and febrile neutropenia. DLTs included fatigue, febrile neutropenia, and elevated aspartate aminotransferase (AST) levels. Two complete responses (CR; 12%) and five partial responses (PR; 31%) were observed at the MTD (overall response rate 44%). Pharmacokinetic results were typical for alvocidib and pharmacodynamic studies yielded variable results. Conclusions: The combination of bortezomib and alvocidib is tolerable and an MTD has been established for the tested schedule. The regimen appears active in patients with relapsed and/or refractory multiple myeloma or non-Hodgkin's lymphoma, justifying phase II studies to determine the activity of this regimen more definitively. Clin Cancer Res; 17(10); 3388-97. (C) 2011 AACR. C1 [Holkova, Beata; Perkins, E. Brent; Ramakrishnan, Viswanathan; Tombes, Mary Beth; Shrader, Ellen; Wellons, Martha D.; Hogan, Kevin T.; Kolla, Sarah; Roberts, John D.; Grant, Steven] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. [Holkova, Beata; Perkins, E. Brent; Roberts, John D.; Grant, Steven] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23298 USA. [Ramakrishnan, Viswanathan] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA 23298 USA. [Grant, Steven] Virginia Commonwealth Univ, Dept Microbiolog & Immunol, Richmond, VA 23298 USA. [Grant, Steven] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Grant, Steven] Virginia Commonwealth Univ, Inst Mol Med, Richmond, VA 23298 USA. [Roodman, G. David] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Coppola, Domenico; Kang, Loveleen; Dawson, Jana; Sullivan, Daniel M.] Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Stuart, Robert K.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Peer, Cody; Figg, William D., Sr.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Doyle, Austin; Wright, John] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. [Coppola, Domenico; Kang, Loveleen; Dawson, Jana; Sullivan, Daniel M.] Univ S Florida, Res Inst, Tampa, FL USA. RP Grant, S (reprint author), Virginia Commonwealth Univ, Massey Canc Ctr, POB 980230, Richmond, VA 23298 USA. EM stgrant@vcu.edu RI Figg Sr, William/M-2411-2016; OI Stuart, Robert/0000-0001-7549-8008 FU NCI [R01 CA93738, R01 CA100866, R21 CA110953, P30 CA016059]; Multiple Myeloma Research Foundation; NCRR [M01-RR00065]; NIH [P50 CA130805] FX The study was supported by grants from NCI R01 CA93738, NCI R01 CA100866, NCI R21 CA110953 and an award from the Multiple Myeloma Research Foundation to S. Grant; NCI P30 CA016059 Cancer Center Support grant to Massey Cancer Center; NCRR M01-RR00065 Clinical Research Center grant to Virginia Commonwealth University and NIH grant P50 CA130805, the Lymphoma SPORE. NR 34 TC 28 Z9 28 U1 0 U2 4 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 MAY 15 PY 2011 VL 17 IS 10 BP 3388 EP 3397 DI 10.1158/1078-0432.CCR-10-2876 PG 10 WC Oncology SC Oncology GA 764EA UT WOS:000290610000031 PM 21447728 ER PT J AU Mukhopadhyay, P Rajesh, M Horvath, B Batkai, S Park, O Tanchian, G Gao, RY Patel, V Wink, DA Liaudet, L Hasko, G Mechoulam, R Pacher, P AF Mukhopadhyay, Partha Rajesh, Mohanraj Horvath, Bela Batkai, Sandor Park, Ogyi Tanchian, Galin Gao, Rachel Y. Patel, Vivek Wink, David A. Liaudet, Lucas Hasko, Gyoergy Mechoulam, Raphael Pacher, Pal TI Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Cannabinoids; Oxidative stress; Inflammation; Ischemia/reperfusion; Free radicals ID ISCHEMIA-REPERFUSION INJURY; MITOCHONDRIAL RESPIRATORY-CHAIN; SIZE LIVER ISCHEMIA; NF-KAPPA-B; NITRIC-OXIDE; OXIDATIVE STRESS; IN-VITRO; CANNABINOID RECEPTORS; REACTIVE OXYGEN; DIABETIC CARDIOMYOPATHY AB Ischemia/reperfusion (I/R) is a pivotal mechanism of liver damage after liver transplantation or hepatic surgery. We have investigated the effects of cannabidiol (CBD), the nonpsychotropic constituent of marijuana, in a mouse model of hepatic I/R injury. I/R triggered time-dependent increases/changes in markers of liver injury (serum transaminases), hepatic oxidative/nitrative stress (4-hydroxy-2-nonenal, nitrotyrosine content/staining, and gp91phox and inducible nitric oxide synthase mRNA), mitochondria! dysfunction (decreased complex I activity), inflammation (tumor necrosis factor alpha (TNF-alpha), cyclooxygenase 2, macrophage inflammatory protein-1 alpha/2, intercellular adhesion molecule 1 mRNA levels: tissue neutrophil infiltration: nuclear factor kappa B (NF-kappa B) activation), stress signaling (p38MAPK and JNK), and cell death (DNA fragmentation, PARP activity, and TUNEL). CBD significantly reduced the extent of liver inflammation, oxidative/nitrative stress, and cell death and also attenuated the bacterial endotoxin-triggered NF-kappa B activation and TNF-alpha production in isolated Kupffer cells, likewise the adhesion molecule expression in primary human liver sinusoidal endothelial cells stimulated with TNF-alpha and attachment of human neutrophils to the activated endothelium. These protective effects were preserved in CB2 knockout mice and were not prevented by CB1/2 antagonists in vitro. Thus, CBD may represent a novel, protective strategy against I/R injury by attenuating key inflammatory pathways and oxidative/nitrative tissue injury, independent of classical CB1/2 receptors. Published by Elsevier Inc. C1 [Mukhopadhyay, Partha; Rajesh, Mohanraj; Horvath, Bela; Batkai, Sandor; Tanchian, Galin; Gao, Rachel Y.; Patel, Vivek; Pacher, Pal] NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. [Park, Ogyi] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. [Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Liaudet, Lucas] Univ Lausanne Hosp, Dept Intens Care Med, Lausanne, Switzerland. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Mechoulam, Raphael] Hebrew Univ Jerusalem, Dept Med Chem & Nat Prod, Fac Med, Jerusalem, Israel. [Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. RP Pacher, P (reprint author), NIH, Lab Physiol Studies, Bldg 10, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Horvath, Bela/A-7368-2009; Pacher, Pal/B-6378-2008; Ji, Haofeng/G-6206-2012; MUKHOPADHYAY, PARTHA/G-3890-2010; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017; OI Pacher, Pal/0000-0001-7036-8108; MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Liaudet, Lucas/0000-0003-2670-4930; Gao, Yue/0000-0002-7890-1605 FU NIH/NIAAA; NIDA [9789]; Hungarian Research Council [OTKA-NKTH-EU MB08-80238] FX This study was supported by the Intramural Research Program of NIH/NIAAA (to P.P.) and by NIDA Grant 9789 (to R.M.). Dr. Bela Horvath is the recipient of a Hungarian Research Council Scientific Research Fund Fellowship (OTKA-NKTH-EU MB08-80238). The authors are indebted to Drs. George Kunos and Bin Gao for providing key resources and support. NR 82 TC 56 Z9 61 U1 1 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 MAY 15 PY 2011 VL 50 IS 10 BP 1368 EP 1381 DI 10.1016/j.freeradbiomed.2011.02.021 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 765HA UT WOS:000290694900018 PM 21362471 ER PT J AU Kim, JA Yang, SY Wamiru, A McMahon, JB Le Grice, SFJ Beutler, JA Kim, YH AF Kim, Jeong Ah Yang, Seo Young Wamiru, Anthony McMahon, James B. Le Grice, Stuart F. J. Beutler, John A. Kim, Young Ho TI New monoterpene glycosides and phenolic compounds from Distylium racemosum and their inhibitory activity against ribonuclease H SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Distylium racemosum; Monoterpene glycosides; Megastigmane glucoside; Ribonuclease H ID WATER-SOLUBLE CONSTITUENTS; GLUCOSIDES; EXTRACTS; LEAVES; BARK; STEM AB Two new monoterpene glycosides, distyloside A-B (1-2), and a new megastigmane glucoside, iso-dihydrodendranthemoside A (3) were isolated from twigs and leaves of Distylium racemosum, along with five known phenolic compounds (4-8). The structures were established via spectroscopic techniques and chemical transformations, and the absolute stereochemistry of 3 was determined by Mosher's esterification. A homogeneous fluorescence resonance energy transfer (FRET) quenching assay was used to determine the inhibitory activity of isolates (1-8) on the ribonuclease H enzymes from HIV-1, 2, human, and Escherichia coli. Among them, 6 ''-O-galloylsalidroside (6) showed potent inhibitory effects with an IC(50) value of 3.5 mu M on HIV-2, and 1.7 mu M on human RNase H, respectively. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Kim, Jeong Ah; Yang, Seo Young; Kim, Young Ho] Chungnam Natl Univ, Coll Pharm, Taejon 305764, South Korea. [Wamiru, Anthony; McMahon, James B.; Beutler, John A.; Kim, Young Ho] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Wamiru, Anthony] NCI, SAIC Frederick, Ctr Canc Res, Frederick, MD 21702 USA. [Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Kim, YH (reprint author), Chungnam Natl Univ, Coll Pharm, Taejon 305764, South Korea. EM yhk@cnu.ac.kr RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU Ministry of Education, Science and Technology [20090093815]; National Cancer Institute, National Institutes of Health [HHSN26120080001E]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (20090093815). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract no. HHSN26120080001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 17 TC 1 Z9 1 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 15 PY 2011 VL 21 IS 10 BP 2840 EP 2844 DI 10.1016/j.bmcl.2011.03.091 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 756OW UT WOS:000290024200009 PM 21489793 ER PT J AU Zhao, XZ Maddali, K Metifiot, M Smith, SJ Vu, BC Marchand, C Hughes, SH Pommier, Y Burke, TR AF Zhao, Xue Zhi Maddali, Kasthuraiah Metifiot, Mathieu Smith, Steven J. Vu, B. Christie Marchand, Christophe Hughes, Stephen H. Pommier, Yves Burke, Terrence R., Jr. TI Development of tricyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE HIV-1 integrase; Inhibit; Raltegravir; Cycloaddition ID DEPROTONATION-CYCLOADDITION CASCADE; IMIDOSULFOXIDES; 2-PYRIDONES; RALTEGRAVIR; RESISTANCE; INFECTION; INTASOME; POTENT AB New tricyclic HIV-1 integrase (IN) inhibitors were prepared that combined structural features of bicyclic pyrimidinones with recently disclosed 4,5-dihydroxy-1H-isoindole-1,3(2H)-diones. This combination resulted in the introduction of a nitrogen into the aryl ring and the addition of a fused third ring to our previously described inhibitors. The resulting analogues showed low micromolar inhibitory potency in in vitro HIV-1 integrase assays, with good selectivity for strand transfer relative to 3'-processing. Published by Elsevier Ltd. C1 [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. [Maddali, Kasthuraiah; Metifiot, Mathieu; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Smith, Steven J.; Vu, B. Christie; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Zhao, XZ (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. EM xuezhi.zhao@nih.gov; tburke@helix.nih.gov RI Zhao, Xue Zhi/N-9594-2014; Burke, Terrence/N-2601-2014 OI Zhao, Xue Zhi/0000-0003-1006-6364; FU NIH, Center for Cancer Research, NCI-Frederick; National Cancer Institute, National Institutes of Health; Joint Science and Technology Office of the Department of Defense FX This work was supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick and the National Cancer Institute, National Institutes of Health and the Joint Science and Technology Office of the Department of Defense. 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 19 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 15 PY 2011 VL 21 IS 10 BP 2986 EP 2990 DI 10.1016/j.bmcl.2011.03.047 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 756OW UT WOS:000290024200041 PM 21493066 ER PT J AU Rosenthal, AS Tanega, C Shen, M Mott, BT Bougie, JM Nguyen, DT Misteli, T Auld, DS Maloney, DJ Thomas, CJ AF Rosenthal, Andrew S. Tanega, Cordelle Shen, Min Mott, Bryan T. Bougie, James M. Nguyen, Dac-Trung Misteli, Tom Auld, Douglas S. Maloney, David J. Thomas, Craig J. TI Potent and selective small molecule inhibitors of specific isoforms of Cdc2-like kinases (Clk) and dual specificity tyrosine-phosphorylation-regulated kinases (Dyrk) SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Clk1; Clk2; Clk3; Clk4; Dyrk1A; Dyrk1B; Pre-mRNA splicing; Kinase inhibition; Quinazoline ID COLON-CANCER CELLS; PROTEIN-KINASE; SUBSTRATE-SPECIFICITY; DOWN-SYNDROME; SURVIVAL; OVEREXPRESSION; FAMILY; DIFFERENTIATION; PROLIFERATION; MIRK/DYRK1B AB Continued examination of substituted 6-arylquinazolin-4-amines as Clk4 inhibitors resulted in selective inhibitors of Clk1, Clk4, Dyrk1A and Dyrk1B. Several of the most potent inhibitors were validated as being highly selective within a comprehensive kinome scan. Published by Elsevier Ltd. C1 [Rosenthal, Andrew S.; Tanega, Cordelle; Shen, Min; Mott, Bryan T.; Bougie, James M.; Nguyen, Dac-Trung; Auld, Douglas S.; Maloney, David J.; Thomas, Craig J.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA. RP Thomas, CJ (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM craigt@mail.nih.gov OI Nguyen, Dac-Trung/0000-0003-2591-9948 FU National Institutes of Health Roadmap; National Human Genome Research Institute FX We greatly appreciate the assistance of William Leister and Thomas Daniel for compound analysis and purification and Chris LeClair, Paul Shinn and Danielle VanLeer for compound management. This research was supported by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute. NR 43 TC 33 Z9 33 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 15 PY 2011 VL 21 IS 10 BP 3152 EP 3158 DI 10.1016/j.bmcl.2011.02.114 PG 7 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 756OW UT WOS:000290024200076 PM 21450467 ER PT J AU Chakrabarti, O Rane, NS Hegde, RS AF Chakrabarti, Oishee Rane, Neena S. Hegde, Ramanujan S. TI Cytosolic aggregates perturb the degradation of nontranslocated secretory and membrane proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID UBIQUITIN-PROTEASOME SYSTEM; QUALITY-CONTROL PATHWAY; PRION PROTEIN; ENDOPLASMIC-RETICULUM; MUTANT HUNTINGTIN; ALPHA-SYNUCLEIN; ER STRESS; CAENORHABDITIS-ELEGANS; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE AB A wide range of diseases are associated with the accumulation of cytosolic protein aggregates. The effects of these aggregates on various aspects of normal cellular protein homeostasis remain to be determined. Here we find that cytosolic aggregates, without necessarily disrupting proteasome function, can markedly delay the normally rapid degradation of nontranslocated secretory and membrane protein precursors. In the case of mammalian prion protein (PrP), the nontranslocated fraction is recruited into preexisting aggregates before its triage for degradation. This recruitment permits the growth and persistence of cytosolic PrP aggregates, explaining their apparent "self-conversion" seen in earlier studies of transient proteasome inhibition. For other proteins, the aggregate-mediated delay in precursor degradation led to aggregation and/or soluble residence in the cytosol, often causing aberrant cellular morphology. Remarkably, improving signal sequence efficiency mitigated these effects of aggregates. These observations identify a previously unappreciated consequence of cytosolic aggregates for nontranslocated secretory and membrane proteins, a minor but potentially disruptive population the rapid disposal of which is critical to maintaining cellular homeostasis. C1 [Chakrabarti, Oishee; Rane, Neena S.; Hegde, Ramanujan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Chakrabarti, O (reprint author), Saha Inst Nucl Phys, Sector 1,Block AF,Room 4622, Kolkata 700064, W Bengal, India. EM oishee.chakrabarti@saha.ac.in; hegder@mail.nih.gov OI Hegde, Ramanujan/0000-0001-8338-852X NR 65 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY 15 PY 2011 VL 22 IS 10 BP 1625 EP 1637 DI 10.1091/mbc.E10-07-0638 PG 13 WC Cell Biology SC Cell Biology GA 762XN UT WOS:000290515600001 PM 21411629 ER PT J AU Lindstrom, KM Mandell, DJ Musa, GJ Britton, JC Sankin, LS Mogg, K Bradley, BP Ernst, M Doan, T Bar-Haim, Y Leibenluft, E Pine, DS Hoven, CW AF Lindstrom, Kara M. Mandell, Donald J. Musa, George J. Britton, Jennifer C. Sankin, Lindsey S. Mogg, Karin Bradley, Brendan P. Ernst, Monique Doan, Thao Bar-Haim, Yair Leibenluft, Ellen Pine, Daniel S. Hoven, Christina W. TI Attention orientation in parents exposed to the 9/11 terrorist attacks and their children SO PSYCHIATRY RESEARCH LA English DT Article DE Trauma; Development; Attention; Emotion; Faces; Children ID BIAS; ANXIETY; PSYCHOPATHOLOGY; ADOLESCENTS; DISORDERS; THREAT; TRAUMA; PREVALENCE; VERSION; FACES AB While trauma affects both parents and their children, minimal research examines the role of information-processing perturbations in shaping reactions to trauma experienced by parents and, in turn, the effect this trauma has on their children. This study examines familial associations among trauma, psychopathology, and attention bias. Specifically, group differences in psychopathology and attention bias were examined in both adults and their children based on trauma exposure. In addition, the association between attention bias in parents and attention bias in their children was examined. Parents exposed to the 9/11 World Trade Center attacks and their children were recruited from the New York City Metropolitan area. Levels of trauma exposure, psychiatric symptoms, and attention bias to threat, as measured with the dot-probe task, were each assessed in 90 subjects, comprising of 45 parents and one of their children. These measures were examined in parents and their children separately; each parent and child was categorized on the presence of high or low levels of trauma exposure. Although trauma exposure did not relate to psychopathology, parents who were highly exposed to trauma showed greater attention bias towards threat than parents with low trauma exposure. However, the children of high trauma-exposed parents did not show enhanced attention bias towards threat, though threat bias in the high trauma-exposed parents did negatively correlate with threat bias in their children. This association between trauma and attention bias in parents was found four-to-five years after 9/11, suggesting that trauma has enduring influences on threat processing. Larger, prospective studies might examine relationships within families among traumatic exposures, psychopathology, and information-processing functions. Published by Elsevier Ireland Ltd. C1 [Lindstrom, Kara M.; Britton, Jennifer C.; Sankin, Lindsey S.; Ernst, Monique; Leibenluft, Ellen; Pine, Daniel S.] NIMH, MAP, NIH, Bethesda, MD 20892 USA. [Lindstrom, Kara M.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Lindstrom, Kara M.] Stockholm Brain Inst, Stockholm, Sweden. [Mandell, Donald J.; Musa, George J.; Doan, Thao; Hoven, Christina W.] Columbia Univ, Dept Psychiat, New York, NY USA. [Mogg, Karin; Bradley, Brendan P.] Univ Southampton, Southampton, Hants, England. [Bar-Haim, Yair] Tel Aviv Univ, Dept Psychol, Adler Ctr Res Child Dev & Psychopathol, IL-69978 Tel Aviv, Israel. RP Lindstrom, KM (reprint author), NIMH, MAP, NIH, 15K North Dr,Room 108,MSC 2670, Bethesda, MD 20892 USA. EM lindstrk@mail.nih.gov RI Britton, Jennifer/J-4501-2013; Mogg, Karin/C-1181-2008; Bradley, Brendan/B-9724-2008; OI Mogg, Karin/0000-0002-2738-7378; Hoven, Christina/0000-0003-1274-2936; Bradley, Brendan/0000-0003-2801-4271 FU National Institute of Mental Health [R01 MH70424]; National Institute of Mental Health, National Institutes of Health FX This research was supported by the National Institute of Mental Health (R01 MH70424; PI C. Hoven) and the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 23 TC 12 Z9 13 U1 7 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 15 PY 2011 VL 187 IS 1-2 BP 261 EP 266 DI 10.1016/j.psychres.2010.09.005 PG 6 WC Psychiatry SC Psychiatry GA 758RL UT WOS:000290183700044 PM 20970198 ER PT J AU Avdoshina, V Garzino-Demo, A Bachis, A Monaco, MCG Maki, PM Tractenberg, RE Liu, CL Young, MA Mocchetti, I AF Avdoshina, Valeriya Garzino-Demo, Alfredo Bachis, Alessia Monaco, Maria C. G. Maki, Pauline M. Tractenberg, Rochelle E. Liu, Chenglong Young, Mary A. Mocchetti, Italo TI HIV-1 decreases the levels of neurotrophins in human lymphocytes SO AIDS LA English DT Article ID WOMENS INTERAGENCY HIV; CHEMOKINE RECEPTORS; ALZHEIMERS-DISEASE; BRAIN; BDNF; CELLS; EXPRESSION; THYMUS; ABUSE; SERUM AB Neurotrophins control cell survival. Therefore, we examined whether HIV-1 reduces neurotrophin levels. Serum of HIV-positive individuals exhibited lower concentrations of brain-derived neurotrophic factor (BDNF), but not of other neurotrophins, than HIV-negative individuals. In addition, R5 and X4 strains of HIV-1 decreased BDNF expression in T cells. Our results support the hypothesis that reduced levels of BDNF may be a risk factor for T-cell apoptosis and for neurological complications associated with HIV-1 infection. C1 [Avdoshina, Valeriya; Bachis, Alessia; Mocchetti, Italo] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. [Garzino-Demo, Alfredo] Univ Maryland, Dept Microbiol & Immunol, Inst Human Virol, Baltimore, MD 21201 USA. [Monaco, Maria C. G.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. [Maki, Pauline M.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Maki, Pauline M.] Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. [Tractenberg, Rochelle E.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. [Liu, Chenglong; Young, Mary A.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20057 USA. RP Mocchetti, I (reprint author), Georgetown Univ, Med Ctr, Dept Neurosci, New Res Bldg WP13,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM moccheti@georgetown.edu FU HHS [DA026174, NS066842]; [UO1-AI-35004]; [UO1-AI-31834]; [UO1-AI-34994]; [UO1-AI-34989]; [UO1-AI-34993]; [UO1-AI-42590]; [UO1-HD-32632]; [UL1 RR024131] FX This study is supported by HHS grants DA026174 (I.M.), NS066842 (A.G.-D.). Women's Interagency HIV Study is funded by UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590, UO1-HD-32632 and UL1 RR024131. NR 22 TC 8 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 15 PY 2011 VL 25 IS 8 BP 1126 EP 1128 DI 10.1097/QAD.0b013e32834671b3 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 758FB UT WOS:000290145800014 PM 21422985 ER PT J AU Boyd, LB Hunicke-Smith, SP Stafford, GA Freund, ET Ehlman, M Chandran, U Dennis, R Fernandez, AT Goldstein, S Steffen, D Tycko, B Klemm, JD AF Boyd, Lauren Becnel Hunicke-Smith, Scott P. Stafford, Grace A. Freund, Elaine T. Ehlman, Michele Chandran, Uma Dennis, Robert Fernandez, Anna T. Goldstein, Stephen Steffen, David Tycko, Benjamin Klemm, Juli D. TI The caBIG (R) Life Science Business Architecture Model SO BIOINFORMATICS LA English DT Article ID CACORE AB Motivation: Business Architecture Models (BAMs) describe what a business does, who performs the activities, where and when activities are performed, how activities are accomplished and which data are present. The purpose of a BAM is to provide a common resource for understanding business functions and requirements and to guide software development. The cancer Biomedical Informatics Grid (caBIG (R)) Life Science BAM (LS BAM) provides a shared understanding of the vocabulary, goals and processes that are common in the business of LS research. Results: LS BAM 1.1 includes 90 goals and 61 people and groups within Use Case and Activity Unified Modeling Language (UML) Diagrams. Here we report on the model's current release, LS BAM 1.1, its utility and usage, and plans for future use and continuing development for future releases. C1 [Boyd, Lauren Becnel] Baylor Coll Med, Dept Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Hunicke-Smith, Scott P.] Univ Texas Austin, Texas Inst Drug & Diagnost Dev, Austin, TX 78712 USA. [Stafford, Grace A.] Jackson Lab, Bar Harbor, ME 04609 USA. [Freund, Elaine T.] 3rd Millennium, Waltham, MA 02451 USA. [Ehlman, Michele] Essex Management, Bethesda, MD 20814 USA. Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15232 USA. [Chandran, Uma; Dennis, Robert] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Fernandez, Anna T.] Booz Allen Hamilton, Rockville, MD 20852 USA. [Goldstein, Stephen] Sapient Govt Serv, Arlington, VA 22201 USA. [Steffen, David] Baylor Coll Med, Dan L Duncan Canc Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA. [Tycko, Benjamin] Columbia Univ, Med Ctr, Dept Pathol, Inst Canc Genet, New York, NY 10032 USA. [Tycko, Benjamin] Columbia Univ, Med Ctr, Dept Pathol, Taub Inst, New York, NY 10032 USA. [Klemm, Juli D.] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD 20852 USA. RP Boyd, LB (reprint author), Baylor Coll Med, Dept Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. FU Booz Allen Hamilton FX Funding: Contracts from Booz Allen Hamilton on behalf of the National Cancer Institute as a part of the cancer Biomedical Informatics Grid (caBIG) Initiative Integrative Cancer Research Workspace. NR 13 TC 8 Z9 8 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAY 15 PY 2011 VL 27 IS 10 BP 1429 EP 1435 DI 10.1093/bioinformatics/btr141 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 760OV UT WOS:000290334500013 PM 21450709 ER PT J AU Zhang, FY Chen, Q Ye, TZ Lipska, BK Straub, RE Vakkalanka, R Rujescu, D St Clair, D Hyde, TM Bigelow, L Kleinman, JE Weinberger, DR AF Zhang, Fengyu Chen, Qiang Ye, Tianzhang Lipska, Barbara K. Straub, Richard E. Vakkalanka, Radhakrishna Rujescu, Dan St Clair, David Hyde, Thomas M. Bigelow, Llewellyn Kleinman, Joel E. Weinberger, Daniel R. TI Evidence of Sex-Modulated Association of ZNF804A with Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Gender; gene-sex interaction; schizophrenia; ZNF804A ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; METAANALYSIS AB Background: The single nucleotide polymorphism (SNP) rs1344706 in ZNF804A (2q32.1) has been associated with schizophrenia in a genome-wide association study (GWAS). A recent candidate gene study, which replicated the positive association with rs1344706, identified another positive SNP (rs7597593) in ZNF804A associated with schizophrenia. Methods: We performed an association study of rs7597593 in four GWAS cohorts of European ancestry. Postmortem human brain expression data of normal Caucasian individuals (n = 89) was also analyzed for examining the effect of rs7597593 on ZNF804A messenger RNA expression, using logistic regression and linear regression. Results: We found that rs7597593 was significantly associated with schizophrenia in the combined GWAS datasets (n = 5023, odds ratio [OR](combined) = 1.15, p = .0011). Analysis of stratification by sex showed that the association was driven by the female subjects (OR = 1.29, p = .0002) and was not significant in male subjects (OR = 1.08, p = .148) in the combined sample of four cohorts. A sex by genotype interaction was near significant in both the Genetic Association Information Network sample (p = .0532) and the combined sample of four cohorts (p(combined) = .0531). Gene expression analysis showed no main effects but a significant female-specific association (p(female) = .047, p(male) = .335) and sex by genotype interaction (p = .0166) for rs7597593. Conclusions: Our data suggest a clinical and molecular modulation by sex of the association of ZNF804A SNP rs7597593 and risk of schizophrenia. C1 [Zhang, Fengyu; Chen, Qiang; Ye, Tianzhang; Lipska, Barbara K.; Straub, Richard E.; Vakkalanka, Radhakrishna; St Clair, David; Hyde, Thomas M.; Bigelow, Llewellyn; Kleinman, Joel E.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Zhang, Fengyu; Chen, Qiang; Ye, Tianzhang; Lipska, Barbara K.; Straub, Richard E.; Vakkalanka, Radhakrishna; St Clair, David; Hyde, Thomas M.; Bigelow, Llewellyn; Kleinman, Joel E.; Weinberger, Daniel R.] NIMH, Brain Disorder Branch, NIH, Bethesda, MD 20892 USA. [Rujescu, Dan] Univ Munich, Sect Mol & Clin Neurobiol, Dept Psychiat, Munich, Germany. [St Clair, David] Univ Aberdeen, Dept Mental Hlth, Royal Cornhill Hosp, Aberdeen, Scotland. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, Room 3C-103A,10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov FU National Institutes of Health, Bethesda, Maryland FX The study is funded by National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland. NR 20 TC 30 Z9 34 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 2011 VL 69 IS 10 BP 914 EP 917 DI 10.1016/j.biopsych.2011.01.003 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 760DF UT WOS:000290302700007 PM 21349497 ER PT J AU Nixon, DC Prust, MJ Sambataro, F Tan, HY Mattay, VS Weinberger, DR Callicott, JH AF Nixon, Devon C. Prust, Morgan J. Sambataro, Fabio Tan, Hao-Yang Mattay, Venkata S. Weinberger, Daniel R. Callicott, Joseph H. TI Interactive Effects of DAOA (G72) and Catechol-O-Methyltransferase on Neurophysiology in Prefrontal Cortex SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Dopamine; efficiency; fMRI; glutamate; prefrontal; working memory ID WORKING-MEMORY; GENE-EXPRESSION; BRAIN-FUNCTION; SCHIZOPHRENIA; G72/G30; COMT; POLYMORPHISMS; EPISTASIS; DISORDER; RISK AB Background: Accumulating evidence indicates that genetic polymorphisms of D-amino acid oxidase activator (DAOA) (M24; rs1421292; T-allele) and catechol-O-methyltransferase (COMT) (Val(158)Met; rs4680) likely enhance susceptibility to schizophrenia. Previously, clinical association between DAOA M24 (T-allele) and a functionally inefficient 3-marker COMT haplotype (that included COMT Val(158)Met) uncovered epistatic effects on risk for schizophrenia. Therefore, we projected that healthy control subjects with risk genotypes for both DAOA M24 (T/T) and COMTVal(158)Met (Val/Val) would produce prefrontal inefficiency, a critical physiological marker of the dorsolateral prefrontal cortex (DLPFC) in schizophrenic patients influenced by both familial and heritable factors. Methods: With 3T blood oxygen level dependent functional magnetic resonance imaging data, we analyzed in SPM5 the proposed interaction of DAOA and COMT in 82 healthy volunteers performing an N-back executive working memory paradigm (2-back > 0-back). Results: As predicted, we detected a functional gene x gene interaction between DAOA and COMT in the DLPFC. Conclusions: The neuroimaging findings here of inefficient information processing in the prefrontal cortex seem to echo prior statistical epistasis between risk alleles for DAOA and COMT, albeit within a small sample. These in vivo results suggest that deleterious genotypes for DAOA and COMT might contribute to the pathophysiology of schizophrenia, perhaps through combined glutamatergic and dopaminergic dysregulation. C1 [Nixon, Devon C.; Prust, Morgan J.; Tan, Hao-Yang; Callicott, Joseph H.] NIMH, Unit Dynam Imaging Genet, Clin Brain Disorders Branch, Div Intramural Res Programs,NIH,Dept Hlth & Human, Bethesda, MD 20892 USA. [Sambataro, Fabio; Mattay, Venkata S.] NIMH, Neuroimaging Core Facil, Clin Brain Disorders Branch, Div Intramural Res Programs,NIH,Dept Hlth & Human, Bethesda, MD 20892 USA. [Nixon, Devon C.; Prust, Morgan J.; Sambataro, Fabio; Tan, Hao-Yang; Mattay, Venkata S.; Weinberger, Daniel R.; Callicott, Joseph H.] NIMH, Cognit & Psychosis Program, Clin Brain Disorders Branch, Div Intramural Res Programs,NIH,Dept Hlth & Human, Bethesda, MD 20892 USA. RP Callicott, JH (reprint author), NIMH, Unit Dynam Imaging Genet, Clin Brain Disorders Branch, Div Intramural Res Programs,NIH,Dept Hlth & Human, 10 Ctr Dr,Room 3C-117,MSC 1379, Bethesda, MD 20892 USA. EM callicottj@mail.nih.gov RI Sambataro, Fabio/E-3426-2010; OI Sambataro, Fabio/0000-0003-2102-416X; Callicott, Joseph/0000-0003-1298-3334 FU National Institutes of Health, Bethesda, Maryland FX This work was graciously supported by the National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland. Author FS is currently affiliated with the Brain Center for Motor and Social Cognition, Italian Institute of Technology, Parma, Italy. All authors report no biomedical financial interests or potential conflicts of interest. NR 18 TC 22 Z9 22 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 2011 VL 69 IS 10 BP 1006 EP 1008 DI 10.1016/j.biopsych.2010.10.031 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 760DF UT WOS:000290302700019 PM 21215384 ER PT J AU Brooks, HD Glisson, BS Bekele, BN Ginsberg, LE El-Naggar, A Culotta, KS Takebe, N Wright, J Tran, HT Papadimitrakopoulou, VA AF Brooks, Heather D. Glisson, Bonnie S. Bekele, B. Nebiyou Ginsberg, Lawrence E. El-Naggar, Adel Culotta, Kirk S. Takebe, Naoko Wright, John Tran, Hai T. Papadimitrakopoulou, Vassiliki A. TI Phase 2 Study of Dasatinib in the Treatment of Head and Neck Squamous Cell Carcinoma SO CANCER LA English DT Article DE head and neck squamous cell cancer; serum markers; dasatinib; activity ID MIGRATION INHIBITORY FACTOR; TUMOR-ASSOCIATED ANGIOGENESIS; TYROSINE KINASE INHIBITOR; LUNG-CANCER; FACTOR MIF; II TRIAL; RECURRENT; GROWTH; EXPRESSION; OVEREXPRESSION AB BACKGROUND: Treatment options for patients with advanced head and neck squamous cell carcinoma (HNSCC) are scarce. This phase 2 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and efficacy of dasatinib in this setting. METHODS: Patients with recurrent and/or metastatic HNSCC after platinum-based therapy were treated with dasatinib either orally or via percutaneous feeding gastrostomy (PFG). Primary endpoints were 12-week progression-free survival (PFS) and objective response rate with a 2-stage design and early withdrawal if the 12-week PFS rate was <= 20% and no patients had an objective response (OR). Forty-nine serum cytokines and angiogenic factors (CAFs) were analyzed from treated patients. RESULTS: Of the 15 patients enrolled, 12 were evaluable for response, and all patients were evaluable for toxicity. No OR was observed and 2 patients (16.7%) had stable disease (SD) at 8 weeks. The median treatment duration was 59 days, the median time to disease progression was 3.9 weeks, and the median survival was 26 weeks. One patient required a dose reduction, 3 patients required dose interruptions, and 4 patients were hospitalized for toxicity. Dasatinib inhibited c-Src both when administered orally and via PFG. Greater mean drug exposure, decreased half-life, and greater maximum concentration were observed in patients receiving dasatinib via PFG. Eleven baseline CAFs were associated with treatment outcome and 1 CAF, macrophage migration inhibitory factor, was found to be differentially modulated in correlation with SD versus disease progression. CONCLUSIONS: Single-agent dasatinib failed to demonstrate significant activity in patients with advanced HNSCC, despite c-Src inhibition. The toxicity profile was consistent with that reported in other solid tumors, and the drug can be given via PFG tube. Cancer 2011; 117: 2112-9. (C) 2010 American Cancer Society. C1 [Glisson, Bonnie S.; Tran, Hai T.; Papadimitrakopoulou, Vassiliki A.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, Houston, TX 77030 USA. [Brooks, Heather D.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. [Bekele, B. Nebiyou] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Ginsberg, Lawrence E.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA. [El-Naggar, Adel] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Culotta, Kirk S.] Univ Texas MD Anderson Canc Ctr, Dept Pharm Pharmacol Res, Houston, TX 77030 USA. [Takebe, Naoko; Wright, John] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Papadimitrakopoulou, VA (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM vpapadim@mdanderson.org FU Bristol-Myers Squibb; [N01-CM-62202] FX Supported in part by N01-CM-62202 and Bristol-Myers Squibb (correlative studies). NR 23 TC 42 Z9 42 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2011 VL 117 IS 10 BP 2112 EP 2119 DI 10.1002/cncr.25769 PG 8 WC Oncology SC Oncology GA 758JQ UT WOS:000290161100012 PM 21523723 ER PT J AU Breen, N Gentleman, JF Schiller, JS AF Breen, Nancy Gentleman, Jane F. Schiller, Jeannine S. TI Update on Mammography Trends Comparisons of Rates in 2000, 2005, and 2008 SO CANCER LA English DT Article DE cancer screening; mammography; early detection of breast cancer; Healthy People objective; National Health Interview Survey ID SERVICES TASK-FORCE; BREAST-CANCER; SCREENING MAMMOGRAPHY; HORMONE-THERAPY; WOMEN; BENEFITS; 40S; AGE AB BACKGROUND: Mammography screening allows for the early detection of breast cancer, which helps reduce mortality from breast cancer, especially in women aged 50 to 69 years. For this report, the authors updated a previous analysis of trends in mammography using newly available data from the National Health Interview Survey (NHIS). METHODS: NHIS data from 2008 were used to update trends in rates of US women who had a mammogram within the 2 years before their interview, and 2 methods of calculating rates were compared. The authors focused particularly on the 2000, 2005, and 2008 mammography rates for women aged >= 40 years, 40 to 49 years, 50 to 64 years, and >= 65 years according to selected sociodemographic and healthcare access characteristics. RESULTS: For women aged 50 to 64 years and >= 65 years, the patterns were similar: Rates rose rapidly from 1987 to 2000, declined, or were stable and then declined, from 2000 to 2005, and increased from 2005 to 2008. Rates for women aged 40 to 49 years rose rapidly from 1987 to 1992 and were relatively stable through 2008. There were large increases in mammography rates among immigrants who had been in the United States for < 10 years, non-Hispanic Asian women, and women aged >= 65 years who were without ambulatory care insurance. CONCLUSIONS: Overall, mammography rates did not continue to decline between 2005 and 2008. Even so, in 2008, the percentage of women aged >= 40 years who had a recent mammogram fell below the Healthy People 2010 objective of 70%, which was met in 2000. However, women aged 50 to 64 years exceeded the Healthy People objective in 2000, 2005, and 2008; and some groups with very low mammography rates currently are catching up. These are important public health achievements. Cancer 2011; 117: 2209-18. (C) 2010 American Cancer Society. C1 [Breen, Nancy] NCI, Hlth Serv, Rockville, MD USA. [Breen, Nancy] NCI, Econ Branch, Appl Res Program, Div Canc Control & Populat Studies,NIH, Rockville, MD USA. [Gentleman, Jane F.; Schiller, Jeannine S.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Interview Stat, Hyattsville, MD 20782 USA. RP Breen, N (reprint author), Execut Plaza N,Suite 4500,6130 Execut Blvd,MSC 73, Rockville, MD 20850 USA. EM breenn@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 26 TC 66 Z9 68 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2011 VL 117 IS 10 BP 2209 EP 2218 DI 10.1002/cncr.25679 PG 10 WC Oncology SC Oncology GA 758JQ UT WOS:000290161100024 PM 21523735 ER PT J AU Yamamoto, N Chang, WS Kelley, MW AF Yamamoto, Norio Chang, Weise Kelley, Matthew W. TI Rbpj regulates development of prosensory cells in the mammalian inner ear SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Hair cell; Notch; Prosensory cell; Cochlea; Saccule ID HAIR-CELLS; DEVELOPING COCHLEA; TRANSCRIPTION FACTOR; FATE DETERMINATION; FAMILY-MEMBERS; NOTCH LIGANDS; B-CELLS; J-KAPPA; ORGAN; CORTI AB The vertebrate inner ear contains multiple sensory patches comprised of hair cells and supporting cells. During development these sensory patches arise from prosensory cells that are specified and maintained through the expression of specific molecular factors. Disruption of Jagged1-mediated notch signaling causes a loss of some sensory patches and disruptions in others, indicating a role in some aspect of prosensory development. However, the presence of some sensory patches suggests that some level of notch activity persists in the absence of Jagged1. Therefore, the transcription factor Rbpj, which is required for nearly all notch function, was deleted in the developing otocyst. Results indicate a nearly complete absence of all prosensory patches in the inner ear with remaining hair cells located predominantly in the extreme apex of the cochlea. However, early markers of prosensory cells are still present in Rbpj-mutants, suggesting that maintenance, rather than induction, of prosensory development is dependent on notch signaling. Moreover, analysis of developing cochleae in Rbpj-mutants indicates changes in the spatiotemporal patterns of expression for p27(kip1), Atoh1 and hair cell differentiation markers implicating notch signaling in the regulation of the timing of cellular differentiation and/or in the maintenance of a stem/progenitor cell stage. Finally, the absence of Rbpj caused increased cell death in the cochlea beginning at E12. These results suggest important roles for Rbpj and notch signaling in multiple aspects of inner ear development including prosensory cell maturation, cellular differentiation and survival. (C) 2011 Elsevier Inc. All rights reserved. C1 [Yamamoto, Norio] Kyoto Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan. [Yamamoto, Norio; Chang, Weise; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, NIDCD, Bethesda, MD 20892 USA. RP Yamamoto, N (reprint author), Kyoto Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med, Sakyo Ku, 54 Shogoin Kawara Cho, Kyoto 6068507, Japan. EM yamamoto@ent.kuhp.kyoto-u.ac.jp OI , Norio/0000-0001-8924-0710 FU NIH; JSPS at NIH; [22791595] FX This project was supported by funds from the NIH Intramural program to MWK and by a grant from the JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH and a Grant-in-Aid for Young Scientists (B) (22791595) to NY. The authors also wish to thank Dr. Tasuku Honjo for providing Rbpj mutant mice and Scott Boyle and Rafi Kopan for sharing unpublished data and providing notch-ICD constructs. The authors also thank Dr. Jennifer Stone and Dr. Ajay Chitnis for making comments on an earlier version of the manuscript. NR 55 TC 48 Z9 48 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 15 PY 2011 VL 353 IS 2 BP 367 EP 379 DI 10.1016/j.ydbio.2011.03.016 PG 13 WC Developmental Biology SC Developmental Biology GA 758UQ UT WOS:000290192900019 PM 21420948 ER PT J AU Martinez, E Brzostowski, JA Long, EO Gross, CC AF Martinez, Emily Brzostowski, Joseph A. Long, Eric O. Gross, Catharina C. TI Cutting Edge: NKG2D-Dependent Cytotoxicity Is Controlled by Ligand Distribution in the Target Cell Membrane SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LIPID RAFTS; IMMUNOLOGICAL SYNAPSE; GRANULE POLARIZATION; IMMUNE-RESPONSES; SURFACE PROTEINS; NK CELLS; T-CELLS; MOLECULE; ACTIVATION; NKG2D AB Although the importance of membrane microdomains in receptor-mediated activation of lymphocytes has been established, much less is known about the role of receptor ligand distribution on APC and target cells. Detergent-resistant membrane domains, into which GPI-linked proteins partition, are enriched in cholesterol and glycosphingolipids. ULBP1 is a GPI-linked ligand for natural cytotoxicity receptor NKG2D. To investigate how ULBP1 distribution on target cells affects NKG2D-dependent NK cell activation, we fused the extracellular domain of ULBP1 to the transmembrane domain of CD45. Introduction of this transmembrane domain eliminated the association of ULBP1 with the detergent-resistant membrane fraction and caused a significant reduction of cytotoxicity and degranulation by NK cells. Clustering and lateral diffusion of ULBP1 was not affected by changes in the membrane anchor. These results show that the partitioning of receptor ligands in discrete membrane domains of target cells is an important determinant of NK cell activation. The Journal of Immunology, 2011, 186: 5538-5542. C1 [Martinez, Emily; Long, Eric O.; Gross, Catharina C.] NIAID, Mol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Brzostowski, Joseph A.] NIAID, Imaging Facil, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Gross, Catharina C.] Univ Hosp Munster, Dept Neurol Inflammatory Dis Nervous Syst & Neuro, ICB, D-48149 Munster, Germany. RP Long, EO (reprint author), NIAID, Mol & Cellular Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM elong@nih.gov; catharina.gross@ukmuenster.de RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 27 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2011 VL 186 IS 10 BP 5538 EP 5542 DI 10.4049/jimmunol.1002254 PG 5 WC Immunology SC Immunology GA 758GJ UT WOS:000290150700003 PM 21464092 ER PT J AU Olkhanud, PB Rochman, Y Bodogai, M Malchinkhuu, E Wejksza, K Xu, M Gress, RE Hesdorffer, C Leonard, WJ Biragyn, A AF Olkhanud, Purevdorj B. Rochman, Yrina Bodogai, Monica Malchinkhuu, Enkhzol Wejksza, Katarzyna Xu, Mai Gress, Ronald E. Hesdorffer, Charles Leonard, Warren J. Biragyn, Arya TI Thymic Stromal Lymphopoietin Is a Key Mediator of Breast Cancer Progression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; CHEMOKINE RECEPTORS; AIRWAY HYPERREACTIVITY; TSLP; INFLAMMATION; EXPRESSION; INDUCE; ASTHMA; LUNG; CCR4 AB Inflammation is a double-edged sword that can promote or suppress cancer progression. In this study, we report that thymic stromal lymphopoietin (TSLP), an IL-7-like type 1 inflammatory cytokine that is often associated with the induction of Th2-type allergic responses in the lungs, is also expressed in human and murine cancers. Our studies with murine cancer cells indicate that TSLP plays an essential role in cancer escape, as its inactivation in cancer cells alone was sufficient to almost completely abrogate cancer progression and lung metastasis. The cancer-promoting activity of TSLP primarily required signaling through the TSLP receptor on CD4(+) T cells, promoting Th2-skewed immune responses and production of immunosuppressive factors such as IL-10 and IL-13. Expression of TSLP therefore may be a useful prognostic marker, and its targeting could have therapeutic potential. The Journal of Immunology, 2011, 186: 5656-5662. C1 [Olkhanud, Purevdorj B.; Bodogai, Monica; Malchinkhuu, Enkhzol; Wejksza, Katarzyna; Xu, Mai; Biragyn, Arya] NIA, Immunotherapeut Unit, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. [Rochman, Yrina; Leonard, Warren J.] NHLBI, Lab Mol Immunol, Ctr Immunol, NIH, Bethesda, MD 20892 USA. [Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Hesdorffer, Charles] NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Biragyn, A (reprint author), NIA, Immunotherapeut Unit, Lab Mol Biol & Immunol, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM wjl@helix.nih.gov; biragyna@mail.nih.gov FU National Institute on Aging; National Heart, Lung, and Blood Institute, National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Institute on Aging and the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 33 TC 45 Z9 48 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2011 VL 186 IS 10 BP 5656 EP 5662 DI 10.4049/jimmunol.1100463 PG 7 WC Immunology SC Immunology GA 758GJ UT WOS:000290150700016 PM 21490155 ER PT J AU Matthews, PC Adland, E Listgarten, J Leslie, A Mkhwanazi, N Carlson, JM Harndahl, M Stryhn, A Payne, RP Ogwu, A Huang, KHG Frater, J Paioni, P Kloverpris, H Jooste, P Goedhals, D van Vuuren, C Steyn, D Riddell, L Chen, F Luzzi, G Balachandran, T Ndung'u, T Buus, S Carrington, M Shapiro, R Heckerman, D Goulder, PJR AF Matthews, Philippa C. Adland, Emily Listgarten, Jennifer Leslie, Alasdair Mkhwanazi, Nompumelelo Carlson, Jonathan M. Harndahl, Mikkel Stryhn, Anette Payne, Rebecca P. Ogwu, Anthony Huang, Kuan-Hsiang Gary Frater, John Paioni, Paolo Kloverpris, Henrik Jooste, Pieter Goedhals, Dominique van Vuuren, Cloete Steyn, Dewald Riddell, Lynn Chen, Fabian Luzzi, Graz Balachandran, Thambiah Ndung'u, Thumbi Buus, Soren Carrington, Mary Shapiro, Roger Heckerman, David Goulder, Philip J. R. TI HLA-A*7401-Mediated Control of HIV Viremia Is Independent of Its Linkage Disequilibrium with HLA-B*5703 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLASS-I ALLELES; LINKED IMMUNOSPOT ASSAY; T-LYMPHOCYTE EPITOPES; ANTIGEN CLASS-I; DISEASE PROGRESSION; VIRAL LOAD; ESCAPE MUTATIONS; HLA-B; SELECTION PRESSURE AB The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of > 2100 C-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1 disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag epitopes appear immunodominant. We identify eight novel putative HLA-A*7401-restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401-restricted response appears to be associated with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which it is in linkage disequilibrium. In addition, these studies identify a factor contributing to different HIV disease outcomes in individuals expressing HLA-B*5703. The Journal of Immunology, 2011, 186: 5675-5686. C1 [Matthews, Philippa C.; Adland, Emily; Payne, Rebecca P.; Paioni, Paolo; Kloverpris, Henrik; Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. [Listgarten, Jennifer; Carlson, Jonathan M.; Heckerman, David] Microsoft Res, eSci Grp, Los Angeles, CA 90024 USA. [Leslie, Alasdair] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. [Mkhwanazi, Nompumelelo; Ndung'u, Thumbi; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa. [Harndahl, Mikkel; Stryhn, Anette; Buus, Soren] Univ Copenhagen, Fac Hlth Sci, Expt Immunol Lab, DK-2200 Copenhagen, Denmark. [Ogwu, Anthony; Shapiro, Roger] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Huang, Kuan-Hsiang Gary; Frater, John] Univ Oxford, Nuffield Dept Med, Oxford OX1 3SY, England. [Jooste, Pieter] Univ Free State, Dept Paediat, ZA-8300 Kimberley, Northern Cape, South Africa. [Goedhals, Dominique] Univ Free State, Natl Hlth Lab Serv, Dept Med Microbiol & Virol, ZA-9300 Bloemfontein, South Africa. [Goedhals, Dominique] Univ Oxford, Dept Internal Med, Oxford OX1 3SY, England. [Riddell, Lynn] Northampton Gen Hosp, Northamptonshire Healthcare Natl Hlth Serv Trust, Dept Genitourinary Med, Northampton NN1 5BD, England. [Chen, Fabian] Royal Berkshire Hosp, Dept Sexual Hlth, Reading RG1 5AN, Berks, England. [Luzzi, Graz] Wycombe Gen Hosp, Sexual Hlth Wycombe Clin, High Wycombe HP11 2TT, Bucks, England. [Balachandran, Thambiah] Luton & Dunstable Hosp, Dept Sexual Hlth, Luton LU4 0DZ, Beds, England. [Carrington, Mary] NCI, Canc & Inflammat Program, Lab Expt Immunol, SAIC Frederick, Frederick, MD 21702 USA. [Carrington, Mary] Massachusetts Gen Hosp, Ragon Inst, Massachusetts Inst Technol & Harvard, Boston, MA 02129 USA. [Shapiro, Roger] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Goulder, PJR (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. EM philip.goulder@paediatrics.ox.ac.uk RI Buus, Soren/F-5446-2010; OI Matthews, Philippa/0000-0002-4036-4269; Buus, Soren/0000-0001-8363-1999; Ndung'u, Thumbi/0000-0003-2962-3992 FU United Kingdom Medical Research Council; Oxford Radcliffe Hospitals; National Institutes of Health [2RO1AI46995]; National Institute of Allergy and Infectious Diseases [HHSN272200900045C]; South African AIDS Vaccine Initiative; Wellcome Trust; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported by the United Kingdom Medical Research Council (to P. C. M.), the Oxford Radcliffe Hospitals Medical Research Fund (to P. C. M), National Institutes of Health Grant 2RO1AI46995, National Institute of Allergy and Infectious Diseases Contract HHSN272200900045C, the South African AIDS Vaccine Initiative, the Wellcome Trust (to A. L. and P.J.R.G.), the National Cancer Institute, National Institutes of Health Contract HHSN261200800001E, and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. P.J.R.G. is an Elizabeth Glaser Pediatric AIDS Foundation Scientist. NR 58 TC 33 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2011 VL 186 IS 10 BP 5675 EP 5686 DI 10.4049/jimmunol.1003711 PG 12 WC Immunology SC Immunology GA 758GJ UT WOS:000290150700018 PM 21498667 ER PT J AU Davidson, S Kaiko, G Loh, Z Lalwani, A Zhang, V Spann, K Foo, SY Hansbro, N Uematsu, S Akira, S Matthaei, KI Rosenberg, HF Foster, PS Phipps, S AF Davidson, Sophia Kaiko, Gerard Loh, Zhixuan Lalwani, Amit Zhang, Vivian Spann, Kirsten Foo, Shen Yun Hansbro, Nicole Uematsu, Satoshi Akira, Shizuo Matthaei, Klaus I. Rosenberg, Helene F. Foster, Paul S. Phipps, Simon TI Plasmacytoid Dendritic Cells Promote Host Defense against Acute Pneumovirus Infection via the TLR7-MyD88-Dependent Signaling Pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; MACROPHAGE-INFLAMMATORY PROTEIN-1-ALPHA; PATTERN-RECOGNITION RECEPTORS; IMMUNE-RESPONSES; PNEUMONIA VIRUS; I INTERFERON; INFLUENZA-VIRUS; INNATE IMMUNITY; PULMONARY INFLAMMATION; CHEMOKINE PRODUCTION AB Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants. In human infants, plasmacytoid dendritic cells (pDC) are recruited to the nasal compartment during infection and initiate host defense through the secretion of type I IFN, IL-12, and IL-6. However, RSV-infected pDC are refractory to TLR7-mediated activation. In this study, we used the rodent-specific pathogen, pneumonia virus of mice (PVM), to determine the contribution of pDC and TLR7 signaling to the development of the innate inflammatory and early adaptive immune response. In wild-type, but not TLR7- or MyD88-deficient mice, PVM inoculation led to a marked infiltration of pDC and increased expression of type I, II, and III IFNs. The delayed induction of IFNs in the absence of TLR7 or MyD88 was associated with a diminished innate inflammatory response and augmented virus recovery from lung tissue. In the absence of TLR7, PVM-specific CD8(+) T cell cytokine production was abrogated. The adoptive transfer of TLR7-sufficient, but not TLR7-deficient pDC to TLR7 gene-deleted mice recapitulated the antiviral responses observed in wild-type mice and promoted virus clearance. In summary, TLR7-mediated signaling by pDC is required for appropriate innate responses to acute pneumovirus infection. It is conceivable that as-yet-unidentified defects in the TLR7 signaling pathway may be associated with elevated levels of RSV-associated morbidity and mortality among otherwise healthy human infants. The Journal of Immunology, 2011, 186: 5938-5948. C1 [Loh, Zhixuan; Lalwani, Amit; Zhang, Vivian; Phipps, Simon] Univ Queensland, Sch Biomed Sci, St Lucia, Qld 4072, Australia. [Loh, Zhixuan; Lalwani, Amit; Zhang, Vivian; Phipps, Simon] Univ Queensland, Australian Infect Dis Res Ctr, St Lucia, Qld 4072, Australia. [Davidson, Sophia; Kaiko, Gerard; Foo, Shen Yun; Hansbro, Nicole; Foster, Paul S.] Univ Newcastle, Ctr Asthma & Resp Dis, Newcastle, NSW 2300, Australia. [Davidson, Sophia; Kaiko, Gerard; Foo, Shen Yun; Hansbro, Nicole; Foster, Paul S.] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2300, Australia. [Spann, Kirsten] Univ Queensland, Sir Albert Sakzewski Virus Res Ctr, Brisbane, Qld 4072, Australia. [Uematsu, Satoshi; Akira, Shizuo] Osaka Univ, World Premier Int Immunol Frontier Res Ctr, Host Def Lab, Suita, Osaka 5650871, Japan. [Matthaei, Klaus I.] Australian Natl Univ, John Curtin Sch Med Res, Stem Cell & Gene Targeting Lab, Canberra, ACT 0200, Australia. [Matthaei, Klaus I.] King Saud Univ, Coll Med, Dept Anat, Stem Cell Unit, Riyadh 11461, Saudi Arabia. [Matthaei, Klaus I.] King Saud Univ, King Khalid Univ Hosp, Riyadh 11461, Saudi Arabia. [Rosenberg, Helene F.] NIAID, NIH, Bethesda, MD 20892 USA. RP Phipps, S (reprint author), Univ Queensland, Sch Biomed Sci, St Lucia, Qld 4072, Australia. EM s.phipps@uq.edu.au RI Akira, Shizuo/C-3134-2009; Klaus, Matthaei/D-8691-2011; Lalwani, Amit/F-6158-2012; Spann, Kirsten/B-4524-2013; Phipps, Simon/F-9170-2010; Foster, Paul/G-5057-2013; Loh, Zhixuan/G-4104-2015 OI Spann, Kirsten/0000-0003-0567-8382; Phipps, Simon/0000-0002-7388-3612; Loh, Zhixuan/0000-0002-4124-9502 FU National Health and Medical Research Council of Australia; National Institute of Allergy and Infectious Diseases Division of Intramural Research [Z01-AI000943]; Australian Lung Foundation/Boehringer Ingelheim Chronic Airflow Limitation FX This work was supported by a National Health and Medical Research Council of Australia Project grant (to S.P. and P.S.F.) and National Institute of Allergy and Infectious Diseases Division of Intramural Research funding (Z01-AI000943 to H.F.R.). S.P. was a recipient of an Australian Lung Foundation/Boehringer Ingelheim Chronic Airflow Limitation Research Fellowship from 2006 to 2007. NR 60 TC 41 Z9 42 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2011 VL 186 IS 10 BP 5938 EP 5948 DI 10.4049/jimmunol.1002635 PG 11 WC Immunology SC Immunology GA 758GJ UT WOS:000290150700045 PM 21482736 ER PT J AU Kuehn, HS Caminha, I Niemela, JE Rao, VK Davis, J Fleisher, TA Oliveira, JB AF Kuehn, Hye Sun Caminha, Iusta Niemela, Julie E. Rao, V. Koneti Davis, Joie Fleisher, Thomas A. Oliveira, Joao B. TI FAS Haploinsufficiency Is a Common Disease Mechanism in the Human Autoimmune Lymphoproliferative Syndrome SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYNDROME ALPS; DEFECTIVE LYMPHOCYTE; MUTATIONS; APOPTOSIS; GENE; EXPRESSION; FAMILIES; ACTIVATION; LYMPHOMAS; PATIENT AB The autoimmune lymphoproliferative syndrome (ALPS) is characterized by early-onset lymphadenopathy, splenomegaly, immune cytopenias, and an increased risk for B cell lymphomas. Most ALPS patients harbor mutations in the FAS gene, which regulates lymphocyte apoptosis. These are commonly missense mutations affecting the intracellular region of the protein and have a dominant-negative effect on the signaling pathway. However, analysis of a large cohort of ALPS patients revealed that similar to 30% have mutations affecting the extracellular region of FAS, and among these, 70% are nonsense, splice site, or insertions/deletions with frameshift for which no dominant-negative effect would be expected. We evaluated the latter patients to understand the mechanism(s) by which these mutations disrupted the FAS pathway and resulted in clinical disease. We demonstrated that most extracellular-region FAS mutations induce low FAS expression due to nonsense-mediated RNA decay or protein instability, resulting in defective death-inducing signaling complex formation and impaired apoptosis, although to a lesser extent as compared with intracellular mutations. The apoptosis defect could be corrected by FAS overexpression in vitro. Our findings define haploinsufficiency as a common disease mechanism in ALPS patients with extracellular FAS mutations. The Journal of Immunology, 2011, 186: 6035-6043. C1 [Kuehn, Hye Sun; Caminha, Iusta; Niemela, Julie E.; Fleisher, Thomas A.; Oliveira, Joao B.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20814 USA. [Rao, V. Koneti; Davis, Joie] NIAID, ALPS Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Oliveira, JB (reprint author), NIH, Dept Lab Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20814 USA. EM oliveirajb@cc.nih.gov OI Oliveira, Joao/0000-0001-9388-8173; Niemela, Julie/0000-0003-4197-3792 FU National Institutes of Health FX This work was supported by the National Institutes of Health Intramural Program. NR 37 TC 17 Z9 18 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2011 VL 186 IS 10 BP 6035 EP 6043 DI 10.4049/jimmunol.1100021 PG 9 WC Immunology SC Immunology GA 758GJ UT WOS:000290150700055 PM 21490157 ER PT J AU Bedognetti, D Zoppoli, G Massucco, C Zanardi, E Zupo, S Bruzzone, A Sertoli, MR Balleari, E Racchi, O Messina, M Caltabiano, G Icardi, G Durando, P Marincola, FM Boccardo, F Ferrarini, M Ansaldi, F De Maria, A AF Bedognetti, Davide Zoppoli, Gabriele Massucco, Carlotta Zanardi, Elisa Zupo, Simonetta Bruzzone, Andrea Sertoli, Mario Roberto Balleari, Enrico Racchi, Omar Messina, Marco Caltabiano, Graziano Icardi, Giancarlo Durando, Paolo Marincola, Francesco M. Boccardo, Francesco Ferrarini, Manlio Ansaldi, Filippo De Maria, Andrea TI Impaired Response to Influenza Vaccine Associated with Persistent Memory B Cell Depletion in Non-Hodgkin's Lymphoma Patients Treated with Rituximab-Containing Regimens SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTI-CD20 MONOCLONAL-ANTIBODY; CHEMOTHERAPY PLUS RITUXIMAB; RHEUMATOID-ARTHRITIS; HYPOGAMMAGLOBULINEMIA; FLUDARABINE; EXPRESSION; ADJUVANT; CRITERIA; DISEASE; YOUNG AB Influenza vaccination is generally recommended for non-Hodgkin's lymphoma (NHL) patients, but no data are available about the activity of this vaccine after treatment with rituximab-containing regimens. We evaluated the humoral response to the trivalent seasonal influenza vaccine in a group of NHL patients in complete remission for >= 6 mo (median, 29 mo) after treatment with rituximab-containing regimens (n = 31) compared with age-matched healthy subjects (n = 34). B cell populations and incidence of influenza-like illness were also evaluated. For each viral strain, the response was significantly lower in patients compared with controls and was particularly poor in patients treated with fludarabine-based regimens. In the patient group, the response to vaccination did not fulfill the immunogenic criteria based on the European Committee for Medicinal Products for Human Use requirements. Among the patients, CD27(+) memory B cells were significantly reduced, and their reduction correlated with serum IgM levels and vaccine response. Episodes of influenza-like illness were recorded only in patients. These results showed that NHL patients treated with rituximab-containing regimens have persisting perturbations of B cell compartments and Ig synthesis and may be at particular risk for infection, even in long-standing complete remission. The Journal of Immunology, 2011, 186: 6044-6055. C1 [Bedognetti, Davide; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Bedognetti, Davide; Marincola, Francesco M.] Trans Natl Inst, Hlth Ctr Human Immunol, NIH, Bethesda, MD 20892 USA. [Bedognetti, Davide; Zanardi, Elisa; Sertoli, Mario Roberto; Messina, Marco; Caltabiano, Graziano; Boccardo, Francesco; Ferrarini, Manlio] Univ Genoa, Dept Oncol Biol & Genet, I-16132 Genoa, Italy. [Bedognetti, Davide; Zanardi, Elisa; Sertoli, Mario Roberto; Messina, Marco; Caltabiano, Graziano; Boccardo, Francesco; Ferrarini, Manlio] Natl Inst Canc Res, Dept Med Oncol, I-16132 Genoa, Italy. [Bedognetti, Davide; Zoppoli, Gabriele; Bruzzone, Andrea; Balleari, Enrico] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy. [Zoppoli, Gabriele] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Massucco, Carlotta; Zupo, Simonetta] Natl Inst Canc Res, Lab Mol Diagnost, I-16132 Genoa, Italy. [Racchi, Omar] Villa Scassi Hosp, Hematol Oncol Unit, I-16132 Genoa, Italy. [Icardi, Giancarlo; Durando, Paolo; Ansaldi, Filippo; De Maria, Andrea] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [De Maria, Andrea] Natl Inst Canc Res, Infect Dis Unit, I-16132 Genoa, Italy. [De Maria, Andrea] Univ Genoa, Ctr Excellence Biomed Res, I-16132 Genoa, Italy. RP Bedognetti, D (reprint author), NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM davide.bedognetti@nih.gov; de-maria@unige.it RI Balleari, Enrico/R-3119-2016; Bedognetti, Davide/A-9090-2012; Zoppoli, Gabriele/B-6935-2016; de maria, andrea/F-7116-2016 OI Balleari, Enrico/0000-0003-2186-8012; Bedognetti, Davide/0000-0002-5857-773X; Ferrarini, Manlio/0000-0002-6154-2570; Zoppoli, Gabriele/0000-0003-3890-5588; de maria, andrea/0000-0001-5782-333X FU National Cancer Research Institute of Genoa; Novartis Vaccines; Sanofi Pasteur; Crucell Berna; GlaxoSmithKline FX This work was supported in part by the National Cancer Research Institute of Genoa.; F.A. participated in speakers' bureaus and advisory board meetings sponsored by Novartis Vaccines and Sanofi Pasteur and received research funding from Novartis Vaccines and Sanofi Pasteur. G.I. participated in speakers' bureaus and advisory board meetings sponsored by Sanofi Pasteur and has received research funding from Crucell Berna, GlaxoSmithKline, and Sanofi Pasteur. P.D. received financial support for scientific research, speaker's fees, and attendance at national and international meetings from influenza vaccine and antiviral manufacturers, not including Cruce/ISB or Roche. He has been and currently is investigator of several clinical trials on innovative vaccines produced by influenza vaccine manufacturers, not including Crucell/ISB or Roche. NR 50 TC 36 Z9 37 U1 0 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 MAY 15 PY 2011 VL 186 IS 10 BP 6044 EP 6055 DI 10.4049/jimmunol.1004095 PG 12 WC Immunology SC Immunology GA 758GJ UT WOS:000290150700056 PM 21498665 ER PT J AU Martin-Manso, G Calzada, MJ Chuman, Y Sipes, JM Xavier, CP Wolf, V Kuznetsova, SA Rubin, JS Roberts, DD AF Martin-Manso, Gema Calzada, Maria J. Chuman, Yoshiro Sipes, John M. Xavier, Charles P. Wolf, Vladimir Kuznetsova, Svetlana A. Rubin, Jeffrey S. Roberts, David D. TI sFRP-1 binds via its netrin-related motif to the N-module of thrombospondin-1 and blocks thrombospondin-1 stimulation of MDA-MB-231 breast carcinoma cell adhesion and migration SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Secreted frizzled-related proteins; Netrin-binding proteins; Thrombospondins; Breast carcinoma ID FRIZZLED-RELATED PROTEIN-1; CANCER-CELLS; TUMOR-GROWTH; ALPHA(3)BETA(1) INTEGRIN; PLATELET-AGGREGATION; SPEMANN ORGANIZER; TERMINAL DOMAIN; IN-VITRO; ANGIOGENESIS; EXPRESSION AB Secreted frizzled-related protein (sFRP)-1 is a Wnt antagonist that inhibits breast carcinoma cell motility, whereas the secreted glycoprotein thrombospondin-1 stimulates adhesion and motility of the same cells. We examined whether thrombospondin-1 and sFRP-1 interact directly or indirectly to modulate cell behavior. Thrombospondin-1 bound sFRP-1 with an apparent K(d) = 48 nM and the related sFRP-2 with a K(d) = 95 nM. Thrombospondin-1 did not bind to the more distantly related sFRP-3. The association of thrombospondin-1 and sFRP-1 is primarily mediated by the amino-terminal N-module of thrombospondin-1 and the netrin domain of sFRP-1. sFRP-1 inhibited alpha 3 beta 1 integrin-mediated adhesion of MDA-MB-231 breast carcinoma cells to a surface coated with thrombospondin-1 or recombinant N-module, but not adhesion of the cells on immobilized fibronectin or type I collagen. sFRP-1 also inhibited thrombospondin-1-mediated migration of MDA-MB-231 and MDA-MB-468 breast carcinoma cells. Although sFRP-2 binds similarly to thrombospondin-1, it did not inhibit thrombospondin-1-stimulated adhesion. Thus, sFRP-1 binds to thrombospondin-1 and antagonizes stimulatory effects of thrombospondin-1 on breast carcinoma cell adhesion and motility. These results demonstrate that sFRP-1 can modulate breast cancer cell responses by interacting with thrombospondin-1 in addition to its known effects on Wnt signaling. Published by Elsevier Inc. C1 [Martin-Manso, Gema; Calzada, Maria J.; Sipes, John M.; Kuznetsova, Svetlana A.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chuman, Yoshiro; Xavier, Charles P.; Wolf, Vladimir; Rubin, Jeffrey S.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM mansog@mail.nih.gov; mcalzada.hlpr@salud.madrid.org; chuman@sci.hokudai.ac.jp; sipesj@mail.nih.gov; Charles.Xavier@nih.gov; vladimir.wolf@qiagen.com; kuznetsova4872@yahoo.co.uk; rubinj@mail.nih.gov; droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Martin Manso, Maria Gema/D-4612-2013 OI Roberts, David/0000-0002-2481-2981; FU NIH, National Cancer Institute, Center for Cancer Research; Instituto de Salud Carlos III (Spanish Ministry of Health) FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (DDR, JSR). Gema Martin-Manso was recipient of a grant BEFI from Instituto de Salud Carlos III (Spanish Ministry of Health). NR 92 TC 18 Z9 19 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 2011 VL 509 IS 2 BP 147 EP 156 DI 10.1016/j.abb.2011.03.004 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 757BS UT WOS:000290059500005 PM 21402050 ER PT J AU Li, TW Santockyte, R Yu, SQ Shen, RF Tekle, E Lee, CGL Yang, DCH Chock, PB AF Li, Tianwei Santockyte, Rasa Yu, Shiqin Shen, Rong-Fong Tekle, Ephrem Lee, Caroline G. L. Yang, David C. H. Chock, P. Boon TI FAT10 modifies p53 and upregulates its transcriptional activity SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE p53; PML-NB (promyelocytic leukemia nuclear bodies); Ubiquitin modifiers; Transcription activation; FATylation; Proteomic ID UBIQUITIN-LIKE PROTEIN; EXPRESSION; GENE; CANCERS; PML; DEGRADATION; SENESCENCE; APOPTOSIS; PATHWAYS AB FAT10, also known as diubiquitin, has been implicated in the regulation of diverse cellular processes, including mitosis, immune response, and apoptosis. We seek to identify FAT10-targeted proteins, an essential step in elucidating the physiological function of FAT10. To this end, human FAT10 or its non-conjugatable derivative, FAT10 Delta GG, was overexpressed in HEK293 cells. We observed a number of high molecular weight FAT10 conjugates in cells expressing wild-type FAT10, but not in FAT10 Delta GG. The FAT10 conjugates are inducible by TNF-alpha and accumulated significantly when cells were treated with proteasome inhibitor, MG132. Among them, tumor suppressor p53 was found to be FATylated. The p53 transcriptional activity was found to be substantially enhanced in FAT10-overexpressing cells. In addition, overexpressing FAT10 in HEK293 cells also reduced the population of p53 which cross reacted with monoclonal anti-p53 antibody, PAB240, known to recognize only the transcriptionally inactive p53. FAT10 in the nucleus was found co-localized with p53 and altered its subcellular compartmentalization. Furthermore, overexpressing FAT10 led to a reduction in the size of promyelocytic leukemia nuclear bodies (PML-NBs) and altered their distribution in the nucleus. Based on these observations, a potential mechanism which correlates FATylation of p53 to its translocation and transcriptional activation is discussed. (C) 2011 Published by Elsevier Inc. C1 [Li, Tianwei; Yu, Shiqin; Tekle, Ephrem; Chock, P. Boon] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Santockyte, Rasa; Yang, David C. H.] Georgetown Univ, Dept Chem, Washington, DC 20057 USA. [Shen, Rong-Fong] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. [Lee, Caroline G. L.] Natl Univ Singapore, Dept Biochem, DUKE NUS Grad Med Sch, Singapore 117548, Singapore. [Lee, Caroline G. L.] Singapore Natl Canc Ctr, Singapore, Singapore. RP Chock, PB (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. EM BChock@nih.gov RI Yang, David/A-7294-2009 FU Intramural NIH HHS [ZIA HL000202-39] NR 27 TC 20 Z9 23 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 2011 VL 509 IS 2 BP 164 EP 169 DI 10.1016/j.abb.2011.02.017 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 757BS UT WOS:000290059500007 PM 21396347 ER PT J AU Kim, HK Chung, YW Chock, PB Yim, MB AF Kim, Ha Kun Chung, Youn Wook Chock, P. Boon Yim, Moon B. TI Effect of CCS on the accumulation of FALS SOD1 mutant-containing aggregates and on mitochondrial translocation of SOD1 mutants: Implication of a free radical hypothesis SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE CCS; FALS SOD1; Mitochondrial translocation of SOD1 mutants; Macroautophagy; Molecular chaperone; Oxidative stress ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN-SUPEROXIDE-DISMUTASE; MOTOR-NEURON DEGENERATION; HUMAN COPPER CHAPERONE; CU,ZN-SUPEROXIDE DISMUTASE; HYDROGEN-PEROXIDE; TRANSGENIC MICE; PROTEASOMAL DEGRADATION; PROTEIN-DEGRADATION; MOUSE MODEL AB Missense mutations of SOD1 are linked to familial amyotrophic lateral sclerosis (FALS) through a yet-to-be identified toxic-gain-of-function. One of the proposed mechanisms involves enhanced aggregate formation. However, a recent study showed that dual transgenic mice overexpressing both G93A and CCS copper chaperone (G93A/CCS) exhibit no SOD1-positive aggregates yet show accelerated FALS symptoms with enhanced mitochondrial pathology compared to G93A mice. Using a dicistronic mRNA to simultaneously generate hSOD1 mutants, G93A, A4V and G85R, and hCCS in AAV293 cells, we revealed: (i) CCS is degraded primarily via a macroautophagy pathway. It forms a stable heterodimer with inactive G85R, and via its novel copper chaperone-independent molecular chaperone activity facilitates G85R degradation via a macroautophagy-mediated pathway. For active G93A and A4V. CCS catalyzes their maturation to form active and soluble homodimers. (ii) CCS reduces, under non-oxidative conditions, yet facilitates in the presence of H(2)O(2), mitochondrial translocation of inactive SOD1 mutants. These results, together with previous reports showing FALS SOD1 mutants enhanced free radical-generating activity, provide a mechanistic explanation for the observations with G93A/CCS dual transgenic mice and suggest that free radical generation by FALS SOD1, enhanced by CCS, may, in part, be responsible for the FALS SOD1 mutant-linked aggregation, mitochondrial translocation, and degradation. Published by Elsevier Inc. C1 [Kim, Ha Kun; Chung, Youn Wook; Chock, P. Boon; Yim, Moon B.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Kim, Ha Kun] Pai Chai Univ, Dept Life Sci & Genet Engn, Taejon 302735, South Korea. RP Chock, PB (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2134,MSC 8012, Bethesda, MD 20892 USA. EM bchock@nih.gov; yimm@nhlbi.nih.gov FU National Institutes of Health, National Heart, Lung, and Blood Institute FX This work was supported, in whole, by the National Institutes of Health, National Heart, Lung, and Blood Institute, Intramural Research Program. NR 61 TC 7 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 2011 VL 509 IS 2 BP 177 EP 185 DI 10.1016/j.abb.2011.02.014 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 757BS UT WOS:000290059500009 PM 21354101 ER PT J AU Kim, SY Rane, SG AF Kim, So Yoon Rane, Sushil G. TI The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1(+) progenitors and Ngn3(+) endocrine precursors SO DEVELOPMENT LA English DT Article DE Cdk4; E2f1; Ngn3 (Neurog3); Pancreas development; Pdx1; Mouse ID BETA-CELL MASS; HOMEODOMAIN TRANSCRIPTION FACTOR; MOUSE PANCREAS; SELF-RENEWAL; IN-VIVO; MICE; ORGANOGENESIS; EXPRESSION; GROWTH; DIFFERENTIATION AB Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1(+) pancreatic progenitor cells. Expression of activated Cdk4(R24C) kinase leads to increased Nkx2.2(+) and Nkx6.1(+) cells and a rise in the number and proliferation of Ngn3(+) endocrine precursors, resulting in expansion of the beta cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes beta cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors. C1 [Kim, So Yoon; Rane, Sushil G.] NIDDK, Regenerat Biol Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Rane, SG (reprint author), NIDDK, Regenerat Biol Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. EM ranes@mail.nih.gov FU NIDDK, NIH FX We thank Michael German (University of California, San Francisco, CA, USA) for providing the human NGN3 promoter plasmids and Raymond MacDonald and Galvin Swift (University of Texas Southwestern Medical Center at Dallas, TX, USA) for providing the ChIP assay protocol and help with standardizing the wholemount staining technique. This work was supported by funds from the NIDDK, NIH intramural program. Deposited in PMC for release after 12 months. NR 59 TC 17 Z9 17 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY 15 PY 2011 VL 138 IS 10 BP 1903 EP 1912 DI 10.1242/dev.061481 PG 10 WC Developmental Biology SC Developmental Biology GA 754VQ UT WOS:000289886200003 PM 21490060 ER PT J AU Senger, S Csokmay, J Tanveer, A Jones, TI Sengupta, P Lilly, MA AF Senger, Stefania Csokmay, John Tanveer, Akbar Jones, Takako Iida Sengupta, Prabuddha Lilly, Mary A. TI The nucleoporin Seh1 forms a complex with Mio and serves an essential tissue-specific function in Drosophila oogenesis SO DEVELOPMENT LA English DT Article DE Seh1 (Nup44A); Mio; NPC; Nup107-160; Nucleoporin; Oogenesis; Meiosis; Germline; Drosophila; Mtor (Tpr); Microtubule ID NUCLEAR-PORE COMPLEX; GERM-CELL DEVELOPMENT; RNA-BINDING PROTEIN; OOCYTE DIFFERENTIATION; EARLY POLARIZATION; SPINDLE MATRIX; CYST FORMATION; MELANOGASTER; FUSOME; MITOSIS AB The nuclear pore complex (NPC) mediates the transport of macromolecules between the nucleus and cytoplasm. Recent evidence indicates that structural nucleoporins, the building blocks of the NPC, have a variety of unanticipated cellular functions. Here, we report an unexpected tissue-specific requirement for the structural nucleoporin Seh1 during Drosophila oogenesis. Seh1 is a component of the Nup107-160 complex, the major structural subcomplex of the NPC. We demonstrate that Seh1 associates with the product of the missing oocyte (mio) gene. In Drosophila, mio regulates nuclear architecture and meiotic progression in early ovarian cysts. Like mio, seh1 has a crucial germline function during oogenesis. In both mio and seh1 mutant ovaries, a fraction of oocytes fail to maintain the meiotic cycle and develop as pseudo-nurse cells. Moreover, the accumulation of Mio protein is greatly diminished in the seh1 mutant background. Surprisingly, our characterization of a seh1 null allele indicates that, although required in the female germline, seh1 is dispensable for the development of somatic tissues. Our work represents the first examination of seh1 function within the context of a multicellular organism. In summary, our studies demonstrate that Mio is a novel interacting partner of the conserved nucleoporin Seh1 and add to the growing body of evidence that structural nucleoporins can have novel tissue-specific roles. C1 [Senger, Stefania; Tanveer, Akbar; Jones, Takako Iida; Sengupta, Prabuddha; Lilly, Mary A.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Csokmay, John] NICHHD, Reprod Biol & Med Program, NIH, Bethesda, MD 20892 USA. RP Lilly, MA (reprint author), NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM mlilly@helix.nih.gov OI Lilly, Mary/0000-0003-1564-619X FU Eunice Kennedy-Shriver National Institute of Child Health and Human Development at the National Institutes of Health FX We thank Valerie Doye, Katrina Katsani and the Bloomington Stock Center for antibodies and stocks. We thank Eva Decotto and Katrina Katsani for comments on the manuscript. This research was supported by the intramural program of the Eunice Kennedy-Shriver National Institute of Child Health and Human Development at the National Institutes of Health. Deposited in PMC for release after 12 months. NR 55 TC 20 Z9 21 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY 15 PY 2011 VL 138 IS 10 BP 2133 EP 2142 DI 10.1242/dev.057372 PG 10 WC Developmental Biology SC Developmental Biology GA 754VQ UT WOS:000289886200024 PM 21521741 ER PT J AU Galbraith, CG Galbraith, JA AF Galbraith, Catherine G. Galbraith, James A. TI Super-resolution microscopy at a glance SO JOURNAL OF CELL SCIENCE LA English DT Editorial Material ID STRUCTURED-ILLUMINATION MICROSCOPY; PHOTOACTIVATED LOCALIZATION MICROSCOPY; OPTICAL RECONSTRUCTION MICROSCOPY; GENETICALLY EXPRESSED PROBES; STIMULATED-EMISSION; FLUORESCENT-PROBES; RESOLUTION LIMIT; STED MICROSCOPY; NANOSCOPY; CELLS C1 [Galbraith, Catherine G.] NICHD, NIH, Bethesda, MD 20892 USA. [Galbraith, James A.] NINDS, Bethesda, MD 20892 USA. RP Galbraith, CG (reprint author), NICHD, NIH, Bethesda, MD 20892 USA. EM cgalbrai@mail.nih.gov; galbraij@ninds.nih.gov FU Intramural NIH HHS NR 36 TC 74 Z9 75 U1 2 U2 33 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 MAY 15 PY 2011 VL 124 IS 10 BP 1607 EP 1611 DI 10.1242/jcs.080085 PG 5 WC Cell Biology SC Cell Biology GA 757QD UT WOS:000290101900002 PM 21536831 ER PT J AU Chu, C Ni, YZ Tan, G Saunders, CJ Ashburner, J AF Chu, Carlton Ni, Yizhao Tan, Geoffrey Saunders, Craig J. Ashburner, John TI Kernel regression for fMRI pattern prediction SO NEUROIMAGE LA English DT Article DE Kernel methods; Machine learning; Kernel ridge regression (KRR); fMRI prediction; Automatic relevance determination (ARD); Relevance vector machines (RVM); Regression Multivariate ID SINGLE-SUBJECT; BOLD FMRI; BRAIN; CORTEX; SIGNAL AB This paper introduces two kernel-based regression schemes to decode or predict brain states from functional brain scans as part of the Pittsburgh Brain Activity Interpretation Competition (PBAIC) 2007, in which our team was awarded first place. Our procedure involved image realignment, spatial smoothing, detrending of low-frequency drifts, and application of multivariate linear and non-linear kernel regression methods: namely kernel ridge regression (KRR) and relevance vector regression (RVR). RVR is based on a Bayesian framework, which automatically determines a sparse solution through maximization of marginal likelihood. KRR is the dual-form formulation of ridge regression, which solves regression problems with high dimensional data in a computationally efficient way. Feature selection based on prior knowledge about human brain function was also used. Post-processing by constrained deconvolution and re-convolution was used to furnish the prediction. This paper also contains a detailed description of how prior knowledge was used to fine tune predictions of specific "feature ratings," which we believe is one of the key factors in our prediction accuracy. The impact of pre-processing was also evaluated, demonstrating that different pre-processing may lead to significantly different accuracies. Although the original work was aimed at the PBAIC, many techniques described in this paper can be generally applied to any fMRI decoding works to increase the prediction accuracy. Published by Elsevier Inc. C1 [Chu, Carlton] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Chu, Carlton; Tan, Geoffrey; Ashburner, John] UCL Inst Neurol, Wellcome Trust Ctr Neuroimaging, London, England. [Ni, Yizhao; Saunders, Craig J.] Univ Southampton, ISIS Grp, Southampton, Hants, England. RP Chu, C (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Room 1D80,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM chuc2@mail.nih.gov RI Ashburner, John/I-3757-2013 OI Ashburner, John/0000-0001-7605-2518 FU Wellcome Trust FX J.A. is supported by Wellcome Trust. The data collection was supported by the Experience Based Cognition Project (Walter Schneider, PI, University of Pittsburgh). NR 32 TC 26 Z9 26 U1 3 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2011 VL 56 IS 2 SI SI BP 662 EP 673 DI 10.1016/j.neuroimage.2010.03.058 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 757JS UT WOS:000290081900024 PM 20348000 ER PT J AU Gandhi, M Ameli, N Bacchetti, P Anastos, K Gange, SJ Minkoff, H Young, M Milam, J Cohen, MH Sharp, GB Huang, Y Greenblatt, RM AF Gandhi, Monica Ameli, Niloufar Bacchetti, Peter Anastos, Kathryn Gange, Stephen J. Minkoff, Howard Young, Mary Milam, Joel Cohen, Mardge H. Sharp, Gerald B. Huang, Yong Greenblatt, Ruth M. TI Atazanavir Concentration in Hair Is the Strongest Predictor of Outcomes on Antiretroviral Therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-INFECTED PATIENTS; CELL COUNT INCREASE; ADHERENCE AB Background. Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay. Methods. Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, < 80 copies/mL). Results. 424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0-961.1]), low hair levels (OR, 132.8 [95% CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3-3069.7]). Conclusions. Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability. C1 [Gandhi, Monica; Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94122 USA. [Ameli, Niloufar; Huang, Yong; Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94122 USA. [Bacchetti, Peter; Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Epidemiol Biostat, San Francisco, CA 94122 USA. [Milam, Joel] Univ So Calif, Dept Med, Los Angeles, CA USA. [Anastos, Kathryn] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Minkoff, Howard] SUNY Downstate Med Ctr, Dept Med, Brooklyn, NY USA. [Gange, Stephen J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Young, Mary] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Cohen, Mardge H.] John Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Dept Med, Chicago, IL 60612 USA. [Sharp, Gerald B.] NIAID, NIH, Bethesda, MD 20892 USA. RP Gandhi, M (reprint author), Univ Calif San Francisco, 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 RO1-AI-65233, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; 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; National Center for Research Resources [UL1 RR024131]; NIAID [K23 A1067065]; HRSA; National Institutes of Health FX This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID RO1-AI-65233) with data collected in the Women's Interagency HIV Study (WIHS). The WIHS 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 Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The WIHS is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding for WIHS is also provided by the National Center for Research Resources (UCSF - CTSI Grant UL1 RR024131). M.G. was additionally supported by a Mentored Patient-Oriented Research Career Development Award (K23 A1067065) from NIAID.; R.M.G. has received payment previously for manuscript preparation from HRSA and all authors have received funding from the National Institutes of Health. All other authors: no conflicts. NR 28 TC 39 Z9 40 U1 0 U2 10 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 MAY 15 PY 2011 VL 52 IS 10 BP 1267 EP 1275 DI 10.1093/cid/cir131 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 753QW UT WOS:000289795700010 PM 21507924 ER PT J AU Carelli, V Schimpf, S Fuhrmann, N Valentino, ML Zanna, C Iommarini, L Papke, M Schaich, S Tippmann, S Baumann, B Barboni, P Longanesi, L Rugolo, M Ghelli, A Alavi, MV Youle, RJ Bucchi, L Carroccia, R Giannoccaro, MP Tonon, C Lodi, R Cenacchi, G Montagna, P Liguori, R Wissinger, B AF Carelli, Valerio Schimpf, Simone Fuhrmann, Nico Valentino, Maria Lucia Zanna, Claudia Iommarini, Luisa Papke, Monika Schaich, Simone Tippmann, Sabine Baumann, Britta Barboni, Piero Longanesi, Lora Rugolo, Michela Ghelli, Anna Alavi, Marcel V. Youle, Richard J. Bucchi, Laura Carroccia, Rosanna Giannoccaro, Maria Pia Tonon, Caterina Lodi, Raffaele Cenacchi, Giovanna Montagna, Pasquale Liguori, Rocco Wissinger, Bernd TI A clinically complex form of dominant optic atrophy (OPA8) maps on chromosome 16 SO HUMAN MOLECULAR GENETICS LA English DT Article ID MITOCHONDRIAL FUSION; EXTERNAL OPHTHALMOPLEGIA; CONGENITAL DEAFNESS; NERVE ATROPHY; HEARING-LOSS; MUTATIONS; NEUROPATHY; GENE; ATAXIA; DYNAMICS AB Dominant optic atrophy (DOA) is genetically heterogeneous and pathogenic mutations have been identified in the OPA1 and OPA3 genes, both encoding for mitochondrial proteins. We characterized clinical and laboratory features in a large OPA1-negative family with complicated DOA. Search for mitochondrial dysfunction was performed by studying muscle biopsies, fibroblasts, platelets and magnetic resonance (MR) spectroscopy. Genetic investigations included mitochondrial DNA (mtDNA) analysis, linkage analysis, copy number variation (CNV) analysis and candidate gene screening. Optic neuropathy was undistinguishable from that in OPA1-DOA and frequently associated with late-onset sensorineural hearing loss, increases of central conduction times at somato-sensory evoked potentials and various cardiac abnormalities. Serum lactic acid after exercise, platelet respiratory complex activities, adenosine triphosphate (ATP) content in fibroblasts and muscle phosphorus MR spectroscopy all failed to reveal a mitochondrial dysfunction. However, muscle biopsies and their mtDNA analysis showed increased mitochondrial biogenesis. Furthermore, patient's fibroblasts grown in the galactose medium were unable to increase ATP content compared with controls, and exhibited abnormally high rate of fusion activity. Genome-wide linkage revealed a locus on chromosome 16q21-q22 with a maximum two-point LOD score of 8.84 for the marker D16S752 and a non-recombinant interval of similar to 6.96 cM. Genomic screening of 45 genes in this interval including several likely candidate genes (CALB2, CYB5B, TK2, DHODH, PLEKHG4) revealed no mutation. Moreover, we excluded the presence of CNVs using array-based comparative genome hybridization. The identification of a new OPA locus (OPA8) in this pedigree demonstrates further genetic heterogeneity in DOA, and our results indicate that the pathogenesis may still involve mitochondria. C1 [Carelli, Valerio; Valentino, Maria Lucia; Iommarini, Luisa; Barboni, Piero; Bucchi, Laura; Carroccia, Rosanna; Giannoccaro, Maria Pia; Montagna, Pasquale; Liguori, Rocco] Univ Bologna, Dept Neurol Sci, I-40123 Bologna, Italy. [Schimpf, Simone; Fuhrmann, Nico; Papke, Monika; Schaich, Simone; Tippmann, Sabine; Baumann, Britta; Alavi, Marcel V.; Wissinger, Bernd] Univ Clin Tuebingen, Mol Genet Lab, Inst Ophthalm Res, Ctr Ophthalmol, D-72076 Tubingen, Germany. [Zanna, Claudia; Rugolo, Michela; Ghelli, Anna] Univ Bologna, Dept Evolutionary & Expt Biol, I-40126 Bologna, Italy. [Longanesi, Lora] Hosp Lugo, Unit Ophthalmol, I-48122 Lugo, Ravenna, Italy. [Youle, Richard J.] Natl Inst Neurol Disorders & Stroke, Biochem Sect, NIH, Bethesda, MD 20810 USA. [Tonon, Caterina; Lodi, Raffaele] Univ Bologna, St Orsola Malpighi Hosp, MR Spect Unit, Dept Internal Med Aging & Nephrol, I-40138 Bologna, Italy. [Cenacchi, Giovanna] Univ Bologna, St Orsola Malpighi Hosp, Clin Dept Radiol & Histocytopathol Sci, I-40138 Bologna, Italy. RP Carelli, V (reprint author), Univ Bologna, Dept Neurol Sci, Via Ugo Foscolo 7, I-40123 Bologna, Italy. EM valerio.carelli@unibo.it OI VALENTINO, MARIA LUCIA/0000-0001-5323-0115; TONON, CATERINA/0000-0002-0506-499X; Rugolo, Michela/0000-0002-4597-0452; Lodi, Raffaele/0000-0003-3878-304X; CARELLI, VALERIO/0000-0003-4923-6404; Liguori, Rocco/0000-0002-1815-1013 FU Waltraud und Sieglinde Hildebrandt Stiftung; Friedrich-Spicker Stiftung; German Ministry of Education and Research [01GM1006]; Telethon-Italy [GGP06233]; Fondazione Gino Galletti FX This work was supported by the Waltraud und Sieglinde Hildebrandt Stiftung, the Friedrich-Spicker Stiftung and the German Ministry of Education and Research (01GM1006 to B.W.); by Telethon-Italy (GGP06233 to V.C.); and by Fondazione Gino Galletti (to V.C.). NR 43 TC 10 Z9 10 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 15 PY 2011 VL 20 IS 10 BP 1893 EP 1905 DI 10.1093/hmg/ddr071 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 754EU UT WOS:000289837400003 PM 21349918 ER PT J AU Chavali, VRM Khan, NW Cukras, CA Bartsch, DU Jablonski, MM Ayyagari, R AF Chavali, Venkata R. M. Khan, Naheed W. Cukras, Catherine A. Bartsch, Dirk-Uwe Jablonski, Monica M. Ayyagari, Radha TI A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration SO HUMAN MOLECULAR GENETICS LA English DT Article ID PIGMENT-EPITHELIUM DEPOSITS; SORSBYS-FUNDUS-DYSTROPHY; FRIZZLED-RELATED PROTEIN; AGE-RELATED MACULOPATHY; ANTERIOR LENS ZONULES; CHEMOKINE RECEPTOR 2; MACULAR DEGENERATION; PHOTORECEPTOR DEGENERATION; DARK-ADAPTATION; ACCELERATED ACCUMULATION AB Late-onset retinal macular degeneration (L-ORD) is an autosomal dominant inherited disorder caused by a single missense mutation (S163R) in the CTRP5/C1QTNF5 protein. Early phenotypic features of L-ORD include: dark adaptation abnormalities, nyctalopia, and drusen deposits in the peripheral macular region. Apart from posterior segment abnormalities, these patients also develop abnormally long anterior lens zonules. In the sixth decade of life the rod and cone function declines, accompanied by electroretinogram (ERG) abnormalities. Some patients also develop choroidal neovascularization and glaucoma. In order to understand the disease pathology and mechanisms involved in retinal dystrophy, we generated a knock-in (Ctrp5(+/-)) mouse model carrying the disease-associated mutation in the mouse Ctrp5/C1QTNF5 gene. These mice develop slower rod-b wave recovery consistent with early dark adaptation abnormalities, accumulation of hyperautofluorescence spots, retinal pigment epithelium abnormalities, drusen, Bruch's membrane abnormalities, loss of photoreceptors, and retinal vascular leakage. The Ctrp5(+/-) mice, which have most of the pathological features of age-related macular degeneration, are unique and may serve as a valuable model both to understand the molecular pathology of late-onset retinal degeneration and to evaluate therapies. C1 [Chavali, Venkata R. M.; Bartsch, Dirk-Uwe; Ayyagari, Radha] Univ Calif San Diego, La Jolla, CA 92037 USA. [Khan, Naheed W.] Univ Michigan, Ann Arbor, MI 48105 USA. [Jablonski, Monica M.] Univ Tennessee, Hlth Sci Ctr, Hamilton Eye Inst, Memphis, TN 38163 USA. [Cukras, Catherine A.] NEI, NIH, Bethesda, MD 20892 USA. RP Ayyagari, R (reprint author), Univ Calif San Diego, La Jolla, CA 92037 USA. EM rayyagari@ucsd.edu FU National Institute of Health [RO1 EY016323, P30EY007003, R01EY013198]; Foundation Fighting Blindness Centre; Research to Prevent Blindness, New York, NY; UCSD Neuroscience Microscopy Shared Facility [P30 NS047101] FX This work is supported by National Institute of Health grants (RO1 EY016323 to D.-U.B., P30EY007003 to M.M.J. and R01EY013198 to R.A.); a Foundation Fighting Blindness Centre grant to R.A.; an unrestricted grant from Research to Prevent Blindness, New York, NY (to M.M.J.); and the UCSD Neuroscience Microscopy Shared Facility grant (P30 NS047101). NR 67 TC 24 Z9 24 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 15 PY 2011 VL 20 IS 10 BP 2000 EP 2014 DI 10.1093/hmg/ddr080 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 754EU UT WOS:000289837400012 PM 21349921 ER PT J AU Bray, M Lawler, J Paragas, J Jahrling, PB Mollura, DJ AF Bray, Mike Lawler, James Paragas, Jason Jahrling, Peter B. Mollura, Daniel J. TI Molecular Imaging of Influenza and Other Emerging Respiratory Viral Infections SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; ACUTE LUNG INJURY; IN-VIVO; PNEUMOCOCCAL PNEUMONIA; PULMONARY INFLAMMATION; ANTIVIRAL RESEARCH; AVIAN INFLUENZA; FDG-PET; A H1N1; VIRUS AB Research on the pathogenesis and therapy of influenza and other emerging respiratory viral infections would be aided by methods that directly visualize pathophysiologic processes in patients and laboratory animals. At present, imaging of diseases, such as swine-origin H1N1 influenza, is largely restricted to chest radiograph and computed tomography (CT), which can detect pulmonary structural changes in severely ill patients but are more limited in characterizing the early stages of illness, differentiating inflammation from infection or tracking immune responses. In contrast, imaging modalities, such as positron emission tomography, single photon emission CT, magnetic resonance imaging, and bioluminescence imaging, which have become useful tools for investigating the pathogenesis of a range of disease processes, could be used to advance in vivo studies of respiratory viral infections in patients and animals. Molecular techniques might also be used to identify novel biomarkers of disease progression and to evaluate new therapies. C1 [Bray, Mike] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Lawler, James; Paragas, Jason; Jahrling, Peter B.] NIAID, Integrated Res Facil, NIH, Ft Detrick, MD USA. RP Bray, M (reprint author), NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. EM mbray@niaid.nih.gov NR 81 TC 6 Z9 6 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 15 PY 2011 VL 203 IS 10 BP 1348 EP 1359 DI 10.1093/infdis/jir038 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 754FC UT WOS:000289838800002 PM 21422476 ER PT J AU Ledgerwood, JE Pierson, TC Hubka, SA Desai, N Rucker, S Gordon, IJ Enama, ME Nelson, S Nason, M Gu, WJ Bundrant, N Koup, RA Bailer, RT Mascola, JR Nabel, GJ Graham, BS AF Ledgerwood, Julie E. Pierson, Theodore C. Hubka, Sarah A. Desai, Niraj Rucker, Steve Gordon, Ingelise J. Enama, Mary E. Nelson, Steevenson Nason, Martha Gu, Wenjuan Bundrant, Nikkida Koup, Richard A. Bailer, Robert T. Mascola, John R. Nabel, Gary J. Graham, Barney S. CA VRC 303 Study Team TI A West Nile Virus DNA Vaccine Utilizing a Modified Promoter Induces Neutralizing Antibody in Younger and Older Healthy Adults in a Phase I Clinical Trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CANDIDATE VACCINE; IMMUNOGENICITY EVALUATION; DISSEMINATED INFECTION; ENCEPHALITIS-VIRUS; IMMUNE-RESPONSES; UNITED-STATES; EPIDEMIOLOGY; PROTECTS; INNATE; SAFETY AB Methods. A DNA vaccine encoding the protein premembrane and the E glycoproteins of the NY99 strain of WNV under the transcriptional control of the CMV/R promoter was evaluated in an open-label study in 30 healthy adults. Half of the subjects were age 18-50 years and half were age 51-65 years. Immune responses were assessed by enzyme-linked immunosorbent assay, neutralization assays, intracellular cytokine staining, and ELISpot. Results. The 3-dose vaccine regimen was safe and well tolerated. Vaccine-induced T cell and neutralizing antibody responses were detected in the majority of subjects. The antibody responses seen in the older age group were of similar frequency, magnitude, and duration as those seen in the younger cohort. Conclusions. Neutralizing antibody responses to WNV were elicited by DNA vaccination in humans, including in older individuals, where responses to traditional vaccine approaches are often diminished. This DNA vaccine elicited T cell responses of greater magnitude when compared with an earlier-generation construct utilizing a CMV promoter. Clinical Trials Registration. NCT00300417. C1 [Ledgerwood, Julie E.; Hubka, Sarah A.; Desai, Niraj; Rucker, Steve; Gordon, Ingelise J.; Enama, Mary E.; Bundrant, Nikkida; Koup, Richard A.; Bailer, Robert T.; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.; VRC 303 Study Team] NIAID, VRC, NIH, Bethesda, MD 20892 USA. [Pierson, Theodore C.; Nelson, Steevenson] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Nason, Martha] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Gu, Wenjuan] NCI, Biostat Res Branch, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Ledgerwood, JE (reprint author), NIAID, VRC, NIH, 9000 Rockville Pike,CRC Bldg 10,Room 5-2440, Bethesda, MD 20892 USA. EM ledgerwood@mail.nih.gov FU National Institute of Allergy and Infectious Diseases FX This work was funded by the National Institute of Allergy and Infectious Diseases' intramural research program. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. NR 41 TC 56 Z9 59 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 15 PY 2011 VL 203 IS 10 BP 1396 EP 1404 DI 10.1093/infdis/jir054 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 754FC UT WOS:000289838800007 PM 21398392 ER PT J AU Xi, LF Hughes, JP Castle, PE Edelstein, ZR Wang, CH Galloway, DA Koutsky, LA Kiviat, NB Schiffman, M AF Xi, Long Fu Hughes, James P. Castle, Philip E. Edelstein, Zoe R. Wang, Chunhui Galloway, Denise A. Koutsky, Laura A. Kiviat, Nancy B. Schiffman, Mark TI Viral Load in the Natural History of Human Papillomavirus Type 16 Infection: A Nested Case-control Study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; CARCINOMA IN-SITU; RISK HUMAN-PAPILLOMAVIRUS; FORMER SOVIET-UNION; DNA LOAD; INDEPENDENT STATES; NORMAL CYTOLOGY; HPV DNA; WOMEN; CLEARANCE AB Methods. This case-control study was nested within the 2-year Atypical Squamous Cells of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study, in which women were followed semiannually for HPV and cervical intraepithelial neoplasia (CIN). Case patients (n = 62) were women diagnosed with CIN3 following HPV-16-positive detection at a follow-up visit. HPV-16-positive controls (n = 152) without CIN2 or CIN3 were matched to cases based on the follow-up visit in which viral load was measured. Real-time polymerase chain reaction was used for HPV-16 DNA quantification. Results. The risk of CIN3 increased with increasing HPV-16 DNA load at the follow-up visit (odds ratio, 1.63; 95% confidence interval, 1.33-1.99 per 1 log(10) unit increase); the association was not affected by whether HPV-16 was present at enrollment. When HPV-16 was present at both enrollment and follow-up, viral load remained high among cases (P = .77) but decreased substantially among controls (P = .004). Among women with HPV-16 found initially during follow-up, viral load in the first HPV-16-positive sample was associated with short-term persistence; load was higher in those with infection, compared with those without infection, 1 visit after the initial positivity (P = .001). Conclusions. Viral load of newly detected infections and changes in viral load predict persistence and progression of HPV-16 infections. C1 [Xi, Long Fu] Univ Washington, Harborview Med Ctr, Dept Pathol, Sch Med, Seattle, WA 98104 USA. [Xi, Long Fu; Edelstein, Zoe R.; Wang, Chunhui; Koutsky, Laura A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98104 USA. [Hughes, James P.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98104 USA. [Galloway, Denise A.; Schiffman, Mark] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Xi, LF (reprint author), Univ Washington, Harborview Med Ctr, Dept Pathol, Sch Med, NJB Ste 1187,325 9th Ave, Seattle, WA 98104 USA. EM longfu@u.washington.edu RI Wang, Chunhui/F-9352-2012 FU Merck Research Laboratories; Public Health Service [CA133569] FX L.A.K. receives research funds from Merck Research Laboratories.; The work was supported by Public Health Service grant CA133569 to L.F.X. NR 43 TC 25 Z9 26 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 15 PY 2011 VL 203 IS 10 BP 1425 EP 1433 DI 10.1093/infdis/jir049 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 754FC UT WOS:000289838800010 PM 21415020 ER PT J AU Troyer, JL Nelson, GW Lautenberger, JA Chinn, L McIntosh, C Johnson, RC Sezgin, E Kessing, B Malasky, M Hendrickson, SL Li, G Pontius, J Tang, MZ An, P Winkler, CA Limou, S Le Clerc, S Delaneau, O Zagury, JF Schuitemaker, H van Manen, D Bream, JH Gomperts, ED Buchbinder, S Goedert, JJ Kirk, GD O'Brien, SJ AF Troyer, Jennifer L. Nelson, George W. Lautenberger, James A. Chinn, Leslie McIntosh, Carl Johnson, Randall C. Sezgin, Efe Kessing, Bailey Malasky, Michael Hendrickson, Sher L. Li, Guan Pontius, Joan Tang, Minzhong An, Ping Winkler, Cheryl A. Limou, Sophie Le Clerc, Sigrid Delaneau, Olivier Zagury, Jean-Francois Schuitemaker, Hanneke van Manen, Danielle Bream, Jay H. Gomperts, Edward D. Buchbinder, Susan Goedert, James J. Kirk, Gregory D. O'Brien, Stephen J. TI Genome-wide Association Study Implicates PARD3B-based AIDS Restriction SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MCP-1 GENE-TRANSCRIPTION; HIV-1 INFECTION; TGF-BETA; TAT; NONPROGRESSION; PROGRESSION; ASTROCYTES; PROTEINS; FUTURE; CELLS AB Methods. European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results. Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 x 10(-9)) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 x 10(-8)). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression. C1 [Troyer, Jennifer L.; Nelson, George W.; Johnson, Randall C.; Kessing, Bailey; Malasky, Michael; Li, Guan; Pontius, Joan; An, Ping; Winkler, Cheryl A.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. [Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-Francois] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Schuitemaker, Hanneke; van Manen, Danielle] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Bream, Jay H.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Gomperts, Edward D.] Childrens Hosp Los Angeles, Dept Hematol, Los Angeles, CA USA. [Buchbinder, Susan] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA. [Goedert, James J.] Conservatoire Natl Arts & Metiers, Chaire Bioinformat, Paris, France. [Kirk, Gregory D.] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Landsteiner Lab, NL-1012 WX Amsterdam, Netherlands. [Kirk, Gregory D.] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, NL-1012 WX Amsterdam, Netherlands. RP Troyer, JL (reprint author), NCI, Lab Genom Divers, SAIC Frederick Inc, Bldg 560,Rm 21-56, Frederick, MD 21702 USA. EM troyerj@mail.nih.gov RI Sezgin, Efe/B-8418-2012; Troyer, Jennifer/B-8415-2012; Johnson, Randall/B-1517-2014 OI Sezgin, Efe/0000-0002-8000-7485; Johnson, Randall/0000-0001-7754-0847 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN26120080001E]; National Institutes of Health, National Institute of Child Health and Human Development [1 R01 HD41224]; Netherlands Organization for Scientific Research [9120.6046] FX The Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E. The Hemophilia Growth and Development Study is funded by the National Institutes of Health, National Institute of Child Health and Human Development, 1 R01 HD41224. Funding for genetic studies on the ACS was provided by the Netherlands Organization for Scientific Research (TOP, registration number 9120.6046). NR 43 TC 28 Z9 28 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 15 PY 2011 VL 203 IS 10 BP 1491 EP 1502 DI 10.1093/infdis/jir046 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 754FC UT WOS:000289838800018 PM 21502085 ER PT J AU Sekine, Y Suzuki, K Remaley, AT AF Sekine, Yoshitaka Suzuki, Kazuhiro Remaley, Alan T. TI HDL and Sphingosine-1-Phosphate Activate Stat3 in Prostate Cancer DU145 Cells Via ERK1/2 and S1P Receptors, and Promote Cell Migration and Invasion SO PROSTATE LA English DT Article DE HDL; S1P; Stat3; prostate cancer; DU145 ID HIGH-DENSITY-LIPOPROTEIN; ARTERY ENDOTHELIAL-CELLS; SPHINGOSINE 1-PHOSPHATE; SIGNAL TRANSDUCER; TUBE FORMATION; PHOSPHORYLATION; PROLIFERATION; TRANSCRIPTION-3; REGULATOR; PATHWAYS AB BACKGROUND. Androgen deprivation therapy in men with prostate cancer leads to a significant increase of high density lipoprotein (HDL), but the effect of HDL on prostate cancer is unknown. Recently, HDL, which transports sphingosine-1-phosphate (S1P), was reported to activate signal transducer and activator of transcription 3 (Stat3) in cardiomyocytes. In this study, we examined the effect of HDL and S1P on Stat3 activation in prostate cancer cells and the involvement of S1P receptors in this process in three prostate cancer cell lines (PC-3, LNCaP, and DU145). METHODS. Discordial reconstituted(r) HDL containing POPC, apoA-1, and S1P were prepared by the cholate dialysis method. The phosphorylations of Stat3, ERK1/2, and Akt were detected by Western blotting. Cell migration and invasion were determined by wound-healing assay and matrigel invasion chamber assay. RESULTS. HDL increased serine 727 phosphorylation of Stat3, but not tyrosine 705 only in DU145 cells. S1P and rHDL-S1P also induced the phosphorylation, but not rHDL without S1P. They also induced DU145 cells migration and invasion. PD98059, a MEK inhibitor, and pertussis toxin, a Gi inhibitor, attenuated HDL-, S1P-, and rHDL-S1P-induced Stat3 phosphorylation, whereas LY294002, a PI3K inhibitor, had no effect. Concerning S1P receptors, S1P1 expression was much lower than S1P2 and S1P3 in DU145 cells. Both JTE013, a S1P2 antagonist, and VPC23019, a S1P1/S1P3 antagonist, attenuated HDL-, S1P-, and rHDL-S1P-induced Stat3 phosphorylations and cell migrations. CONCLUSIONS. These results suggest that the change in HDL plasma levels by androgen deprivation therapy may alter prostate cancer growth and metastasis. Prostate 71: 690-699, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Sekine, Yoshitaka; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Sekine, Yoshitaka; Suzuki, Kazuhiro] Gunma Univ, Dept Urol, Grad Sch Med, Maebashi, Gunma 371, Japan. RP Sekine, Y (reprint author), NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bldg 10,Room 8N224,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ysekine@showa.gunma-u.ac.jp FU National Institutes of Health FX Grant sponsor: National Institutes of Health. NR 31 TC 25 Z9 25 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 15 PY 2011 VL 71 IS 7 BP 690 EP 699 DI 10.1002/pros.21285 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 750AV UT WOS:000289516900003 PM 20979115 ER EF